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Background: Mother-to-newborn transmission of obesity-associated microbiota may be modified by birth mode (vaginal vs. Cesarean delivery). Prospective data to test this hypothesis are still sparse., Objective: To examine prospective associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome by birth-mode strata., Subjects/methods: In 335 mother-infant pairs in the New Hampshire Birth Cohort, we ascertained data from questionnaires and medical records, and generated microbiome data from 6-week-old infants' stool using Illumina 16s rRNA gene sequencing (V4-V5 region). Analyses were stratified by birth mode and conducted before and after adjusting for potential confounders, which included maternal age, education, parity, and Mediterranean diet score., Results: Among 335 mothers, 56% had normal pre-pregnancy BMI ( < 25, referent), 27% were overweight (BMI 25-30), and 18% obese (BMI > 30). Among the 312 mothers with weight gain data, 10% had inadequate weight gain, 30% adequate (referent), and 60% excess. Birth mode modified associations of pre-pregnancy BMI with several genera, including the most abundant genus, Bacteroides (P for interaction = 0.05). In the vaginal-delivery group, maternal overweight or obesity was associated with higher infant gut microbiome diversity and higher relative abundance of 15 operational taxonomic units (OTUs), including overrepresentation of Bacteroides fragilis, Escherichia coli, Veillonella dispar, and OTUs in the genera Staphylococcus and Enterococcus. In the Cesarean-delivered group, there were no significant associations of pre-pregnancy BMI with infant microbiome (alpha) diversity or OTUs. Gestational weight gain was not associated with differential relative abundance of infant gut microbial OTUs or with measures of microbial diversity in infants delivered vaginally or by Cesarean section., Conclusions: Among vaginally-delivered infants, maternal overweight and obesity was associated with altered infant gut microbiome composition and higher diversity. These associations were not observed in Cesarean-delivered infants, whose microbiome development differs from vaginally-delivered infants. Our study provides additional evidence of birth-mode dependent associations of maternal body weight status with the infant gut microbiota. The role of these associations in mediating the intergenerational cycle of obesity warrants further examination.

BackgroundInadequate or excessive intake of micronutrients in pregnancy has potential to negatively impact maternal/offspring health outcomes.ObjectiveThe aim was to compare risks of inadequate or excessive micronutrient intake in diverse females with singleton pregnancies by strata of maternal age, race/ethnicity, education, and prepregnancy BMI.MethodsFifteen observational cohorts in the US Environmental influences on Child Health Outcomes (ECHO) Consortium assessed participant dietary intake with 24-h dietary recalls (n = 1910) or food-frequency questionnaires (n = 7891) from 1999-2019. We compared the distributions of usual intake of 19 micronutrients from food alone (15 cohorts; n = 9801) and food plus dietary supplements (10 cohorts with supplement data; n = 7082) to estimate the proportion with usual daily intakes below their age-specific daily Estimated Average Requirement (EAR), above their Adequate Intake (AI), and above their Tolerable Upper Intake Level (UL), overall and within sociodemographic and anthropometric subgroups.ResultsRisk of inadequate intake from food alone ranged from 0% to 87%, depending on the micronutrient and assessment methodology. When dietary supplements were included, some women were below the EAR for vitamin D (20-38%), vitamin E (17-22%), and magnesium (39-41%); some women were above the AI for vitamin K (63-75%), choline (7%), and potassium (37-53%); and some were above the UL for folic acid (32-51%), iron (39-40%), and zinc (19-20%). Highest risks for inadequate intakes were observed among participants with age 14-18 y (6 nutrients), non-White race or Hispanic ethnicity (10 nutrients), less than a high school education (9 nutrients), or obesity (9 nutrients).ConclusionsImproved diet quality is needed for most pregnant females. Even with dietary supplement use, >20% of participants were at risk of inadequate intake of ≥1 micronutrients, especially in some population subgroups. Pregnancy may be a window of opportunity to address disparities in micronutrient intake that could contribute to intergenerational health inequalities.

Background Trimethylamine N-oxide (TMAO) and its precursors choline, betaine, and carnitine have been associated with cardiometabolic disease in nonpregnant adults. However, studies examining TMAO and its precursors in relation to cardiometabolic conditions during pregnancy are lacking. Objectives The primary objective was to estimate the association of TMAO and its precursors in maternal and cord plasma with gestational diabetes mellitus (GDM) and pre-eclampsia (PE) among women in the Boston Birth Cohort. A secondary objective was to determine whether associations vary by race/ethnicity. Methods ORs for each outcome according to tertiles and to an SD increment of TMAO, choline, betaine, and carnitine were estimated using logistic regression. Final models were adjusted for covariates. Results Among 1496 women, 115 women had GDM and 159 had PE during the index pregnancy. Intermetabolite correlations of TMAO and its precursors were stronger within cord plasma (r = 0.38–0.87) than within maternal plasma (r = 0.08–0.62). Maternal TMAO was associated with higher odds of GDM (third compared with first tertile OR: 1.75; 95% CI: 1.04, 2.94), whereas maternal choline, betaine, and carnitine were not associated with GDM. Maternal TMAO and choline were not associated with PE, whereas carnitine was associated with higher (OR: 1.86; 95% CI: 1.18, 2.94) and betaine with lower odds of PE (OR: 0.37; 95% CI: 0.23, 0.59). In cord plasma, TMAO was not associated with GDM or PE, but choline, betaine, and carnitine were associated with higher odds of PE (OR: 3.11; 95% CI: 1.62, 5.96; OR: 2.65; 95% CI: 1.42, 4.93; OR: 2.56; 95% CI: 1.39, 4.69, respectively). Cord choline was associated with lower odds of GDM (OR: 0.52; 95% CI: 0.27, 0.99), whereas other cord metabolites were not significantly associated with GDM. Associations did not vary by race/ethnicity. Conclusions TMAO and its precursors were associated with GDM and PE, but the associations differed based on the metabolite medium (maternal compared with cord plasma). This trial was registered at clinicaltrials.gov as NCT03228875. [ABSTRACT FROM AUTHOR]

