How 25(OH)D Levels during Pregnancy Affect Prevalence of Autism in Children: Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
2.1. Literature Search
2.2. Study Inclusion/Exclusion Criteria and Data Extraction
- Human study of vitamin D supplementation during pregnancy or vitamin D status of pregnancy or vitamin D status of ASD children;
- Available information of circulation concentration of 25(OH)D in maternal blood during pregnancy or in newborn blood at birth;
- Original research article and review in humans (abstracts, case reports, ecological studies, and comments were excluded);
- Outcomes including incidence of autism, measures of autism, severity, measures of neurophysiological aspects of autism, or expression of autism-related genes and vitamin D during pregnancy; and
- Article written in English
- Any study between 2010 and January 2020.
2.3. Study Quality
3. Results
3.1. Study Characteristics
3.2. Original Research Studies
3.3. Review and Meta-Analysis Studies
3.4. Summary of Findings
4. Discussion
Strengths and Limitations of This Review
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Grade | Risk of Bias | Description |
---|---|---|
1 | 1++ | High-quality meta-analyses, systematic reviews of RCTs, or RCTs with very low risk of bias |
1+ | Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with low risk of bias | |
1−− | Meta-analyses, systematic reviews, or RCTs with high risk of bias | |
2 | 2++ | High-quality systematic reviews of case-control or cohort studies; high-quality case-control or cohort studies with very low risk of confounding or bias and high probability of casual relationship |
2+ | Well-conducted case-control or cohort studies with low risk of confounding or bias and moderate probability of casual relationship | |
2−− | Case-control or cohort studies with high risk of confounding or bias and significant risk of noncausal relationship | |
3 | Nonanalytic studies, e.g., case reports, case series | |
4 | Expert opinion |
Grade | Description |
---|---|
A | At least one meta-analysis, systematic review, or RCT rated 1++, and directly applicable to target population A body of evidence consisting principally of studies rated 1+, directly applicable to the target population, and demonstrating overall consistency of results |
B | A body of evidence including studies rated 2++, directly applicable to target population, and demonstrating overall consistency of results Extrapolated evidence from studies rated 1++ or 1+ |
C | A body of evidence including studies rated 2+, directly applicable to the target population, and demonstrating overall consistency of results Extrapolated evidence from studies rated 2++ |
D | Evidence level 3 or 4Extrapolated evidence from studies rated 2+ |
Ref. | Location | Study Design | Period of Study | Participant | Sample Size | Target Pop. | Exposure Assessment Vitamin D | Major Findings | LE | GR | NOS |
---|---|---|---|---|---|---|---|---|---|---|---|
Wu et al. (2018) [32] | Beijing, China | Case-control | 2008–2010 | Newborn screening in Beijing (NBSIB) | n = 32,912 (n = 310 ASD and n = 1240 controls) | Children monitored from birth to age 3 years | Tiny sample of blood; liquid chromatography–tandem mass spectrometry | Neonatal vitamin D status was significantly (p < 0.0001) associated with risk of ASDs and intellectual disability. Compared with the fourth quartiles, the RR of ASDs was significantly increased for neonates in each of the three lower quartiles of the distribution of 25(OH)D3, and increased risk of ASDs by 260% (RR for lowest quartile, 3.6; 95% CI, 1.8 to 7.2; p < 0.001), 150% (RR for second quartile: 2.5; 95% CI, 1.4 to 3.5; p = 0.024), and 90% (RR for third quartile: 1.9; 95% CI, 1.1 to 3.3; p = 0.08), respectively. | 2++ | B | 8 |
