Publications

CONTEXT: Leptin and adiponectin play important roles in systemic metabolic homeostasis, beginning in utero. Limited data exist on the levels and trajectories of these 2 hormones at birth and in childhood and their biological and social determinants.

OBJECTIVE: We examined the longitudinal trajectories of leptin and adiponectin from birth to early childhood, along with influential prenatal and infancy factors, and whether the trajectories and risk factors differ by preterm birth status.

METHODS: We included mother-infant pairs in the Boston Birth Cohort, a predominantly Black, indigenous, and people of color (BIPOC) study population. We measured infant plasma leptin and adiponectin levels at birth and in early childhood. We examined longitudinal trajectories and the associated prenatal maternal and infancy factors. We analyzed 716 infants (158 preterm) who had leptin and adiponectin measured at birth and in early childhood (mean corrected age 2.18 years [interquartile range, 0.4-10.4]).

RESULTS: Cord leptin was higher in term infants (40 230 vs 20 481 in preterm, P < 0.0001) but childhood leptin did not differ by prematurity (4123 in term vs 4181 in preterm, P = 0.92). Adiponectin was higher in term infants at birth (18 416 vs 11 223, P < 0.0001) and in childhood (12 108 vs 10532, P = 0.04). In stepwise regression, Black race was associated with higher childhood leptin and lower childhood adiponectin. Female sex was associated with higher childhood leptin levels and lower childhood adiponectin levels in multivariable regression models.

CONCLUSION: Our results highlight preterm status, race, and biological sex as predictors of adipokine trajectory throughout childhood. These findings raise the possibility that early life programming of adipokines may contribute to higher metabolic risk in life, especially among Black children born preterm.

BACKGROUND: Plastic exposures have been shown to impact the microbiome, metabolism and growth of animals. However, no human studies have examined how plastic exposures are associated with fecal microbiota, microbial metabolites, or growth. Here we examine the association of plastic bottle feeding with infant fecal microbiota, microbial short-chain fatty acid (SCFA) metabolites, and anthropometry in the first year of life.

METHODS: 462 infants from the prospective Nurture Birth Cohort were included to examine frequency of plastic bottle feeding (every feeding vs. less than every feeding) at 3 months with anthropometric outcomes (skinfolds, length-for-age, and weight-for-length) at 1 year. A subset of 64 and 67 infants were included in analyses examining the fecal microbiota and fecal SCFAs, respectively. Microbial taxa were measured by 16S rRNA gene sequencing of the V4 region and SCFA concentrations were quantified using gas chromatography at 3 and 12 months of age.

RESULTS: After adjustment for potential confounders, less frequent plastic bottle use was associated with lower fecal microbiota alpha Shannon diversity at 3 months (mean difference for plastic bottle used less than every feeding vs. every feeding = -0.53, 95% CI: -0.90, -0.17, p < 0.01) and lower propionic acid concentration at 3 months (mean log + 1 difference for plastic bottle used every feeding vs. less than every feeding = -0.53, 95% CI: -1.00, -0.06, p = 0.03). Furthermore, compared to infants who used plastic bottle at every feeding, infants who were plastic bottle-fed less frequently (1 -3 times/day) at 3 months had significantly lower length-for-age z-scores at 12 months (mean difference= -0.40, 95% CI: -0.72, -0.07, p = 0.016).

CONCLUSION: Plastic bottle exposure may impact early infant gut microbiota and microbial SCFAs, which may in turn affect growth.

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless combined exposure index, which collapses census-tract level data into a single relative measure of exposure ranging from 0-1 (where higher values indicate higher exposure to hazards), includes indicators for major air pollutants and air toxics, features of the built environment, traffic exposures, and social determinants of health (e.g., lower educational attainment) drawn from existing data sources. We observed temporal and geographic variations in index values, with exposures being highest among participants living in the West and Northeast regions. Pregnant people who identified as Black or Hispanic (of any race) were at higher risk of living in a "high" exposure census tract (defined as an index value above 0.5) relative to those who identified as White or non-Hispanic. Index values were also higher for pregnant people with lower educational attainment. Several recommendations follow from our work, including that environmental and social stressor datasets with higher spatial and temporal resolutions are needed to ensure index-based tools fully capture the total environmental context.

