Maternal Nutritional Status Predicts Adverse Birth
Outcomes among HIV-Infected Rural Ugandan Women
Receiving Combination Antiretroviral Therapy
Sera Young1, Katherine Murray2, Julia Mwesigwa3, Paul Natureeba3, Beth Osterbauer4, Jane Achan5,
Emmanuel Arinaitwe3, Tamara Clark4, Veronica Ades6, Albert Plenty2, Edwin Charlebois2,
Theodore Ruel7, Moses Kamya8, Diane Havlir4, Deborah Cohan6*
1Division of Nutritional Sciences, Cornell University, Ithaca, New York, United States of America, 2Center for AIDS Prevention Studies, University of California San
Francisco, San Francisco, California, United States of America, 3Makerere University-University of California San Francisco Research Collaboration, Kampala, Uganda,
4Department of Medicine, University of California San Francisco, San Francisco, California, United States of America, 5Department of Paediatrics and Child Health,
Makerere University College of Health Sciences, Kampala, Uganda, 6Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San
Francisco, San Francisco, California, United States of America, 7Department of Pediatrics, University of California San Francisco, San Francisco, California, United States of
America, 8Department of Medicine, Makerere University Medical School, Kampala, Uganda
Objective: Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional
status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the
relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb)
among 166 women initiating cART in rural Uganda.
Design: Prospective cohort.
Methods: HIV-infected, ART-naı ¨ve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a
protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was
assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis.
Results: Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were
anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%),
stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected.
Gaining ,0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome.
Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age
decreased by 52%.
Conclusions: In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was
common. Infants whose mothers gained ,0.1 kg/week were at increased risk for LBW, preterm delivery, and composite
adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among
Trial Registration: Clinicaltrials.gov NCT00993031
Citation: Young S, Murray K, Mwesigwa J, Natureeba P, Osterbauer B, et al. (2012) Maternal Nutritional Status Predicts Adverse Birth Outcomes among HIV-
Infected Rural Ugandan Women Receiving Combination Antiretroviral Therapy. PLoS ONE 7(8): e41934. doi:10.1371/journal.pone.0041934
Editor: Claire Thorne, UCL Institute of Child Health, University College London, United Kingdom
Received February 2, 2012; Accepted June 29, 2012; Published August 7, 2012
Copyright: ? 2012 Young et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The primary sponsor of the PROMOTE-Pregnant Women and Infants trial is the National Institute for Child Health and Human Development (http://
www.nichd.nih.gov/). This nutritional sub-study was supported by PEPFAR (President’s Emergency Plan For AIDS Relief), the Office of the Global AIDS Coordinator,
and the Office of AIDS Research. Abbott Laboratories provides Lopinavir/ritonavir for the parent trial. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have the following interests to declare: Abbott Laboratories provides Lopinavir/ritonavir for the parent trial. There are no
patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and
materials, as detailed online in the guide for authors.
* E-mail: firstname.lastname@example.org
As the availability of combination antiretroviral therapy (cART)
for HIV-infected pregnant women broadens and perinatal HIV
transmission is reduced, there are increasing numbers of HIV-
exposed, uninfected children worldwide . Studies to date
suggest that these children have worse outcomes compared to their
HIV-unexposed counterparts [2–6]. Preterm delivery (PTD), low
birth weight (LBW), stunting, and other markers of fetal growth
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restriction are important predictors of neonatal mortality, post-
neonatal infant mortality, and infant and child morbidity [7–16].
Among the many factors that predict poor gestational outcomes,
maternal nutritional status before and during pregnancy has
emerged as a major modifiable determinant [15,17–21]. Specif-
ically, pre-pregnancy body mass index (BMI) and gestational
weight gain (GWG) have repeatedly been associated with LBW
[22–28]. Little is known, however, about the relationship between
maternal nutritional status and birth outcomes among HIV-
infected women on cART, particularly in the resource-constrained
settings of rural sub-Saharan Africa.
Given that nutritional status is a strong modifiable predictor of
birth outcomes, we sought to characterize the baseline nutritional
status of pregnant women initiating cART in rural Uganda and
examine the associations between their nutritional status and
adverse birth outcomes.
