A Systematic Review into the Association Between Maternal Hypothyroidism and Neurodevelopmental Disorders in Childhood

Background In the previous 20 years, numerous studies have shown associations between maternal hypothyroidism during pregnancy and various types of neurodevelopmental disorders in children. However, other studies have not found significant associations and the field is complicated by differing definitions of hypothyroidism. Aim This systematic review aimed to collect all articles on this topic, both observational studies and RCTs, and where possible perform meta-analysis to find out the overall significance of a given association, with a particular focus on the outcomes of intellectual disability, autism and attention deficit hyperactivity disorder (ADHD) with the exposure as the three types of hypothyroidism (overt, subclinical and hypothyroxinaemia). Method This involved searching through MEDLINE, EMBASE, PSYCHINFO, CINAHL, AMED, BNI, Cochrane, Scopus and Web of Science, as well as grey literature searching and citation chasing. Articles were screened for inclusion by two reviewers, and data extraction and quality appraisal was carried out by the primary reviewer and checked by a secondary reviewer. Random-effects meta-analysis and narrative analysis were used. Results 37 relevant articles were discovered and underwent data extraction. In total, we found that the association between indicators of intellectual disability and maternal hypothyroxinaemia was significant, with a combined odds ratio of 2.69 (1.47-4.95). However, we did not find an association between subclinical hypothyroidism and indicators of intellectual disability or with maternal hypothyroidism with autism and ADHD. Conclusion This study shows that the evidence supports the link between intellectual disability and maternal hypothyroxinaemia. Future studies should focus more on school age children and on autism and ADHD, and have larger cohorts.