1 209
C H A PT E R 64
I nfect iou s D i sea ses
MATERNAL AND FETAL I M M U NOLOGY . . . . . . . . . . . . 1 209
VIRAL I N F ECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . 1210
. .
BACTERIAL IN FECTIONS . . . . . . . . . . . . . . . . . . . . . . . . 1 220
PROTOZOAL I N FECTIONS . . . . . . . . . . . . . . . . . . . . . 1 225
. .
BIOTERRORISM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 228
According to many authorities, inluena exerts a very per­
nicious influence upon pregnancy. t would appear that the
fects ofinluena must vary with the severiy ofthe epidemic,
and more particuary with the frequeny ofpneumonic com­
plications. As a rule, any septic condition oers a worse prog­
nosis in prenany. Several instances have been reported of
transmission ofthe oending bacteria to the oetus.
-J. Whitridge Williams ( 1 903)
Infections have historically been a major cause of maternal and
fetal morbidity and mortality worldwide, and they remain so
in the 2 1 st century. he unique maternal-fetal vascular con­
nection in some cases serves to protect the fetus from infec­
tious agents, whereas in other instances it provides a conduit
for their transmission to the fetus. Maternal serological status,
gestational age at the time infection is acquired, the mode of
acquisition, and the immunological status of both the mother
and her fetus all inluence disease outcome.
MATERNAL AND FETA L I MM U NOLOGY
• Pregnancy-Induced I mmunological Changes
Even after intensive study, many of the maternal immunologi­
cal adaptations to pregnancy are not well elucidated. It is known
that pregnancy is associated with an increase in the CD4 + T
cells that secrete h2-type cytokines-for example interleu­
kins (Fragiadakis, 20 1 6) . Th 1 -type cytokine production-for
example, interferon gamma and interleukin 2-appears to be
somewhat suppressed, leading to a h2 bias in pregnancy. This
bias afects the ability to rapidly eliminate certain intracellular
pathogens during pregnancy, although the clinical implica­
tions of this suppression are unknown (Kourtis, 20 1 4; Svens­
son-Arvelund, 20 14) . Importantly, the h2 humoral immune
response remains intact. It also appears that human leukocyte
antigen (HA)-C expressed by extravillous trophoblasts elic­
its responses from decidual natural killer (dNK) and decidual
CD8 + T cells (Crespo, 20 1 7) .
I n describing infections, horizontal transmission is the spread
of an infectious agent from one individual to another. Vertical
transmission refers to passage from the mother to her fetus of an
infectious agent through the placenta, during labor or delivery,
or by breastfeeding. Thus, preterm rupture of membranes, pro­
longed labor, and obstetrical manipulations may enhance the
risk of neonatal infection (Centers for Disease Control and Pre­
vention, 20 1 0) . Table 64- 1 details speciic infections by mode
and timing of acquisition. A inal term, the seconday attack
rate, is the probability that infection develops in a susceptible
individual following known contact with an infectious person.
• Fetal a nd Newborn Immunology
The active immunological capacity of the fetus and neonate
is compromised compared with that of older children and
adults. That said, fetal cell-mediated and humoral immunity
begin to develop by 9 to 1 5 weeks' gestation (Warner, 2 0 1 0) .
The primary fetal response to infection is immunoglobulin M
(Ig.1) . Passive immunity is provided by IgG transferred across
the placenta. By 1 6 weeks, this transfer begins to rise rapidly,
and by 26 weeks, fetal concentrations are equivalent to those
of the mother. After birth, breastfeeding is protective against
some infections, although this protection begins to decline at
1210 Med i ca l a n d S u rg ical Com p l icati o n s
TABLE 4-1 . Specific Causes of Some Feta l a n d
Neonata l I nfect i o n s
I ntra uteri ne
Tra n s pl acenta l
Vi ruses: va rice l la-zoster, coxsackie, h u m a n pa rvovi rus
B 1 9, rubel la, CMV, H IV, Z i ka
Bacteria: Listeria, syp h i l is, Borrelia
Protozoa : toxopl a s m os i s, m a l a ria
Asce n d i ng i nfection
Bacteria : g ro u p B streptococcus, col iforms
Vi ruses: H IV
I ntra partum
Mate rn a l exposu re
Bacte ria: gonorrhea, c h l a myd i a , g ro u p B
s treptococcus, tu bercu losis, mycop l a s m a s
Vi ruses: HSV, H PV, H IV, h e patitis B, h e patitis C, Z i ka
Externa l conta m i nation
Bacteria: sta phylococcus, col ifo r m s
Vi ru ses: HSV, va rice l l a zoster
Neonatal
H u m a n tra ns m i ssion: sta phylococcu s, H SV
Res p i rato rs a n d catheters: sta p hy l ococc u s, col iforms
C MV = cyto mega lovi rus; H IV h u ma n i m m u nodefici e n cy
=
v i rus; H PV =h u ma n pa p i l lomavirus; H SV herpes s i m plex
=
v i r u s.
2 months of age. Current World Health Organization (20 1 3)
recommendations are to exclusively breastfeed for the first
6 months of life with partial breastfeeding until 2 years of age.
Neonatal infection, especially in its early stages, may be dif­
icult to diagnose because these newborns often fail to express
classic clinical signs. If the fetus was infected in utero, there
may be depression and acidosis at birth for no apparent rea­
son. The neonate may suck poorly, vomit, or show abdominal
distention. Respiratory insuiciency can develop, which may
present similarly to idiopathic respiratory distress syndrome.
he neonate may be lethargic or jittery. he response to sepsis
may be hypothermia rather than hyperthermia, and the total
leukocyte and neutrophil counts may be depressed.
VIRAL INFECTIONS
• Ctomegalovirus
Several viruses cause severe maternal infections, and some can
also cause devastating fetal infections. Of these, cytomegalovi­
rus (CMV) is a ubiquitous DNA herpes virus that eventually
infects most humans. CMV is also the most common perinatal
infection in the developed world. Speciically, some evidence
of fetal infection is found in 0.2 to 2 . 2 percent of all neonates
(American College of Obstetricians and Gynecologists, 20 1 7) .
The virus i s secreted into all body luids, and person-to-person
contact with viral-laden saliva, semen, urine, blood, and naso­
pharyngeal and cervical secretions can transmit infection. The
fetus may become infected by transplacental viremia, or the
neonate is infected at delivery or during breastfeeding. vlore­
over, acquisition continues to accrue. Day-care centers, for
example, are a frequent source. Revello and coworkers (2008)
reported that amniocentesis in women whose blood is positive
for CMV DNA does not result in iatrogenic fetal transmission.
Up to 85 percent of women from lower socioeconomic back­
grounds are seropositive by the time of pregnancy, whereas only
half of women in higher income groups are immune. Follow­
ing primary CMV infection, and in a manner similar to other
herpesvirus infections, the virus becomes latent with periodic
reactivation characterized by viral shedding. This occurs despite
high serum levels of anti-CMV IgG antibody. These antibodies
do not prevent maternal recurrence, reactivation, or reinfection,
nor do they totally mitigate fetal or neonatal infection.
Matern a l I nfection
Women who are seronegative before pregnancy, but who
develop primary CMV infection during pregnancy, are at
greatest risk to have an infected fetus. It is estimated that 25
percent of congenital CMV infections in the United States are
from primary maternal infection (Wang, 20 1 1 ) . Most CMV
infections are clinically silent, but they can be detected by sero­
conversion, and this may be as high as 1 to 7 percent annu­
ally (Hyde, 20 1 0) . Conversely, diagnosis of CMV nonprimary
infection is a challenge (Picone, 20 1 7) .
Pregnancy does not increase the risk o r severity o f maternal
CMV infection. Most infections are asymptomatic, but 1 0 to
1 5 percent of infected adults have a mononucleosis-like syn­
drome characterized by fever, pharyngitis, lymphadenopathy,
and polyarthritis. Immunocompromised women may develop
myocarditis, pneumonitis, hepatitis, retinitis, gastroenteritis, or
meningoencephalitis. Nigro and associates (2003) reported that
most women in a cohort with primary infection had elevated
serum aminotransferases or lymphocytosis. Reactivation disease
usually is asymptomatic, although viral shedding is common.
Transmission rates for primary infection are 30 to 36 per­
cent in the first trimester, 34 to 40 percent in the second, and
40 to 72 percent in the third trimester (American College
of Obstetricians and Gynecologists, 20 1 7; Picone, 20 1 7) . In
contrast, recurrent maternal infection infects the fetus in only
0 . 1 5 to 1 percent of cases. Naturally acquired immunity during
pregnancy results in a 70-percent risk reduction of congenital
CMV infection in future pregnancies (Fowler, 2003; Leruez­
Ville, 20 1 7) . However, as noted earlier, maternal immunity
does not prevent recurrences, and maternal antibodies do not
prevent fetal infection (Ross, 20 1 1 ) .
Feta l I nfecti o n
Newborns with apparent sequelae of in-utero-acquired CMV
infection are described as having symptomatic CMV inection.
Congenital infection is a syndrome that may include growth
restriction, microcephaly, intracranial calcifications, chorio­
retinitis, mental and motor retardation, sensorineural deficits,
hepatosplenomegaly, jaundice, hemolytic anemia, and throm­
bocytopenic purpura (Cheeran, 2009) . An example of periven­
tricular calcifications is shown in Figure 64- 1 . Of the estimated
40,000 infected neonates born each year, only 5 to 1 0 per­
cent demonstrate this syndrome (Fowler, 1 992) . hus, most
 I nfectiou 5 Di seases 1 21 1

infected infants are asymptomatic at birth, but some develop

late-onset sequelae. Complications may include hearing loss,
neurological deicits, chorioretinitis, psychomotor retardation,
and learning disabilities. Infections in dichorionic twins most
1 ikely are nonconcordant (Egana-Ugrinovic, 20 1 6) .

P re n ata l Diag nosis

F I G U R E 64- 1 Coro n a l view of cra n ia l sonogram from a neonate
with congenita l cytomeg a l ovirus i n fection showi ng m u ltiple
periventricu l a r ca l c ifications.
Routine prenatal CMV serological screening is currently not rec­
ommended by the Society for Maternal-Fetal Medicine (20 1 6) .
An algorithm for management is shown in Figure 64-2 . Preg­
nant women should be tested for CMV if they present with a
mononucleosis-like illness or if congenital infection is suspected
based on abnormal sonographic indings. Primary infection is
diagnosed using CMV-speciic IgG testing of paired acute and
convalescent sera. CMV IgM does not accurately relect timing
of seroconversion because IgM antibody levels may be elevated
for more than a year (Stagno, 1 985). Moreover, CMV IgM
may be found with reactivation disease or reinfection with a
new strain. Thus, specific CMV IgG avidity testing is valuable

Abnormal Maternal CMV Screening

CMV IgG : positive

!
CMV IgM : positive

CMV-specific IgG and IgM by EIA,

.--CMV-specific IgG avidity by EIA, and
CMV-specific IgM by immunoblot
CMV IgG : n egative

!
CMV IgM : negative

CMV uninfected ;
N o further evaluation

CMV IgG : positive CMV IgG : positive U ncertain CMV IgG : positive
IgG avidity index: high or seroconversion serologic IgG avidity index: high
CMV IgM : negative IgG avidity index: low results CMV IgM : positive
CMV IgM : positive

!
Latent CMV
!
Primary CMV
!
Undefined
!
Recurrent CMV

! !
infection infection CMV infection i nfection

I I
No further
evaluation I
I nvasive
Noninvasive
follow-up

follow-up

F I G U R E 64-2 Algorithm for eva l ua tion o f suspected maternal pri m a ry cytomegalovirus (CM) i nfection i n p reg n a ncy. EIA = enzyme
i m m u noa ssay; IgG = i m m u nog l o b u l i n G; IgM = i m m u nog lobu l i n M.
1 21 2 Med i c a l a n d S u rg ica l Com p l ications
in conirming primary CMV infection. High anti-CMV IgG
avidity indicates primary maternal infection >6 months before
testing (Kanengisser-Pines, 2009) . Finally, viral culture may be
useful, although a minimum of 2 1 days is required before find­
ings are considered negative.
Several fetal abnormalities associated with CMV infection
may be seen with sonography, computed tomography, or mag­
netic resonance imaging. In some cases, they are found at the
time of routine prenatal sonographic screening, but in others
they are part of a specific evaluation in women with CMV infec­
tion. Findings include microcephaly, ventriculomegaly, and
cerebral calciications; ascites, hepatomegaly, splenomegaly, and
hyperechoic bowel; hydrops; and oligohydramnios (Society for
Maternal-Fetal Medicine, 20 1 6) . Abnormal sonographic find­
ings seen in combination with positive findings in fetal blood or
amnionic fl u id are predictive of an approximate 75-percent risk
of symptomatic congenital infection (Enders, 200 1 ) .
CMV nucleic acid amplification testing (NAAT) o f amni­
onic luid is considered the gold standard for the diagnosis of
fetal infection. Sensitivities range from 70 to 99 percent and
depend on amniocentesis timing. Sensitivity is highest when
amniocentesis is performed at least 6 weeks after maternal
infection and after 2 1 weeks' gestation (Azam, 200 1 ; Guerra,
2000) . A negative result from amnionic luid polymerase chain
reaction (PCR) testing does not exclude fetal infection and may
need to be repeated if suspicion for fetal infection is high.
M a n a g e m e nt a n d Preve ntion
The management of the immunocompetent pregnant woman
with primary or recurrent CMV is limited to symptomatic
treatment. If recent primary CMV infection is conirmed,
amnionic fluid analysis should be ofered. Counseling regard­
ing fetal outcome depends on the gestational age during which
primary infection is documented. Despite the high infection
rate with primary infection in the first half of pregnancy, most
fetuses develop normally. However, pregnancy termination
may be an option for some.
Currently, no proven treatments are available for CMV infec­
tion (Society for Maternal-Fetal Medicine, 20 1 6) . Leruez-Ville
and associates (20 1 6) recently reported that oral treatment with
valacyclovir, 8 g daily, apparently mitigated adverse outcomes
in eight of 1 1 afected fetuses treated beginning at median of
2 5 . 9 weeks' gestation. Kimberlin and colleagues (20 1 5) previ­
ously showed that intravenous valganciclovir administered for
6 weeks to neonates with symptomatic central nevous system
(CNS) disease prevented hearing deterioration at 6 months
and possibly later. Passive immunization with CMV-specific
hyperimmune globulin may lower the risk of congenital CMV
infection when given to pregnant women with primary dis­
ease (Nigro, 2005, 20 1 2; Visentin, 20 1 2) . he Maternal-Fetal
Medicine Units Network currently is conducting a randomized
trial designed to address this.
here is no CMV vaccine, although several clinical trials
are underway (Arvin, 2004; Schleiss, 20 1 6) . Prevention of
congenital infection relies on avoiding maternal primary infec­
tion, especially in early pregnancy. Basic measures such as good
hygiene and hand washing have been promoted, particularly
for women with toddlers in day-care settings (Fowler, 2000) .
CMV may be sexually transmitted among infected partners, but
no data address the eicacy of preventive strategies.
• Varicella-Zoster Virus
M ater n a l I n fection
Varicella-zoster virus (VZV) is a double-stranded DNA her­
pesvirus acquired predominately during childhood, and 90 per­
cent of adults have serological evidence of immunity (Whitley,
20 1 5). The incidence of adult varicella declined by 82 percent
after the introduction of varicella vaccination, and this has
resulted in a drop in maternal and fetal varicella rates (Ameri­
can College of Obstetricians and Gynecologists, 20 1 7) . In the
United States between 2003 and 20 1 0, the incidence of mater­
nal varicella among 7.7 million pregnancy admissions was 1 .2 1
per 1 0,000 (Zhang, 201 5) .
Primary infection-varicela or chickenpox-is transmitted
by direct contact with an infected individual, although respira­
tory transmission has been reported. The incubation period is 1 0
to 2 1 days, and a nonimmune woman has a 60- to 95-percent
risk of becoming infected after exposure (Whitley, 20 1 5). Pri­
mary varicella presents with a 1 - to 2-day flulike prodrome,
which is followed by pruritic vesicular lesions that crust after 3
to 7 days. Infection tends to be more severe in adults (Marin,
2007) . Afected patients are then contagious from 1 day before
the onset of the rash until the lesions become crusted.
Mortality is predominately due to VZV pneumonia, which
is thought to be more severe during adulthood and particu­
larly in pregnancy. Although the incidence was once thought
to be higher, only 2 to 5 percent of infected pregnant women
develop pneumonitis (Marin, 2007; Zhang, 20 1 5) . Risk factors
for VZV pneumonia include smoking and having more than
1 00 cutaneous lesions. Maternal mortality rates with pneumo­
nia have decreased to 1 to 2 percent (Chandra, 1 998) .
Symptoms of VZV pneumonia usually appear 3 to 5 days
into the course of illness. Fever, tachypnea, dry cough, dyspnea,
and pleuritic pain are characteristic. Nodular iniltrates are sim­
ilar to other viral pneumonias (Chap. 5 1 , p. 994) . Although
resolution of pneumonitis parallels that of skin lesions, fever
and compromised pulmonary function may persist for weeks.
If primary varicella is reactivated years later, it causes herpes
zoster or shingles (Whirley, 20 1 5) . This presents as a unilateral
dermatomal vesicular eruption associated with severe pain.
Zoster does not appear to be more frequent or severe in preg­
nant women. Congenital varicella syndrome rarely develops
in cases of maternal herpes zoster (hn, 20 1 6; Enders, 1 994) .
Zoster is contagious if blisters are broken, although less so than
with primary varicella.
Feta l a n d Neonata l I nfecti o n
In women with varicella during the irst half of pregnancy, the
fetus may develop congenital varicella syndrome. Some features
include chorioretinitis, microphthalmia, cerebral cortical atro­
phy, growth restriction, hydronephrosis, limb hypoplasia, and
cicatricial skin lesions as shown in Figure 64-3 (Ahn, 20 1 6;
Auriti, 2009) . Enders and coworkers ( 1 994) evaluated 1 3 3
pregnant women with varicella. When maternal infection
developed before 1 3 weeks, only two of 472 pregnancies-O.4

F I G U R E 64-3 Atrophy of the l owe r extrem ity with bony defects
a n d sca rri ng in a fetus i nfected d u ri ng the first trimester by va ri­
cel la . (Reproduced with perm ission from Pa rya n i SG, Arvin AM:
I ntra uteri n e i nfection with va rice l l a zoster vi rus after materna l
va rice l l a, N E n g l J Med. 1 986 J u n 1 2;3 1 4(24) : 1 542- 1 546.)
percent-had neonates with congenital varicella syndrome.
he highest risk was between 1 3 and 20 weeks, during which
time seven of 35 1 exposed fetuses-2 percent-had evidence
of congenital varicella. Mter 20 weeks' gestation, the research­
ers found no clinical evidence of congenital infection. Ahn and
colleagues (20 1 6) recently described similar findings. hat said,
sporadic reports have described CNS abnormalities and skin
lesions in fetuses who developed congenital varicella in weeks
2 1 to 28 of gestation (Lamont, 2 0 1 1 a; Marin, 2007) .
If the fetus or neonate is exposed to active infection j ust
before or during delivery, and therefore before maternal anti­
body has been formed, the newborn faces a serious threat. Attack
rates range from 25 to 50 percent, and mortality rates approach
30 percent. In some instances, neonates develop disseminated
visceral and CNS disease, which is commonly fatal. For this rea­
son, varicella-zoster immune globulin (VZIG) should be adminis­
tered to neonates born to mothers who have clinical evidence of
varicella 5 days before and up to 2 days ater delivery.
Diagnosis
Maternal varicella is usually diagnosed clinically. Infection may
be confirmed by NAAT of vesicular fluid, which is very sensi­
tive. The virus may also be isolated by scraping the vesicle base
during primary infection and performing a Tzanck smear, tis­
sue culture, or direct luorescent antibody testing. Congenital
varicella may be diagnosed using NAAT analysis of amnionic
luid, although a positive result does not correlate well with
the development of congenital infection (Mendelson, 2006) . A
detailed anatomical sonographic evaluation performed at least
5 weeks after maternal infection may disclose abnormalities,
but the sensitivity is low (Mandelbrot, 20 1 2) .
M a n a g ement
Maternal Vira l Exposure. Several aspects of maternal VZV expo­
sure and infection in pregnancy afect management. Exposed
gravidas with a negative history for chickenpox should undergo
I n fectious D i sea ses 1 21 3
VZV serological testing. At least 70 percent of these women will
be seropositive, and thus immune. Exposed pregnant women
who are susceptible (seronegative) should be given varicella-zos­
ter immune globulin (VariZIG). Although best given within 96
hours of exposure, its use is approved for up to 10 days to pre­
vent or attenuate varicella infection (Centers for Disease Control
and Prevention, 20 1 2, 20 1 3d) . Passive immunization appears
to be highly efective Qespersen, 20 1 6) . In women with known
history of varicella, VariZIG is not indicated.
Materna l I nfection. Any patient dianosed with primay varicella
inection or herpes zoster should be isolatedrom pregnant women.
Because VZV pneumonia often presents with few symptoms,
a chest radiograph is recommended by many. Most women
require only supportive care, but those who require intravenous
(IV) luids and especially those with pneumonia are hospital­
ized. IV acyclovir therapy is given to women requiring hospital­
2
ization-500 mg/m or 1 0 to 1 5 mg/kg every 8 hours.
Vaccination. An attenuated live-virus vaccine is recommended
for nonpregnant adolescents and adults with no history of vari­
cella. Two doses of Varivax are given 4 to 8 weeks apart, and the
seroconversion rate is 98 percent (Marin, 2007) . Importantly,
vaccine-induced immunity diminishes over time, and the
breakthrough infection rate approximates 5 percent at 1 0 years
(Chaves, 2007) .
The vaccine is not recommended or pregnant women or or
those who may become prenant within a month olowing each
vaccine dose. That said, a registry of more than 1 000 vaccine­
exposed pregnancies reports no cases of congenital varicella syn­
drome or other associated congenital malformations (Marin,
20 1 4; Wilson, 2008). he attenuated vaccine virus is not
secreted in breast milk. hus, postpartum vaccination should
not be delayed because of breastfeeding (American College of
Obstetricians and Gynecologists, 20 1 6c) .
• I nfluenza Virus
hese respiratory infections are caused by members of the
family Orthomyxoviridae. Inluenza A and B form one genus
of these RNA viruses, and both cause epidemic human disease
(Cohen, 20 1 5b) . Inluenza A viruses are subclassiied further
by hemagglutinin (H) and neuraminidase (N) surface antigens.
Inluenza outbreaks occur annually, and the most recent epi­
demic was in 20 1 6 to 20 1 7 caused by an inluenza A/H3N2
strain (Shang, 20 1 6) .
Mate r n a l a n d Feta l I nfection
Fever, dry cough, and systemic symptoms characterize this
infection, which usually is not life-threatening in otherwise
healthy adults. However, pregnant women appear to be more
susceptible to serious complications, particularly pulmonary
involvement (Cohen, 2 0 1 5b; Mertz, 20 1 7; Rasmussen, 2 0 1 2) .
Severe infection has a maternal mortality rate o f 1 percent
(Duryea, 20 1 5) . And from 2009 to 20 1 0, widespread inluenza
A infection afected pregnant women and caused 1 2 percent of
pregnancy-related deaths (Callaghan, 20 1 5) .
N o firm evidence links inluenza A virus and congeni­
tal malformations (Irving, 2000; Zerbo, 20 1 7) . Conversely,
1 214 Medical a n d S u rg i ca l C o m p l ications
TABLE 64-2. O utpatient I nfl uenza A a n d B Virus
Testi ng Methods
Methoda Test Time
Viral cel l c u lt u re 3-1 0 d
R a p i d ce l l c u l t u re 1 -3 d
D i rect (DFA) or i n d i rect (I FA) fl u o resce nt 1 -4 h r
a n t i body a ssay
RT-PCR and other m o lecu l a r assays 1 -6 h r
R a p i d i nfl uenza d iag nostic tests (RI DT) < 30 m i n
a N a so p h a ryngea l or t h roat swa b.
RT-PCR = reverse tra n scription-polym e rase c ha i n reaction .
Data fro m Ce nters for D i sease Control a nd P revention,
2 0 1 7e.
Lynberg and colleagues ( 1 994) reported higher rates of neural­
tube defects in neonates born to women with inluenza early
in pregnancy. his was possibly associated with hyperthermia.
Viremia is infrequent, and transplacental passage is rare (Ras­
mussen, 20 1 2) . Stillbirth, preterm delivery, and irst-trimester
abortion have all been reported, but usually correlate with the
severity of maternal infection (Centers for Disease Control and
Prevention, 20 1 1 ; Fell, 20 1 7; vleijer, 20 1 5) .
Inluenza may b e detected i n nasopharyngeal swabs using
viral antigen rapid detection assays (Table 64-2) . Reverse tran­
scriptase-polymerase chain reaction (RT-PCR) is the more sen­
sitive and specific test, although not widely available (Cohen,
20 1 5 b) . In contrast, rapid influenza diagnostic tests (RIDTs)
are least indicative, with sensitivities of 40 to 70 percent. Deci­
sions to administer antiviral medications or inluenza treatment
or chemoprophylaxis should be based on clinical symptoms and epi­
demiologicalactors. Specifically, the start of therapy should not
be delayed pending testing results (Centers for Disease Control
and Prevention, 20 1 7 e) .
Management
Two classes of antiviral medications are currently available.
Neuraminidase inhibitors are highly efective for the treatment
of early inluenza A and B. hese include oseltamivir (Tamilu) ,
which is taken orally for treatment and for chemoprophylaxis;
zanamivir (Relenza) , which is inhaled for treatment; and pera­
mivir (Rapivab), which is administered intravenously.
he adamantanes include amantadine and rimantadine,
which were used for years for treatment and chemoprophylaxis
of inluenza A. In 2005, inluenza A resistance to adamantine
was reported to exceed 90 percent in the United States. hus,
its use is not currently recommended. It is possible that these
drugs may again be efective for subsequently mutated strains.
Patterns of resistance are available at cdc.gov/flu.
Experience with all of these antiviral agents in pregnant
women is limited (Beau, 20 1 4; Beigi, 20 1 4; Dunstan, 20 1 4) .
hey are Food and Drug Administration category C drugs and
thus used when potential benefits outweigh risks. At Parkland
Hospital, we start oral oseltamivir treatment within 48 hours
of symptom onset-75 mg twice daily for 5 days. Early admin­
istration may reduce length of hospital stays (Meijer, 20 1 5;
Oboho, 20 1 6) . Prophylaxis with oseltamivir, 75 mg orally once
daily for 7 days, is also recommended for signiicant exposures.
Antibacterial medications are added when a secondary bacterial
pneumonia is suspected (Chap. 5 1 , p. 993) .
Va cci nation
Efective vaccines are formulated annually. Vaccination against
inluenza throughout the influenza season, but optimally
in October or November, is recommended by the Centers
for Disease Control and Prevention (CDC) (20 1 3a) and the
American College of Obstetricians and Gynecologists (20 1 6b)
for all women who will be pregnant during the influenza sea­
son. his is especially important for those afected by chronic
medical disorders such as diabetes, heart disease, asthma, or
human immunodeficiency virus (HIV) infection. Inactivated
vaccine prevents clinical illness in 70 to 90 percent of healthy
adults. Importantly, there is no evidence of teratogenicity or
other adverse maternal or fetal events (Chambers, 20 1 6; Fell,
20 1 7; Kharbanda, 20 1 7; Polyzos, 20 1 5; Sukumaran, 20 1 5) .
Moreover, for mothers vaccinated during pregnancy, several
studies found lower rates of influenza in their infants up to
6 months of age (Nunes, 20 1 7; Steinhof, 20 1 2; Zaman,
2008) . Immunogenicity of the trivalent inactivated seasonal
inluenza vaccine in pregnant women is similar to that in the
nonpregnant individual. A live attenuated influenza virus vac­
cine is available for intranasal use but is not recommended for
pregnant women (Cohen, 20 1 5b).
• Mumps Virus
his uncommon adult infection is caused by an RNA para­
myxovirus. Because of childhood immunization, up to 90
percent of adults are seropositive (Rubin, 20 1 2) . The virus
primarily infects the salivary glands but also may involve the
gonads, meninges, pancreas, and other organs. It is transmitted
by direct contact with respiratory secretions, saliva, or through
fomites. Most transmission occurs before and within 5 days
of parotitis onset, and droplet isolation is recommended dur­
ing this time (Kutty, 20 1 0) . Treatment is symptomatic, and
mumps during pregnancy is no more severe than in nonpreg­
nant adults.
Women who develop mumps in the fi r st trimester may have
a greater risk of spontaneous abortion. Infection in pregnancy is
not associated with congenital malformations, and fetal infec­
tion is rare (McLean, 20 1 3) .
h e live attenuated J eryl-Lynn vaccine strain is part of the
MMR vaccine-measles, mumps, and rubella. This vaccine is
contraindicated in pregnancy according to the CDC (McLean,
20 1 3) . No malformations attributable to MMR vaccination
in pregnancy have been reported, but pregnancy should be
avoided for 30 da) s after mumps vaccination. The vaccine may
be given to susceptible women postpartum, and breastfeeding
is not a contraindication.
• Measles Virus
his is a highly contagious RNA virus of the family Paramyxo­
viridae that only infects humans. I n endemic areas, annual out­
breaks of measles, also called rubeola, occur in late winter and
early spring, transmission is primarily by respiratory droplets,