Study Design and Population
We analyzed nutritional data from an ongoing prospective
clinical trial in Tororo, Uganda, evaluating malaria outcomes
among women randomized to receive an HIV protease inhibitor
or non-nucleoside reverse transcriptase inhibitor based cART
regimen (NCT00993031, http://clinicaltrials.gov). The protocol
for this trial and supporting CONSORT checklist are available as
supporting information; see Checklist S1 and Protocol S1. Women
with HIV-1 infection and a documented pregnancy between 12
and 28 weeks of gestation were enrolled (Figure S1). Women were
excluded if they had ever used cART, had received single-dose
nevirapine within 2 years, had prior dose-limited toxicity to
trimethoprim-sulfamethoxazole (TS) within 2 weeks, received any
contraindicated medications, had any WHO stage 4 diseases, had
cardiac abnormalities, or if they had abnormal laboratory values at
screening, including hemoglobin (Hb) ,7.5 g/dL. All women
gave written informed consent. The study protocol was approved
by the Faculty of Medicine’s Research and Ethics Committee at
Makerere University, the Uganda National Council of Science
and Technology, and the Committee on Human Research at the
University of California San Francisco.
Trained study staff collected baseline demographic data and
general medical, HIV, and obstetric history. Close birth spacing
was defined as ,2 years between births (either live born or
stillbirth) based on self-reported obstetric history. Socioeconomic
status (SES) was assessed by performing principle component
analysis of a series of questions about possession of a radio,
telephone, television, motorcycle, or bicycle. We used the first two
components of the principle component analysis which accounted
for over 55% of the information contained in the 6 asset holding
Maternal height was measured to the nearest 0.1 cm using a
Seca 206 wall-mounted measuring tape and maternal weight was
measured to the nearest 500 g using a Seca 876 mechanical scale.
Gestational age was estimated based on last menstrual period
(LMP) and fetal ultrasound at the screening visit. All women
received a fetal ultrasound. Final pregnancy dating was based on
ultrasound if the discrepancy between LMP and ultrasound was
greater than 1 week in the 1sttrimester, 2 weeks in the 2nd
trimester or 3 weeks in the 3rdtrimester . Ultrasound was used
to date 50.5% of second trimester pregnancies (n=105) and
43.4% of third trimester pregnancies (n=53), for a total of 48.1%
of the 158 pregnancies in these analyses. HIV status was
documented with a positive rapid HIV antibody test (Determine,
Inverness Medical Japan Co., Japan) plus a confirmatory test (Stat-
Pak, Chembio Diagnostic Systems, Inc., NY, USA). All women
received multivitamins containing iron and folic acid, iron
supplements, prophylactic mebendazole, an insecticide-treated
bed net, and were started on either zidovudine/lamivudine/
efavirenz or zidovudine/lamivudine/lopinavir/ritonavir. Women
were also started on daily TS if they were not already receiving TS
prophylaxis prior to study enrollment.
Women returned to the study clinic every four weeks until
delivery for scheduled study visits as well as when they experienced
adverse events or any health conditions requiring evaluation. At
scheduled monthly visits, maternal weight was measured as
described above. Laboratory evaluations were regularly conducted
throughout pregnancy including Hb, HIV RNA PCR, and CD4/
CD8 lymphocyte subsets. Clinical progression of HIV disease was
categorized according to 2007 WHO criteria . Adverse events
were classified according to the standardized Toxicity Table for
Grading Severity of Adult and Pediatric Adverse Events .
