Racial/ethnic disparities in environmental endocrine disrupting chemicals and women's reproductive health outcomes: epidemiological examples across the life course.

In this review, we focused on phthalates, phenols, and PBDEs, and their relations to women’s reproductive health outcomes during 3 selected periods across the life course to determine the state of the literature on the role of environmental EDCs as a mediator of racial/ethnic differences in women’s reproductive health outcomes. We presented our argument by first describing racial/ethnic disparities in EDC exposure for these selected chemicals in the U.S. Next, in each section we highlighted disparities in specific women’s reproductive health outcomes. We then evaluated the literature on EDCs and adverse women’s reproductive health outcomes to determine whether the research warrants further evaluation for assessing these chemicals as a partial explanation for racial/ethnic disparities in these health outcomes. While most studies found no association or inverse associations between the selected EDCs and pubertal outcomes, few studies evaluated the higher exposure/higher risk groups separately to determine if associations may have differed. Studies evaluating fibroids, infertility, and pregnancy complications were similar, in that they either adjusted for race/ethnicity or evaluated predominantly white populations. Several studies were cross-sectional, which limited the ability to evaluate EDCs as potential mediators of the racial/ethnic disparities in women’s reproductive health outcomes due to temporality issues. Finally, certain reproductive time periods were better studied than others. For example, only one cross-sectional study evaluated EDCs and menopause-related outcomes [ 113 ]. Therefore, we suggest the following to fill important gaps in epidemiologic research related to racial/ethnic health disparities in women’s reproductive health outcomes: Evaluation of environmental chemical exposures and women’s health outcomes in more diverse study populations Examination of individual and contextual determinants of racial/ethnic disparities in EDC exposures Assessment of whether differences in EDC exposures contribute to disparities in women’s reproductive health outcomes through mediation and stratified analyses Examination of relatively understudied EDCs that are racially/ethnically patterned, such as certain parabens and metals that are able to affect the endocrine system, such as cadmium. Increased research in less-studied racial/ethnic minority groups, such as Asian subgroups, as well as more research in areas of women’s reproductive health, including certain pregnancy complications and menopausal outcomes Evaluation of environmental chemical exposures and women’s health outcomes in more diverse study populations Examination of individual and contextual determinants of racial/ethnic disparities in EDC exposures Assessment of whether differences in EDC exposures contribute to disparities in women’s reproductive health outcomes through mediation and stratified analyses Examination of relatively understudied EDCs that are racially/ethnically patterned, such as certain parabens and metals that are able to affect the endocrine system, such as cadmium. Increased research in less-studied racial/ethnic minority groups, such as Asian subgroups, as well as more research in areas of women’s reproductive health, including certain pregnancy complications and menopausal outcomes Several studies have taken initial steps toward evaluating racial/ethnic differences in exposure as a possible explanation for racial/ethnic disparities in outcomes. These studies have prospectively addressed research questions in more diverse study populations, which could facilitate future studies that look at EDCs as a potential contributor to racial/ethnic disparities in outcomes. These studies have also reported out racial/ethnic differences in exposures and/or outcomes, which allow for future work to build on these established findings. Specifically, Wolff [ 75• ] and Windham [ 73• ] provided detailed information about racial/ethnic differences in pubertal outcomes in a racially/ethnically diverse study population. Ferguson [ 103• ] and Werner [ 33• ] evaluated two different racially/ethnically disparate pregnancy outcomes in two racially/ethnically diverse pregnancy cohorts. In the future, these studies may provide needed insight into racial/ethnic disparities in puberty, preterm birth, and pregnancy hypertension, as they relate to EDC exposures.

