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Published in final edited form as: Environ Res. 2022 Nov 15;216(Pt 4):114830. doi: 10.1016/j.envres.2022.114830

Prenatal Exposure to Polybrominated Diphenyl Ethers and Birth Outcomes

Aalekhya Reddam 1,*, Andreas Sjödin 2, Whitney Cowell 3, Richard Jones 2, Shuang Wang 4, Frederica Perera 1, Julie B Herbstman 1, Allison Kupsco 1
PMCID: PMC9729424  NIHMSID: NIHMS1851518  PMID: 36400221

Abstract

Background

Polybrominated diphenyl ethers (PBDEs) were used as flame retardants and from their end-use products they can be released to accumulate within indoor environments. This may result in exposures to pregnant women with potential adverse effects on the developing fetus. While studies have shown associations between prenatal PBDE exposure and poor birth outcomes, research has mainly focused on birth weight and gestational age and may miss important indicators of newborn size.

Methods

The sample included a cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners (BDE-47, BDE-99, BDE-100, and BDE-153) were measured in cord serum at birth and dichotomized into low (<80th percentile) and high (>80th percentile) categories. Weight, length, head circumference, and gestational age were measured at birth and the ponderal index (birth weight/length x 100), size for gestational age, and population-based z-scores were calculated (n = 305). Separate regression analyses were conducted to estimate associations between PBDEs or PBDE sum (ng/g lipid) and birth outcomes. Quantile g-computation was performed to estimate the effect of total PBDE mixture. We also assessed effect modification by sex and ethnicity.

Results

Adjusting for relevant covariates, the high exposure category of BDE-153 was associated with lower birth weight z-score (−0.25, 95% CI: −0.5, 0.0) and longer gestation (0.43 weeks, 95% CI: 0.07, 0.79). The high exposure category of BDE-99 was associated with lower birth length z-score (−0.55, 95% CI: −0.98, −0.12). There was a negative association between the overall PBDE mixture and birth length z-score (−0.10, 95% CI: −0.21, 0.00) per 1 quintile increase in PBDEs. There was no effect modification by sex or ethnicity.

Conclusions

These results suggest that prenatal exposures to BDE-153, BDE-99, and total PBDE mixture are associated with birth outcomes in a cohort of Dominican and African American newborns.

Keywords: Polybrominated Diphenyl Ethers, Birth Outcomes, Prenatal Exposure, Mixtures

Introduction

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants that were widely used in furniture, insulation, and electronics from 1975 to 2004 (Stapleton et al., 2005). While PBDEs have been either restricted, banned, or phased out in the United States, China, Japan, India, and countries in the European Union (Olisah et al., 2018; Sharkey et al., 2020), they are still widely detected in high concentrations within indoor dust and air (Allen et al., 2007; Stapleton et al., 2005). This could be attributed to the fact that PBDEs are not covalently bonded to their end use products, and therefore with time and use, they can leach out and accumulate within indoor environments (Allen et al., 2008). From there, oral ingestion, inhalation and dermal contact with the dust leads to exposure of PBDEs to humans (Frederiksen et al., 2009). As pregnant women are more likely to spend a longer time at home, especially during later stages of pregnancy, there is a potential for higher PBDE exposures during pregnancy compared to the general population (Nethery et al., 2009). Food sources may act as an additional route of exposure, with research reporting that consumption of processed meat and solid dairy products is associated with increased PBDE exposure in pregnant women (Horton et al., 2013). These chronic exposures to PBDEs in pregnant women can in turn lead to potential adverse effects to the developing fetus. Ruis et al., (2019) reported that PBDE concentrations were higher in the fetal section of the placenta compared to the maternal side, and studies have detected PBDEs in both maternal and umbilical cord blood at delivery, suggesting that PBDEs are transported to the fetus across the placental interface (Frederiksen et al., 2010; Li et al., 2013; Ruis et al., 2019).

