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Folic Acid Intake, Fetal Brain Growth, and Maternal Smoking in Pregnancy: A Randomized Controlled Trial.

ABSTRACT: Background:Folic acid supplementation during pregnancy plays an important role in fetal growth and development. To our knowledge, no experimental study has examined the effect of folic acid on fetal brain growth in women who smoke cigarettes during pregnancy. Objectives:The aim of this study was to investigate the efficacy of higher-dose compared with standard-dose folic acid supplementation on prenatal fetal brain growth, measured by head circumference, brain weight, and brain-body weight ratio (BBR). Design:In this randomly assigned, double-blind, controlled clinical trial, we recruited 345 smoking pregnant women attending a community health center in Tampa, FL between 2010 and 2014. Participants were randomly assigned in a 1:1 ratio to receive either 0.8 mg folic acid/d (standard of care at the study center) or 4 mg folic acid/d (higher strength). Participants were also enrolled in a smoking cessation program. A 2-level linear growth model was used to assess treatment effect and factors that predict intrauterine growth in head circumference over time. Multiple linear regression analyses were conducted to estimate the effect of higher-strength folic acid on head circumference at birth, fetal brain weight, and fetal BBRs. Results:Mothers who received the higher dose of folic acid had infants with a 1.18 mm larger mean head circumference compared with infants born to mothers who received the standard dose, but this difference was not statistically significant (P = 0.2762). Higher-dose folic acid also had no significant effect on brain weight. The BBR of infants of mothers who received higher-dose folic acid was, however, 0.33 percentage points lower than that for infants of mothers who received the standard dose of folic acid (P = 0.044). Conclusions:Infants of smokers in pregnancy may benefit from higher-strength maternal folic acid supplementation. We noted a decrease in the proportion of infants with impaired BBR among those on higher-dose folic acid. This trial was registered at clinicaltrials.gov as NCT01248260.

SUBMITTER: Yusuf KK

PROVIDER: S-EPMC6529553 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Folic Acid Intake, Fetal Brain Growth, and Maternal Smoking in Pregnancy: A Randomized Controlled Trial.

Yusuf Korede K KK Salihu Hamisu M HM Wilson Roneé R Mbah Alfred A Sappenfield William W Bruder Karen K Wudil Usman J UJ Aliyu Muktar H MH

Current developments in nutrition 20190404 6

<h4>Background</h4>Folic acid supplementation during pregnancy plays an important role in fetal growth and development. To our knowledge, no experimental study has examined the effect of folic acid on fetal brain growth in women who smoke cigarettes during pregnancy.<h4>Objectives</h4>The aim of this study was to investigate the efficacy of higher-dose compared with standard-dose folic acid supplementation on prenatal fetal brain growth, measured by head circumference, brain weight, and brain-bo ...[more]

PMID: 31139766

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Project description:BackgroundIn previous studies, maternal exposure to folic acid antagonists was associated with increased risks of neural tube defects, cardiovascular defects, oral clefts and urinary tract defects. The objective of the current study was to assess the possible effects of using folic acid antagonists in pregnancy on placenta-mediated adverse outcomes of pregnancy.MethodsWe used data from an administrative database to retrospectively compare the occurrence of placenta-mediated adverse pregnancy outcomes between pregnant women exposed to folic acid antagonists and women without exposure to these agents.ResultsWe included in the analysis a total of 14 982 women who had been exposed to folic acid antagonists and 59 825 women who had not been exposed. Sulfamethoxazole-trimethoprim was the most frequently prescribed dihydrofolate reductase inhibitor (a total of 12 546 exposures during the preconception period and all 3 trimesters), and phenobarbital was the most frequently prescribed among the other folic acid antagonists (a total of 1565 exposures). The risks of preeclampsia (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] 1.39-1.66), severe preeclampsia (OR 1.77, 95% CI 1.38-2.28), placental abruption (OR 1.32, 95% CI 1.12-1.57), fetal growth restriction defined as less than the 10th percentile (OR 1.07, 95% CI 1.01-1.13), fetal growth restriction defined as less than the 3rd percentile (OR 1.22, 95% CI 1.11-1.34) and fetal death (OR 1.35, 95% CI 1.07-1.70) were greater among mothers with exposure to folic acid antagonists. In general, the risks associated with exposure to other folic acid antagonists were higher than those associated with exposure to dihydrofolate reductase inhibitors. Supplementary analyses involving tight matching with propensity score, restriction of the analysis to women with exposure during the first and second trimesters and restriction of the analysis to specific categories of folic acid antagonists yielded similar results.InterpretationMaternal exposure to folic acid antagonists appears to increase the risk of placenta-mediated adverse outcomes of pregnancy.

Dataset Information

Folic Acid Intake, Fetal Brain Growth, and Maternal Smoking in Pregnancy: A Randomized Controlled Trial.

Publications

Folic Acid Intake, Fetal Brain Growth, and Maternal Smoking in Pregnancy: A Randomized Controlled Trial.

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