and the secondary attack rate among contacts exceeds 90 per­
cent (Rainwater-Lovett, 20 1 5). Resurgences in measles have
been linked to clusters of vaccine-eligible but unvaccinated
individuals (Fiebelkorn, 20 1 0; Phadke, 20 1 6) . Fever, coryza,
conjunctivitis, and cough are typical symptoms. he charac­
teristic erythematous maculopapular rash develops on the face
and neck and then spreads to the back, trunk, and extremities.
Koplik spots are small white lesions with surrounding erythema
found within the oral cavity. Immediate or delayed neurologi­
cal sequelae of measles may manifest in several forms, making
diagnosis diicult (Buchanan, 20 1 2; Chiu, 20 1 6) . Diagnosis
of acute infection is most commonly performed by serological
evidence of IgM antibodies, although RT-PCR tests are avail­
able. Treatment is supportive.
Pregnant women without evidence of measles immunity
should be administered passive immunoprophylaxis with
immune globulin, 400 mg/kg intravenously (Centers for Dis­
ease Control and Prevention, 20 1 7d) . Active vaccination is not
performed during pregnancy, however, susceptible women can
be vaccinated routinely postpartum, and breastfeeding is not
contraindicated (Ohji, 2009) .
he virus does not appear to be teratogenic (Siegel, 1 973) .
However, rates o f spontaneous abortion, pre term delivery, and
low-birthweight neonates are increased with maternal measles
(Rasmussen, 20 1 5) . If a woman develops measles shortly before
birth, risk of serious infection developing in the neonate is con­
siderable, especially in a preterm neonate.
• Rubella Virus
his RNA togavirus causes rubella, also called German measles,
which is of minor importance in the absence of pregnancy.
Rubella inection in the irst trimester, however, poses signicant
risk or abortion and severe congenital maormations. T ransmis­
sion occurs via nasopharyngeal secretions, and the transmission
rate is 80 percent to susceptible individuals. he peak incidence
is late winter and spring in endemic areas (Lambert, 20 1 5) .
Maternal rubella i s usually a mild febrile illness with a general­
ized maculopapular rash beginning on the face and spreading to
the trunk and extremities. hat said, 25 to 50 percent of infec­
tions are asymptomatic. Other symptoms may include arthralgias
or arthritis, head and neck lymphadenopathy, and conjunctivitis.
he incubation period is 12 to 23 days. Viremia usually precedes
clinical signs by about a week, and adults are infectious during
viremia and through 7 days after the rash appears. Up to half of
maternal infections are subclinical despite viremia that may cause
devastating fetal infection (McLean, 20 1 3) .
D i a g nosis
Rubella virus may be isolated from the urine, blood, naso­
pharynx, and cerebrospinal fluid for up to 2 weeks after rash
onset. The diagnosis is usually made, however, with serological
analysis. In one study, 6 percent of nonimmune women sero­
converted to rubella virus during pregnancy (Hutton, 20 1 4) .
Specific IgM antibody can b e detected using enzyme-linked
immunoassay for 4 to 5 days after onset of clinical disease,
but antibody can persist for up to 6 weeks after appearance of
the rash. Importantly, rubella virus reinfection can give rise to
I nfect i o u s D i s ea ses 1215
transient low levels of IgM . With this, fetal infection can rarely
occur, but no adverse fetal efects have been described. S erum
IgG antibody titers peak 1 to 2 weeks after rash onset. his
rapid antibody response may complicate serodiagnosis unless
samples are initially collected within a few days after the onset
of the rash. If, for example, the fi r st specimen was obtained 1 0
days after the rash, detection o f IgG antibodies would fail to
diferentiate between very recent disease and preexisting i mmu­
nity to rubella. IgG avidity testing is performed concomitant
with the serological tests above. High-avidity IgG antibodies
indicate an infection at least 2 months in the past.
Feta l Effects
The rubella virus is one of the most complete teratogens, and
efects of fetal infection are worst during organogenesis (Adams
Waldorf, 20 1 3) . Pregnant women with rubella and a rash dur­
ing the first 1 2 weeks of gestation have an afected fetus with
congenital infection in up to 90 percent of cases (Miller, 1 982) .
At 1 3 to 1 4 weeks' gestation, this incidence is 50 percent, and
by the end of the second trimester, it is 25 percent. Defects are
rare after 20 weeks' gestation. Features of congenital rubella syn­
drome amenable to prenatal diagnosis are cardiac septal defects,
pulmonary stenosis, microcephaly, cataracts, microphthalmia,
and hepatosplenomegaly (Yazigi, 20 1 7) . Other abnormalities
include sensorineural deafness, intellectual disability, neona­
tal purpura, and radiolucent bone disease. Neonates born with
congenital rubela may shed the virus or many months and thus
be a threat to other inants and to susceptible adults who contact
them. Reports of delayed morbidities associated with congenital
rubella syndrome may include a rare, progressive panencepha­
litis, insulin-dependent diabetes mellitus, and thyroid disorders
(Sever, 1 985; Webster, 1 998) .
M a n a g e m ent a nd Preve ntion
here is no speciic treatment for rubella. Droplet precautions for
7 days after the onset of the rash are recommended. Postexposure
passive immunization with polyclonal immunoglobulin may be
of benefit if given within 5 days of exposure (Young, 20 1 5) .
Although large epidemics of rubella have virtually disap­
peared in the United States because of immunization, up to
1 0 percent of women in the United States are susceptible.
Cluster outbreaks during the 1 990s mainly involved p ersons
born outside the United States, as congenital rubella is still
common in developing nations (Centers for Disease Control
and Prevention, 20 1 3f) . To eradicate rubella and prevent
congenital rubella syndrome completely, a comprehensive
approach is recommended for immunizing the adult popula­
tion (Grant, 20 1 5) .
MMR vaccine should b e ofered to nonpregnant women
of childbearing age who do not have evidence of immunity
whenever they make contact with the health-care system. Vac­
cination of all susceptible hospital personnel who might be
exposed to patients with rubella or who might have contact
with pregnant women is important. Rubella vaccination should
be avoided 1 month before or during pregnancy because the
vaccine contains attenuated live virus. No observed evidence
links the vaccine and induced malformations, although the
overall theoretical risk is up to 2.6 percent (McLean, 20 1 3;
1 21 6 Med ica l a n d S u rg ical Co m p l ications
Swamy, 20 1 5) . MMR vaccination is not an indication for preg­
nancy termination.
Prenatal serological screening for rubella is indicated for all
pregnant women. Women found to be nonimmune are ofered
the MMR vaccine postpartum.
• Respiratory Viruses
More than 200 antigenically distinct respiratory viruses cause
the cominon cold, pharyngitis, laryngitis, bronchitis, and pneu­
monia. Rhinovirus, coronavirus, and adenovirus are major
causes of the common cold. The RNA-containing rhinovirus
and coronavirus usually produce a trivial, self-limited illness
characterized by rhinorrhea, sneezing, and congestion. he
DNA-containing adenovirus is more likely to produce cough
and lower respiratory tract involvement, including pneumonia.
The potential teratogenic efects of respiratory viruses are
controversial. In a case-control study using data from the Finn­
ish Register of Congenital vlalformations, 393 gravidas with
a common cold had a four- to ivefold greater risk of fetal
anencephaly (Kurppa, 1 99 1 ) . In another population study of
California births from 1 989 to 1 99 1 , low attributable risks
for neural-tube defects were associated with many illnesses in
early pregnancy (Shaw, 1 998) . Adams and colleagues (20 1 2)
performed amnionic fluid viral PCR studies in 1 1 9 1 women
undergoing amniocentesis for fetal karyotyping. Viral PCR
was positive in 6.5 percent, with adenovirus being the virus
most frequently identified. There was an association with fetal­
growth restriction, nonimmune hydrops, foot/hand abnormali­
ties, and neural-tube defects. Adenoviral infection is a known
cause of childhood myocarditis. T owbin ( 1 994) and Forsnes
( 1 998) and their associates used PCR tests to identiy and link
adenovirus to fetal myocarditis and nonimmune hydrops.
• Hantavi ruses
hese RNA viruses are members of the family Bunyaviridae.
They are associated with a rodent reservoir, and transmis­
sion involves inhalation of virus excreted in rodent urine and
feces. Outbreaks of hantaviruses including Sin Nombre virus
and Seoul virus have been reported in the United States, the
most recent in early 20 1 7 (Centers for Disease Control and
Prevention, 20 1 7b) . H antaviruses are a heterogenous group of
viruses with low and variable rates of transplacental transmis­
sion. Howard and associates ( 1 999) reported the Hantavirus
pulmonay syndrome to cause maternal death, fetal demise, and
preterm birth. hey found no evidence of vertical transmission
of the causative Sin N ombre virus.
• Enteroviruses
hese viruses are a major subgroup of RNA picornaviruses
that include coxsackievirus, poliovirus, and echovirus. They
are trophic for intestinal epithelium but can also cause wide­
spread maternal, fetal, and neonatal infections that may
include the CNS , skin, heart, and lungs. Most maternal
infections are subclinical yet can be fatal to the fetus-neonate
(Tassin, 20 1 4) . Hepatitis A is an enterovirus that is discussed
in Chapter 55 (p. 1 063) .
Coxsackievirus infections with group A and B are usually
asymptomatic. Symptomatic infections-usually with group
B-include aseptic meningitis, polio-like illness, hand foot and
mouth disease, rashes, respiratory disease, pleuritis, pericardi­
tis, and myocarditis. No treatment or vaccination is available
(Cohen, 20 1 5a) . Coxsackievirus may be transmitted by mater­
nal secretions to the fetus at delivery in up to half of mothers
who seroconverted during pregnancy (Modlin, 1 988) . Trans­
placental passage has also been reported (Ornoy, 2006) .
Congenital malformation rates may be slightly increased in
fetuses of pregnant women who had serological evidence of cox­
sackievirus (Brown, 1 972) . Viremia can cause fetal hepatitis, skin
lesions, myocarditis, and encephalomyelitis, all of which may be
fatal. Some have reported higher rates of cardiac anomalies and
of low-birthweight, preterm, and small-for-gestational-age new­
borns (Chen, 20 1 0; Koro'lkova, 1 989) . Maternal-fetal infection
has been associated with massive perivillous ibrin deposition
and fetal death (Yu, 20 1 5) . Finally, a rare association between
maternal coxsackievirus infection and insulin-dependent diabe­
tes in ofspring has been described (Viskari, 20 1 2) .
Polio viruses cause highly contagious infections that are sub­
clinical or mild. he virus is trophic for the CNS, and it can
cause paralytic poliomyelitis (Cohen, 20 1 5a) . Siegel ( 1 95 5)
demonstrated that pregnant women not only were more sus­
ceptible to polio but also had a higher death rate. Perinatal
transmission has been observed, especially when maternal
infection developed in the third trimester (Bates, 1 95 5) . Inac­
tivated subcutaneous polio vaccine is recommended for sus­
ceptible pregnant women who must travel to endemic areas or
are placed in other high-risk situations. Live oral polio vaccine
has been used for mass vaccination during pregnancy without
harmful fetal efects (Harjulehto, 1 989) .
• Parvovirus
This B 1 9 virus causes erythema inectiosum, or ith disease. It is a
small, single-stranded DNA virus that replicates in rapidly pro­
liferating cells such as erythroblast precursors (Brown, 20 1 5) .
his can lead t o anemia, which i s its primary fetal efect. Only
individuals with the erythrocyte globoside membrane P antigen
are susceptible. In women with severe hemolytic anemia-for
example, sickle-cell disease-parvovirus infection may cause an
aplastic crisis.
The main mode of parvovirus transmission is respiratory
or hand-to-mouth contact, and the infection is common in
spring months. The maternal infection rate is highest in women
with school-aged children and in day-care workers, but not
in schoolteachers. An infected person develops viremia 4 to
14 days after exposure, and an otherwise immunocompetent
individual is no longer infectious at the onset of the rash. By
adulthood, only 40 percent of women are susceptible. The
annual seroconversion rate is 1 to 2 percent but is > 10 percent
during epidemic periods (Brown, 20 1 5) . The secondary attack
rate approaches 50 percent.
Mate r n a l I nfection
In 20 to 30 percent of adults, infection is asymptomatic. Fever,
headache, and flulike symptoms may begin in the last few days

of the viremic phase. Several days later, a bright red rash with
erythroderma afects the face and gives a slapped-cheek appear­
ance. The rash becomes lacelike and spreads to the trunk and
extremities. Adults often have milder rashes and develop sym­
metrical polyarthralgia that may persist several weeks. Mayama
and associates (20 1 4) described a pregnant woman in whom
B 1 9 infection was associated with hemophagocytic lympho­
histiocytosis. No evidence suggests that parvovirus infection is
altered by pregnancy. With recovery, IgM antibody is gener­
ated 7 to 1 0 days postinfection, and production persists for
3 to 4 months. Several days after IgM is produced, IgG anti­
body is detectable and persists for life with natural immunity
(American College of Obstetricians and Gynecologists, 20 1 7) .
Feta l I nfection
here is vertical transmission to the fetus in up to a third of
maternal parvovirus infections (de long, 20 1 1 ; Lamont, 20 1 1 b).
Fetal infection has been associated with abortion, nonimmune
hydrops, and stillbirth (Lassen, 20 1 2; Mace, 20 14; McClure,
2009) . According to the American College of Obstetricians and
Gynecologists (20 1 7) , the rate of fetal loss with serologically
proven parvovirus infection is 8 to 1 7 percent before 20 weeks'
gestation, and 2 to 6 percent after midpregnancy. Currently,
no data support evaluating asymptomatic mothers and stillborn
fetuses for parvovirus infection.
Hydrops develops in only approximately 1 percent of
fetuses of women infected with parvovirus (American College
of Obstetricians and Gynecologists, 20 1 7; Pasquini, 20 1 6;
Puccetti, 20 1 2) . Still, it is the most frequent infectious agent
of nonimmune hydrops in autopsied fetuses (Rogers, 1 999) .
Hydrops usually stems from infection in the irst half of gesta­
tion. In one report, more than 80 percent of hydrops cases
were found in the second trimester, with a mean gestational
age of 22 to 23 weeks (Yaegashi, 2000) . At least 85 percent of
cases of fetal infection developed within 10 weeks of maternal
infection, and the mean interval was 6 to 7 weeks. he criti­
cal period for maternal infection leading to fetal hydrops was
estimated to be between 1 3 and 1 6 weeks' gestation, which
coincided with the period in which fetal hepatic hemopoiesis
is greatest.
Diag nosis a n d M a n a g e m e n t
An algorithm for diagnosis of maternal parvoviral infection
is illustrated in Figure 64 4 . Diagnosis is generally made by
maternal serological testing for speciic IgG and IgM antibodies
(Bonvicini, 20 1 1 ; Brown, 20 1 5). Viral DNA may be detectable
by PCR in maternal serum during the prodrome and persist for
months to years after infection. Fetal infection is diagnosed by
detection of B 1 9 viral DNA in amnionic luid or IgM antibod­
ies in fetal serum obtained by cordocentesis (de long, 20 1 1 ;
Weifenbach, 20 1 2) . Fetal and maternal viral loads do not pre­
dict fetal morbidity and mortality (de Haan, 2007) .
Most cases of parvovirus-associated hydrops develop in the
first 1 0 weeks after infection. Thus, serial sonography every
2 weeks should be performed in women with recent infection
(see Fig. 64-4) . As discussed in Chapter 1 0 (p. 2 1 4) , middle
cerebral artery (MCA) Doppler interrogation can also be used
to predict fetal anemia (Chauvet, 20 1 1 ) . Fetal blood sampling
I nfecti ous D i s ea ses 1217
is warranted with hydrops to assess the degree of fetal anemia.
Comorbid fetal myocarditis may induce hydrops with lesser
degrees of anemia.
Depending on gestational age, fetal transfusion for hydrops
may improve outcome in some cases (Enders, 2004) . Mortal­
ity rates as high as 30 percent have been reported in hydropic
fetuses without transfusions. With transfusion, 94 percent of
hydrops cases resolve within 6 to 1 2 weeks, and the overall
mortality rate is < 1 0 percent. Most fetuses require only one
transfusion because hemopoiesis resumes as infection resolves.
Concurrent fetal thrombocytopenia worsens the prognosis
(Melamed, 20 1 5) .
Lon g -Term Prog nosis
Reports describing neurodevelopmental outcomes in fetuses
transfused for B 1 9 infection-induced anemia are conlicting. In
one review of 24 transfused hydropic fetuses, abnormal neuro­
development was noted in ive of 16 survivors-32 percent-at
6 months to 8 years (Nagel, 2007) . Outcomes were not related
to severity of fetal anemia or acidemia, and these investigators
hypothesized that the infection itself induced cerebral dam­
age. In another study of 28 children treated with intrauterine
transfusion, 1 1 percent had neurodevelopmental impairment
during evaluation at a median age of 5 years (de long, 2 0 1 2) .
Conversely, Dembinski (2003) found n o signiicant neurode­
velopmental delay despite severe fetal anemia.
Prevention
Currently, no parvovirus vaccine is available, and no evidence
suggests that antiviral treatment prevents maternal or fetal
infection. Decisions to avoid higher-risk work settings are com­
plex and require assessment of exposure risks. Pregnant women
should be counseled that risks for infection approximate 5
percent for casual, infrequent contact; 20 percent for intense,
prolonged work exposure such as for teachers; and 50 percent
for close, frequent interaction such as in the home. Workers at
day-care centers and schools need not avoid infected children
because infectivity is greatest before clinical illness. Finally,
infected children do not require isolation.
• West Nile Virus
This mosquito-borne RNA flavivirus is a human neuropatho­
gen. It has become the most common cause of arthropod-borne
viral encephalitis in the United States (Centers for Disease
Control and Prevention, 20 1 7f; Krow-Lucal, 20 1 7) . West Nile
viral infections are typically acquired through mosquito bites in
late summer or perhaps through blood transfusion. The incu­
bation period is 2 to 14 days, and most persons have mild or
no symptoms. Fewer than 1 percent of infected adults develop
meningoencephalitis or acute laccid paralysis (Granwehr,
2004) . Presenting symptoms may include fever, mental s tatus
changes, muscle weakness, and coma (Stewart, 20 1 3) .
Diagnosis o f West Nile infection i s based o n clinical symp­
toms and the detection of viral IgG and IgM in serum and IgM
in cerebrospinal fluid. There is no known efective antiviral
treatment, and management is supportive. he primary strat­
egy for preventing exposure in pregnancy is the use of insect
1 21 8 Med i ca l a n d S u rg ica l Co m pl ication s

Clinical disease:
Exposu re to rash, pruritis, headache, fever, pharyngitis, Nonimmune
parvovirus 81 9 arthralgias, myalgias, joint swelling, nausea, hydrops fetalis
anorexia, transient aplastic crisis

______.
.-
!
Maternal serological testing: -______�
parvovirus 81 9 IgM and IgG

I
IgG (+)
J !
IgG (-)
!
IgG (-)
l
IgG (+)
IgM (-) IgM (-) IgM (+) IgM (+)

! !
Prior Repeat test
infection in 2-4 weeks

I mmune
1 ｾ＠
IgG (-) IgG (+/-) ____ .
. Recent parvovirus
no further
IgM (-) IgM (+) 81 9 i nfection
evaluation

!
Not infected;
!
Targeted ultrasound
no further +/- MCA velocimetry every
evaluation 2 weeks for 1 0 weeks after
exposure or infection
Sonographic evidence of fetal
infection: hydrops fetalis,
hepatomegaly, splenomegaly, ..
.-------.I
. I
placentomegaly, elevated
MCA peak systolic velocity

I
J
Yes
l
No

!
Cordocentesis for
!
No further evaluation;
C8C, reticulocyte count, notify pediatric
parvovirus 8 1 9 RNA (PCR); service at delivery
consider intrauterine
transfusion

F I G U R E 64-4 Algorith m for eva l uatio n a n d m a n agement of h u m a n pa rvovirus B 1 9 i nfection in preg nancy. eBe = com plete blood cou nt;
IgG = i m m u noglobu l i n G; IgM = i m m u n og l o b u l i n M; MeA = m i d d l e cerebra l a rtery; peR = polymera se c h a i n reaction; RNA = ribo n ucleic
acid.

repellant containing ,N-diethyl-m-toluamide (DEET) . This is
considered safe for use among pregnant women (Wylie, 20 1 6) .
Avoiding outdoor activity and stagnant water and wearing pro­
tective clothing are also recommended.
Adverse efects of West Nile viremia on pregnancy are
unclear. Animal data suggest that embryos are susceptible, and
a case report of human fetal infection at 27 weeks' gestation
described chorioretinitis and severe temporal and occipital lobe
leukomalacia (Alpert, 2003; Julander, 2006) . In 77 maternal
infections initially reported to the West Nile Virus Pregnancy
Registry, there were four miscarriages, two elective abortions,
and 72 live births, 6 percent of which were preterm (O'Leary,
2006) . Three of these 72 newborns were shown to have West
Nile infection, and it could not be established conclusively that
infection was acquired congenitally. Of three major malforma­
tions possiby associated with viral infection, none was deini­
tively conirmed. Similar conclusions were reached by Pridjian
and colleagues (20 1 6) , who analyzed data from the CDC

West Nile Virus Registry. Transmission of West Nile virus
through breastfeeding is rare.
• Coronavirus I nfections
hese are single-stranded RNA viruses that are prevalent world­
wide. In 2002, an especially virulent strain of coronavirus­
severe acute respiratory syndrome (SARS-Co 1 was irst noted in
China. It rapidly spread throughout Asia, Europe, and North
and South America. he case-fatality rate approached 1 0 percent
in the nonpregnant population and was as high as 25 percent in
pregnant women (Lam, 2004; Wong, 2004) . Although no addi­
tional cases have been conirmed since 2004, the CDC (20 1 3b)
now lists SARS-CoV as a "select agent" that has the potential to
pose a severe threat to public health and safety.
Another novel regional coronavirus with a high case-fatality
rate was detected in 20 1 2-Middle East respiratory syndrome
coronavirus eMERS-Co ) (Arabi, 20 1 7) . Although experience
with MERS-Co V is sparse in pregnancy, infection has been
reported to cause maternal and perinatal deaths (Assiri, 20 1 6) .
• Ebola Virus
A member of the RNA Filoviridae family, the Ebola virus is
transmitted by direct person-to-person contact (Kuhn, 20 1 5) .
Infection produces a severe hemorrhagic fever with pronounced
immunosuppression and disseminated intravascular coagulopa­
thy. Treatment is supportive, and the mortality rate approaches
50 percent.
Data are few concerning Ebola viral infection in pregnancy
(Beigi, 20 1 7; Money, 20 1 5 ; Oduyebo, 20 1 5) . The CDC con­
cludes that pregnant women are at increased risk for severe
illness and death a amieson, 20 1 4) . hat said, no evidence
suggests that pregnant women are more susceptible to Ebola
virus infection. One report described trophoblast infection
(Muehlenbachs, 20 1 7) .
• Zika Virus
This RNA virus of the Flavivirdae family has recently been
recognized as the first major mosquito-borne teratogen (Ras­
mussen, 20 1 6) . Although Zika virus is primaril) transmitted
by mosquito bite, sexual transmission is also possible, and the
virus may be detected in body fluids for months following acute
infection (Hills, 20 1 6; Joguet, 20 1 7; Paz-Bailey, 20 1 7) .
Mate r n a l-Feta l I nfection
Reminiscent of the rubella epidemic in the 1 960s, in adults
Zika infection may be asymptomatic or cause mild symptoms
of rash, fever, headache, arthralgia, and conjunctivitis lasting a
few days. Virus is typically detectable in blood around the time
of symptom onset and may persist days to months in preg­
nant women (Driggers, 20 1 6; Meaney-Delman, 20 1 6) . Serum
IgM antibodies typically become detectable within the first
two weeks after symptom onset and remain a median of four
months (Oduyebo, 20 1 7) . Rarely, Guillain-Barre syndrome
may develop following infection (da Silva, 20 1 7; Parra, 20 1 6) .
The fetus can b e severely infected whether o r not the
mother is symptomatic. Honein and coworkers (20 1 7) describe
I nfectious D i s ea ses 1 219
F I G U R E 64-5 Sonogra p h i c tra nsverse view of the cra n i u m fro m
a fetus with congen ita l Z i ka i n fection. F i n d i ngs s h own i n c l u d e a
t h i n cerebra l cortex, increased extraaxia l space (, d i l ated ventricles
(F,), and a bsent cavum sept u m pe l l ucid u m . (Re p rod uced with
perm ission from Driggers RW, Ho (Y, Korhonen EM, et al: Z i ka virus
i nfection with prolonged mate rn a l viremia a n d fetal b ra i n a b n o r­
m a l ities, N E n g l J Med. 2 0 1 6 J u n 2;374(22):2 1 42-2 1 5 1 .)
a 6-percent overall fetal infection rate. In one report of 1 34
women with positive RT-PCR results, fetal mortality was
7 percent (Brasil, 20 1 6) . Among live births, the rate of fetal
birth defects ranges from 5 percent-among women with pos­
sible Zika infection-to 1 5 percent among pregnant women
with laboratory-confirmed infection in the irst trimester (Reyn­
olds, 20 1 7) . In the most severely afected fetuses, a congenital
Zika syndrome has been described that includes microcephaly,
lissencephaly, ventriculomegaly, intracranial calcifi c ations, ocu­
lar abnormalities, and congenital contractures (Honein, 2 0 1 7;
Moore, 20 1 7; Soares de Oliveira-Szejnfeld, 20 1 6) . Sonographic
findings from a Zika-infected fetus are shown in Figure 64-5 .
D i a g nosis a n d M a n a g e ment
Diagnosis of this infection in pregnant women is made with
detection of Zika virus RNA in blood or urine or by serological
testing. Detection of Zika virus RNA by PCR confirms infec­
tion. Serological assays for Zika IgM antibodies may cross react
with other flaviviruses. Thus, a positive assay result is followed by
another assay containing virus-specific neutralizing antibodies
(Oduyebo, 20 1 7) . Testing recommendations and interpreta­
tion have evolved for pregnant women who are symptomatic
and those who are asymptomatic but have ongoing exposure
risk. his risk includes living in or traveling to an area with
active local transmission. Large-scale screening programs have
been described to identiy women at high risk for travel­
associated Zika infection (Adhikari, 20 1 7) .
Currently, n o specific treatment o r vaccine is available for
Zika infection, although several vaccine candidates are in devel­
opment (Beigi, 20 1 7; World Health Organization, 20 1 7) . Pro­
phylaxis includes protective netting and insect spray to control
the vector mosquito and avoidance of sexual contact with part­
ners recently exposed. he CDC has established a pregnancy
hotline (770-488-7 1 00) and U.S. Zika Pregnanc) Registry
1 220 Med ica l a n d S u rg ica l Co m pl i cat i o n s
(ZikaPregnancy@cdc.gov) for clinicians with concerns related
to management of women with Zika infection or exposure.
BACTERIAL I N F ECTIONS
• G roup A Streptococcus
Infections caused by Streptococcus pyogenes are important in
pregnant women. his organism is the most frequent bacterial
cause of acute pharyngitis and is associated with several sys­
temic and cutaneous infections. S pyogenes produces numerous
toxins and enzymes responsible for its local and systemic tox­
icity. Pyrogenic exotoxin-producing strains are usually associ­
ated with severe disease (Shinar, 20 1 6; Wessels, 20 1 5) . In most
cases, streptococcal pharyngitis, scarlet fever, and erysipelas are
not life threatening. Treatment, usually with penicillin, is simi­
lar in pregnant and nonpregnant women.
In the United States, Spyogenes infrequently causes puerperal
infection. Still, it remains the most common cause of severe
maternal postpartum infection and death worldwide, and the
incidence of these infections is rising (Deutscher, 20 1 1 ; Ham­
ilton, 2 0 1 3; Wessels, 20 1 5) . Puerperal infections are discussed
in detail in Chapter 37. he early 1 990s saw the emergence of
streptococcal toxic shock syndrome, manifested by hypotension,
fever, and evidence of multiorgan failure with associated bactere­
mia. Group A puerperal sepsis is seriously complicated in 20 per­
cent of cases (Shinar, 20 1 6) . The case-fatality rate approximates
30 percent, and morbidity and mortality rates are improved
with early recognition. Treatment includes clindamycin plus
penicillin therapy and often surgical debridement (Chapter 47,
p. 924). No vaccine for group A streptococcus is commercially
available.
• G roup B Streptococcus
Streptococcus agalactiae is a group B organism that can be found
to colonize the gastrointestinal and genitourinary tract in 1 0 to
25 percent of pregnant women (Kwatra, 20 1 6) . Throughout
pregnancy, group B Streptococcus (GBS) is isolated in a tran­
sient, intermittent, or chronic fashion. Although the organism
is most likely always present in these same women, their isola­
tion is not always homologous.
Mate r n a l a n d Pe ri n ata l I nfecti o n
he spectrum of maternal and fetal G BS efects ranges from
asymptomatic colonization to septicemia. S agalactiae has been
implicated in adverse pregnancy outcomes that include preterm
labor, prematurely ruptured membranes, clinical and subclini­
cal chorioamnionitis, and fetal infections (Randis, 20 1 4) . GBS
can also cause maternal bacteriuria, pyelonephritis, osteomyeli­
tis, postpartum mastitis, and puerperal infections. It remains
the leading infectious cause of morbidity and mortality among
infants in the United States (Centers for Disease Control and
Prevention, 20 1 0; Schrag, 20 1 6) .
Neonatal sepsis has received the most attention due t o its
devastating consequences and available efective preventative
measures. Infection <7 days after birth is deined as eary-onset
disease and is seen in 0.2 1 / 1 000 live births (Centers for Dis­
ease Control and Prevention, 20 1 5) . Many investigators use a
threshold of < 72 hours of life as most compatible with intra­
partum acquisition of disease (Stoll, 2 0 1 1 ) . We and others have
also encountered unexpected intrapartum stillbirths from GBS
infections (Nan, 20 1 5) . Tudela and associates (20 1 2) reported
that newborns with early-onset CBS infection often had clini­
cal evidence of fetal infection during labor or at delivery.
In many neonates, septicemia involves signs of serious ill­
ness that usually develop within 6 to 1 2 hours of birth. These
include respiratory distress, apnea, and hypotension. At the
outset, therefore, neonatal infection must be diferentiated
from respiratory distress syndrome caused by insuicient sur­
factant production (Chap. 34, p. 636) . he mortality rate with
early-onset disease has declined to approximately 4 percent,
and preterm newborns are disparately afected.
Late-onset disease caused by GBS is noted in 0.32 per 1 000
live births and usually manifests as meningitis 1 week to 3
months after birth (Centers for Disease Control and Preven­
tion, 20 1 5) . he mortality rate, although appreciable, is less for
late-onset meningitis than for early-onset sepsis. Unfortunately,
it is not uncommon for surviving infants of both early- and
late-onset disease to exhibit devastating neurological sequelae.
Pro p hylaxis for Peri nata l I nfect i o n s
As GBS neonatal infections evolved beginning in the 1 970s
and before widespread intrapartum chemoprophylaxis, rates of
early-onset sepsis ranged from 2 to 3 per 1 000 live births. By
20 1 0, these outcomes led to a policy of universal rectovaginal
culture screening for GBS at 35 to 37 weeks' gestation fol­
lowed by intrapartum antibiotic prophylaxis for women identi­
fied to be carriers. hese outcomes stimulated development of
expanded laboratory identiication criteria for GBS; updated
algorithms for screening and intrapartum chemoprophylaxis
for women with preterm prematurely ruptured membranes,
preterm labor, or penicillin allergy; and described new dosing
for penicillin G chemoprophylaxis. Following these changes,
the incidence of early-onset G BS neonatal sepsis decreased to
0.2 1 cases per 1 000 live births by 20 1 5 (Centers for Disease
Control and Prevention, 20 1 5) .
hus, during the past three decades, several strategies have
been proposed to prevent perinatal acquisition of GBS infec­
tions. These strategies have not been compared in random­
ized trials and are either culture-based or risk-based guidelines
(Ohlsson, 20 1 4) . hese methods have been adopted in the
United States, but not all European countries have guidelines
(Di Renzo, 20 1 5) .
Cultu re-Based Prevention. h e CDC (20 1 0) GBS guidelines
recommend a culture-based approach, which was also adopted
by the American College of Obstetricians and Gynecologists
(20 1 6e) . Shown in Figure 64-6, this strategy is designed to
identiy women who should be given intrapartum antimicro­
bial prophylaxis. Women are screened for GBS colonization at
35 to 37 weeks' gestation, and intrapartum antimicrobials are
given to women with rectovaginal GBS-positive cultures. Selec­
tive enrichment broth followed by subculture improves detec­
tion. In addition, more rapid techniques such as DNA probes
and NAATs are being developed (Helali, 20 1 2) . A previous
sibling with GBS invasive disease and identiication of GBS
 I nfectious Di seases 1 22 1

