The higher rate of multiple births after periconceptional multivitamin supplementation: an analysis of causes

A randomized controlled trial of periconceptional multivitamin supplementation (including 0.8 mg folic acid--see the Materials and Methods section for the precise composition of the multivitamin and trace-element supplementation) was carried out for at least 28 days before conception. The trial was continued until at least until the second missed menstrual period to test the effectiveness of this new primary preventive method in the reduction of neural tube defects. However, other pregnancy outcomes were also evaluated. Of a total of 5,502 pregnant women, 4,846 births were analysed in the final data base. The rate of multiple births was significantly higher in the multivitamin group (3.8%) than in the placebo-like trace-element control group (2.7%), and in both groups exceeded the multiple birth rate of 2.2% in the Hungarian population at large. 7.3% of women in the multivitamin and 7.9% of women in the trace-element groups had received ovarian stimulation treatment (mainly clomiphene) for hormonal dysfunctions, eg. anovulation. Nonetheless, our study showed that periconceptional multivitamin supplementation, with or without ovarian stimulation, increases the rate of multiple births.