Prenatal exposure to common infections and newborn DNA methylation: A prospective, population-based study

• Published in: Brain, behavior, and immunity behavior, and immunity, 2024-10, Vol.121, p.244-256
• Main Authors: Suleri, Anna, Salontaji, Kristina, Luo, Mannan, Neumann, Alexander, Mulder, Rosa H., Tiemeier, Henning, Felix, Janine F., Marioni, Riccardo E., Bergink, Veerle, Cecil, Charlotte A.M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; ALSPAC; Asthma; Child development; DNA Methylation; Epigenesis, Genetic; Epigenetics; Female; Fetal Blood - metabolism; Generation R; Genome-Wide Association Study; Humans; Infant, Newborn; Infections - epidemiology; Infections - genetics; Male; Maternal immune activation; Maternal infections; Mental health; Pregnancy; Pregnancy Complications, Infectious - epidemiology; Pregnancy Complications, Infectious - genetics; Prenatal Exposure Delayed Effects - genetics; Prospective Studies
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2024.07.046

•Largest EWAS study on self-reported clinically evident prenatal infections with 2,338 mother–child dyads.•Weak associations between exposure to common infections (based on cumulative score) and newborn DNA methylation.•Suggestive sites implicate genes related to neurodevelopment and immune function.•Epigenetic proxy of infections not predictive ofchild mental or physical outcomes.•No link between prenatal infections and offspring epigenetic age acceleration. Infections during pregnancy have been robustly associated with adverse mental and physical health outcomes in offspring, yet the underlying molecular pathways remain largely unknown. Here, we examined whether exposure to common infections in utero associates with DNA methylation (DNAm) patterns at birth and whether this in turn relates to offspring health outcomes in the general population. Using data from 2,367 children from the Dutch population-based Generation R Study, we first performed an epigenome-wide association study to identify differentially methylated sites and regions at birth associated with prenatal infection exposure. We also examined the influence of infection timing by using self-reported cumulative infection scores for each trimester. Second, we sought to develop an aggregate methylation profile score (MPS) based on cord blood DNAm as an epigenetic proxy of prenatal infection exposure and tested whether this MPS prospectively associates with offspring health outcomes, including psychiatric symptoms, BMI, and asthma at ages 13–16 years. Third, we investigated whether prenatal infection exposure associates with offspring epigenetic age acceleration – a marker of biological aging. Across all analysis steps, we tested whether our findings replicate in 864 participants from an independent population-based cohort (ALSPAC, UK). We observed no differentially methylated sites or regions in cord blood in relation to prenatal infection exposure, after multiple testing correction. 33 DNAm sites showed suggestive associations (p