Vaginal and rectal G B S screening cultures at 35-37 weeks' gestation for ALL
pregnant women (unless patient had GBS bacteriuria du ring the current
pregnancy or a previous infant with i nvasive GBS disease)

Intrapartu m Intrapartum
prophylaxis indicated prophylaxis not indicated

•
Previous infant with invasive G BS
disease
•
GBS bacteriuria during current
pregnancy
•
Positive G BS screening culture
during current pregnancy (unless
a planned cesarean delivery, in
the absence of labor or amniotic
membrane rupture, is performed)
Unknown GBS status (culture not
done, incomplete, or results
unknown) and any of the following :
•
Previous pregnancy with a positive
G BS screening culture (unless a
culture was also positive during the
current pregnancy)
•
Planned cesarean delivery performed
in the absence of labor or membrane
rupture (regardless of maternal G B S
culture status)
•
Negative vaginal and rectal GBS
screening cultu re in late gestation
during the current pregnancy,
regardless of intrapartum risk factors

•
Delivery at < 37 weeks' gestation

•
Amnionic membrane rupture
� 1 8 hours

•
I ntrapartu m temperature
� 1 OOAoF (� 38.0°C)

•
I ntrapartum n ucleic acid
amplification test (NAAT)
positive for G BS

F I G U R E 64-6 I n d ications for i ntra pa rt u m prophylaxis to prevent peri natal g ro u p B streptococcal (GBS) d isease u nder a u n iversal prenata l
scree n i n g strategy based o n com b i n ed vag i n a l a n d rectal cu ltures obta i ned a t 3 5 t o 3 7 weeks' gestation. (From Centers for Disease Control
a nd Prevention, 2 0 1 0.)

bacteriuria in the current pregnancy are also considered indica­
tions for prophylaxis.
Risk-Based Preventi o n . This approach is recommended for
women in labor and whose GBS culture results are not known.
It relies on risk factors associated with intrapartum GBS trans­
mission. Intrapartum chemoprophylaxis is given to women
who have any of the following: delivery < 37 weeks, ruptured
membranes � 1 8 hours, or intrapartum temperature � 1 00.4°F
(�38.0°C) . Women with GBS during the current pregnancy
and women with a prior infant with invasive early-onset GBS
disease are also given chemoprophylaxis.
At Parkland Hospital in 1 995-and prior to consensus guide­
lines-we adopted and continue to use the risk-based approach
for intrapartum treatment of women at high risk. Importantly,
in addition, all term neonates who were not given intrapartum
prophylaxis were treated in the delivery room with aqueous
penicillin G, 50,000 to 60,000 units intramuscularly. Rates of
early-onset GBS sepsis decreased to 0.4 to 0.66 per 1 000 live
births (Staford, 20 1 2; Wendel, 2002) . Non-GBS early-onset
sepsis decreased from 0.66 to 0.24 per 1 000 live births (Staford,
20 1 2) . Thus, this approach has results similar to those reported
by the CDC (20 1 0) for culture-based prevention.
G B S Vac c i n e
Serotype-specific capsular antibody concentrations clinically
correlate with GBS neonatal disease. Antibody-producing
vaccines have been tested, but none are clinically available
(Donders, 20 1 6; Kobayashi, 20 1 6; Madhi, 20 1 6) .
I nt ra pa rt u m Antim icro b i a l Pro p hy la x i s
Preventive antimicrobials administered 4 or more hours
before delivery are highly efective (Fairlie, 20 1 3) . Regardless
of screening method, penicillin remains the first-line agent
1 222 Medical a n d S u rg i ca l Com p l ications

TABLE 64-3. Reg i m e n s for I nt rapart u m Ant i m icrobial Prophylaxis for Peri nata l GBS Disease
Regi men
Recom mended
Alternative
Penici l l i n a l l erg ic
Patients n ot at h i g h risk for a na p hylaxis
Patie nts at high risk for a n a phylaxis a nd with GBS
s u scepti b l e to c l i nd a myci n
Patients at h i g h ris k for a na p hylaxis a n d with GBS
resista nt to c l i nda myc i n or su scepti b i l ity u n kn ow n
Treatment
P e n i c i l l i n G, 5 m i l l io n u n its IV i n it i a l dose, then 2.5 to 3.0 m i l l io n u n its
IV every 4 h o u rs u nt i l del ivery
A m p i ci l l i n , 2 g IV i n itia l d ose, then 1 9 IV every 4 h o u rs or 2 g every
6 h o u rs u nt i l d e l ivery
Cefazo l i n , 2 9 I V i n it i a l dose, then 1 9 I V every 8 h o u rs u nt i l d e l ivery
C l i nd a myci n , 900 mg IV every 8 h o u rs u nt i l d e l ivery
Va ncomyc i n , 1 9 IV every 1 2 h o u rs u nti l del ive ry

GBS g ro u p B Streptococcus; IV
= = i ntrave n o u s.
Data from the Vera n i, 20 1 0

for prophylaxis, and ampicillin is an acceptable alternative
(T able 64-3) . Women with a penicillin allergy and no his­
tory of anaphylaxis are given cefazolin (Briody, 20 1 6) . hose
at high risk for anaphylaxis should have antimicrobial suscep­
tibility testing performed to exclude clindamycin resistance.
Clindamycin-sensitive but erythromycin-resistant isolates
should have a D-zone test performed to assess for inducible
clindamycin resistance. If clindamycin resistance is conirmed,
vancomycin should be administered. Eythromycin is no longer
usedor penicilin-alergic patients.
Further recommendations for management of spontane­
ous preterm labor, threatened preterm delivery, or preterm
prematurely ruptured membranes are shown in Figure 64-7.
Women undergoing cesarean delivery before labor onset with
intact membranes do not need intrapartum GBS chemoprophy­
laxis, regardless of GBS colonization status or gestational age.
• Methicillin-Resistant Staphylococcus aureus
Staphylococcus aureus is a pyogenic gram-positive organism and
is considered the most virulent of the staphylococcal species.
It primarily colonizes the nares, skin, genital tissues, and oro­
pharynx. Approximately 20 percent of normal individuals are
persistent carriers, 30 to 60 percent are intermittent carriers,
and 20 to 50 percent are noncarriers (Gorwitz, 2008) . Colo­
nization is considered the greatest risk factor for infection

Onset of labor or ruptu re of membranes at < 37 weeks'

gestation with significant risk for imminent preterm delivery

I
No GBS cu ltu re
I
GBS positive
I
GBS negative

! ! !
Obtain vaginal and
rectal GBS culture -
GBS
IV anti microbials
. . . for
positive
hours � 48 No GBS
prophylaxis

!
and initiate IV (during tocolysis)

48
antimicrobials

I Repeat vaginal-rectal

�
No growth at hours
GBS culture if patient
reaches 35-37 weeks
and is undelivered
Stop antimicrobials I ntrapartum
antimicrobial
prophylaxis at
delivery

F I G URE 64-7 Sa m p l e a lg orithm for prophylaxis for women with g ro u p B streptococca l (G BS) disease a n d th reatened preterm del ivery. This
algorithm is not a n excl u s ive cou rse of management, and va riatio n s that i ncorporate i nd ivid u a l c i rcu m sta nces or i n stitution a l prefere nces
may be a ppropriate. IV i ntravenous. (Ada pted from Centers for Disease Control a nd P revention, 2 0 1 6a.)
=

(Marzec, 20 1 6; Sheield, 20 1 3) . Methicillin-resistant 5 aureus
(MRSA) colonizes only 2 percent of adults but is a signiicant
contributor to the health-care burden (Gorwitz, 2008) . MRSA
infections are associated with increased cost and higher mortal­
ity rates compared with those by methicillin-sensitive 5 aureus
(NISSA) (Beigi, 2009; Butterly, 20 1 0) .
Community-acquired MRSA (CA-MRSA) i s diagnosed
when identified in an outpatient setting or within 48 hours
of hospitalization in a person without traditional risk factors.
Such risk factors include prior MRSA infection, hospitaliza­
tion, dialysis or surgery within the past year, and indwelling
catheters or devices (Dantes, 20 1 3) . Hospital-associated MRSA
(HA-MRSA) infections are nosocomial. Most cases of \1RSA
in pregnant women are CA-MRSA.
M RSA a n d P reg n a ncy
Anovaginal colonization with 5 aureus is identified in 10 to
25 percent of obstetrical patients (Top, 20 1 0) . Skin and soft
tissue infections are the most common presentation of MRSA
in pregnant women (Fig. 64-8) . Mastitis and breast abscesses
have been reported in up to a fourth of cases of MRSA compli­
cating pregnancy (Laibl, 2005 ; Lee, 20 1 0) . Perineal abscesses,
wound infections at sites such as abdominal and episiotomy
incisions, and chorioamnionitis are also associated with MRSA
(Pimentel, 2009; hurman, 2008). Finally, osteomyelitis has
been reported (Nguyen, 20 1 5 ; Tanamai, 20 1 6) .
A rise in CA-MRSA infections has been reported i n neonatal
intensive care units and newborn nurseries. In these settings,
infection is frequently associated with maternal and health-care
worker skin infections and infected breast milk. Vertical trans­
mission is rare (Jimenez-Truque, 20 1 2; Pinter, 2009).
M a n a g e m e nt
he Infectious Diseases Society of America has published
guidelines for the treatment of M RSA infections (Liu, 20 1 1 ) .
Uncomplicated supericial infections are primarily managed
by drainage and local wound care. Although historically
F I G U R E 64-8 Th is a ntepa rtu m patient p resented with mu ltiple
small m icroa bscesses for which c u l t u re identified methici l l i n ­
resista nt Staphylococcus aureus. (Used with perm ission from
Dr. Step han Shivvers.)
I nfectious D i s ea ses 1 223
de-emphasized, recent evidence suggests benefi t from antibi­
otic therapy in addition to incision and drainage of s maller
abscesses (Daum, 20 1 7; Forcade, 2 0 1 2) . Severe superficial
infections, especially those that fail to respond to local care
or those in patients with medical comorbidities, are treated
with MRSA-appropriate antibiotics. P urulent cellulitis s hould
be treated empirically for CA-MRSA until culture results are
available.
Most CA-MRSA strains are sensitive to trimethoprim-sul­
famethoxazole and clindamycin (\1iller, 20 1 5; Talan, 2 0 1 6) .
Rifampin rapidly develops resistance and should not be used
for mono therapy. Linezolid, although efective against M RSA,
is expensive, and there is little information regarding its use
in pregnancy. Doxycycline, minocycline, and tetracycline,
although efective for MRSA infectio ns, should not be used
in pregnancy. Vancomycin remains the irst-line therapy for
inpatient serious MRSA infections.
he control and prevention of HA-NIRSA and CA-M RSA
rely on appropriate hand hygiene and prevention of skin-to­
skin contact or contact with wound dressings. Decolonization
should be considered only in cases in which a patient develops
recurrent supericial infections despite optimal hygiene mea­
sures or if ongoing transmission occurs among household or
close contacts (Liu, 20 1 1 ) . Decolonization measures include
nasal treatment with mupirocin, chlorhexidine gluconate baths,
and oral rifampin therapy if previous measures have failed.
Routine decolonization is not efective in the general o bstet­
rical population. For women with culture-proven CA-M RSA
infection during pregnancy, we add single-dose vancomycin
to routine beta-Iactam perioperative prophylaxis for cesarean
deliveries and higher-order perineal lacerations. Breastfeeding
in these women is not prohibited, but optimal hygiene and
attention to minor skin breaks is encouraged.
• Listeriosis
Listeria monocytogenes is an uncommon but probably under­
diagnosed cause of neonatal sepsis (Kylat, 20 1 6) . This faculta­
tive intracellular gram-positive bacillus can be isolated fro m the
feces of 1 to 5 percent of adults. Nearly all cases of listeriosis are
thought to be foodborne. Outbreaks have been caused by raw
vegetables, coleslaw, apple cider, melons, milk, fresh Mexican­
style cheese, smoked ish, and processed foods such as pate,
hummus, wieners, and sliced deli meats (Centers for Disease
Control and Prevention, 20 1 3e) .
Listerial infections are more common in pregnant women,
immunocompromised patients, and the very old or young. he
incidence of such infections in pregnancy is estimated to be
up to 1 00 times that in the general population (Kourtis, 2 0 1 4;
Rouse, 20 1 6) . In 1 65 1 cases reported in 2009 to 20 1 1 , the
CDC found that 1 4 percent were in pregnant women (Silk,
20 1 3) . It is unclear why pregnant women still account for a
significant number of these reported cases. One hypothesis is
that pregnant women are susceptible because of decreased cell­
mediated immunity (Baud, 20 1 1 ) .
Maternal a n d Feta l I nfecti o n
Listeriosis during pregnancy may be asymptomatic or may cause
a febrile illness that is confused with influenza, pyelonephritis,
1 224 Med ica l a nd S u rg i c a l Co m p l icat i o n s
A antimicrobials are given as discussed below. Rare case reports
F I G U R E 64-9 The pale placenta (A) a nd sti l l born i nfant (B) resu lted
from maternal listeriosis.
or meningitis (Centers for Disease Control and Prevention,
2 0 1 3e) . he diagnosis usually is not apparent until blood cul­
tures are reported as positive. Occult or clinical infection also
may stimulate labor. Discolored, brownish, or meconium­
stained amnionic fl u id is common with fetal infection, even in
preterm gestations. VIaternal listeriosis causes fetal infection that
characteristically produces disseminated granulomatous lesions
with microabscesses (Fig. 64-9) . Chorioamnionitis is common,
and placental lesions include multiple, well-demarcated mac­
roabscesses. Early- and late-onset neonatal infections are simi­
lar to group B streptococcal sepsis. In a review of 222 cases,
infection resulted in abortion or stillbirth in 20 percent, and
neonatal sepsis developed in 68 percent of surviving newborns
(Mylonakis, 2002) . In one large, prospective cohort study,
24 percent of mothers experienced fetal loss, but none after
29 weeks' gestation (Charlier, 20 1 7) . However, a neonatal-case
fatality rate of 2 1 percent has been reported (Sapuan, 20 1 7) .
Treatment with ampicillin plus gentamicin is usually rec­
ommended because of synergism against Listeria species
(Rouse, 20 1 6) . Trimethoprim-sulfamethoxazole can be given
to penicillin-allergic women. Maternal treatment in most cases
is also efective for fetal infection (Chan, 20 1 3) . No vaccine is
available. Prevention is by washing raw vegetables, cooking all
raw food, and avoiding the implicated foods listed previously
(American College of Obstetricians and Gynecologists, 20 1 6d) .
• Salmonellosis
Infections from Salmonella species continue to be a major cause
of foodborne illness (Peques, 20 1 2) . Six serotypes, including
Salmonella subtypes yphimurium and enteritidis, account for
most cases in the United States. Nontyphoid Salmonella gastro­
enteritis is contracted through contaminated food. Symptoms
that include nonbloody diarrhea, abdominal pain, fever, chills,
nausea, and vomiting begin 6 to 48 hours after exposure. Diag­
nosis is made by stool studies (Chap. 54, p. 1 048) . Intravenous
crystalloid solutions are given for rehydration. ntimicrobials
are not given in uncomplicated infections because they do not
commonly shorten illness and may prolong the convalescent
carrier state. If gastroenteritis is complicated by bacteremia,
have linked Salmonella bacteremia with abortion (Coughlin,
2002) .
Typhoid fever caused by Salmonela yphi remains a global
health problem, although it is uncommon in the United States.
Infection is spread by oral ingestion of contaminated food,
water, or milk. In pregnant women, the disease is more likely to
be encountered during epidemics or in those with HIV infec­
tion (Hedriana, 1 995). In former years, antepartum typhoid
fever resulted in abortion, preterm labor, and maternal or fetal
death (Dildy, 1 990) .
Fluoroquinolones and third-generation cephalosporins are
the preferred treatment. For enteric (typhoid) fever, antimi­
crobial susceptibility testing is important because of the devel­
opment of drug-resistant strains (Crump, 20 1 5) . Typhoid
vaccines appear to exert no harmful efects when administered
to pregnant women and are given in an epidemic or before
travel to endemic areas.
• Shigellosis
Bacillary dysentery caused by Shigela is a relatively common,
highly contagious cause of inlammatory exudative diarrhea in
adults. Shigellosis is more common in children attending day­
care centers and is transmitted via the fecal-oral route. Clinical
manifestations range from mild diarrhea to severe dysentery,
bloody stools, abdominal cramping, tenesmus, fever, and sys­
temic toxicity. Although shigellosis may be self-limited, careful
attention to treatment of dehydration is essential in severe cases.
We have cared for pregnant women in whom secretory diarrhea
exceeded l O Ll day! Antimicrobial therapy is imperative, and
efective treatment during pregnancy includes fluoroquino­
lones, ceftriaxone, or azithromycin. Antimicrobial resistance is
rapidly emerging, and antibiotic susceptibility testing can help
guide appropriate therapy (Centers for Disease Control and
Prevention, 20 1 6) . Shigellosis can stimulate uterine contrac­
tions and cause preterm birth (Parisot, 20 1 6) .
• Hansen Disease
Also known as leprosy, this chronic infection is caused by Myco­
bacterium leprae and is rare in this country. Diagnosis is con­
firmed by PCR. Multidrug therapy with dapsone, rifampin, and
clofazimine is recommended for treatment and is generally safe
during pregnancy (Gimovsky, 20 1 3; Ozturk, 20 1 7) . Duncan

( 1 980) reported an excessive incidence of low-birthweight new­
borns among infected women. The placenta is not involved, and
neonatal infection apparently is acquired from skin-to-skin or
droplet transmission (Duncan, 1 984) . Vertical transmission is
common in untreated mothers (Moschella, 2004) .
• Lyme Disease
Caused by the spirochete Borrelia burgdoeri, Lyme disease is
the most commonly reported vectorborne illness in the United
States (Centers for Disease Control and Prevention, 20 1 7c) .
Lyme borreliosis follows tick bites of the genus Ixodes. There are
three stages (Steere, 20 1 5) . Early infection-stage I-causes a
distinctive local skin lesion, erythema migrans, which may be
accompanied by a flulike syndrome and regional adenopathy. If
untreated, disseminated infection-stage 2-follows in days to
weeks. Multisystem involvement is frequent, but skin lesions,
arthralgia, myalgia, carditis, and meningitis predominate. If still
untreated after several weeks to months, late or persistent infec­
tion-stage 3-manifests in perhaps half of patients. Native
immunity is acquired, and the disease enters a chronic phase
in about 1 0 percent. Some patients remain asymptomatic, but
others in the chronic phase develop various skin, joint, or neu­
rological manifestations (Shapiro, 20 1 4) .
Clinical diagnosis is important because serological and PCR
testing has many pitfalls (Steere, 20 1 5) . IgM and IgG serologi­
cal testing is recommended in early infection and is followed
by Western blotting for conirmation. Ideally, acute and conva­
lescent serological evaluation is completed if possible, however,
false-positive and -negative rates are high.
Optimal treatment of Lyme disease was published by the
Infectious Diseases Society of America (Sanchez, 20 1 6) . For
early infection, treatment with doxycycline, amoxicillin, or
cefuroxime is recommended for 14 days, although doxycycline
is usually avoided in pregnancy. A 1 4- to 28-day course of
IV ceftriaxone, cefotaxime, or penicillin G is given for com­
plicated early infections that include meningitis, carditis, or
disseminated infections. Chronic arthritis and post-Lyme dis­
ease syndrome are treated with prolonged oral or IV regimens,
however, symptoms respond poorly to treatment (Steere,
20 1 5) .
N o vaccine i s commercially available. Avoiding areas with
endemic Lyme disease and improving tick control in those
areas is the most efective prevention. Self-examination with
removal of unengorged ticks within 36 hours of attachment
reduces infection risk (Hayes, 2003) . For tick bites recognized
within 72 hours, a single 200-mg oral dose of doxycycline may
reduce infection development.
Several reports describe Lyme disease in pregnancy, although
large series are lacking. Transplacental transmission has been
confirmed, but no congenital efects of maternal borrelio­
sis have been conclusively identiied (Shapiro, 20 1 4; Walsh,
2006) . Prompt treatment of maternal early infection should
prevent most adverse pregnancy outcomes (Mylonas, 20 1 l ) .
• Tuberculosis
Diagnosis and management of tuberculosis during pregnancy is
discussed in detail in Chapter 5 1 (p. 995) .
I nfectious D iseases 1 22 5
PROTOZOAL I N F ECTIONS
• Toxoplasmosis
The obligate intracellular parasite Toxoplasma gondii has a life
cycle with two distinct stages (Kim, 20 1 5) . heeline stage takes
place in the cat-the deinitive host-and its prey. Unsporu­
lated oocysts are excreted in feces. In the noneline stage, tissue
cysts containing bradyzoites or oocysts are ingested by the inter­
mediate host, including humans. Gastric acid digests the cysts
to release bradyzoites, which infect small-intestinal epithelium.
Here, they are transformed into rapidly dividing tachyzoites,
which can infect all cells within the host mammal. Humoral
and cell-mediated immune defenses eliminate most of these,
but tissue cysts develop. Their lifelong persistence is the chronic
form of toxoplasmosis.
H uman infection is acquired by eating raw or undercooked
meat infected with tissue cysts or by contact with oocysts from
cat feces in contaminated litter, soil, or water. Prior infection is
conirmed by serological testing, and its prevalence depends on
geographic locale and parasite genotype. In the United S tates,
seroprevalence in persons aged 1 0 to 1 9 years is 5 to 30 per­
cent, and this can exceed 60 percent in those older than 50
(Kim, 20 1 5) . Thus, a significant segment of pregnant women
in this country are susceptible to infection. The incidence of
prenatal infection resulting in birth of a newborn with con­
genital toxoplasmosis varies from 0.8 per 1 0,000 live births in
the United States to 1 0 per 1 0,000 in France (Cook, 2000) .
Between 400 and 4000 cases of congenital toxoplasmosis are
diagnosed annually in the United States Oones, 20 1 4) .
Mate rn a l a n d Feta l I nfect i o n
Most acute maternal infections are subclinical and are detected
only by prenatal or newborn serological screening. In some
cases, maternal symptoms may include fatigue, fever, headache,
muscle pain, and sometimes a maculopapular rash and posterior
cervical lymphadenopathy. In immunocompetent adults, initial
infection confers immunity, and prepregnancy infection nearly
eliminates any risk of vertical transmission. Infection in immu­
nocompromised women, however, may be severe, and reactiva­
tion may cause encephalitis, retinochoroiditis, or mass lesions.
Maternal infection is associated with a fourfold increased pre­
term delivery rate before 37 weeks (Freeman, 2005) .
The incidence and severity of fetal toxoplasmosis depend on
gestational age at the time of maternal infection. Risks for fetal
infection rise with gestational age. A metaanalysis estimated the
risk to be 1 5 percent at 1 3 weeks, 44 percent at 26 weeks,
and 7 1 percent at 36 weeks (SYROCOT Study Group, 2 007) .
Conversely, the severity of fetal infection is much greater in
early pregnancy, and these fetuses are much more likely to have
clinical findings of infection (American College of Obstetri­
cians and Gynecologists, 20 1 7) .
Importantly, most infected fetuses are born without obvi­
ous stigmata of toxoplasmosis. Clinically afected neonates
usually have generalized disease expressed as low birthweight,
hepatosplenomegaly, jaundice, and anemia. Some primarily
have neurological disease with intracranial calciications and
with hydrocephaly or microcephaly (Dhombres, 20 1 7) . Many
1 226 M ed ica l and S u rg ica l C o m p l icatio n s
eventually develop chorioretinitis and exhibit learning dis­
abilities. This classic triad-chorioretinitis, intracranial cal­
cifi c ations, and hydrocephalus-is often accompanied by
convulsions. Infected neonates with clinical signs are at risk for
long-term complications (Abdoli, 20 1 4; Wallon, 20 1 4) .
Scree n i n g a n d D i ag nos i s
With IgG antibody conirmed before pregnancy, there is no
risk for a congenitally infected fetus. he American College of
Obstetricians and Gynecologists (20 1 7) does not recommend
prenatal screening for toxoplasmosis in areas of low prevalence,
including the United States. Screening should be performed in
immunocompromised pregnant women, including those with
H IV infection. In areas of high toxoplasmosis prevalence-for
example, France and Austria-routine screening has resulted
in diminished congenital disease (Kim, 20 1 5 ; Wallon, 20 1 3) .
Pregnant women with suspected toxoplasmosis should be
tested. he parasite is rarely detected in tissue or body fluids.
Antitoxoplasma IgG develops within 2 to 3 weeks after infec­
tion, peaks at 1 to 2 months, and usually persists for life­
sometimes in high titers. Although IgM antibodies appear by
1 0 days after infection and usually become negative within 3
to 4 months, they may remain detectable for years. hus, IgM
antibodies are not used alone to diagnose acute toxoplasmosis
(Dhakal, 20 1 5) . Best results are obtained with the Toxoplasma
Serologic Proile performed at the Palo Alto Medical Founda­
tion Research Institute (ww. toxolab@pamf.org) . Toxoplasma
IgG avidity increases with time. hus, if a high-avidity IgG
result is found, infection in the preceding 3 to 5 months is
excluded. Multiple tests are available that allow high avidity
results to conirm latent infection with a 1 00-percent positive­
predictive value (Villard, 20 1 3) .
Congenital toxoplasmosis i s suspected when sonography
reveals findings such as hydrocephaly, intracranial or hepatic
calciications, ascites, placental thickening, hyperechoic bowel,
and growth restriction. Prenatal diagnosis of congenital toxo­
plasmosis is performed using PCR ampliication of toxoplasma
DNA in amnionic luid (Filisetti, 20 1 5 ; Montoya, 2008) . he
sensitivity of PCR varies with gestational age and is lowest
before 1 8 weeks (Romand, 200 1 ) .
M a n a g e m e nt
No randomized clinical trials have assessed the benefit and ei­
cacy of treatment to decrease the risk for congenital infection. A
systematic review of data from 1 438 treated pregnancies found
weak evidence for early treatment to reduce congenital toxo­
plasmosis risks (SYROCOT Study Group, 2007) . Treatment
has been associated with a reduction in rates of serious neu­
rological sequelae and neonatal demise (Cortina-Borja, 20 1 0) .
Prenatal treatment is based o n two regimens-spiramycin
alone or a pyrimethamine-sulfonamide combination given
with folinic acid (American College of Obstetricians and Gyne­
cologists, 20 1 7) . These two regimens have also been used con­
secutively (Hotop, 20 1 2) . Little evidence supports the use of a
speciic regimen (Montazeri, 20 1 7; Valentini, 20 1 5) . hat said,
most experts will use spiramycin in women with acute infection
early in pregnancy to reduce vertical transmission. Because it
does not cross the placenta, spiramycin may not be used to treat
fetal infection. Pyrimethamine-sulfadiazine with folinic acid is
selected for maternal infection after 1 8 weeks' gestation or if
fetal infection is suspected.
Prevention
There is no vaccine for toxoplasmosis, so avoidance of infection
is necessary if congenital infection is to be prevented. Eforts
include: ( 1 ) cooking meat to safe temperatures; (2) peeling or
thoroughly washing fruits and vegetables; (3) cleaning all food
preparation surfaces and utensils that have contacted raw meat,
poultry, seafood, or unwashed fruits and vegetables; (4) wearing
gloves when changing cat litter, or else delegating this duty; and
(5) avoiding feeding cats raw or undercooked meat and keeping
cats indoors. Although these preventive steps are recommended,
no data support their efectiveness (American College of Obste­
tricians and Gynecologists, 20 1 7; Di Mario, 20 1 5) .
• Malaria
his protozoan infection remains a global health crisis and
causes 2000 deaths per day worldwide (White, 20 1 5) . Malaria
has been efectively eradicated in Europe and in most of North
America, and worldwide mortality rates have fallen more than
25 percent. In the United States, most cases of malaria are
imported-some in returning military personnel (Mace, 20 1 7) .
Transmitted b y infected Anopheles mosquitoes, six species of
Plasmodium cause human disease-alciparum, vivax, two spe­
cies of ovale, malariae, and knowlesi.
M a l a ria a n d Preg na ncy
Pregnant women have increased susceptibility to malarial
infections (Kourtis, 20 1 4) . Antibodies to the parasite surface
antigen VAR2CSA mediate placental accumulation of infected
erythrocytes and lead to the harmful efects of malaria (Mayor,
20 1 5) . hrough this mechanism, some immunity accrues with
parity and is called pregnancy-specic antimalarial immuniy.
Ironically, malaria treatment dampens this immunity, and
resurgence in pregnancy has been documented in Mozambique
(Mayor, 20 1 5) .
Mate r n a l a n d Feta l I nfection
Clinical findings are fever, chills, and flulike symptoms includ­
ing headaches, myalgia, and malaise, which may occur at inter­
vals. Symptoms are less severe with recurrences. Malaria may be
associated with anemia and jaundice, and aciparum infections
may cause kidney failure, coma, and death. That said, many
otherwise healthy but infected adults in endemic areas are
asymptomatic because of partial immunity. Pregnant women,
although often asymptomatic, are said to be more likely to
develop traditional symptoms (Desai, 2007) .
Malarial
. infections during pregnancy-whether symp­
tomatic or asymptomatic-are associated with higher rates of
perinatal morbidity and mortality (Menendez, 2007; Nosten,
2007) . Adverse outcomes include stillbirth, preterm birth, low
birthweight, and maternal anemia. The latter two are docu­
mented most frequently (Machado Filho, 20 1 4; McClure,
20 1 3) . Maternal infection is associated with a 1 4-percent rate
of low-birthweight newborns worldwide (Eisele, 20 1 2) . These

