Exposure to Bisphenol A and Phthalates during Pregnancy and Ultrasound Measures of Fetal Growth in the INMA-Sabadell Cohort

Casas, Maribel; Valvi, Damaskini; Ballesteros‐Gómez, Ana; Gascón, Mireia; Fernández, Mariana F.; Garcia-Esteban, Raquel; Íñiguez, Carmen; Martínez, David; Murcia, Mario; Monfort, Núria; Luque, Noelia; Rubio, Soledad; Ventura, Rosa; Sunyer, Jordi; Vrijheid, Martine

doi:10.1289/ehp.1409190

Cited by 140 publications

(124 citation statements)

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“…1), which is consistent with observations in other studies. 9, 34 However, we additionally created models containing measures from visit 2 for comparison. Effect estimates for all analyses were presented as SD change in growth measures in association with an interquartile range (IQR) increase in visit 4 cumulative and specific gravity corrected phthalate metabolite or BPA concentrations.…”

Section: Methodsmentioning

confidence: 99%

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Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth

Ferguson

Meeker

Cantonwine

et al. 2016

Environment International

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Growth of the fetus is highly sensitive to environmental perturbations, and disruption can lead to problems in pregnancy as well as later in life. This study investigates the relationship between maternal exposure to common plasticizers in pregnancy and fetal growth. Participants from a longitudinal birth cohort in Boston were recruited early in gestation and followed until delivery. Urine samples were collected at up to four time points and analyzed for concentrations of phthalate metabolites and bisphenol A (BPA). Ultrasound scans were performed at four time points during pregnancy for estimation of growth parameters, and birthweight was recorded at delivery. Growth measures were standardized to a larger population. For the present analysis we examined cross-sectional and repeated measures associations between exposure biomarkers and growth estimates in 482 non-anomalous singleton pregnancies. Cross-sectional associations between urinary phthalate metabolites or BPA and growth indices were imprecise. However, in repeated measures models, we observed significant inverse associations between di-2-ethylhexyl phthalate (DEHP) metabolites and estimated or actual fetal weight. An interquartile range increase in summed DEHP metabolites was associated with a 0.13 standard deviation decrease in estimated or actual fetal weight (95% confidence interval=−0.23, −0.03). Associations were consistent across different growth parameters (e.g., head circumference, femur length), and by fetal sex. No consistent associations were observed for other phthalate metabolites or BPA. Maternal exposure to DEHP during pregnancy was associated with decreased fetal growth, which could have repercussive effects.

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Section: Methodsmentioning

confidence: 99%

“…9-14 However, biologic plausibility exists for an impact of these chemicals on physical development. Phthalates and BPA have been shown to cause oxidative stress, hormonal disturbances, and epigenetic modifications that all could have deleterious effects on growth.…”

Section: Introductionmentioning

confidence: 99%

Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth

Ferguson

Meeker

Cantonwine

et al. 2016

Environment International

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“…Our most conservative paternal model included gestational age as a covariate. Several recent studies have also found suggestive sex-specific patterns in birth weight in relation to some prenatal phthalate metabolites and similarly report increased birth weight among boys but not girls (Watkins et al 2016; Casas et al 2016; Sathyanarayana et al 2016). …”

Section: Discussionmentioning

confidence: 82%

“…Others have found that DEHP and DBP exposure resulted in fewer litters, fewer live pups, and a decrease in the proportion of pups born alive, in a dose-dependent manner (Lamb et al 1987; Gray et al 2006). Over a dozen studies have examined the association between prenatal phthalate exposure and fetal weight or birth weight in humans, however results and conclusions varied by study design, frequency of exposure assessment (most relied on a single measurement in pregnancy), and biological matrix (not all measured phthalate metabolites in urine) (Marie et al 2015; Casas et al 2016; Lenters et al 2016; Shoaff et al 2016; de Cock et al 2016; Huang et al 2014). A well-designed study by Ferguson et al (2016) assessing prenatal urinary phthalates reported robust inverse associations of ΣDEHP metabolites and ultrasound based fetal weight (Ferguson et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Substantial experimental evidence in animals shows that phthalates are developmental and reproductive toxicants (Lyche et al 2009; Lovekamp-Swan and Davis 2003; Gray et al 2000; Marsman 1995; Tanaka 2002; Lamb et al 1987; Gray et al 2006). While there has been legitimate emphasis on studying the effects of prenatal phthalate exposure in humans, these studies have largely produced inconsistent findings due in part to considerable heterogeneity in design, study population and methods (Marie et al 2015; Louis et al 2008; Smarr et al 2015; Watkins et al 2016; Casas et al 2016; Sathyanarayana et al 2016). Given that phthalates may exert effects on both gametes and embryos, studies assessing exposure before conception as well as during pregnancy are necessary.…”

Section: Introductionmentioning

confidence: 99%

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Paternal and maternal urinary phthalate metabolite concentrations and birth weight of singletons conceived by subfertile couples

Messerlian

Braun

Mínguez-Alarcón

et al. 2017

Environment International

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Background Ortho-phthalates are known endocrine disruptors. Prenatal phthalate exposure has been inconsistently associated with fetal growth and infant birth weight; however, the effect of paternal and maternal preconception exposure remains understudied. Objectives To investigate associations of paternal and maternal preconception and maternal prenatal urinary phthalate metabolite concentrations with birth weight. Methods The study comprised 364 singletons born to 364 mothers and 195 fathers (195 couples) from the EARTH Study, a prospective cohort of couples from Boston, MA. Births were categorized by mode of conception: in-vitro fertilization based (IVF) (n=208) or non-IVF based (n=156, intrauterine insemination or non-medically assisted/natural conception). We measured urinary concentrations of eleven phthalate metabolites in maternal (n=1,425) and paternal (n=489) preconception and maternal prenatal (n=781) samples. Birth weight was abstracted from delivery records. Covariate-adjusted associations between loge-phthalate metabolite concentrations and birth weight were evaluated separately by mode of conception using multivariable linear regression. Results Each loge-unit increase in paternal urinary concentration of the sum of di(2-ethylhexyl) phthalate (ΣDEHP) metabolites was associated with a 90 gram (95% CI: −165, −15) decrease in birth weight among IVF singletons, but not among non-IVF singletons (18 grams; 95% CI: −76, 113). Additional adjustment for maternal prenatal ΣDEHP concentrations modestly strengthened findings among IVF singletons. While few associations were found with maternal preconception phthalate metabolites, we observed an inverse relationship between several maternal prenatal urinary phthalate metabolite concentrations and birth weight among IVF singletons in covariate-adjusted models. However, with further adjustment for specific paternal phthalate metabolite concentrations, these associations were attenuated and no longer significant. Conclusions Paternal preconception urinary concentration of ΣDEHP metabolites was associated with a decrease in birth weight among IVF-conceived singletons. These results, if replicated, highlight the importance of preconception health, especially among subfertile couples.

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Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth

et al. 2022

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and the Pooled Phthalate Exposure and Preterm Birth Study Group IMPORTANCE Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.OBJECTIVE To 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.EXPOSURES Urinary 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.

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Exposure to Bisphenol A and Phthalates during Pregnancy and Ultrasound Measures of Fetal Growth in the INMA-Sabadell Cohort

Cited by 140 publications

References 42 publications

Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth

Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth

Paternal and maternal urinary phthalate metabolite concentrations and birth weight of singletons conceived by subfertile couples

Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth

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