The moderating and mediating role of the placenta in the association between prenatal exposure to air pollutants and birth weight: A twin study.

Prenatal exposure to air pollution has been linked to lower birth weight, yet the role of the placenta in this association is often overlooked. This study investigates whether placental characteristics act as moderators or mediators in the association between prenatal exposure to particulate matter (PM10) and nitrogen dioxide (NO2) and birth weight in twins. The study included 3340 twins (born 2002-2013) from the East Flanders Prospective Twin Survey. Prenatal exposure was estimated using spatial-temporal interpolation for the whole pregnancy and its trimesters. Moderation (interaction) and mediation (direct, indirect, and total effects) of placental weight and umbilical cord insertion were assessed with analyses stratified a priori based on the presence of one or two placentas. Sensitivity analyses included stratification by prematurity. Placental weight acted as both a moderator and mediator. Moderation analysis: in twins with low placental weight, birth weight decreased with -93.18 g per 10 μg/m3 PM10 (95% CI: -164.17, -22.19) and -69.28 g per 10 μg/m3 NO2 (95% CI: -124.81, -13.76) for the whole pregnancy. Mediation analysis showed positive indirect effects of placental weight indicating an increase of 36.05 g (95% CI: 0.88, 70.61) birth weight per 10 μg/m3 PM10 over the whole pregnancy, particularly in twins born <35 weeks. Direct effects were mainly negative, but not significant. For NO2, significant negative indirect effects were observed in the third trimester. Moderation was most pronounced in the second half of pregnancy, while both moderation and mediation were more evident in twins with separate placentas. Positive indirect effects prevailed in the first half of pregnancy, while negative indirect effects were observed in the second half. Umbilical cord insertion was neither a moderator nor a mediator. To conclude, the placenta acts both as moderator and mediator in the association between air pollution and birth weight, highlighting the need to consider these pathways in future research.