F I G U R E 64- 1 0 Photomicrog raph of placental m a l a ria. A. M u ltiple
i nfected red blood cel ls (long black arrow) a re seen i n the i ntervillous
space of this placenta. M u ltiple vi l l i cut i n cross section a re shown,
and th ree a re h ig h l i g hted (short arrows). B. I ncreased magn ification
of i mage (A). M u ltiple i nfected e ryth rocytes a re seen, and two a re
identified (arrows).
adverse perinatal outcomes correlate with high levels of pla­
cental parasitemia (Rogerson, 2007) . The latter occurs when
parasitized erythrocytes, monocytes, and macrophages accumu­
late in the vascular areas of the placenta (Fig. 64- 1 0) . Infec­
tions with Paciparum are the worst, and early infection raises
the risk for abortion. The incidence of malaria increases sig­
niicantly in the latter two trimesters and postpartum (Diagne,
2000) . Despite this, congenital malaria occurs in < 5 percent of
neonates born to infected mothers.
D i a g n o s i s a n d Ma n a g e ment
Identiication of parasites by microscopical evaluation of a thick
and thin blood smear remains the gold standard for diagnosis.
In women with low parasite densities, however, the sensitivity
of microscopy is poor. Malaria-speciic antigens are now being
used for rapid diagnostic testing. Not only is their sensitivity
still an issue in pregnancy, but these tests are not routinely
available (Kashif, 20 1 3; White, 20 1 5) .
For treatment, the most frequently used antimalarial drugs
are not contraindicated in pregnancy. The World Health Orga­
nization recommends that all infected patients living in or trav­
eling from endemic areas be treated with an artemisinin-based
regimen for uncomplicated falciparum malaria (Taming,
I nfectious D i seases 1 22 7
20 1 6) . The CDC (20 1 3c) recommends using atovaquone­
proguanil or artemether-Iumefantrine only if other treatment
options are not available or tolerated.
he CDC (20 1 3c) recommends that pregnant women diag­
nosed with uncomplicated malaria caused by P vivax, malariae,
ovale, and chloroquine-sensitive P aciparum should be
treated with chloroquine or hydroxychloroquine. For women
infected with multidrug-resistant P aciparum, one irst-line
agent for nonpregnant persons is artemether-Iumefantrine.
Another primary option is artesunate plus meRoquine or arte­
sunate plus dihydroartemisinin-piperaquine (White, 20 1 5) .
h e PREGACT Study Group (20 1 6) recently compared four
artemisinin-based drugs in 3428 pregnant women with falci­
parum malaria and reported no serious maternal or perinatal
adverse efects. Second-line treatment regimens are artesunate;
quinine plus either tetracycline, doxycycline, or clindamycin;
or atovaquone-proguanii. Chloroquine-resistant P vivax should
be treated with meRoquine. Chloroquine-sensitive P vivax or
P ovale should be treated with chloroquine throughout preg­
nancy and then primaquine postpartum. Resistance to all the
antimalarial drugs has been reported, including the recently
added artemisinin-based compounds.
Treatment regimens for uncomplicated and severe malarial
infections in pregnancy are detailed at: ww. cdc.gov/malaria/
diagnosis_treatment. he CDC also maintains a malaria hot­
line for treatment recommendations (8 5 5-856-47 1 3) .
Preve ntion a n d C h e m o p ro p hy l a x i S
Malaria control and prevention relies on chemoprophylaxis
when traveling to or living in endemic areas. Vector control is
also important. Insecticide-treated netting, pyrethroid insecti­
cides, and DEET-based insect repellent lower malarial rates in
endemic areas. hese are well tolerated in pregnancy (Menendez,
2007) . If travel is necessary, chemoprophylaxis is recommended.
Chloroquine and hydroxychloroquine prophylaxis is safe and
well tolerated in pregnancy. Prophylaxis lowers placental infec­
tion rates from 20 percent to 4 percent in asymptomatic infected
women in areas without chloroquine resistance (Cot, 1 992) . For
travelers to areas with chloroquine-resistant Paciparum, meRo­
quine prophylaxis is recommended (Freedman, 20 1 6) . One
evaluation compared prophylaxis during pregnancy with either
sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine
and found the latter to be more efective (Kakuru, 20 1 6) . Pri­
maquine and doxycycline are contraindicated in pregnancy, and
data are insuicient for atovaquone/proguanil use. The latest
chemoprophylaxis regimens for pregnancy can be obtained from
the CDC Travelers ' Health website at: ww. cdc.gov/malaria/
travelers/drugs.htmi. The CDC also publishes Health Inorma­
tion or Intenational Travel (The Yellow Book) at: ww. cdc.
gov/yellowbook. For women living in endemic areas, intermit­
tent preventive treatment was found to be superior to intermit­
tent screening with treatmet (Desai, 20 1 5) .
• Amebiasis
Approximately 10 percent of the world population is infected
with Entamoeba histo6ltica, and most are asymptomatic (Andrade,
201 5). Amebic dysentelY, however, may take a fulminant course
1 228 Med i ca l and S u rg ical Co m p l ications
during pregnancy, with fever, abdominal pain, and bloody stools.
Prognosis is worse if complicated by a hepatic abscess. Diagnosis
is made by identiying E histoytica cysts or trophozoites within
a stool sample. herapy is similar to that for the nonpregnant
woman, and metronidazole or tinidazole are the preferred drugs
for amebic colitis and invasive disease. Noninvasive infections
may be treated with iodoquinol or paromomycin.
MYCOTIC I N F ECTIONS
Disseminated fungal infection-usually pneumonitis-during
pregnancy is uncommon with coccidiomycosis, blastomyco­
sis, cryptococcosis, or histoplasmosis. heir identification and
management are considered in Chapter 5 1 (p. 995).
TRAVEL PRECAUTIONS DURING PREGNANCY
Pregnant travelers face general medical, obstetrical, and poten­
tially hazardous destination risks. Several sources provide travel
information (Freedman, 20 1 6) . he International Federation
for Tropical Medicine has comprehensive information avail­
able at ww. iftm-hp.org, and the International Society of
Travel Medicine publishes information at www.istm.org/
bodyofknowledge. lso, 1he Yelow Book, mentioned earlier, by
the CDC has extensive travel information regarding pregnancy
and breastfeeding.
BIOTERRORISM
The concept ofbioterrorism involves the deliberate release ofbac­
teria, viruses, or other infectious agents to cause illness or death.
hese natural agents are often altered to increase their infectiv­
ity or their resistance to medical therapy. Health-care providers
should be alert for signiicant increases in the number of persons
with febrile illnesses accompanied by respiratory symptoms or
with rashes not easily associated with common illnesses. Cli­
nicians are urged to contact their state health department or
the CDC for current information and recommendations. The
merican College of Obstetricians and Gynecologists (20 1 6a)
has addressed disaster preparedness for obstetricians. It provides
both general considerations and recommendations for hospital
readiness and obstetrics-specific issues.
• Smallpox
he variola virus causes smallpox and is considered a serious
weapon. The virus is highly transmissible and carries an over­
all 30-percent case-fatality rate. The last case of smallpox in
the United States was reported in 1 949, and worldwide it was
reported in Somalia in 1 977. Nishiura (2006) has reviewed the
severe perinatal and maternal morbidity and mortality caused by
smallpox. The case-fatality rate of smallpox in pregnancy is 6 1
percent i f the pregnant woman i s unvaccinated. Rates o f still­
birth, abortion, preterm labor and delivery, and neonatal demise
rise significantly in pregnancies complicated by this infection.
Because the smallpox vaccine currently available is made
with live vaccinia virus, pregnancy should be delayed for
4 weeks in recipients. It is generally not given to pregnant
women because of the risk of fetal vaccinia, a rare but serious
complication. Inadvertent smallpox vaccination during preg­
nancy has not, however, been convincingly associated with fetal
malformations or preterm birth (Badell, 20 1 5) . Moreover, no
cases of fetal vaccinia have been reported with second-genera­
tion smallpox vaccine exposure. The Smallpox Vaccine in Preg­
nancy Registry remains active, and vaccinated women are still
being enrolled: DOD .NHRC-birthregistry@mail. mil.
• Anthrax
Bacillus anthracis is a gram-positive, spore-forming, aerobic bac­
terium. It can cause three main types of clinical anthrax: inha­
lational, cutaneous, and gastrointestinal (Centers for Disease
Control and Prevention, 20 1 7a) . The bioterrorist anthrax attacks
of 200 1 involved inhalational anthrax (Inglesby, 2002). Spores
are inhaled and deposited in the alveoli. They are engulfed by
macrophages and germinate in mediastinal lymph nodes. The
incubation period is usually less than 1 week but may be as long
as 2 months. Within 1 to 5 days of symptom onset, the second
stage is heralded by the abrupt onset of severe respiratory distress
and high fevers. Mediastinitis and hemorrhagic thoracic lymph­
adenitis are common. Chest radiographs show a widened medias­
tinum. Case-fatality rates with inhalational anthrax are high, even
with aggressive antibiotic and supportive therapy (Holty, 2006).
Anthrax afecting pregnant women and its treatment were
reviewed by Meaney-Delman and coworkers (20 1 2, 20 1 3) .
They reported data o n 20 pregnant and postpartum women.
The overall mortality rate was 80 percent, with a 60-percent
fetal or neonatal loss rate. Of note, most cases were published
'
before the advent of antibiotics.
Regimens for postexposure anthrax prophylaxis are given for
2 months. The CDC recommend that asymptomatic pregnant
and lactating women with documented exposure to B anthracis
be given postexposure prophylaxis with ciproloxacin, 500 mg
orally twice daily for 60 days (Hendricks, 20 1 4; Meaney-Del­
man, 20 1 3) . Amoxicillin, 500 mg orally three times daily, can
be substituted if the strain is proven sensitive. In the case of
ciproloxacin allergy and either penicillin allergy or resistance,
doxycycline, 1 00 mg orally twice daily, is given for 60 days.
Risks from anthrax far outweigh any fetal risks from doxycy­
cline (lvleaney-Delman, 20 1 3) .
The anthrax vaccine i s a n inactivated, cell-free product that
requires three injections over 28 days. Vaccination is generally
avoided in pregnancy because safety data are limited. Inadver­
tent vaccination of pregnant women with the vaccine has not
been linked with a significant increase in fetal malformation
or miscarriage rates (Conlin, 20 1 5; Ryan, 2008) . The anthrax
vaccine is an essential adjunct to postexposure antimicrobial
prophylaxis, even in pregnancy.
• Other Bioterrorism Agents
Other category A bioterrorism agents include Francisella tula­
remis-tularemia, Clostridium botulinum-botulism, Yersinia
pestis-plague, and viral hemorrhagic fevers-for example,
Ebola, Marburg, Lassa, and Machupo. The guidelines for these
biological agents are evolving and are detailed at the CDC Bio­
terrorism website: emergency.cdc.gov/bioterrorism/index.asp.

REFERENCES
Abdoli A, Dalimi A, Arbabi M, et a l : Neuropsychiatric manifestations of latent
toxoplasmosis on mothers and their ofspring. J Matern Fetal Neonatal Med
27( 1 3 ) : 1 368, 20 1 4
Adams LL, Gungor S, Turan S , e t al: When are amniotic luid viral PCR stud­
ies indicated in prenatal diagnosis? Prenat Diagn 3 2 ( 1 ) :88, 20 1 2
Adams Waldorf KM, McAdams M : Inluence o f infection during pregnancy
on fetal development. Reproduction 1 46(5) : R 1 5 1 , 20 1 3
Adhikari EH, Nelson DF, Johnson A , e t al: Infant outcomes among women
with Zika virus infection during pregnancy: results of a large prenatal Zika
screening program. Am J Obstet Gynecol 2 1 6:292.e 1 , 20 1 7
Ahn KH, Park YJ, Hong SC, e t al: Congenital varicella syndrome: a systematic
review. J Obstet Gynaecol 36(5): 563, 20 1 6
Alpert SG, Fergerson J , Noel LP: Intrauterine West Nile virus: ocular and
systemic indings. Am J Ophthalmol 1 36(4) :733, 2003
American College of Obstetricians and Gynecologists: Hospital disaster pre­
paredness for obstetricians and facilities providing materniry care. Commit­
tee Opinion No. 5 5 5 , March 20 1 3, Reairmed 20 1 6a
American College of Obstetricians and Gynecologists: Inluenza vaccination
during pregnancy. Committee Opinion No. 608, September 2014, Reaf­
firmed 20 1 6b
American College of Obstetricians and Gynecologists: Integrating immuniza­
tions into practice. Committee Opinion No. 66 1 , April 2 0 1 6c
American College of Obstetricians and Gynecologists: Management of preg­
nant women with presumptive exposure to Listeria monocytogenes. Com­
mittee Opinion No. 6 1 4, December, 2 0 1 4, Reairmed 20 1 6d
American College of Obstetricians and Gynecologists: Prevention of early­
onset group B streptococcal disease in newborns. Committee Opinion No.
485, April 20 1 1 , Reairmed 20 1 6e
American College of Obstetricians and Gynecologists: Cytomegalovirus, par­
vovirus B9, varicella zoster, and toxoplasmosis in pregnancy. Practice Bul­
letin No. 1 5 1 , June 20 1 5 , Reairmed 20 1 7
Andrade M , Reed SL: Amebiasis and infection with free-living amebas. I n
Kasper D L , Fauci A S , Hauser S L , et al (eds): Harrison's Principles of Inter­
nal Medicine, 1 9th ed. New York, McGraw-Hill, 2 0 1 5 , p. 1 363
Arabi YM , Balkhy H H , Hayden FG, et al: Middle East respiratory syndrome.
N Engl J Med 376(6) :584, 20 1 7
Arvin AM, Fast P , Myers M , e t al: Vaccine development to prevent cytomega­
lovirus disease: report from the National Vaccine Advisory Committee. Clin
Infect Dis 39:233, 2004
Assiri A, Abedi GR, Al Masri M, et al: Middle East respiratory syndrome coro­
navirus infection during pregnancy: a report of 5 cases from Saudi Arabia.
Clin Infect D is 63(7) : 95 1 , 20 1 6
Auriti C , Piersigilli F, De Gasperis M R, et al: Congenital varicella syndrome:
still a problem? Fetal Diagn Ther 25 (2) : 224, 2009
Azam AZ, Vial Y, Fawer CL, et al: Prenatal diagnosis of congenital cytomega­
lovirus infection. Obstet Gynecol 97:443, 200 1
Badell ML, Meaney-Delman D, Tuuli M G , et al: Risks associated with small­
pox vaccination in pregnancy: a systematic review and meta-analysis. Obstet
Gynecol 1 2 5 (6) : 1 439, 20 1 5
Bates T : Poliomyelitis i n pregnancy, fetus and newborn. Am J Dis Child 90:
1 89, 1 9 55
Baud D , Greub G : Intracellular bacteria and adverse pregnancy outcomes. Clin
Microbiol Infect 1 7: 1 3 1 2 , 20 1 1
Beau AB, Hurault-Delarue C, Vial T, et al: Sfery of oseltamivir during pregnancy:
a comparative study using the EFEMERIS database. BJOG 1 2 1 (7):895, 20 14
Beigi RH: Emerging infectious diseases in pregnancy. Obstet Gynecol
1 29(5): 896, 20 1 7
Beigi R H , Bunge K , Song Y , e t al: Epidemiologic and economic efects of
methicillin-resistant Staphylococcus aureus in obstetrics. Obstet Gynecol
1 1 3 :983, 2009
Beigi RH, Venkataramanan R, Caritis SN: Oseltamivir for inluenza in preg­
nancy. Semin PerinatoI 38(8): 503, 20 1 4
Bonvicini F, Puccetti C, Salfi NC, et al: Gestational and fetal outcomes in B 1 9
matenal infection: a problem o f diagnosis. J Clin MicrobioI 49( 1 0):35 14, 20 1 1
Brasil P, Pereira JP, Moreira ME, et al: Zika virus infection in pregnant women
in Rio de Janeiro. N Engl J Med 375(24): 232 1 , 20 1 6
Briody VA, Albright CM, Has P , e t al: Use o f cefazolin for group B strepto­
cocci prophylaxis in women reporting a penicillin allergy without anaphy­
laxis. Obstet Gynecol 1 27(3) : 5 7, 20 1 6
Brown GC, Karunas RS: Relationship o f congenital anomalies and maternal
infection with selected enteroviruses. Am J Epidemiol 95 :207, 1 972
Brown E: Parvovirus infections. In Kasper DL, Fauci AS, Hauser SL,
et al (eds): Harrison's Principles of Internal Medicine, 1 9th ed. New York,
McGraw-Hill, 20 1 5
I nfectious Di sea ses 1 22 9
Buchanan R , Bonthius DJ: Measles virus and associated central nervous system
sequelae. Semin Pediatr Neuro1 1 9 : 1 0 , 20 1 2
Butterly A , Schmidt U , Wiener-Kronish J : Methicillin-resistant Staphylococ­
cus aureus colonization, its relationship to nosocomial infection, and eicacy
of control methods. Anesthesiology 1 1 3: 1 4 5 3 , 20 1 0
Callaghan WM, Creanga A , Jamieson DJ : Pregnancy related mortality result­
ing from inluenza in the United States during the 2009-20 1 0 pandemic.
Obstet Gynecol 1 26(3):486, 20 1 5
Centers for Disease Control and Prevention: Prevention of perinatal group B
streptococci disease. Revised guidelines from the CDC. MvfWR 5 9 ( 1 0) : 1 ,
20 1 0
Centers for Disease Control and Prevention: Maternal and infant outcomes
among severely ill pregnant and postpartum women with 2009 pandemic
influenza A (H 1 N 1 )-United States, April 2009-August 20 1 0 . M MWR
60(35) : 1 1 93, 20 1 1
Centers for Disease Control and Prevention: FDA approval of an extended
period for administering VariZIG for postexposure prophylaxis of varicella.
MMWR 6 1 ( 1 2) :2 1 2, 20 1 2
Centers for Disease Control and Prevention: Prevention and control o f sea­
sonal inluenza with vaccines: recommendations of the Advisory Committee
on Immunization Practices-United States, 20 1 3-20 14. MMWR 62(7) : 1 ,
20 1 3a
Centers for Disease Control and Prevention: Severe acute respiratory syn­
drome (SARS) . 20 1 3b . Available at: https:llwww.cdc.gov/sars/index.html.
Accessed October 7, 20 1 7
Centers for Disease Control and Prevention: Treatment of malaria: guidelines
for clinicians (United States). Part 3: Alternatives for pregnant women
and treatment of severe malaria. 20 1 3c. Available at: http://www.cdc.
gov/malaria/diagnosis_treatment/clinicians3.html. Accessed October 7,
20 1 7
Centers for Disease Control and Prevention: Updated recommendations for
use of VariZIG-United States. MMWR 62(28): 574, 20 1 3d
Centers for Disease Control and Prevention: Vital signs: listeria illnesses,
deaths, and outbreaks-United States, 2009-20 1 1 . MMWR 62(22) : 1 48,
20 1 3e
Centers for Disease Control and Prevention (CDC) : Rubella and congenital
rubella syndrome control and elimination-global progress, 2000-20 1 2.
MMWR 62(48)983, 20 1 3f
Centers for Disease Control and Prevention: Active Bacterial Core surveillance
(ABCs): group B Streptococcus, 20 1 5 . Available at: http://www.cdc.gov/
abcslreports-indingslsurvreportslgbs 1 5 . pdf. Accessed October 6, 20 1 7
Centers for Disease Control and Prevention: Shigella-shigellosis. 20 1 6. Avail­
able at: https:/Iwww.cdc.gov/shigella/general-information.html. Accessed
October 7, 20 1 7
Centers for Disease Control and Prevention: Anthrax. 20 1 7a. Available at:
https:llwww.cdc.gov/anthrax/index.html. Accessed October , 20 1 7
Centers for Disease Control and Prevention: Hantavirus. 20 1 7b. Available at:
https: !lwww.cdc.gov/hantavirus.l Accessed October 7, 20 1 7
Centers for Disease Control and Prevention: Lyme disease: data and statistics.
20 1 7c. Available at: https: llwww.cdc.gov/lyme/stats/index.html. Accessed
October 7, 20 1 7
Centers for Disease Control and Prevention: Measles (rubeola): for healthcare
professionals. 20 1 7d. Available at: https:llwww.cdc.gov/measles/hcp/index.
html. Accessed October , 20 1 7
Centers for Disease Control and Prevention: Seasonal influenza (flu): guidance
for clinicians on the use of rapid influenza diagnostic tests. 20 1 e. Available
at: http://www.cdc.gov/flu/professionals/diagnosis/clinician_guidance_ridt.
htm. Accessed October 7, 20 1 7
Centers for Disease Control and Prevention: West Nile virus. 20 1 7f. Available
at: https:llwww.cdc.gov/westnile/index.html. Accessed October 7, 20 1
Chambers CD, Johnson DL, Xu R, et al: Safery of the 20 1 0- 1 1 , 20 1 1 - 1 2,
20 1 2- 1 3 , and 20 1 3- 1 4 seasonal inluenza vaccines in pregnancy: birth
defects, spontaneous abortion, preterm delivery, and small for gestational
age infants, a study from the cohort arm ofVAMPSS. Vaccine 34(37):4443,
20 1 6
Chan BT, Hohmann E , Barshak M B , e t al : Treatment o f listeriosis in first
trimester of pregnancy. Emerg Infect Dis 1 9:839, 20 1 3
Chandra Pc, Patel H , Schiavello HJ, et a l : Successful pregnancy outcome after
complicated varicella pneumonia. Obstet Gynecol 92:680, 1 998
Charlier C, Perrodeau E, Leclercq A, et al: Clinical features and prognostic fac­
tors of listeriosis: the MONALISA national prospective cohort study. Lancet
Infect Dis 1 7: 5 1 0, 20 1 7
Chauvet A , Dewilde A , homas D, e t a l : Ultrasound diagnosis, management
and prognosis in a consecutive series of 2 cases of fetal hydrops following
maternal parvovirus B 1 9 infection. Fetal Diagn her 30( 1 ) :4 1 , 201 1
Chaves SS, Gargiullo P, Zhang JX, et al: Loss of vaccine-induced immuniry to
varicella over time. N Engl J Med 356: 1 1 2 1 , 2007
1 230 Medical and S u rg ica l Co m p l i cat i o n s
Cheeran M C , Lokensgard JR, Schleiss M R: Neuropathogenesis o f congenital
cytomegalovirus infection: disease mechanisms and prospects for interven­
tion. Clin Microbiol Rev 22( 1 ) :99, 2009
Chen H, Lin HC, Lin HC: I ncreased risk of adverse pregnancy outcomes
among women afected by herpangina. Am J Obstet Gynecol 203 ( 1 ):49.
e 1 , 20 1 0
Chiu M H , Meatherall B, Nikolic A, et al: Subacute sclerosing panencephalitis
in pregnancy. Lancet Infect Dis 1 6(3) :366, 20 1 6
Cohen J I : Enterovirus, parechovirus and reovirus infection. I n Kasper DL,
Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Internal v Iedicine,
1 9th ed. New York, McGraw-Hill, 20 1 5a
Cohen YZ, Dolin R: Influenza. In Kasper DL, Fauci AS, Hauser SL, et al (eds):
Harrison's Principles of Internal Medicine, 1 9th ed. New York, lcGraw­
H ill, 20 1 5b
Conlin M , Bukowinski AT, G umbs G R, et al: Analysis of pregnancy and
infant health outcomes among women in the National Smallpox Vaccine
in Pregnancy Registry who received anthrax vaccine adsorbed. Vaccine
33 (36) :4387, 20 1 5
Cook AJ, Gilbert E, Bufolano W, et al: Sources of toxoplasma infection in
pregnant women: European multicentre case-control study. mv IJ 32 1 : 1 42 ,
2000
Cortina-Borja MTan HK, Wallon M , et al: Prenatal treatment for serious neu­
rological sequelae of congenital toxoplasmosis: an observational prospective
cohort study. PLoS Med 7( 1 0) : l , 20 1 0
Cot M, Roisin A , Barro 0, e t al : Efect o f chloroquine chemoprophylaxis dur­
ing pregnancy on birth weight: results of a randomized trial. Am J Trop
Med Hyg 46:2 1 , 1 992
Coughlin LB, McGuigan J, Haddad NG, et al: Salmonella sepsis and miscar­
riage. Clin Microbiol Infect 9 : 866, 2002
Crespo AC, van der Zwan A, Ramalho-Santos J, et al: Cytotoxic potential of
decidual NK cells and CD8 + T cells awakened by infections. J Reprod
I m munoI I 1 9:85, 20 1 7
Crump JA, Sjolund-Karlsson M , Gordon A, e t al: Epidemiology, clinical pre­
sentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial
management of invasive salmonella infections. Clin Microbiol Rev 28(4):
90 1 , 20 1 5
da Silva I RF , Frontera JA, Bispo de Filippis AN , et al: Neurologic compli­
cations associated with the Zika virus in Brazilian adults. JlA Neurol
74( 1 0) : 1 1 90 , 20 1 7
Dantes R , M u Y, Belflower R , e t al: National burden o f invasive methicillin­
resistant Staphylococcus aureus infections, United States, 20 1 1 . JAv1A
Intern Med 1 73 (2 1 ) : 1 970, 20 1 3
Daum RS, Miller LG, Immergluck L : A placebo-controlled trial o f antibiotics
for smaller skin abscesses. N Engl J Med 376:2345, 20 1 7
d e Haan TR, Beersman MF, Oepkes 0 , e t al: Parvovirus B 1 9 infection i n
pregnancy: maternal and fetal viral load measurements related to clinical
parameters. Prenat Diagn 27:46, 2007
de Jong EP, Lindenburg IT, van Klink JM, et al: I ntrauterine transfusion for
parvovirus B 1 9 infection: long-term neurodevelopmental outcome. Am J
Obstet Gynecol 206:204.e l , 20 1 2
d e J ong E P, Walther FJ, Kroes AC, e t al: Parvovirus B 1 9 infection i n preg­
nancy: new insights and management. Prenat Diagn 3 1 (5):4 1 9 , 20 1 1
Dembinski J, Eis-Hubinger vf, Maar J , et al: Long term follow up of serosta­
tus after maternofetal parvovirus B 1 9 infection. Arch Dis Child 88:2 1 9 ,
2003
Desai M , Gutman J, L'lanziva A, et al: Intermittent screening and treatment or
intermittent preventive treatment with dihydroartemisinin-piperaquine ver­
sus intermittent preventive treatment with sulfadoxine-pyrimethamine for
the control of malaria during pregnancy in western Kenya: an open-label,
three-group, randomised controlled superiority trial. Lancet 386( 1 00 1 2) :
2 507, 20 1 5
Desai M , ter Kuile F , Nosten F , et al: Epidemiology and burden of malaria i n
pregnancy. Lancet Infect D i s 7:93, 2007
Deutscher M, Lewis M, Zell ER, et al: Incidence and severity of invasive
Streptococcus pneumoniae, group A Streprococcus, and group B Strepto­
coccus infections among pregnant and postpartum women. Clin Infect Dis
53(2): 1 1 4, 201 1
Dhakal R, Gajurel K, Pomares C, et al : Signiicance of a positive toxoplasma
immunoglobulin M test result in the United States. J Clin MicrobioI 53( 1 1 ) :
360 1 , 20 1 5
Dhombres F , Friszer S , Maurice P , et al: Prognosis o f fetal parenchymal cere­
bral lesions without ventriculomegaly in congenital toxoplasmosis infection .
Fetal Diagn Ther 4 1 ( 1 ):8, 20 1 7
Diagne N, Rogier C, Sokhna C S , e t al: I ncreased susceptibility t o malaria dur­
ing the early postpartum period. N Engl J Med 343: 598, 2000
Dildy GA III, Martens MG, Faro S, et al: Typhoid fever in pregnancy: a case
report. J Reprod Med 35:2 3, 1 990
D i Mario S, Basevi V, Gagliotti C, et al: Prenatal education for congenital
toxoplasmosis. Cochrane Database Syst Rev 1 0:CD006 1 1 , 20 1 5
D i Renzo GC, Melin P , Berardi A, et al: Intrapartum GBS screening and anti­
biotic prophylaxis: a European consensus conference. J Matern Fetal Neo­
natal Med 28(7):766, 20 1 5
Donders GG, Halperin SA, Devlieger R, et al: Maternal immunization with an
investigational trivalent group B streptococcal vaccine: a randomized con­
trolled trial. Obstet GynecoI 1 27 (2) :2 1 3, 2 0 1 6
Driggers RW, Ho CY, Korhonen E M , et a l : Zika virus infection with pro­
longed maternal viremia and fetal brain abnormalities. N Engl J Med
374(22) :2 142, 20 1 6
Duncan ME: Babies o f mothers with leprosy have small placentae, low birth
weights and grow slowly. BJOG 8 :46 1 , 1 980
Duncan ME, Fox H, Harkness A, et al: The placenta in leprosy. Placenta
5 : 1 89, 1 984
Dunstan HJ, Mill AC, Stephens S, et al: Pregnancy outcome following mater­
nal use of zanamivir or oseltamivir during the 2009 influenza AlH 1 N 1 pan­
demic: a national prospective surveillance study. BJOG 1 2 1 (7):90 1 , 2 0 1 4
Duryea E L , Sheield JS: Influenza: threat t o maternal health. Obstet Gynecol
Clin North Am 42(2):355, 20 1 5
Egana-Ugrinovic G , Gonce A, Garcia L, et al: Congenital cytomegalovirus
infection among twin pairs. J Matern Fetal Neonatal Med 29(2 1 ) :3439,
20 1 6
Eisele TP, Larsen DA, Anglewicz PA, e t al: Malaria prevention i n pregnancy,
b irthweight, and neonatal mortality: a meta-analysis of 32 national cross­
sectional datasets in Africa. Lancet I nfect D is 1 2:942, 20 1 2
Enders G , Bader U , Lindemann L , e t al: Prenatal diagnosis o f congenital cyto­
megalovirus infection in 1 89 pregnancies with known outcome. Prenat
Diagn 2 1 :362, 200 1
Enders G, Miller E, Cradock-Watson J, et al: Consequences of varicella and
herpes zoster in pregnancy: prospective study of 1 739 cases. Lancet 343:
1 548, 1 994
Enders M, Weidner A, Zoellner I, et al: Fetal morbidity and mortality after
acute human parvovirus B 1 9 infection in pregnancy: prospective evaluation
of 1 0 1 8 cases. Prenat Diagn 24: 5 1 3, 2004
Fairlie T, Zell ER, Schrag S: Efectiveness of i ntrapartum antibiotic prophylaxis
for prevention of early-onset Group B streptococcal disease. Obstet Gynecol
1 2 1 (3) : 5 70, 20 1 3
Fell D B , Savitz DA, Kramer M S , e t al : Maternal influenza and birth outcomes:
systematic review of comparative studies. BJOG 1 24 ( 1 ) :48, 20 1
Fiebelkorn AP, Redd SB, Gallagher K, et al: Measles in the United States dur­
ing the postelimination era. J Infect D is 202( 1 0) : 1 520, 20 1 0
Filisetti 0 , Year H, Villard 0 , e t al: Contribution o f neonatal amniotic
fluid testing to diagnosis of congenital toxoplasmosis. J Clin Microbiol
53(5): 1 7 1 9, 20 1 5
Forcade NA, Wiederhold NP, Ryan L, et al: Antibacterials as adjuncts to inci­
sion and drainage for adults with purulent methicillin-resistant Staphylococ­
cus aureus (MRSA) skin infections. Drugs 72: 339, 2 0 1 2
Forsnes EV, Eggleston M K , Wax J R: Diferential transmission o f adenovirus i n
a twin pregnancy. Obstet Gynecol 9 1 : 8 1 , 1 998
Fowler KB, Stagno S, Pass RF, et al: The outcome of congenital cytomegalovi­
rus infection in relation to maternal antibody status. N Engl J Med 326:663,
1 992
Fowler KB, Stagno S, Pass F: Maternal immunity and prevention of
congenital cytomegalovirus infection. J1A 289: 1 008, 2003
Fowler SL: A light in the darkness: predicting outcomes for congenital cyto­
megalovirus infections. J Pediatr 1 37:4, 2000
Fragiadakis G K, Baca QJ, Gherardini PF, et al: Mapping the fetomaternal
peripheral immune system at term pregnancy. J I mmunol 1 97( 1 1 ) :4482,
20 1 6
Freedman DO, Chen LH, Kozarsky PE: Medical considerations before inter­
national travel. N Engl J Med 375(3):247, 20 1 6
Freeman K , Oakley L , Pollak A , e t al: Association between congenital toxo­
plasmosis and preterm birth, low birthweight and small for gestational age
birth. BJOG 1 1 2:3 1 , 2005
G imovsky AC, Macri CJ: Leprosy in pregnant woman, United States. Emerg
Infect Dis 1 9: 1 0, 20 1 3
Gotwitz J , Kruszon-Moran 0, McAllister SK: Changes in the prevalence of
nasal colonization with Staphylococcus aureus in the United States, 200 1 -
2004. J Infect D i s 1 97 : 1 226, 2008
Grant GB, Reef SE, Dabbagh A, et al: Global progress roward rubella and con­
genital rubella syndrome control and elimination-2004-20 14. MMWR
64(37) : 1 052, 20 1 5
Granwehr BP, Lillibridge M , Higgs S , et al: West Nile virus: where are we
now? Lancet Infect Dis 4: 547, 2004
Guerra B , Lazzarotto T, Quarta S, et al: Prenatal diagnosis of symptomatic
congenital cytomegalovirus infection. Am J Obstet GynecoI 1 83:476, 2000

