Prenatal perfluoroalkyl substances exposure and maternal sex steroid hormones across pregnancy.

BACKGROUND: Poly- and perfluoroalkyl substances (PFAS) are ubiquitous and persistent environmental contaminants that may act as endocrine disruptors in utero, but the specific endocrine pathways are unknown. OBJECTIVE: We examined associations between maternal serum PFAS and sex steroid hormones at three time points during pregnancy. METHODS: Pregnant women participating in the Understanding Pregnancy Signals and Infant Development (UPSIDE) study contributed biospecimens, questionnaire, and medical record data in each trimester (n = 285). PFAS (including perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA)) were analyzed in second-trimester serum samples by high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). Total testosterone [TT], free testosterone [fT], estrone [E1], estradiol [E2], and estriol [E3]) were measured by LC-MS/MS in serum samples from each trimester. Linear mixed models with random intercepts were used to examine associations between log-transformed PFAS concentrations and hormone levels, adjusting for covariates, and stratifying by fetal sex. Results are presented as the mean percentage difference (Δ%) in hormone levels per ln-unit increase in PFAS concentration. RESULTS: In adjusted models, PFHxS was associated with higher TT (%Δ = 20.0, 95%CI: 1.7, 41.6), particularly among women carrying male fetuses (%Δ = 15.3, 95%CI: 1.2, 30.7); this association strengthened as the pregnancy progressed. PFNA (%Δ = 7.9, 95%CI: 3.4, 12.5) and PFDA (%Δ = 7.2, 95%CI: 4.9, 9.7) were associated with higher fT, with associations again observed only in women carrying male fetuses. PFHxS was associated with higher levels of E2 and E3 in women carrying female fetuses (%Δ = 13.2, 95%CI: 0.5, 29.1; %Δ = 17.9, 95%CI: 3.2, 34.8, respectively). No associations were observed for PFOS and PFOA. CONCLUSION: PFHxS, PFNA, and PFDA may disrupt androgenic and estrogenic pathways in pregnancy in a sex-dependent manner.

Cohort profile: Understanding Pregnancy Signals and Infant Development (UPSIDE): a pregnancy cohort study on prenatal exposure mechanisms for child health.

PURPOSE: Extensive research suggests that maternal prenatal distress is reliably related to perinatal and child health outcomes-which may persist into adulthood. However, basic questions remain regarding mechanisms involved. To better understand these mechanisms, we developed the Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort study, which has several distinguishing features, including repeated assessments across trimesters, analysis of multiple biological pathways of interest, and incorporation of placental structure and function as mediators of child health outcomes. PARTICIPANTS: Women with normal risk pregnancies were recruited at <14 weeks gestation. Study visits occurred in each trimester and included extensive psychological, sociodemographic, health behaviour and biospecimen collection. Placenta and cord blood were collected at birth. Child visits (ongoing) occur at birth and 1, 6, 12, 24, 36 and 48 months of age and use standard anthropometric, clinical, behavioural, biological and neuroimaging methods to assess child physical and neurodevelopment. FINDINGS TO DATE: We recruited 326 pregnancies; 294 (90%) were retained through birth. Success rates for prenatal biospecimen collection were high across all trimesters (96%-99% for blood, 94%-97% for urine, 96%-99% for saliva, 96% of placentas, 88% for cord blood and 93% for buccal swab). Ninety-four per cent of eligible babies (n=277) participated in a birth examination; postnatal visits are ongoing. FUTURE PLANS: The current phase of the study follows children through age 4 to examine child neurodevelopment and physical development. In addition, the cohort participates in the National Institutes of Health's Environmental influences on Child Health Outcomes programme, a national study of 50 000 families examining early environmental influences on perinatal outcomes, neurodevelopment, obesity and airway disease. Future research will leverage the rich repository of biological samples and clinical data to expand research on the mechanisms of child health outcomes in relation to environmental chemical exposures, genetics and the microbiome.