INFECTION IN PREGNANCY

TORCH
 Mode of Transmission

Horizontal transmission

Vertical transmission
Congenital infection
Perinatal infection
Neonatal infection
Postnatal infection
Infection during pregnancy:

Transplacental infection

Non placental infection:

Ascending infection
Intrapartum infection
Postnatal infection
 General Principles
Pregnancy does not alter resistance to infection
Severe infections have greater effects on the
fetus
Maternal antibodies cross the placenta and give
passive immunity to the fetus
Fetus becomes immunologically competent
from the 14th week
 Fetus and Infection
• Indirect effect - O2 transport, nutrient
exchange

• Direct effect - invasion of placenta and

infection of fetus
• Viruses more than bacteria
• rarely effect fetus unless maternal infection is severe
– exception: Rubella, CMV, Herpes Simplex
 Fetus and Infection
Infections cause
- miscarriage
- congenital anomalies
- fetal hydrops
- fetal death
- preterm delivery
- preterm rupture of the membranes
TORCH

T = Toxoplasma gondii
O= Others
R= Rubella Virus
C= Cytomegalovirus
H= Herpes Simplex Virus
 Toxoplasmosis
• Caused by protozoan – Toxoplasma gondii
• Domestic cat is the definitive host with infections via:
– Ingestion of cysts (meats, garden products)
– Contact with oocysts in feces
• Much higher prevalence of infection in European
countries (ie France, Greece)
• Acute infection usually asymptomatic
• 1/3 risk of fetal infection with primary maternal
infection in pregnancy
– Infection rate higher with infxn in 3rd trimester
– Fetal death higher with infxn in 1st trimester
Toxoplasma Infection

•Acquired infection
–immunocompetent individuals:
Asymptomatic or very mild infection
–immunocompromised individuals:
high risk of fatal disseminated infection;
often reactivation

•Congenital infection (in pregnancy):

- high risk of fetal damage or death after
- primary infection during pregnancy
 Risk Factors for Congenital Toxoplasmosis

Primary Toxoplasma infection during pregnancy:

–no known risk for congenital infection of infants

born to immune women

–no known risk of congenital infection in case of

primary infection before conception
Time point of infection during pregnancy
 Clinical Manifestations
• Most (70-90%) are asymptomatic at birth
• Classic triad of symptoms:
– Chorioretinitis
– Hydrocephalus
– Intracranial calcifications

• Other symptoms include fever, rash, HSM, microcephaly,

seizures, jaundice, thrombocytopenia, lymphadenopathy,
premature-birth, still-birth/IUFD

• Initially asymptomatic infants are still at high risk of

developing abnormalities, especially chorioretinitis
Chorioretinitis of congenital toxo
 Diagnosis
• Maternal IgG testing indicates past infection
(but when…?)
• Can be isolated in culture from placenta,
umbilical cord, infant serum
• PCR testing on WBC, CSF, placenta
– Not standardized
 Toxo Screening
• Prenatal testing with varied sensitivity not
useful for screening

• Neonatal screening with IgM testing

implemented in some areas
– Identifies infected asymptomatic infants who may
benefit from therapy
 Treatment
• Treatment for pregnant mothers diagnosed
with acute toxo
– Spiramycin daily
• Macrolide antibiotic
– Small studies have shown this reduces likelihood
of congenital transmission (up to 50%)

