Correction: Racial and geographic variation in effects of maternal education and neighborhood-level measures of socioeconomic status on gestational age at birth: Findings from the ECHO cohorts.

[This corrects the article DOI: 10.1371/journal.pone.0245064.].

Racial and geographic variation in effects of maternal education and neighborhood-level measures of socioeconomic status on gestational age at birth: Findings from the ECHO cohorts.

Preterm birth occurs at excessively high and disparate rates in the United States. In 2016, the National Institutes of Health (NIH) launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate the influence of early life exposures on child health. Extant data from the ECHO cohorts provides the opportunity to examine racial and geographic variation in effects of individual- and neighborhood-level markers of socioeconomic status (SES) on gestational age at birth. The objective of this study was to examine the association between individual-level (maternal education) and neighborhood-level markers of SES and gestational age at birth, stratifying by maternal race/ethnicity, and whether any such associations are modified by US geographic region. Twenty-six ECHO cohorts representing 25,526 mother-infant pairs contributed to this disseminated meta-analysis that investigated the effect of maternal prenatal level of education (high school diploma, GED, or less; some college, associate's degree, vocational or technical training [reference category]; bachelor's degree, graduate school, or professional degree) and neighborhood-level markers of SES (census tract [CT] urbanicity, percentage of black population in CT, percentage of population below the federal poverty level in CT) on gestational age at birth (categorized as preterm, early term, full term [the reference category], late, and post term) according to maternal race/ethnicity and US region. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Cohort-specific results were meta-analyzed using a random effects model. For women overall, a bachelor's degree or above, compared with some college, was associated with a significantly decreased odds of preterm birth (aOR 0.72; 95% CI: 0.61-0.86), whereas a high school education or less was associated with an increased odds of early term birth (aOR 1.10, 95% CI: 1.00-1.21). When stratifying by maternal race/ethnicity, there were no significant associations between maternal education and gestational age at birth among women of racial/ethnic groups other than non-Hispanic white. Among non-Hispanic white women, a bachelor's degree or above was likewise associated with a significantly decreased odds of preterm birth (aOR 0.74 (95% CI: 0.58, 0.94) as well as a decreased odds of early term birth (aOR 0.84 (95% CI: 0.74, 0.95). The association between maternal education and gestational age at birth varied according to US region, with higher levels of maternal education associated with a significantly decreased odds of preterm birth in the Midwest and South but not in the Northeast and West. Non-Hispanic white women residing in rural compared to urban CTs had an increased odds of preterm birth; the ability to detect associations between neighborhood-level measures of SES and gestational age for other race/ethnic groups was limited due to small sample sizes within select strata. Interventions that promote higher educational attainment among women of reproductive age could contribute to a reduction in preterm birth, particularly in the US South and Midwest. Further individual-level analyses engaging a diverse set of cohorts are needed to disentangle the complex interrelationships among maternal education, neighborhood-level factors, exposures across the life course, and gestational age at birth outcomes by maternal race/ethnicity and US geography.

Prenatal Exposure to PM2.5 and Cardiac Vagal Tone during Infancy: Findings from a Multiethnic Birth Cohort.

BACKGROUND: The autonomic nervous system plays a key role in maintaining homeostasis and responding to external stimuli. In adults, exposure to fine particulate matter (PM2.5) has been associated with reduced heart rate variability (HRV), an indicator of cardiac autonomic control. OBJECTIVES: Our goal was to investigate the associations of exposure to fine particulate matter (PM2.5) with HRV as an indicator of cardiac autonomic control during early development. METHODS: We studied 237 maternal-infant pairs in a Boston-based birth cohort. We estimated daily residential PM2.5 using satellite data in combination with land-use regression predictors. In infants at 6 months of age, we measured parasympathetic nervous system (PNS) activity using continuous electrocardiogram monitoring during the Repeated Still-Face Paradigm, an experimental protocol designed to elicit autonomic reactivity in response to maternal interaction and disengagement. We used multivariable linear regression to examine average PM2.5 exposure across pregnancy in relation to PNS withdrawal and activation, indexed by changes in respiration-corrected respiratory sinus arrhythmia (RSAc)-an established metric of HRV that reflects cardiac vagal tone. We examined interactions with infant sex using cross-product terms. RESULTS: In adjusted models we found that a 1-unit increase in PM2.5 (in micrograms per cubic meter) was associated with a 3.53% decrease in baseline RSAc (95% CI: -6.96, 0.02). In models examining RSAc change between episodes, higher PM2.5 was generally associated with reduced PNS withdrawal during stress and reduced PNS activation during recovery; however, these associations were not statistically significant. We did not observe a significant interaction between PM2.5 and sex. DISCUSSION: Prenatal exposure to PM2.5 may disrupt cardiac vagal tone during infancy. Future research is needed to replicate these preliminary findings. https://doi.org/10.1289/EHP4434.

