Postpartum obesity and weight gain among human immunodeficiency virus‐infected and human immunodeficiency virus‐uninfected women in South Africa

Abstract In South Africa, up to 40% of pregnant women are living with human immunodeficiency virus (HIV), and 30–45% are obese. However, little is known about the dual burden of HIV and obesity in the postpartum period. In a cohort of HIV‐uninfected and HIV‐infected pregnant women initiating antiretroviral therapy in Cape Town, South Africa, we examined maternal anthropometry (weight and body mass index [BMI]) from 6 weeks through 12 months postpartum. Using multinomial logistic regression, we estimated associations between baseline sociodemographic, clinical, behavioural, and HIV factors and being overweight–obese I (BMI 25 to <35), or obese II‐III (BMI >35), compared with being underweight or normal weight (BMI <25), at 12 months postpartum. Among 877 women, we estimated that 43% of HIV‐infected women and 51% of HIV‐uninfected women were obese I‐III at enrollment into antenatal care, and 51% of women were obese I‐III by 12 months postpartum. On average, both HIV‐infected and HIV‐uninfected women gained, rather than lost, weight between 6 weeks and 12 months postpartum, but HIV‐uninfected women gained more weight (3.3 kg vs. 1.7 kg). Women who were obese I‐III pre‐pregnancy were more likely to gain weight postpartum. In multivariable analyses, HIV‐infection status, being married/cohabitating, higher gravidity, and high blood pressure were independently associated with being obese II‐III at 12 months postpartum. Obesity during pregnancy is a growing public health concern in low‐ and middle‐income countries, including South Africa. Additional research to understand how obesity and HIV infection affect maternal and child health outcomes is urgently needed.


| INTRODUCTION
Globally, many low-and middle-income countries are facing increasingly complex burdens of disease, with the rise of noncommunicable conditions alongside ongoing burdens of infectious diseases. For example, in South Africa, the prevalence of human immunodeficiency virus (HIV) is remarkably high, whereas obesity and related conditions are major public health concerns (Karim et al., 2011;Kharsany et al., 2015;Sartorius, Veerman, Manyema, Chola, & Hofman, 2015). Pregnancy is a critical time when both obesity and HIV can impact women and infants' health during the perinatal period and beyond (Aviram, Hod, & Yogev, 2011;Begum, Sachchithanantham, & De Somsubhra, 2011;Brocklehurst & French, 1998;Malaba et al., 2017;Marchi, Berg, Dencker, Olander, & Begley, 2015;Xiao et al., 2015). Postpartum weight retention, although heterogeneous in nature, has the potential to contribute significantly to the obesity epidemic in South Africa (Chetty, Carter, Bland, & Newell, 2014). In some areas of South Africa, up to 40% of pregnant women are living with HIV, and 30-45% of pregnant women are obese (Basu, Jeketera, & Basu, 2010;Davies et al., 2012;Kharsany et al., 2015; Stephanie V. Wrottesley, Ong, Pisa, & Norris, 2018). Despite the importance of comanaging both obesity and HIV during pregnancy and the postpartum period to optimize maternal and child health outcomes, little research has examined postpartum weight change in routine care settings with a high burden of HIV (Anderson et al., 2018;Basu et al., 2010;Cames et al., 2014).
Obesity during pregnancy is a well-known risk factor for complications during pregnancy, adverse pregnancy outcomes, an influences ongoing maternal and child health (Aviram et al., 2011;Begum et al., 2011;Marchi et al., 2015). Obese women may be at higher risk for gestational weight gain during pregnancy, subsequent postpartum weight retention, and the development of hypertension and diabetes in women (Begum et al., 2011;Rong et al., 2015). Until recently, for women living with HIV, undernutrition rather than obesity has been the primary concern during pregnancy ( Grinspoon et al., 1998;Karim et al., 2011;Kindra, Coutsoudis, & Esposito, 2011;Lartey, 2008;Villamor et al., 2006;Widen et al., 2013;Widen et al., 2019;Young et al., 2012). However, with rapid urbanization, changing diets, and improved access to lifelong combination antiretroviral therapy (ART), the nutritional status of HIV-infected women during pregnancy may be changing and postpartum weight retention becoming more common (Chetty et al., 2014;Meintjes et al., 2015;Meintjes et al., 2017;Murnane et al., 2010;Villamor et al., 2006;Wilkinson et al., 2015; V. Wrottesley, Pisa, & Norris, 2017). In order to develop effective health promotion approaches in countries experiencing dual epidemics of HIV and obesity, a clear understanding of factors that influence postpartum body mass index (BMI) and weight retention among pregnant HIV-infected and HIV-uninfected women is needed.
The aim of this paper is to describe maternal anthropometry, including weight, BMI, and weight change from 6 weeks through 1 year postpartum in a cohort of HIV-infected women on ART and HIVuninfected women in South Africa. Additionally, we explore sociodemographic, clinical, HIV, and behavioural factors associated with being overweight or obese at 12 months postpartum and postpartum weight change.

