Dataset Information

New Perspective on Impact of Folic Acid Supplementation during Pregnancy on Neurodevelopment/Autism in the Offspring Children - A Systematic Review.

ABSTRACT: It has been conclusively established that folic acid supplementation prior to and during early pregnancy (up to 12 weeks of gestation) can prevent neural tube defects (NTDs). We hypothesized that folate effects may extend from neuro-structural defects to alterations in neuro-behavioural and emotional skills including autism spectrum disorders (ASDs) and other developmental disorders. The objective of this review was to comprehensively evaluate evidence on the impact of folic acid on neurodevelopment other than NTDs. We conducted an online search of relevant literature compiled by the National Library of Medicine from Medline and EMBASE (searched on Dec 31, 2014: http://www.ncbi.nlm.nih.gov/entrez/query/fcgi and http://www.elsevier.com/online-tools/embase). We first created 3 files (search restricted to English literature) using the following key words: 1) folate or folic acid (171322 papers identified by this search); 2) maternal or pregnancy or pregnant or gestation or gestational or prenatal or antenatal or periconception or periconceptional (1349219 papers identified by this search); and 3) autism or autism spectrum disorders or developmental delay or development or neurodevelopment or mental or cognitive or language or personal-social or gross motor or fine motor or behaviour or intellectual or intelligence or Bayley Scale (8268145 papers identified by this search). We then merged the 3 files and reviewed the papers that addressed these three issues simultaneously. A total of 22 original papers that examined the association between folic acid supplementation in human pregnancy and neurodevelopment/autism were identified after the screening, with 15 studies showing a beneficial effect of folic acid supplementation on neurodevelopment/autism, 6 studies showed no statistically significant difference, while one study showed a harmful effect in > 5 mg folic acid supplementation/day during pregnancy. Folic acid supplementation in pregnancy may have beneficial effects on the neurodevelopment of children beyond its proven effect on NTDs.

SUBMITTER: Gao Y

PROVIDER: S-EPMC5119728 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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New Perspective on Impact of Folic Acid Supplementation during Pregnancy on Neurodevelopment/Autism in the Offspring Children - A Systematic Review.

Gao Yunfei Y Sheng Chao C Xie Ri-Hua RH Sun Wen W Asztalos Elizabeth E Moddemann Diane D Zwaigenbaum Lonnie L Walker Mark M Wen Shi Wu SW

PloS one 20161122 11

It has been conclusively established that folic acid supplementation prior to and during early pregnancy (up to 12 weeks of gestation) can prevent neural tube defects (NTDs). We hypothesized that folate effects may extend from neuro-structural defects to alterations in neuro-behavioural and emotional skills including autism spectrum disorders (ASDs) and other developmental disorders. The objective of this review was to comprehensively evaluate evidence on the impact of folic acid on neurodevelop ...[more]

PMID: 27875541

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Project description:BACKGROUND:It has been proposed that maternal folic-acid supplement use may alter the DNA-methylation patterns of the offspring during the in-utero period, which could influence development and later-life health outcomes. Evidence from human studies suggests a role for prenatal folate levels in influencing DNA methylation in early life, but this has not been extended to consider persistent effects into adulthood. METHODS:To better elucidate the long-term impact of maternal folic acid in pregnancy on DNA methylation in offspring, we carried out an epigenome-wide association study (EWAS) nested within the Aberdeen Folic Acid Supplementation Trial (AFAST-a trial of two different doses: 0.2 and 5?mg, folic acid vs placebo). Offspring of the AFAST participants were recruited at a mean age of 47?years and saliva samples were profiled on the Illumina Infinium Human Methylation450 array. Both single-site and differentially methylated region analyses were performed. RESULTS:We found an association at cg09112514 (p?=?4.03×10-9), a CpG located in the 5' untranslated region of PDGFRA, in the main analysis comparing the intervention arms [low- (0.2?mg) and high-dose (5?mg) folic acid combined (N?=?43)] vs placebo (N?=?43). Furthermore, a dose-response reduction in methylation at this site was identified in relation to the intervention. In the regional approach, we identified 46 regions of the genome that were differentially methylated in response to the intervention (Sidak p-value <0.05), including HLA-DPB2, HLA-DPB1, PAX8 and VTRNA2-1. Whereas cg09112514 did not replicate in an independent EWAS of maternal plasma folate, there was suggested replication of differential methylation in PAX8. CONCLUSIONS:The results of this study suggest that maternal folic-acid supplement use is associated with changes in the DNA methylation of the offspring that persist for many years after exposure in utero. These methylation changes are located in genes implicated in embryonic development, immune response and cellular proliferation. Further work to investigate whether these epigenetic changes translate into detectable phenotypic differences is required.

Project description:BACKGROUND:Evidence suggests a strong association between nutrition during the first 1000 days (conception to 2 years of life) and cognitive development. Maternal docosahexaenoic acid (DHA) supplementation has been suggested to be linked with cognitive development of their offspring. DHA is a structural component of human brain and retina, and can be derived from marine algae, fatty fish and marine oils. Since Indian diets are largely devoid of such products, plasma DHA levels are low. We are testing the effect of pre- and post-natal DHA maternal supplementation in India on infant motor and mental development, anthropometry and morbidity patterns. METHODS:DHANI is a double-blinded, parallel group, randomized, placebo controlled trial supplementing 957 pregnant women aged 18-35 years from ?20 weeks gestation through 6 months postpartum with 400 mg/d algal-derived DHA or placebo. Data on the participant's socio-demographic profile, anthropometric measurements and dietary intake are being recorded at baseline. The mother-infant dyads are followed through age 12 months. The primary outcome variable is infant motor and mental development quotient at 12 months of age evaluated by Development Assessment Scale in Indian Infants (DASII). Secondary outcomes are gestational age, APGAR scores, and infant anthropometry. Biochemical indices (blood and breast-milk) from mother-child dyads are being collected to estimate changes in DHA levels in response to supplementation. All analyses will follow the intent-to-treat principle. Two-sample t test will be used to test unadjusted difference in mean DASII score between placebo and DHA group. Adjusted analyses will be performed using multiple linear regression. DISCUSSION:Implications for maternal and child health and nutrition in India: DHANI is the first large pre- and post-natal maternal dietary supplementation trial in India. If the trial finds substantial benefit, it can serve as a learning to scale up the DHA intervention in the country. TRIAL REGISTRATION:The trial is retrospectively registered at clinicaltrials.gov ( NCT01580345 , NCT03072277 ) and ctri.nic.in ( CTRI/2013/04/003540 , CTRI/2017/08/009296 ).

Dataset Information

New Perspective on Impact of Folic Acid Supplementation during Pregnancy on Neurodevelopment/Autism in the Offspring Children - A Systematic Review.

Publications

New Perspective on Impact of Folic Acid Supplementation during Pregnancy on Neurodevelopment/Autism in the Offspring Children - A Systematic Review.

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