Project description:ObjectivesTo examine the relation between prenatal urinary phthalate metabolite concentrations and preterm birth (PTB).MethodsThe data were drawn from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1857 pregnant women enrolled between 2008 and 2011. We quantified urinary concentrations of 7 phthalate metabolites that were detected in > 70% of urine samples collected during the first trimester. Gestational age was obtained from either the last menstrual period or early ultrasound. We used Cox proportional hazard models to examine the associations of urinary phthalate metabolite concentrations, plus the molar sum of di-2-ethylhexyl phthalate metabolites (∑DEHP), with time to delivery before 37 weeks of gestation. We also examined PTB by clinical presentation. PTBs presented with either spontaneous labour or premature rupture of the membrane were considered spontaneous PTB (sPTB). Additionally, we used multiple linear regression to model changes in mean gestational age in relation to phthalate exposure.ResultsWe found no evidence of an association between first trimester phthalate metabolite concentrations and PTB among the MIREC study participants. For example, each 2-fold increase in any of the 7 phthalate concentrations or ∑DEHP was associated with hazard ratios (HRs) for PTB ranging from 0.95 to 1.07 with 95% confidence intervals including the null. An assessment of non-linear trends showed some evidence of non-monotonic dose-response relationships between phthalates and PTB. Furthermore, male infants exposed to MCPP showed higher sPTB risk compared with female infants.ConclusionPhthalate exposure during early pregnancy is not clearly associated with the risk of PTB among this Canadian population.
Project description:Prenatal cadmium exposure at non-occupational levels has been associated with poor birth outcomes. The intake of essential metals, such as iron and selenium, may mitigate cadmium exposure effects. However, at high levels, these metals can be toxic. The role of dietary patterns rich in these metals is less studied. We used a linear and logistic regression in a cohort of 185 mother-infant pairs to assess if a Mediterranean diet pattern during pregnancy modified the associations between prenatal cadmium exposure and (1) birth weight and (2) preterm birth. We found that increased cadmium exposure during pregnancy was associated with lower birth weight (β = -210.4; 95% CI: -332.0, -88.8; p = 0.008) and preterm birth (OR = 0.11; 95% CI: 0.01, 0.72; p = 0.04); however, these associations were comparable in offspring born to women reporting high adherence to a Mediterranean diet (β = -274.95; 95% CI: -701.17, 151.26; p = 0.20) and those with low adherence (β = -64.76; 95% CI: -359.90, 230.37; p = 0.66). While the small sample size limits inference, our findings suggest that adherence to a Mediterranean dietary pattern may not mitigate cadmium exposure effects. Given the multiple organs targeted by cadmium and its slow excretion rate, larger studies are required to clarify these findings.
Project description:BackgroundPerfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are used in consumer products for their water repellent and flame retardant properties, respectively. However, there is widespread prenatal exposure and concern about their potential harm to the developing fetus. Here, we utilized data from a demographically diverse cohort of women in San Francisco, CA to examine associations between prenatal exposure to PFAS and PBDEs with gestational age and birth weight for gestational age z-scores.MethodsWomen included in this analysis were enrolled in the Chemicals in our Bodies (CIOB) cohort study (N = 506). PFAS and PBDEs were measured in serum obtained during the second trimester of pregnancy. Linear regression models were used to calculate crude and adjusted β coefficients for the association between PFAS and PBDE concentrations in tertiles and gestational age and birth weight z-scores. Individual PFAS and PBDE concentrations, as well as their sums, were examined in separate models.ResultsThe highest compared to lowest tertile of BDE-47 was associated with shorter gestational age (β = - 0.49, 95% confidence interval [CI] = - 0.95, - 0.02). Additionally, exposure to BDE-47 and BDE-99 in the middle tertile was also associated with a reduction in birth weight z-scores (β = - 0.26, 95% CI = -0.48, - 0.04; β = - 0.25, 95% CI = -0.47, - 0.04, respectively) compared to those in the lowest tertile of exposure. No consistent associations were observed between increasing PFAS concentrations and gestational age or birth weight z-scores.DiscussionAmong a diverse group of pregnant women in the San Francisco Bay Area, we found non-linear associations between prenatal exposure to PBDEs during the second trimester of pregnancy and birth weight z-scores. However, most PFAS congeners were not associated with adverse birth outcomes. PFAS and PBDE concentrations were lower in our cohort relative to other studies. Future research should assess the effects of emerging and persistent PFAS and PBDEs on birth outcomes, as some congeners are being phased out and replaced by chemically similar structures.