PBDEs are shown to act as endocrine disrupting chemicals and, as their chemical structure closely resembles thyroid hormones, they can act specifically as thyroid disruptors (Costa et al., 2014; Kitamura et al., 2008). The thyroid hormones triiodothyronine (T3) and thyroxine (T4) play an essential role in fetal growth and development during the gestational period (Bernasconi et al., 2015; Forhead and Fowden, 2014), and therefore, PBDE induced thyroid disruption may have downstream effects on birth outcomes. PBDEs exposure is also associated with placental epigenetic dysregulation, altered mRNA expression, and metabolomic disruption (Park et al., 2020; Y. Wang et al., 2022; Zhao et al., 2017). This is especially important, because adverse birth outcomes are associated with a host of adult diseases such as obesity, hypertension, heart diseases, diabetes, and stroke (Barker, 2004; Calkins and Devaskar, 2011; Visentin et al., 2014).

Animal and human studies have shown associations between prenatal exposures to PBDEs and adverse birth outcomes. Studies in rats have shown that prenatal exposures to PBDEs leads to a significant decrease in birth weight (Zhao et al., 2017). Within human populations, prenatal exposure to PBDEs have shown disparate associations. PBDEs have been associated with a decrease in birth weight, birth length, gestational age, birth weight z-scores, and head circumference (Chen et al., 2015; Eick et al., 2020; Lopez-Espinosa et al., 2015), but have also been positively associated with gestational age and head circumference (Chen et al., 2018). Studies, however, have not focused on other potential important indicators of newborn health, such as the ponderal index and size for gestational age. Hence, using a prospective birth cohort of Dominican and African American mother-child pairs, our aim was to examine the associations between prenatal PBDE exposure and a suite of birth outcomes. We further examined whether these effects were sex- or ethnicity-specific and if there was an overall mixture effect of the PBDEs. We hypothesized that 1) prenatal BDE-47, BDE-99, BDE-100, and BDE-153 exposures are individually associated with adverse birth outcomes; 2) that exposure to the total PBDE mixture is associated with adverse birth outcomes; and 3) child sex and race/ethnicity will modify the association between individual and total PBDE exposure and birth outcomes.

Methods

Sample Population

Participants in this study were a subset of mother-child pairs from the Mothers and Newborns prospective birth cohort from the Columbia Center for Children’s Environmental Health (CCCEH) (N = 727) (Perera et al., 2006). Dominican and African American pregnant individuals between 18-35 years of age were recruited between 1998 and 2006 from Northern Manhattan and South Bronx in New York City. Exclusionary criteria included maternal smoking during current pregnancy, a first prenatal visit after the 20th gestational week, documented or reported substance abuse, and presence of gestational diabetes, hypertension, or human immunodeficiency virus. Children were excluded from our analysis if they had elevated cord cotinine levels (> 25 ng/ml) or if they were missing outcome data, resulting in 678 participants. Another 8 women were missing the majority of potential covariates and were excluded from the analysis. Of these 670 participants, 305 had PBDE concentrations measured in cord serum samples, and had measures of infant birth weight and gestational age measures. The study protocol was approved by the Institutional Review Board of Columbia University Medical Center and the Centers for Disease Control and Prevention. Mothers were informed about all study procedures before each visit and provided written informed consent to participate.

Measurement of PBDEs in Cord Serum

Umbilical cord blood at delivery was collected, processed and stored at the CCCEH laboratory. The CDC’s Persistent Organic Pollutants Biomonitoring Laboratory measured eleven PBDE congeners in umbilical cord serum (BDEs: 17, 28, 47, 66, 85, 99, 100, 153, 154, 183, and 209) (Sjödin et al., 2004a). Details of the analytical methods have been previously published (Jones et al., 2012; Sjödin et al., 2004b). In brief, internal standards were added to the serum samples (~1mL) after which, they underwent extraction and lipid removal. The extracts were then spiked with recovery standards and final analytical concentrations were determined by gas chromatography isotope dilution high-resolution mass spectrometry. Blanks (N =3) were processed, and the median values were subtracted from the final concentration. Detection frequencies of the eleven PBDEs ranged from 2 to 80% (Sjödin et al., 2004b). Using a detection frequency cutoff of 35%, we selected the four most frequently detected PBDE congeners in umbilical cord serum (BDE-47, BDE-99, BDE-100, and BDE-153) for subsequent analysis. Serum lipids (total cholesterol and triglycerides) were measured and total blood lipids were estimated using a cord blood-specific formula (Cowell et al., 2018).