Health disparities are defined as differences that systematically and negatively impact less-advantaged subgroups of the population [ 1 ]. Within the U.S. race/ethnicity is a determinant of health [ 2 – 4 ]. Much research has documented racial/ethnic disparities in women’s reproductive health outcomes [ 5 – 7 ], noting both social and biological determinants. While geographic region of one’s ancestral origin may explain some genetic or underlying biological differences, race is predominately a social construct related to societal structure, behaviors, cultural traditions, and environmental factors [ 8 , 1 ]; the latter has received limited attention in disparities research. When considering environmental factors, environmental endocrine disrupting chemicals (EDCs) warrant attention in racial/ethnic disparities research because many sources of EDCs such as consumer product use [ 9 – 12 ], diet [ 13 , 14 ], and the built environment [ 15 – 17 ] are socially patterned [ 18 , 19 ]. Consequently, non-whites have been found to have higher concentrations of many of these chemicals in numerous epidemiologic studies. Higher exposures in non-whites may contribute to increasing disparities in the incidence of adverse health outcomes due to the unequal distribution of both chronic exposures to non-persistent and persistent chemicals, along with an unequal distribution of protective factors ( Figure 1 ). These differences could lead to disparate health outcomes, which may become magnified across the life course due to weathering or cumulative wear and tear. Yet, the link between racial/ethnic disparities in exposure patterns and their impact on disparities in adverse health outcomes is not well understood. Of interest, is that EDC exposure can be modifiable with implications for identification of and interventions for reducing disparities in exposures and associated outcomes. While studies have presented racial/ethnic differences in EDC exposures (i.e. phthalates, bisphenol A, parabens, and polybrominated diphenyl ethers), as well as racial/ethnic differences in women’s health outcomes, few studies have evaluated whether racial/ethnic differences in EDC exposures contributes to differences we see in these outcomes. The purpose of this paper is to call attention to this important gap in disparities research. Here, we will 1) review the current state of the literature for racial/ethnic disparities in women’s exposures to 4 types of environmental EDCs – phthalates, bisphenol A (BPA), parabens, and polybrominated diphenyl ethers (PBDEs); and 2) summarize the existing literature on associations between EDCs and selected and disparate women’s reproductive health outcomes—puberty, fibroids, infertility, and pregnancy complications. Given that one of the 2012–2017 strategic goals for the National Institute of Environmental Health Sciences is to reduce health disparities, a better understanding for how these chemicals affect racial/ethnic health disparities is a critical public health question [ 20 ].

To conduct a literature review of racial/ethnic disparities in environmental chemicals and the effects on women’s health outcomes in the U.S., we searched all English articles in PubMed and EMBASE from the inception of all databases to Jan 15, 2016. We pre-specified four major EDCs (phthalates, BPA, parabens and PBDEs) and specific women’s reproductive health outcomes (i.e. puberty, fibroids, pregnancy, and pregnancy complications). In article searching for chemical exposures from Pubmed, we combined the Medical Subject Headings (MeSH) terms and key words as follows: “phthalic acids,” “bisphenol A-glycidyl methacrylate,” “parabens,” or “halogenated diphenyl ethers,” as MeSH terms, and phthalic acid, phthalate, bisphenol A, methylparaben, butylparaben, propylparaben, polybrominated diphenyl ether, and organobromine compound as specific key words in texts. For women’s health outcomes, the MeSH terms included “puberty,” “puberty, delayed,” “puberty, precocious,” “pregnancy,” “infertility, female,” “ovarian reserve,” “ovarian follicle,” “pregnancy complications,” “premature birth,” and “leiomyoma,” key words included menarche, thelarche, breast development, antral follicle count, preeclampsia, gestational diabetes and preterm. Similarly, in our EMBASE search for chemical exposure, we combined Emtree terms and key words as follows: “phthalic acid derivative,” “phthalate,” “4,4 isopropylidenediphenol,” “4 hydroxybenzoic acid ester,” “propyl paraben,” “methyl paraben,” “ethyl paraben,” “butyl paraben,” “benzyl paraben,” and “polybrominated diphenyl ether” searched as Emtree terms; phthalate, BPA, paraben, polybrominated diphenyl ethers, and PBDE as key words in text. For women’s health outcomes, we used all the Emtree terms including “puberty,” “delayed puberty,” “precocious puberty,” “adrenarche,” “breast development,” “pregnancy diabetes mellitus,” “preeclampsia,” “premature labor,” “pregnancy complication,” “pregnancy rate,” “uterus myoma,” and “leiomyoma. After excluding in vitro studies, animal studies, studies conducted outside of the U.S., as well as studies that did not assess the outcomes of interests, the searching strategies yielded a total of 612 articles in Pubmed and EMBASE. We reviewed these articles and identified 46 discrete studies examining the association between environmental EDCs and women’s reproductive health outcomes among women living in the U.S. We also documented whether race-specific measures of association were reported in the main findings.

