Gender-specific relationship between prenatal exposure to phthalates and intrauterine growth restriction

Abstract

Background:No study has examined the association between prenatal phthalate exposure and intrauterine growth retardation (IUGR). This study aimed to investigate whether prenatal exposure to phthalates was associated with increased risk of IUGR. Methods: A total of 126 mother-newborn pairs, including 42 IUGR cases and 84 control newborns and their mothers, were enrolled in this case-control study. Spot urine samples were collected during the third trimester of pregnancy, and 5 phthalate metabolites (mono-n-butyl phthalate (MBP), monomethyl phthalate (MMP), mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)) were measured. results: Concentrations of MMP, MEHHP, MEOHP, and SumDEHP (MEHP, MEHHP, and MEOHP) were significantly higher in IUGR cases than in normal controls. In all subjects, urinary concentrations of MEHHP and MEOHP were significantly inversely associated with fetal growth indicators (birth weight and Quetelet's index). When mothers were stratified by infant sex, MEHHP and MEOHP concentrations were still negatively associated with fetal growth indicators, while no significant association was observed in females. In addition, exposureresponse relationships were observed between MEHHP/ SumDEHP concentrations in maternal urine and IUGR. conclusion: Prenatal exposure to phthalates was associated with increased risk of IUGR, and male newborns were more sensitive to phthalates than females. Phthalates, diesters of phthalic acid, are a group of chemicals that are widely used as plasticizers in many applications, including medical devices, toys, food wraps, shoe soles, and interior building surfaces (1). Because phthalates are additives and, as such, noncovalently bound to the plastic, they leach from the products with time and use, thus becoming ubiquitous environmental contaminants (2). Humans can be exposed to phthalates through inhalation, ingestion, dermal exposure, and medical treatments (3).Once taken into the body, phthalates are metabolized to their respective monoesters within a few hours or days, and then glucuronidated and excreted in the urine and feces. A notable human burden of phthalates has been reported and the consensus is that phthalate metabolites in urine could be used for assessing phthalate exposure in humans (4-11). In most cases, it is the monoester metabolites that have been claimed to be responsible for adverse health effects (12,13).Because phthalates can penetrate the placenta in humans (14), high phthalate levels in general, and in pregnant women in particular, have raised the urgent issue of prenatal exposure to phthalates. Fetuses are specifically vulnerable to a variety of toxicants because of the immaturity of their developing immune systems and the rapid development of their organs (15,16). During the fetal period, there is a "critical window" for the development of cardiovascular, nervous, reproductive, endocrine, immune, and respiratory systems when even a subtle exposure to chemicals may adverse...

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

“…39, 40 Additionally, the majority of these studies had sample sizes of ~200 or smaller. 14, 20, 41-43 These previous investigations have had mixed, but largely null, results. 10, 13, 14, 20, 23, 38, 41-46 The largest studies (n~300-400) reported null associations between phthalate metabolite measurements from spot urine samples collected during pregnancy and birthweight, length, and head circumference.…”

“…Finally, we examined adjusted models stratified by infant sex as previous studies have identified sex differences in these relationships (Models 3 and 4 for males and females, respectively). 14 Differences in coefficient estimates from male vs. female models were tested using a z statistic. We additionally created cross-sectional models with z-scored growth measures from visits 2-4 with the corresponding cumulative exposure metrics.…”

“…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.…”

Racial and ethnic variations in phthalate metabolite concentration changes across full-term pregnancies

“…For example, a recent study found associations between higher in utero exposure to certain phthalate metabolites and intrauterine growth restriction. 21 Interestingly, a greater proportion of Non-Hispanic black women have infants born small-for-gestational age compared to other racial/ethnic groups, 35 which is likely related to a host of factors, but could also be partly due to higher phthalate exposure in utero. Higher phthalate levels could explain some portion of racial/ethnic differences in maternal health outcomes.…”

“…For example, in pregnant women, higher urinary phthalate metabolite concentrations are associated with preterm birth 4619–20 and intrauterine growth restriction. 1921 In the offspring, in utero exposure to higher levels of phthalates is associated with changes in reproductive organ development, 5 eczema and allergic conditions, 22 as well as adverse neurobehavioral outcomes in children. 223–25 While previous studies have evaluated the variability of phthalate levels across pregnancy, 26–27 no study has characterized phthalate metabolite levels by race/ethnicity in a multi-racial population of pregnant women.…”