Birth Outcomes

Birth weight (g), birth length (cm), head circumference (cm), and gestational age (weeks) data were retrieved from infant medical records by trained research workers. We calculated the ponderal index (birth weight/length3 x 100) (g/cm3), size for gestational age, and population-based z-score for weight (sd), length (sd), and head circumference (sd) using the Fenton Preterm Growth Charts (Calgary, CA) (Fenton and Kim, 2013). There were missing data for ponderal index (N = 21 missing), length z-score (N = 28 missing), and head circumference z-score (N = 40 missing). Additionally, three abnormally low and high length z-scores (> or < 5 standard deviations) were determined to be potential clerical errors and were removed from the analysis, resulting in N = 274 for length z-score analyses. Size for gestational age was dichotomized into small for gestational age (SGA) (<10th percentile for weight based on Fenton charts) and normal/large for gestational age (>10th percentile).

Covariate Selection

Covariates were selected based on studies that identified key factors that may confound the effect of PBDEs on birth outcomes (Cowell et al., 2019, 2018). Models were adjusted for covariates collected from maternal questionnaires at birth, including maternal age (in years), race/ethnicity (Dominican/African American), pre-pregnancy BMI (in kg/m2), completion of high school (yes/no), parity (nulliparous/multiparous), environmental tobacco smoke exposure (yes/no, as described in (Rauh et al., 2004)), receipt of public assistance (yes/no), any reports of financial hardship (none/unable to afford food, a place to stay, utilities, housing, medical care or on Medicaid), and married or partnered at birth (unmarried/married or with the same partner for seven years or more). Models assessing birth weight (in grams) were additionally adjusted for gestational age (in weeks).

Statistical Analysis

We imputed missing data based on the full CCCEH population for completion of high school (N=1), maternal BMI (N=7), environmental tobacco smoke exposure (N=3), recipient of public assistance (N=3), reports of financial hardship (N=5), and married or partnered at birth (N=4) with logistic regression (binary variables) or predictive mean matching (continuous variables) from the Multiple Imputation by Chained Equations (MICE) R package (Buuren and Groothuis-Oudshoorn, 2011). PBDE concentrations below the limit of detection (LOD) were also imputed using a distribution-based multiple imputation approach that incorporated sample-specific limits of detection (Cowell et al., 2018). We repeated all imputations 10 times and pooled parameter estimates using Rubin’s Rules for all subsequent analysis (Rubin, 2004).

Individual PBDE congeners were summed to create the total PBDE concentration in cord serum. As the distribution of PBDEs are log normal, their lipid standardized concentrations (ng/g lipid) were dichotomized into low and high exposure categories based on the 80th percentiles to evaluate the effect of exposures at the high end of the distribution (Herbstman et al., 2010). We used separate multivariable linear regression analysis to estimate the associations between continuous and dichotomized PBDE congeners (ng/g lipid) or PBDE sum (ng/g lipid) in cord serum and birth outcomes. We used logistic regression analysis to estimate associations between PBDE congeners and SGA. We performed additional logistic regression analyses examining associations between PBDE congeners and large for gestational age (LGA). Estimates and confidence intervals from models examining SGA and LGA were exponentiated to give odds ratios (ORs).

Additional analyses were performed with dichotomized PBDE congeners. Maternal gestational weight gain (in kgs) was only available in a subset of participants (N=289), so we conducted sensitivity analysis in the smaller subset to evaluate the influence of gestational weight gain on fully adjusted models. As gestational age may act as a collider in the relationship between PBDE exposure and birth weight, we performed a sensitivity analysis where the associations between PBDEs and birth weight were not additionally adjusted for gestational age. Lastly, birth outcomes differed between our study population and population of mother-child pairs with no PBDEs measured, i.e. excluded population (Table S1). We performed inverse probability weighting using the ipw R package to account for differential treatment probabilities (Wal and Geskus, 2011). Weights were calculated for each outcome using maternal ethnicity, age, parity, BMI, environmental tobacco smoke exposure, reports of public assistance or any hardship, married/partnered, and completion of high school. Additional sensitivity analysis was conducted with the generated weights to evaluate the influence of the participants selected.

