Anne P. Starling

Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study

BACKGROUND Maternal obesity and weight gain during pregnancy are risk factors for child obesity. Associations may be attributable to causal effects of the intrauterine environment or genetic and postnatal environmental factors. OBJECTIVE We estimated associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) overall and in early pregnancy, midpregnancy, and late pregnancy with neonatal adiposity. DESIGN Participants were 826 women enrolled in a Colorado prebirth cohort who delivered term infants (2010-2013). GWG to 39 wk of gestation was predicted by using mixed models, and early pregnancy, midpregnancy, and late pregnancy rates of GWG (0-17, 17-27, and 27 wk to delivery) were calculated from repeated weight measures. Neonatal body composition was measured by using air-displacement plethysmography ≤3 d after birth. RESULTS Each1-kg/m(2) increase in maternal BMI was associated with increased neonatal fat mass (5.2 g; 95% CI: 3.5, 6.9 g), fat-free mass (7.7 g; 95% CI: 4.5, 10.9 g), and percentage of body fat (0.12%; 95% CI: 0.08%, 0.16%). Each 0.1-kg/wk increase in predicted GWG was associated with increased fat mass (24.0 g; 95% CI: 17.4, 30.5 g), fat-free mass (34.0 g; 95% CI: 21.4, 46.6 g), and percentage of body fat (0.55%; 95% CI: 0.37%, 0.72%). No interaction was detected between BMI and GWG in their effects on neonatal body composition. Early pregnancy, midpregnancy, and late pregnancy rates of GWG were independently associated with fat mass and percentage of body fat. Midpregnancy and late pregnancy GWGs were associated with fat-free mass. An observed GWG that exceeded recommendations was associated with higher neonatal fat mass and fat-free mass but not percentage of body fat relative to adequate GWG. CONCLUSIONS Maternal prepregnancy BMI and GWG, including period-specific GWG, were positively and independently associated with neonatal adiposity. Associations of early and midpregnancy weight gain with neonatal adiposity support the hypothesis that greater maternal weight gain during pregnancy, regardless of prepregnancy BMI, is directly related to offspring adiposity at birth. The Healthy Start study was registered as an observational study at clinicaltrials.gov as NCT02273297.

Perfluoroalkyl substances and lipid concentrations in plasma during pregnancy among women in the Norwegian Mother and Child Cohort Study

BACKGROUND Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia. METHODS This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003-2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted. RESULTS Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2mg/dL per inter-quartile shift (95% CI=0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per inter-quartile shift (95% CI=2.5, 4.9). CONCLUSION Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal.

Pesticide use and incident diabetes among wives of farmers in the Agricultural Health Study

Objective To estimate associations between use of specific agricultural pesticides and incident diabetes in women. Methods We used data from the Agricultural Health Study, a large prospective cohort of pesticide applicators and their spouses in Iowa and North Carolina. For comparability with previous studies of farmers, we limited analysis to 13 637 farmers’ wives who reported ever personally mixing or applying pesticides at enrolment (1993–1997), who provided complete data on required covariates and diabetes diagnosis and who reported no previous diagnosis of diabetes at enrolment. Participants reported ever-use of 50 specific pesticides at enrolment and incident diabetes at one of two follow-up interviews within an average of 12 years of enrolment. We fit Cox proportional hazards models with age as the time scale and adjusting for state and body mass index to estimate HRs and 95% CIs for each of the 45 pesticides with sufficient users. Results Five pesticides were positively associated with incident diabetes (n=688; 5%): three organophosphates, fonofos (HR=1.56, 95% CI 1.11 to 2.19), phorate (HR=1.57, 95% CI 1.14 to 2.16) and parathion (HR=1.61, 95% CI 1.05 to 2.46); the organochlorine dieldrin (HR=1.99, 95% CI 1.12 to 3.54); and the herbicide 2,4,5-T/2,4,5-TP (HR=1.59, 95% CI 1.00 to 2.51). With phorate and fonofos together in one model to account for their correlation, risks for both remained elevated, though attenuated compared with separate models. Conclusions Results are consistent with previous studies reporting an association between specific organochlorines and diabetes and add to growing evidence that certain organophosphates also may increase risk.