Phthalates, phenols, and PBDEs are suspected EDCs because they can interfere with hormone regulation and action [ 57 ]. In vitro and animal studies suggest that certain phthalates, such as DEHP and DnBP, exert their toxicity primarily through disruption of androgen production [ 58 ]. Phthalates may also interact with peroxisome proliferator–activated receptor γ, estrogen, and thyroid receptors [ 59 , 60 ]. Animal studies demonstrate that exposure to phthalate mixtures results in greater risk than exposure to individual phthalates [ 61 , 58 ]. Consequently, the National Academy of Sciences has recommended that simultaneous exposure to phthalates be examined using a cumulative risk assessment framework [ 58 ]. BPA is a reproductive toxicant that can act through physiological receptors, such as genomic estrogen receptors 1 and 2, membrane-bound estrogen receptors, androgen receptor, peroxisome proliferator–activated receptor γ, and thyroid hormone receptor [ 62 ]. Parabens exhibit weak estrogenic activity and can bind to both the estrogen receptor-α and estrogen receptor-β [ 60 , 59 ]. PBDEs can affect thyroid homeostasis through multiple pathways. They can alter the binding of thyroid hormones to thyroid transport proteins as well as thyroid hormone receptors [ 63 , 64 ]. PBDEs can also exhibit weak estrogenic and anti-androgenic activity [ 65 , 66 ]. These chemicals can also affect other biological pathways. For example, there is increasing attention on the ability of chemicals such as phthalates and BPA to induce oxidative stress and inflammation as well as epigenetic modifications such as DNA methylation and microRNA expression [ 67 – 69 ].

In 2010, a call was made by the Institute of Medicine’s Committee on Women’s Health Research to identify and better understand the physical and social environmental determinants of women’s health disparities [ 114 ]. Data suggest that certain groups have higher exposure to the discussed chemicals across the life course, with implications for a higher incidence for adverse conditions relative to more advantaged groups ( Figure 1 ). Furthermore, chronic and cumulative exposure to these EDCs coupled with a lack of protective factors could lead to cumulative wear and tear thereby increasing disparities in adverse health outcomes across the life course for these high-exposure/high-risk groups. While the literature is still in its infancy for EDC—women’s reproductive health outcomes, the current research suggests that certain EDCs are associated with a number of adverse women’s reproductive health outcomes. By evaluating EDCs’ contribution to racial/ethnic health disparities and identifying modifiable sources of EDC exposure in these vulnerable populations, this work could provide opportunities for prevention and reduction in racial/ethnic health disparities.