| Study setting and population
To address this aim, we conducted a secondary analysis using data from HIV-infected women enrolled in the Strategies to Optimize ART Services for maternal and child health (MCH-ART) trial and a parallel cohort of HIV-uninfected pregnant women (HIV-unexposed-uninfected study) conducted in Cape Town, South Africa. Details of both studies have been published previously (le Roux et al., 2019;Myer et al., 2016;Myer et al., 2018). Briefly, the two cohorts had similar inclusion and exclusion criteria, enrolling HIV-infected pregnant women initiating ART and HIV-uninfected pregnant women who were > 18 years of age between March 2013 and August 2015 at their first antenatal care (ANC) visit at a primary care center in Gugulethu in Cape Town. Women who were breastfeeding at their first postpartum visit, scheduled 7 days after delivery, were enrolled and followed through 12 months postpartum. Out of 1,087 mother-infant pairs screened at their first postpartum visit, 92 women (79 HIV-infected women and 14 HIV-uninfected women; 8% overall) were excluded due to not breastfeeding (le Roux et al., 2019).
Gugulethu is an urban community of approximately 300,000 people outside of Cape Town and is characterized by high levels of poverty and HIV (Myer et al., 2018;Strategic Development Information & GIS Department, 2013). Over 95% of women in this setting receive ANC prior to delivery (Myer et al., 2015). Provision of ART and

Key messages
• In a cohort of HIV-uninfected and HIV-infected pregnant women initiating antiretroviral treatment obesity was common; 47% were obese (BMI >30) at their first antenatal care visit, and 51% were obese at 12 months postpartum.
• On average, both HIV-infected and HIV-uninfected women gained weight between 6 weeks and 12 months postpartum, but weight gain was lower among HIVinfected women. Postpartum weight gain was most common among women who were obese at their first antenatal care visit.
• Women who were married/cohabiting, had higher gravidity, or high blood pressure at enrollment in antenatal care were more likely to be obese II or III (BMI ≥35), whereas HIV-infected women were less likely to be obese II or III at 12 months postpartum.
prevention of mother-to-child transmission (PMTCT) services are provided at no cost as a part of routine ANC at all public sector clinics, in accordance with local guidelines. Starting in 2013, all HIV-infected women attending ANC were eligible for lifelong ART, regardless of CD4 count of WHO clinical stage (WHO, 2013). All HIV-infected women in the study initiated the local first-line ART regimen of tenofovir (300 mg) + emtricitabine (200 mg)/lamivudine (300 mg) + efavirenz (600 mg), provided as a fixed-dose combination pill taken once daily.
HIV-uninfected and HIV-infected women initiating ART were included in the present analysis if they met eligibility criteria, were followed through 12 months postpartum (n = 884), and had a singleton pregnancy (n = 7 excluded). Participants completed study visits at enrollment into ANC (baseline), delivery, 6 weeks, and 3, 6, 9, and 12 months postpartum.

| Measures
Maternal anthropometry was assessed by maternal weight (in kilograms), BMI (calculated as kilograms/meters 2 ), and changes in maternal weight from 6 weeks (baseline) through 12 months postpartum.
Postpartum weight change was defined as either no weight change (within +/−2 kg), weight loss more than 2 kg, or weight gain more than 2 kg, between 6 weeks postpartum and each time point. Women were weighed, and their height was measured at enrollment into ANC  ing type and access to household assets, was used to categorize women as "most," "moderate," or "least" disadvantaged . Perinatal depression was measured using the Edinburgh Postnatal Depression Scale (range 0-30; Chorwe-Sungani & Chipps, 2017; Cox, Holden, & Sagovsky, 1987). A score of >13 was used to indicate probable depression (Redinger, Norris, Pearson, Richter, & Rochat, 2018). Alcohol use was measured using the 3-item Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; range 0-12).

