Research www. AJOG.

org

OBSTETRICS
Pregnancy outcomes in young women with perinatally
acquired human immunodeficiency virus-1
Shauna F. Williams, MD; Megan H. Keane-Tarchichi, MD;
Linda Bettica, RN; Arry Dieudonne, MD; Arlene D. Bardeguez, MD, MPH

OBJECTIVE: The objective of the study was to review pregnancy and
neonatal outcomes among perinatally infected pregnant patients at our
institution.
STUDY DESIGN: A retrospective review of maternal and neonatal
records for all 10 perinatally infected adolescents between 1997 and
2007 was performed. Demographics, CD4 and viral load, antiretroviral
treatment, medical comorbidities, pregnancy outcomes, and neonatal
human immunodeficiency virus (HIV) status were abstracted.
RESULTS: The median age at first pregnancy was 18.5 years and 70%
were African American. The most common comorbidities were hema-
tologic abnormalities (70%) and cervical dysplasia/sexually transmit-
ted infections (STIs) (80%). Initial median CD4 and viral load were 317
cells/mm3 and 8780 copies/mL, respectively. The median gestational
age at delivery was 38 weeks. The most common obstetrical complica-
tions were preeclampsia (23%) and premature rupture of membranes/
preterm delivery (31%). The cesarean delivery (CD) rate was 62%, with
HIV as the indication in 75%. All infants were born alive; 1 was HIV
infected.
CONCLUSION: Despite high rates of STIs, CD, preterm delivery, and
hypertensive disorders, perinatal outcomes were favorable.
Key words: adolescent pregnancy, human immunodeficiency virus,
perinatal infection

Cite this article as: Williams SF, Keane-Tarchichi MH, Bettica L, et al. Pregnancy outcomes in young women with perinatally acquired human immunodeficiency
virus-1. Am J Obstet Gynecol 2009;200:149.e1-149.e5.

A dolescent pregnancies account for

more than 400,000 deliveries/year
in the United States and have been asso- deficiency virus (HIV)/acquired immuno-
With the introduction of combination
therapy with protease inhibitors in 1996,
the mortality of perinatally infected pa-
ciated with preterm labor, anemia, hy- deficiency syndrome (AIDS) living in the tients has decreased.8,9 Reduction in dis-
pertensive disorders of pregnancy, low United States.6 This group is comprised of ease progression and improved survival
birthweight, and a higher neonatal death both patients infected perinatally and with earlier initiation of combination
rate.1-3 Preterm birth rates as high as 13- those who acquired the disease during ad- antiretroviral therapy in children has
18% have been reported among adoles- olescence. As of June 2006, more than 1300 been reported by US as well as interna-
cents 10-17 years of age, and the rates of cumulative pediatric HIV/AIDS cases have tional investigators. The European Col-
preeclampsia have been as high as been reported in New Jersey, and about a laborative Study documented a lower
17-19% in a high schoolaged cohort.4,5 third of them are now in their teen years. rate of progression to category C (severe
Currently there are 5678 adolescents, The majority of these children acquired symptoms) by 1 year of age among chil-
aged 13-19 years, with human immuno- HIV-1 by perinatal transmission.7 dren born from 1995 to 1999 compared
with those born from 1985 to 1988 (5%
compared with 25%).10 In the United
From the Department of Obstetrics, Gynecology, and Womens Health (Drs Williams, States, the Pediatrics AIDS Clinical Tri-
Keane-Tarchichi, and Bardeguez) and the Division of Allergy, Immunology, and Infectious als (PACTG) protocol 219 cohort
Diseases, Department of Pediatrics (Ms Bettica and Dr Dieudonne), University of Medicine showed that of children and adolescents
and Dentistry of New JerseyNew Jersey Medical School, Newark, NJ.
who received combination therapy,
Presented in part at the Fourth International AIDS Society Conference on Pathogenesis,
there was a decrease in mortality from
Treatment, and Prevention, Sydney, NSW, Australia, July 22-25, 2007.
5.3% to 0.7% from 1996 to 1999.11
Received Feb. 13, 2008; revised June 24, 2008; accepted Aug. 12, 2008.
Our knowledge of the sexual behav-
Reprints: Shauna F. Williams, MD, Department of Obstetrics, Gynecology, and Womens Health,
University of Medicine and Dentistry of New JerseyNew Jersey Medical School, 185 South
iors, reproductive choices, and preg-
Orange Ave, MSB E561, Newark, NJ 07101. williash@umdnj.edu. nancy outcomes of HIV-infected adoles-
0002-9378/free 2009 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2008.08.020 cents and young adulthood is limited. In
1998 a case of a 14 year old adolescent
who delivered a term, HIV-negative in-
For Editors Commentary, see Table of Contents fant was reported by Crane et al.12 More
recently Zorrilla et al13 have described