B.K. Lee et al. (2019) [30] | Stockholm County, Sweden | Cohort | Participants born in Sweden, 1996–2000 | Stockholm Youth Cohort (n = 98,597) | Maternal sample consisted of 449 ASD cases and 574 controls, the neonatal sample: 1399 ASD cases and 1607 controls; and the paired maternal–neonatal sample: 340 ASD cases and 426 controls | Cohort of all children aged 0–17 years living in Stockholm County | Maternal sample examining prenatal 25(OH)D in maternal sera; neonatal sample examining neonatal 25(OH)D in dried blood spots taken soon after birth; neonatal sibling sample examining neonatal 25(OH)D in cases matched to unaffected siblings; and paired maternal–neonatal sample examining both maternal and neonatal 25(OH)D. 25(OH)D was measured using a tandem mass spectrometry assay. | In Nordic-born mothers, maternal 25(OH)D insufficiency (25–<50 nmol/L) at ~11 weeks’ gestation was associated with 1.58 times higher odds of ASD (95% CI, 1.00 to 2.49) than 25(OH)D sufficiency (≥50 nmol/L). Neonatal 25(OH)D <25 nmol/L was associated with 1.33 times higher odds of ASD (95% CI, 1.02 to 1.75) than 25(OH)D ≥50 nmol/L. | 2++ | B | 8 |
M.L. Vicente et al. (2019) [68] | Spain: Asturias, Gipuzkoa, Menorca, Sabadell, Valencia | Cohort | Feb. 1997–Sept. 1998, Menorca; Nov. 2003–Feb. 2008, other regions | Embedded in the Infancia y Medio Ambiente (INMA) Project, a population-based birth cohort based in regions across Spain | N = 3216; n = 2107 (mother–child pairs) | 10–13 weeks of gestation and their child’s neurodevelopmental assessment at 5, 8, 14, and 18 years old | Maternal blood and child plasma concentrations of 25(OH)D3 by high-performance liquid chromatography method using a Bio-Rad kit according to Clinical and Laboratory Standard Institute protocols | Per each 10-ng/mL increment of maternal vitamin D3, children obtained higher social competence scores (β-coefficient = 0.77; 95% CI, 0.19 to 1.35) at 5 y old | 2++ | B | 8 |
Ref. | Design | Studies Included | Location and Year | Participants | Sample Size (Case with ASD/Control) | ASD Diagnosis | Findings | Major Findings | LE | GR | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Common | Different | Design | ||||||||||
E. Kocovska et al. (2012) [73] | Review | Humble et al. (2010) | No controls, cross-sectional | Sweden | European adults psychiatric disorder incl. autism | N = 117 (117/0) | Significant difference (p < 0.005) The median (25th–75th percentile) is in autistic patients, 31.5 ng/mL (23–39); and in all patients, 45 ng/mL (31–60) | Vitamin D deficiency in pregnancy or early childhood may be an environmental trigger for ASD in people genetically susceptible to autism. | 2++ | B | ||
Meguid et al. (2010) | Case-control, cross-sectional | Egypt | Children with or without autism | n = 112 (70/42) | DSM-IV for clinical diagnosis | Significant difference (p < 0.005) In autistic children, 28.5 ng/mL Controls: typically developing children 40.1 ng/mL In addition, children with autism had significantly lower 25(OH)D (p < 0.00001) and 1,25(OH)(2)D (p < 0.005) as well as lower calcium (p < 0.0001) serum values than the controls. | ||||||
Molloy et al. (2010) | Case-control, cross-sectional | USA | White male children aged 4–8 years with ASD | n = 89 (49/40) | DSM-IV/ADOS | No significant difference (p = 0.4) Cases: 20 ng/mL All Participants <31 ng/mL. | ||||||
Fernell et al. (2010) | Case-control, cross-sectional | Sweden | Mothers of Somali or Swedish origin with a child with or without autism | n = 80 (40/40) | Significant difference Somali vs. Swedish mothers Cases: Somali mothers with autism child 6.7 ng/mL; Swedish mothers with autistic child 24.8 ng/mL Controls: Somali mothers with nonautistic child 9.6 ng/mL; Swedish mothers with nonautistic child 20.7 ng/mL. | |||||||