Project description:BackgroundPreterm birth is a disease of multifactorial etiologies that has environmental, social, and maternal health components. Individual studies have shown that exposure to arsenic contaminated drinking water, child marriage, and low maternal weight gain during pregnancy contribute to preterm birth. These factors are highly prevalent and often co-exist in Bangladesh, a country in South Asia with one of the world's highest prevalences of preterm birth.ObjectiveTo evaluate the individual and interactive effects of prenatal arsenic exposure, child marriage, and pregnancy weight gain on preterm birth in a prospective birth cohort in Bangladesh.MethodsDuring 2008-2011, we recruited 1613 pregnant women aged ≥18years at ≤16weeks of gestation and followed them until 1-month post-partum. We measured total arsenic in drinking water (n=1184) and in maternal toenails (n=1115) collected at enrollment and ≤1-month post-partum, respectively using inductively coupled plasma mass spectrometry. Child marriage (<18years old) was defined using self-report, and 2nd and 3rd trimester pregnancy weight gain was calculated using monthly records. Gestational age was determined at enrollment by ultrasound.ResultsIn multivariate adjusted Poisson regression models, the risk ratios (RR) for preterm birth were 1.12 (95% CI: 1.07-1.18) for a unit change in natural log water arsenic exposure, 2.28 (95% CI: 1.76-2.95) for child marriage, and 0.64 (95% CI: 0.42-0.97) for a pound per week increase in maternal weight during the 2nd and 3rd trimesters. In stratified analysis by child marriage, pregnancy weight gain was inversely associated with preterm birth among women with a history of child marriage (RR=0.58; 95% CI: 0.37-0.92), but not among women with no history of child marriage (RR=86; 95% CI: 0.37-2.01). Mediation analysis revealed that both arsenic exposure and child marriage had small but significant associations with preterm birth via lowering pregnancy weight gain. Similar associations were observed when arsenic exposure was assessed using maternal toenail arsenic concentrations.ConclusionsReducing arsenic exposure and ending child marriage could reduce the risk of preterm birth in Bangladesh. Furthermore, enhancing nutritional support to ensure adequate weight gain during pregnancy may provide additional benefits especially for women with a history of child marriage.
Project description:BackgroundPerfluoroalkylated substances (PFAS) are man-made, persistent organic compounds with immune-modulating potentials. Given that pregnancy itself represents an altered state of immunity, PFAS exposure-related immunotoxicity is an important environmental factor to consider in SARS-CoV-2 infection during pregnancy as it may further affect humoral immune responses.AimTo investigate the relationship between maternal plasma PFAS concentrations and SARS-CoV-2 antibody levels in a NYC-based pregnancy cohort.MethodsMaternal plasma was collected from 72 SARS-CoV-2 IgG + participants of the Generation C Study, a birth cohort established at the beginning of the COVID-19 pandemic in New York City. Maternal SARS-CoV-2 anti-spike IgG antibody levels were measured using ELISA. A panel of 16 PFAS congeners were measured in maternal plasma using a targeted UHPLC-MS/MS-based assay. Spearman correlations and linear regressions were employed to explore associations between maternal IgG antibody levels and plasma PFAS concentrations. Weighted quantile sum (WQS) regression was also used to evaluate mixture effects of PFAS. Models were adjusted for maternal age, gestational age at which SARS-CoV-2 IgG titer was measured, COVID-19 vaccination status prior to IgG titer measurement, maternal race/ethnicity, parity, type of insurance and pre-pregnancy BMI.ResultsOur study population is ethnically diverse with an average maternal age of 32 years. Of the 16 PFAS congeners measured, nine were detected in more than 60% samples. Importantly, all nine congeners were negatively correlated with SARS-CoV-2 anti-spike IgG antibody levels; n-PFOA and PFHxS, PFHpS, and PFHxA reached statistical significance (p < 0.05) in multivariable analyses. When we examined the mixture effects using WQS, a quartile increase in the PFAS mixture-index was significantly associated with lower maternal IgG antibody titers (beta [95% CI] = -0.35 [-0.52, -0.17]). PFHxA was the top contributor to the overall mixture effect.ConclusionsOur study results support the notion that PFAS, including short-chain emerging PFAS, act as immunosuppressants during pregnancy. Whether such compromised immune activity leads to downstream health effects, such as the severity of COVID-19 symptoms, adverse obstetric outcomes or neonatal immune responses remains to be investigated.