Validity of Pre-Eclampsia Registration in the Medical Birth Registry of Norway for Women Participating in the Norwegian Mother and Child Cohort Study, 1999–2010

BACKGROUND The Norwegian Mother and Child Cohort Study (MoBa), a prospective population-based pregnancy cohort, is a valuable database for studying causes of pre-eclampsia. Pre-eclampsia data in MoBa come from the Medical Birth Registry of Norway (MBRN); thus, we wanted to study the validity of MBRN pre-eclampsia registration for MoBa women. METHODS We selected all MoBa pregnancies with pre-eclampsia registered in the MBRN (n = 4081) and a random control group (n = 2000) without pre-eclampsia registrations. After excluding two delivery units not participating in MoBa and one no longer operating, units were asked to provide copies of antenatal charts with blood pressure and urinary measurements from all antenatal visits during pregnancy, and hospital discharge codes from the delivery stay. We received data for 5340 pregnancies delivered 1999-2010 (87% of all eligible). We calculated positive predictive value (PPV), and sensitivity and specificity of MBRN registration, using hypertension and proteinuria on the antenatal charts and/or hospital discharge codes indicating pre-eclampsia as gold standard. RESULTS Overall PPV was 83.9% [95% CI 82.7, 85.1] and was higher when women were primiparous, or delivered preterm or low birthweight infants. Severe pre-eclampsia in the MBRN was found to be a true severe pre-eclampsia in 70% of cases. Extrapolating to the total MoBa population, the estimated sensitivity was low - 43.0% (38.7, 48.2) - while specificity was high - 99.2% (99.2, 99.3). False negative cases seemed to have mild forms of pre-eclampsia. CONCLUSIONS PPV and specificity of pre-eclampsia registration in the MBRN during 1999-2010 was satisfactory, while sensitivity was low.

Maternal diet quality in pregnancy and neonatal adiposity: the Healthy Start Study.

Background/Objectives:Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass (%FM)) at birth by increasing the fat mass (FM) component of neonatal body composition.Methods:Our analysis was conducted using a prebirth observational cohort of 1079 mother–offspring pairs. Pregnancy diet was assessed via repeated Automated Self-Administered 24-h dietary recalls, from which Healthy Eating Index-2010 (HEI-2010) scores were calculated for each mother. HEI-2010 was dichotomized into scores of ⩽57 and >57, with low scores representing poorer diet quality. Neonatal %FM was assessed within 72 h after birth with air displacement plethysmography. Using univariate and multivariate linear models, we analyzed the relationship between maternal diet quality and neonatal %FM, FM, and fat-free mass (FFM) while adjusting for prepregnancy body mass index (BMI), physical activity, maternal age, smoking, energy intake, preeclampsia, hypertension, infant sex and gestational age.Results:Total HEI-2010 score ranged between 18.2 and 89.5 (mean: 54.2, s.d.: 13.6). An HEI-2010 score of ⩽57 was significantly associated with higher neonatal %FM (β=0.58, 95% confidence interval (CI) 0.07–1.1, P<0.05) and FM (β=20.74; 95% CI 1.49–40.0; P<0.05) but no difference in FFM.Conclusions:Poor diet quality during pregnancy increases neonatal adiposity independent of maternal prepregnancy BMI and total caloric intake. This further implicates maternal diet as a potentially important exposure for fetal adiposity.

Perfluoroalkyl Substances During Pregnancy and Validated Preeclampsia Among Nulliparous Women in the Norwegian Mother and Child Cohort Study