Hamilton SM, Stevens DL, Bryant AE: Pregnancy-related Group A streptococ­
cal infections: temporal relationship between bacterial acquisition, infection
onset, clinical findings, and outcome. Clin Infect Dis 57:8 0, 20 1 3
Harjulehto T, Aro T, Hovi T, e t a l : Congenital malformations and oral polio­
virus vaccination during pregnancy. Lancet 1 :77 1 , 1 989
Hayes EB, Piesman J: How can we prevent Lyme disease? N Engl J Med 348:
2424, 2003
Hedriana HL, Mitchell J L, Williams SB: Salmonella ryphi chorioamnionitis
in a human immunodeiciency virus-infected pregnant woman. J Reprod
Med 40: 1 57, 1 995
Helali NE, Giovangrandi Y, Guyot K, et al: Cost and efectiveness of intrapar­
tum Group B streptococcus polymerase chain reaction screening for term
deliveries. Obstet Gynecol 1 1 9(4) :822, 20 1 2
Hendricks A , Wright ME, Shadomy SV, e t al: Centers for Disease Con­
trol and Prevention expert panel meetings on prevention and treatment of
anthrax in adults. Emerg Infect D is 20(2) : 1 , 20 1 4
H ills SL, Russell K , Hennessey M , e t a l : Transmission o f Zika virus through
sexual contact with travelers to areas of ongoing transmission-Continental
United States. MMWR 65 (8):2 1 5 , 2 0 1 6
Holry J E, Bravata O M , Liu H , e t a l : Systemic review: a century o f inhalational
anthrax cases from 1 900 to 2005. Ann Intern Med 1 44:270, 2006
Honein A, Dawson AL, Petersen EE, et al: Birth defects among fetuses and
infants of US women with evidence o f possible Zika virus infection during
pregnancy. JAMA 3 1 7 ( 1 ) : 5 9 , 20 1 7
Hotop A, Hlobil H , Gross U: Eicacy o f rapid treatment initiation following
primary Toxoplasma gondii infection during pregnancy. Clin I nfect Dis
54( 1 1 ) : 1 545, 20 1 2
Howard MJ , Doyle TJ, Koster FT, e t al: Hantavirus pulmonary syndrome in
pregnancy. Clin Infect Dis 29: 1 538, 1 999
Hutton J , Rowan P, Greisinger A, et al: Rubella monitoring in pregnancy
as a means for evaluating a possible reemergence of rubella. Am J Obstet
GynecoI 2 1 1 (5): 534.e 1 , 20 1 4
Hyde T B , Schmid O S , Cannon MJ: Cytomegalovirus seroconversion rates and
risk factors: implications for congenital CMV. Rev Med Virol 20:3 1 1 , 20 1 0
Inglesby TV, O'Toole T , Henderson DA, et al: Anthrax as a biological weapon,
2002. JAMA 287:2236, 2002
Irving WL, James O K, Stephenson T, et al: Influenza virus infection in the
second and third trimesters of pregnancy: a clinical and seroepidemiological
study. BJOG 1 07: 1 282, 2000
Jamieson OJ, Uyeki TM, Callaghan WM, et al: Xfhat obstetrician-gynecologists
should know about Ebola: a perspective from the Centers for Disease Con­
trol and Prevention. Obstet GynecoI 1 24(5) : 1 005, 20 1 4
Jespersen C , Helmuth I G , Krause TG: Varicella-zoster immunoglobulin treatment
in pregnant women in Denmark from 2005 to 20 1 5: descriptive epidemiology
and follow-up. Epidemiol Infect August 1 8, 20 1 6 [Epub ahead of print]
Jimenez-Truque N, Tedeschi S, Saye EJ, et al: Relationship between maternal
and neonatal Staphylococcus aureus colonization. Pediatrics 1 29:e1 252, 20 1 2
Joguet G , Mansuy JM, Matusali G , e t al: Efect o f acute Zika virus infection on
sperm and virus clearance in body fluids: a prospective observational study.
Lancet Infect Disease August 2 1 , 20 1 7 [Epub ahead of print]
Jones JL, Parise ME, Fiore AE: Neglected parasitic infecrions in the United
States: toxoplasmosis. Am J Trop Med Hyg 90(5) :794, 20 1 4
Julander J G , Winger QA, Rickords LF, et al: West Nile virus infection o f the
placenta. Virology 347: 1 75 , 2006
Kakuru A, Jagannathan P, Muhindo M K, et al: Dihydroartemisinin-Pipera­
quine for the prevention of malaria in pregnancy. N Engl J Med 374( 1 0) :
928, 20 1 6
Kanengisser-Pines B , Hazan Y , Pines G , et al: High cytomegalovirus I g G avid­
ity is a reliable indicator of past infection in patients with positive IgM
detected during the first trimester of pregnancy. J Perinat Med 37: 1 5 , 2009
Kashif AH, Adam G K, Mohammed AA, et al: Reliabiliry of rapid diagnostic
test for diagnosing peripheral and placental malaria in an area of unstable
malaria transmission in Eastern Sudan. Diagn Pathol 8:59, 20 1 3
Kharbanda EO, Vasquez-Benitez G , Romitti PA, et al: First trimester influenza
vaccination and risks for major structural birth defects in ofspring. J Pediatr
1 87:234, 20 1 7
Kim , Kasper LH: Toxoplasma infections. I n Kasper DL, Fauci AS , Hauser
SL, et al (eds): Harrison's Principles o f Intenal Medicine, 1 9th ed. New
York, McGraw-Hili, 20 1 5
Kimberlin OW, Sanchez PJ, Ahmed A, et al: Valganciclovir for symptomatic
congenital cytomegalovirus disease. N Engl J Med 3 2( 1 0) : 933, 20 1 5
Kobayashi M, Schrag SJ, Alderson M R, et al: WHO consultation on group B
streptococcus vaccine development: report from a meeting held on 2 -28
April 20 16. Vaccine December 22, 20 1 6 [Epub head of print]
Koro'ikova EL, Lozovskaia LS , Tadtaeva U, et al : The role of prenatal cox­
sackie virus infection in the etiology of congenital heart defects in children.
Kardiologiia 29:68, 1 989
I n fectious D i sea ses 1 23 1
Kourtis AP, Read JS, Jamieson OJ: Pregnancy and infection. N Engl J Med
370 (23) :22 1 1 , 20 1 4
Krow-Lucal E , Lindsey N P , Lehman J, et al: West Nile virus and other nation­
ally notifiable diseases-United States. M MWR 66(2) : 5 1 , 20 1 7
Kuhn J H : Ebolavirus and marburgvirus infections. I n Kasper OL, Fauci AS,
Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 1 9th ed.
New York, McGraw-Hili, 20 1 5
Kurppa K, Holmberg PC, Kuosma E , e t al: Anencephaly and maternal com­
mon cold. Teratology 44: 5 1 , 1 99 1
Kutty PK, Kyaw MH, Dayan G H , e t al: Guidance for isolation precautions
for mumps in the US: a review of the scientiic basis for policy change. Clin
Infect Disease 50( 1 1 2) : 1 69, 20 1 0
Kwatra G, Cunnington MC, Merrall E, et al: Prevalence of maternal coloni­
zation with group B streptococcus: a systematic review and meta-analysis.
Lancet Infect Dis 1 6(9) : 1 076, 20 1 6
Kylat RI, Bartholomew A , Cramer N , e t al: Neonatal listeriosis: uncommon or
misdiagnosed? J Neonatal Perinatal Med 9(3) : 3 1 3 , 20 1 6
Laibl VR, Sheield JS, Roberts S , e t al: Clinical presentation o f com muniry­
acquired methicillin-resistant Staphylococcus aureus in pregnancy. Obstet
Gynecol 1 06:46 1 , 2005
Lam CM, Wong SF, Leung TN, et al: A case-controlled study comparing clini­
cal course and outcomes of pregnant and non-pregnant women with severe
acute respiratory syndrome. BJOG 1 1 1 :77 1 , 2004
Lambert N, Strebel P, Orenstein W: Rubella. Lancet 385 :2297, 20 1 5
Lamont RF, Sobel JD, Carrington D , et al: Varicella-zoster virus (chickenpox)
infection in pregnancy. BJOG 1 1 8 : 1 1 5 5 , 20 1 1 a
Lamont RF, Sobel JD, Vaisbuch E, et al: Parvovirus B 1 9 infection in human
pregnancy. BJOG 1 1 8(2) : 1 75 , 20 1 1 b
Lassen J, Jensen AK, Bager P, et al: Parvovirus B 1 9 infection in the first trimes­
ter of pregnancy and risk of fetal loss: a population-based case-control study.
Am J Epidemiol 1 76(9) :803, 20 1 2
Lee IW, Kang L, Hsu HP, et al: Puerperal mastitis requiring hospitalization
during a nine-year period. Am J Obstet Gynecol 203:332.e 1 , 20 J 0
Leruez- Ville M, Ghout I, Bussieres L, et al: In utero treatment of congenital
cytomegalovirus infection with valacyclovir in a multicenter, open-label,
phase II study. Am J Obstet Gynecol 2 1 5 (4) :462.e 1 , 20 1 6
Leruez-Ville M , Magny JF, Couderc S , e t al: Risk factors for congenital cyto­
megalovirus infection following primary and nonprimary maternal infec­
tion: a prospective neonatal screening study using polymerase chain reaction
in saliva. Clin Infect Dis 65 (3) :398, 20 1 7
Li u C , Bayer A , Cosgrove SE, e t al: Clin ical practice guidelines by the I nfec­
tious Diseases Society of America for the treatment of methicillin-resistant
Staphylococcus aureus infections in adults and children. Clin Infect Dis
52: e 1 8 , 20 1 1
Lynberg 'v [C, Khoury MJ, Lu X, et al : Maternal lu, fever, and the risk of
neural tube defects: a population-based case-control study. Am J Epidemiol
140:244, 1 994
Mace E, Arguin PM: Malaria Surveillance-United States, 20 1 4. MMWR
66( 1 2) : 1 , 20 1 7
Mace G , Sauvan M , Castaigne V , e t al: Clinical presentation and outcome of
20 fetuses with parvovirus B 1 9 infection complicated by severe anemia and/
or fetal hydrops. Prenat Diagn 34 ( 1 1 ) : 1 023, 2 0 1 4
Machado Filho A C , d a Costa E P , da Costa EP, e t al : Efects of vivx malaria
acquired before 20 weeks of pregnancy on subsequent changes in fetal
growth. Am J Trop Med Hyg 90(2) :37 1 , 20 1 4
Madhi SA, Cudand CL, Jose L , e t al: Safety and immunogenicity o f an i nvesti­
gational maternal trivalent group B streptococcus vaccine in healthy women
and their infants: a randomised phase 1 b/2 trial. Lancet Infect Dis 1 6(8):
923, 20 1 6
Mandelbrot : Fetal varicella-diagnosis, management, and outcome. Prenat
Diagn 32 (6) : 5 1 1 , 20 1 2
Marin M , Giiris 0 , Chaves SS, et al: Prevention of varicella: recommendations
of the Advisoty Committee on I mmunization Practices (ACIP) . MM'R
56(4) : 1 , 200
M arin M , Willis ED, Marko A, e t al: Closure of varicella-zoster virus­
containing vaccines pregnancy registry-United States . MMWR 2 2 : 6 3 ,
20 1 4
Marzec NS, Bessesen MT: Risk and outcomes o f methicillin-resistant Staphy­
lococcus aureus (tvI RSA) bacteremia among patients admitted with and
without M RSA nares colonization. Am J Infection Control 44:405, 2 0 1 6
Mayama M , Yoshihara M , Kokabu T , e t al: Hemophagocytic Iymphohistiocy­
rosis associated with a parvovirus B 1 9 infection during pregnancy. Obstet
Gynecol 1 24(Pt 2 Suppl 1 ) :438, 20 1 4
Mayor A, Bardajf A, Macete E , e t al: Changing trends in P . falciparum b urden,
immunity, and disease in pregnancy. N Engl J Med 373 ( 1 ) : 1 607, 20 1 5
McClure EM, Goldenberg RL: Infection and stillbirrh. Semin Fetal Neonatal
Med 1 4(4) : 1 82, 2009
1 232 M ed i ca l and S u rg ica l Co m p l i cat i o n s
McClure E M , Goldenberg L, Dent E, et al: A systematic review of the
impact of malaria prevention in pregnancy on low birth weight and mater­
nal anemia. Int J Gynaecol Obstet 1 2 1 : 1 03, 20 1 3
McLean HQ, Fiebelkorn AP, Temte JL, e t al: Prevention o f measles, rubella,
congenital rubella syndrome, and mumps, 20 1 3: summary recommenda­
tions of the Advisory Committee on I mmunization Practices (ACIP).
MMWR 62(4) : 1 , 20 1 3
Meaney-Delman 0, Oduyebo T , Polen KN, e t al: Prolonged detection of Zika
virus RNA in pregnant women. Obstet Gynecol 1 28 (4) :724, 20 1 6
Meaney-Delman 0 , Rasmussen SA, Beigi RH, e t al: Prophylaxis and treatment
of anthrax in pregnant women. Obstet Gynecol 1 22 (4) : 8 8 5 , 20 1 3
Meaney-Delman 0 , Zotti ME, Rasmussen SA, e t al: Anthrax cases i n pregnant
and postpartum women. Obstet GynecoI 1 20(6) : 1 439, 20 1 2
Meijer J , van Noortwijk AG , Bruinse HW, e t al: I n fluenza virus infection i n
pregnancy: a review. Acta Obstet Gynecol Scand 94 (8):797, 20 1 5
Melamed N , Whittle W, Kelly EN, et al: Fetal thrombocytopenia i n preg­
nancies with fetal human parvovirus-B 1 9 infection. Am J Obstet Gynecol
2 1 2 :793.e 1 , 20 1 5
Mendelson E , Aboundy Y, Smetana Z , et al: Laboratory assessment and
diagnosis of congenital viral infections: rubella, cytomegalovirus (CMV) ,
varicella-zoster virus (VZV) , herpes simplex virus (HSV), parvovirus B 1 9
and human immunodeficiency virus (HI). Reprod Toxicol 2 1 :350, 2006
Menendez C, D'Alessandro U, ter Kuile FO: Reducing the burden of malaria
i n pregnancy by preventive strategies. Lancet I nfect Dis 7: 1 26, 2007
Mertz 0, Geraci J, Winkup J, et al: Pregnancy as a risk factor for severe out­
comes from inluenza virus infection: a systematic review and meta-analysis
of observational studies. Vaccine 3 5 (4) : 5 2 1 , 20 1 7
Miller E , Cradock-Watson JE, Pollock TM: Consequences o f conirmed
maternal rubella at successive stages of pregnancy. Lancet 2:78 1 , 1 982
Miller LG, Daum RS, Creech CB, et al: Clindamycin versus trimethoprim­
sulfamethoxazole for uncomplicated skin infections. N Engl J Med
372 ( 1 2) : 1 093, 20 1 5
Modlin F : Perinatal echovirus and group B coxsackievirus infections. Clin Peri­
natoI 1 5 :233, 1 988
Money 0, Infectious Disease Committee Members, Yudin MH, et al: SOBC
committee opinion on the management of a pregnant woman exposed to
or infected with Ebola virus disease i n Canada. J Obstet Gynaecol Can
37(2): 1 82, 20 1 5
Montazeri M , Sharif M , Sarvi S , e t al: A systematic review o f i n vitro and
in vivo activities of anti-toxoplasma drugs and compounds (2006-20 1 6) .
Front Microbiol 8(25): 1 , 2 0 1 7
Montoya JG, Remington J S : Management of Toxoplasma gondii infection
during pregnancy. Clin Infect Dis 47:5 54, 2008
Moore CA, Staples JE, Dobyns B , et al: Characterizing the pattern of anom­
alies i n congenital Zika syndrome for pediatric clinicians. JAMA Pediatr
1 7 1 (3) :288, 2 0 1 7
Moschella S L : A n update o n the diagnosis and treatment of leprosy. J A m Acad
Dermatol 5 1 :4 1 7, 2004
Muehlenbachs A, de la Rosa Vazquez 0 , Bausch DG, et al: Ebola virus disease
in pregnancy: clinical, histopathologic, and immunohistochemical findings.
J Infect Dis 2 1 5 ( 1 ) :64, 20 1 7
Mylonakis E, Paliou M, Hohmann EL, e t al: Listeriosis during pregnancy.
Medicine 8 1 : 260, 2002
Mylonas I: Borreliosis during pregnancy: a risk for the unborn child? Vector
Borne Zoonotic Dis 1 1 (7):89 1 , 20 1 1
Nagel HT, de Haan TR, Vandenbussche FP, et al: Long-term outcome after
fetal transfusion for hydrops associated with parvovirus B 1 9 infection.
Obstet Gynecol 1 09 ( 1 ) :42, 2007
Nan e, Dangor Z, Cutland CL: Maternal group B streptococcus-related still­
birth: a systematic review. BJOG 1 22( 1 1 ) : 1 437, 20 1 6
Nguyen LN, Lopes e , Folk JJ: vertebral osteomyelitis in pregnancy from a
methicillin-resistant Staphylococcus aureus vulvar abscess. A case report.
J Reprod Med 60(7-8):362, 20 1 5
Nigro G , Adler SP, La Torre R, e t al: Passive immunization during pregnancy
for congenital cytomegalovirus infection. N Engl J Med 353 : 1 350, 2005
Nigro G , Adler SP, Parruti G, et al: Immunoglobulin therapy of fetal cytomeg­
alovirus infection occurring in the first half of pregnancy-a case-control
study of the outcome in children. J Infect Dis 205:2 1 5 , 20 1 2
Nigro G , Anceschi MM, Cosmi EV, e t al: Clinical manifestations and abnor­
mal laboratory findings in pregnant women with primary cytomegalovirus
infection. BJOG 1 1 0 : 572, 2003
Nishiura H: Smallpox during pregnancy and maternal outcomes. Emerg Infect
Dis 1 2: 1 1 1 9, 2006
Nosten F, McGready R, Mutabingwa T: Case management of malaria in preg­
nancy. Lancet Infect Dis 7: 1 1 8 , 2007
Nunes Me, Cutland CL, Jones S , et al: Eicacy of maternal influenza vac­
cination against all-cause lower respiratory tract infection hospitalizations in
young infants: results from a randomized control trial. Clin Infect Disease
May 29, 20 1 7 [Epub ahead of print]
O'Leary DR, Kuhn S, Kniss L, et al: B irth outcomes following West Nile
virus infection of pregnant women i n the United States: 2003-2004. Pedi­
atrics 1 1 7:e537, 2006
Oboho I K, Reed C, Gargiullo P, et al: Benefit of early initiation of influ­
enza antiviral treatment to pregnant women hospitalized with laboratory­
confirmed influenza. J Infect Dis 2 1 4(4) : 5 07, 20 1 6
Oduyebo T , Pineda 0, Lamin M , e t al: A pregnant patient with Ebola virus
disease. Obstet GynecoI 1 26 (6) : 1 273, 20 1 5
Oduyebo T , Polen KD, Walke HT, et al: Update: interim guidance for
health care providers caring for pregnant women with possible Zika virus
exposure-United States (including U.S. Territories), July 2017. MMWR
66(29) : 78 1 , 20 1 7
Ohji G , Satoh H , Satoh H , e t al: Congenital measles caused b y transplacental
infection. Pediatr I nfect Dis J 28 (2) : 1 66, 2009
Ohlsson A, Shah VS: I ntrapartum antibiotics for known maternal Group B
streptococcal colonization. Cochrane Database Syst Rev (6):CD007467,
20 1 4
Ornoy A , Tenenbaum A : Pregnancy outcome following infections b y cox­
sackie, echo, measles, mumps, hepatitis, polio and encephalitis viruses.
Reprod ToxicoI 2 1 :446, 2006
Ozturk Z, Tatliparmak A: Leprosy treatment during pregnancy and breastfeed­
ing: a case report and brief review of literature. Dermatol her 30( 1 ) : 1 , 20 1 7
Parisot M , Jolivet A , Boukhari R, et al: Shigellosis and pregnancy i n French
Guiana: obstetric and neonatal complications. Am J Trop Med Hyg
9 5 ( 1 ) :26, 20 1 6
Parra B , Lizarazo J , Jimenez-Arango JA, et al: Guillain-Barre syndrome associ­
ated with Zika virus infection in Colombia. N Engl J Med 375 ( 1 6) : 1 5 1 3 ,
20 1 6
Paryani SG, Arvin AM: Intrauterine infection with varicella zoster virus ater
maternal varicella. N Engl J Med 3 1 4: 1 542, 1 986
Pasquini L, Seravilli V, Sisti G , et al: Prevalence of a positive TORCH and
parvovirus B 1 9 screening in pregnancies complicated by polyhydramnios.
Prenat Diagn 36(3) :290, 20 1 6
Paz-Bailey G , Rosenberg ES, Doyle K , e t al: Persistence o f Zika virus i n body
fluids-preliminary report. N Engl J Med February 1 4 , 20 1 7 [Epub ahead
of print]
Peques DA, Miller SI: Salmonellosis. In Longo DL, Fauci AS, Kasper DL, et
al (eds): Harrison's Principles of Internal Medicine, 1 8th ed. New York,
McGraw-Hill
Phadke K, Bednarczyk A, Salmon DA, et al: Association between vac­
cine refusal and vaccine-preventable diseases in the United States. JAMA
3 1 5 ( 1 1 ) : 1 1 49, 20 1 6
Picone 0, Grangeot-Keros L , Senat M , e t al: Cytomegalovirus non-primary
infection during pregnancy. Can serology help with diagnosis? J Matern
Fetal Neonatal Med 30(2):224, 20 1 7
Pimentel JD, Meier FA, Samuel LP: Chorioamnionitis and neonatal sepsis
from community-acquired MRSA. Emerg I nfect Dis 1 5 : 2069, 2009
Pinter OM, Mandel J, Hulten KG, et al: Maternal-infant perinatal transmis­
sion of methicillin-resistant and methicillin-sensitive Staphylococcus aureus.
Am J PerinatoI 26: 1 45, 2009
Polyzos A, Konstantelias A, Pitsa CE, et al: Maternal influenza vaccina­
tion and risk for congenital malformations: a systematic review and meta­
analysis. Obstet Gynecol 1 26(5) : 1 075, 20 1 5
PREGACT Study Group, Pekyi 0 , Ampromfi A, e t al: Four artemisinin­
based treatments in African pregnant women with malaria. N Engl J Med
374( 1 ) : 9 1 3, 20 1 6
Pridjian G , Sirois PA, McRae S , e t al: Prospective study o f pregnancy and new­
born outcomes in mothers with West Nile illness during pregnancy. Birth
Oefects Res A Clin Mol Teratol 1 06(8):7 1 6, 20 1 6
Puccetti e , Contoli M , Bonvicini F , e t al: Parvovirus B 1 9 i n pregnancy:
possible consequences of vertical transmission. Prenat Diagn 32(9) :897,
20 1 2
Rainwater-Lovett K , Moss WJ : Measles (rubeola). I n Kasper DL, Fauci AS,
Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 1 9th ed.
New York, McGraw-Hill, 20 1 5
Randis TM, Gleber SE, Hooven TA: Group B streptococcus beta-hemolysin/
cytolysin breaches maternal-fetal barriers to cause preterm birth and IUFO
in vivo. J I nfect Ois 2 1 0:65, 20 1 4
Rasmussen SA, Jamieson OJ : What obstetric health care providers need to
know about measles and pregnancy. Obstet GynecoI 1 26 ( 1 ) : 1 63, 20 1 5
Rasmussen SA, Jamieson OJ, Honein MA, e t al: Zika virus and birth
defects-reviewing the evidence for causality. N Engl J Med 374 (20) : 1 98 1 ,
20 1 6
Rasmussen SA, Jamieson OJ, Uyeki TM: Efects o f inluenza o n pregnant
women and infants. Am J Obstet Gynecol 207(3 Suppl) :S3, 20 1 2

