Background: The 1984-1991 Hungarian randomized controlled trial (RCT) of periconceptional multivitamin supplementation containing folic acid (0.8 mg) showed a significant reduction in the first occurrence of neural tube defects (NTDs), and of urinary tract and cardiovascular abnormalities, but no reduction in orofacial clefts. A controlled cohort trial was designed to confirm or deny these results.
Methods: Supplemented women were recruited from the Hungarian Periconceptional Service using the same multivitamin as the Hungarian RCT. Unsupplemented pregnant women were recruited in the standard regional antenatal care clinics and were matched to each supplemented pregnant woman on the basis of age, socioeconomic status, place of residence, and year of pregnancy.
Results: A total of 3056 informative offspring were evaluated in each cohort. The occurrence of congenital cardiovascular malformations (31 vs. 50) was reduced (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.38-0.96) in the supplemented cohort, accounted for mainly by ventricular septal defects (5 vs. 19; OR, 0.26; 95% CI, 0.09-0.72). There was no significant difference (14 vs. 19) in the occurrence of urinary tract defects between the two cohorts, but stenosis/atresia of pelvic-ureteric junction (2 vs. 13) showed a significant reduction (OR, 0.19; 95% CI, 0.04-0.86). The protective effect of the folic acid-containing multivitamin for NTDs (one offspring in the supplemented vs. nine in the unsupplemented cohort) was confirmed (OR, 0.11; 95% CI, 0.01-0.91). There was, however, no protective effect on orofacial clefts or on multiple congenital abnormalities.
Conclusions: The results of this cohort-controlled trial support the findings of the previous Hungarian RCT. The primary prevention of some major structural birth defects by multivitamins containing folic acid or by folic acid has great public health importance.