Table 1.

Studies on the association between maternal FA supplementation and the risk of ASDs in offspring.

No	Study	Type of Study	Sample Size	Supplement Used	Period of Intake	ASDs Cases	Study Outcome Parameters	Outcomes
1	Virk J et al., (2016) [34]	Population-based cohort study	n = 35,059 women	FA and/or multivitamin supplements (containing at last 400 μg of FA)	4 weeks prior to 8 weeks after pregnancy	552 (1.6%)	Autism and Asperger’s syndrome. Pervasive developmental disorder—not otherwise specified (PDD-NOS)	No association has been found between early folate or multivitamin intake for autism spectrum disorder [34].
2	Levine SZ et al., (2018) [35]	Case-control cohort study	n = 45,300 children	FA and/or multivitamin supplements	Before but not during pregnancy/during but not before pregnancy/before and during pregnancy from 4 weeks before and 8 weeks into pregnancy2 years before pregnancy	572 (1.3%)	Risk of ASDs in offspring	Maternal exposure to FA and multivitamin supplements before and during pregnancy is associated with a reduced risk of ASDs in the offspring compared with the offspring of mothers without such exposure [35].
3	Surén Pet al., (2013) [36]	Cohort study	n = 85,176 children	Multivitamin supplements (400 μg of FA) fish oil and FA	4 weeks before to 8 weeks after the start of pregnancy	270 (0.32%)	Autistic disorder risk. Asperger syndrome. PDD-NOS	Maternal use of supplemental folic acid before conception and early in pregnancy was associated with a lower risk of autism spectrum disorders in children [36].
4	DeVilbiss EA et al., (2017) [37]	Population- based cohort study	n = 273,107 mother–child pairs	Multivitamins supplements FA supplements (400 μg)	First trimester (400μg/day)	158 (0.26%) in the maternal multivitamin use group 430 (0.48%) in the no-nutritional supplementation use group	Risk of ASDs with and without intellectual disability in offspring	Maternal multivitamin supplementation during pregnancy may be inversely associated with ASDs with intellectual disability in offspring [37].
5	Raghavan R et al., (2018) [38]	Cohort study	n = 1257 mother–infant pairs	Multivitamin Supplements	During pregnancy≤2 times/week3–5 times/week>5 times/week	86 (6.8%)	Risk of ASDs in offspring.Maternal B12 levels 2–3 days after birthMTHFR genotype	The results show that moderate intake (3–5 times/week) of multivitamin supplements during pregnancy is associated with decreased risk of ASDs in offspring. Low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASDs. There was a “U” shaped relationship between maternal multivitamin supplementation frequency and ASDs risk [38].
6	Schmidt RJ et al., (2019) [39]	Cohort study	n = 332 children and theirn = 305 mothers	FA (600 μg) and iron (27 mg) supplements	First month of pregnancy 6 months before and each month during the pregnancy	18 (14.1%) following mother supplementation and 37 (32.7%) from mothers receiving no supplementation	ASD recurrence in siblings of children with ASDs in high-risk families	Maternal prenatal vitamin intake during the first month of pregnancy may reduce ASDs recurrence in siblings of children with ASDs in high-risk families [39].
7	Steenweg-de Graaff J et al., (2015) [40]	Population-based birth cohort study	n = 5591 mothers of single live-born neonates	FA supplements	Preconceptional within the first 10 weeks of pregnancy After the first 10 weeks of pregnancy	3893 (70%)	Maternal plasma folate concentrations at 13 weeks of gestation. Autistic traits in the offspring at the age of six years	Maternal folate was not associated with autistic traits in the offspring. In contrast, prenatal folic acid use was associated with less child autistic traits [40].
8	Nilsen RM et al., (2013) [41]	Population-based cohort study	n = 507,856 Medical Birth Registry of Norway nationwide population children n = 89 836 MoBa cohort sample children	FA supplements	Prenatal exposure	234 (0.26%) in the cohort and 2072 (0.41%) in the nationwide population	Specialist-confirmed diagnosis ASDs.Estimated the risk of ASDs associated with: primipara pregnancy (no, yes), prenatal folic acid use (no, yes), prenatal smoking (no, yes), low birth weight (no, yes), preterm birth (no, yes), offspring sex (female, male), and caesarean section history (no, yes).	Was observed that maternal prenatal folic acid supplement use was associated with a 14–17% adjusted risk reduction for ASDs [41].
9	Christian P et al., (2010) [42]	Cohort study	n = 676 children	FA (400 μg) FA and iron (60 mg) FA, iron and zinc (30 mg) FA, iron, zinc and vitamins D (10 μg), E (10 mg), B1 (1.6 mg), B2 (1.8 mg), B6 (2.2 mg), B12 (2.6 μg), C (100 mg), and K (65 μg); niacin (20 mg); copper (2.0 mg); magnesium (100 mg), with 1000-μg vitamin A	early pregnancy for 3 months postpartum	N.S	Estimation of children’s intellectual functioning:universal nonverbal intelligence test (UNIT); tests of executive function, including go/no-go, the Stroop test, backward digit span test; movement assessment battery for children (MABC); finger-tapping test	Maternal prenatal FA and iron supplementation was associated with better test scores in offspring at 7 to 9 years compared to the control group with only vitamin A supplementation [42].
10	Roth C et al., (2011) [43]	Cohort study	n = 38,954 children	FA and/or multivitamin supplements	4 weeks before to 8 weeks after conception	204 (0.5%) severe language delay and 1290 (3.3%) moderate language delay	Risk of child with severe language delay. Assessment of severe language delay and motor delay	Maternal FA use was associated with a reduced risk of severe language delay in offspring at age 3 years. Instead, no significant association with motor skills delay risk was found [43].