Folate supplementation and twin pregnancies

Background: Women in many countries are advised to increase their folate intake to lower the risk of neural tube defects. For this purpose several countries add folate to the flour. Therefore, it is important to monitor possible adverse effects of this B vitamin. We have assessed the effect of folate on twin pregnancies. Methods: We conducted a retrospective, population-register based study of 176,042 women who gave birth from December 1998 through the end of 2001. Use of folate and multivitamin supplements was recorded on the mandatory birth notification form of the Medical Birth Registry of Norway. Pregnancies after in vitro fertilization (lVF) were reported separately. Results: With adjustment for maternal age and parity, we observed an increased risk of twin pregnancies associated with preconceptional use of folate (odds ratio = 1.59; 95% confidence interval = 1.41-1.78). This association was largely explained by confounding with IVF pregnancies, which were strongly associated both with twin pregnancies and folate use. After exclusion of known lVF pregnancies, and accounting for underreporting of both IVF pregnancies and folate use, the risk was no longer elevated (1.02; 0.85-1.24). Weak associations with twin pregnancies were observed for use of multivitamins and folate during pregnancy, but could be due to increased use of vitamins after a recognized twin pregnancy. Conclusions: The association between preconceptional folate use and twin pregnancies was strongly confounded by IVF. After accounting for IVF pregnancies and underreporting, we found no evidence for an association between preconceptional folate supplements and twinning.