Clinical malaria was defined using standardized WHO criteria as
the presence of fever within the past 24 hours and a positive thick
blood smear. At each scheduled visit, women were given a 5-week
supply of multivitamins, antiretroviral therapy, and TS. Data were
collected on socioeconomic status (SES) during a scheduled visit
If delivery took place in the hospital, trained study staff assessed
infant anthropometry immediately after birth. Infant weight was
measured to the nearest 10 g using a calibrated digital Seca 354
scale. Birth length was obtained using a locally made infant length
board. Head circumference was measured to the nearest 0.1 cm
using non-stretchable tape (Seca 212). If delivery occurred outside
the study-affiliated hospital and infants were brought to the clinic,
the anthropometric assessments were performed by study staff as
described above. Only those infants who were measured within 12
hours of birth were included in this analysis. Infant HIV status at
birth was determined by HIV-1 DNA PCR (Cobas Amplicor,
The following markers of maternal nutritional status were
assessed: body mass index (BMI) at enrollment, baseline Hb, mean
Hb during pregnancy, maternal weight at 24–28 weeks gestation
, and maternal weight change during pregnancy. Because
there are no BMI standards for pregnant women, only non-
pregnant adults , we categorized BMI at enrollment based on
tertiles (,20.43, 20.43–22.59, and .22.59). Hb concentrations
were categorized into 3 groups: severe anemia (#8.5 g/dL), mild-
to-moderate anemia (8.5–10.9 g/dL), and no anemia ($11 g/dL).
Because weekly maternal weight gain should be linear in the
second and third trimesters , weekly maternal weight change
was calculated by dividing the weight change between enrollment
and last weight before delivery by the number of weeks elapsed
between the two. For the categorical GWG variable, weight loss
was defined as a rate of weight change ,0 kg/wk. Those who had
a positive average weekly weight gain were categorized as ,25th
percentile of gainers (,0.1 kg per week) or $25thpercentile
($0.1 kg per week). Maternal weight at 7 months gestation was
defined as the woman’s weight in kg between 24 and 28 weeks of
Infant outcomes included LBW, small for gestational age (SGA),
stunting, wasting, underweight, preterm delivery, head-sparing
growth restriction, and fetal death. LBW was defined as ,2500
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grams. SGA newborns were those with birth weight ,10th
percentile for their gestational age [34,35]. Stunting, wasting, and
underweight were defined as standardized, sex-specific Z-scores of
#22 using length-for-age, weight-for-length and weight-for-age
respectively. Z-scores were created using the WHO 2007 SAS
Macro package . Head-sparing growth restriction was defined
as the presence of LBW, SGA, stunting, wasting, or underweight
with a head circumference standardized Z-score of 21 or better
. Preterm delivery was defined as birth at less than 37 weeks
gestation. Fetal death was defined as either miscarriage (12–20
weeks of gestation) or stillbirth (intrauterine fetal demise .20
weeks of gestation). Lastly, we created a composite dichotomous
adverse birth outcome variable including LBW, SGA, stunting,
wasting, underweight, preterm delivery, and fetal death.
We restricted the analysis to singleton pregnancies because of
the well-established relationship between multiple births and LBW
and preterm delivery . In addition, analyses of weight change
during pregnancy were restricted to those women whose weights
had been measured at least twice before delivery, with their last
weight evaluated within two weeks prior to date of delivery.
We calculated descriptive statistics and created scatterplots to
assess distribution of the data and to inform regression modeling.
Chi-square and Fisher’s exact tests were performed, as appropri-
ate, to test for associations between categorical variables. Wilcoxon
signed-rank tests were performed to compare the means of
continuous characteristics by categorical variables. For all logistic
and linear regression models, univariate analyses were first
performed to assess relationships. Subsequently, multivariate
logistic regression models were fit with dichotomous outcomes
and clinically important predictors: birth spacing (,2 years) and
CD4+ count at screening. Multivariate linear regression models
were also built for continuous outcome variables. Birth spacing
and CD4+ count were included in all models because of their
clinical significance, as were any other predictors meeting the
p#0.2 threshold in univariate analysis. Multivariate model inputs
were evaluated for significant multi-collinearity and where highly
correlated, the variable with strongest association was retained.
Model fit was assessed between model versions using differences in
the 22 log likelihood and the difference in degrees of freedom
between models relative to the Chi-square distribution. All
analyses were conducted using SAS version 9.2 (Cary, North
There were 232 women enrolled in the randomized clinical trial
between December 15, 2009 and May 24, 2011. Of these, 166
outside the hospital. Birthweight was obtained within 12 hours of
birth for 153 (96.8%)of the 158women with singleton births.
The median age of participants at baseline was 29 years, and
they were enrolled at a mean gestational age of 21.6 weeks
(Table 1). Nearly 94% of participants were multigravidae. Over
90% of participants were diagnosed with WHO Stage 1 HIV
disease and half of the women had baseline CD4 counts .350.