Moreover, given the sex-dependent, endocrine disrupting potential of PBDEs and possible differences in the uptake of PBDEs based on sex (Leonetti et al., 2016), we examined the potential effect modification by child sex by including interaction terms in fully adjusted models. We also ran sex-stratified models to determine sex-specific associations. We examined the potential effect modification by maternal ethnicity, using interaction and ethnicity-stratified models.

Mixture analysis with quantile g-computation

We investigated the associations of the total mixture of all BDE congeners with the seven birth outcomes using quantile g-computation using the R package qgcomp (Keil et al., 2020). Quantile g-computation calculates a weighted sum of all BDEs and estimates the effect of increasing all PBDEs by one quantile simultaneously on the birth outcomes, using a generalized linear mixed model based on the implementation of g-computation. Furthermore, with positive exposure effects, quantile g-computation is more statistically powerful compared to other mixture methods (Keil et al., 2020). We converted the PBDEs into quintiles, to correspond to our individual PBDE analyses (80th percentile) and ran 500 bootstraps to estimate the confidence bounds of the overall mixture. This can be interpreted as the effect of increasing total PBDEs by one quintile on child birth outcomes. Quantile g-computation also calculates a weight for each PBDE that is unconstrained in either negative or positive directions. When directional homogeneity does not hold (i.e. there are both positive and negative weights), the weights are the proportion of the partial effect of a single PBDE. The positive and negative weights are individually defined to sum up to one. Weights should be interpreted for significant associations and in the direction of the effect estimates.

All analyses were conducted in R statistical software (v4.1, Vienna, Austria) and statistical significance was assessed at alpha = 0.05.

Results

Study Population Characteristics

Table 1 and S1 describe the characteristics of the study population (N = 305) and original cohort (N= 727) respectively. All mother-child pairs were either African American (36%) or Dominican (64%) and an average of 25 years old. The mothers in the study were primarily single at birth (74%) and the majority had at least a high school education (62%). Approximately 41% of the population received public assistance and 43% reported at least one instance of financial hardship at birth of their child. For the most part, our study sample characteristics were similar to the overall Mothers and Newborns sample, however a larger percent of the participants who were excluded (Table S1) had a higher parity (60%).

Table 1:

Descriptive characteristics of the mothers and anthropometry measurement of children in the CCCEH cohort (N = 305)

Maternal Characteristics N Mean ± SD/ %
Ethnicity: African American 111 36
Ethnicity: Dominican 194 64
Multiparous 150 49
Environmental Tobacco Smoke Exposure 103 34
Receipt of Public Assistance at Birth 122 40
Mother Reports of Financial Hardship at Birth 133 44
Married and/or Partnered at Birth 77 25
Completed High School 187 61
Maternal Age (years) 305 25 ± 4.9
Maternal BMI (kg/m2) 305 26 ± 6.1
Gestational Weight Gain (kg) 289 17 ± 7.7
Birth Outcomes
Male 139 46
Female 166 54
Birth Weight (g) 305 3444 ± 460
Weight z-score 305 −0.051 ± 0.86
Length z-score 277 0.21 ± 0.95
Head Circumference z-score 265 −0.32 ± 0.90
Ponderal Index (g/cm3) 284 2.6 ± 0.32
Gestational Age (weeks) 305 39 ± 1.30
Large for Gestational Age 23 7
Large for Gestational Age 262 86
Small for Gestational Age 20 7
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The results of anthropometric measurements of 305 newborns are also described in Table 1. There were more females (54%) than males (46%), with an average birth weight of 3.4 kg and gestational age of 39 weeks. The average ponderal index was 2.6 g/cm3 and 7% of the population were small for their gestational age. The average Fenton z-scores for birth weight, birth length, and head circumference were −0.51, 0.21, and −0.32 respectively. Our included study sample had a higher birth weight and birth length z-score as well as a lower proportion of small for gestational age compared to the participants who were excluded (Table S1).

Table 2 summarizes the concentrations of PBDEs in cord serum, across samples and congeners (BDE-47, −99, −100, −153). Limit of detection for lipid adjusted cord serum PBDE concentrations ranged from 0.29 to 11.6 ng/g lipid. BDE-47, −99, 100, and −153 had an 80th percentile of 37 ng/g lipid, 8 ng/g lipid, 5.6 ng/g lipid, and 3.8 ng/g lipid respectively. While the concentrations of PBDEs was higher in males, there was no significant difference between the two sexes (Table S2).