H. Mazahery et al. (2016) [72] | Review | Humble et al. (2010) | No controls, cross-sectional | Sweden | European adults psychiatric disorder incl. autism | n = 117 (117/0) | Significant difference (p < 0.005) In autistic patients, 31.5 ng/mL (23–39) In all patients, 45 ng/mL (31–60). | Low vitamin D status in utero, postnatal, and early childhood might affect different brain regions, and that situation might cause different neurodevelopmental and cognitive outcomes in infants. | 2++ | B | ||
Stubbs et al. (2016) | Prospective cohort (uncontrolled) | USA | Pregnant mothers of autistic children aged 18 months–3 years | n = 20 (no control) | MCHAT and PDDBI | Although autism recurrence rate reported in the literature is 20%, recurrence rate of autism in newborns was 5%. | ||||||
Saad et al. (2015) | Open-label intervention | Egypt | Autistic children with 25(OH)D <75 nmol/L | n = 222 (122/100) | DSM-IV/CARS, ABC 2 | 13% (n = 16): normal serum 25(OH)D concentration 57% (n = 70): vitamin D deficiency, 30% (n = 36): vitamin D insufficiency Mean 25(OH)D levels in patients with severe autism were significantly lower than patients with mild or moderate autism (p < 0.0001). Serum 25(OH)D levels showed significant negative correlation with CARS scores (r = −0.502, p < 0.0001). | ||||||
Azzam HME et al. (2015) | RCT | Egypt; from January 2009 until June 2010 | Children with ASD | n = 21 (21/0) | DSM-IV | No significant difference (three groups: 2.7 ± 1.9 y for vitamin D–supplemented group, 5.8 ± 2.9 y for unsupplemented autistic group, 5 ± 1.8 y for neurotypical control group) Mean presupplementation CARS scores for the two autistic groups were 33.9 ± 2.9 and 33 ± 3 (p > 0.05). Mean VABS was 51.4 ± 16 and 55.7 ± 20 (p > 0.05). | ||||||
Ucuz İİ et al. (2015) | Open-label intervention | Turkey | Toddlers aged 2–5 years with developmental delay without and with ASD | n = 66; 25(OH)D <50 nmol/L (n = 11 cases) and ≥50 nmol/L (n =10 controls) | ABC 1 Denver II | No significant difference between groups with normal and low vitamin D levels in terms of ADSI, Denver II, CBCL, and ABC scores, and NGF and GDNF levels (p > 0.05). | ||||||
Jia F et al. (2015) | Case | China | 32-month-old male toddler with ASD | ABC 1 CARS | Some autism symptoms improved significantly after vitamin D3 supplementation. | |||||||
Feng J et al. (2016) | Open-label intervention | China | Children with ASD | n = 500 (215/285) | DSM-IV/ADOS | Vitamin D3 may play an important role in etiology of ASD. Serum levels of 25(OH)D were significantly lower in ASD children than control group (p < 0.05). | ||||||
T. Wang et al. (2016) [74] | Systematic review and meta-analysis | Fernell et al. (2015) | Sibling–control | Sweden, 2005–2008 | Gothenburg catchment area group and Stockholm Somali group; children aged 4+ years | n = 116 (58/58) | Clinical report; ASD diagnosis | Collapsed group of children with ASD had significantly lower vitamin D levels (Mean = 24.0 nM, SD = 19.6) than siblings (Mean = 31.9 nM, SD = 27.7) (p = 0.013). | Decreased vitamin D levels in patients, decreased maternal vitamin D levels during pregnancy, and decreased exposure to solar UVB might increase the risk for ASD. | 2++ | B | |
Meguid et al. (2010) | Case-control, cross-sectional | Egypt | Children with or without autism | n = 112 (70/42) | DSM-IV for clinical diagnosis | Significant difference (p < 0.005) In autistic children, 28.5 ng/mL Controls: typically developing children 40.1 ng/mL In addition, children with autism had significantly lower 25(OH)D (p < 0.00001) and 1,25(OH)(2)D (p < 0.005) as well as lower calcium (p < 0.0001) serum values than the controls. | ||||||
