Investigating low birthweight and preterm birth as potential mediators in the relationship between prenatal infections and early child development: A linked administrative health data analysis

Background: Prenatal infections are associated with childhood developmental outcomes such as reduced cognitive abilities, emotional problems and other developmental vulnerabilities. However, there is currently a lack of research examining whether this arises due to potential intermediary variables like low birth weight or preterm birth, or due to some other mechanisms of maternal immune activation arising from prenatal infections. Methods: Administrative data from the National Health Service health board of Greater Glasgow & Clyde, Scotland, were used, linking birth records to hospital records and universal child health review records for 55 534 children born from 2011 to 2015, and their mothers. Causal mediation analysis was conducted to examine the extent to which low birth weight and preterm birth mediate the relationship between hospital-diagnosed prenatal infections and having developmental concern(s) identified by a health visitor during 6-8 weeks or 27-30 months child health reviews. Results: Model estimates suggest that 5.18% (95% CI 3.77% to 7.65%) of the positive association observed between hospital-diagnosed prenatal infections and developmental concern(s) was mediated by low birth weight, while 7.37% (95% CI 5.36 to 10.88%) was mediated by preterm birth. Conclusion: Low birth weight and preterm birth appear to mediate the relationship between prenatal infections and childhood development, but only to a small extent. Maternal immune activation mechanisms unrelated to low birth weight and preterm birth remain the most likely explanation for associations observed between prenatal infections and child developmental outcomes, although other factors (for example, genetic factors) may also be involved.