• If infant diagnosed prenatally, treat mom

– Spiramycin, pyrimethamine (anti-malarial,
dihydrofolate reductase inhib), and sulfadiazine
(sulfa antibiotic)
– Leucovorin rescue with pyrimethamine
 Syphilis
• T.Pallidum
• <1:1000 pregnant women
• Can infect trans placenta from 15th week
• Second stage by birth if not treated
• Screening – VDRL, RPR
• Diagnostic tests – TPI, FTA-Abs
• High dose Penicillin's
 Syphilis
• Treponema pallidum (spirochete)
• Transmitted via sexual contact
• Placental transmission as early as 6wks gestation
– Typically occurs during second half
– Mom with primary or secondary syphilis more likely to
transmit than latent disease
• Large decrease in congenital syphilis since late 1990s
– In 2002, only 11.2 cases/100,000 live births reported
 Congenital Syphilis
• 2/3 of affected live-born infants are
asymptomatic at birth
• Clinical symptoms split into early or late (2
years is cut off)
• 3 major classifications:
– Fetal effects
– Early effects
– Late effects
 Clinical Manifestations
• Fetal:
– Stillbirth
– Neonatal death
– Hydrops fetalis
• Intrauterine death in 25%
• Perinatal mortality in 25-30% if untreated
 Clinical Manifestations
• Early congenital (typically 1st 5 weeks):
– Cutaneous lesions (palms/soles)
– HSM
– Jaundice
– Anemia
– Snuffles
– Periostitis and metaphysial dystrophy
– Funisitis (umbilical cord vasculitis)
Periostitis of long bones seen in
neonatal syphilis
 Clinical Manifestations
• Late congenital:
– Frontal bossing
– Short maxilla
– High palatal arch
– Hutchinson teeth
– 8th nerve deafness
– Saddle nose
– Perioral fissures
• Can be prevented with appropriate treatment
Hutchinson teeth – late result of
congenital syphilis
 Diagnosing Syphilis
(Not in Newborns)
• Available serologic testing
– RPR/VDRL: nontreponemal test
• Sensitive but NOT specific
• Quantitative, so can follow to determine disease activity and
treatment response
– MHA-TP/FTA-ABS: specific treponemal test
• Used for confirmatory testing
• Qualitative, once positive always positive
• RPR/VDRL screen in ALL pregnant women early in
pregnancy and at time of birth
– This is easily treated!!
 Definition of Congenital Syphilis
• Confirmed if T. pallidum identified in skin lesions,
placenta, umbilical cord, or at autopsy
• Presumptive diagnosis if any of:
– Physical exam findings
– CSF findings (positive VDRL)
– Osteitis on long bone x-rays
– Funisitis (“barber shop pole” umbilical cord)
– RPR/VDRL >4 times maternal test
– Positive IgM antibody
 Treatment
• Penicillin G is THE drug of choice for ALL syphilis
infections
• Maternal treatment during pregnancy very effective
(overall 98% success)
• Treat newborn if:
– They meet CDC diagnostic criteria
– Mom was treated <4wks before delivery
– Mom treated with non-PCN med
– Maternal titers do not show adequate response (less than
4-fold decline)
 Rubella
• Togavirus: single-stranded RNA virus
• Incubation - 14-21 days
• Respiratory droplet inoculation
– only modestly contagious
• Fever, rash (3 days), cough, arthralgias, post auricular
and suboccipital lymphadenopathy
• Usually mild, overt clinical symptoms 50-75% of
cases
• Encephalitis, bleeding diathesis & arthritis are rare
complications
• Infection earlier in pregnancy has a higher
probability of affected infant
 Rubella and the Fetus

• Sensorineural hearing loss (50-75%)

• Cataracts and glaucoma (20-50%)
• Cardiac malformations (20-50%)
• Neurologic (10-20%)
• Others to include growth retardation, bone
disease, HSM, thrombocytopenia, “blueberry
muffin” lesions
“Blueberry muffin” spots representing
extramedullary hematopoesis
• Purpura, Splenomegaly, jaundice,
meningoencephalitis, thrombocytopenia are
transient
• Congenital cataracts, Glaucoma, heart
disease, deafness, microcephaly and mental
retardation are permanent abnormalities
• Sequele: Diabetes, thyroid abnormalities,
precocious puberty & progressive
panencephalitis
 Diagnosis

