Prenatal maternal infections and early childhood developmental outcomes: Analysis of linked administrative health data for Greater Glasgow & Clyde, Scotland

Background: Previous research has linked prenatal maternal infections to later childhood developmental outcomes and socioemotional difficulties. However, existing studies have relied on retrospectively self-reported survey data, or data on hospital-recorded infections only, resulting in gaps in data collection. Methods: This study used a large linked administrative health dataset, bringing together data from birth records, hospital records, prescriptions and routine child health reviews for 55,856 children born in Greater Glasgow & Clyde, Scotland, in 2011-2015, and their mothers. Logistic regression models examined associations between prenatal infections, measured as both hospital-diagnosed prenatal infections and receipt of infection-related prescription(s) during pregnancy, and childhood developmental concern(s) identified by health visitors during 6-8 weeks or 27-30 months health reviews. Secondary analyses examined whether results varied by (a) specific developmental outcome types (gross-motor-skills, hearing-communication, vision-social-awareness, personal-social, emotional-behavioural-attention, and speech-language-communication), and (b) the trimester(s) in which infections occurred. Results: After confounder/covariate adjustment, hospital-diagnosed infections were associated with increased odds of having at least one developmental concern (OR: 1.30; 95% CI: 1.19-1.42). This was consistent across almost all developmental outcome types, and appeared to be specifically linked to infections occurring in pregnancy trimesters 2 (OR: 1.34; 95% CI: 1.07-1.67) and 3 (OR: 1.33; 95% CI: 1.21-1.47), i.e. the trimesters in which fetal brain myelination occurs. Infection-related prescriptions were not associated with a significant increase in odds of having at least one developmental concern after confounders/covariate adjustment (OR: 1.03; 95% CI: 0.98-1.08), but were associated with slightly increased odds of concerns specifically related to personal-social (OR: 1.12; 95% CI: 1.03-1.22) and emotional-behavioural-attention (OR: 1.15; 95% CI: 1.08-1.22) development. Conclusions: Prenatal infections, particularly those which are hospital-diagnosed (and likely more severe) are associated with early childhood developmental outcomes. Prevention of prenatal infections, and monitoring of support needs of affected children, may improve childhood development, but causality remains to be established. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study received funding by Economic and Social Research Council (ES/W001519/1) This study received funding by the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No.813546 This study received funding by the Baily Thomas Charitable Fund TRUST/VC/AC/SG/469207686 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of the School of Philosophy, Psychology and Language Sciences at the University of Edinburgh gave ethical approval for this work. NHS Scotland Public Benefit and Privacy Panel for Health and Social Care gave information governance approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The administrative health datasets used for this study are not publicly available. However, they can be accessed via successfully applying to the NHS Scotland Public Benefit and Privacy Panel for Health and Social Care