Background: Manganese, an essential micronutrient, has been found in lower concentrations among women with preeclampsia in cross-sectional and case-control studies without establishment of a temporal relationship.Methods: We evaluated the prospective association of manganese (in red blood cells) in first trimester of pregnancy with incidence of preeclampsia (ascertained by reviewing medical records) among 1,312 women in eastern Massachusetts (Project Viva, 1999-2002). We used log-binomial regression to examine the manganese-preeclampsia relationship, adjusting for maternal age, race/ethnicity, parity, prepregnancy body mass index, blood pressure, and hematocrit.Results: The median (25th, 75th percentile) manganese concentrationin red blood cells was 16.2 ng/g (13.1, 20.4) and 48 (4%) women developed preeclampsia. We observed an inverse dose-response relationship between manganese and preeclampsia. Compared with women in the lowest tertile, women in the middle manganese tertile had 0.81 times the risk of preeclampsia (95% CI: 0.43, 1.5) and those in the highest tertile had 0.50 (95% CI: 0.25, 0.99) times the risk.Conclusions: Our results provide insight into a potentially modifiable way to prevent preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Evidence used to guide the current Institute of Medicine (IOM) gestational weight gain (GWG) recommendations is largely derived from studies of European descent, and as such the guidelines are the same for all races and ethnicities. The guidelines are also the same for prepregnancy obesity classes I through III. Objective: Considering these literature gaps, we aim to (1) determine the association between the IOM GWG guidelines and three common pregnancy complications: preeclampsia, gestational diabetes mellitus, and cesarean delivery in a racially and ethnically diverse population; and (2) assess whether the association between GWG and pregnancy complications differs by race/ethnicity or prepregnancy body mass index (BMI) categories, particularly obesity classes I through III. Methods: To address these aims, we analyzed data from the Boston Birth Cohort. We calculated GWG using data from electronic medical records or, when missing, from a postdelivery questionnaire. We examined GWG continuously and categorically using the IOM formula. Results: Of the 5,568 women included, 54.5% met the IOM criterion for excessive GWG. Compared to women who had adequate GWG, women who gained excessive weight had 1.65 (95% confidence interval [CI] 1.27–2.14) times greater odds of preeclampsia; 1.68 (95% CI 1.15–2.46) times greater odds of gestational diabetes; and no significant change in odds of cesarean delivery (odds ratio [OR] = 1.14, 95% CI 0.99–1.31). Associations did not differ by race, ethnicity, or prepregnancy BMI categories including comparisons of obesity class I versus II or III (all p-values for interaction >0.05). Conclusions: In this racially and ethnically diverse population, excessive GWG was associated with higher odds of preeclampsia, gestational diabetes, and nonsignificantly, with cesarean delivery. Associations did not differ appreciably by race, ethnicity, or prepregnancy BMI categories. Our results support the relevance of the IOM GWG recommendations in racially and ethnically diverse populations, and in women in the higher prepregnancy obesity classes. [ABSTRACT FROM AUTHOR]

Exposure to ambient air pollution has been associated with greater risk of elevated blood pressure (BP) in adults and children. Recent evidence suggests that air pollution exposure in pregnancy may also portend increased risk for the next generation; however, few studies have examined this relationship. We conducted a prospective study of 1293 mothers in the Boston Birth Cohort (enrolled 1998-2012) and their children who had follow-up visits between 3 and 9 years of age and complete exposure and outcome data. Our primary exposure, ambient particulate matter ≤2.5 µm (PM2.5) concentration during pregnancy, was estimated by matching mother's residential address to the US Environmental Protection Agency's air quality monitors. We defined our primary outcome child systolic BP (SBP) percentile according to US reference (Fourth Report) and classified elevated BP as SBP ≥90th percentile. Our multivariable-adjusted cubic spline showed a sharp increase in offspring SBP percentile and risk for elevated BP when third-trimester PM2.5 concentration was ≥13 μg/m3 The highest versus lowest tertile of third-trimester PM2.5 exposure was associated with a 4.85 (95% confidence interval: 1.38-8.37) percentile increase in child SBP or a 1.61 (95% confidence interval: 1.13-2.30) times higher risk of child elevated BP. A 5-μg/m3 increment in PM2.5 during the third trimester was associated with a 3.49 (95% confidence interval: 0.71-6.26) percentile increase in child SBP or a 1.47 (95% confidence interval: 1.17-1.85) times higher risk of elevated BP. Our findings suggest that exposure to ambient PM2.5 during the third trimester of pregnancy is associated with elevated BP in children, ages 3 to 9 years. [ABSTRACT FROM AUTHOR]

