Background: Exposure to metals lead (Pb), mercury (Hg), and cadmium (Cd) and trace elements selenium (Se) and manganese (Mn) has been linked to the developmental origins of cardiometabolic diseases, but the mechanisms are not well-understood. Objective: Conduct a metabolome-wide association study to understand how in utero exposure to Pb, Hg, Cd, Se, and Mn affects the metabolic programming of fetuses. Methods: We used data from mother-infant pairs in the Boston Birth Cohort. We measured metals and trace elements in maternal red blood cells (RBCs) collected 24-72 hours after delivery, and metabolites in cord blood collected at birth. We used multivariable linear regression to examine associations of metals and trace elements with metabolites and Bonferroni correction to account for multiple comparisons. We assessed non-linear associations of metals and trace elements with metabolites using restricted cubic spline plots. Results: This analysis included 690 mother-infant pairs (57% Black and 24% Hispanic). After Bonferroni correction, 25 cord metabolites were associated with at least one metal or trace element (Figure). Pb was negatively associated with the xenobiotic piperine, Cd was positively associated with xenobiotics cotinine and hydroxycotinine, and Hg was associated with 8 lipid metabolites (in both directions). Mn and Se shared associations with 6 metabolites (in both directions), which mostly included nucleotides and amino acids; Mn was additionally associated C36:4 hydroxy phosphatidylcholine and Se was additionally associated with 7 metabolites (mostly amino acids, nucleotides, and carnitines). Most associations were linear. Discussion: Maternal RBC metal and trace element concentrations were associated in a dose-dependent fashion with cord blood metabolites. What remains to be determined is whether these metals- and trace elements-associated changes in cord metabolites can influence a child’s future risk of cardiometabolic diseases.
Introduction: A recent study of mother-child pairs in Canada (Miliku et al., JAHA 2021) found that ever (vs. never) breastfeeding was associated with lower blood pressure (BP) in early childhood. The authors posited the effect is modulated by the microbiome. However, they did not examine if the breastfeeding effect is stronger in vaginally-delivered infants, whom host more bacterial species (e.g., Bifidobacteria ) that bioconvert human milk oligosaccharides into BP-lowering butyrate. Given their population was majority White, it is unknown if breastfeeding lowers BP in non-White populations. Hypothesis: Introduction to breast milk in infancy lowers BP in childhood, particularly among vaginally delivered infants, in a racially diverse population. Methods: We used data from the Boston Birth Cohort. We assessed breastfeeding status during the postnatal follow up at <2 years of age. Ever breastfeeding was defined as exclusively breastfed or a mix of breastfed and bottle-fed. We obtained repeated clinical measures of childhood systolic BP (SBP) across 0-17 years of age. We calculated age-, sex-, and height- specific child BP percentiles according to the 2017 American Academy of Pediatrics Clinical Practice Guidelines. We used linear regression with GEE with a link function and AR-1 correlation to examine the association of ever breastfeeding with child SBP. We controlled for maternal age, education, smoking, parity, pre-pregnancy BMI, hypertension, and child low birthweight, preterm birth, age, and sex. We assessed effect modification by race and delivery mode. Results: Our analytic sample comprised 19,597 BP measurements from 2,077 children, who were 52% male, 66% black, and had a mean age of 8 years. Among our sample, 33% were born preterm, 59% were vaginally delivered, and 74% were ever breastfed. Ever (vs. never) breastfeeding was associated with 1.74 percentile (95% CI: -3.66, 0.19; p=0.08) lower SBP. In children who were delivered vaginally, ever breastfeeding was associated with 2.63 percentile (95% CI: -5.12, -0.14; p=0.04) lower SBP. In contrast, among children delivered by Cesarean section, SBP percentile was not significantly reduced (95% CI: -3.45, 2.59; p=0.78) among ever breastfed. Moreover, ever breastfeeding was more strongly associated with lower BP among participants who self-identified as non-Black (3.40 percentile lower SBP; 95% CI: -6.30, -0.49; p=0.02) vs. Black (0.98 percentile lower SBP; 95% CI: -3.42, 1.45; p=0.43). Conclusion: In our racially diverse cohort, ever vs. never breastfeeding was associated with lower BP among children who were delivered vaginally, but not among those delivered by Cesarean section. The protective association of ever breastfeeding on child BP was also weaker in those born to mothers who self-identified as Black, highlighting the need for more research on the effects of breastfeeding on cardiometabolic health in racial minority groups.
