Lower maternal serum 25(OH) D in first trimester associated with higher autism risk in Chinese offspring

Chen, Jianzhang; Xin, Kuolin; Wei, Junjie; Zhang, Kangli; Hu, Xin

doi:10.1016/j.jpsychores.2016.08.013

Cited by 88 publications

(68 citation statements)

References 27 publications

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“…Similarly, in the same cohort ( n = 4,334), vitamin D deficiency in cord blood was not associated with ASD diagnosis, while low maternal mid‐gestation 25(OH)D was associated [Vinkhuyzen et al, ]. Taken together, these studies and a study that found low maternal first trimester 25(OH)D was associated with higher risk for ASD diagnosis [Chen et al, ], suggest that there may be a critical period for gestational vitamin D and ASD earlier in pregnancy, that was not well‐measured in this study. Further, given that concentrations in our overall study population were high and our proportion with vitamin D deficiency were low relative to other study populations, it is possible our study was not powered to detect associations at very low 25(OH)D concentrations.…”

Section: Discussionmentioning

confidence: 50%

“…Animal studies show long‐lasting neurodevelopmental effects of transient vitamin D deficiency during gestation leading to autism‐relevant structural and functional changes in the brain and behaviors of the offspring [Eyles et al, ; Eyles et al, ; Grecksch, Ruthrich, Höllt, & Becker, ; Levenson & Figueiroa, ]. Several studies have recently found associations between gestational vitamin D status and ASD diagnosis [Chen, Xin, Wei, Zhang, & Xiao, ; Fernell et al, ; Vinkhuyzen et al, ] and autism‐related traits [Vinkhuyzen et al, ], but findings have been inconsistent, and the number of children diagnosed with ASD has been relatively small and did not allow for investigation of effect modification by race and sex. There is biological potential for heterogeneous effects across sex given that sex hormones like estrogen and testosterone have very different effects on calcitriol's metabolism [Cannell, ], and males are more prone to vitamin D deficiency [Tonnesen, Hovind, Jensen, & Schwarz, ].…”

Section: Introductionmentioning

confidence: 99%

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Neonatal vitamin D status in relation to autism spectrum disorder and developmental delay in the CHARGE case–control study

et al. 2019

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Vitamin D appears essential for normal neurodevelopment and cognitive and behavioral function. We examined neonatal vitamin D in relation to the child's later diagnosis of autism spectrum disorder (ASD) or developmental delay (DD). Children aged 24-60 months enrolled in the population-based CHARGE case-control study were evaluated clinically for ASD (n = 357), DD (n = 134), or typical development (TD, n = 234) at the MIND Institute (Sacramento, CA) using standardized assessments. Total 25-hydroxyvitamin D (25[OH]D) was measured using sensitive isotope dilution liquid chromatography-tandem mass spectrometry in archived dried blood spots collected for the California Department of Public Health's Newborn Screening Program. Multinomial logistic regression was used to calculate ORs as measures of the associations between 25 nmol/L change in 25(OH)D and ASD and DD. Associations between 25(OH)D and scores on Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales were assessed using robust linear regression. Effect modification was examined using stratified models and interaction product terms.Unadjusted mean (SD) 25(OH)D was lower for DD (73.2 [37.6]) than for TD (82.7 [39.3]) and ASD (80.1 [37.4]). After adjustment for maternal prepregnancy body mass index and education, a 25 nmol/L increase in total 25(OH)D was not associated with ASD (OR = 0.97; CI: 0.87-1.08) or DD (OR = 0.91; 95% CI: 0.78-1.06). Neonatal 25(OH)D was associated with significantly reduced ASD only in females (adjusted OR = 0.74; 95% CI: 0.55-0.99, P interaction = 0.03), and significantly reduced DD only in non-Hispanic white children (adjusted OR = 0.79; 95% CI: 0.63-0.98, P interaction = 0.11 for Hispanic, P interaction = 0.31 for other), driven by DD children with trisomy 21. This study provides evidence that neonatal vitamin D could be associated with ASD in females and with DD in non-Hispanic white children. Autism Res 2019, 12: 976-988.Lay Summary: Vitamin D appears essential for brain development and function. We examined neonatal total 25hydroxyvitamin D (25[OH]D) measured in dried blood spots in relation to later diagnoses of autism spectrum disorder (ASD) or developmental delay (DD) and related assessment scores. Higher neonatal 25(OH)D was associated with a 26% reduction in the odds for ASD only in females. After taking into account factors that could contribute to vitamin D status, a significant association with 21% reduced odds for DD was found only in non-Hispanic white children. Though results were nonsignificant overall, certain subgroups might benefit from higher neonatal vitamin D.