• Maternal IgG may represent immunization or past

infection - Useless!
• Can isolate virus from nasal secretions
– Less frequently from throat, blood, urine, CSF
• Serologic testing
– IgM = recent postnatal or congenital infection
– Rising monthly IgG titers suggest congenital infection
• Diagnosis after 1 year of age difficult to establish
 Prevention and Treatment
• Vaccination (95% seroconversion)
@ 15 months and early adulthood
• Immune status checking in teenagers, pre-
college and pre-pregnancy
• Antenatal testing
• Serology testing for presumed exposures
(paired Sera)
• No in-utero therapy
 Cytomegalovirus
• DNA virus
• Congenital infection - 1%
• 5-10% of those infected show clinical illness at
birth
• Neonatal MR - 20-30%
• 90% of survivors get late complications
• 5-15% with no demonstrable disease at birth
get some abnormality (deafness)
 Cytomegalovirus (CMV)
• Most common congenital viral infection
– ~40,000 infants per year in the U.S.
• Mild, self limiting illness
• Transmission can occur with primary infection or
reactivation of virus
– 40% risk of transmission in primary infxn
• Studies suggest increased risk of transmission
later in pregnancy
– However, more severe sequalae associated with
earlier acquisition
 Clinical Manifestations

• 90% are asymptomatic at birth!

– Up to 15% develop symptoms later, notably
sensorineural hearing loss
• Symptomatic infection
– SGA, HSM, petechiae, jaundice, chorioretinitis,
periventricular calcifications, neurological
deficits
– >80% develop long term complications
• Hearing loss, vision impairment, developmental
delay
 CMV Congenital Infection
• Hepatomegaly }
• Spleenomegaly }
• Jaundice }TORCH
• Thrombocytopenia }Syndrome
• Petechiae }
• Microcephaly }
• Intrauterine growth retardation }
 CMV Congenital Infection (Late)
• Venticulomegaly
• Cerebral atrophy
• Mental retardation
• Psychomotor delay
• Seizures
• Learning difficulties and language delay
• Chorioretinitis / Optic atrophy
• Intracranial calcifications
• Long bone radiolucencies, dental abnormalities
• Pneumonitis
Ventriculomegaly and
calcifications of
congenital CMV
 Diagnosis
• Maternal IgG shows only past infection
– Infection common – this is useless
• Viral isolation from urine or saliva in 1st 3weeks of
life
– Afterwards may represent post-natal infection
• Viral load and DNA copies can be assessed by PCR
– Less useful for diagnosis, but helps in following viral
activity in patient
• Serologies not helpful given high antibody in
population
 Treatment
• Ganciclovir 6wks in symptomatic infants
– Studies show improvement or no progression of hearing
loss at 6mos
– No other outcomes evaluated (development, etc.)
– Neutropenia often leads to cessation of therapy
• Treatment currently not recommended in
asymptomatic infants due to side effects
• Area of active research to include use of
valgancyclovir, treating asymptomatic patients, etc.
• No vaccination
 Herpes Simplex (HSV)
• HSV1 or HSV2
• Primarily transmitted through infected
maternal genital tract
– Rationale for C-section delivery prior to
membrane rupture
• Primary infection with greater transmission
risk than reactivation
 Clinical Manifestations
• Most are asymptomatic at birth
• 3 patterns of ~ equal frequency with symptoms
between birth and 4wks:
– Skin, eyes, mouth (SEM)
– CNS disease
– Disseminated disease (present earliest)
• Initial manifestations very nonspecific with skin
lesions NOT necessarily present
Presentations of congenital HSV
 Diagnosis
• Culture of maternal lesions if present at delivery
• Cultures in infant:
– Skin lesions, oro/nasopharynx, eyes, urine, blood,
rectum/stool, CSF
• CSF PCR
• Serologies again not helpful given high prevalence of
HSV antibodies in population
 Treatment
• High dose acyclovir 60mg/kg/day divided
q8hrs
– X21days for disseminated, CNS disease
– X14days for SEM
• Ocular involvement requires topical therapy
as well
 Index of Suspicion
• When do you think of TORCH infections?
– IUGR infants
– HSM
– Thrombocytopenia
– Unusual rash
– Concerning maternal history
– “Classic” findings of any specific infection
 Conclusion
The main issues include
• General principles
• Infection and the fetal affects
• Specific problems for the fetus with maternal
infections.
• Congenital syndromes - main features
Which TORCH Infections Can Absolutely Be
Prevented?
• Rubella

• Syphilis