Antenatal active maternal asthma and other atopic disorders is associated with ADHD behaviors among school-aged children.

BACKGROUND: Identifying modifiable risk factors for neuropsychological correlates of attention deficit hyperactivity disorder (ADHD) in early childhood can inform prevention strategies. Prenatal inflammatory states, such as maternal asthma and other atopic disorders, have been increasingly linked to enhanced risk for neurobehavioral disorders in children, with some studies suggesting sex-specific effects. OBJECTIVES: To assess the association between maternal active asthma and/or atopy in the antenatal period and child symptoms of ADHD during mid-childhood and, given the male-bias in ADHD prevalence, to examine modifying effects of child sex. STUDY DESIGN: The study sample includes 250 maternal-child pairs enrolled in the Boston-based Asthma Coalition on Community, Environment and Social Stress (ACCESS) pregnancy cohort. We defined antenatal active atopy based on maternal report of current asthma, allergic rhinitis or atopic dermatitis during and/or in the year before pregnancy. When children were approximately 6 years old, mothers completed a battery of standardized child behavior rating scales designed for evaluating symptoms of ADHD. We used multivariable quantile regression to assess the relations between maternal antenatal atopy and symptoms of ADHD among children. RESULTS: In adjusted models, maternal atopy was significantly associated with greater risk for ADHD behaviors, as indicated by scores on the Conners' Parent Rating Scale-Revised ADHD index (ß = 3.32, 95% CI: 0.33, 6.32). In sex-stratified models this association was stronger among girls (5.96, 95% CI = 0.95, 10.96) compared to boys (-2.14, 95% CI = -5.75, 1.45, p-interaction = 0.01). Among girls, we observed a similar finding for the Behavior Assessment System for Children 2nd Edition Parent Rating Scale Attention Problems subscale (ß = 7.77, 95% CI = 1.57, 13.97). Results from other outcome subscales were similar in magnitude and direction, however, associations did not reach statistical significance at the p = 0.05 level. CONCLUSIONS: Maternal antenatal active atopy may be a risk factor for the development of ADHD-like symptoms, especially among girls.

Pre- and Postnatal Polybrominated Diphenyl Ether Concentrations in Relation to Thyroid Parameters Measured During Early Childhood.

Background: Penta-brominated diphenyl ethers (PentaBDEs) are endocrine-disrupting chemicals that structurally resemble thyroid hormones and were widely used as flame retardants in household consumer products from 1975 to 2004. Polybrominated diphenyl ethers (PBDEs) cross the placenta, and evidence suggests that for many children, body burdens may peak during the toddler years. This study aimed to understand the impact of exposure timing by examining both pre- and postnatal exposure to BDE-47, the predominant penta-brominated diphenyl ether congener detected in humans, in relation to thyroid hormone parameters measured during early childhood. Methods: The Columbia Center for Children's Environmental Health Mothers and Newborns Study is a prospective birth cohort of African American and Dominican maternal-child pairs. Pregnant women were recruited from two prenatal clinics in Northern Manhattan and the South Bronx between 1998 and 2006. Participants included 158 children with (i) plasma PBDE concentrations measured at birth and in the toddler years (age 2-3 years), and (ii) serum thyroid parameters measured at three and/or five years of age. Outcomes included concentrations of serum thyrotropin, free thyroxine, and total thyroxine. Results: Children with high exposure to BDE-47 during the prenatal period (-17% [confidence interval -29 to -2]) or toddler age (-19% [confidence interval -31 to -5]) had significantly lower geometric mean thyrotropin levels compared to children with low BDE-47 exposure throughout early life. Associations with thyroxine were also inverse; however, they did not reach statistical significance at the p = 0.05 level. Sex-stratified models suggest associations with postnatal exposure may be stronger among boys compared to girls. Conclusions: The thyroid regulatory system may be sensitive to BDE-47 during pre- and postnatal periods.

