Per- and Polyfluoroalkyl Substances (PFAS) and miscarriage: The Norwegian Mother, Father and Child Cohort Study

Miscarriage is prevalent, occurring in around 15% of recognized pregnancies. Yet modifiable determinants remain elusive. Per- and polyfluoroalkyl substances (PFAS) can disrupt endocrine- and other biological pathways crucial for reproduction. Whether PFAS is associated with miscarriage in humans remains uncertain. To examine the association between PFAS concentrations and a recent miscarriage. We conducted a nested case-control study within The Norwegian Mother, Father, and Child Cohort Study (MoBa), which recruited pregnant women from 1999 to 2008. We utilized plasma concentrations of PFAS measured at enrolment from several MoBa sub-studies: Perfluorohexane sulfonate (PFHxS), Perfluoroheptane sulfonate (PFHpS), Perfluorooctane sulfonate (PFOS), Perfluorooctanoate (PFOA), Perfluorononanoate (PFNA), Perfluorodecanoate (PFDA) and Perfluoroundecanoate (PFUnDA). Associations with miscarriage were examined by comparing women with a single recent miscarriage to those with no prior pregnancies at enrollment, aiming to reduce the influence of parity on women’s PFAS concentrations. Recency was defined as a miscarriage occurring within two calendar years before the MoBa child's birth. Logistic regression models, adjusted for age, education, and birth year, estimated associations between PFAS concentrations during the current pregnancy and recent miscarriage. The joint effect of the total PFAS mixture was evaluated using quantile-based g-computation. Among 2525 nulliparous women with mid-pregnancy PFAS measurements, 253 experienced a recent miscarriage before MoBa enrolment. No clear associations between PFAS concentrations and recent miscarriage were identified in single-pollutant models nor for the overall PFAS mixture (OR 0.95 (95 % CI: 0.83-1.09, per quartile increase in PFAS). Additional adjustments for potential confounding factors, including body mass index, menstrual cycle characteristics and use of oral contraceptives did not alter the observation of overall null-findings. We found no clear association between PFAS concentrations and miscarriage among nulliparous women. • The association between PFAS and miscarriage was examined • Targeted nulliparous women to reduce parity's impact on PFAS levels • Participating women were exposed to multiple legacy PFAS • No clear PFAS-miscarriage association in nulliparous women was found