Phthalic acid esters, also known as phthalates, are a class of industrial chemicals that are ubiquitously used in commercial products. Low molecular weight phthalates, such as diethyl phthalate (DEP), di- n -butyl phthalate (DnBP), and di-iso-butyl phthalate (DiBP), are used in personal care products, solvents, adhesives, and medications [ 21 – 23 ]. High molecular weight phthalates, such as butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), di-iso-nonyl phthalate (DiNP), and di-iso-decyl phthalate (DiDP) are primarily used as plasticizers in polyvinyl chloride (PVC) applications found in building materials, medical equipment, and food packaging [ 21 , 24 , 25 ]. Phthalates are non-persistent chemicals in humans, with half-lives of about 12–24 hours, so measured levels of metabolites in urine reflect recent exposures. Virtually all U.S. women are exposed to multiple phthalates [ 26 ]. Among reproductive-aged women in the U.S. general population, non-Hispanic black and Mexican American women have higher metabolite concentrations of the low-molecular weight phthalates (e.g. DEP, DnBP) than non-Hispanic white women[ 27 , 12 , 28 ]. Similar exposure disparities between non-white and white subpopulations have also been observed in pregnant women [ 29 , 30 ] and girls aged 6–8 years [ 31 , 32 ]. While socio-cultural differences in personal care product use have been hypothesized as a possible driver of disparities in low-molecular weight phthalate exposure, only one study has attempted to characterize this relationship. Branch et al [ 12 ] found that differences in vaginal douching practices may contribute to black/white disparities in DEP exposure. Racial/ethnic patterns in DEHP or other high molecular weight phthalates among women are less consistent; most studies report that levels of DEHP metabolites are similar across race/ethnicity [ 27 , 29 , 32 , 31 ], with a few studies reporting higher exposures among white compared to non-white women [ 33• , 28 ]. Phenols are used in consumer products, including food can linings, plastic bottles, thermal receipt paper, antimicrobial agents, and preservatives [ 34 , 35 ]. Phenols, including bisphenol A (BPA) and parabens, are non-persistent chemicals that are rapidly metabolized and eliminated, with half-lives in the human body between 6 and 30 hours [ 36 ]. Most U.S. women are exposed to BPA, and levels among women are higher than men [ 37 ]. Among studies that have reported BPA levels by race in female populations, approximately one-third report no racial/ethnic differences [ 31 , 38 – 40 ], one-third report higher levels among black women compared to white women [ 41 – 43 ], and the remainder report significant racial/ethnic differences; but the groups with elevated levels are heterogeneous (e.g. non-Hispanic, non-Asian or other) making it difficult to compare across studies [ 44 – 46 ]. Methyl paraben (MP) and propyl paraben (PP) are two of the most used parabens with detection frequencies above 90% in the U.S., while butyl paraben (BP) and ethyl paraben (EP) are detected less frequently. Women have higher levels of MP and PP than men [ 47 ]. Racial/ethnic differences in paraben levels have been less studied; however, most studies find that black women have significantly higher total paraben burden than white women [ 31 , 48 ] Personal care product use and diet have been hypothesized as sources of variability for BPA and parabens but have not been confirmed by empirical studies [ 49 ]. PBDE flame retardants are commonly found in consumer products such as upholstered furniture, electronics, and textile products [ 34 ]. Most PBDE flame retardants are no longer used in the U.S., and replacement flame retardants have been developed as alternatives. Consequently, PBDE exposures appear to be declining in some U.S. populations [ 50 ]; however, because PBDEs are lipophilic, persistent chemicals similar to PCBs, with half-lives between a few months to over 10 years in adult human adipose tissue, they will likely persist for decades [ 50 ]. The majority of PBDE body burden studies find higher levels among non-white women compared to white women. For example, among adolescent girls in the U.S., whites had lower total PBDE concentrations than Mexican Americans and others [ 51 ]. Furthermore, higher total PBDE levels have been observed in blacks compared to whites among pre-adolescent girls [ 52 ] as well as pregnant women [ 53 ]. Similarly, a study of mostly post-menopausal women from California found that non-white women consisting of blacks, Asians, and Hispanics, had higher levels of PBDE-47, -100, and -153 than white women [ 54 ]. In contrast, another study of California women found that non-Hispanic women (white, Asian, or Native American) had higher levels of BDE-100 and -153 than Hispanic women although the differences in ethnicity were largely driven by one Native American women with very high levels [ 55 ]. Since an important source of human exposure to PBDEs is household dust, exposure disparities in PBDEs by race/ethnicity are hypothesized to stem from differences in housing stock and furniture quality [ 56 ] although more work is needed in this area.