FEBRUARY 2009 American Journal of Obstetrics & Gynecology 149.e1

Research Obstetrics
mother-to-child transmission (MTCT)
rates and characteristics of perinatally
infected pregnant adolescents. Although
there were no cases of MTCT in this co-
hort, no details were provided regarding
obstetrical or medical complications.13
Pregnancy rates and issues of reproduc-
tive health in the PACTG 219C cohort
have also been described, revealing sex-
ually transmitted infection rates up to
12% and abnormal cervical cytology in
47.5% of tested adolescents.14
Therefore, given the significant uncer-
tainties regarding pregnancy outcomes
among perinatally infected patients, our
objective was to describe the medical and
obstetric complications of this group
over the past decade at our institution.
This can provide information to be uti-
lized for assessment of the resources re-
quired to optimize maternal and neona-
tal outcomes for this unique population.
M ATERIALS AND M ETHODS
This study was approved by the Institu-
tional Review Board at University of
Medicine and Dentistry of New Jersey
New Jersey Medical School. Perinatally
infected patients were included if re-
ferred to the high-risk obstetric clinic at
University Hospital in Newark, NJ, and
delivered between November 1997 and
March 2007. Their exposure route was
documented by the Francois-Xavier
Bagnoud (FXB) Pediatric Infectious Dis-
ease Clinic at birth or upon entry into
care in infancy or early childhood.
A retrospective review of pediatric and
prenatal charts was performed. Data ab-
stracted included demographics (age,
race/ethnicity); medical history includ-
ing HIV-related complications; repro-
ductive history (number of pregnancies,
births, or abortions); gestational age at
initiation of care and at delivery;
prepregnancy medical, social, and surgi-
cal history; mode of delivery; and preg-
nancy, postpartum, and gynecologic
complications. HIV-related data ab-
stracted included treatment regimens
prior to and during pregnancy, HIV-1
viral load, and absolute CD4 counts at
initial prenatal visit and throughout
pregnancy.
149.e2 American Journal of Obstetrics & Gynecology FEBRUARY 2009
Sex, birthweight, Apgar scores at 5 and
10 minutes, and HIV status of the infants
were abstracted. HIV deoxyribonucleic
acid (DNA) polymerase chain reaction
(PCR) testing for the evaluation of infant
status was performed within 48 hours of
birth and at 1 and 4 months. If HIV DNA
PCR was negative, HIV antibody testing
was performed at 12 and 18 months of
age. If all tests were negative, the infant
was deemed HIV negative. If HIV DNA
PCR was positive at any point, a confir-
matory test was repeated as soon as pos-
sible. An infant was considered to have in
utero transmission if there were 2 posi-
tive HIV DNA PCR tests within 2 weeks
of birth. Neonatal status was docu-
mented in pediatric charts of the FXB
clinic and reviewed by 2 of the authors
(A.D., L.B.).
R ESULTS
Ten patients were seen during the study
period. Three patients had 2 deliveries
each for a total of 13 pregnancies. The
median age at time of first pregnancy was
18.5 years (range, 16-21 years). Seven pa-
tients were African American, 2 were
Hispanic, and 1 patient was white.
All patients had a diagnosis of a med-
ical comorbidity or a sexually transmit-
ted infection, either before or during
pregnancy, as listed in Table 1. Hemato-
logic abnormalities, defined as anemia or
history of thrombocytopenia, were
present in 7 patients. One patient had se-
vere thrombocytopenia, with a platelet
nadir of 7000/mm3 during pregnancy re-
quiring WinRho, corticosteroids during
pregnancy, and platelet transfusion at
delivery. Six patients had a history of
pulmonary disease, with asthma or reac-
tive airway disease being the most com-
mon. One patient had a history of
cardiomyopathy prior to pregnancy
with normal cardiac function during
pregnancy.
Obstetric complications included pre-
eclampsia (n 3), gestational diabetes
controlled with insulin (n 1), and oli-
gohydramnios (n 1) (Table 2). The
median gestational age at delivery was 38
weeks (range, 33-41 weeks) and 4 pa-
tients delivered preterm. Eight of the 13
infants (62%) were delivered by cesarean
www.AJOG.org
TABLE 1
Medical history and sexually
transmitted infections
Pulmonary 6
..................................................................................................
Asthma/reactive airway disease 6
..................................................................................................
Bronchiectasis 1