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Section: Discussionmentioning

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Neonatal vitamin D status in relation to autism spectrum disorder and developmental delay in the CHARGE case–control study

et al. 2019

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“…Relatively recently a few studies with measured neonatal, or prenatal (maternal), vitamin D status in relation to ASD were published, generally reporting an inverse association, including two small studies (<75 cases) based on newborn blood spots [Fernell et al, ] or first trimester maternal serum [Chen et al, ], which did not adjust for many other factors. A cohort study in the Netherlands with a similar small number of cases ( N = 68), but adjustment for multiple confounders, showed a twofold increased risk of ASD with maternal 25(OH)D deficiency (defined as <25 nmol/L) mid‐pregnancy [Vinkhuyzen et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies examining the association between vitamin D and ASD were published after Cannell's hypothesis; however, many examined surrogates of vitamin D status, such as latitude or season, or measured vitamin D levels after ASD diagnosis, so are likely to reflect current lifestyle [Du et al, ; Fernell et al, ; Humble et al, ; Meguid, Hashish, Anwar, & Sidhom, ; Molloy, Kalkwarf, Manning‐Courtney, Mills, & Hediger, ; Mostafa & Al‐Ayadhi, ]. Only recently have vitamin D levels (typically as total 25‐hydroxyvitamin D, e.g., 25(OH)D) been measured prenatally or perinatally, a critical period for brain development; two small studies found lower 25(OH)D levels among ASD cases compared with controls but did not adjust for many other factors [Chen, Xin, Wei, Zhang, & Xiao, ; Fernell et al, ], as did a larger study from China [Wu et al, ] that also reported increased ASD risk with neonatal vitamin D deficiency in a thoroughly matched analysis. Other studies with measured perinatal 25(OH)D levels have examined related neurobehavioral metrics, with several finding adverse outcomes associated with lower vitamin D levels [Darling et al, ; Hanieh et al, ; Morales et al, ; Vinkhuyzen et al, ; Whitehouse et al, ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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“…A case-control study carried out in China found that lower first trimester maternal circulating concentration of 25(OH)D was associated with increased risk of developing autism in offspring at age 3-7 [79]. A register-based total population study carried out in Sweden found a positive association between lifetime diagnoses of maternal vitamin D deficiency (serum 25(OH)D level of less than 25 nmol/L) and risk of ASD in children aged 4-17, which was especially noticeable for ASD with intellectual disability, and for children of non-immigrant mothers [80].…”

Section: Autism Spectrum Disordermentioning

confidence: 99%

Maternal and Foetal Health Implications of Vitamin D Status during Pregnancy

Larqué

Morales

Leis³

et al. 2018

Ann Nutr Metab

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Background: To what extent does the circulating 25-hydroxyvitamin D (25[OH]D) concentration help to meet the physiological needs of humans is an ongoing subject of debate. Remaining unexposed to the sun to reduce melanoma cancer risk, current lifestyle with less out door activities, and increasing obesity rates, which in turn increases the storage of vitamin D in the adipose tissue, are presumably factors that contribute to the substantial upsurge in the prevalence of vitamin D deficiency in humans. Since evidence is lacking regarding the appropriate cut-off points to define vitamin D status during pregnancy, references used to establish the intake recommendations and vitamin D content of prenatal vitamin supplements are quite conservative. Summary: The foetus depends fully on maternal 25(OH)D supply. 25(OH)D readily crosses the placenta and it is activated into 1,25(OH)₂D by foetal kidneys. Moreover, 1,25(OH)₂D can also be synthesized within the placenta to regulate placental metabolism. The importance of vitamin D during pregnancy for maintaining maternal calcium homeostasis and therefore for foetal bone development is well recognized; major discussions are in progress regarding the potential maternal detrimental effects on pregnancy outcomes, foetal development, and the long-term health of children. Interventional studies have also evaluated the effect of vitamin D for reduction on preterm birth and asthma programming. Key Messages: Clinically, by understanding the effects of vitamin D on perinatal outcomes, we could individualize antenatal counselling regarding vitamin D supplementation to ensure vitamin D repletion without increasing the risk of foetal hypercalcemia.

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Lower maternal serum 25(OH) D in first trimester associated with higher autism risk in Chinese offspring

Cited by 88 publications

References 27 publications

Neonatal vitamin D status in relation to autism spectrum disorder and developmental delay in the CHARGE case–control study

Neonatal vitamin D status in relation to autism spectrum disorder and developmental delay in the CHARGE case–control study

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

Maternal and Foetal Health Implications of Vitamin D Status during Pregnancy

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