Project description:Infants whose mothers experience greater psychosocial stress and environmental chemical exposures during pregnancy may face greater rates of preterm birth, lower birth weight, and impaired neurodevelopment. ECHO.CA.IL is composed of two cohorts, Chemicals in Our Bodies (CIOB; n = 822 pregnant women and n = 286 infants) and Illinois Kids Development Study (IKIDS; n = 565 mother-infant pairs), which recruit pregnant women from San Francisco, CA and Urbana-Champaign, IL, respectively. We examined associations between demographic characteristics and gestational age, birth weight z-scores, and cognition at 7.5 months across these two cohorts using linear models. We also examined differences in biomarkers of exposure to per- and polyfluoroalkyl substances (PFAS), measured in second-trimester serum, and psychosocial stressors by cohort and participant demographics. To date, these cohorts have recruited over 1300 pregnant women combined. IKIDS has mothers who are majority white (80%), whereas CIOB mothers are racially and ethnically diverse (38% white, 34% Hispanic, 17% Asian/Pacific Islander). Compared to CIOB, median levels of PFOS, a specific PFAS congener, are higher in IKIDS (2.45 ng/mL versus 1.94 ng/mL), while psychosocial stressors are higher among CIOB. Across both cohorts, women who were non-white and single had lower birth weight z-scores relative to white women and married women, respectively. Demographic characteristics are not associated with cognitive outcomes at 7.5 months. This profile of the ECHO.CA.IL cohort found that mothers and their infants who vary in terms of socioeconomic status, race/ethnicity, and geographic location are similar in many of our measures of exposures and cognitive outcomes. Similar to past work, we found that non-white and single women had lower birth weight infants than white and married women. We also found differences in levels of PFOS and psychosocial stressors based on geographic location.
Project description:Environmental phenols and parabens are commonly used in personal care products and other consumer products and human exposure to these chemicals is widespread. Although human and animal studies suggest an association between exposure to phenols and parabens and thyroid hormone levels, few studies have investigated the association of in utero exposure to these chemicals and thyroid hormones in pregnant women and their neonates. We measured four environmental phenols (triclosan, benzophenone-3, and 2,4- and 2,5-dichlorophenol), and three parabens (methyl-, propyl-, and butyl paraben) in urine collected from mothers at two time points during pregnancy as part of the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in serum of the pregnant women (N = 454) and TSH in their neonates (N = 365). We examined potential confounding by a large number of additional chemical exposures and used Bayesian Model Averaging (BMA) to select the most influential chemicals to include in regression models. We observed negative associations of prenatal urinary concentrations of propyl paraben and maternal TSH (β for two-fold increase = -3.26%, 95% CI: -5.55, -0.90) and negative associations of 2,4-dichlorophenol and maternal free T4 (β for two-fold increase = -0.05, 95% CI: -0.08, -0.02), after controlling for other chemical exposures. We observed negative associations of triclosan with maternal total T4 after controlling for demographic variables, but this association became non-significant after controlling for other chemicals (β for two-fold increase = -0.05, 95% CI: -0.11, 0.00). We found evidence that environmental phenols and parabens are associated with lower TSH and free T4 in pregnant women after controlling for related chemical exposures.
Project description:ImportancePhthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.ObjectiveTo investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US.Design, setting, and participantsIndividual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included.ExposuresUrinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated.Main outcomes and measuresLogistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth.ResultsThe final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively.Conclusions and relevanceResults from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.
