Elizabeth M. Widen

Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity

Background/Objectives:Cesarean section (CS) and antibiotic use during pregnancy may alter normal maternal-offspring microbiota exchange, thereby contributing to aberrant microbial colonization of the infant gut and increased susceptibility to obesity later in life. We hypothesized that (i) maternal use of antibiotics in the second or third trimester of pregnancy and (ii) CS are independently associated with higher risk of childhood obesity in the offspring.Subjects/Methods:Of the 727 mothers enrolled in the Northern Manhattan Mothers and Children Study, we analyzed the 436 mother–child dyads followed until 7 years of age with complete data. We ascertained prenatal antibiotic use by a questionnaire administered late in the third trimester, and delivery mode by medical record. We derived age- and sex-specific body mass index (BMI) z-scores using the CDC SAS Macro, and defined obesity as BMI z⩾95th percentile. We used binary regression with robust variance and linear regression models adjusted for maternal age, ethnicity, pre-gravid BMI, maternal receipt of public assistance, birth weight, sex, breastfeeding in the first year and gestational antibiotics or delivery mode.Results:Compared with children not exposed to antibiotics during the second or third trimester, those exposed had 84% (33–154%) higher risk of obesity, after multivariable adjustment. Second or third trimester antibiotic exposure was also positively associated with BMI z-scores, waist circumference and % body fat (all P<0.05). Independent of prenatal antibiotic usage, CS was associated with 46% (8–98%) higher offspring risk of childhood obesity. Associations were similar for elective and non-elective CS.Conclusions:In our cohort, CS and exposure to antibiotics in the second or third trimester were associated with higher offspring risk of childhood obesity. Future studies that address the limitations of our study are warranted to determine if prenatal antibiotic use is associated with offspring obesity. Research is also needed to determine if alterations in neonatal gut microbiota underlie the observed associations.

Bisphenol A and Adiposity in an Inner-City Birth Cohort.

Background: Early-life exposure to the endocrine disruptor bisphenol A (BPA) may contribute to the development of obesity. Prospective evidence in humans on this topic is limited. Objectives: We examined prenatal and early-childhood BPA exposures in relation to childhood measures of adiposity in the Columbia Center for Children’s Environmental Health (CCCEH) New York City birth cohort. Methods: BPA concentrations were measured in prenatal (n = 375) and child ages 3 (n = 408) and 5 years (n = 518) spot urine samples. Childhood anthropometric and bioelectrical impedance outcomes included body mass index z-scores (BMIZ) at 5 and 7 years, and fat mass index (FMI), percent body fat (%BF), and waist circumference (WC) at 7 years. Associations were evaluated using multiple linear regression with continuous and tertile BPA concentrations. Results: Prenatal urinary BPA concentrations were positively associated with child age 7 FMI (β = 0.31 kg/m2; 95% CI: 0.01, 0.60, p = 0.04), %BF (β = 0.79; 95% CI: 0.03, 1.55, p = 0.04), and WC (β = 1.29 cm; 95% CI: 0.29, 2.30, p = 0.01), but not BMIZ, or change in BMIZ between ages 5 and 7 years (all p-values > 0.1). FMI results were sex-specific. Child urinary BPA concentrations were not associated with child anthropometric outcomes (all p-values > 0.05). Conclusions: Analyses of the CCCEH longitudinal birth cohort found associations between prenatal urinary BPA concentrations and FMI, %BF, and WC. Our results suggest that prenatal BPA exposure may contribute to developmental origins of adiposity. These findings are consistent with several prior studies, raising concern about the pervasiveness of BPA. Citation: Hoepner LA, Whyatt RM, Widen EM, Hassoun A, Oberfield SE, Mueller NT, Diaz D, Calafat AM, Perera FP, Rundle AG. 2016. Bisphenol A and adiposity in an inner-city birth cohort. Environ Health Perspect 124:1644–1650; http://dx.doi.org/10.1289/EHP205

Excessive gestational weight gain is associated with long-term body fat and weight retention at 7 y postpartum in African American and Dominican mothers with underweight, normal, and overweight prepregnancy BMI