Perfluoroalkyl substances (PFAS) are persistent and ubiquitous environmental contaminants, and human exposure to these substances may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFAS to be positively associated with pregnancy-induced hypertension and preeclampsia in a population with high levels of exposure to perfluorooctanoate. Whether this association exists among pregnant women with background levels of PFAS exposure is unknown. Using data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health, we carried out a study of nulliparous pregnant women enrolled in 2003-2007 (466 cases, 510 noncases) to estimate associations between PFAS concentrations and an independently validated diagnosis of preeclampsia. We measured levels of 9 PFAS in maternal plasma extracted midpregnancy; statistical analyses were restricted to 7 PFAS that were quantifiable in more than 50% of samples. In proportional hazards models adjusted for maternal age, prepregnancy body mass index (weight (kg)/height (m)(2)), educational level, and smoking status, we observed no strongly positive associations between PFAS levels and preeclampsia. We found an inverse association between preeclampsia and the highest quartile of perfluoroundecanoic acid concentration relative to the lowest quartile (hazard ratio = 0.55, 95% confidence interval: 0.38, 0.81). Overall, our findings do not support an increased risk of preeclampsia among nulliparous Norwegian women with background levels of PFAS exposure.

Maternal Dietary Patterns during Pregnancy Are Associated with Newborn Body Composition

Background: Maternal dietary intake during pregnancy may influence offspring growth and adiposity. Specific dietary patterns associated with newborn adiposity have not been identified.Objective: We aimed to identify patterns of maternal dietary intake associated with gestational weight gain (GWG) and fasting glucose during pregnancy and to evaluate whether adherence to these patterns is associated with newborn adiposity.Methods: In the Healthy Start prospective cohort, dietary intake during pregnancy was assessed via 24-h recalls. Reduced-rank regression identified dietary patterns predictive of GWG and fasting glucose. Associations between dietary patterns and newborn fat mass, fat-free mass, and adiposity were estimated by using linear regression models among 764 ethnically diverse mother-infant pairs.Results: Two dietary patterns were identified. Pattern 1, correlated with greater GWG (r = 0.22, P < 0.01), was characterized by a higher consumption of poultry, nuts, cheese, fruits, whole grains, added sugars, and solid fats. Greater adherence to pattern 1 (upper compared with lower tertile) predicted a greater newborn fat-free mass (61 g; 95% CI: 12, 110 g) but no difference in fat mass or adiposity. Pattern 2, correlated with greater maternal fasting glucose (r = 0.16, P < 0.01), was characterized by a higher consumption of eggs, starchy vegetables, solid fats, fruits, and nonwhole grains and a lower consumption of dairy foods, dark-green vegetables, and whole grains. Greater adherence to pattern 2 was associated with a greater newborn birth weight (80 g; 95% CI: 15, 145 g), fat mass (33 g; 95% CI: 8, 59 g), and adiposity (0.9%; 95% CI: 0.3%, 1.6%).Conclusions: Among pregnant women, adherence to a dietary pattern characterized by an intake of poultry, nuts, cheese, and whole grains was associated with greater GWG but not maternal fasting glucose or newborn adiposity. Adherence to a pattern characterized by an intake of eggs, starchy vegetables, and nonwhole grains was associated with higher maternal fasting glucose and greater newborn adiposity. Maternal dietary patterns during pregnancy may influence newborn body composition.

Predictors and long-term reproducibility of urinary phthalate metabolites in middle-aged men and women living in urban Shanghai.

Phthalate esters are man-made chemicals commonly used as plasticizers and solvents, and humans may be exposed through ingestion, inhalation, and dermal absorption. Little is known about predictors of phthalate exposure, particularly in Asian countries. Because phthalates are rapidly metabolized and excreted from the body following exposure, it is important to evaluate whether phthalate metabolites measured at a single point in time can reliably rank exposures to phthalates over a period of time. We examined the concentrations and predictors of phthalate metabolite concentrations among 50 middle-aged women and 50 men from two Shanghai cohorts, enrolled in 1997-2000 and 2002-2006, respectively. We assessed the reproducibility of urinary concentrations of phthalate metabolites in three spot samples per participant taken several years apart (mean interval between first and third sample was 7.5 years [women] or 2.9 years [men]), using Spearmans rank correlation coefficients and intra-class correlation coefficients. We detected ten phthalate metabolites in at least 50% of individuals for two or more samples. Participant sex, age, menopausal status, education, income, body mass index, consumption of bottled water, recent intake of medication, and time of day of collection of the urine sample were associated with concentrations of certain phthalate metabolites. The reproducibility of an individuals urinary concentration of phthalate metabolites across several years was low, with all intra-class correlation coefficients and most Spearman rank correlation coefficients ≤0.3. Only mono(2-ethylhexyl) phthalate, a metabolite of di(2-ethylhexyl) phthalate, had a Spearman rank correlation coefficient ≥0.4 among men, suggesting moderate reproducibility. These findings suggest that a single spot urine sample is not sufficient to rank exposures to phthalates over several years in an adult urban Chinese population.