| Statistical analyses
The goals of the statistical analysis were to describe maternal weight, BMI, and weight change overtime and by HIV status during the postpartum period, as well as to estimate associations between demographic, clinical, behavioural factors and HIV status, and being overweight or obese at 12 months postpartum. Maternal anthropometry overtime and by HIV status was examined descriptively and graphically. To explore associations with being overweight or obese, we categorized women into one of three groups: underweight or normal weight (BMI <25), overweight or obese I (BMI 25 to <35), or obese II or III (BMI >35). Because only 4% of the population was underweight, effect estimates could not be estimated separately for this group. Therefore, we grouped underweight women with normal weight women in order to retain as much of the sample as possible to maximize statistical precision. We used multinomial logistic regression to estimate odds ratios (OR) for associations between baseline factors and being overweight-obese I (outcome 1), or obese II-III (outcome 2), compared with being underweight or normal weight (referent), at 12 months postpartum.
In bivariable analyses, all factors with a p value <.05 were considered for inclusion into the multivariable model. All variables considered for inclusion into the multivariable model were evaluated for collinearity using pairwise correlation coefficients. For variables with a pairwise correlation coefficient >.50, we selected the variable with the stronger bivariable association for inclusion into the multivariable model. When evaluating associations with BMI at 12 months postpartum, BMI at first ANC visit was highly collinear with BMI at 12 months postpartum and, therefore, was not included due to model convergence issues. Gestational age at enrollment into ANC and breastfeeding duration are likely intermediary variables, between several variables in the model and BMI category at 12 months postpartum, and therefore were not included in models (Ananth & Schisterman, 2017;Hernandez-Diaz, Schisterman, & Hernan, 2006).
As an exploratory, secondary analysis, we explored predictors of change in maternal weight (categorized as weight loss, no weight change, and weight gain using the category definition above) between 6 weeks postpartum and 12 months among the 596 women with a weight measurement at 6 weeks and 12 months postpartum.
Bivariable and multivariable analyses were analogous to those described above. Among HIV-infected women (n = 464), we examined whether HIV-related factors, including timing of HIV diagnosis, previous PMTCT during pregnancy, viral load, and CD4 count, were associated with BMI at 12 months postpartum. Previous ART use was not included due to the majority of participants initiating ART for the first time.
Missing BMI and blood pressure data at enrollment into ANC were common (10-12%) and more frequent among HIV-infected women. To address potential bias due to missing data, we conducted a sensitivity analysis where we used multiple imputation to impute all missing data from a multivariate normal distribution (N = 50 imputations; Rubin, 1987). We then explored associations between baseline factors and BMI at 12 months postpartum in the imputed data. All statistical analyses were conducted in Stata version 15 (StataCorp, College Station, TX).