BACKGROUND Excessive gestational weight gain (GWG) is associated with postpartum weight retention (PPWR) and abdominal adiposity, but long-term effects are understudied in low-income and minority populations at high risk of obesity and associated sequelae. OBJECTIVE We examined associations between GWG and long-term PPWR and adiposity in a prospective cohort of African American and Dominican mothers in the Bronx and Northern Manhattan. DESIGN Women (n = 302) were enrolled during pregnancy and were followed for 7 y postpartum. Linear regression was used to relate excessive GWG [greater than 2009 Institute of Medicine (IOM) guidelines] to outcomes [percentage body fat and long-term PPWR (change in weight from prepregnancy to 7 y postpartum)], adjusting for covariates and included an interaction term between prepregnancy body mass index (BMI; in kg/m(2)) and GWG. RESULTS Mean ± SD prepregnancy BMI and total GWG were 25.6 ± 5.8 (42% of women had BMI ≥25) and 16.6 ± 7.8 kg (64% of women had total GWG greater than IOM guidelines), respectively. Associations between GWG and long-term PPWR and the percentage body fat varied by prepregnancy BMI (P-interaction ≤ 0.06); excessive GWG was associated with a higher percentage body fat and greater long-term PPWR in mothers with lower prepregnancy BMI. To illustrate the interaction, a predicted covariate-adjusted model, which was used to derive estimates for the percentage body fat and PPWR associated with excessive GWG, was estimated for 2 prepregnancy BMI examples. For a woman with prepregnancy BMI of 22, excessive GWG was associated with 3.0% higher body fat (P < 0.001) and a 5.6-kg higher PPWR (P < 0.001); however, for a woman with a prepregnancy BMI of 30, excessive GWG was associated with 0.58% higher body fat (P = 0.55) and 2.06 kg PPWR (P = 0.24). CONCLUSIONS Long-term adiposity and PPWR in low-income African American and Dominican mothers were predicted by interacting effects of prepregnancy BMI and excessive GWG. The provision of support for mothers to begin pregnancy at a healthy weight and to gain weight appropriately during pregnancy may have important lasting implications for weight-related health in this population. This study was registered at clinicaltrials.gov as NCT00043498.

Gestational weight gain and obesity, adiposity and body size in African–American and Dominican children in the Bronx and Northern Manhattan

Gestational weight gain (GWG) is potentially modifiable and is associated with infant size and body composition; however, long-term effects on childhood obesity have not been reported among multi-ethnic urban populations. We examined the association between GWG and child anthropometric measures and body composition at 7 years [waist circumference (WC), body mass index z-score (BMIZ), obesity (BMIZ ≥95%ile) and bioelectrical impedance analysis estimates of percentage body fat (%fat)] in African-American and Dominican dyads (n = 323) in the Columbia Center for Childrens Environmental Health prospective birth cohort study from 1998 to 2013. Linear and logistic regression evaluated associations between excessive GWG [>Institute of Medicine (IOM) 2009 guidelines] and outcomes, adjusting for pre-pregnancy BMI and covariates. Pre-pregnancy BMI (mean ± standard deviation, all such values) and total GWG were 25.8 ± 6.2 kg m(-2) (45% overweight/obese) and 16.4 ± 7.9 kg (64% > IOM guidelines), respectively. Excessive GWG was associated with higher BMIZ {0.44 [95% confidence interval (CI): 0.2, 0.7], P < 0.001}, WC [β: 2.9 cm (95% CI: 1.1, 4.6), P = 0.002], %fat at 7 years [β: 2.2% (95% CI: 1.0, 3.5), P = 0.001)] and obesity [odds ratio: 2.93 (95% CI: 1.5, 5.8), P = 0.002]. Pre-pregnancy BMI was positively associated with child size, adiposity and obesity (all P < 0.05). Excessive GWG was highly prevalent and was associated with child obesity, greater percentage body fat and abdominal adiposity. Strategies to support healthy GWG are warranted to promote healthy growth and prevent childhood obesity.

Maternal Weight Loss during Exclusive Breastfeeding Is Associated with Reduced Weight and Length Gain in Daughters of HIV-Infected Malawian Women

Maternal weight loss during exclusive breastfeeding may influence the growth of exclusively breast-fed infants through impaired quality or quantity of breast milk. This study evaluated how maternal weight loss from 2 to 24 wk postpartum was related to infant weight and length gain in 1309 lactating HIV-infected mothers and their exclusively breast-fed infants. Malawian mother-infant pairs in the Breastfeeding, Antiretrovirals, and Nutrition Study were randomized with a 2 × 3 factorial design to a 2-arm nutritional intervention with a lipid-based nutrient supplement (LNS), meeting nutritional needs of lactation, or no LNS and a 3-arm antiretroviral (ARV) intervention (maternal, infant, or no ARV regimen). Linear regression models were used to relate maternal weight loss (weight loss vs. no weight loss) to infant weight and length gain from birth to 24 mo, stratifying by gender and controlling for maternal BMI at 2 wk (mean ± SD: 23.2 ± 3.0 kg/m(2)) and interacting maternal BMI with weight loss. In adjusted models, compared with daughters of women who did not lose weight, length and weight gain were lower in daughters whose mothers had a lower BMI at 2 wk postpartum coupled with the weight loss. For example, among mothers with an initial BMI of 18 kg/m(2), daughters of those who lost weight gained less weight [β = -0.29 kg (95% CI: -0.53, -0.06)] and length [β = -0.88 cm (95% CI: -1.52, -0.23)] from birth to 24 wk than daughters of those who gained weight. Though effects were only observed in girls, suggesting possible gender differences in suckling and feeding behavior, these findings indicate that maternal weight loss with low energy reserves represents a risk factor for poor infant growth outcomes.