Table 2:

Prenatal PBDE levels in cord blood serum (ng/g lipid) measured across 10 imputations (N = 305). LOD = limit of detection

PBDE N Mean ± SD Min Median Max 80th
Percentile		 % <LOD
BDE-47 305 28 ± 46 1.3 12 364 37 20
BDE-99 304 6.7 ± 11 0.46 2.8 85 8 49
BDE-100 305 4.6 ± 6.3 0.62 2.5 45 5.6 58
BDE-153 305 3.3 ± 3.1 0.74 2.4 25 3.8 63
Σ PBDE 304 43 ± 64 5.60 20 484 56
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Associations between PBDE exposure and birth outcomes

The higher exposure category of BDE-153 was associated with a lower birth weight z-score (β = −0.25, 95% CI: −0.5, 0.0) and longer gestation (β = 0.43 weeks, 95% CI: 0.07, 0.79) (Figure 1). We also observed that the higher exposure category of BDE-99 was associated with a lower birth length z-score (β = −0.40, 95% CI: −0.68, −0.12). Additionally, in models estimating associations with continuous PBDE congeners, BDE-99 was negatively associated with birth length z-score (β = −0.14, 95% CI: −0.27, −0.02) (Table S3). Neither BDE-47, −100 ΣPBDEs were associated with any birth outcomes. Furthermore, we did not observe any significant associations between PBDE congeners and LGA (Figure S3).

Figure 1:

Figure 1:

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Effect estimates from multivariable regression models examining the associations of dichotomized PBDE concentrations in cord blood serum on child birth outcomes. Error bars around effect estimates represent 95% confidence intervals. Models were adjusted for maternal age, race/ethnicity, pre-pregnancy BMI, completion of high school, parity, environmental tobacco smoke exposure, receipt of public assistance, any reports of financial hardship, and married or partnered at birth. Models assessing birth weight were additionally adjusted for gestational age.

Mixture effect of PBDE exposure and birth outcomes

Using quantile g-computation, increasing all PBDEs in the mixture by one quintile was associated with a decrease in birth length z-score (mean change in length z-score by quintile increased = −0.10, 95% CI: −0.21, 0.0) (Table 3). Furthermore, the PBDE mixture was suggestively associated with weight z-score (psi = −0.08, 95% CI: −0.16, 0.01) and gestational age (psi = 0.11, 95% CI: −0.01, 0.24). When examining the weights of the individual congeners (Figure 2), BDE-99 was assigned the largest negative weight in length z-score, and BDE-99 and BDE-153 were assigned the largest negative weights in birth weight z-score.

Table 3:

Overall mixture effect representing the effect of each PBDE increased by one quintile on birth outcomes. Small for gestational age effect estimates are odds ratios. Values in brackets represent 95% confidence intervals.

Outcome Effect Estimate (psi) p-value
Birth Weight (g) −26 (−68,17) 0.23
Weight z-score (sd) −0.08 (−0.16,0.01) 0.07
Length z-score (sd) −0.10 (−0.21,0.0) 0.05*
Head Circ z-score (sd) −0.09 (−0.19,0.02) 0.10
Ponderal Index 0.01 (−0.03,0.04) 0.65
Gestational Age (weeks) 0.11 (−0.01,0.24) 0.07
Small for Gestational Age 0.99 (0.96,1.01) 0.20
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Models were adjusted for maternal age, race/ethnicity, pre-pregnancy BMI, completion of high school, parity, environmental tobacco smoke exposure, receipt of public assistance, any reports of financial hardship, and married or partnered at birth. Models assessing birth weight were additionally adjusted for gestational age.

Figure 2:

Figure 2:

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Proportion of overall effect from each PBDE on birth outcomes averaged across 10 imputations.