| Ethical approval
Ethical approval for both the MCH-ART and HU2 studies was provided by the University of Cape Town's Human Research Ethics Committee. The MCH-ART study also received ethical approval from the Columbia University Institutional Review Board.
The mean age at enrollment was 28 years (SD 5.8), and the mean gestational age was 20 weeks (SD 7.8, range 4-39 weeks
weight. Postpartum weight gain was also more common among women who were obese at their first ANC visit. In multivariable analyses, HIV infection, being married/cohabiting, higher gravidity, and elevated blood pressure at enrollment were associated with being either obese II or II, compared with normal weight or underweight, at 12 months postpartum.
In high-resource settings, the rising prevalence of obesity throughout pregnancy and postpartum weight retention are well-recognized risk factors for poor maternal and child health outcomes and increased healthcare service utilization (Chu et al., 2008;Mariona, 2016;Robbins et al., 2014). However, the prevalence and implications of postpartum weight retention in low-and middle-income countries, particularly in the context of the HIV epidemic, has received less attention (Ramlal et al., 2013;Widen et al., 2017). In our analysis, we estimated that 51% of women were obese by 12 months postpartum, including 43% of HIV-infected women. In addition, similar to previous studies, both HIV-uninfected and HIV-infected women tended to gain, rather than lose weight, in the first year postpartum (Chetty et al., 2014;Murnane et al., 2010). For HIV-uninfected women, postpartum weight gain translated into the median BMI moving from "overweight" (median BMI 28.7) at 6 weeks postpartum to "obese" (median BMI 31.6) at 12 months postpartum. For HIV-infected women, the median BMI was overweight throughout the postpartum period.
Weight at 12 months postpartum is a risk factor for obesity, which over times increases the risk of hypertension, Type 2 diabetes, cardiovascular disease later in life, and obesity in subsequent pregnancies (Catalano & Shankar, 2017;Endres et al., 2015;Kew et al., 2014;Puhkala, Luoto, Ahotupa, Raitanen, & Vasankari, 2013). In our analysis, being married or cohabitating, higher gravidity, and having high blood pressure at enrollment into ANC were associated with an increased risk of being obese II or III at 12 months postpartum, whereas being HIV infected was associated with a reduced risk of obesity at 12 months postpartum; HIV infection has been associated in previous studies in sub-Saharan Africa with being T A B L E 3 Bivariable and multivariable associations for the relationship between characteristics at enrollment into antenatal care and being overweight/obese I or obese II/III, compared with underweight or normal (referent) at 12 months postpartum among HIV-infected and HIVuninfected women in South Africa underweight (Grinspoon et al., 1998;Karim et al., 2011;Kindra et al., 2011;Lartey, 2008;Villamor et al., 2006;Widen et al., 2013;Widen et al., 2019;Young et al., 2012). Here, only 1% of HIV-infected women were underweight at their first ANC visit, whereas 43% were obese I-III. Despite the high prevalence of obesity, HIV-infected women were less likely than HIV-uninfected women to be obese II or III at 12 months postpartum, which may, in part, reflect natural heterogeneity in postpartum weight retention. Unlike others in highresource settings, baseline education and employment status were not associated with obesity status at 12 months postpartum, highlighting the complexity of factors associated with obesity overtime (Gaillard et al., 2013).
Strengths of this analysis included the availability of detailed sociodemographic, clinical, behavioural, and HIV-related characteristics that could be related to obesity in a large cohort of HIV-infected and HIV-uninfected women. In addition, the ability to compare directly measures of maternal anthropometry at enrollment into ANC and through 12 months postpartum between HIV-infected and HIVuninfected women is unique. Limitations include the lack of information on obstetric morbidity such as gestational diabetes or hypertension, as well as measured pre-pregnancy BMI and gestational weight gain during pregnancy. The median gestational age at enrollment into ANC in our cohort was 20 weeks, past the first trimester of pregnancy when ultrasound is the most accurate for estimating gestational age (Butt & Lim, 2014). However, recent evidence supports the accuracy of ultrasound to estimate gestational age after the first trimester during pregnancy (Butt & Lim, 2014;Papageorghiou et al., 2016). Finally, we note as a limitation that breastfeeding duration and modality was not accounted for in the analysis due it being an intermediary variable between several predictors examined and obesity at 12 months postpartum. In South Africa, nearly 60% of women exclusively breastfeed in early infancy (Jackson et al., 2019). However, in one study, HIVinfected women in South Africa were less likely to exclusively breastfeed compared with HIV-uninfected women; but duration of exclusive breastfeeding did not differ by HIV status (Chetty et al., 2014). Duration and modality of breastfeeding through 12 months was likely heterogeneous in this population and could have played an important role in the weight gain patterns.

| CONCLUSION
Throughout sub-Saharan Africa, the dual burden of infectious and chronic diseases remains a major focus of efforts to improve maternal and child health. In some areas of South Africa, obesity affects nearly half of all pregnant women, and postpartum weight retention is a growing concern. HIV infection and its treatment may contribute to weight gain and metabolic changes during pregnancy and postpartum that could further exacerbate the adverse effects of obesity on maternal and child health outcomes. For these reasons, the combined impact of obesity and HIV infection in South Africa is likely to have important implications for the health of women and their children during pregnancy and beyond. Our analysis beings to address these concerns by describing maternal anthropometry and factors associated with being overweight or obese at 12 months postpartum in a cohort of HIV-infected and HIV-uninfected women. Future studies of the prevalence and impact of obesity during pregnancy and postpartum weight retention in low-resource settings with a high burden of HIV are urgently needed to generate an evidence-base to guide clinical decision-making, prevention efforts, and public health interventions to optimize maternal and child health outcomes in the coming years.

ACKNOWLEDGMENTS
The researchers thank the study participants, research, and clinical staff that made this study possible. We also thank the President's Emer-

CONFLICTS OF INTEREST
The authors declare that they have no conflicts of interest.

CONTRIBUTIONS
TKP, SML, EJA, and LM designed the study and oversaw data collection. AMB analyzed the data and drafted the manuscript. All authors critically reviewed the manuscript.