Joline Asp: Alcohol and pregnancy: Between Measurement and Biology

Abstract

Prenatal alcohol exposure is a major preventable cause of adverse pregnancy and offspring outcomes. While the effects of heavy alcohol exposure on fetal development are well established, less is known about the biological mechanisms linking alcohol exposure before and during pregnancy to maternal, placental, and inflammatory processes. The overall aim of this thesis was to investigate how alcohol exposure before and during pregnancy affects placenta- and inflammation-mediated pregnancy outcomes.

This thesis comprises four studies based on complementary study designs. Papers I and II used nationwide Swedish register data. Paper III was based on placental tissue from the South African Safe Passage Study, and Paper IV on maternal blood samples from the Swedish Biology, Affect, Stress, Imaging and Cognition (BASIC) cohort. Together, the studies combined epidemiological analyses with placental histopathology, transcriptomics, and proteomic analyses of inflammatory markers.

Hazardous alcohol consumption before pregnancy, assessed using the Alcohol Use Disorders Identification Test (AUDIT), was associated with an increased risk of maternal and neonatal infections, whereas associations with other obstetric outcomes were largely explained by maternal and socioeconomic factors. AUDIT showed high specificity but low sensitivity for identifying women with alcohol-related disorders, indicating that many women with documented alcohol-related disorders were not identified through routine antenatal screening. Prenatal alcohol exposure showed no consistent association with placental inflammatory lesions or altered placental gene expression. Likewise, alcohol consumption before pregnancy showed some associations with inflammatory marker levels in late pregnancy, but the findings were inconsistent and none remained significant after correction for multiple testing.

In conclusion, this thesis provides limited support for persistent placental or systemic inflammation as a major pathway linking alcohol exposure to adverse pregnancy outcomes. Instead, the findings suggest that alcohol-related immune dysfunction may contribute to increased susceptibility to maternal and neonatal infections. The results also highlight limitations of routine AUDIT screening and the need for improved methods to identify women with hazardous alcohol use in antenatal care.