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

Abstract

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.

Association of Parental Preconception Exposure to Phthalates and Phthalate Substitutes With Preterm Birth

“…[63][64][65] It is accepted that early disruption to peri-implantation processes such as alterations in embryo spacing or development, decidualization, and placentation may perpetuate throughout pregnancy, manifesting later as preterm birth, among other adverse outcomes. 66 Based on previous results from the EARTH Study team and those of others, including fertile populations, we hypothesize that an early action of DEHP metabolites at the ovary may interfere with normal fertility and implantation processes, 67,68 predisposing to a syndrome of complications throughout gestation that may be associated with altered placental function, 69,70 embryo and fetal growth restriction, 71 preeclampsia, 72 pregnancy loss, 73 and ultimately preterm birth. Of relevance for preventive care, this syndrome could have its roots in the preconception or periconception period.…”

Evaluating effects of prenatal exposure to phthalate mixtures on birth weight: A comparison of three statistical approaches

“…In a population-based birth cohort study in Spain (n=488 mother-child pairs), Casas et al showed that prenatal urinary MBzP concentrations were positively associated with birth weight among boys but not in girls. By contrast, three studies, including a prospective multiethnic cohort in New York city (n=404)(Wolff et al, 2008), a case-control study (n=191) in France,(Philippat et al, 2012) and a recent prospective study from the EARTH cohort (Messerlian et al, 2017) (n=321) reported that neither the individual prenatal phthalate metabolites nor the grouping of phthalate metabolites based on molecular weight were associated with birth weight. Of note, however, in the latter study (Messerlian et al, 2017), Messerlian et al .…”

Urinary Phthalate Metabolites in Common Bottlenose Dolphins (Tursiops truncatus) From Sarasota Bay, FL, USA

“…Bottlenose dolphin exposure to DEHP and DEP is concerning due to laboratory and human studies linking these chemicals to adverse health effects including altered hormone synthesis and transport (ATSDR, ; Meeker & Ferguson, ; Sathyanarayana et al, ], male genital developmental abnormalities (ATSDR, ; Swan, ), reproductive impairment (e.g., lower birth weight, Messerlian et al, ; preterm birth, Meeker et al, ; delayed time to pregnancy, Thomsen et al, ; pregnancy loss, H. Gao et al, ), and liver toxicoses including liver cancer (ATSDR, ). In fact, MEHP concentrations measured in the dolphins in this study (GM = 1.9 ng/ml; Range = 0.9–5.9 ng/ml) were at comparable levels reported to be associated with a reduced probability of reproductive success in humans (Hauser et al, ).…”