Racial/ethnic differences in puberty have been well-documented [ 70 ]. For example, black girls are more likely to reach menarche earlier, with 62% of black girls reaching menarche by age 12 compared to 35% of white girls. These age differences can be seen for breast and pubic hair development, as well. Environmental factors are thought to contribute to this difference. Ten studies that met our criteria evaluated the association between EDCs and indicators of pubertal development [ 48 , 51 , 71 , 41 , 72 – 75• , 32 , 31 ]. Specifically, the studies assessed a range of outcomes, from central precocious puberty to hormone levels and self-reported age at menarche (See Table 1 ). Most studies adjusted for race/ethnicity, with a few presenting stratified analyses. In general, sample sizes ranged from 56 to 1239; however, almost all of the studies found no association between urinary phthalate metabolite concentrations measured at different time points in early life/childhood and any of the pubertal outcomes. The one study by Wolff et al showed that higher concentrations of high molecular weight phthalates, including DEHP metabolites were associated with later age of pubic hair development [ 32 ]. There was signal of this finding in an earlier evaluation of the same study population [ 31 ]. A number of these same studies also evaluated BPA. Two cross-sectional studies using data from the National Health and Nutrition Examination Survey (NHANES) found discordant results for the BPA and age at menarche, with an earlier study finding no association and a later study finding a slightly reduced risk for earlier age at menarche with higher BPA concentrations [ 48 , 41 ]. When looking longitudinally with a different pubertal outcome, data from the Breast Cancer and Environment Research Program (BCERP) found no association between BPA and age at pubertal staging [ 75• ]. In the 3 studies that evaluated parabens, two came from the BCERP study population at different time points. In the first study of 1,151 girls, no association was found [ 31 ]. However, the later study of 1,239 girls found that higher paraben concentrations were associated with earlier age at stage B2 for breast development [ 75• ]. Interestingly, after adjustment for race/ethnicity and caregiver education, the association no longer existed. The third study, which was a cross-sectional study of the NHANES population, found no association between parabens and age at menarche [ 48 ]. Only two studies have evaluated PBDEs and pubertal outcomes, and the findings were not entirely consistent. Specifically, the longitudinal study found higher PBDE concentrations to be associated with a delay in breast development [ 73• ], while the cross-sectional study found an association between higher PBDEs and earlier age at menarche [ 51 ]. When considering other life stages, a number of studies have documented racial/ethnic disparities in the incidence of gynecologic disorders, such as uterine leiomyoma, or uterine fibroids. In fact, compared to white women, black women have a higher incidence of fibroid tumors [ 77 , 78 ] and have larger and more symptomatic fibroids [ 78 , 77 , 79 ]. While a number of studies have attempted to evaluate reasons for these disparities associations, studies evaluating associations between environmental risk factors and fibroids have only recently emerged ( Table 2 ). Two papers evaluated associations between phthalates with fibroids [ 80 , 28 ]. While differences in exposure and outcome patterns existed by race/ethnicity, associations were conflicting. In the Endometriosis, Natural history, Diagnosis, and Outcomes (ENDO) Study, no association was found between higher concentrations of any of the urinary metabolite concentrations and surgically confirmed fibroids [ 80 ]. In a cross-sectional study, there were weak positive associations for MBP in relation to self-reported history of fibroids [ 28 ]. On the other hand, higher concentrations of MEHP were associated with a reduced odds of fibroids [ 28 ]. One paper evaluated BPA and fibroids. In this paper, cases had higher BPA levels compared to controls, but these differences were not statistically significant in adjusted models [ 80 ]. Based on research conducted in U.S. populations, the association between parabens and fibroids, as well as the association between PBDE concentrations and fibroids has not been explored in published epidemiological papers. Infertility is a common disease affecting 15% of couples during reproductive years in the U.S. [ 81 ]. It has been reported that black and Hispanic women had higher infertility rates [ 82 ] and greater risk of pregnancy loss compared to white women despite non-white women being less likely to utilize assisted reproductive technology (ART) [ 83 ]. In addition, black women also experienced lower live birth rates than white women following ART even under the “equal access-to-care” settings from military ART centers [ 84 ], suggesting that other important factors are at play. When looking at U.S.