Revello MG, Furione M, Zavattoni M, et al: Human cytomegalovirus
(HCMV) DNAemia in the mother at amniocentesis as a risk factor for iat­
rogenic H CMF infection of the fetus. ] Infect Dis 19 : 593, 2008
Reynolds M R, Jones AM, Peterson EE, et al: Vital signs: Update on Zika
virus-associated birth defects and evaluation of all U.S. infants with con­
genital Zika virus exposure-U.S. Zika pregnancy registry, 20 1 6. MMWR
66(1 3) :366 20 1 7
Rogers B B : Parvovirus B 1 9 : twenty-five years i n perspective. Pediatr Dev
Pathol 2:296, 1 999
Rogerson S], Hviid L, Duy PE, et al: Malaria in pregnancy: pathogenesis and
immunity. Lancet Infect Dis 7: 1 0 5 , 2007
Romand S, Wallon M, Franck ], et al: Prenatal diagnosis using polymerase
chain reaction on amniotic luid for congenital toxoplasmosis. Obstet
Gynecol 97(2): 296, 200 1
Ross SA, Novak Z, Pati S, et al: Mixed infection and strain diversity in
congenital cytomegalovirus infection. ] Infect Dis 204: 1 003, 20 1 1
Rouse D], Keimig W, Riley LE, et al: Case Records of the Massachusetts
General Hospital. Case 1 6-20 16. A 3 1 -year-old pregnant woman with
fever. N Engl ] Med 3 4(2 1 ) :2076, 2 0 1 6
Rubin S , Carbone M : Mumps. In Longo D L , Fauci AS , Kasper D L , et
al (eds): Harrison's Principles of Internal Medicine, 1 8th ed. New York,
McG raw-Hill, 20 1 2
Ryan MA, Smith T C , Sevick C]: Birth defects among infants born t o women
who received anthrax vaccine in pregnancy. Am ] EpidemioI 1 68:434, 2008
Sanchez E, Vannier E, Wormser GP, et al: Diagnosis, treatment, and preven­
tion of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a
review. ]MA 3 1 5 ( 1 6) : 1 67, 2 0 1 6
Sapuan S , Kortsalioudaki C , Anthony M , e t al: Neonatal listeriosis in the U K
2004-20 1 4 . ] Infect 74(3):236, 20 1
Schleiss MR: Cytomegalovirus vaccines under clinical development. J Virus
Erad 2(4) : 1 98, 20 1 6
Schrag 5], Farley M M , Petit S: Epidemiology o f invasive early-onset neonatal
sepsis, 2005-20 14. Pediatrics 1 3 8 (6) :e20 1 620 1 3, 20 1 6
Sever ] L, South MA, Shaver A : Delayed manifestations o f congenital rubella.
Rev Infect Dis 7( 1 ) : S 1 64, 1 985
Shang M, Blanton L, Kniss K, et al: Update: influenza activity-United States,
October 2-December 1 7, 20 1 6 . MMWR 65(50 5 1 ) : 1 439, 20 1 6
Shapiro E D : Lyme disease. N Engl ] Med 370 ( 1 8) : 1 24, 20 1 4
Shaw G M , Todorof K , Velie EM, e t al: Maternal illness, including fever, and
medication use as risk factors for neural tube defects. Teratology 57: 1 , 1 998
Sheield ]S: Methicillin-resistant Staphylococcus aureus in obstetrics. An ]
PerinatoI 30(2) : 1 2 5 , 20 1 3
Shinar S , Fouks Y, Anit S , e t al: Clinical characteristics o f and preventative
strategies for periparrum group A streptococcal infections. Obstet Gynecol
1 27(2) :227, 20 1 6
Siegel M : Congenital malformations following chickenpox, measles, mumps,
and hepatitis: results of a cohort study. ]AMA 226: 1 52 1 , 1 973
Siegel M, Goldberg M: Incidence of poliomyelitis in pregnancy. N Engl ] Med
253:84 1 , 1 9 5 5
Silk B], Mahon BE, Griin PM, e t al: Vital signs: Listeria illness, deaths, and
outbreaks-United States, 2009-20 1 1 . MMWR 62(22):448, 20 1 3
Soares d e Oliveira-Szejnfeld P , Levine D , Melo AS, e t a l : Congenital brain
abnormalities and Zika virus: what the radiologist can expect to see prena­
tally and postnatally. Radiology 28 1 0 ) :203, 20 1 6
Society for Maternal-Fetal Medicine (SMFM) , Hughes BL, Gyami-Banner­
man C: Diagnosis and antenatal management of congenital cytomegalovirus
infection. Am ] Obstet Gynecol 2 1 4(6) : B 5 , 20 1 6
Staford LA, Stewart RD, Sheield ] S , e t al: Eicacy o f maternal and neona­
tal chemoprophylaxis for early-onset group B streptococcal disease. Obstet
Gynecol 1 20 ( 1 ) : 1 23, 20 1 2
Stagno S , Tinker MK, Elrod C , et al: I mm unoglobulin M antibodies detected
by enzyme-linked immunosorbent assay and radioimmunoassay in the
diagnosis of cytomegalovirus infections in pregnant women and newborn
infants. ] C1in Microbiol 21 (6) :930, 1 98 5
Steere A C : Lyme borreliosis. In Kasper D L, Fauci AS, Hauser S L , e t a l (eds):
Harrison's Principles of Internal Medicine, 1 9th ed. New York, McG raw­
Hill, 20 1 5
Steinhof MC, Omer SB: A review o f fetal and infant protection associated
with antenatal inluenza immunization. Am J Obstet Gynecol 207(3 Suppl) :
S2 1 , 20 1 2
Stewart R D , Bryant S N , Sheield ]S: West Nile virus infection in pregnancy.
Case report. Infect Dis 20 1 3 :35 1 872, 20 1 3
Stoll B], Hansen N I , Sanchez P], e t al: h e burden o f group B streptococcal
and E. coli disease continues. Pediatrics 1 27(5) : 8 1 , 20 1 1
Sukumaran L, McCarthy NL, Kharbanda EO, et al: Safety of tetanus toxoid,
reduced diphtheria toxoid and acellular pertussis and inluenza vaccinations
in pregnancy. Obstet Gynecol 1 26(5): 1 069, 20 1 5
I nfectious Di sea ses 1 23 3
Svensson-Arvelund ] , Ernerudh ] , B use E, e t al: h e placenta i n toxicology. Part
II: systemic and local immune adaptations in pregnancy. Toxicol Pathol
42(2) :32 , 20 1 4
Swamy G K, Heine RP: Vaccinations for pregnant women. Obstet Gynecol
1 2 5 ( 1 ) :2 1 2, 20 1 5
SYROCOT (Systematic Review o n Congenital Toxoplasmosis) Study Group:
Efectiveness of prenatal treatment for congenital toxoplasmosis: a meta­
analysis of individual patients' data. Lancet 369: 1 1 5 , 2007
Talan DA, Mower WR, Krishnadasan A, et al: Trimethoprim-sulfamethoxazole
versus placebo for uncomplicated skin abscess. N Engl ] Med 374 (9):823,
20 1 6
Tanamai VW, Seagle BL, Luo G : Methicillin-resistant Staphylococcus aureus
intracranial epidural abscess with osteomyelitis during pregnancy: a case
report. ] Reprod Med 6 1 (5-6) :295, 20 1 6
Tarning ]: Treatment o f malaria i n pregnancy. N Engl ] Med 374 ( 1 ) : 98 1 ,
20 1 6
Tassin M , Martinovic ] , Mirand A , e t al: A case of congenital echovirus 1 1
infection acquired early in pregnancy. ] Clin Virol 59:7 1 , 20 1 4
Thurman AR, Satterield RM, Soper D E : Methicillin-resistant Staphylococcus
aureus as a common cause of vulvar abscesses. Obstet Gynecol 1 1 2: 538,
2008
Top A, Huard RC, Fox Z, et al: Trends in methicillin-resistant Staphylococ­
cus aureus anovaginal colonization in pregnant women in 2005 versus 2009.
] C1in Microbiol 48 :3675, 20 1 0
Towbin ]A, Griin L D , Martin A B , e t al : I ntrauterine adenoviral myocarditis
presenting as nonimmune hydrops fetalis: diagnosis by polymerase chain
reaction. Pediatr Infect Dis ] 1 3 : 1 44, 1 994
Tudela CM, Stewart RD, RobertS SW, et al : Intrapartum evidence of early­
onset group B streptococcus. Obstet Gynecol 1 1 9 (3) :626, 20 1 2
Valentini P , Buonsenso 0, Barone G , e t al: Spiramycin/cotrimoxazole ver­
sus pyrimethamine/sulfonamide and spiramycin alone for the treatment of
toxoplasmosis in pregnancy. ] Perinatol 3 5 (2):90, 20 1 5
Villard 0 , Breit L , Cimon B , et al: Comparison o f four commercially available
avidity tests for Toxoplasma gondii-speciic IgG antibodies. Clin Vaccine
ImmunoI 20(2) : 1 97, 20 1 3
Visentin S , Manara R , Milanese L , e t al : Early primary cytomegalovirus infec­
tion in pregnancy: maternal hyperimmunoglobulin therapy improves out­
comes among infants at 1 year of age. Clin Infect Dis 5 5 (4) :497, 20 1 2
Viskari H , Knip M , Tauriainen S , et al: Maternal enterovirus infection s a risk fac­
tor for type 1 diabetes in the exposed ofspring. D iabetes Care 35(6) : 1 328, 20 1 2
Wallon M , Gatweg ]G, Abrahamowicz M, e t al: Ophthalmic outcomes of con­
genital toxoplasmosis followed until adolescence. Pediatrics 1 33(3):e60 1 , 20 1 4
Wallon M , Peyron F, Cornu C, et al: Congenital toxoplasma infection:
monthly prenatal screening decreases transmission rate and improves clini­
cal outcome at age 3 years. Clin Infect Dis 56(9) : 1 223, 20 1 3
Walsh CA, Mayer EQ, Baxi LV: Lyme disease i n pregnancy: case report and
review of the literature. Obstet Gynecol Surv 62:4 1 , 2006
Wang C, Zhang X, Bialek S , et al: Attribution of congenital cytomegalovirus
infection to primary versus non-primary matenal infection. Clin Infect Dis
52:e1 1 , 20 1 1
Waner M], Ozanne SE: Mechanisms involved in the developmental program­
ming of adulthood disease. Biochem ] 427:333, 20 1 0
W ebster WS: Teratogen update: congenital rubella. Terarology 5 8 : 1 3 , 1 998
Weifenbach ], Bald R, Gloning KP, et al: Serological and virological analysis of
maternal and fetal blood samples in prenatal human parvovirus B 19 infec­
tion. ] Infect Dis 205 ( 5) : 782, 20 1 2
Wendel G O Jr, Leveno K], Sanchez P], e t al: Prevention o f neonatal group B
streptococcal disease: a combined intrapartum and neonatal protocol. Am ]
Obstet Gynecol 1 86:6 1 8, 2002
Wessels MR: Streptococcal infections. I n Kasper DL, Fauci AS, Hauser SL,
et al (eds): Harrison's Principles of Intenal Medicine, 1 9th ed. New York,
McGraw-Hill, 20 1 5
White N], Breman ]G: Malaria infections. I n Kasper DL, Fauci AS, Hauser SL,
et al (eds): Harrison's Principles of Intenal Medicine, 1 9th ed. New York,
McGraw-Hill, 20 1 5
Whitley R]: Varicella-zoster virus infections. I n Kasper DL, Fauci AS, H auser
SL, et al (eds): Harrison's Principles of I ntenal Medicine, 1 9th ed. New
York, McGraw-Hili, 20 1 5
Wilson E , Goss vA, Marin M , e t al: Varicella vaccine exposure during preg­
nancy: data from 10 years of the pregnancy registry. ] I nfect Dis 1 97(S uppl
2): S l 78, 2008
Wong SF, Chow M, Leung TN, et al: Pregnancy and perinatal outcomes
of women with severe acute respiratory syndrome. Am ] Obstet Gynecol
1 9 1 : 292, 2004
World Health Organization: Long-term efects of breastfeeding: a systematic
review, 20 1 3 . Available at: htrp:l/ww.who. int/maternal_child_adolescent/
documents/breastfeedingJon�term_efects. Accessed October 9, 20 1 7
1 234 Med i c a l and S u rg ical Co m p l i catio n s
World Health Organization: WHO vaccine pipeline tracker, 20 1 7. Available
at: www.who. int/immunization/research/vaccine_pi peline_trackecspread­
sheet/en.! Accessed September 1 0, 20 1 7
Wylie B , Hauptman M , Woolf AD: Inset repellants during pregnancy i n the
era of the Zika virus. Obstet Gynecol 1 28(5): 1 1 1 1 , 20 1 6
Yaegashi N: Pathogenesis o f nonimmune hydrops fetalis caused b y intrauterine
B 1 9 infection. Tohoku ] Exp Med 1 90:65, 2000
Yazigi A, De Pecoulas E, Vauloup-Fellous C, et l: Fetal and neonatal abnor­
malities due to congenital rubella syndrome: a review of literature. ] Matern
Fetal Neonatal Med 30(3) :274, 20 1 7
Young M K, Cripps AW, Nimmo GR, e t al: Post-exposure passive immuni­
zation for preventing rubella and congenital rubella syndrome. Cochrane
Database Syst Rev 9:CD0 1 05 86, 20 1 5
Yu W , Tellier R, Wright ]R ] : Coxsackie virus A 1 6 infection of placenta with
massive perivillous ibrin deposition leading to intrauterine fetal demise at
36 weeks gestation. Pediatr Dev Pathol 1 8 (4):33 1 , 20 1 5
Zaman K , Roy E , Arifeen SE, e t al: Efectiveness o f maternal influenza
immunization in mothers and infants. N Engl ] Med 359( 1 5) : 1 5 5 5 ,
2008
Zerbo 0, Qian Y, Yoshida C, et al: Association berween inluenza infection and
vaccination during pregnancy and risk of autism spectrum disorder. ]AlA
Pediarr 1 7 1 ( 1 ) :e 1 63609, 20 1 7
Zhang H], Patenaude V, Abenhaim A : Maternal outcomes in pregnan­
cies afected by varicella zoster virus infections: population-based study
on 7.7 million pregnancy admissions. ] Obstet Gynaecol Res 4 1 ( 1 ) :62,
20 1 5
Infectious Diseases
Crisostomo Santos O. Ordoño Jr. MD, FPOGS, MBAH
Introduction

´ Infections + pregnancy =
fetal effect ??
´ Depends on:
´ Maternal serological status
´ Gestational age of
exposure
´ Mode of acquisition
´ Immunologic status of
mother & child
Maternal Immunology

´ Not well understood

´ What is known:
´ Increase in CD4 + T cells
´ Th1-type cytokines suppressed
´ Th2 type cytokines increased
´ EFFECT: Th2 bias in pregnancy
“..type  2  dominance  is  credited  with  tolerance  
of  xenografts  and  of  the  fetus  during  
pregnancy..”  https://www.ncbi.nlm.nih.gov/pubmed/12946237
Fetal & Neonatal immunology

´ Largely compromised
´ CMI & Humoral Immune
response: 9 to 15 weeks
AOG
´ 1o fetal response: IgM
´ IgG source; maternal origin
´ At birth:
´ IgA dominant
immunoglobulin in breast
milk
 Fetal & Neonatal immunology

´ Type of Transmission:
´ Vertical Transmission
´ Placenta
´ During labor & delivery
´ Breast feeding
´ Therefore:
´ PROM
´ Prolonged labor
´ OB manipulations
..increases risk of neonatal infection
Fetal & Neonatal immunology
´ Neonatal infection is hard
to diagnosed due to non
classical presentations
´ Depressed & acidotic w/o
reason at birth
´ Poor suck
´ Vomiting
´ Abdominal distention
´ Respiratory insufficiency
´ Lethargic
´ Hypothermic
´ Low WBC count
Viral Infections

´ Varicella Zoster
´ Influenza
´ Mumps
´ Rubeola (Measles)
´ Rubella (German
Measles)
Viral Infections

´ Varicella Zoster ´ Double stranded DNA

´ Influenza ´ 95% of adults are serologically

immune
´ Mumps ´ Transmission: direct contact
´ Rubeola (Measles) ´ Incubation period 10 – 21 days
´ Rubella (German ´ Non-immune women: 60% -
Measles) 95% risk of acquisition
´ Contagious: 1 day before
onset of rash to crusted lesions
Viral Infections

´ Varicella Zoster ´ Maternal Infection

´ 1 – 2 days flu-like prodrome
´ Influenza
´ Followed by pruritic vesicular
´ Mumps lesion that crust within 3 – 7 days
´ Rubeola (Measles) ´ Maybe lethal for immune
compromise patients
´ Rubella (German ´ Varicella Pneumonia
Measles) ´ Appears 3 – 5 days
´ Herpes Zoster reactivation years
after acquiring the disease
Viral Infections

´ Varicella Zoster ´ Fetal & Neonatal Infection

´ 1st half of pregnancy
´ Influenza
´ May develop congenital
´ Mumps Varicella syndrome
´ Some features;
´ Rubeola (Measles)
´ Chorioretinitis
´ Rubella (German ´ Micropthalmia
Measles) ´ Greatest risk when infected
between 13 & 20 weeks
AOG
Viral Infections

´ Varicella Zoster ´ Fetal & Neonatal Infection

´ Before / during delivery
´ Influenza
´ May have serious effects on the
´ Mumps neonate
´ Mortality approaches 30%
´ Rubeola (Measles)
´ May develop disseminated
´ Rubella (German visceral & CNS disease
Measles) ´ MUST be given Varicella – Zoster
immunoglobulin if mother has
clinical evidence of disease 5
days before and up to 2 days
after delivery
Viral Infections

´ Varicella Zoster ´ Diagnosis

´ Clinical
´ Influenza
´ Labs:
´ Mumps ´ Tzanck smear
´ Rubeola (Measles) ´ Tissue culture
´ Direct Flourescent antibody
´ Rubella (German testing
Measles) ´ Nucleic acid amplification test

´ Congenital Varicella
syndrome:
´ Nucleic acid amplification test
of Amniotic Fluid
Viral Infections

´ Varicella Zoster ´ Management

´ Maternal Exposure
´ Influenza
´ If (-) exposure on history: request
´ Mumps for VZV serological test
´ If (+) history of disease: 70% are
´ Rubeola (Measles) serologically immune
´ Rubella (German ´ If sero (-) give Varicella Immune
globulin within:
Measles)
´ 96 hours (4days) from
exposure
Viral Infections

´ Varicella Zoster ´ Management

´ Maternal Infection
´ Influenza
´ Isolate the pregnant woman
´ Mumps ´ Chest X-ray is recommended
´ Rubeola (Measles) ´ Supportive care
´ Acyclovir therapy at 10 – 15
´ Rubella (German mg/kg every 8 hours
Measles)
Viral Infections

´ Varicella Zoster ´ Management

´ Vaccination
´ Influenza
´ Two (2) doses
´ Mumps ´ 4 – 9 weeks apart
´ Rubeola (Measles) ´ 98% seroconversion
´ Not given during pregnancy
´ Rubella (German
´ But safe for breastfeeding
Measles) moms
Viral Infections

´ Varicella Zoster ´ Caused by Orthomyxoviridae

family of viruses
´ Influenza
´ Influenza A & B
´ Mumps ´ Subclassification:
´ Rubeola (Measles) ´ Hemagglutinin (H)
´ Rubella (German ´ Neuraminidase (N)
Measles)
Viral Infections

´ Varicella Zoster ´ Maternal Infection:

´ Fever, cough & systemic
´ Influenza symptoms
´ Mumps ´ Pregnant women susceptible
to pulmonary complications
´ Rubeola (Measles)
´ Rubella (German
Measles)
Viral Infections

´ Varicella Zoster ´ Fetal Effect:

´ No firm evidence of
´ Influenza congenital effects
´ Mumps ´ Suspected effect:
´ Rubeola (Measles) ´ neural tube defect
´ Stillbirth
´ Rubella (German
´ Preterm delivery
Measles)
´ abortion
Viral Infections

´ Varicella Zoster ´ Diagnosis:

´ Clinical
´ Influenza
´ Labs:
´ Mumps ´ Reverse Transcription –
Polymerase chain reaction (RT-
´ Rubeola (Measles) PCR) sensitive & specific
´ Rubella (German ´ Management:
Measles) ´ Oseltamivir: (category C)
´ Treatment: 75 mg P.O. x 5 days
´ Prophylaxis: 75 mg O.D. x 10 days
Viral Infections

´ Varicella Zoster ´ Vaccination

´ Recommended for:
´ Influenza
´ Diabetes mellitus
´ Mumps ´ Heart disease
´ Rubeola (Measles) ´ Asthma
´ HIV
´ Rubella (German
Measles) ´ Live Attenuated vaccine NOT
recommended to pregnant
women
Viral Infections

´ Varicella Zoster ´ Caused by RNA

paramyxovirus
´ Influenza
´ Primarily infects the salivary
´ Mumps glands
´ Rubeola (Measles) ´ Transmitted by direct contact

´ Rubella (German ´ Treatment is symptomatic

Measles)
Viral Infections

´ Varicella Zoster ´ Effect on the pregnancy:

´ Increase risk for spontaneous
´ Influenza abortion
´ Mumps ´ Not associate with congenital
malformations
´ Rubeola (Measles)
´ Fetal infection is rare
´ Rubella (German
´ Vaccination:
Measles)
´ Part of MMR
´ Pregnancy should be avoided
for 30 days after vaccination
´ Safe for breastfeeding moms
Viral Infections

´ Varicella Zoster ´ Caused by RNA

Paramyxoviridae
´ Influenza
´ Infection is characterized by:
´ Mumps ´ Fever
´ Rubeola (Measles) ´ Coryza

´ Rubella (German ´ Conjunctivitis

Measles) ´ Cough
´ Maculopapular rash
´ Kopliks spot
Viral Infections

´ Varicella Zoster ´ Diagnosis:

´ Serological testing
´ Influenza
´ Treatment:
´ Mumps
´ Supportive
´ Rubeola (Measles) ´ Exposure if sero (-)
´ Rubella (German ´ IV immunoglobulin 400mg/kg
Measles) within 6 days of exposure
Viral Infections

´ Varicella Zoster ´ Effect on the pregnancy:

´ No teratogenic effect
´ Influenza
´ Increase risk for:
´ Mumps ´ Abortions
´ Rubeola (Measles) ´ Preterm delivery
´ Low birth weight
´ Rubella (German
Measles) ´ Exposure during labor & delivery:
´ Considerable risk of developing
serious infection on the neonate
Viral Infections

´ Varicella Zoster ´ Caused by RNA togavirus

´ Influenza ´ Transmission:
´ Airborne
´ Mumps
´ Direct transmission
´ Rubeola (Measles) ´ 80% transmission rate
´ Rubella (German ´ Incubation Period: 12 – 23 days
Measles) ´ Viremia precedes clinical
symptoms by 1 week
´ Infectious: viremia period to 5 – 7
days w/ rashes
Viral Infections

´ Varicella Zoster ´ Diagnosis:

´ Serological analysis
´ Influenza
´ IgM antibody
´ Mumps ´ increase 4 – 5 days after
onset of clinical disease
´ Rubeola (Measles)
´ May persist for 6 weeks
´ Rubella (German from appearance of rash
Measles) ´ IgG antibody
´ Peak at 1 – 2 weeks after
rashes
Viral Infections

´ Varicella Zoster ´ Maternal Effect:

´ Mild febrile episodes
´ Influenza
´ Generalized maculopapular
´ Mumps rashes
´ Rubeola (Measles) ´ Arthralgia
´ Lymphadenopathy
´ Rubella (German
Measles) ´ Conjunctivitis
Viral Infections

´ Varicella Zoster ´ Pregnancy effect:

´ Increase risk for:
´ Influenza
´ Abortions
´ Mumps
´ Fetal Effects:
´ Rubeola (Measles) ´ Congenital Rubella Syndrome
´ Rubella (German ´ Neonates may also shed the
Measles) virus months after delivery
Viral Infections

´ Varicella Zoster ´ Management:

´ Supportive
´ Influenza
´ Prevention:
´ Mumps
´ Vaccination (MMR)
´ Rubeola (Measles) ´ Droplet precautions for 7 days
´ Rubella (German after onset of rashes

Measles)
Viral Infections

´ Respiratory viruses ´ Caused by Human parvovirus B19

´ Parvovirus ´ Causes Erythema Infectiosum/ 5th
disease
´ Cytomegalovirus
´ Transmission
´ Respiratory
´ Hand to mouth contact
´ Horizontal transmission:
´Mothers with school-aged
children
´ ONLY individuals with erythrocyte
globoside membrane P antigens
are susceptible
Viral Infections

´ Respiratory viruses ´ Maternal Infection

´ Parvovirus ´ 20% - 30% are asymptomatic
´ Fever
´ Cytomegalovirus
´ Headache
´ Flu like symptoms
´ Bright red rashes on face
(slapped cheek appearance)
´ Rashes spread through out
the body
Viral Infections

´ Respiratory viruses ´ Fetal Infection

´ Parvovirus ´ Non-immune hydrops fetalis
´ Stillbirth
´ Cytomegalovirus
´ Fetal Management:
´ Fetal Transfusion
´ Long Term Prognosis
´ 11% - 32% risk of abnormal
neurodevelopment
Viral Infections

´ Respiratory viruses ´ Pregnancy Effect

´ Parvovirus ´ Abortions
´ Stillbirth
´ Cytomegalovirus
´ Critical exposure period:
´ Between 13 – 16 weeks
AOG
Viral Infections

´ Respiratory viruses ´ Diagnosis

´ Parvovirus ´ Maternal serological test for
specific antibodies
´ Cytomegalovirus
´ Ig G
´ IgM
Viral Infections

´ Respiratory viruses ´ Prevention:

´ Parvovirus ´ No vaccine available

´ Cytomegalovirus
Viral Infections

´ Respiratory viruses ´ Most common perinatal

infection
´ Parvovirus
´ Virus is secreted in all body
´ Cytomegalovirus fluids
´ Transmission: direct contact
´ Anti-CMV Ig G Ab does not
prevent re-infection,
recurrence nor reactivation
´ Women who are sero (-) are at
greatest risk to have infected
fetus
Viral Infections

´ Respiratory viruses ´ Maternal Infection

´ Parvovirus ´ Pregnancy does not increase
severity of the infection
´ Cytomegalovirus
´ Mostly asymptomatic
´ Fever
´ Pharyngitis
´ Lymphadenopathy
´ Polyarthritis
Viral Infections

´ Respiratory viruses ´ Maternal Infection

´ Parvovirus ´ Immunocompromised:
´ Myocarditis
´ Cytomegalovirus
´ Pneumonitis
´ Hepatitis
´ Retinitis
´ Gastroenteritis
´ Meningoencephalitis
Viral Infections

´ Respiratory viruses ´ Fetal Infection

´ Parvovirus ´ Symptomatic CMV infection
´ Cytomegalovirus ´ Growth restriction
´ Microcephaly
´ Intracranial calcifications
´ Chorioretinitis
´ Mental and motor retardation
´ Sensorineural deficits
´ Hepatosplenomegaly
´ Jaundice
´ Hemolytic anemia
´ Thrombocytopenic purpura
´ ONLY 5% - 10% have this syndrome
Viral Infections

´ Respiratory viruses ´ Fetal Infection

´ Parvovirus ´ Late – onset sequelae
´ Cytomegalovirus ´ Hearing loss
´ Neurological deficits
´ Chorioretintis
´ Psychomotor retardation
´ Learning disabilities
Viral Infections

´ Respiratory viruses ´ Prenatal diagnosis

´ Parvovirus ´ Testing done only if:

´ Cytomegalovirus ´ Presents w/ mononucleosis- like

symptoms
´ Abnormal anatomic ultrasound
´ Microcephaly
´ Ventriculomegaly
´ Cerebral calcifications
´ Ascites
´ Hepatosplenomegaly
´ Hyperechoic bowels
´ Hydrops
´ oligohydramnios
Viral Infections

´ Respiratory viruses ´ Prenatal diagnosis

´ Parvovirus ´ Serologic test for CMV
specific:
´ Cytomegalovirus
´ Ig G
´ Ig M
´ (+) US findings & (+) AF
serological test = 75% risk of
symptomatic CMV infection
Viral Infections

