Nineteen studies were included in the review (n=unclear as the supplementary online table was not available). The evidence was fairly consistent across different study designs. The authors judged that there was high quality evidence for the effect of folic acid supplementation on the recurrence of neural tube defects. For primary prevention the evidence was judged to be of moderate quality.
Recurrence of neural tube defects: Folic acid supplementation reduced the risk of the recurrence of neural tube defects in women with previously affected pregnancies (RR 0.30, 95% CI 0.14 to 0.65; three studies with no heterogeneity, p=0.867).
First occurrence of neural tube defects: Folic acid supplementation reduced the risk of a first neural tube defect (RR 0.38, 95% CI 0.29 to 0.51; four studies with low heterogeneity, p=0.244). The effect size was increased if a further four case-control studies were included in this meta-analysis, but they did not alter the conclusion. For folic acid fortification, a meta-analysis of eight before-and-after studies showed a reduced risk of a first occurrence neural tube defect (RR 0.54, 95% CI 0.46 to 0.63), but there was considerable heterogeneity (p=0.002). Sensitivity analyses showed that the heterogeneity was mostly due to one study, and that removal of this study made little difference to the pooled result. Restricting the analysis to three studies from low to middle-income countries showed that folic acid supplementation reduced neural tube defects (RR 0.56, 95% CI 0.50 to 0.63).
The authors also provided estimates of the number of neonatal deaths due to neural tube defects by geographical region. Further details were reported in the paper.