Association of the Maternal Folic Acid Supplementation with the Autism Spectrum Disorder: A Systematic Review

Abstract

Objective To analyze the scientific production regarding maternal folic acid (FA) supplementation and its relationship with autistic spectrum disorder (ASD). Data Sources We performed unrestricted electronic searches in the BIREME virtual bank, Virtual Health Library (VHL) and Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed) databases. Selection of Studies For sample selection, articles that met the proposed objectives were included, published in English, Spanish and Portuguese, the use of Health Sciences Descriptors (DeCS): autistic OR autism AND autism spectrum disorder AND folic acid, AND, with the use of the Medical Subject Headings (MeSH): autistic OR autism AND autistic spectrum disorder AND folic acid. Data Collection Data extraction was performed by the reviewers with a preestablished data collection formulary. Data Synthesis The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) was used based on a checklist with 27 items and a 4-step flowchart. Results A total of 384 articles was found by the search strategies, of which 17 were eligible following the pre-established criteria. The main findings of the present review point to maternal FA supplementation in the pre-conception period and beginning of pregnancy as a protective effect in relation to ASD, which should be indicated in this period as prevention to the problem. Conclusion According to the research analyzed, more studies are necessary to know its effects on pregnancy, since the consumption of excessive FA may not be innocuous.

Guideline No. 427: Folic Acid and Multivitamin Supplementation for Prevention of Folic Acid–Sensitive Congenital Anomalies

“…Studies have evaluated fetal exposure to folic acid and the biology (DNA methylation, hypomethylation, imprinting, and epigenetics) of neonatal childhood neurodevelopmental disorders but have not yet determined any benefit or risk. 45 A scoping review suggested that inadequate nutrient intake during pregnancy was associated with brain and neuro-behavioral deficits, and that future studies should establish and quantify the benefits of maternal nutrition during pregnancy on neurodevelopment and recommend adequate supplementation. 46 Murray et al 47 reviewed the risks of high-dosage supplementation of folic acid during pregnancy, including in animal models.…”

Use of antianemics in prenatal care: A population cohort from a capital city in the North region of Brazil

“…Prescribing folic acid as a prophylactic measure to prevent adverse outcomes in live births is widely endorsed and substantiated in the literature. Beyond its role in preventing neural tube defects ( Martinez et al, 2021 , van Gool et al, 2018 ), there are reports of its potential in averting early placental rupture, prematurity, reducing low birth weight, preventing cardiac anomalies, brain tumors, and even mitigating autism risk in early childhood ( Al-mashhadane and Amer, 2018 , Sampaio et al, 2021 , van Gool et al, 2018 ). However, a cohort of researchers aims to discern potential adverse effects of folic acid supplementation during preconception and pregnancy.…”

“…Folic acid supplementation is widely endorsed for preventing birth-related complications, including neural tube defects ( Martinez et al, 2021 , van Gool et al, 2018 ). It also contributes to averting issues like early placental rupture, prematurity, low birth weight, cardiac anomalies, brain tumors, and even reducing autism risk in early childhood ( Al-mashhadane and Amer, 2018 , Sampaio et al, 2021 , van Gool et al, 2018 ). However, some studies suggest a potential association between folic acid supplementation and respiratory diseases in newborns and children, including wheezing, asthma, respiratory allergies, and bronchitis ( Al-mashhadane and Amer, 2018 , Guo et al, 2019 , Nasir et al, 2020 ).…”

Review Article : Implikasi Suplemen Asam Folat Prenatal terhadap Risiko Autism Spectrum Disorder (ASD) pada Keturunannya

“…Gangguan spektrum autisme (autism spectrum disorders; ASD) merupakan gangguan perkembangan saraf yang kompleks pada anak, yang dapat menyebabkan berbagai masalah pada interaksi sosial dan komunikasi serta perilaku repetitif dan restriktif dengan tingkat keparahan gejala penyakit yang bervariasi dari satu pasien ke pasien lainnya (Lord et al, 2018;CDC, 2021;Zeidan et al, 2022). Penderita ASD ditandai dengan adanya defisit dalam interaksi sosial, keterampilan komunikasi verbal dan nonverbal, hipersensitivitas sensorik, dan kesulitan menyesuaikan diri dengan perubahan yang tidak terduga, serta pola perilaku, minat, atau aktivitas yang terbatas dan berulang (American Psychiatric Association, 2013;CDC, 2021;Hoxha et al, 2021;Sampaio et al, 2021;Salari et al, 2022). ASD umumnya dapat didiagnosis sejak usia 18-24 bulan, dimana pada usia inilah gejala karakteristik dapat dibedakan dari perkembangan normal dan dari keterlambatan atau kondisi perkembangan lainnya (Zeidan et al, 2022).…”