Saad et al. (2015) | Open-label intervention | Egypt | Children with ASD | n = 222 (122/100) | DSM-IV/CARS, ABC 2 | 13% (n = 16): normal serum 25(OH)D concentration 57% (n = 70): vitamin D deficiency, 30% (n = 36): vitamin D insufficiency Mean 25(OH)D levels in patients with severe autism were significantly lower than patients with mild or moderate autism (p < 0.0001). Serum 25(OH)D levels showed significant negative correlation with CARS scores (r = −0.502, p < 0.0001). | ||||||
Adams et al. (2011) | Randomized, double-blind, placebo-controlled | U.S. | Two groups, an Arizona group aged 5–16 years and a National group aged 3–60 y; children and adults with autism | n = 141 (53/88) | DSM-V | No significant differences between ASD and control group in vitamin D3 [25(OH)D in plasma; p = 0.04]. | ||||||
Mostafa et al. (2012) | Cross-sectional | Saudi Arabia, April–September 2012 | Children aged 5–12 years with and without ASD | n = 80 (50/30) | DSM-IV | Autistic children had significantly lower serum levels of 25(OH)D than healthy children (p < 0.001). In addition, serum 25(OH)D levels had significant negative correlations with CARS (p < 0.001) and serum levels of anti-MAG autoantibodies (p < 0.001). | ||||||
Neumeyer et al. (2013) | Cohort | U.S. | Boys aged 8–14 years with and without ASD | n = 37 (18/19) | DSM-IV | Serum 25(OH)D levels were lower in boys with ASD than in controls (p = 0.05). | ||||||
Uğur et al. (2014) | Case-control | Turkey | ASD (recruited for the study); non-ASD healthy controls | n = 108 (54/54) | DSM-IV | No difference between ASD and healthy controls. | ||||||
Gong et al. (2014) | Case-control | China, January–December 2012 | Children with and without ASD; consecutive patients with ASD admitted to Dept. of Neurology | n = 96 (48/48) | DSM-IV, CARS (all cases) | Significant negative association between serum 25(OH)D levels and CARS scores (p = 0.000). | ||||||
Bener et al. (2014) | Case-control | Qatar, June 2011–May 2013 | Children aged 3–8 years; children with and without ASD | n = 508 (254/254) | DSM-IV | Significant difference found in mean values of vitamin D between autism (18.39 ± 8.2 ng/mL with median 18) and versus control children (21.59 ± 8.4 ng/mL) (p < 0.0001) and with median 21 (p = 0.004). | ||||||
DU et al. (2015) | Cohort | China | Children with and without ASD | n = 226 (117/109) | Lower 25(OH)D in ASD group (p < 0.01). | |||||||
Tostes et al. (2012) | Cohort | Brazil | Children with and without ASD | n = 48 (24/24) | DSM-IV | Serum levels of 25(OH)D were lower in children with autism (26.48 ± 3.48 ng/mL) than in typically developing subjects (40.52 ± 3.13 ng/mL) (p < 0.001). | ||||||
A.M. Garcia-Serna and E. Morales (2019) [71] | Systematic review and meta-analysis | Stubbs et al. (2016) | Prospective cohort (uncontrolled) | U.S. | Pregnant mothers of autistic children; 18 months–3 years | n = 20 (no control) | MCHAT and PDDBI | Although the autism recurrence rate reported in the literature is 20%, the recurrence rate of autism in newborns was 5%. | Meta-analysis showed higher levels of prenatal 25(OH)D to be associated with a lower risk of autistic traits. | 2++ | B | |
Fernell et al. (2015) | Sibling–control | Sweden, 2005–2008 | Gothenburg catchment area group and Stockholm Somali group; children aged 4+ years | n = 116 (58/58) | Clinical report; ASD | Collapsed group of children with ASD had significantly lower vitamin D levels (M = 24.0 nM, SD = 19.6) than their siblings (M = 31.9 nM, SD = 27.7) (p = 0.013). | ||||||