The mean baseline BMI of participants was 21.8. Nearly 45% of
participants were diagnosed with anemia (Hb ,11 g/dL) prior to
the initiation of cART. A diagnosis of clinical malaria during
pregnancy was made for 7.6% of participants.
Maternal Weight Gain During Pregnancy
The median weekly GWG during study participation was
0.17 kg (interquartile range [IQR]: 0.06, 0.3). Data on median
weekly GWG were unavailable for two participants who were not
weighed within two weeks of delivery. Twenty-three women
(14.6%) lost weight during pregnancy. The median total GWG
during study participation was 3 kg (IQR: 1, 5). In addition, the
median maternal weight at 7 months gestation was 58 kg (IQR:
52, 63) and the median BMI at 7 months gestation was 22 (IQR:
20.5, 24.1). Adjusting for birth spacing, baseline CD4 count,
baseline weight, mean Hb during pregnancy, and Grade 3 or 4
adverse events, there were no significant predictors of gestational
weight gain. (Univariate relationships and the full linear regression
model can be found in Table S1).
Table 1. Baseline Characteristics of Women at Enrollment
Age, Median (IQR)29 (26, 34)
Gestational age, Mean (SE)21.6 (0.3)
Weight in kg, Median (IQR) (n=157)57 (52, 62)
Height in cm, Median (IQR) (n=156)162 (158, 166)
BMI, Mean (SE) (n=155)21.8 (0.2)
First tertile (,20.43) 50 (32.3%)
Second tertile (20.43–22.59)55 (35.5%)
Third tertile (.22.59)50 (32.3%)
Gravidity, Mean (SE)4.8 (0.2)
Parity, Mean (SE) (n=157) 3.4 (0.2)
Primigravid [n (%)]10 (6.3%)
Number of living children, Mean (SE)2.9 (0.14)
History of preterm delivery8 (5.1%)
Years since last term birth, Mean (SE)
Less than primary130 (82.3%)
Primary or more 28 (17.7%)
Bednet at home
HIV diagnosis during index pregnancy52 (32.9%)
WHO Stage 1145 (91.8%)
WHO Stage 2 12 (7.6%)
WHO Stage 3 1 (0.6%)
CD4 cell count (n=157)
.350 78 (49.7%)
Log(10) Viral Load, Mean (SE) (n=154)4.08 (0.1)
Hb, Mean (SE)11.05 (0.1)
Anemia, Hb ,1171 (44.9%)
1Data are from entire sample (n=158) unless otherwise noted.
2All data are represented as n (%) unless otherwise noted.
IQR: Interquartile range.
SE: standard error.
BMI: Body mass index (kg/m2).
Nutritional Status, cART and Birth Outcomes
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Obstetric and Neonatal Outcomes
There were no infants infected with HIV at birth. The
prevalence of LBW was 19.6%, preterm delivery 17.7%, and
fetal death 3.9% (Table 2). Stunting was the most common
anthropometric marker of growth restriction seen among live-born
newborns (21.1%), followed by SGA (15.1%) and underweight
(15.1%). Twenty six percent of live-born infants were diagnosed
with head-sparing growth restriction. Seventy three percent of
participants experienced a full-term delivery of a live-born infant
with normal birth weight.
Risk Factors for Adverse Outcomes
Low birth weight.
spacing (,2 years) and baseline CD4 count, each kg increase in
maternal weight at enrollment was associated with a 30%
decreased odds of LBW (aOR 0.70, 95% CI 0.52–0.95,
p=0.022, cf. Table S2). Each cm increase in maternal height
was associated with an 8% lower odds of LBW (aOR 0.92, 95%
CI 0.85–1.00, p=0.046). Moreover, women who gained ,0.1 kg
per week had greater than 6-fold increase in odds of LBW
compared to women who gained $0.1 kg per week (aOR 6.18,
95% CI 1.80–21.1, p=0.004). Lastly, each kg decrease in total
maternal weight at 7 months gestation was associated with a 38%
increased odds of LBW (aOR 1.38, 95% CI 1.03–1.90, p=0.034).
years), baseline CD4 count, and any GWG, each g/dL increase in
mean maternal Hb between enrollment and final measurement
was associated with a 52% decreased odds of SGA (aOR 0.48,
95% CI 0.29–0.80, p=0.004, cf. Table S3).