Antiretroviral Treatment Is Associated With Iron Deficiency in HIV-Infected Malawian Women That Is Mitigated With Supplementation, but Is Not Associated With Infant Iron Deficiency during 24 Weeks of Exclusive Breastfeeding

Objective:In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (through fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks. Methods:The Breastfeeding, Antiretrovirals, and Nutrition study was a randomized controlled trial conducted in Lilongwe, Malawi, from 2004 to 2010. HIV-infected mothers (CD4 >200 cells/&mgr;L) and their infants were randomly assigned to 28-week interventions: maternal LNS/maternal ARV (n = 424), maternal LNS/infant ARV (n = 426), maternal LNS (n = 334), maternal ARV (n = 425), infant ARV (n = 426), or control (n = 334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n = 537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR), and ferritin were tested with linear and Poisson regression. Results:In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR >8.3 mg/L) (risk ratio: 3.1, P < 0.01), but not in ARV-treated mothers receiving LNS (P = 0.17). LNS without ARVs was not associated with iron deficiency or anemia (P > 0.1). In subsample infants, interventions were not associated with impaired iron status (all P > 0.1). Conclusions:Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not seem to influence infant iron status; however, extended use needs to be evaluated.

Changes in Soluble Transferrin Receptor and Hemoglobin Concentrations in Malawian Mothers Are Associated with Those Values in their Exclusively Breastfed, HIV-Exposed Infants

Infant iron status at birth is influenced by maternal iron status during pregnancy; however, there are limited data on the extent to which maternal iron status is associated with infant iron status during exclusive breastfeeding. We evaluated how maternal and infant hemoglobin and iron status [soluble transferrin receptors (TfR) and ferritin] were related during exclusive breastfeeding in HIV-infected women and their infants. The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial in Lilongwe, Malawi, in which HIV-infected women were assigned with a 2 × 3 factorial design to a lipid-based nutrient supplement (LNS), or no LNS, and maternal, infant, or no antiretroviral drug, and followed for 24 wk. Longitudinal models were used to relate postpartum maternal hemoglobin (n = 1926) to concurrently measured infant hemoglobin, adjusting for initial infant hemoglobin values. In a subsample, change in infant iron status (hemoglobin, log ferritin, log TfR) between 2 (n = 352) or 6 wk (n = 167) and 24 wk (n = 519) was regressed on corresponding change in the maternal indicator, adjusting for 2 or 6 wk values. A 1 g/L higher maternal hemoglobin at 12, 18, and 24 wk was associated with a 0.06 g/L (P = 0.01), 0.10 g/L (P < 0.001), and 0.06 g/L (P = 0.01), respectively, higher infant hemoglobin. In the subsample, a reduction in maternal log TfR and an increase in hemoglobin from initial measurement to 24 wk were associated with the same pattern in infant values (log TfR β = -0.18 mg/L, P < 0.001; hemoglobin β = 0.13 g/L, P = 0.01). Given the observed influence of maternal and initial infant values, optimizing maternal iron status in pregnancy and postpartum is important to protect infant iron status. This trial was registered at clinicaltrials.gov as NCT00164736.

Food insecurity, but not HIV-infection status, is associated with adverse changes in body composition during lactation in Ugandan women of mixed HIV status.

BACKGROUND Body composition is an important indicator of nutritional status and health. How body composition changes during 12 mo of breastfeeding in HIV-infected women receiving antiretroviral therapy (ART) is unknown. OBJECTIVE We assessed whether HIV or food insecurity was associated with adverse postpartum body-composition changes in Ugandan women. DESIGN A cohort of 246 women [36.5% of whom were HIV positive (HIV+) and were receiving ART] were followed to 12 mo postpartum. Repeated measures included weight, fat mass, fat-free mass, midupper arm circumference, triceps skinfold thickness [which allowed for the derivation of arm muscle area (AMA) and arm fat area (AFA)], breastfeeding, and individual food insecurity. Longitudinal regression models were constructed to assess associations between HIV and food insecurity and changes in body composition over time. RESULTS At baseline, HIV+ women compared with HIV-negative women had a higher mean ± SD food-insecurity score (11.3 ± 5.5 compared with 8.6 ± 5.5, respectively; P < 0.001) and lower AMA (40.6 ± 5.7 compared with 42.9 ± 6.9 cm3, respectively; P = 0.03). Participants were thin at 1 wk postpartum [body mass index (BMI; in kg/m2): 22.9 ± 2.9]. From 1 wk to 12 mo, the weight change was -1.4 ± 4.4 kg. In longitudinal models of body-composition outcomes, HIV was not associated with body composition (all P > 0.05), whereas food insecurity was inversely associated with body weight and BMI at 6, 9, and 12 mo and with AFA at 6 and 12 mo (all P < 0.05). At 6 mo, every 1-unit increase in the food-insecurity score was associated with a 0.13-kg lower body weight (P < 0.001) and a 0.26-cm3 lower AFA (P < 0.01). CONCLUSIONS Body-composition changes are minimal during lactation. HIV is not associated with body composition; however, food insecurity is associated with changes in body composition during lactation. This trial was registered at clinicaltrials.gov as NCT02922829 and NCT02925429.