-based studies, 18 studies were published evaluating environmental chemicals and infertility and associated pregnancy outcomes ( Table 3 ). One main issue of these studies is that there was a low minority representation in fertility centers, and as a result, these studies were unable to explore whether differences in higher exposure patterns among non-whites might contribute to different patterns of infertility and its related outcomes. Five U.S. studies have recently assessed associations between urinary phthalate metabolites and infertility and related outcomes, including results from natural conception and pregnancies following ART treatment [ 85 – 89 ]. For the former, studies evaluated the probability of being pregnant, time to pregnancy, length of follicular and luteal phases, and pregnancy loss. For the evaluation of pregnancies following ART treatment, chronological endpoints ranged from ovarian reserve (e.g., antral follicle count), ovarian stimulation response (e.g., oocyte yields, peak estradiol levels), fertilization rates, embryo quality, implantation, pregnancy to live birth, were evaluated. While consistency across studies was difficult given the multiple endpoints, the research points to both DEHP and its replacement chemicals, DiNP and DIDP as being related to fertility potential. For example, DEHP was associated with reduced antral follicle count [ 89 ] and oocyte yield at retrieval [ 87 ]. Other studies have shown that metabolites of DiNP was associated with shorter luteal phase [ 88 ]. Another study pointed to higher concentrations of DEHP metabolites among women with fertility issues [ 85 ]. This same study also found MEP, a metabolite of DEP, to be higher in women with reported infertility that sought ART [ 85 ]. Nine studies evaluated the association between BPA and fertility outcomes based on studies conducted in the U.S. [ 45 , 86 , 90 , 91 , 88 , 92 – 95 ]. Of these, two cohorts of healthy women without known fertility problems found that urinary BPA was unrelated to time to pregnancy despite a shorter luteal phase being reported in one study [ 86 , 88 ]. On the other hand, studies conducted in fertility centers suggested BPA exposure was associated with lower ovarian reserve [ 95 ], poor ovarian stimulation responses [ 94 ], and higher risk of miscarriage [ 92 ]. While BPA was associated with worse earlier endpoints following ART, higher concentrations of this chemical was unrelated to live birth rate [ 93 ], the most relevant outcomes for fertility patients and their care providers. These studies suggest that BPA may affect ovarian functions and early process of conception. However, only one study presented strata-specific racial/ethnic differences. They found that Asian women had an increased oocyte maturity rate, but this group had substantially lower BPA concentrations in this study [ 91 ]. Two studies from the same population evaluated the association between parabens and infertility outcomes [ 96 , 97 ]. One study found an association between higher propyl paraben and diminished ovarian reserves [ 96 ]. The other study found no association between parabens and IVF treatment outcomes [ 97 ]. Three U.S. studies have evaluated PBDEs as they relate to reproductive success [ 98 – 100 ]. These studies found an association between certain congeners of PBDEs with pregnancy outcomes. For example, a study conducted among predominantly white women living in Texas and Michigan found a suggestively inverse association between PBDE 183 and fecundity as measured by time to pregnancy [ 98 ]. Another study comprised predominantly of Mexican population living in California found an association with higher PBDE153 and PBDE100 concentrations with a decreased fecundity odds ratio, a measure of longer time to pregnancy [ 99 ]. In a separate study conducted in the Boston area, which was comprised of over 80% white women, there was an association between PBDE153 and increased odds of failed embryo implantation [ 100 ]. For the last decade researchers investigated the role of certain EDCs in maternal pregnancy complications. Much of this work has focused on preterm birth, pregnancy hypertensive disorders, gestational