After adjusting for birth spacing (,2 years) and
baseline CD4 count, risk factors for neonatal stunting included
male infant sex (aOR 6.02, 95% CI 1.64–22.06, p=0.007),
gestational age at delivery (aOR 0.51, 95%CI 0.37–0.71,
In multivariate analysis adjusting for birth
Adjusting for birth spacing (,2
p,0.001) and clinical malaria diagnosed during pregnancy
(aOR 0.18, 95% CI 0.03–0.97, p=0.047, cf. Table S4).
Head-sparing fetal growth restriction.
statistically significant predictors of head-sparing growth restric-
tion in multivariate analysis adjusting for birth spacing, baseline
CD4 count and mean maternal Hb during the study, cf. Table S5.
Adjusting for birth spacing, baseline CD4
count and history of preterm delivery, GWG ,0.1 kg per week
was associated with a 4-fold increased odds of preterm delivery
(aOR 3.46, 95% CI 1.18–10.15, p=0.024, cf. Table S6).
Composite adverse birth outcome.
the composite dichotomous adverse birth outcome included GWG
,0.1 kg per week, higher SES status, and birth from June to
October (the rainy season), adjusting for CD4 count and birth
spacing (Table 3). In particular, gaining ,0.1 kg per week was
associated with a nearly 3 fold increased odds of an adverse birth
outcome (aOR 2.85, 95% CI 1.32–6.15, p,0.01).
There were no
Lastly, predictors of
Combination antiretroviral therapy is being delivered to
increasing numbers of rural HIV-infected pregnant women in
developing countries [38–40]. Goals of treatment include protect-
ing the health of these women and promoting the birth of HIV-
uninfected, healthy infants. However, cART alone may not be
sufficient to achieve these goals, particularly when these women
also often face other challenges besides HIV, including food
insecurity and malnutrition .
In our cohort of HIV-infected pregnant women in rural Uganda
initiating cART, TS and prenatal care, we found evidence of
significant nutritional deficiencies. These women had low BMIs
upon study entry and well into their pregnancy, despite having
relatively preserved CD4 cell counts. Their mean weight gain of
0.17 kg/week was far below the 0.5 kg/week recommended by
the Institute of Medicine for underweight women in industrialized
countries in the second and third trimester . Although all
infants were HIV-uninfected at delivery, adverse birth outcomes
were highly prevalent and likely attributable at least in part to poor
maternal nutritional status.
Interestingly, HIV severity, measured as baseline CD4 count,
viral load, or WHO stage, was not predictive of adverse birth
outcomes. This could have been due to our sample size and the
relatively small proportion of women with severe immune
suppression. Indeed, 50% of our cohort had baseline CD4 counts
above 350 and the majority of the women (91.8%) were WHO
Maternal nutritional predictors of preterm delivery and growth
restriction have primarily been evaluated among HIV-infected
women not receiving cART. The Pregnancy and HIV Study
Group of 177 ARV-naı ¨ve women in Rwanda found that each kg
increment in final weight before delivery was associated with a 6%
decreased odds of LBW . Villamor et al. found that low
maternal weight at first prenatal visit was associated with lower
mean birth weight and SGA but not preterm delivery among 1002
ARV-naı ¨ve women in Tanzania . Similar to our study, the
prevalence of gestational weight loss was 10%, and weight loss was
associated with LBW, preterm delivery and fetal death. In
Zambia, Banda et al. found infant birth weight increased by
28.3 g for every unit increase in BMI at 36 weeks of gestation; they
did not assess the risk of preterm delivery or other markers of
growth restriction . Finally, Mehta et al. analyzed outcomes of
2294 ARV-naı ¨ve pregnant women enrolled in HIVNET 024 .
They found enrollment maternal BMI in the lowest tertile to be
associated with LBW and preterm delivery. As observed in our
Table 2. Obstetric and Fetal Outcomes (n=158)1.