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 Children's 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. [ABSTRACT FROM AUTHOR]

Previous studies have suggested a positive association between self-reported maternal acetaminophen use during pregnancy and risk of attention deficit hyperactivity disorder (ADHD) in offspring. We sought to examine the prospective association between maternal plasma biomarkers of acetaminophen intake and ADHD diagnosis in the offspring. This report analyzed 1180 children enrolled at birth and followed prospectively as part of the Boston Birth Cohort, including 188 with ADHD diagnosis based on electronic medical record review. Maternal biomarkers of acetaminophen intake were measured in plasma samples obtained within 1–3 days postpartum. Odds ratios for having ADHD diagnosis or other developmental disorders were estimated using multinomial logistic regression models, adjusting for pertinent covariables. Compared to neurotypical children, we observed significant positive dose-responsive associations with ADHD diagnosis for each maternal acetaminophen biomarker. These dose–responsive associations persisted after adjusting for indication of acetaminophen use and other pertinent covariates; and were specific to ADHD, rather than other neurodevelopmental disorders. In the stratified analyses, differential point estimates of the associations were observed across some strata of covariates. However, these differences were not statistically significant. Maternal acetaminophen biomarkers were specifically associated with increased risk of ADHD diagnosis in offspring. Additional clinical and mechanistic investigations are warranted. [ABSTRACT FROM AUTHOR]

• We examined heavy metals and trace minerals mixture and blood pressure in pregnancy. • Overall, the mixture was positively associated with blood pressure in early pregnancy. • Cu and Se was each individually linked with blood pressure and its weekly change. • The mixture was not associated with hypertensive disorders during pregnancy. While several heavy metals and trace minerals have been linked with hypertensive disorders during pregnancy (HDP) in women, no studies have estimated the relationship of exposure to these chemicals, both independently and as a mixture, with systolic blood pressure (SBP) or diastolic blood pressure (DBP) over gestation. We examined individual and joint effects of 1st trimester chemicals with SBP and DBP over gestation, and whether those chemicals were associated with HDP. We used data from 1832 non-obese pregnant women with low-risk antenatal profiles from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies - Singleton cohort (2009–2013). In plasma collected from women at 8–13 weeks' gestation (baseline enrollment), we measured heavy metals, barium (Ba), cesium (Cs), antimony (Sb), as well as trace minerals, cobalt (Co), copper (Cu), molybdenum (Mo), selenium (Se), and zinc (Zn). We obtained BP at baseline and throughout gestation until delivery and diagnosis of HDP from medical records. We used Bayesian Kernel Machine Regression (BKMR) as well as traditional linear and logistic regressions to examine the cross-sectional associations of chemicals with baseline BP and HDP. We used linear mixed effect regression to examine longitudinal associations between chemicals and rate of weekly change in BP in each trimester. We adjusted for sociodemographic and lifestyle factors and pre-pregnancy body mass index in all models. BKMR revealed that comparing the entire chemical mixture at the 90th percentile vs. the 50th percentile was associated with a 1.61 mmHg (95% CI: 0.41, 2.81) higher SBP and a 1.09 mmHg (0.10, 2.09) higher DBP. No interactions were observed between chemicals. Accounting for chemical co-exposure in BKMR, each interquartile range (IQR) increment in Cu was associated with a 0.67 mmHg (0.02, 1.32) higher SBP and a 0.60 mmHg (0.08, 1.12) higher DBP at baseline; each IQR increment in Se was associated with a 0.67 mmHg (0.05, 1.29) higher SBP but not DBP. In longitudinal analyses, women with higher (i.e., above median concentration) baseline Cu had a 0.09 mmHg (0.01, 0.17) and 0.06 mmHg (0.001, 0.12) larger weekly decrease in SBP and DBP in 2nd trimester, respectively. Women with higher baseline Ba had a 0.12 mmHg (0.04, 0.20) larger weekly increase in SBP in 2nd trimester, while women with higher Cs had a 0.05 mmHg (0.01, 0.10) larger weekly increase in DBP in 3rd trimester. None of the chemicals examined were significantly associated with HDP. In this multi-ethnic cohort of women with low antenatal risk, plasma metals and trace minerals in early pregnancy, both individually and as a mixture, were statistically significantly associated with BP during gestation in small magnitude and in different directions, but not with HDP. The implications of these findings for women's postpartum BP and future cardiovascular health remains to be investigated. [ABSTRACT FROM AUTHOR]