..................................................................................................
Lymphoid interstitial pneumonitis 1
...........................................................................................................
Hematologic 7
..................................................................................................
Anemia a
5
..................................................................................................
Thrombocytopenia b
3
...........................................................................................................
AIDS-related illnesses 4
..................................................................................................
Esophageal candidiasis 3
..................................................................................................
Wasting syndrome 3
..................................................................................................
Lymphoid interstitial pneumonitis 1
...........................................................................................................
Sexually transmitted infections 8
..................................................................................................
Chlamydia 4
..................................................................................................
Gonorrhea 1
..................................................................................................
Condyloma 2
..................................................................................................
Genital herpes simplex virus 3
..................................................................................................
Trichomonas 2
...........................................................................................................
a
Hemoglobin 10.5 g/dL; b Platelets 150,000/
mm3.
...........................................................................................................
Williams. Pregnancy outcomes in young women with
perinatally acquired HIV-1. Am J Obstet Gynecol
2009.
delivery (CD): 6 for HIV indication, 1 for
previous CD, and 1 for active genital her-
pes outbreak.
Eight patients had a history or a diag-
nosis of a sexually transmitted infection
(STIs) during pregnancy including (in
descending order of frequency) Chla-
mydia, genital herpes simplex virus,
Trichomonas, condyloma, or gonorrhea
(Table 1). In this group, 7 had an STI
diagnosed during the pregnancy. Abnor-
mal cervical cytology was seen in 5 pa-
tients in the cohort with cervical intra-
epithelial neoplasia (CIN) confirmed by
biopsy in 4 patients: 2 with CIN 3 and 2
with CIN 1. Two patients underwent
cone biopsy prior to pregnancy, and 1
patient underwent loop electrosurgical
excision procedure after her second
pregnancy.
Nine patients had previously been
exposed to Zidovudine (ZDV) during
childhood. Four patients had been
treated with 3 or fewer antiretroviral
agents prior to the first pregnancy,
 www.AJOG.org
TABLE 2
Delivery data, medical/obstetric complications, and neonatal outcomes
Gestational Initial CD4 Viral load Hospitalizations and Delivery mode
age at (cells/ Initial viral load at delivery Adherence postpartum and indication Neonatal
Case delivery mm3) (copies/mL) (copies/mL) (%)a Medical history complications Obstetric complications for CD status
1 33 28 21,000 17,000 50 Bronchiectasis/ Death from Preterm labor, low NSVD HIV
RAD, candidiasis, pulmonary birthweight/small for negative,
anemia complications (2000) gestational age CMV
positive
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
2a 39 324 8780 4100 0 Asthma None Oligohydramnios NSVD Positive
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
2b 33 98 47,000 400 90 Asthma, anemia, Hospitalizations for PPROM, GDM, CD: HSV Negative
severe thrombocytopenia, preeclampsia, low
thrombocytopenia, gestational diabetes, birthweight
wasting syndrome, pneumonia, vomiting,
candidiasis postpartum
endometritis
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
3 38 558 66,837 21,500 100 Herpes zoster None Preeclampsia, low CD: HIV Negative
birthweight/small for
gestational age
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
4a 39 275 757 864 67 Cardiomyopathy None None CD: HIV Negative
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
4b 41 177 12,400 57 92 Cardiomyopathy None None CD: repeat CD Negative
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
5 38 321 858 25,232 100 LIP, asthma, Periventricular None CD: HIV Negative
FEBRUARY 2009 American Journal of Obstetrics & Gynecology