Male sex (n=155)83(53.6%)
Overall low birth weight (n=153)30 (19.6%)
Overall preterm delivery28 (17.7%)
Full term, normal birth weight (n=152) 111 (73.0%)
Full term, low birth weight (n=152) 13 (8.6%)
Preterm, normal birth weight (n=152) 11 (6.6%)
Preterm, low birth weight (n=152)12 (7.9%)
Miscarriage (12–20 weeks) (n=152) 1 (0.6%)
Stillbirth (.20 weeks) (n=152) 5 (3.3%)
Composite adverse obstetric/fetal outcome 64 (40.5%)
Live born infants only (n=152)1
Stunting (LAZ2# 22) at birth (n=142)30 (21.1%)
Small for gestational age (,10th percentile) 23 (15.1%)
Underweight (WAZ3# 22) at birth23 (15.1%)
Wasting (WLZ4# 22) at birth (n=128)11 (8.6%)
Small head circumference (HCZ5# 22) at birth (n=150) 10 (6.7%)
Head-sparing growth restriction (n=150)39 (26.0%)
1All data are represented as n (%).
2LAZ: length-for-age Z-score.
3WAZ: weight-for-age Z-score.
4WLZ: weight-for-length Z-score.
5HCZ: head circumference Z-score.
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study, weight gain ,0.1 kg per week was associated with increased
risk of LBW.
Very few studies have evaluated nutritional predictors of
pregnancy outcomes among HIV-infected women on cART.
Ekouevi and colleagues studied 151 pregnant women receiving
cART as part of the ANRS Ditrame Plus and the MTCT-Plus
Projects in Cote d’Ivoire . Similar to the Pregnancy and HIV
Study Group in Rwanda, these researchers found maternal BMI
at delivery to be predictive of LBW. In particular, the odds of
LBW was 2.43 fold higher among women with a delivery BMI
,25. Conversely, Powis et al recently reported that change in BMI
one month following the initiation of cART in pregnancy was not
significantly associated with preterm delivery among 530 HIV-
infected pregnant women in Botswana .
It is reasonable to postulate that pregnant women treated with
cART would have improved nutritional status compared to those
without access to cART. Women receiving effective cART should
experience less HIV morbidity, including diarrhea and wasting,
which should outweigh the toxicity of the antiretroviral agents.
However, our study and the two others examining nutritional
markers among pregnant women receiving cART can neither
support nor refute this assumption because all women received
cART, and it would be unethical to randomize to non-cART
treatment regimens. Furthermore, even if cART does improve
nutritional status, we demonstrate in this cohort that there remain
significant nutritional deficiencies and that these are associated
with poor birth outcomes.
Mechanisms to explain these poor outcomes are likely
numerous and not yet fully understood. For example, head-
sparing, or asymmetric, growth restriction is thought to be due to
preferential blood flow to the brain in the setting of placental
insufficiency . Indeed, the inverse association between head-
sparing growth restriction and weekly GWG suggests a nutritional
basis for this placental insufficiency.
Much work is needed to determine factors that contribute to low
GWG and weight loss among HIV-infected pregnant women,
including the impact of initiating HAART during pregnancy
versus use of HAART prior to conception. It is also necessary to
develop strategies to identify those women at greatest risk for poor
birth outcomes. Pre-pregnancy BMI has consistently been
associated with adverse birth outcomes. However, because most
women do not know their pre-pregnancy weight and do not have
regular access to preconception care, this indicator is not clinically
useful. In order to identify another relevant maternal anthropo-
metric predictor of adverse fetal outcomes, Kelly and colleagues
conducted a meta-analysis of 25 studies including over 111,000
births worldwide . They found that low maternal weight
attained at 7 months gestation was a significant risk factor for fetal
growth restriction, particularly among women with below average
pre-pregnancy weight. Indeed in our study, those women with low
weight at 7 months gestation were at particularly high risk of
LBW. Because increased GWG in the 3rdtrimester was associated
with a diminished odds of LBW, preterm delivery, and overall
adverse birth outcome, these women with low weight at 7 months
may benefit from a nutritional intervention.
Preterm delivery, LBW, neonatal stunting, SGA, and wasting
are strong predictors of infants’ future health trajectories .