Project description:BackgroundPer- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals widely used in consumer and industrial products. Numerous studies have linked prenatal PFAS exposures to increased risks of adverse pregnancy outcomes such as preterm birth (PTB) and small-for-gestational age (SGA).However, limited evidence is available for the effects of PFAS on PTB subtypes and large-for-gestational age (LGA).ObjectiveTo examine the associations of PFAS with PTB [overall, placental (pPTB), spontaneous (sPTB)], BW Z-score, and size-for-gestational age (SGA, LGA).MethodsOur nested case-control study included 128 preterm cases and 373 term controls from the LIFECODES cohort between 2006 and 2008 (n = 501). Plasma concentrations of nine PFAS were measured in early pregnancy samples. Logistic regression was used to assess individual PFAS-birth outcome associations, while Bayesian Kernel Machine Regression (BKMR) was used to evaluate the joint effects of all PFAS. Effect modification by fetal sex was examined, and stratified analyses were conducted to obtain fetal sex-specific estimates.ResultsCompared to term births, the odds of pPTB were higher from an interquartile range increase in perfluorodecanoic acid (PFDA) (OR = 1.60, 95% CI: 1.00-2.56), perfluorononanoic acid (PFNA) (OR = 1.67, 95% CI: 1.06-2.61), and perfluoroundecanoic acid (PFUA) (OR = 1.77, 95% CI: 1.00-3.12), with stronger associations observed in women who delivered males. BKMR analysis identified PFNA as the most important PFAS responsible for pPTB (conditional PIP = 0.78), with increasing ORs at higher percentiles of PFAS mixture. For LGA, positive associations were observed with PFDA and perfluorooctanoic acid in females only, and with PFUA in males only. BKMR analysis showed increasing, but null effects of PFAS mixture on LGA.ConclusionsThe effect of prenatal exposure to single and multiple PFAS on PTB and LGA depended on fetal sex. Future studies should strongly consider examining PTB subtypes and sex-specific effects of PFAS on pregnancy outcomes.
Project description:BackgroundPhenol exposure during pregnancy has been associated with preterm birth, but the potential effect of preconception exposure in either parent is unknown. There is a growing body of evidence to suggest that the preconception period is a critical window of vulnerability for adverse pregnancy outcomes.ObjectiveWe examined whether maternal and paternal preconception urinary concentrations of select phenols were associated with the risk of preterm birth among couples attending fertility care.MethodsThe analysis included 417 female and 229 male participants of the Environment and Reproductive Health (EARTH) Study who gave birth to 418 singleton infants between 2005 and 2018 and for whom we had phenol biomarkers quantified in at least one urine sample collected before conception. Mothers and fathers provided an average of 4 and 3 urine samples during the preconception period, respectively. We calculated the geometric mean of bisphenol A (BPA), bisphenol S (BPS), benzophenone-3, triclosan, and the molar sum of parabens (ΣParabens) urinary concentrations to estimate each participant's preconception exposure. Risk ratios (RRs) of preterm birth (live birth before 37 completed weeks' gestation) were estimated using modified Poisson regression models adjusted for covariates.ResultsThe mean (SD) gestational age among singletons was 39.3 (1.7) weeks with 8% born preterm. A natural log-unit increase in maternal preconception BPA (RR 1.94; 95% CI: 1.20, 3.14) and BPS (RR 2.42; 95% CI: 1.01, 5.77) concentration was associated with an increased risk of preterm birth. These associations remained after further adjustment for maternal prenatal and paternal preconception biomarker concentrations. Paternal preconception ΣParabens concentrations showed a possible elevated risk of preterm birth (RR 1.36; 95% CI: 0.94, 1.96). No consistent pattern of association was observed for benzophenone-3 or triclosan biomarkers in either parent.DiscussionMaternal preconception urinary BPA and BPS concentrations, as well as paternal preconception urinary parabens concentrations were prospectively associated with a higher risk of preterm birth. Subfertile couples' exposure to select phenols during the preconception period may be an unrecognized risk factor for adverse pregnancy outcomes.