Temporal trends and developmental patterns of plasma polybrominated diphenyl ether concentrations over a 15-year period between 1998 and 2013.

Polybrominated diphenyl ethers (PBDEs) were used extensively as flame retardants in furniture containing polyurethane foam until they were phased out of use, beginning in 2004. We examined temporal changes in plasma PBDE concentrations from 1998 to 2013 and characterized patterns of exposure over the early lifecourse among 334 children (903 samples) between birth and 9 years. We examined time trends by regressing PBDE concentration on year of sample collection in age-adjusted models and characterized developmental trajectories using latent class growth analysis (LCGA). Controlling for age, BDE-47 concentrations decreased 5% (95% confidence interval (CI): -9, -2) per year between 1998 and 2013. When considering only postnatal samples, this reduction strengthened to 13% (95% CI: -19, -9). Findings for BDE-99, 100 and 153 were similar, except that BDE-153 decreased to a lesser extent when both prenatal and postnatal samples were considered (-2%, 95% CI: -7, 0). These findings suggest that, on average, pentaBDE body burdens have decreased since the 2004 phase-out of these chemicals. When examining developmental period, PBDE concentrations peaked during toddler years for the majority of children, however, our observation of several unique trajectories suggests that a single measure may not accurately reflect exposure to PBDEs throughout early life.

Associations between prenatal and childhood PBDE exposure and early adolescent visual, verbal and working memory.

BACKGROUND: Prenatal and childhood exposure to polybrominated diphenyl ether (PBDE) flame retardants has been inversely associated with cognitive performance, however, few studies have measured PBDE concentrations in samples collected during both prenatal and postnatal periods. METHODS: We examined prenatal (cord) and childhood (ages 2, 3, 5, 7 and 9 years) plasma PBDE concentrations in relation to memory outcomes assessed between the ages of 9 and 14 years. The study sample includes a subset (n = 212) of the African American and Dominican children enrolled in the Columbia Center for Children's Environmental Health Mothers and Newborns birth cohort. We used multivariable linear regression to examine associations between continuous log10-transformed PBDE concentrations and performance on tests of visual, verbal and working memory in age-stratified models. We additionally used latent class growth analysis to estimate trajectories of exposure across early life, which we analyzed as a categorical variable in relation to memory outcomes. We examined interactions between PBDE exposure and sex using cross-product terms. RESULTS: Associations between prenatal exposure and working memory significantly varied by sex (p-interaction = 0.02), with inverse relations observed only among girls (i.e. ßBDE-47 = -7.55, 95% CI: -13.84, -1.24). Children with sustained high concentrations of BDEs-47, 99 or 100 across childhood scored approximately 5-8 standard score points lower on tests of visual memory. Children with PBDE plasma concentrations that peaked during toddler years performed better on verbal domains, however, these associations were not statistically significant. CONCLUSIONS: Exposure to PBDEs during both prenatal and postnatal periods may disrupt memory domains in early adolescence. These findings contribute to a substantial body of evidence supporting the developmental neurotoxicity of PBDEs and underscore the need to reduce exposure among pregnant women and children.

Determinants of prenatal exposure to polybrominated diphenyl ethers (PBDEs) among urban, minority infants born between 1998 and 2006.

Polybrominated diphenyl ethers (PBDEs) are environmentally persistent chemicals that structurally resemble legacy pollutants, such as polychlorinated biphenyls (PCBs). PBDEs were added to consumer products for over 30 years, before being phased out due to evidence of toxicity. We examined temporal changes in prenatal exposure to PBDEs, as well as other sources of variation. We measured PBDEs in umbilical cord plasma from 327 minority infants born in New York City between 1998 and 2006. We used linear regression to examine changes in concentrations over time and in relation to lifestyle characteristics collected during pregnancy. We detected BDE-47 in 80% of samples with a geometric mean concentration of 14.1 ng/g lipid. Ethnicity was the major determinant of PBDE exposure; African American infants had 58% higher geometric mean cord plasma concentrations of BDE-47 (p < 0.01) compared to Dominican infants. Notably, African American mothers were more likely to be born in the United States, which itself was associated with 40% (p < 0.01) higher concentrations. We observed small decreases in PBDE concentrations by date of birth and no difference before and after their phase-out in 2004. Final multivariable models explained 8-12% of variability in PBDE concentrations depending on the congener. Our finding that prenatal exposure to PBDEs decreased only modestly between 1998 and 2006 is consistent with the persistent properties of PBDEs and their ongoing release from existing consumer products.

