Prenatal Exposure to Select Phthalates and Phenols and Associations with Fetal and Placental Weight among Male Births in the EDEN Cohort (France)

Abstract

Background: The placenta performs crucial physiological functions to ensure normal fetal development. Few epidemiological studies investigated placental weight sensitivity to phthalates and phenols. Objective: Our goal was to explore whether maternal exposure to select phthalates and phenols is associated with changes in placental weight at birth and in placental–to–birth weight ratio (PFR). Methods: Placental weight and birth weight were available for 473 mother–son pairs in the EDEN (Etude des Déterminants pré et postnatals du développement et de la santé de l’Enfant) cohort for whom 9 phenols (4 parabens, 2 dichlorophenols, triclosan, benzophenone-3, bisphenol A) and 11 phthalate metabolites were measured in spot urine samples collected between weeks 23 and 29 of gestation. We used adjusted Elastic Net penalized regression models (ENET) to select biomarkers associated with placental weight, birth weight and PFR. Unpenalized effect estimates were then obtained by fitting linear regression models simultaneously adjusted for the ENET-selected biomarkers and a priori chosen confounders. Results: The multipollutant ENET model for placental weight retained four biomarkers: triclosan and monocarboxy-isononyl phthalate (MCNP), which were negatively associated with placental weight, and benzophenone-3 and the sum of parabens, which were positively associated with this outcome. The ENET model for PFR retained two phthalate metabolites [MCNP and monocarboxy-isooctyl phthalate (MCOP)], which were negatively associated with this outcome. Discussion: The positive association between the sum of parabens and placental weight was consistent with results of a previous study among 49 male births. Our results provide preliminary evidence of possible associations between other compounds such as triclosan, benzophenone-3, MCNP, and MCOP and both placental weight and PFR. These associations were not reported in previous studies and should be seen as hypothesis generating. Studies relying on repeated assessments of exposure in prospective mother–child cohorts are needed to substantiate the plausibility of the hypotheses generated by our results. https://doi.org/10.1289/EHP3523

Impact of prenatal triclosan exposure on gestational age and anthropometric measures at birth: A systematic review and meta-analysis

“…From 15 selected studies, 12 studies were cohort and 3 studies were cross-sectional studies. The number of studies that reported the association of TCS exposure with birth weight, birth length, birth head, and gestational age was 13,[ 4 7 10 11 12 18 19 20 21 22 23 24 25 ] 9,[ 4 6 7 11 12 18 22 23 26 ] 8,[ 4 6 7 12 18 19 22 26 ] and 6,[ 4 6 11 12 22 25 ] respectively. All studies had evaluated the prenatal exposure to TCS and growth in both male and female neonates, except 2 studies that investigated it in male infants.…”

“…All studies had evaluated the prenatal exposure to TCS and growth in both male and female neonates, except 2 studies that investigated it in male infants. [ 18 21 ]…”

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.…”

Oestrogenic Endocrine Disruptors in the Placenta and the Fetus

“…Phthalates can cross the placental barrier as a result of continuous exposure during pregnancy, with profoundly negative consequences for the future health of infants, by increasing the risk of developing defects such as low birth weight, cardiovascular diseases, cryptorchidism, and cancer later in life [111,112]. The metabolites of DEHP have been detected by mass spectrometry in amniotic fluid.…”