wasting syndrome, multifocal

thrombocytopenia leukomalacia (2006)
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
6 37 341 7407 2204 88 None None Gestational hypertension CD: HIV Negative
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
7a 39 858 81 115 100 Thrombocytopenia, None None NSVD Negative
asthma
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
7b 38 590 50 50 100 Thrombocytopenia, None Low birthweight/small for NSVD Negative
asthma gestational age
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
8 35 2 750,000 5240 100 Asthma, anemia, None Preeclampsia CD: HIV Negative

Obstetrics
wasting syndrome,
candidiasis
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
9 36 197 400 48,042 82 Anemia None PPROM, low birthweight/ CD: HIV Negative
small for gestational age
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
400

Research
10 40 317 15,200 100 Asthma, anemia, Hospitalized for None NSVD Negative
neuropathy neuropathy
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
NSVD, normal spontaneous vaginal delivery; CMV, cytomegalovirus; GDM, gestational diabetes; HSV, herpes simplex virus; LIP, lymphoid interstitial pneumonitis; PPROM, preterm premature rupture of membranes; RAD, reactive airway disease.
a
Percent of visits with documentation of self-reported adherence to antiretroviral regimen.
............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
149.e3

Williams. Pregnancy outcomes in young women with perinatally acquired HIV-1. Am J Obstet Gynecol 2009.
Research Obstetrics www.AJOG.org

TABLE 3
Demographic characteristics and medication regimens
Year of Age at Number of past
Case Year of birth pregnancy delivery ARVs Regimen during pregnancy
1 1980 1997 16 2 ZDV, DDI, indinavira
................................................................................................................................................................................................................................................................................................................................................................................
b
2a 1979 1999 20 2 None
................................................................................................................................................................................................................................................................................................................................................................................
2b 1979 2006 27 10 Lamivudine, abacavir, lopinavir/ritonavir
................................................................................................................................................................................................................................................................................................................................................................................
3 1983 2001 17 3 ZDV, DDI, indinavir/ritonavir
................................................................................................................................................................................................................................................................................................................................................................................
4a 1985 2002 16 6 Abacavir/lamivudine/ZDV
................................................................................................................................................................................................................................................................................................................................................................................
4b 1985 2006 21 7 Abacavir/lamivudine/ZDV
................................................................................................................................................................................................................................................................................................................................................................................
5 1984 2003 19 5 ZDV, DDI, lopinavir/ritonavir
................................................................................................................................................................................................................................................................................................................................................................................
6 1986 2004 18 6 ZDV, lamivudine, nelfinavir
................................................................................................................................................................................................................................................................................................................................................................................
7a 1982 2004 21 3 ZDV, lamivudine, nelfinavir
................................................................................................................................................................................................................................................................................................................................................................................
7b 1982 2007 24 3 ZDV, lamivudine, nelfinavir
................................................................................................................................................................................................................................................................................................................................................................................
a
8 1983 2005 21 6 ZDV, DDI, nelfinavir
................................................................................................................................................................................................................................................................................................................................................................................
a
9 1988 2006 18 4 Tenofovir, DDI, lopinavir/ritonavir
................................................................................................................................................................................................................................................................................................................................................................................
10 1987 2007 19 7 Lamivudine, tenofovir, lopinavir/ritonavir
................................................................................................................................................................................................................................................................................................................................................................................
ARV, antiretroviral medication; DDI, didanosine; ZDV, zidovudine.
a
Regimen changed during pregnancy; b Patient refused antiretroviral therapy.
................................................................................................................................................................................................................................................................................................................................................................................

Williams. Pregnancy outcomes in young women with perinatally acquired HIV-1. Am J Obstet Gynecol 2009.

whereas 1 patient was exposed to 10 complaints, pneumonia, and diabetes C OMMENT

antiretroviral (ARV) medications control (Table 2). Case 2 also developed This review of our experience over the
prior to her second pregnancy. Pa- postpartum endometritis. All other pa- past 10 years suggests that even with high
tients were maintained on their previ- tients had uncomplicated postpartum rates of medical comorbidities and ob-
ously prescribed treatment regimens courses. In addition, there was 1 death in stetric complications, neonatal out-
unless there was evidence of genotype this cohort 3 years after her pregnancy comes are favorable in most pregnancies
resistance or inadequate viral suppres- secondary to pulmonary disease. (92%) of perinatally infected adoles-
sion on their ARV regimen. Protease There were no neonatal deaths or con- cents. All infants were live born and ex-
inhibitor-based regimens were used in genital anomalies in this cohort. Four perienced few neonatal complications.
11 out of the 13 pregnancies; 1 patient patients delivered prior to 37 completed The perinatal HIV transmission rate was
received a nonprotease inhibitor- weeks. Birthweights ranged from 1200 to higher than the expected national rate,
based regimen (abacavir/lamivudine/ 3730 g, 5 (38%) infants were less than which can be attributed to 1 patients
ZDV) in both of her pregnancies with
2500 g, of which 2 were term infants and noncompliance with recommendations
adequate viral suppression (Table 3).
4 were less than the 10th percentile for to reduce MTCT.
ZDV was excluded from the ARV reg-
gestational age. Care for these HIV- Adolescent pregnancy has previously
imen in 3 patients based on evidence of
exposed neonates was provided at the been reported to be associated with hy-
resistance or documentation of previ-
FXB clinic. Only 1 child was perinatally pertensive disorders in pregnancy. Satin
ous prolonged monotherapy exposure
during childhood. Regimen changes infected for a MTCT rate of 7.7%. In this et al5 reported a 17% rate of pregnancy-
were made in 3 cases because of adverse case, the mother refused ARV medica- induced hypertension among 16-19 year
effects (nausea), evidence of resistance, tions as well as cesarean delivery. There old females. In our cohort, 4 pregnancies
or inappropriate viral suppression be- was also 1 infant diagnosed with congen- (30.8%) were complicated by gestational
cause of the lack of adherence. ital cytomegalovirus who was HIV nega- hypertension or preeclampsia; of these, 3
Inpatient admissions were required tive. The mother of this infant had test were between the ages of 17 and 21 years.
for 2 patients: 1 (case 10) for evaluation results during pregnancy consistent with Adolescent pregnancies have also been
of worsening peripheral neuropathy past exposure (cytomegalovirus immu- associated with preterm delivery.2 In our
during pregnancy, and the other patient noglobulin M negative, immunoglobu- group, premature preterm rupture of
(case 2) was admitted several times lin G positive), but it is uncertain membranes and preterm labor compli-
throughout her second pregnancy for se- whether she was reinfected during cated 3 pregnancies, 2 of which were of
vere thrombocytopenia, gastrointestinal pregnancy. mothers 18 years of age or younger. In

