Association of phthalate exposure with low birth weight in couples conceiving naturally or via assisted reproductive technology in a prospective birth cohort

Abstract

BackgroundFew studies have investigated the adverse effects of preconception phthalate (PAE) exposure on birth weight in couples receiving assisted reproductive technology (ART) compared to naturally conceived newborns. ObjectivesWe examined the association between parental preconception/prenatal urinary phthalate exposure and low birth weight (LBW) risk in couples who conceived using ART or naturally. MethodsFrom the Jiangsu Birth Cohort Study (China), we recruited 544 couples who conceived after infertility treatment and 940 couples who conceived naturally and gave birth to a singleton infant between November 2014 and December 2019. Seventeen metabolites of phthalate and three metabolites of phthalate alternatives were analyzed in parental spot urine samples. Clinical data were collected from medical records. We used generalized linear models, elastic net regression, Bayesian kernel machine regression, and quantile-based g-computation to examine the individual and joint effects of parental phthalate exposure on birth weight and LBW risk ratios (RR). ResultsThe relationship between parental phthalate exposure and birth weight was consistent between ART and natural conception. Maternal exposure to mono-ethyl phthalate and mono-carboxyisooctyl phthalate was associated with an increased risk of LBW in ART-conceived infants (RR = 1.27; 95 % confidence interval (CI): 1.03, 1.56; and RR = 1.31; 95 % CI: 1.03, 1.67, respectively). In contrast, in the spontaneously conceived infants, higher paternal prenatal concentrations of mono-benzyl phthalate and mono-carboxyisononyl phthalate were associated with a 40 % and 53 % increase in LBW risk, respectively. Exposure to PAE mixtures was associated with LBW in ART-conceived infants, with the effects primarily driven by di-ethyl phthalate, benzylbutyl phthalate, and di-isononyl phthalate metabolites. Sex-specific LBW was observed, with females appearing to be more susceptible than males. ConclusionsMaternal preconception and paternal prenatal exposure to phthalates were associated with increased risk of LBW in infants. Compared with natural conception, ART-conceived fetuses were more sensitive to PAE mixtures, which requires further attention.