Effects of vitamin D deficiency on neurobehavioural outcomes in children: a systematic review [version 1; peer review: 1 approved]

Introduction: Vitamin D plays an important role in brain development in experimental studies; however, the effect of vitamin D deficiency on child development remains inadequately characterized. We aimed to estimate the effects of vitamin D deficiency on neurobehavioural outcomes in children up to 18 years of age. Methods: We searched PubMed, EMBASE, PsycINFO, Scopus, Cochrane Library, Web of Science and Open Grey for published studies up to 10th January 2020. We included all studies that assessed the effects of maternal or child vitamin D status or vitamin D supplementation on neurobehavioural outcomes in children. Study findings were synthesized qualitatively as the high level of heterogeneity in study populations and methodologies precluded a quantitative meta-analysis. Results: Our search identified 5,633 studies, of which 32 studies with 31,445 participants from 18 countries were included in the systematic review. Of the studies identified, two were randomized controlled trials (RCTs) of vitamin D supplementation in children, while 30 were observational. One RCT (n=55) reported a beneficial effect of supplementation with lower doses compared to higher doses of vitamin D on motor development while the other RCT (n=70) found no beneficial effect of vitamin D supplementation on cognition in extremely preterm infants. Twelve mother-child studies (n=17,136) and five studies in children (n=1,091) reported an association between low maternal or child 25-hydroxyvitamin D levels and impaired neurobehavioural outcomes in children, while 15 mother-child studies (n=20,778) and eight studies in children (n=7,496) reported no association. Conclusions: Although animal studies point to an effect of vitamin D deficiency on brain development, there are few studies on the effects of vitamin D deficiency on neurobehavioural outcomes in children and their findings are inconsistent. There is a need for well-conducted, adequately powered studies to further determine these effects in children. Registration: PROSPERO ID CRD42018087619 ; registered on 15 February 2018