Prenatal Folic Acid Supplements and Offspring’s Autism Spectrum Disorder: A Meta-analysis and Meta-regression

Xian, Liu; Zou, Mingyang; Sun, Chongde; Wu, Lijie; Chen, Wenxiong

doi:10.1007/s10803-021-04951-8

Cited by 37 publications

(41 citation statements)

References 77 publications

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“…Hence, women who become pregnant before folate restoration is complete are at increased risk of folate insufficiency (Doyle et al, 2001;Smits & Essed 2001), which could lead to altered neurodevelopment and partly responsible for the development of ODD in the early childhood period (Brown & Susser 2008;Freedman et al, 2021). While low maternal red blood cell folate in early pregnancy has been associated with higher risk of mental health outcomes in offspring (Roth et al, 2011;Roza et al, 2010;Schlotz et al, 2010), offspring of mothers who took folic acid supplements in the preconception, and/or early pregnancy period have been found to have reduced risk of neurodevelopmental and behavioral problems, including ASD, hyperactivity, inattention, and peer problems (Liu et al, 2021;Roza et al, 2010;Wang et al, 2017). In our study, adjustment for folic acid and iron supplementations prior to and/or during pregnancy did not change the observed association between short IPI (< 6 months) and offspring ODD.…”

Section: Discussionmentioning

confidence: 99%

Interpregnancy interval and the risk of oppositional defiant disorder in offspring

et al. 2022

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The study aimed to investigate the association between interpregnancy interval (IPI) and parent-reported oppositional defiant disorder (ODD) in offspring at 7 and 10 years of age. We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), an ongoing population-based longitudinal study based in Bristol, United Kingdom (UK). Data included in the analysis consisted of more than 3200 mothers and their singleton children. The association between IPI and ODD was determined using a series of log-binomial regression analyses. We found that children of mothers with short IPI (<6 months) were 2.4 times as likely to have a diagnosis of ODD at 7 and 10 years compared to mothers with IPI of 18–23 months (RR = 2.45; 95%CI: 1.24–4.81 and RR = 2.40; 95% CI: 1.08–5.33), respectively. We found no evidence of associations between other IPI categories and risk of ODD in offspring in both age groups. Adjustment for a wide range of confounders, including maternal mental health, and comorbid ADHD did not alter the findings. This study suggests that the risk of ODD is higher among children born following short IPI (<6 months). Future large prospective studies are needed to elucidate the mechanisms explaining this association.

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Section: Discussionmentioning

confidence: 99%

Interpregnancy interval and the risk of oppositional defiant disorder in offspring

et al. 2022

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“…Treatment with folate is important during pregnancy to reduce the risk of ASD. [ 23 ] Folate may be particularly important in mitigating the effects of environmental factors during pregnancy. Folate supplementation prevents the development of ASD like behaviors in the prenatal valproic acid exposure environmentally induced rodent models of ASD.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, epigenetics can explain some of the transgenerational effects associated with ASD [18] and could link ASD to prenatal psychological stressors, [19] inflammation and infectious triggers, [20] prenatal toxicant exposures, [21] changes in the microbiome [22] and the importance of folate during pregnancy. [23] Other prenatal environmental factors not specifically identified by network analysis…”

Section: Common Themes Within Environmental Exposures and Physiological Disturbancesmentioning

confidence: 99%

Physiological mediators of prenatal environmental influences in autism spectrum disorder

et al. 2021

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Recent research has pointed to the importance of the prenatal environment in the etiology of autism spectrum disorder (ASD) but the biological mechanisms which mitigate these environmental factors are not clear. Mitochondrial metabolism abnormalities, inflammation and oxidative stress as common physiological disturbances associated with ASD. Network analysis of the scientific literature identified several leading prenatal environmental factors associated with ASD, particularly air pollution, pesticides, the microbiome and epigenetics. These leading prenatal environmental factors were found to be most associated with inflammation, followed by oxidative stress and mitochondrial dysfunction. Other prenatal factors associated with ASD not identified by the network analysis were also found to be significantly associated with these common physiological disturbances. A better understanding of the biological mechanism which mediate the effect of prenatal environmental factors can lead to insights of how ASD develops and the development of targeted therapeutics to prevent ASD from occuring.

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“…The continued intake of FA in the second and third trimester of pregnancy has identified important folate-mediated epigenetic changes in genes related to brain development and function, with limited evaluations ( Caffrey et al, 2019 , Irwin et al, 2016 , Liu et al, 2020 , Liu et al, 2021 ). The clinical message for continued FA exposure throughout pregnancy may be most important for countries without FA food fortification ( Irwin et al, 2016 ).…”

Section: Evidence For Oral Folic Acid Supplementation and The Maternal And Fetal-pediatric Benefit And Riskmentioning

confidence: 99%

“…Preconception management for timing and dosing of FA prior to conception is required ( Liu et al, 2021 , Roffman, 2018 ). Pre-conceptional supplements may provide the sufficient folate reserves against both, NTDs and neuropsychiatric risk ( Murray et al, 2018 ).…”

Section: Evidence For Oral Folic Acid Supplementation and The Maternal And Fetal-pediatric Benefit And Riskmentioning

confidence: 99%

Maternal folic acid and multivitamin supplementation: International clinical evidence with considerations for the prevention of folate-sensitive birth defects

Wilson

O'Connor

2021

Preventive Medicine Reports

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More evidence is available for maternal intake, absorption, distribution, tissue specific concentrations, and pregnancy outcomes with folic acid (fortification/supplementation) during preconception – first trimester. This Quality Improvement prevention review used expert guidelines/opinions, systematic reviews, randomized control trials/controlled clinical trials, and observational case control/case series studies, published in English, from 1990 to August 2021. Optimization for an oral maternal folic acid supplementation is difficult because it relies on folic acid dose, type of folate supplement, bio-availability of the folate from foods, timing of supplementation initiation, maternal metabolism/genetic factors, and many other factors. There is continued use of high dose pre-food fortification ‘RCT evidenced-based’ folic acid supplementation for NTD recurrence pregnancy prevention. Innovation requires preconception and pregnancy use of ‘carbon one nutrient’ supplements (folic acid, vitamin B12, B6, choline), using the appropriate evidence, need to be considered. The consideration and adoption of directed personalized approaches for maternal complex risk could use serum folate testing for supplementation dosing choice. Routine daily folic acid dosing for low-risk women should consider a multivitamin with 0.4 mg of folic acid starting 3 months prior to conception until completion of breastfeeding. Routine folic acid dosing or preconception measurement of maternal serum folate (after 4–6 weeks of folate supplementation) could be considered for maternal complex risk group with genetic/medical/surgical co-morbidities. These new approaches for folic acid oral supplementation are required to optimize benefit (decreasing folate sensitive congenital anomalies; childhood morbidity) and minimizing potential maternal and childhood risk.

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Prenatal Folic Acid Supplements and Offspring’s Autism Spectrum Disorder: A Meta-analysis and Meta-regression

Cited by 37 publications

References 77 publications

Interpregnancy interval and the risk of oppositional defiant disorder in offspring

Interpregnancy interval and the risk of oppositional defiant disorder in offspring

Physiological mediators of prenatal environmental influences in autism spectrum disorder

Maternal folic acid and multivitamin supplementation: International clinical evidence with considerations for the prevention of folate-sensitive birth defects

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