149.e4 American Journal of Obstetrics & Gynecology FEBRUARY 2009

www.AJOG.org
this cohort, medical comorbidities were
seen in the majority of patients, particu-
larly anemia, but did not lead to adverse
maternal or fetal outcomes. Indeed,
these observations appear to be consis-
tent with expected complications previ-
ously reported by other authors in non
HIV-infected adolescents.2,4
There was a high rate of CD (62%) in
this group of patients compared with our
institutional rate of 32.8%. HIV-indi-
cated cesarean deliveries accounted for
75% of these, highlighting the likelihood
of CD secondary to inadequate viral sup-
pression. Inadequate viral suppression
frequently seen in HIV-infected adoles-
cent cohorts reinforces the need for close
surveillance and counseling on treat-
ment adherence to decrease operative
deliveries.15 Complications following
CD in our cohort were rare, but prior
studies have shown increased morbidity
rates in HIV-positive patients after
CD.16 Prior CD is the most common in-
dication for repeat cesarean section;
thus, this group of patients is likely to
experience repeat abdominal deliveries
in future pregnancies with its associated
morbidities.17
High-risk sexual behavior is also of
concern in this group of patients. Abnor-
mal cervical cytology and STIs affected
80% of the patients in our cohort, and 7
patients (70%) were diagnosed with an
STI during pregnancy. High rates of
STIs, specifically chlamydia and gonor-
rhea (6-22%), have also been reported in
HIV-infected adolescents enrolled in the
REACH (Reaching for Excellence in Ad-
olescent Care and Health) and PACTG
219 cohorts.14,18 Abnormal cervical cy-
tology was seen in 50% of our patients,
similar to a report from the PACTG
219C cohort.14 These observations dem-
onstrate the importance of safe-sex prac-
tices counseling because this group of
adolescents and young adults not only
have the potential to transmit HIV to
their partners but are at high risk for ac-
quiring new STIs.
Although our study is limited by the
cohort size and retrospective design, it
provides information on the issues and
concerns of this group of patients who
are now reaching child-bearing age. Sim-
ilar to observations in adult populations,
use of highly active antiretroviral therapy
has lead to reduced mortality and mor-
bidity of perinatally infected adolescents
and young adults. Nonetheless, our cur-
rent challenges include how and when to
address reproductive health issues such
as safe-sex practices counseling, contra-
ception, and STI prevention including
early access to human papilloma virus
immunization to prevent premalignant
and malignant genital lesions.
It is also imperative that we support
treatment adherence to achieve and
maintain viral suppression to avert oper-
ative deliveries for an HIV indication,
which can compromise future reproduc-
tive health. As we decrease HIV MTCT
globally, we must monitor and address
the reproductive health issues experi-
enced by this population of perinatally
infected adolescents in both high- and
low-income countries to improve peri-
natal outcomes and long-term maternal
health. f
ACKNOWLEDGMENTS
We thank Drs James Oleske, Joseph Apuzzio,
and Barry Dashefsky, Jocelyn Grandchamp,
RN, and Charmaine Calilap-Bernardo, RN, for
their care of this population and input in the
preparation of this manuscript as well as to the
clinic staff at University Obstetric Associates
and University Hospital (Newark, NJ) for their
excellent support and assistance in the care of
these patients.
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149.e5