diabetes, and related factors known to be more common in racial/ethnic minorities. Below, we describe the associations between the selected EDCs, pregnancy complications and related factors ( Table 4 ). Most studies adjust for race/ethnicity, but do not present stratified analyses or assess whether EDCs explain racial/ethnic disparities in the pregnancy complications under study. Preterm birth is one of the most studied pregnancy complications in terms of EDC exposures [ 101 , 102 , 69 , 103• , 104 , 46 , 105 , 106 , 33• , 107 , 108 , 115 ]. Two studies have found an association between higher DEHP concentrations with earlier gestational ages and preterm birth [ 103• , 107 ]. Another study found associations with higher maternal concentrations of metabolites of DiNP and DIDP, and dimethyl phthalate with shorter gestation length [ 106 ]. However, this study and an earlier study found associations between higher DEHP concentrations and reduced risk of shorter gestation length and preterm birth [ 101 , 106 ]. These conflicting results may be attributed to differences in timing, adjusted potential confounders, and differences in the distribution of phthalate metabolites across the populations. In fact, of the studies with positive associations with preterm birth, one was in a diverse population [ 108 ] and the other was composed of only blacks and Hispanics [ 107 ]. To explore potential pathways by which phthalates could be associated with preterm birth, Ferguson et al evaluated risk factors of preterm birth [ 109 , 69 , 102 ]. In these studies, a DEHP replacement was found to be associated with higher levels of a pro-inflammatory marker, interleukin-6 [ 102 ]. In another study, DEHP metabolites were found to be associated with decreases in the angiogenic marker, placental growth factor, a marker of good placental vasculature [ 109 ]. Likewise, there was an association between higher DEHP metabolites and sFLT-1/PLGF ratio, an indicator of preeclampsia and subsequently preterm birth [ 109 ]. Several phthalate metabolites were also found to be associated with elevated markers of oxidative stress in this same population [ 69 ]. Five studies evaluated BPA with pregnancy related outcomes, albeit the majority evaluated preterm birth [ 46 , 104 , 110 , 44 , 108 ]. Two studies found no association between BPA and gestation length or preterm birth [ 106 , 108 ]. However, these studies assessed BPA concentrations at different time points, with one looking at pre-conception concentrations [ 106 ], while the other assessed 3 rd trimester concentrations [ 108 ]. On the other hand, two studies found an association between BPA concentrations and an increased risk of preterm birth [ 104 , 110 ]; however, one study was cross-sectional making it difficult to determine temporality [ 110 ]. Only one study found an association between BPA and longer gestational age, but BPA was measured in serum possible contamination issues present [ 44 ]. These contradictory findings could point to the need to replicate the studies and take into account the high variability of BPA with respect to the timing of sample collection, type of study design, and the population under study. Of these studies, only one presented BPA concentrations stratified by race/ethnicity which showed that gestational age was shorter by almost 1 day among African Americans than Dominican women for each logarithmic unit increase in MEHP metabolites [ 107 ]. While five studies have examined gestation length, studies of other outcomes are only starting to emerge. Specifically, a small case-control study examined BPA in second trimester and GDM finding no association [ 46 ]. Another study evaluated BPA and angiogenic biomarkers, finding that sFLt-1 and the ratio between sFlt-1to PlGF was positively associated [ 109 ]. To our knowledge, studies have not evaluated the role of parabens and pregnancy complications in populations living in the U.S. Two U.S. studies have evaluated PBDEs and pregnancy complications. One study used a nested case-control design to evaluate the PBDEs at the time of delivery and risk of preterm birth finding that higher concentrations of PBDE-47 were associated with an increased odds of preterm birth [ 111 ]. Another study evaluated pre-conception PBDEs in a prospective cohort study examining several outcomes, including GDM and gestational hypertension [ 112 ]. They found associations between PBDE-153 and an increased odds of GDM, but did not find an association with any PBDEs and gestational hypertension. Both studies were predominantly white and adjusted for race/ethnicity in statistical models.