Morales et al. (2012) | Cohort | Spain, 2003–2008 | Mothers (13 weeks) 25(OH)D; children aged 14 months | n = 1820 | Psychologist report; BSID | Infants of mothers with 25(OH)D3 concentrations in pregnancy >30 ng/mL showed higher mental score (β = 2.60; 95% CI, 0.63 to 4.56) and higher psychomotor score (β = 2.32; 95% CI, 0.36 to 4.28) than those of mothers with 25(OH)D3 concentrations <20 ng/mL. The median plasma value of 25(OH)D (3) in pregnancy was 29.6 ng/mL (interquartile range, 21.8–37.3). | ||||||
Morales et al. (2015) | Cohort | Spain; 1997–2008 | Mothers (13 weeks) 25(OH)D; children aged 4–8 years | n = 1650 | DSM-IV | Total ADHD-like symptoms in children decreased by 11% per 10-ng/mL increment of maternal 25(OH)D3 concentration (IRR = 0.89; 95% CI, 0.80 to 0.98). Similarly, number of symptoms in the ADHD subscales decreased in relation to higher maternal 25(OH)D3 concentration (IRR per 10-ng/mL increment = 0.89; 95% CI, 0.79 to 0.99 for inattention scale; and IRR = 0.88; 95% CI, 0.78 to 0.99 for hyperactivity-impulsivity scale). Using diagnostic criteria, researchers found that association of increasing maternal 25(OH)D3 with a lower risk of ADHD DSM-IV (relative risk ratio per 10-ng/mL increment = 0.87; 95% CI, 0.72, 1.06) and ICD-10 hyperkinetic disorder (relative risk ratio = 0.72; 95% CI, 0.49, 1.04) in children. | ||||||
Zhu et al. (2015) | Cohort | China, 2008 | Children aged 16–18 months | n = 363 | Certified examiners; BSID | Toddlers in lowest quintile of cord blood 25(OH)D exhibited a deficit of 7.60 (95% CI, 212.4 to 22.82; p = 0.002) and 8.04 (95% CI, 212.9 to 23.11; p = 0.001) points in the MDI and PDI scores, respectively, compared with the reference category. Mean 25(OH)D (range): 4.9 (2.2–44.4). | ||||||
Chen et al. (2016) | Case-control | China, January 2014–December 2015 | Mothers (1st trimester) 25(OH)D; children aged 3–7 years | n = 136 (68/68) | DSM-V | Mothers in autistic group had significantly lower maternal serum levels of 25(OH) D than in typically developing group [19.2 (IQR: 15.8–22.9) ng/mL vs. 24.3 (19.3–27.3) ng/mL, p < 0.001] with 55.9% and 29.4% being vitamin D deficient, respectively (p < 0.001). Levels of 25(OH) D increased with decreasing severity of ASD as defined by CARS score (r = −0.302, p < 0.001). Maternal first-trimester serum levels of 25(OH)D in the lower 3 quartiles (quartile 1, 2, 3) (compared to the highest quartile) were associated with increased odds of ASD diagnosis in offspring [OR (95% CI) Q1: 1.36 (0.84 to 2.58, p = 0.25); Q2: 2.68 (1.44 to 4.29, p = 0.006); Q3: 3.99 (2.58 to 7.12, p < 0.001)]. | ||||||
Magnusson et al. (2016) | Cohort | Sweden, 2001–2011 | Stockholm Youth Cohort; Swedish-born individuals aged 4–17 years (no control) | N = 509,639 (9882 ASD cases; 2476 with intellectual disability, 7406 without intellectual disability) | National and regional registers; ASD diagnosis | Maternal vitamin D deficiency was associated with offspring risk of ASD with, but not without, intellectual disability (aORs 2.51; 95% CI, 1.22 to 5.16 and 1.28, 95% CI, 0.68 to 2.42). | ||||||
Darling et al. (2017) | Cohort | UK, 1991–1992 | Mothers (29 weeks) 25(OH)D; children aged 6–42 months; 7–9 years | n = 7065 | Maternal report; SDQ | Children of vitamin D–deficient mothers (<50.0 nmol/L) were more likely to have scores in the lowest quartile for gross motor development at 30 months (OR 1.20; 95% CI, 1.03 to 1.40), fine-motor development at 30 months (OR 1.23; 95% CI, 1.05 to 1.44), and social development at 42 months (OR 1.20; 95% CI; 1.01 to 1.41) than vitamin D–sufficient mothers (≥50.0 nmol/L). Median (IQR) 25(OH)D: 24.5 (17.2–33.9). | ||||||