Impact of housing instability on child behavior at age 7.

Housing instability is a thought to be a major influence on children's healthy growth and development. However, little is known about the factors that influence housing instability, limiting the identification of effective interventions. The goals of this study were to 1) explore factors, including material hardship, satisfaction with living conditions and housing disrepair, that predict housing instability (total number of moves that a child experienced in the first seven years); and 2) examine the relationship between housing instability and child behavior at age 7, measured by the Child Behavior Checklist. We analyzed these associations among children enrolled in the Columbia Center for Children's Environmental Health (CCCEH) Mothers and Newborns study. In our analysis, we found that housing disrepair predicted residential change after 3 years of age, but not before. Persistent material hardship over the seven-year time period from pregnancy through age 7 was associated with increased number of moves. Children who experienced more than three moves in the first 7 years had significantly more thought- and attention-related problems compared to children who experienced less than 3 moves over the same time period. Children who experienced more than 3 moves also had higher total and internalizing problem behavior scores, although these differences were not statistically significant. We conclude that housing instability is significantly associated with problem behavior in early childhood and that interventions to reduce socioeconomic strain may have the greatest impact in breaking the cycle of children's environmental health disparities related to housing instability.

Prevalence of historical and replacement brominated flame retardant chemicals in New York City homes.

BACKGROUND: Until their phase-out between 2005 and 2013, polybrominated diphenyl ethers (PBDEs) were added to household products including furniture, rugs, and electronics to meet flammability standards. Replacement brominated flame retardant (BFR) chemicals, including 2-ethylhexyl-2,3,4,5 tetrabromobenzoate (TBB) and bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH), which are components of the Firemaster 550® commercial mixture, are now being used to meet some flammability standards in furniture. The objective of this analysis was to evaluate the extent to which mothers and their children living in New York City are exposed to PBDEs, TBB, and TBPH. METHODS: We measured PBDEs, TBB, and TBPH using gas chromatography mass spectrometry in dust (n = 25) and handwipe (n = 11) samples collected between 2012 and 2013 from mothers and children living in New York City. We defined dust as enriched if the proportional distribution for a given BFR exceeded two-thirds of the total BFR content. RESULTS: We detected PBDEs and TBPH in 100% of dust and handwipe samples and TBB in 100% of dust samples and 95% of handwipe samples. Dust from approximately two-thirds of households was enriched for either PBDEs (n = 9) or for TBB + TBPH (n = 8). Overall, the median house dust concentration of TBB + TBPH (1318 ng/g dust) was higher than that of ΣPentaBDE (802 ng/g dust) and BDE-209 (1171 ng/g dust). Children generally had higher BFR handwipe concentrations compared to mothers (ΣPentaBDE: 73%, BDE-209: 64%, TBB + TBPH: 55%) and within households, BFR concentrations from paired maternal-child handwipes were highly correlated. Among mothers, we found a significant positive relation between house dust and handwipe BDE-209 and TBB + TBPH concentrations. CONCLUSION: PBDEs, TBB and TBPH are ubiquitous in house dust and handwipes in a sample of mother-child pairs residing in New York City.

Sex-Specific Effects of Combined Exposure to Chemical and Non-chemical Stressors on Neuroendocrine Development: a Review of Recent Findings and Putative Mechanisms.

