Publications

BACKGROUND: PFAS may impair bone health, but effects of PFAS exposure assessed during pregnancy and the perimenopause-life stages marked by rapidly changing bone metabolism-on later life bone health are unknown.

METHODS: We studied 531 women in the Boston-area Project Viva cohort. We used multivariable linear, generalized additive, and mixture models to examine associations of plasma PFAS concentrations during early pregnancy [median (IQR) maternal age 32.9 (6.2) years] and midlife [age 51.2 (6.3)] with lumbar spine, total hip, and femoral neck areal bone mineral density (aBMD) and bone turnover biomarkersassessed in midlife. We examined effect modification by diet and physical activity measured at the time of PFAS exposure assessment and by menopausal status in midlife.

RESULTS: Participants had higher PFAS concentrations during pregnancy [1999-2000; e.g., PFOA median (IQR) 5.4 (3.8) ng/mL] than in midlife [2017-2021; e.g.

, PFOA: 1.5 (1.2) ng/mL]. Women with higher PFOA, PFOS and PFNA during pregnancy had higher midlife aBMD, especially of the spine [e.g., 0.28 (95% CI: 0.07, 0.48) higher spine aBMD T-score, per doubling of PFOA], with stronger associations observed among those with higher diet quality. In contrast, higher concentrations of all PFAS measured in midlife were associated with lower concurrent aBMD at all sites [e.g., -0.21 (-0.35, -0.07) lower spine aBMD T-score, per doubling of PFOA]; associations were stronger among those who were postmenopausal. The associations of several PFAS with bone resorption (loss) were also stronger among postmenopausal versus premenopausal women.

DISCUSSION: Plasma PFAS measured during pregnancy versus in midlife had different associations with midlife aBMD. We found an adverse association of PFAS measured in midlife with midlife aBMD, particularly among postmenopausal women. Future studies with longer follow-up are needed to elucidate the effect of PFAS on bone health during the peri- and postmenopausal years.

IMPORTANCE: Fertility status is a marker for future health, and infertility has been associated with risk for later cancer and diabetes, but associations with midlife cardiovascular health (CVH) in female individuals remain understudied.

OBJECTIVE: To evaluate the association of infertility history with CVH at midlife (approximately age 50 years) among parous individuals.

DESIGN, SETTING, AND PARTICIPANTS: Project Viva is a prospective cohort study of pregnant participants enrolled between 1999 and 2002 who delivered a singleton live birth in the greater Boston, Massachusetts, area. Infertility history was collected at a midlife visit between 2017 and 2021, approximately 18 years after enrollment. Data analysis was performed from January to June 2023.

EXPOSURES: The primary exposure was any lifetime history of infertility identified by self-report, medical record, diagnosis, or claims for infertility treatment.

MAIN OUTCOMES AND MEASURES: The American Heart Association's Life's Essential 8 (LE8) is a construct for ranking CVH that includes scores from 0 to 100 (higher scores denote better health status) in 4 behavioral (diet, physical activity, sleep, and smoking status) and 4 biomedical (body mass index, blood pressure, blood lipids, and glycemia) domains to form an overall assessment of CVH. Associations of a history of infertility (yes or no) with mean LE8 total, behavioral, biomedical, and blood biomarker (lipids and glycemia) scores were examined, adjusting for age at outcome (midlife visit), race and ethnicity, education, household income, age at menarche, and perceived body size at age 10 years.

RESULTS: Of 468 included participants (mean [SD] age at the midlife visit, 50.6 [5.3] years) with exposure and outcome data, 160 (34.2%) experienced any infertility. Mean (SD) LE8 scores were 76.3 (12.2) overall, 76.5 (13.4) for the behavioral domain, 76.0 (17.5) for the biomedical domain, and 78.9 (19.2) for the blood biomarkers subdomain. In adjusted models, the estimated overall LE8 score at midlife was 2.94 points lower (95% CI, -5.13 to -0.74 points), the biomedical score was 4.07 points lower (95% CI, -7.33 to -0.78 points), and the blood subdomain score was 5.98 points lower (95% CI, -9.71 to -2.26 points) among those with vs without history of infertility. The point estimate also was lower for the behavioral domain score (β = -1.81; 95% CI, -4.28 to 0.66), although the result was not statistically significant.

CONCLUSIONS AND RELEVANCE: This cohort study of parous individuals found evidence for an association between a history of infertility and lower overall and biomedical CVH scores. Future study of enhanced cardiovascular preventive strategies among those who experience infertility is warranted.

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.

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.

BACKGROUND: Findings on the associations between prenatal PFAS exposures and offspring adiposity are inconsistent. Whether such associations may extend to adolescence is especially understudied.

OBJECTIVES: We investigated associations of prenatal PFAS exposures with offspring adiposity and body composition at 16-20 years of age.

METHODS: We studied 545 mother-child pairs in the prospective prebirth cohort Project Viva (Boston, Massachusetts). We measured six PFAS (PFOA, PFOS, PFNA, PFHxS, EtFOSAA, and MeFOSAA) in maternal early pregnancy (median age=9.6wk, range: 5.7-19.6 wk) plasma samples. At the late adolescence visit (median age=17.4 y, range: 15.9-20.0 y), we obtained anthropometric measures and assessed body composition using bioelectrical impedance analysis and dual-energy X-ray absorptiometry. We examined associations of individual PFAS with obesity [i.e., age- and sex-specific body mass index (BMI) ≥95th percentile] and adiposity and body composition using multivariable Poisson and linear regression models, respectively. We assessed PFAS mixture effects using Bayesian kernel machine regression (BKMR) and quantile g-computation. We used fractional-polynomial models to assess BMI trajectories (at 3-20 years of age) by prenatal PFAS levels.

RESULTS: Thirteen percent (n=73) of the children had obesity in late adolescence. After multivariable adjustment, higher prenatal PFAS concentrations were associated with higher obesity risk [e.g., 1.59 (95% CI: 1.19, 2.12), 1.24 (95% CI: 0.98, 1.57), and 1.49 (95% CI: 1.11, 1.99) times the obesity risk per doubling of PFOS, PFOA, and PFNA, respectively]. BKMR showed an interaction between PFOA and PFOS, where the positive association between PFOS and obesity was stronger when PFOA levels were lower. Each quartile increment of the PFAS mixture was associated with 1.52 (95% CI: 1.03, 2.25) times the obesity risk and 0.52 (95% CI: -0.02, 1.06) kg/m2 higher BMI. Children with higher prenatal PFOS, EtFOSAA, and MeFOSAA concentrations had higher rates of BMI increase starting from 9-11 years of age.

DISCUSSION: Prenatal PFAS exposures may have obesogenic effects into late adolescence. https://doi.org/10.1289/EHP12597.