Chawla et al. (2017) | Prospective | U.S., 2009–2011 | Newborn Epigenetic Study; mothers who measured 25(OH)D concn in plasma samples in first or second trimester; children aged 12–24 months | n = 218 mother–infant pairs | Maternal report; ITSEA | Black mothers had much lower 25(OH)D concentrations than white and Hispanic mothers. | ||||||
Gould et al. (2017) | RCT of DHA supplementation in pregnancy | Australia; 2005–2008 | Children aged 18 months–4 years | 299–323 | Psychologist report; BSID-III | 25(OH)D was not associated with cognitive, motor, social-emotional or adaptive behavior scores at 18 months or cognitive score at age 4 years. | ||||||
Laird et al. (2017) | Cohort | Republic of Seychelles, 2001 | Mothers 25(OH)D; children aged 5 years | n = 189 | CBCL; total t score | Maternal 25(OH)D concentrations were not associated with child anthropometric or neurodevelopmental outcomes. Mean (SD) 25(OH)D: 22.4 (11.4) ng/ml | ||||||
Mossin et al. 2017) | Cohort | Denmark, 2010–2012 | Newborns (cord blood) 25(OH)D; children aged 1.5–5 y | n = 1233 | Parental report; CBCL; ADHD score | Cord blood 25(OH)D levels > 25 nmol/L and >30 nmol/L were associated with lower attention deficit hyperactivity disorder scores than levels = 25 nmol/L or <25 nmol/L (p = 0.035) and =30 nmol/L or <30 nmol/L (p = 0.043), respectively. | ||||||
Daraki et al. (2018) | Cohort | Greece, 2006–2007 | Mothers (13 weeks) 25(OH)D; children aged 4 y | n = 487 | SDQ | Children of mothers with high 25(OH)D levels had also fewer total behavioral difficulties (β-coeff: −1.25, 95% CI, −2.32, to –0.19) and externalizing symptoms (β-coeff: −0.87, 95% CI to −1.58, −0.15) at preschool age. | ||||||
Vinkhuyzen et al. (2017) | Cohort | Netherlands, April 2002 and January 2006 | Embedded in the Generation R Study; mothers (mid-gestation) 25(OH)D; children aged 6 y | n = 3895, n = 2870 | Clinical records; ASD diagnosis | Individuals in the 25(OH)D-deficient group at mid-gestation had more than twofold increased risk of ASD (OR = 2.42, 95% CI, 1.09 to 5.07, p = 0.03) compared with the 25(OH)D-sufficient group. | ||||||
Vinkhuyzen et al. (2018) | Prospective cohort | Netherlands, April 2002 and January 2006 | Embedded in the Generation R Study; mothers (mid gestation) 25(OH)D; children aged 6 y | n = 4229 | Parental report; SRS: autism-related traits | Compared with the 25OHD sufficient group (25OHD >50 nmol/L), those who were 25(OH)D deficient had significantly higher (more abnormal) SRS scores (mid- gestation n = 2866, β = 0.06, p < 0.001; cord blood n = 1712, β = 0.03, p = 0.01). | ||||||
Wang et al. (2018) | Cohort | China, 2012–2013 | Newborns (cord blood) 25(OH)D; children aged 2 y | n = 552 | Parental report; ASQ: gross and fine-motor skills | Median of the 25(OH)D concentration in cord blood was 22.4 ng/mL (IQR, 27.3–8.6). Infants born in winter had lower 25(OH)D concentration. 25(OH)D deficiency was not associated with weight z-score (mean difference, 0.07; 95% CI, −0.09 to 0.23), length z-score (mean difference, 0.01; 95% CI, −0.19 to 0.21), head circumference z-score (mean difference, −0.06; 95% CI, −0.27 to 0.15) and BMI z-score (mean difference, 0.09; 95% CI, −0.07 to 0.25) or neurodevelopment during infancy, adjusting for sex, socioeconomic position, prepregnancy maternal BMI, and maternal and neonatal characteristics. | ||||||
Veena et al. (2017) | Cohort | India, 1997–1998 | Mothers (30 weeks) 25(OH)D; children aged 9–10 and 13–14 y | n = 468; n = 472 | Psychologist report; KABC | No evidence of an association between maternal vitamin D status and offspring cognitive function. | ||||||
Tylavsky et al. (2015) | Cohort | U.S., 2006–2011 | CANDLE Study Mothers (2nd trimester) 25(OH)D; children aged 2 years | n = 1020 mother; 16–28 weeks of gestation | BSID | Gestational 25(OH)D was positively associated with cognitive scaled scores, receptive language, and expressive language (p < 0.001) Mean (range) 25(OH)D: 22.3 (5.9–68.4) ng/ml | ||||||