PURPOSE OF REVIEW: Environmental toxicants and psychosocial stressors share many biological substrates and influence overlapping physiological pathways. Increasing evidence indicates stress-induced changes to the maternal milieu may prime rapidly developing physiological systems for disruption by concurrent or subsequent exposure to environmental chemicals. In this review, we highlight putative mechanisms underlying sex-specific susceptibility of the developing neuroendocrine system to the joint effects of stress or stress correlates and environmental toxicants (bisphenol A, alcohol, phthalates, lead, chlorpyrifos, and traffic-related air pollution). RECENT FINDINGS: We provide evidence indicating that concurrent or tandem exposure to chemical and non-chemical stressors during windows of rapid development is associated with sex-specific synergistic, potentiated and reversed effects on several neuroendocrine endpoints related to hypothalamic-pituitary-adrenal axis function, sex steroid levels, neurotransmitter circuits, and innate immune function. We additionally identify gaps, such as the role that the endocrine-active placenta plays, in our understanding of these complex interactions. Finally, we discuss future research needs, including the investigation of non-hormonal biomarkers of stress. We demonstrate multiple physiologic systems are impacted by joint exposure to chemical and non-chemical stressors differentially among males and females. Collectively, the results highlight the importance of evaluating sex-specific endpoints when investigating the neuroendocrine system and underscore the need to examine exposure to chemical toxicants within the context of the social environment.

Associations between Prenatal Exposure to Black Carbon and Memory Domains in Urban Children: Modification by Sex and Prenatal Stress.

BACKGROUND: Whether fetal neurodevelopment is disrupted by traffic-related air pollution is uncertain. Animal studies suggest that chemical and non-chemical stressors interact to impact neurodevelopment, and that this association is further modified by sex. OBJECTIVES: To examine associations between prenatal traffic-related black carbon exposure, prenatal stress, and sex with children's memory and learning. METHODS: Analyses included N = 258 mother-child dyads enrolled in a Boston, Massachusetts pregnancy cohort. Black carbon exposure was estimated using a validated spatiotemporal land-use regression model. Prenatal stress was measured using the Crisis in Family Systems-Revised survey of negative life events. The Wide Range Assessment of Memory and Learning (WRAML2) was administered at age 6 years; outcomes included the General Memory Index and its component indices [Verbal, Visual, and Attention Concentration]. Relationships between black carbon and WRAML2 index scores were examined using multivariable-adjusted linear regression including effect modification by stress and sex. RESULTS: Mothers were primarily minorities (60% Hispanic, 26% Black); 67% had ≤12 years of education. The main effect for black carbon was not significant for any WRAML2 index; however, in stratified analyses, among boys with high exposure to prenatal stress, Attention Concentration Index scores were on average 9.5 points lower for those with high compared to low prenatal black carbon exposure (P3-way interaction = 0.04). CONCLUSION: The associations between prenatal exposure to black carbon and stress with children's memory scores were stronger in boys than in girls. Studies assessing complex interactions may more fully characterize health risks and, in particular, identify vulnerable subgroups.

Prenatal exposure to polybrominated diphenyl ethers and child attention problems at 3-7 years.

INTRODUCTION: Polybrominated diphenyl ethers (PBDEs) comprise a class of halogenated compounds used extensively as flame retardant chemicals in consumer products resulting in nearly ubiquitous human exposure. Mounting evidence suggests that PBDEs are developmental neurotoxicants; however, associations between early life exposure and child behavior have been largely limited to a single developmental time point. METHODS: The study population consists primarily of white, black and Chinese women who were pregnant on 11 September 2001 and delivered at 1 of 3 downtown New York City hospitals. Maternal-child pairs were followed through age 7 years. Cord blood was collected at delivery and PBDE plasma levels for 210 samples were analyzed by the U.S. Centers for Disease Control and Prevention. The Child Behavior Checklist, a validated maternal-report instrument used for assessing child behavior, was administered annually between the ages of 3 and 7 years. We analyzed the association between natural log-transformed and dichotomized (low vs. high) PBDEs and attention problems using multivariable adjusted negative binomial regression. RESULTS: We detected 4 PBDE congeners in more than 50% of samples, with concentrations highest for BDE-47 (median±IQR: 11.2±19.6 ng/g). In adjusted analyses, we detected associations between BDE-47 (1.21, 95% CI: 1.00, 1.47), and BDE-153 (1.18, 95% CI: 1.00, 1.39) in cord plasma and increased attention problems among children at age 4 (n=109) but not 6 (n=107) years. CONCLUSIONS: Our findings demonstrate a positive trend between prenatal PBDE exposure and early childhood attention problems, and are consistent with previous research reporting associations between prenatal PBDE exposure and disrupted child behaviors.