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

Abstract

Background: Prenatal phthalate exposure has been inconsistently associated with fetal growth and infant birth weight. However, the effect of exposure during the paternal and maternal preconception period 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=1425) 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 (18g; 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.

Keywords: Birth weight; Maternal exposure; Paternal exposure; Phthalates; Preconception.

Copyright © 2017 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Association between loge-unit increase in paternal preconception (A), maternal preconception (B), and maternal prenatal phthalate (C) concentrations and birth weight (g) among IVF-conceived singletons. Abbreviations: DEHP: di(2-ethylhexyl) phthalate; MEHP: mono(2-ethylhexyl) phthalate; MEHHP: mono(2-ethyl-5-hydroxyhexyl) phthalate; MEOHP: mono(2-ethyl-5-oxohexyl) phthalate; MECPP: mono(2-ethyl-5-carboxypentyl) phthalate; MEP: monoethyl phthalate; MBP: mono-n-butyl phthalate; MiBP: mono-isobutyl phthalate; MBzP: monobenzyl phthalate;MCPP: mono(3-carboxypropyl) phthalate; MCOP: monocarboxyisooctyl phthalate; MCNP: monocarboxyisononyl phthalate. Models 1: Unadjusted analysis. Paternal Model: N=119; Maternal Preconception Model: N=204; Maternal Prenatal Model: N=174. Paternal Model 2: Adjusted for maternal and paternal age (continuous), maternal and paternal Body Mass Index (continuous), maternal education (<college, college, graduate degree), maternal and paternal smoking (ever/never), gestational age (days), infertility diagnosis (male, female, unexplained), N=116. Paternal Model 3: Adjusted for covariates from Model 2 + maternal prenatal phthalate metabolite concentrations, N=105. Maternal Models 2: Adjusted for maternal age (continuous), Body Mass Index (continuous), education (<college, college, graduate degree), smoking (ever/never), and infertility diagnosis (male, female, unexplained); Maternal Preconception Model: N=195; Maternal Prenatal Model: N=169. Maternal Models 3: Adjusted for covariates from Model 2 + paternal preconception phthalate metabolite concentrations; Maternal Preconception Model: N=115; Maternal Prenatal Model: N=105.

Figure 2

Association between loge-unit increase in paternal preconception (A), maternal preconception (B), and maternal prenatal phthalate (C) concentrations and birth weight (g) among non-IVF conceived singletons. Abbreviations: DEHP: di(2-ethylhexyl) phthalate; MEHP: mono(2-ethylhexyl) phthalate; MEHHP: mono(2-ethyl-5-hydroxyhexyl) phthalate; MEOHP: mono(2-ethyl-5-oxohexyl) phthalate; MECPP: mono(2-ethyl-5-carboxypentyl) phthalate; MEP: monoethyl phthalate; MBP: mono-n-butyl phthalate; MiBP: mono-isobutyl phthalate; MBzP: monobenzyl phthalate;MCPP: mono(3-carboxypropyl) phthalate; MCOP: monocarboxyisooctyl phthalate; MCNP: monocarboxyisononyl phthalate. Models 1: Unadjusted analysis. Paternal Model: N=76; Maternal Preconception Model: N=155; Maternal Prenatal Model: N=147. Paternal Model 2: Adjusted for maternal and paternal age (continuous), maternal and paternal Body Mass Index (continuous), maternal education (<college, college, graduate degree), maternal and paternal smoking (ever/never), gestational age (days), and infertility diagnosis (male, female, unexplained), N=72. Paternal Model 3: Adjusted for covariates from Model 2 + maternal prenatal phthalate metabolite concentrations, N=69. Maternal Models 2: Adjusted for maternal age (continuous), Body Mass Index (continuous), education (<college, college, graduate degree), smoking (ever/never), and infertility diagnosis (male, female, unexplained); Maternal Preconception Model: N=143; Maternal Prenatal Model: N=135. Maternal Models 3: Adjusted for covariates from Model 2 + paternal preconception phthalate metabolite concentrations; Maternal Preconception Model: N=72; Maternal Prenatal Model: N=69.