Predictors of Infant Body Composition at 5 Months of Age: The Healthy Start Study

Objective To examine associations of demographic, perinatal, and infant feeding characteristics with offspring body composition at approximately 5 months of age. Study design We collected data on 640 mother/offspring pairs from early pregnancy through approximately 5 months of age. We assessed offspring body composition with air displacement plethysmography at birth and approximately 5 months of age. Linear regression analyses examined associations between predictors and fat‐free mass, fat mass, and percent fat mass (adiposity) at approximately 5 months. Secondary models further adjusted for body composition at birth and rapid infant growth. Results Greater prepregnant body mass index and gestational weight gain were associated with greater fat‐free mass at approximately 5 months of age, but not after adjustment for fat‐free mass at birth. Greater gestational weight gain was also associated with greater fat mass at approximately 5 months of age, independent of fat mass at birth and rapid infant growth, although this did not translate into increased adiposity. Greater percent time of exclusive breastfeeding was associated with lower fat‐free mass (‐311 g; P < .001), greater fat mass (+224 g; P < .001), and greater adiposity (+3.51%; P < .001). Compared with offspring of non‐Hispanic white mothers, offspring of Hispanic mothers had greater adiposity (+2.72%; P < .001) and offspring of non‐Hispanic black mothers had lower adiposity (‐1.93%; P < .001). Greater adiposity at birth predicted greater adiposity at approximately 5 months of age, independent of infant feeding and rapid infant growth. Conclusions There are clear differences in infant body composition by demographic, perinatal, and infant feeding characteristics, although our data also show that increased adiposity at birth persists through approximately 5 months of age. Our findings warrant further research into implications of differences in infant body composition.

An observational cohort study of weight- and length-derived anthropometric indicators with body composition at birth and 5 mo: the Healthy Start study

Background: Despite widespread use of weight- and length-based anthropometric indexes as proxies for adiposity, little is known regarding the extent to which they correspond with fat mass (FM) or fat-free mass (FFM) during infancy.Objective: This study aimed to examine associations of 3 derived indicators-weight-for-age z score (WFAZ), weight-for-length score (WFLZ), and body mass index z score (BMIZ)-with FM, percentage of FM, and FFM measured by air-displacement plethysmography during the first 5 mo of life.Design: Applying prospectively collected data from 1027 infants in a Colorado prebirth cohort, we used multivariate regression to evaluate associations between the derived indicators and body composition at birth and at 5 mo, and with change (Δ) during follow-up.Results: At birth, all 3 derived indicators were more strongly associated with FFM than with FM. Each unit of WFAZ corresponded with 0.342 kg FFM (95% CI: 0.331, 0.351 kg FFM), compared with 0.121 kg FM (95% CI: 0.114, 0.128 kg FM) (P < 0.0001); similar trends were observed for WFLZ and BMIZ. By 5 mo, WFLZ and BMIZ were more strongly associated with FM than with FFM, whereas WFAZ correlated similarly with the 2 components of body composition. ΔWFLZ and ΔBMIZ were both more strongly related to ΔFM than to ΔFFM; however, a direct comparison of the 2 indexes with respect to change in the percentage of FM indicated that ΔBMIZ was the optimal proxy of adiposity gain (P < 0.0001, pairwise difference).Conclusions: Weight- and length-based indexes are poor surrogates for newborn adiposity. However, at 5 mo, WFLZ and BMIZ are suitable proxies of FM. When assessing adiposity gain, ΔBMIZ is the best indicator of fat accrual during the first 5 postnatal months. This trial was registered at clinicaltrials.gov as NCT02273297.