Associations of PBDEs and birth outcomes when stratified by sex and ethnicity

We observed no sex-specific (Figure 3) or ethnicity-specific (Figure S1) associations between PBDE concentrations in cord serum and birth weight, head circumference z-score, ponderal index, and proportion of small for gestational age. BDE-153 was positively associated with gestational age in males (β = 0.52, 95% CI: 0, 1.04) but not in females (β = 0.41, 95% CI: −0.11, 0.94) and in the African American population (β = 0.73, 95% CI: 0.11, 1.35) but not the Dominican population (β = 0.28, 95% CI: −0.17, 0.72). BDE-153 was also negatively associated with birth weight z-score in males (β = −0.37, 95% CI: −0.73, −0.02) but not in the females (β = −0.12, 95% CI: −0.50, 0.25). Lastly, BDE-99 was negatively associated with birth length in the Dominican (β = −0.46, 95% CI: −0.83, −0.09) population but not the African American population (β = −0.45, 95% CI: −0.94, 0.07). However, no significant interactions between sex or race/ethnicity were observed (p interactions > 0.05).

Figure 3:

Figure 3:

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Associations of dichotomized PBDEs in cord blood with birth outcomes stratified by sex. Error bars around effect estimates represent 95% confidence intervals.

Sensitivity Analyses

The addition of maternal gestational weight gain and IPW weighting for treatment had no meaningful impact on the results (Table S2 & S3). The removal of gestational age as a covariate had no meaningful impact on the association between PBDEs and birth weight (Figure S2).

Discussion

We found that higher concentrations of PBDEs in cord blood serum were associated with altered birth outcomes in a minority population living in Northern Manhattan and the South Bronx. In this study, BDE-47 was the most abundant PBDE congener in cord serum, followed by BDE-99. These results are similar to the trends detected in other American populations (Herbstman et al., 2010, 2007; Mazdai et al., 2003), however concentrations detected in our study are either lower (Herbstman et al., 2007; Mazdai et al., 2003; Vuong et al., 2015) or comparable (Herbstman et al., 2010) to other studies measuring PBDE congeners in cord blood. Higher concentration of BDE-99 was associated with a decrease in birth length z-score. Higher concentration of BDE-153 in cord serum was associated with a decrease in birth weight z-score and an increase in gestational age. There were no statistically significant associations between PBDEs and birth weight, head circumference z-score, ponderal index, and small/large for gestational age, although the direction of the association for birth weight was consistently negative. Furthermore, there was no significant associations between the overall PBDE mixture and birth outcomes other than birth length z-score.

While no other studies have reported significant associations between 1) BDE-153 and weight z-score and gestational age; or 2) BDE-99 and birth length z-score, they have reported other similar birth outcomes associated with other prenatal PBDE exposures. In a population of low-income and predominantly Mexican families, BDE-47, −99, and −100 measured in maternal serum was negatively associated with birth weight (Harley et al., 2011). Additionally, in a low-income population, higher BDE-47 and −99 in maternal serum were associated with decreased birth weight z-scores (Eick et al., 2020). BDE-100 measured in maternal serum was also associated with a decrease in birth length in a rural Chinese birth cohort (Chen et al., 2015). In a Taiwanese population of mother-child pairs, BDE-47 in breast milk was associated with a decrease in birth weight, and BDE-99 and −100 was associated with a decrease in both birth length and birth weight (Chao et al., 2007). Similarly, in a Swedish population, sum of BDE-47, −99, −100, and −153 measured in breast milk was associated with a decrease in birth weight (Lignell et al., 2013). While we can’t directly compare PBDE exposure in these studies with ours due differences in sample matrix, our results are in concordance with the literature and suggest that higher PBDE exposure is associated with reduced birth weight and length.

Interestingly, our study also observed that BDE-153 was associated with a longer gestational age. Research on the effects of PBDEs and gestational age are mixed. Studies have reported higher BDE-47 and −153 in maternal serum are associated with decreased gestational age and preterm birth (Eick et al., 2020; Gao et al., 2016; Peltier et al., 2015; Z. Wang et al., 2022). However, similar to our findings, BDE-47, BDE-100 and sum of four BDE congeners (BDE-28, BDE-47, BDE-99, and BDE-100) measured in cord blood were positively associated with gestational age in a Chinese birth cohort (Chen et al., 2018). While additional studies looking at other chemicals and gestational age have reported positive associations as well (Birks et al., 2016; Smarr et al., 2015), there is no consensus for the mechanism behind this relationship.

