Newborn vitamin D levels in relation to autism spectrum disorders and intellectual disability: A case–control study in california

Abstract

Vitamin D deficiency has been increasing concurrently with prevalence of autism spectrum disorders (ASD), and emerging evidence suggests vitamin D is involved in brain development. Most prior studies of ASD examined vitamin D levels in children already diagnosed, but a few examined levels during perinatal development, the more likely susceptibility period. Therefore, we examined newborn vitamin D levels in a case-control study conducted among births in 2000-2003 in southern California. Children with ASD (N = 563) or intellectual disability (ID) (N = 190) were identified from the Department of Developmental Services and compared to population controls (N = 436) identified from birth certificates. 25-hydroxyvitamin D (25(OH)D) was measured in archived newborn dried blood spots by a sensitive assay and corrected to sera equivalents. We categorized 25(OH) D levels as deficient (<50 nmol/L), insufficient (50-74 nmol/L), and sufficient (≥75 nmol/L), and also examined continuous levels, using logistic regression. The adjusted odds ratios (AOR) and 95% confidence intervals for ASD were 0.96 (0.64-1.4) for 25(OH)D deficiency (14% of newborns) and 1.2 (0.86-1.6) for insufficiency (26% of newborns). The AORs for continuous 25(OH)D (per 25 nmol/L) were 1.0 (0.91-1.09) for ASD and 1.14 (1.0-1.30) for ID. Thus, in this relatively large study of measured newborn vitamin D levels, our results do not support the hypothesis of lower 25(OH)D being associated with higher risk of ASD (or ID), although we observed suggestion of interactions with sex and race/ethnicity. 25(OH)D levels were relatively high (median 84 nmol/L in controls), so results may differ in populations with higher prevalence of low vitamin D levels. Autism Res 2019, 12: 989-998.Lay Summary: We studied whether vitamin D levels measured at birth were related to whether a child later developed autism (or low IQ). Our results did not show that children with autism, or low IQ, overall had lower vitamin D levels at birth than children without autism. Vitamin D levels were fairly high, on average, in these children born in Southern California.

Maternal circulating Vitamin D3 levels during pregnancy and behaviour across childhood

“…In our study, we observed a weak negative association between prenatal 25(OH)D 3 and ASD symptoms at 5 years of age that was not significant upon adjustment for potential confounding variables. These results are in line with two Californian studies 20,21 . On the contrary, previous research carried out in Australian 15 and Dutch birth cohort studies 6,19 found stronger associations with this outcome.…”

“…Two other studies, one of them developed in our cohort, the Spanish population-based birth cohort INMA (INfancia y Medio Ambiente [Childhood and Environment]), also reported negative associations between prenatal 25(OH)D 3 and ADHD symptoms at preschool age 13,14 . The evidence for an association between prenatal levels of 25(OH)D and autism spectrum disorder (ASD) symptoms is inconsistent, while some studies found negative relationships 6,15–19 , others obtained null results 20,21 . Nevertheless, a recently conducted meta-analysis showed negative associations between prenatal 25(OH)D 3 and both ADHD and ASD symptoms 22 .…”

Vitamin D Status Is Not Associated with Cognitive or Motor Function in Pre-School Ugandan Children

“…Our findings of no association between vitamin D status and cognitive or motor function, agree with nine previous observational studies [34][35][36][37][38][39][40][41][42]. On the contrary, a small dose-response randomized controlled trial (n = 55) of vitamin D supplementation in Canadian infants reported that a lower dose of 400 international units (IU) of vitamin D was more beneficial for gross motor development than higher doses of 800 IU or 1200 IU [16].…”

Maternal Dietary Factors and the Risk of Autism Spectrum Disorders: A Systematic Review of Existing Evidence

“…We identified 11 studies evaluating maternal and/or neonatal biomarker‐measured Vitamin D status in relation to ASD, including 4 prospective cohort studies (2 of these from the Generation R cohort) [Lopez‐Vicente et al, 2019; Vinkhuyzen et al, 2017, 2018; Whitehouse et al, 2013] and 7 case–control studies [Chen et al, 2016; Fernell et al, 2015; Lee et al, 2019; Schmidt, Niu, Eyles, Hansen, & Iosif, 2019; Windham et al, 2019; Wu et al, 2018].…”

“…Neonatal levels of Vitamin D level are dependent on maternal Vitamin D during pregnancy, reflecting 60-80% maternal Vitamin D level [Hollis, Johnson, Hulsey, Ebeling, & Wagner, 2011;Kiely, Hemmingway, & O'Callaghan, 2017;Marshall, Mehta, Ayers, Dhumal, & Petrova, 2016]; hence, studies examining neonatal levels were considered to meet our inclusion criteria of representing gestational exposures. We identified 11 studies evaluating maternal and/or neonatal biomarker-measured Vitamin D status in relation to ASD, including 4 prospective cohort studies (2 of these from the Generation R cohort) [Lopez-Vicente et al, 2019;Vinkhuyzen et al, 2017Vinkhuyzen et al, , 2018Whitehouse et al, 2013] and 7 case-control studies [Chen et al, 2016;Fernell et al, 2015;Lee et al, 2019;Schmidt, Niu, Eyles, Hansen, & Iosif, 2019;Windham et al, 2019;Wu et al, 2018].…”