Gale et al. (2008) | Cohort | UK (Southampton), 1991–1992 | Mothers (32 weeks) 25(OH)D; children aged 9 y | n = 178 | Mother report; SDQ | No statistically significant associations between maternal 25(OH)D concn and full-scale, verbal or performance IQ, assessed by the Wechsler Abbreviated Scale of Intelligence (p > 0.005) Median (IQR) 25(OH)D:25 (15–30.1) ng/ml | ||||||
Hanieh et al. (2014) | Cohort | Vietnam, 2010–2012 | Mothers (32 weeks) 25(OH)D; children aged 6 months | n = 960 | Psychologist report; BSID | Infants born to women with 25(OH)D deficiency (<37.5 nmol/L) had lower developmental language scores than infants born to women who were vitamin D replete (≥75 nmol/L) (mean difference, −3.48; 95% CI, −5.67 to –1.28). | ||||||
Whitehouse et al. (2012) | Cohort | Perth, Western Australia, 1989–1991 | Mothers (18 weeks) 25(OH)D; children aged 2–17 y | 412–652 | Parental report; CBCL: total behavior, internalizing behavior, externalizing behavior | No significant associations between maternal 25(OH)D serum quartiles and offspring behavioral/emotional problems at any age. | ||||||
Whitehouse et al. (2013) | Cohort | Australia, May 1989 and Nov. 1991 | Raine Study Mothers gestational age 16–20 wks; children aged 5–17 y | n = 406 | Parental report; ASD diagnosis; autism spectrum quotient | Offspring of mothers with low 25(OH)D concentrations (<49 nmol/L) were at increased risk for “high” scores (≥2 SD above mean) on the Attention Switching subscale (OR, 5.46; 95% CI, 1.29 to 23.05). | ||||||
Strøm et al. (2014) | Cohort | Denmark, 1988–1989 | Mothers (>30 weeks) 25(OH)D; children aged 22 y | n = 850 | Population-based registry; prescription for medication or hospital admission for: ADHD | Direct association between maternal vitamin D status and offspring depression (ptrend = 0.01). | ||||||
Gustafsson et al. (2015) | Cohort | Sweden, 1978–2000 | Newborns (cord blood) 25(OH)D3; children aged 5–17 y | n = 404 (202/202) | DSM-III-R used before 1994 and DSM-IV used after 1994 | No differences in cord blood vitamin D concentration were found between children with ADHD (median 13.0 ng/mL) and controls (median 13.5 ng/mL) (p = 0.43). | ||||||
Keim et al. (2014) | Case-control | U.S., 1959–1965 | Collaborative Perinatal Project; n = 55,000 pregnant women; children aged 8 month and 4–7 y | 3146–3587 | Psychologist report; BSID | IQ at age 7 was associated with both maternal and cord blood 25(OH)D (β for 5-nmol/L increment of maternal 25(OH)D = 0.10; 95% CI, 0.00 to 0.19). |
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Uçar, N.; Grant, W.B.; Peraita-Costa, I.; Morales Suárez-Varela, M. How 25(OH)D Levels during Pregnancy Affect Prevalence of Autism in Children: Systematic Review. Nutrients 2020, 12, 2311. https://doi.org/10.3390/nu12082311
Uçar N, Grant WB, Peraita-Costa I, Morales Suárez-Varela M. How 25(OH)D Levels during Pregnancy Affect Prevalence of Autism in Children: Systematic Review. Nutrients. 2020; 12(8):2311. https://doi.org/10.3390/nu12082311
Chicago/Turabian StyleUçar, Nazlı, William B. Grant, Isabel Peraita-Costa, and María Morales Suárez-Varela. 2020. "How 25(OH)D Levels during Pregnancy Affect Prevalence of Autism in Children: Systematic Review" Nutrients 12, no. 8: 2311. https://doi.org/10.3390/nu12082311
APA StyleUçar, N., Grant, W. B., Peraita-Costa, I., & Morales Suárez-Varela, M. (2020). How 25(OH)D Levels during Pregnancy Affect Prevalence of Autism in Children: Systematic Review. Nutrients, 12(8), 2311. https://doi.org/10.3390/nu12082311