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

Abstract

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 birthweight 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 (NHS) health board of Greater Glasgow & Clyde, Scotland, was used, linking birth records to hospital records and universal child health review records for 55,534 children born from 2011-2015, and their mothers. Causal mediation analysis was conducted to examine the extent to which low birthweight and preterm birth mediate the relationship between hospital-diagnosed prenatal infections and having developmental concern(s) identified by a health visitor during 6-8 week or 27-30 month child health reviews. Results: Model estimates suggest that 5.18% [95% CI: 3.77-7.65%] of the positive association observed between hospital diagnosed prenatal infections and developmental concern(s) was mediated by low birthweight, whilst 7.37% [95% CI: 5.36-10.88%] was mediated by preterm birth. Conclusion: Low birthweight 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 birthweight and preterm birth remain the most likely explanation for associations observed between prenatal infections and child developmental outcomes, although other factors (e.g. genetic factors) may also be involved.