´ Respiratory viruses
´ Parvovirus
´ Cytomegalovirus
Viral Infections

´ Respiratory viruses ´ Management & Prevention

´ Parvovirus ´ Symptomatic treatment
´ Counselling on fetal outcome
´ Cytomegalovirus
´ No vaccine available
´ Good hygiene
Bacterial Infections

´ Group A Streptococcus
´ Group B Streptococcus
´ Methicillin-Resistant
Staphylococcus aureus
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
Bacterial Infections

´ Group A Streptococcus ´ most common cause of:

´ Acute pharyngitis
´ Group B Streptococcus
´ Also associated with other
´ Methicillin-Resistant infections:
Staphylococcus aureus ´ Systemic
´ Listeria Moncytogenes ´ Cutaneous
´ Salmonellosis ´ Treatment:
´ Shigella ´ Penicillin
´ Most common cause of
´ Mycobacterium leprae Puerperal infection
Bacterial Infections

´ Group A Streptococcus ´ S. agalactiae found to

´ Group B Streptococcus
´ Methicillin-Resistant ´ Maternal Infection
Staphylococcus aureus
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
colonize the GIT and GUT in
20% - 30% of pregnant women
´ Maternal bacteruria
´ Pyelonephritis
´ Ostemyelitis
´ Postpartum mastitis
´ Puerperal infections
 Bacterial Infections
´ Group A Streptococcus ´ Fetal Infection
´ Group B Streptococcus
´ Methicillin-Resistant
Staphylococcus aureus
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
´ Leading cause of neonatal
infections
´ Early-onset disease:
´ Infection of < 7 days from birth
´ Intrapartum acquisition if (+)
symptoms < 72 hours from
birth
´ Septicemia
´ Develop < 6 – 12 hours
from birth
´ Respiratory distress
´ Apnea
´ hypotension
Bacterial Infections

´ Group A Streptococcus ´ Fetal Infection

´ Group B Streptococcus
´ Methicillin-Resistant
Staphylococcus aureus
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
´ Late-onset disease:
´ Manifest 1 week to 3
months from birth
´ Lesser mortality rate
´ However, devastating
neurological sequelae is
common to both onset
Bacterial Infections
´ Group A Streptococcus ´ Prophylaxis for Perinatal
´ Group B Streptococcus
´ Methicillin-Resistant
Staphylococcus aureus
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
Infections
´ Rectovaginal screening 35 –
37 weeks AOG
´ Proposed strategies to
prevent perinatal acquisition
of GBS
´ Culture – Based
prevention
´ Risk – Based prevention
Bacterial Infections

´ Group A Streptococcus ´ Pregnancy Effect

´ Group B Streptococcus ´ Preterm labor

´ PROM
´ Methicillin-Resistant
Staphylococcus aureus ´ Chorioamnionitis
´ Recommendations for
´ Listeria Moncytogenes Management
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
Bacterial Infections

´ Group A Streptococcus ´ Intrapartum Antimicrobial

Prophylaxis
´ Group B Streptococcus ´ Given 4 or more hours before
delivery is effective
´ Methicillin-Resistant
´ Antibiotic:
Staphylococcus aureus
´ 1. Penicillin
´ Listeria Moncytogenes ´ 2. Ampicillin
´ Salmonellosis ´ 3. Cefazolin if allergic to
Penicillin
´ Shigella Regiments for Intrapartum
´ Mycobacterium leprae Antimicrobial Prophylaxis for
Perinatal GBS
Bacterial Infections

´ Group A Streptococcus ´ S. aureus

´ Most virulent of the Staph
´ Group B Streptococcus species
´ Methicillin-Resistant ´ Colonizes the:
Staphylococcus aureus ´Nares
´ Listeria Moncytogenes ´Skin,
´Genitals
´ Salmonellosis
´Oropharynx
´ Shigella
´ 20% persistent carriers
´ Mycobacterium leprae ´ 30% - 60% intermittent carriers
´ 20% - 50% non carriers
Bacterial Infections
´ Group A Streptococcus ´ MRSA & Pregnancy
´ Group B Streptococcus
´ Methicillin-Resistant
Staphylococcus aureus
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
´ (+) anovaginal in 10% - 20% of
OB cases (S. aureus)
´ MRSA isolated in 0.5% - 3.5%
´ MRSA presentation
´ Skin & Soft tissue most
common (Fig. 64-7)
´ Mastitis
´ Perineal Abscess
´ Wound infections
´ Chorioamnionitis
Bacterial Infections

´ Group A Streptococcus ´ Management

´ Local wound care
´ Group B Streptococcus
´ Drainage
´ Methicillin-Resistant
´ Antibiotics:
Staphylococcus aureus
´ Vancomycin – 1st Line
´ Listeria Monocytogenes treatment

´ Salmonellosis ´ Prevention:
´ Prevention of skin to skin
´ Shigella contact
´ Mycobacterium leprae ´ Prevent contact with wound
dressing
Bacterial Infections

´ Not common but probably

´ Group A Streptococcus underdiagnosed
´ Group B Streptococcus ´ Gram (+) bacillus isolated in feces
´ Transmission: Oro-fecal route
´ Methicillin-Resistant
´ Causes of outbreak from eating:
Staphylococcus aureus
´ Raw vegetables
´ Listeria Moncytogenes ´ Coleslaw
´ Salmonellosis ´ Apple cider
´ Melons
´ Shigella
´ Milk
´ Mycobacterium leprae ´ Fresh Mexican-cheese
´ Smoked - fish
Bacterial Infections

´ Group A Streptococcus ´ Commonly Affects:

´ Group B Streptococcus
´ Methicillin-Resistant
Staphylococcus aureus
´ Hypothesis why pregnant women
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
´ Very old/ young people
´ Pregnant women
´ Immunocompromised patients
are susceptible:
´ Decrease Cell-mediated
immunity
´ Placental trophoblast are
susceptible to Listeria invasion
Bacterial Infections
´ Group A Streptococcus ´ Maternal Infection
´ Group B Streptococcus
´ Methicillin-Resistant
Staphylococcus aureus
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
´ May be:
´Asymptomatic
´Non – specific
symptoms similar to:
´Influenza
´Pyelonephritis
´Meningitis
´ Diagnosis: Blood Culture
Bacterial Infections

´ Group A Streptococcus ´ Fetal Infection

´ Group B Streptococcus
´ Methicillin-Resistant
Staphylococcus aureus
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
´ Discolored AF (brownish/
Meconium stained)
´ Disease onset:
´ Early – onset infection
´ Late Onset neonatal
infection
Bacterial Infections

´ Group A Streptococcus ´ Treatment:

´ Group B Streptococcus ´ Ampicillin + Gentamycin

´ Trimethoprim-
´ Methicillin-Resistant sulfamethoxazole if
Staphylococcus aureus penicillin allergic
´ Listeria Moncytogenes ´ No Vaccine Available
´ Salmonellosis ´ Prevention:

´ Shigella ´ Thorough washing of raw

vegetables and fruits
´ Mycobacterium leprae ´ Adequate cooking of food
Bacterial Infections

´ Group A Streptococcus ´ Non-typhoid gastroenteritis

´ Group B Streptococcus
´ Methicillin-Resistant
Staphylococcus aureus
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Treatment: Hydration
´ Mycobacterium leprae
type
´ Non-bloody diarrhea
´ Abdominal pain
´ Fever
´ Chills
´ Nausea & vomiting 6 – 8
hours post exposure
Bacterial Infections

´ Group A Streptococcus ´ Typhoid type

´ Group B Streptococcus ´ Transmission: oro-fecal

´ Methicillin-Resistant
Staphylococcus aureus
´ Listeria Moncytogenes
´ Salmonellosis
route
´ In pregnancy, may be
encountered in:
´Epidemics
´HIV infection

´ Shigella ´ Treatment:
´ Fluoroquinolones
´ Mycobacterium leprae
´ 3rd Generation
cephalosporins
Bacterial Infections

´ Group A Streptococcus ´ Highly contagiuous

´ Group B Streptococcus ´ More common in children

´ Transmission: Oro-fecal route
´ Methicillin-Resistant
Staphylococcus aureus ´ Manifestation:
´ Mild diarrhea to severe
´ Listeria Moncytogenes dysentery
´ Salmonellosis ´ Bloody stools
´ Shigella ´ Abdominal cramps
´ Mycobacterium leprae ´ Tenesmus
´ Fever
´ Systemic toxicity
Bacterial Infections

´ Group A Streptococcus ´ Treatment:

´ Group B Streptococcus ´ Hydration

´ Antibiotics:
´ Methicillin-Resistant
Staphylococcus aureus ´Fluoroquinolones
´Ceftriaxone
´ Listeria Moncytogenes
´Azithromycin
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
Bacterial Infections

´ Group A Streptococcus ´ Hansen Disease

´ Group B Streptococcus ´ Multiple drug therapy once

diagnosed
´ Methicillin-Resistant ´ Treatment generally safe
Staphylococcus aureus for pregnant women
´ Listeria Moncytogenes
´ Salmonellosis
´ Shigella
´ Mycobacterium leprae
Protozoal Infections

´ Toxoplasmosis
´ Malaria
´ Amebiasis
Protozoal Infections

´ Toxoplasmosis ´ Toxoplasma gondii

´ Malaria ´ Obligate intracellular parasite

´ Infection acquired by eating
´ Amebiasis
´ raw/ undercooked
infected meat
´ Food contaminated with
soil
´ Drinking infected water
Protozoal Infections

´ Toxoplasmosis ´ Maternal Infection

´ Malaria ´ May be asymptomatic

´ Fatigue
´ Amebiasis
´ Fever
´ Headache
´ Muscle pain
´ Maculopapular rash
´ Posterior cervical
lymphadenopathy
Protozoal Infections

´ Toxoplasmosis ´ Pregnancy Effect

´ Malaria ´ 4 fold increase in preterm

labor
´ Amebiasis ´ Fetal Infection
´ Low birthweight
´ Hepatosplenomegaly
´ Jaundice
´ Anemia
Protozoal Infections

´ Toxoplasmosis ´ Fetal Infection

´ Malaria ´ Severe infections:

´Intracranial
´ Amebiasis calcifications
´Hydrocephaly
´Chorioretinitis
´Convulsions
Protozoal Infections
´ Screening & Diagnosis:
´ Screening recommended for
´ Toxoplasmosis
endemic areas
´ Malaria ´ Incidence in South East Asia is
´ Amebiasis between <2% to 70% - “Veeranoot
Nissapatorn , 2007. Toxoplasmosis: A Silent Threat in
Southeast Asia . Research Journal of Parasitology, 2: 1-12.”

´ Diagnosis:
´Serum Anti-toxoplasma IgG
´Serum Anti-toxoplasma IgM, IgA,
IgE (Acute infection)
Protozoal Infections

´ Toxoplasmosis ´ Prenatal Diagnosis:

´ Malaria ´ DNA amplification technique
´ PCR of Amniotic Fluid or Fetal
´ Amebiasis blood
´ Sensitivity is lowest at < 18 weeks
´ US evaluation
´ Intracranial calcifications
´ Hydrocephaly
´ Liver calcifications
´ Ascites
´ Placental thickening
´ Hyperechoic bowels
´ IUGR
Protozoal Infections

´ Toxoplasmosis ´ Management:
´ Prenatal Treatment:
´ Malaria
´ Spiramycin – early pregnancy
´ Amebiasis ´ Pyrimethamine-sulfonamide + folic
acid – after 18 weeks / if w/ possible
fetal infection

´ Prevention:
´ No vaccine
´ Thorough cleaning of food
Protozoal Infections

´ Toxoplasmosis ´ Caused by Plasmodium sp.

´ Malaria ´ 5 species infect humans:

´ falciparum
´ Amebiasis
´ vivax
´ ovale
´ malariae
´ knowlesi
Protozoal Infections

´ Toxoplasmosis ´ Maternal Infection

´ Malaria ´ Fever
´ Chills
´ Amebiasis
´ Headache
´ Myalgia
´ Malaise
´ Jaundice
Protozoal Infections

´ Toxoplasmosis ´ Pregnancy Effect increase

rates of:
´ Malaria
´ Stillbirth
´ Amebiasis ´ Preterm birth
´ Low birthweight
´ Maternal anemia
Protozoal Infections

´ Toxoplasmosis ´ Diagnosis:

´ Malaria ´ Identification of parasite thru

blood smear – gold standard
´ Amebiasis ´ Management:
´ Artemether – Lumefanthrine
´ Atovaquone – Proguanil
´ Prophylaxis: (But NOT
recommended)
´ Sulfadoxine-pyrimethamine
´2 doses 2nd and 3rd
trimester
Protozoal Infections

´ Toxoplasmosis ´ Prevention:

´ Malaria ´ Vector control

´ Chemoprophylaxis:
´ Amebiasis
´ Chloroquine
´ Hydrocloroquine
(decrease 20% to 4% in
asymptomatic women in areas
w/o chloroquine resistance)
´ Mefloquine (for chloroquine
resistant falciparum)
Protozoal Infections

´ Toxoplasmosis ´ Caused by Entamoeba

histolytica
´ Malaria
´ Manifest:
´ Amebiasis ´ Fever
´ Abdominal pain
´ bloody stools
´ Diagnosis: ID cyst/ trophozoite
in stool
´ Treatment: Metronidazole
Thank You for
trying to listen
Emerging Infections

´ West Nile Virus

´ Corona Virus
Travel Precautions during Pregnancy
Bioterrorism

´ Smallpox
´ Anthrax
´ Other Bioterrorism Agents
Culture – Based Prevention

´ Designed to identify women who

would be given intrapartum
antibiotic treatment
´ Rectovaginal swabs are cultured
´ If (+) intrapartum antibiotic
treatment is given
´ Other indications for prophylaxis:
´ Previous delivery with a neonate
with early onset GBS
´ (+) GBS bacteriuria
Risk-Based Prevention

´ Recommended for women in ´ Risk Factors :

labor whose GBS result is unknown
´ 1. Gestational age less than 37
´ Relies on risk factors associated weeks AOG
w/ intrapartum GBS transmission
´ 2. Membrane rupture of = or > 18
hours
´ 3. Temp of = or > 38.0oC
´ 4. (+) GBS current pregnancy
´ 5. history of delivering a neonate
with early onset GBS disease
..Erythromycin is no longer used for penicillin-allergic patients
Vulvar Abscess

´ Begins as a cellulitis
´ Risk Factors:
´ Diabetes
´ Obesity
´ Perineal Shaving
´ Immunosuppresion
Vulvar Abcess

´ Management:
´ Early
´ hot sitz bath
´ Oral antibiotics

´ (+) Abscess
´ Incision & drainage
´ Antibiotics
 Treatment  of  malaria   shall  follow  the  recommended   therapeutic   regimen:
2.1  The  Artemether-­Lumefantrine   (AL)  combination  will  be  the  first  line  medicine  in  the  
treatment   of
confirmed  uncomplicated  and  severe  Plasmodium  falciparum  malaria,   replacing   CQ+SP  
combination;;
2.2  If  AL  is  not  available,   whether  the  patient  is  conscious  or  unconscious,  and  in  case  of  
treatment   failure,  quinine  (QN)  in  combination  with  either  tetracycline   or  doxycycline  or  
clindamycin  (QN+T/D/C  x  7  days),  will  be  the  second-­line  treatment.
2.3  In  severe   malaria   cases  wherein   the  patient  is  unconscious,  and  the  facility  has  no  
capacity  to  adequately   manage  the  patient  (e.g.  naso-­gastric  tube  or  intravenous  therapy),  
Artesunate (AS)  suppository  can  be  introduced  pending  transfer  of  patient  to  the  next  level  
of  care."
2.4  ACT  can  be  used  for  all  Plasmodium  species  and  mixed  infections;;
2.5  All  anti-­malarial   drugs  will  be  selected   based  on  pre-­qualifications  by  WHO  or  Good  
Manufacturing  Procedures  (GMP)  certifications
Sulfadoxine-pyrimethamide should only be
considered for travelers when:

´ going to areas where

chloroquine-resistant P.
falciparum malaria is
endemic
´ sensitive to Sulfadoxine
and pyrimethamine
´ when alternative drugs
are not available or are
contraindicated
 If not later, When?

OB: INFECTIOUS DISEASES • Early stages:
COO (November 5, 2018) o May be difficult to diagnose because neonates often
fail to express classic clinical signs.
Disease Outcome Depends on:
o Maternal serological status • If the fetus was infected in utero:
o Gestational age at the time infection is acquired o depression and acidosis at birth for no apparent
o The mode of acquisition reason.
o Immunological status of both the mother and her fetus o The neonate may suck poorly, vomit, or show
abdominal distention.
MATERNAL & FETAL IMMUNOLOGY o Respiratory insufficiency may develop, which may
Ø Pregnancy – Induced Immunological Changes present similarly to idiopathic respiratory distress
• Many of the maternal immunological adaptations to pregnancy syndrome.
are not well elucidated. o may be lethargic or jittery.
• Th2 Type Bias o The response to sepsis may be hypothermia rather
o An increase in CD4-positive T cells secreting Th2-type than hyperthermia
cytokines o the total leukocyte and neutrophil counts may be
§ E.g. interleukins 4, 5, 10, and 13. depressed.
o Suppressed Th1-type cytokine production
§ E.g. interferon gamma and interleukin 2
• This bias affects the ability to rapidly eliminate certain
intracellular pathogens during pregnancy, although the clinical
implications of this suppression are unknown.
• Importantly, the Th2 humoral immune response remains
intact.
• Type 2 dominance is credited with tolerance of xenografts and
of the fetus during pregnancy

Ø Fetal & Newborn Immunology
• The active immunological capacity of the fetus and neonate is
compromised compared with that of older children and adults.
• Fetal cell-mediated and humoral immunity begin to develop by
9 to 15 weeks’ gestation.
• The primary fetal response to infection is immunoglobulin M
(IgM).
• IgA- dominant Ig in breastmilk at birth


IgG
• Maternal in origin
• Passive immunity is provided by IgG transferred across the
placenta.
• By 16 weeks, this transfer begins to increase rapidly, and by 26
weeks, fetal concentrations are equivalent to those of the
mother. VIRAL INFECTIONS
• After birth, breast-feeding is protective against some
infections, although this protection begins to decline at 2 VARICELLA – ZOSTER
months of age.
• Varicella-zoster virus (VZV) is a double stranded DNA herpes
Neonatal Infection virus acquired predominately during childhood, and 95 percent
• Vertical transmission refers to passage from the mother to her of adults have serological evidence of immunity.
fetus of an infectious agent through the: • DNA herpes virus remain dormant in the DRG after primary
o Placenta infection
o During labor or delivery
o Breast-feeding Vaccination
• Increase the risk of neonatal infection: • The incidence of adult varicella infections declined by 74
o Preterm rupture of membranes percent after the introduction of varicella vaccination,
o Prolonged labor probably secondary to herd immunity.
o Obstetrical manipulations • This has resulted in a decrease in maternal and fetal varicella
infections.
• Those occurring less than 72 hours after delivery are usually
caused by bacteria acquired in utero or during delivery, • Primary infection—varicella or chicken pox—is transmitted by
whereas infections after that time most likely were acquired direct contact with an infected individual, although respiratory
afterward transmission has been reported.

 If not later, When?

• The incubation period is 10 to 21 days, and a non-immune Exposure Before or During Delivery
woman has a 60- to 95-percent risk of becoming infected after • If the fetus or neonate is exposed to active infection just before
exposure. or during delivery, and therefore before maternal antibody has
• Contagious from 1 day before the onset of the rash until the been formed, then there is a serious threat to newborns.
lesions are crusted over. • Attack rates range from 25 to 50 percent, and mortality rates
approach 30 percent.
Maternal Infection • Neonates may develop disseminated visceral and central
• Primary varicella infection presents with a 1 - to 2-day flu-like nervous system disease, which is commonly fatal.
prodrome, which is followed by pruritic vesicular lesions that • Varicella-zoster immune globulin should be administered to
crust over in 3 to 7 days. neonates born to mothers who have clinical evidence of
• Infection tends to be more severe in adults, and a quarter of varicella 5 days before and up to 2 days after delivery.
varicella deaths are within the 5 percent of non-immune
adults. Diagnosis
• Maternal varicella infection is usually diagnosed clinically.
Varicella Pneumonia
• Mortality is predominately due to varicella pneumonia, which Laboratory Test:
is thought to be more severe • Scraping the vesicle base during primary infection
• during adulthood and particularly in pregnancy. • Tzanck smear
• Between 5 and 20 percent of infected pregnant women • tissue culture
developed pneumonitis • direct fluorescent antibody testing.
• Nucleic acid amplification tests (NAATs) are very sensitive.
Risk factors for VZV pneumonia include: • Congenital varicella may be diagnosed using NAAT analysis of
• Smoking and having more than 100 cutaneous lesions. amnionic fluid
• Maternal mortality rates with pneumonia have decreased to 1
to 2 percent Management
Maternal Viral Exposure
• Symptoms of pneumonia usually appear 3 to 5 days into the • Because most adults are VZV seropositive, exposed pregnant
course of illness. women with a negative history for chicken pox should undergo
o Characterized by: VZV serologic testing.
§ Fever • At least 70 percent of these women will be seropositive, and
§ Tachypnea thus immune.
§ dry cough • Exposed pregnant women who are susceptible should be given
§ dyspnea VariZIG
§ pleuritic pain. • Although best given within 96 hours of exposure, its use is
• Nodular infiltrates are similar to other viral pneumonias approved for up to 10 days to prevent or attenuate varicella
• Although resolution of pneumonitis parallels that of skin infection
lesions, fever and compromised pulmonary function may
persist for weeks. Maternal Infection
• Any patient diagnosed with primary varicella infection should
ZOSTER OR SHINGLES be isolated from pregnant women.
• If primary varicella infection is reactivated years later, it causes • Because pneumonia often presents with few symptoms: Many
herpes zoster or shingles. recommend chest radiograph.
• This presents as a unilateral dermatomal vesicular eruption • Most women require only supportive care, but those who
associated with severe pain. require intravenous (IV) fluids and especially those with
• Zoster does not appear to be more frequent or severe in pneumonia are hospitalized.
pregnant women. • Intravenous acyclovir therapy is given to women requiring
hospitalization—500 mg/m2 or 10 to 15 mg/kg every 8 hours.
Fetal & Neonatal Infection
Congenital Varicella Syndrome Vaccination
• In women with chicken pox during the first half of pregnancy, • An attenuated live-virus vaccine—Varivax— was approved in
the fetus may develop congenital varicella syndrome. 1995.
• Some features include: • Two doses, given 4 to 8 weeks apart, are recommended for
• Chorioretinitis adolescents and adults with no history of varicella.
• Microphthalmia • This results in 98-percent seroconversion
• Cerebral cortical atrophy • The vaccine is not recommended for pregnant women or for
• Growth restriction those who may become pregnant within a month following
• Hydronephrosis each vaccine dose.
• Limb hypoplasia • The attenuated vaccine virus is not secreted in breast milk
• Cicatricial skin lesions (Safe to give)
• Postpartum vaccination should not be delayed because of
• The highest risk was between 13 and 20 weeks breast – feeding
• Congenital infections, particularly after 20 weeks are
uncommon.

 If not later, When?

INFLUENZA • There is limited experience with all five of these antiviral agents
• Members of the family Orthomyxoviridae cause these in pregnant women.
respiratory infections. • They are Food and Drug Administration Category C drugs, used
• Influenza A and B form one genus of these RNA viruses, and when the potential benefits outweigh the risks.
both cause epidemic human disease.
• Influenza A viruses are subclassified further by: Recommended:
o Hemagglutinin (H) • Starting Oseltamivir treatment within 48 hours of symptom
o Neuraminidase (N) surface antigens onset—75 mg orally twice daily for5 days.
• Prophylaxis with Oseltamivir, 75 mg orally once daily for 10
Maternal & Fetal Infection days, is also recommended for
• Maternal influenza is characterized by fever, dry cough, and • significant exposures.
systemic symptoms. • Antibacterial medications should be added when a
• pregnant women appear to be more susceptible to serious secondary bacterial pneumonia is suspected
complications, particularly pulmonary involvement • Pregnant women with confirmed or suspected H1N1 infection:
Oseltamivir for 5 days
Fetal Effects • Pregnant women in close contact with infected person:
• no firm evidence that influenza A virus causes congenital Oseltamivir x 10 days
malformations
• increased neural-tube defects in neonates born to women with Vaccination
influenza early in pregnancy • Important for those affected by chronic medical disorders such
• Viremia is infrequent, and transplacental passage is rare as diabetes, heart disease, asthma, or human
• Stillbirth, preterm delivery, and first-trimester abortion have all immunodeficiency virus (HIV) infection
been reported, usually correlated to severity of maternal • Importantly, there is no evidence of teratogenicity or other
infection adverse maternal or fetal events
• Moreover, several studies have found decreased rates of
Detection influenza in infants up to 6 months of age whose mothers were
Influenza may be detected in nasopharyngeal swabs using viral antigen vaccinated during pregnancy
rapid detection assays • Immunogenicity of the trivalent inactivated seasonal influenza
vaccine in pregnant women is similar to that in the
nonpregnant individual
• A live attenuated influenza virus vaccine is available for
intranasal use but is not recommended for pregnant women.

MUMPS
• This uncommon adult infection is caused by an RNA
paramyxovirus.
• The virus primarily infects the salivary glands, and hence its
name—mumps—is derived from Latin, “to grimace.”
• Infection also may involve the gonads, meninges, pancreas,
and other organs.
• It is transmitted by direct contact with respiratory secretions,
saliva, or through fomites.
• Treatment is symptomatic, and mumps during pregnancy is no
more severe than in nonpregnant adults.


• Reverse transcriptase–polymerase chain reaction (RT-PCR): Effects
more sensitive and specific • Women who develop mumps in the first trimester may have
an increased risk of spontaneous abortion.
Management • Infection in pregnancy is not associated with congenital
• Two classes of antiviral medications are currently available. malformations, and fetal infection is rare
• Neuraminidase inhibitors are highly effective for the treatment
of early influenza A and B. Vaccines
• These include oseltamivir (Tamiflu), which is taken orally for • Because of childhood immunization, up to 90 percent of adults
treatment and for chemoprophylaxis, and zanamivir (Relenza), are seropositive.
which is inhaled for treatment. • The live attenuated Jeryl-Lynn vaccine strain is part of the MMR
• Peramivir is an investigational drug administered vaccine—measles, mumps, and rubella—and is
intravenously. contraindicated in pregnancy according to the CDC.
• • No malformations attributable to MMR vaccination in
• The Adamantanes include amantadine and rimantadine pregnancy have been reported, but pregnancy should be
• Used for years for treatment and chemoprophylaxis of avoided for 30 days after mumps vaccination.
influenza A • The vaccine may be given to susceptible women postpartum,
• It is possible that these drugs may be effective for subsequently and breast-feeding is not a contraindication.
mutated strains.

 If not later, When?

RUBEOLA/MEASLES Diagnosis
• Measles is caused by a highly contagious RNA virus of the • Rubella may be isolated from the urine, blood, nasopharynx,
family Paramyxoviridae that only infects humans. and cerebrospinal fluid for up to 2 weeks after rash onset.
• Annual outbreaks occur in late winter and early spring, • The diagnosis is usually made with serological analysis.
transmission is primarily by respiratory droplets, and the • Specific IgM antibody can be detected using enzyme-linked
secondary attack rate among contacts exceeds 90 percent. immunoassay from 4 to 5 days after onset of clinical disease,
but it can persist for up to 6 weeks after appearance of the
• Infection is characterized by: rash.
o Fever
o Coryza Immunoglobulins
o Conjunctivitis • Rubella reinfection can give rise to transient low levels of IgM.
o Cough • Serum IgG antibody titers peak 1 to 2 weeks after rash onset.
• This rapid antibody response may complicate serodiagnosis
• The characteristic erythematous maculopapular rash develops unless samples are initially collected within a few days after the
on the face and neck and then spreads to the back, trunk, and onset of the rash.
extremities. • IgG avidity testing is performed concomitant with the
• Koplik spots are small white lesions with surrounding erythema serological tests above.
found within the oral cavity. • High-avidity IgG antibodies indicate an infection at least 2
• Diagnosis is most commonly performed by serology, although months in the past.
RT-PCR tests are available.
Fetal Effects
Treatment • Rubella is one of the most complete teratogens, and sequelae
• Supportive. of fetal infection are worst during organogenesis.
• Pregnant women without evidence of measles immunity
should be administered intravenous immune globulin (IVIG), Congenital Rubella Syndrome
400 mg/kg within 6 days of a measles exposure. • According to Reef and colleagues (2000), congenital rubella
syndrome includes one or more of the following:
Vaccination o Eye defects—cataracts and congenital glaucoma
• Active vaccination is not performed during pregnancy. o Congenital heart defects—patent ductus arteriosus
• However, susceptible women can be vaccinated routinely and pulmonary artery stenosis
postpartum, and breast-feeding is not contraindicated. o Sensorineural deafness—the most common single
defect
Effects o Central nervous system defects—microcephaly,
• The virus does not appear to be teratogenic developmental delay, mental retardation, and
• However, an increased frequency of abortion, preterm meningoencephalitis
delivery, and low-birthweight neonates is noted with maternal o Pigmentary retinopathy
measles. o Neonatal purpura
• If a woman develops measles shortly before birth, there is o Hepatosplenomegaly and jaundice
considerable risk of serious infection developing in the o Radiolucent bone disease
neonate, especially in a preterm neonate.
• Neonates born with congenital rubella may shed the virus for
RUBELLA/GERMAN MEASLES many months and thus be a threat to other infants and to
• This RNA togavirus typically causes infections of minor susceptible adults who contact them.
importance in the absence of pregnancy.
• Incubation period is 12 to 23 days. Management & Prevention
• Peak incidence is late winter and spring. • There is no specific treatment for rubella.
• Viremia usually precedes clinical signs by about a week, and
adults are infectious during viremia and through 5 to 7 days of Precautions
the rash. • Droplet precautions for 7 days after the onset of the rash are
• Rubella infection in the first trimester, poses significant risk for recommended.
abortion and severe congenital malformations. • Primary prevention relies on comprehensive vaccination
• Transmission occurs via nasopharyngeal secretions, and the programs.
transmission rate is 80 percent to susceptible individuals
MMR Vaccine
Maternal Rubella • MMR vaccination is not an indication for pregnancy
• Maternal rubella infection is usually a mild, febrile illness with termination.
a generalized maculopapular rash beginning on the face and • To eradicate rubella and prevent congenital rubella syndrome
spreading to the trunk and extremities. completely, a comprehensive approach is recommended for
• Other symptoms may include arthralgias or arthritis, head and immunizing the adult population (McLean, 2013).
neck lymphadenopathy, and conjunctivitis. • MMR vaccine should be offered to nonpregnant women of
• Up to half of maternal infections are subclinical despite viremia childbearing age who do not have evidence of immunity
that may cause devastating fetal infection whenever they make contact with the health-care system.