To identify a postpartum lipidomic signature associated with gestational diabetes mellitus (GDM) and investigate the role of the identified lipids in the progression to type 2 diabetes (T2D).
Lower respiratory tract infections (LRTIs) remain the leading cause of infant morbidity and mortality worldwide and affect long-term respiratory health. Identifying immunological determinants of LRTI susceptibility may help stratify disease risk and identify therapies. This study aimed to identify neonatal immunological factors predicting LRTI risk in infancy. Cord blood plasma from 191 neonates from the Boston Birth Cohort was analyzed for 28 soluble immune factors. LRTI was defined as bronchiolitis, bronchitis, or pneumonia during the first year of life. Welch's
Introduction: Age at menarche onset reflects many health aspects in women. Later age at menarche has been associated with lower risk of several cardiometabolic disease outcomes, including diabetes and various cardiovascular diseases. However, no studies have reported the association of maternal menarche age with risk of preterm birth (PTB)—a pregnancy outcome with significant racial disparities and cardiometabolic etiology. Hypothesis: Later age at menarche onset is associated with lower risk of PTB. Methods: We conducted a case-control study in the Boston Birth Cohort, including 2242 mothers with PTB [gestational age (GA) <37 wks], and 6022 mothers with term birth (GA ≥37 wks). We used a maternal postpartum questionnaire (administered 24-72 hrs after delivery) to collect data on age at menarche, sociodemographic and lifestyle factors. We used medical records to ascertain GA. We used multivariable-adjusted logistic regression models and restricted cubic splines to examine the association between age at menarche and odds of PTB. Results: Of the 8264 mothers in our study, 46.9% identified as Black and 28.8% as Hispanic. Maternal age at delivery was 28.1y ±6.5y and age at menarche was 12.85y ±1.86y. Our multivariable-adjusted cubic spline suggested a linear dose-response association of age at menarche with odds of PTB and GA (Figure). Per 1-year later menarche onset of menarche was associated with 5% (95% CI: 2%-8%) lower odds of PTB, after adjustment for maternal place of birth, education, smoking status, Mediterranean diet score, and pre-pregnancy BMI. We found a similar pattern (5% lower odds per 1-year later, 95% CI: 1%-8%) in Black mothers. Conclusion: In a large cohort of racially and ethnically diverse women, later age at menarche is associated with lower risk for PTB. Our findings suggests that the origins of higher risk for PTB start early in life, before puberty, and appear to be independent of adiposity. Future studies are needed to identify mechanisms and points of intervention.
Introduction: Later menarche onset portends lower risk of cardiometabolic outcomes in adults (e.g., obesity, diabetes, hypertension, and myocardial infarction) and in pregnancy (e.g., preterm birth). However, the underlying mechanisms underlying these associations are unclear. Metabolome-wide association studies afford an opportunity to identify mechanistic pathways. Objective: To identify metabolome signatures of age at menarche in a diverse sample of women. Methods: This analysis includes 1301 women from the Boston Birth Cohort who were enrolled 24-72 hrs. after delivery, when we collected maternal plasma sample for metabolome and information on maternal age at menarche (range 7-18y) via a standard questionnaire interview. We used linear regression and restricted cubic splines to examine the association between age at menarche and metabolites. We adjusted for maternal year of birth, place of birth, education, smoking status, Mediterranean diet score, pre-pregnancy BMI, hypertensive disorders, and diabetes. Results: Of the 1301 study women, 63.7% identified as Black and 21.3% as Hispanic. Maternal age at delivery was 28.3y ±6.6y and age at menarche was 12.87y ±1.95y. Of the 389 metabolites we examined, 63 were associated with late menarche (>15y vs. menarche 12-13y; Fig., A ). A 1-yr increment in menarche age was associated with 7 metabolites ( Fig., B ); of these, imidazole propionate and C18:2 SM were (inverse) linear dose-response ( Fig., C ). Other metabolites, including some implicated in cardiovascular disease (e.g., dimethylguanidino valeric acid), showed a threshold effect starting at menarche >14 years (Fig., C). Conclusion: In this racially and ethnically diverse cohort of women from Boston, later age at menarche is associated with many metabolites, including inverse associations with metabolites that have been previously implicated in cardiovascular disease. Our findings help inform mechanistic pathways and that, if replicated, could be targeted for cardiometabolic prediction and prevention.