With the increased availability of cART during pregnancy and
breastfeeding, there is an expanding generation of HIV-exposed,
uninfected children. Nutritional interventions that increase
maternal weight gain during pregnancy have the potential to
decrease the burden of a range of adverse birth outcomes among
women infected with HIV. As such, the improvement of maternal
nutritional status may be a golden opportunity to not only protect
the health of the mother, but to improve birth outcomes and
create a thriving generation of HIV-exposed, uninfected offspring.
There are several limitations to our study. Small sample size
may have impaired our ability to find statistically significant
predictors of head-sparing fetal growth restriction and other poor
outcomes. Our findings may not be generalizable to other cohorts
of HIV-infected pregnant women receiving cART (e.g. [38,39,40])
because our participants were older, nearly all were multigravidae
Table 3. Predictors of Composite Adverse Obstetric/Fetal Outcome1, Univariate and Multivariate Analysis.
Univariate Analysis Final Multivariate Model
N Outcome (%)ORP aOR2
Birth spacing ,2 years158 77 (44.4%)1.190.80 0.89 0.20–3.920.88
Baseline CD4 count (continuous)157 64 (40.8%)1 0.951 0.99–1.000.84
Maternal weight at 7 months gestation3
155 62 (40%)0.97 0.150.95 0.91–1.000.07
Weekly weight gain
,0.1 kg/week5428 (52%) 2.12 0.032.851.32–6.15
0.1 kg/week or greater 101 34 (33.7%)–1
14830 (47%)1.67 0.132.611.20–5.67 0.02
Season of birth
June to October 5616 (28.6%) 0.450.03 0.33 0.15–0.74
November to May 102 48 (47.1%)1–1
1Composite adverse obstetric/fetal outcome includes any of the following: low birth weight, SGA, stunting, wasting, underweight, preterm delivery, and fetal death.
2Adjusted odds ratio using multivariate logistic regression, adjusting for all variables listed in table.
3Per kg increment in maternal weight at 7 months gestation.
4Indicator variable for household being in the upper quartile of either the first or second component of the SES principal component analysis based on possession of a
radio, telephone, television, motorcycle, bicycle or none of the above.
OR: Odds Ratio.
aOR: Adjusted Odds Ratio.
95% CI: Confidence Interval.
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and mean BMI was lower [38–40]. Further, our results may not be
generalizable to those women on cART prior to conceiving. We
excluded multiple births because of its known effect on adverse
birth outcomes, which may further limit the generalizability of our
findings. Our finding that higher SES was associated with an
increased odds of an adverse birth outcome may be spurious
because the SES measure was generated using principal compo-
nent analysis of specific asset holding questions and not a validated
poverty scale. Such a measurement could have been vulnerable to
unmeasured confounding. Finally, we analyzed data from an on-
going randomized trial and differences by study treatment arm
cannot be addressed until study completion and data unblinding.
In conclusion, initiating cART during pregnancy among HIV–
infected women in rural Uganda successfully prevented HIV
transmission to their infants but did not prevent poor nutritional
status during pregnancy that independently predicted poor birth
outcomes. More attention is needed to characterize the scope and
causes of nutritional deficiencies among this population and to
design interventions that improve both the health of HIV-infected
mothers and optimize the health and development of their
models of weekly gestational weight gain.
Univariate and multivariate linear regression
sion models of low birthweight.
Univariate and multivariate logistic regres-
sion models of small for gestational age.
Univariate and multivariate logistic regres-
sion models of stunting.
Univariate and multivariate logistic regres-
sion models of head-sparing growth restriction.
Univariate and multivariate logistic regres-
sion models of preterm delivery.
Univariate and multivariate logistic regres-
The authors would like to sincerely thank the women who have
participated in the PROMOTE-Pregnant Women and Infants trial. We
would also like to acknowledge the dedicated PROMOTE study team,
members of the Makerere University-University of California San
Francisco Research Collaboration, and the midwives at Tororo District
Conceived and designed the experiments: SY EA EC TR DH DC.
Performed the experiments: JM PN BO TC VA JA. Analyzed the data: SY
KM AP EC TR DH DC. Wrote the manuscript: SY VA JA EC TR MK
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