Background Evidence is limited regarding the associations of prenatal and childhood per- and polyfluoroalkyl substance (PFAS) exposures with blood pressure (BP) trajectories in children. Methods and Results Participants are from Project Viva, a prospective prebirth cohort in eastern Massachusetts. We measured PFAS in early-pregnancy maternal (median, 9.6 weeks) and midchildhood (median, 7.7 years) plasma samples. We conducted standardized BP measurements at 6 research visits: birth, infancy (median, 6.3 months), early childhood (median, 3.2 years), midchildhood (median, 7.7 years), early adolescence (median, 12.9 years), and late adolescence (median, 17.5 years). We used linear regression to examine associations of individual PFASs with BP at each visit, linear spline mixed-effects regression to model BP trajectories, and a mixture approach to estimate PFAS exposure burden. We included 9036 BP measures from 1506 participants. We observed associations between particular individual prenatal PFASs and child BP at specific time points, for example, prenatal 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) with higher systolic BP at birth; prenatal perfluorooctane sulfonate (PFOS) and EtFOSAA with lower diastolic BP in infancy; and prenatal PFOS, perfluorooctanoate (PFOA), and EtFOSAA with higher systolic BP at midchildhood. No prenatal or childhood PFAS was consistently associated with BP across all visits. Diastolic BP trajectories from 0 to 20 years differed slightly by prenatal PFOA, perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) (P values 0.01-0.09). Diastolic BP trajectories from 6 to 20 years differed slightly by midchildhood PFHxS and MeFOSAA (P-values 0.03-0.08). Prenatal or childhood PFAS mixture burden scores were not associated with BP. Conclusions We found associations of prenatal and childhood PFAS exposures with BP at specific time points between birth and late adolescence but no consistent associations across all time points or PFAS types.

BACKGROUND/OBJECTIVES: Murine models show that plastics, via their chemical constituents (e.g., phthalates), influence microbiota, metabolism, and growth. However, research on plastics in humans is lacking. Here, we examine how the frequency of plastic bottle exposure is associated with fecal microbiota, short-chain fatty acids (SCFAs), and anthropometry in the first year of life.

SUBJECTS/METHODS: In 442 infants from the prospective Nurture birth cohort, we examined the association of frequency of plastic bottle feeding at 3 months with anthropometric outcomes (skinfolds, length-for-age, and weight-for-length) at 12 months of age and growth trajectories between 3 and 12 months. Furthermore, in a subset of infants (n = 70) that contributed fecal samples at 3 months and 12 months of age, we examined plastic bottle frequency in relation to fecal microbiota composition and diversity (measured by 16S rRNA gene sequencing of V4 region), and fecal SCFA concentrations (quantified using gas chromatography mass spectrometry).

RESULTS: At 3 months, 67.6% of infants were plastic bottle fed at every feeding, 15.4% were exclusively breast milk fed, and 48.9% were exclusively formula fed. After adjustment for potential confounders, infants who were plastic bottle fed less than every feeding compared to those who were plastic bottle fed at every feeding at 3 months did not show differences in anthropometry over the first 12 months of life, save for lower length-for-age z-score at 12 months (adjusted β = -0.45, 95% CI: -0.76, -0.13). Infants who were plastic bottle fed less than every feeding versus every feeding had lower fecal microbiota alpha diversity at 3 months (mean difference for Shannon index: -0.59, 95% CI: -0.99, -0.20) and lower isovaleric acid concentration at 3 months (mean difference: -2.12 μmol/g, 95% CI: -3.64, -0.60), but these results were attenuated following adjustment for infant diet. Plastic bottle frequency was not strongly associated with microbiota diversity or SCFAs at 12 months after multivariable adjustment. Frequency of plastic bottle use was associated with differential abundance of some bacterial taxa, however, significance was not consistent between statistical approaches.

CONCLUSIONS: Plastic bottle frequency at 3 months was not strongly associated with measures of adiposity or growth (save for length-for-age) over the first year of life, and while plastic bottle use was associated with some features of fecal microbiota and SCFAs in the first year, these findings were attenuated in multivariable models with infant diet. Future research is needed to assess health effects of exposure to other plastic-based products and objective measures of microplastics and plastic constituents like phthalates.

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless combined exposure index, which collapses census-tract level data into a single relative measure of exposure ranging from 0-1 (where higher values indicate higher exposure to hazards), includes indicators for major air pollutants and air toxics, features of the built environment, traffic exposures, and social determinants of health (e.g., lower educational attainment) drawn from existing data sources. We observed temporal and geographic variations in index values, with exposures being highest among participants living in the West and Northeast regions. Pregnant people who identified as Black or Hispanic (of any race) were at higher risk of living in a "high" exposure census tract (defined as an index value above 0.5) relative to those who identified as White or non-Hispanic. Index values were also higher for pregnant people with lower educational attainment. Several recommendations follow from our work, including that environmental and social stressor datasets with higher spatial and temporal resolutions are needed to ensure index-based tools fully capture the total environmental context.

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 the Boston Birth Cohort, which enrolled mother-child pairs from Boston, MA. We measured metals and trace elements in maternal red blood cells (RBCs) collected 24-72 h 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 670 mother-child pairs (57% non-Hispanic Black and 24% Hispanic). After Bonferroni correction, there were 25 cord metabolites associated with at least one of the metals or trace elements. 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). Se and Mn shared associations with 6 metabolites (in both directions), which mostly included nucleotides and amino acids; Se was additionally associated with 7 metabolites (mostly amino acids, nucleotides, and carnitines) and Mn was additionally associated with C36:4 hydroxy phosphatidylcholine. Restricted cubic spline plots showed that 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 risk of cardiometabolic diseases.