In addition, we observed negative associations of BDE-153 and birth weight z-score in males. This finding is consistent with other studies that found a stronger effect of PBDE exposure on adverse birth outcomes in male populations compared to female populations (Liu et al., 2022; Zhao et al., 2017). While the mechanisms behind the sex-specific differences in associations are unknown, studies have detected higher PBDE concentrations in male placental samples compared to female placental samples, suggesting that infant sex may have an effect on the bioaccumulation and metabolism of PBDEs in the placenta during pregnancy (Leonetti et al., 2016; Liu et al., 2022).

PBDEs may be affecting birth outcomes through impacts on thyroid homeostasis. As PBDEs mimic the thyroid hormones, they can disrupt the necessary role these hormones play in fetal grown and development (Costa et al., 2014; Forhead and Fowden, 2014). A study by Zhao et al., (2019) also reported that PBDE congeners were associated with placental DNA methylation, and these changes may partially mediate the association between the sum of 13 individual PBDE congeners and fetal growth (Zhao et al., 2019). Thus, placental DNA methylation and function may be another potential mechanism when considering associations between prenatal PBDE exposure and abnormal birth outcomes. Birth outcomes are an extremely important indicator of future adult health, and specifically, studies have found that a lower birth length z-score, which is indicative of a lower length compared to the general population, is associated with decreased adult height, obesity, increased fracture risk, and pulmonary diseases (Calkins and Devaskar, 2011; Javaid et al., 2011; Jung et al., 2019; Lundgren et al., 2003). Likewise, a decreased birth weight z-score is associated with increased fat deposition, incidence of diabetes and cardiovascular diseases, and higher mortality (Barker, 2004; Labayen et al., 2008; Steurer et al., 2021).

Our study has several strengths, including the estimation of birth outcomes that are not commonly studied in relation to PBDE exposure (i.e., ponderal index, small for gestational age, and head circumference). We also performed a novel mixture analysis to assess the overall effect of the PBDE mixture on birth outcomes. PBDEs bioaccumulate and have a long half-life in blood, therefore our measures in cord serum likely reflects exposure occurring during pregnancy. Moreover, as the PBDEs were measured in cord serum, providing a closer estimate of fetal exposure compared PBDEs measured in maternal serum. This study was also conducted in a minority population, where a large proportion of the pregnant mothers were on public assistance or have experienced hardship. This is especially important in the context of PBDE exposure, as Zota et al., (2010) has reported that PBDEs disproportionately affect communities of lower socio-economic status due to higher use of older furniture that still have PBDEs within them (Zota et al., 2010).

Conversely, a limitation of this study was that it was conducted in a subgroup population in Northern Manhattan, and therefore may not be generalizable to other populations. Our cohort was also largely a term cohort and therefore also does not generalize to the US preterm birth rate of 10%. Furthermore, the average age of the mothers in our cohort (25 years) is younger than the average age of first-time mothers in the United States (26 years). Another limitation is that while the PBDE sum metric is unique, it is for the most part indicative of BDE-47 as it is the congener with the highest concentration. Lastly, although we adjusted for several relevant confounders in our analyses, our associations may be affected by other variables, such as maternal diet or lifestyle factors. Specifically, other pollutants such as polycyclic aromatic hydrocarbons and bisphenol A, which may be correlated with PBDE exposures, may impact birth outcomes; however, not enough of these values were not available for our population subset. Additionally, given our small study population, we are likely underpowered to detect sex-specific or race/ethnicity-specific associations.

Conclusion

In this analysis of prenatal PBDE exposure and birth outcomes, we found that BDE-153 in cord blood serum was associated with a lower birth weight z-score and a longer gestation period. We also detected negative associations between BDE-99 and birth length z-score. Furthermore, we found that cord serum concentrations of PBDEs, as a mixture, were associated with lower birth length z-score. Overall, this study adds to the weight of evidence that PBDEs are significantly associated with adverse birth outcomes.

Supplementary Material

1

Highlights.

  • Higher prenatal exposure to BDE-153 was associated with lower birth weight z-score and longer gestation.

  • Higher prenatal exposure BDE-99 was associated with lower birth length z-score.

  • A significant negative association was detected between the overall PBDE mixture and birth length z-score.

Acknowledgements

This work was supported by grants from the National Institute of Environmental Health (P30ES009089, R00ES030749 to A.K, and R01 ES021806 to J.B.H.).

Footnotes

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services.

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