 If not later, When?

• Vaccination of all susceptible hospital personnel who might be Diagnosis
exposed to patients with rubella or who might have contact Cordocentesis
with pregnant women is important. • Fetal infection is diagnosed by detection of B19 viral DNA in
• Rubella vaccination should be avoided 1 month before or amnionic fluid or IgM antibodies in fetal serum obtained by
during pregnancy because the vaccine contains attenuated live cordocentesis
virus. • Diagnosis is generally made by maternal serological testing for
• Women found to be nonimmune should be offered the MMR specific IgG and IgM antibodies
vaccine postpartum. • Viral DNA may be detectable by PCR in maternal serum during
the prodrome and persist for months to years after infection.
• Prenatal serological screening for rubella is indicated for all
pregnant women. Serial Sonography
• Most cases of parvovirus-associated hydrops develop in the
first 10 weeks after infection
RESPIRATORY VIRUSES • Serialsonography every 2 weeks should be performed in
women with recent infection
PARVOVIRUS
• Human parvovirus B19 causes erythema infectiosum, or fifth MCA Doppler
disease. • Middle cerebral artery (MCA) Doppler interrogation can also
• The B19 virus is a small, single-stranded DNA virus that be used to predict fetal anemia
replicates in rapidly proliferating cells such as erythroblast • Elevated peak systolic velocity values in the fetal MCA
precursors accurately predict fetal anemia
• This can lead to anemia, which is its primary fetal effect.
• Only individuals with the erythrocyte globoside membrane P
antigen are susceptible.
• infection may cause an aplastic crisis.
• The main mode of parvovirus transmission is respiratory or
hand-to-mouth contact, and the
• infection is common in spring months.
• Viremia develops 4 to 14 days after exposure.
• The maternal infection rate is highest in women with school-
aged children and in day-care workers but not usually in school
teachers.

Maternal Infection
• In 20 to 30 percent of adults, infection is asymptomatic.

Symptoms:
• Fever, headache, and flu-like symptoms may begin in the last
few days of the viremic phase.
• Several days later, a bright red rash with erythroderma affects
the face and gives a slapped cheek appearance
• The rash becomes lacelike and spreads to the trunk and
extremities.
• Adults often have milder rashes and develop symmetrical
polyarthralgia that may persist several weeks.

Fetal Infection
• There is vertical transmission to the fetus in up to a third of
maternal parvovirus infections
• Fetal infection has been associated with abortion, nonimmune
hydrops, and stillbirth
• Parvovirus is the most frequent infectious cause of nonimmune
hydrops in autopsied fetuses
• The critical period for maternal infection leading to fetal
Hydrops Management
hydrops was estimated to be between 13 and 16 weeks—
• Fetal blood sampling is warranted with hydrops to assess the
coincidental with the period in which fetal hepatic hemopoiesis
degree of fetal anemia.
is greatest.
• Fetal myocarditis may induce hydrops with less severe anemia.

Diagnosis & Management • Most fetuses require only one transfusion because
An algorithm for diagnosis of maternal parvoviral infection. hemopoiesis resumes as infection resolves.




 If not later, When?

Prevention Prenatal Diagnosis
• There is currently no approved vaccine for human parvovirus Serological Testing
B19, and there is no evidence that antiviral treatment prevents • Routine prenatal CMV serological screening is currently not
maternal or fetal infection recommended.
• Decisions to avoid higher-risk work settings are complex and • Pregnant women should be tested for CMV if they present with
require assessment of exposure risks. a mononucleosis-like illness or if congenital infection is
suspected based on abnormal sonographic findings.
CYTOMEGALOVIRUS
• This ubiquitous DNA herpes virus eventually infects most • IgM
humans. o CMV IgM does not accurately reflect timing of
• Cytomegalovirus (CMV) is the most common perinatal seroconversion because IgM antibody levels may be
infection in the developed world. elevated for more than a year
• The virus is secreted into all body fluids, and person -to-person o CMV IgM may be found with reactivation disease or
contact with viral-laden saliva, semen, urine, blood, and reinfection with a new strain.
nasopharyngeal and cervical secretions can transmit infection.
• IgG
Transmission o Primary infection is diagnosed using CMV-specific
• The fetus may become infected by transplacental viremia, or IgG testing of paired acute and convalescent sera.
the neonate is infected at delivery or during breast-feeding. o Specific CMV IgG avidity testing is valuable in
confirming primary CMV infection
Maternal Infection o High anti-CMV IgG avidity indicates primary maternal
• Pregnancy does not increase the risk or severity of maternal infection > 6 months before testing
CMV infection.
• Most infections are asymptomatic Imaging Modalities
• 0 to 15 percent of infected adults have a mononucleosis-like • Several fetal abnormalities associated with CMV infection may
syndrome characterized by: be seen with sonography, computed tomography, or magnetic
o Fever resonance imaging.
o Pharyngitis
o Lymphadenopathy Findings:
o polyarthritis • Microcephaly
• Ventriculomegaly
• cerebral calcifications
Immunocompromised women may develop:
• Myocarditis • Abnormal sonographic findings seen in combination with
• Pneumonitis positive findings in fetal blood or amnionic fluid are predictive
• Hepatitis of an approximate 75-percent risk of symptomatic congenital
• Retinitis infection
• Gastroenteritis • CMV nucleic acid amplification testing of amnionic fluid is
• meningoencephalitis. considered the gold standard for the diagnosis of fetal
infection.
Fetal Infection
• When a newborn has apparent sequelae of in utero-acquired Management & Prevention
CMV infection, it is referred to as symptomatic CMV infection. • symptomatic treatment.
• If recent primary CMV infection is confirmed, amnionic fluid
• Congenital infection is a syndrome that may include: analysis should be offered.
o Growth restriction; Microcephaly; Intracranial • Counseling regarding fetal outcome depends on the
calcifications; Chorioretinitis o Mental and motor gestation age during which primary infection is documented.
retardation; Sensorineural deficits • Even with the high infection rate with primary infection in the
o Hepatosplenomegaly; Jaundice first half of pregnancy, mostfetuses develop normally.
o Hemolytic anemia; Thrombocytopenic purpura • However, pregnancy termination may be an option for some.
• There is no CMV vaccine.
• only 5 to 10 percent demonstrate this syndrome • Prevention of congenital infection relies on avoiding maternal
• Thus, most infected infants are asymptomatic at birth, but primary infection, especially in early pregnancy.
some develop late-onset sequelae. • Basic measures such as good hygiene and hand washing have
• They may include: been promoted, particularly for women with toddlers in day-
o hearing loss care settings
o neurological deficits
o chorioretinitis
o psychomotor
o retardation
o learning disabilities



 If not later, When?

• Postpartum mastitis
• Puerperal infections

• It remains the leading infectious cause of morbidity and
mortality among infants in the United States


Neonatal Sepsis
• Neonatal sepsis has received the most attention due to its
devastating consequences and available effective preventative
measures.

Periods, Onset, Manifestations
• threshold of < 72 hours of life as most compatible with
intrapartum acquisition of disease
• Infection < 7 days after birth is defined as early-onset disease
• In many neonates, septicemia involves signs of serious illness
that usually develop within 6 to 12 hours of birth.
• These include:
o Respiratory distress
o Apnea
o Hypotension

• Late-onset disease caused by usually manifests as meningitis 1
week to 3 months after birth
BACTERIAL INFECTIONS • The mortality rate, although appreciable, is less for late-onset
meningitis than for early-onset sepsis.
GROUP A STREPTOCOCCUS • not uncommon for surviving infants of both early- and late-
• Streptococcus pyogenes onset disease to exhibit devastating neurological sequelae.
• Infections caused by Streptococcus pyogenes are important in
pregnant women. Prophylaxis for Perinatal Infections
• It is the most frequent bacterial cause of acute pharyngitis and • They recommended universal rectovaginal culture screening
is associated with several systemic and cutaneous infections. for GBS at 35 to 37 weeks’ gestation followed by intrapartum
• S pyogenes produces numerous toxins and enzymes antibiotic prophylaxis for women identified to be carriers.
responsible for the local and systemic toxicity associated with • either culture-based or risk-based guidelines
this organism.
• Pyrogenic exotoxin-producing strains are usually associated Culture based prevention
with severe disease
• In most cases, streptococcal pharyngitis, scarlet fever, and
erysipelas are not life threatening.
• remains the most common cause of severe maternal
postpartum infection and death worldwide, and the incidence
of these infections is increasing

GROUP B STREPTOCOCCUS
• Streptococcus agalactiae:
• Major cause of neonatal morbidity and mortality
• A group B organism that can be found to colonize the
gastrointestinal and genitourinary tract in 20 to 30 percent of
pregnant women.

Maternal & Perinatal Infection
• The spectrum of maternal and fetal GBS ranges from
asymptomatic colonization to septicemia.
• Streptococcus agalactiae has been implicated in:
• Adverse pregnancy outcomes:
o Preterm labor
o Prematurely ruptured membranes
o Clinical and subclinical chorioamnionitis
o Fetal infections
Maternal:
• Bacteriuria
• Pyelonephritis

• Osteomyelitis
 If not later, When?

• Those at high risk for anaphylaxis should have antimicrobial
• Adopted by the American College of Obstetricians and susceptibility testing performed to exclude clindamycin
Gynecologists resistance.
• This approach is designed to identify women who should be • Clindamycin-sensitive but erythromycin-resistant isolates
given intrapartum antimicrobial prophylaxis. should have a D-zone test performed to assess for inducible
• Women are screened for GBS colonization at 35 to 37 weeks’ clindamycin resistance.
gestation, and intrapartum antimicrobials are given to women • If clindamycin resistance is confirmed, vancomycin should be
with rectovaginal GBS-positive cultures. administered.
• Selective enrichment broth followed by subculture improves • Erythromycin is no longer used for penicillin allergic patients.
detection.
• In addition, more rapid techniques such as DNA probes and • Further recommendations for management of spontaneous
nucleic acid amplification tests are being developed preterm labor, threatened preterm delivery, or preterm
• A previous sibling with GBS invasive disease and identification prematurely ruptured membranes
of GBS bacteriuria in the current pregnancy are also considered
indications for prophylaxis.

Risk based prevention
• A risk-based approach is recommended for women in labor
and whose GBS culture results are not known.
• This approach relies on risk factors associated with intrapartum
GBS transmission.

Risk Factors:
• Gestational age less than 37 weeks AOG
• Membrane rupture of = or > 18 hours
• Temp of = or > 38C
• (+) GBS current pregnancy Methicillin – Resistant Staphylococcus Aureus
• History of delivering a neonate with early onset GBS disease • Staphylococcus aureus
• Pyogenic gram-positive organism
• Considered the most virulent of the staphylococcal species.
• It primarily colonizes the nares, skin, genital tissues, and
oropharynx.
• Approximately 20 percent of normal individuals are persistent
carriers, 30 to 60 percent are intermittent carriers, and 20 to
50 percent are noncarriers
• Colonization is considered the greatest risk factor for infection


Methicillin-resistant S aureus (MRSA)
• Methicillin-resistant S aureus (MRSA) colonizes only 2 percent
of people but is a significant
• contributor to the healthcare burden
• MRSA infections are associated with increased cost and higher
mortality rates compared with those by methicillin-sensitive S
aureus (MSSA)

Community-associated MRSA (CA-MRSA):
• Diagnosed when identified in an outpatient setting or within 48
hours of hospitalization in a person without traditional risk
factors.
• The latter include prior MRSA infection, hospitalization, dialysis
or surgery within the past year, and indwelling catheters or
devices.
Intrapartum Antimicrobial Prophylaxis
• Prophylaxis administered 4 or more hours before delivery is • Hospital-associated MRSA (HA-MRSA) infections are
highly effective nosocomial.
• Regardless of screening method, penicillin remains the first- • Most cases of MRSA in pregnant women are CA-MRSA.
line agent for prophylaxis, and ampicillin is an acceptable
alternative MRSA & Pregnancy
• Women with a penicillin allergy and no history of anaphylaxis • Skin and soft tissue infections are the most common
should be given cefazolin presentation of MRSA in pregnant women
• Mastitis has been reported in up to a fourth of cases of MRSA
complicating pregnancy
 If not later, When?

• Perineal abscesses, wound infections at sites such as • If present, a small abscess can be incised and drained, wound
abdominal and episiotomy incisions, and chorioamnionitis are cultures obtained, abscess cavity packed, and surrounding
also associated with MRSA cellulitis treated with oral antibiotics.
• These infections are typically polymicrobial, and suitable
Management broad-spectrum antimicrobials are given along with coverage
• managed by drainage and local wound care. for MRSA
• Severe superficial infections, especially those that fail to • For severe infections, especially in immunosuppressed or
respond to local care or those in patients with medical pregnant patients, hospitalization and intravenous
comorbidities, should be treated with MRSA-appropriate antimicrobial therapy are often warranted due to increased
antibiotics. risks for necrotizing fasciitis.
• Purulent cellulitis should be treated empirically for CA-MRSA • Large abscesses are best drained in the operating room with
until culture results are available. adequate analgesia or anesthesia.
• Cysts of the Bartholin gland duct are usually unilateral, sterile,
Antibiotics and need no treatment during pregnancy.
• Most CA-MRSA strains are sensitive to • If a cyst is sufficiently large to obstruct delivery, then needle
trimethoprimsulfamethoxazole. aspiration is an appropriate temporary measure.
• If clindamycin treatment is considered, inducible resistance • With gland duct infection, a localized unilateral vulvar bulge,
must be excluded by a D-zone tenderness, and erythema are present.
• test for erythromycin resistant, clindamycin-sensitive isolates. • Treatment is given with broad-spectrum antimicrobials, and
• Rifampin rapidly develops resistance and should not be used drainage is established.
for monotherapy. • In addition to obtaining wound cultures, testing is done for
• Linezolid, although effective against MRSA, is expensive, and Neisseria gonorrhoeae and Chlamydia trachomatis.
there is little information regarding its use in pregnancy. • For a small abscess, incision and placement of a Word catheter
• Doxycycline, minocycline, and tetracycline, although effective may be suitable.
for MRSA infections, should not • For larger abscesses with extensive cellulitis, drainage is best
• be used in pregnancy. performed in the operating room.
• Vancomycin remains the first line therapy for inpatient MRSA • In these cases, the incised edges of the abscess cavity may be
infections. marsupialized.
• Occasionally, abscesses of the periurethral glands develop.
• The control and prevention of HA-MRSA and CA-MRSA rely on • The largest of these, the Skene gland, may require drainage
appropriate hand hygiene and prevention of skin-to-skin and broad-spectrum antimicrobial treatment if there is
contact or contact with wound dressings. suppuration.
• Decolonization
• Decolonization should be considered only in cases in which a LISTERIOSIS
patient develops recurrent • Listeria monocytogenes:
• superficial infections despite optimal hygiene measures or if • Uncommon but probably underdiagnosed cause of neonatal
ongoing transmission occurs among household or close sepsis.
contacts • This facultative intracellular gram-positive bacillus can be
• Decolonization measures include nasal treatment with isolated from the feces of 1 to 5 percent of adults.
mupirocin, chlorhexidine gluconate baths, and oral rifampin • Nearly all cases of listeriosis are thought to be food-borne
therapy. • Outbreaks have been caused by raw vegetables, coleslaw,
• Routine decolonization has not been shown to be effective in apple cider, melons, milk, fresh Mexican-style cheese, smoked
the obstetrical population. fish, and processed foods, such as p.t., hummus, wieners, and
• For women with culture-proven CA-MRSA infection during sliced deli meats
pregnancy, we add single-dose vancomycin to routine β -
lactam perioperative prophylaxis for cesarean deliveries and Incidence
fourth-degree perineal lacerations. • more common in the very old or young, pregnant women,
• Breast- feeding in these women is not prohibited, but optimal and immunocompromised patients.
hygiene and attention to minor skin breaks is encouraged. • pregnant women are susceptible because of decreased cell-
mediated immunity
Vulvar Abscess • placental trophoblasts are susceptible to invasion by Listeria
• Labia majora infections, which begin as cellulitis, have the monocytogenes
potential for significant expansion and abscess formation.
• Risk factors include: Maternal & Fetal Infection
o Diabetes • The diagnosis usually is not apparent until blood cultures are
o Obesity reported as positive.
o Perineal shaving • Occult or clinical infection also may stimulate labor
o Immunosuppression • Discolored, brownish, or meconium-stained amnionic fluid is
common with fetal infection, even preterm gestations.
Management
• For early cellulitis, sitz baths and oral antibiotics are reasonable Maternal Infection
treatment. • Maternal listeriosis causes fetal infection that characteristically
produces disseminated granulomatous lesions with
microabscesses
 If not later, When?

• Chorioamnionitis is common with maternal infection, and SHIGELLOSIS
placental lesions include multiple, well-demarcated • Bacillary dysentery caused by Shigella is a relatively common,
macroabscesses. highly contagious cause of inflammatory exudative diarrhea in
adults.
Fetal Infection • Shigellosis is more common in children attending daycare
• Early- and late-onset neonatal infections are similar to GBS centers and is transmitted via the fecal-oral route.
sepsis.
• Clinical manifestations:
Treatment & Prevention o Mild diarrhea to severe dysentery
• Treatment with ampicillin plus gentamicin is usually o Bloody stools
recommended because of synergism against Listeria species. o Abdominal cramping
• Trimethoprim-sulfamethoxazole can be given to o Tenesmus, fever
penicillinallergic women. Maternal treatment o Systemic toxicity
• in most cases is also effective for fetal infection
• No vaccine is available, and prevention is by washing raw Management
vegetables and cooking all raw food • Although shigellosis may be self-limited, careful attention to
• Pregnant women should also avoid the implicated foods listed treatment of dehydration is essential in severe cases.
previously. • We have cared for pregnant women in whom secretory
diarrhea exceeded 10 L/day
SALMONELLOSIS • Antimicrobial therapy is imperative, and effective treatment
• Six serotypes account for most cases in the United States, during pregnancy includes fluoroquinolones, ceftriaxone, or
including Salmonella subtypes typhimurium and enteritidis. azithromycin (& trimethoprim – sulfamethoxazole)
• Antimicrobial resistance is rapidly emerging, and antibiotic
• Non-typhoid Salmonella gastroenteritis is contracted through susceptibility testing can help guide appropriate therapy
contaminated food.
• Symptoms including: HANSEN DISEASE
o Nonbloody diarrhea o Abdominal pain • Also known as leprosy, this chronic infection is caused by
o Fever Mycobacterium leprae
o Chills • Diagnosis is confirmed by PCR.
o Nausea, and vomiting begin 6 to 48 hours after • Multidrug therapy with dapsone, rifampin, and clofazimine is
exposure. recommended for treatment and is generally safe during
pregnancy
• Diagnosis is made by stool studies. • excessive incidence of low-birthweight newborns among
infected women.
Management • The placenta is not involved, and neonatal infection apparently
• Intravenous crystalloid is given for rehydration. is acquired from skin-to-skin or droplet transmission
• Antimicrobials are not given in uncomplicated infections • Vertical transmission is common in untreated mothers
because they do not commonly shorten illness and may
prolong the convalescent carrier state. PROTOZOAL INFECTIONS
• If gastroenteritis is complicated by bacteremia, antimicrobials
are given as discussed below. TOXOPLASMOSIS
• obligate intracellular parasite Toxoplasma gondii has a life
• Rare case reports have linked Salmonella bacteremia with cycle with two distinct stages
abortion • The feline stage takes place in the cat—the definitive host—
and its prey.
Typhoid Fever • Unsporulated oocysts are secreted in feces.
• Typhoid fever caused by Salmonella typhi • In the nonfeline stage, tissue cysts containing bradyzoites or
• Infection is spread by oral ingestion of contaminated food, oocysts are ingested by the intermediate host, including
water, or milk. humans.
• In pregnant women, the disease is more likely to be • Gastric acid digests the cysts to release bradyzoites, which
encountered during epidemics or in those with HIV infection infect small-intestinal epithelium.
• Here, they are transformed into rapidly dividing tachyzoites,
Management & Prevention which can infect all cells within the host mammal.
• Fluoroquinolones and third-generation cephalosporins are the • Humoral and cell-mediated immune defenses eliminate most
preferred treatment. of these, but tissue cysts develop.
• For enteric (typhoid) fever, antimicrobial susceptibility testing • Their lifelong persistence is the chronic form of toxoplasmosis.
is important because of the development of drug-resistant
strains • Human infection is acquired by eating raw or undercooked
• Typhoid vaccines appear to exert no harmful effects when meat infected with tissue cysts or by contact with oocysts from
administered to pregnant women and should be given in an cat feces in contaminated litter, soil, or water.
epidemic or before travel to endemic areas. • Prior infection is confirmed by serological testing, and its
prevalence depends on geographic locale and parasite
genotype.

 If not later, When?

Maternal & Fetal Infection • IgG
• subclinical and are detected only by prenatal or newborn • Anti-toxoplasma IgG develops within 2 to 3 weeks after
serological screening. infection, peaks at 1 to 2 months, and usually persists for life—
sometimes in high titers.
Maternal symptoms may include:
• Fatigue • IgM
• Fever • Although IgM antibodies appear by 10 days after infection and
• Headache usually become negative within 3 to 4 months, they may
• Muscle pain remain detectable for years.
• Maculopapular rash • Thus, IgM antibodies should not be used alone to diagnose
• Posterior cervical lymphadenopathy acute toxoplasmosis.

• In immunocompetent adults, initial infection confers • IgA & IgE
immunity, and prepregnancy infection nearly eliminates any • IgA and IgE antibodies are also useful in diagnosing acute
risk of vertical transmission. infection.

• Infection in immunocompromised women, however, may be • IgG Avidity
severe, and reactivation may cause: • Toxoplasma IgG avidity increases with time.
o Encephalitis • Thus, if a high-avidity IgG result is found, infection 100-percent
o Retinochoroiditis positive predictive value of high avidity confirming latent
o Mass lesions infection

• Toxoplasmosis serotype NE-II is most commonly associated • PCR testing has a high sensitivity and specificity.
with preterm birth and severe neonatal infection
• The incidence and severity of fetal toxoplasmosis infection Prenatal Diagnosis
depend on gestational age at the time of maternal infection. • Prenatal diagnosis of toxoplasmosis is performed using DNA
amplification techniques and sonographic evaluation.
Infected Neonates • PCR of amnionic fluid or fetal blood has improved sensitivity
• Conversely, the severity of fetal infection is much greater in compared with standard isolation techniques
early pregnancy, and thesefetuses are much more likely to • The sensitivity varies with gestational age, and it is lowest at <
have clinical findings of infection. 18 weeks
• Importantly, most infected fetuses are born without obvious
stigmata of toxoplasmosis. Sonographic evidence can help confirm the diagnosis:
• Intracranial calcifications, Hydrocephaly
• Clinically affected neonates usually have generalized disease • Liver calcifications, ascites
expressed as: • placental thickening
o Low birthweight • Hyperechoic bowel
o Hepatosplenomegaly • Growth restriction
o Jaundice
o Anemia Prenatal Treatment
• Prenatal treatment is based on two regimens—spiramycin
• Some primarily have neurological disease with intracranial alone or a pyrimethamine– sulfonamide combination with
calcifications and with hydrocephaly or microcephaly. folinic acid.
• Many eventually develop chorioretinitis and exhibit learning • These two regimens have also been used consecutively
disabilities. • Little evidence supports the use of a specific regimen.
• Classic triad—chorioretinitis, intracranial calcifications, and
hydrocephalus— is often accompanied by convulsions. Acute Infection in Early Pregnancy
• Infected neonates with clinical signs are at risk for long-term • Most experts would use spiramycin in women with acute
complications. infection early in pregnancy.
• Pyrimethamine– sulfadiazine with folinic acid is selected for
Screening & Diagnosis maternal infection after 18 weeks or if fetal infection is
Pre - Pregnancy suspected.
• With IgG antibody confirmed before pregnancy, there is no risk
for a congenitally infected fetus Prevention
• Screening should be performed in immunocompromised • There is no vaccine for toxoplasmosis, so avoidance of infection
pregnant women, regardless of country of residence. is necessary if congenital infection is to be prevented.

During Pregnancy Efforts include:
• Pregnant women suspected of having toxoplasmosis should be • Cooking meat to safe temperatures;
tested. The parasite is rarely detected in tissue or body fluids. • Peeling or thoroughly washing fruits and vegetables;
• Cleaning all food preparation surfaces and utensils that have
contacted raw meat, poultry, seafood, or unwashed fruits and
vegetables;

 If not later, When?

• Wearing gloves when changing cat litter, or else delegating this • For women infected with chloroquine-resistant P falciparum:
duty; and Mefloquine or quinine sulfate with clindamycin should be used
• Avoiding feeding cats raw or undercooked meat and keeping • Chloroquineresistant P vivax should be treated with
cats indoors. mefloquine.
• Chloroquine-sensitive P vivax or P ovale should be treated with
MALARIA chloroquine throughout pregnancy and then primaquine
• Transmitted by infected Anopheles mosquitoes, five species of postpartum.
Plasmodium cause human disease—falciparum, vivax, ovale,
malariae, and knowlesi • The World Health Organization (2011) allows for the use of
intermittent preventative therapy during pregnancy.
Maternal & Fetal Infection • This consists of at least two treatment doses of sulfadoxine –
Clinical Findings: pyrimethamine in the second
• Fever • and third trimesters.
• Chills • The rationale is that each dose will clear placental
• flu-like symptoms including headaches, myalgia, and malaise, asymptomatic infections and provide up to 6 weeks of
which may occur at intervals. posttreatment prophylaxis.
• Symptoms are less severe with recurrences. • This ideally will decrease the rate of low-birthweight newborns
in endemic areas
• Malaria may be associated with:
• Anemia and jaundice, and falciparum infections may cause Prevention & Chemoprophylaxis
kidney failure, coma, and death. • Malaria control and prevention relies on chemoprophylaxis
when traveling to or living in endemic areas.
• Pregnant women, although often asymptomatic, are said to be • Vector control is also important.
more likely to develop traditional symptoms • Insecticide-treated netting, pyrethroid insecticides, and N, N-
• Malarial infections during pregnancy—whether symptomatic diethyl-m-toluamide (DEET)-based insect repellent decrease
or asymptomatic—are associated with increased rates of malarial rates in endemic areas.
perinatal morbidity and mortality • These are well tolerated in pregnancy
• Adverse outcomes include: • If travel is necessary, chemoprophylaxis is recommended.
o Stillbirth • Chloroquine and hydroxychloroquine prophylaxis is safe and
o preterm birth well tolerated in pregnancy.
o Low birthweight • For travelers to areas with chloroquine-resistant P falciparum,
o maternal anemia mefloquine remains the only chemoprophylaxis
recommended.
• Infections with P falciparum are the worst, and early infection
increases the risk for abortion Contraindicated Drugs
• The incidence of malaria increases significantly in the latter two • Primaquine and doxycycline are contraindicated in pregnancy,
trimesters and postpartum and there are insufficient data on atovaquone/proguanil to
recommend them at this time.
Diagnosis • Likewise, amodiaquine is used in Africa, but data are limited in
• Identification of parasites by microscopical evaluation of a pregnant women.
thick and thin blood smear remains the gold standard for
diagnosis. AMOEBIASIS
• In women with low parasite densities, however, the sensitivity • Most persons infected with Entamoeba histolytica are
of microscopy is poor. asymptomatic.
• Malaria-specific antigens are now being used for rapid • Amebic dysentery, however, may take a fulminant course
diagnostic testing. during pregnancy, with fever, abdominal pain, and bloody
• Not only is their sensitivity still an issue in pregnancy, but these stools.
tests are not routinely available • Prognosis is worse if complicated by a hepatic abscess.
• Diagnosis is made by identifying E histolytica cysts or
Management trophozoites within a stool sample.
• The most frequently used antimalarial drugs are not • Therapy is similar to that for the nonpregnant woman, and
contraindicated in pregnancy. metronidazole or tinidazole is the preferred drug for amebic
• The World Health Organization recommends all infected colitis and invasive disease.
patients living in or traveling from endemic areas be treated • Noninvasive infections may be treated with paromomycin
with an artemisinin-based regimen for uncomplicated
falciparum malaria.

The Centers for Disease Control and Prevention (2013g)
• Atovaquone-proguanil or artemether-lumefantrine only if
other treatment options are not available or tolerated.
• Pregnant women diagnosed with uncomplicated malaria
caused by P vivax, P malariae, P ovale, and chloroquine-
sensitive P falciparum should be treated with chloroquine or
hydroxychloroquine.
 If not later, When?