Women planning pregnancy often are urged to take extra folic acid or fortified food to lower the risk of a neural tube defect and other malformations. Some studies have found evidence of an increased rate of dizygotic twinning in women taking folic acid supplements, but others have failed to confirm such an effect. This study explored the putative association between folic acid supplementation and twinning in 6953 women in the Swedish Medical Birth Registry who had a total of 7181 infants and who had taken folic acid in early pregnancy. Of 8676 women who had different-sexed dizygotic twins, 232 reported having used folic acid. In Sweden, folic acid is available in doses of 400 μg over the counter and 5 mg by prescription.
After adjusting for year of birth, maternal age, parity, smoking, and years of unplanned childlessness, the odds ratio (OR) for folic acid use by women with a body mass index (BMI) less than 19.8 was 0.96, and for those with a BMI greater than 26, 0.89. Those with a BMI less than 19.8 had a lowered risk of dizygotic twinning (OR, 0.75), whereas the others had an increased risk (OR, 1.13). The use of gestagens or ovulation-stimulating drugs was associated with both folic acid use and having dizygotic twins. When nonSwedish women and those born outside Sweden were excluded along with those who were involuntarily childless or had used ovarian stimulants or gestagens, the OR for dizygotic twinning was 1.71 after adjusting for year of birth, maternal age, parity, and smoking.
An increased risk of dizygotic twinning associated with folic acid supplementation must be weighed against the lowered risk of congenital malformations, especially neural tube defects.
Tornblad Institute, University of Lund, Lund, Sweden
Early Hum Dev 2004;80:143–151