Folic acid supplements and risk of facial clefts: national population based case-control study

In the abstract of this paper, folic acid supplementation (at least
400 microgram/day) is reported to reduce the risk of isolated cleft lip
with or without cleft palate, with a (statistically significant) adjusted
odds ratio of 0.61.(1) This is misleading, because the reader would expect
the comparator for this figure to be no supplementation. However, in the
table, none of the adjusted risks do attain statistical significance, and
the significance of the result in the abstract appears to have been
constructed by combining the group using less than 400 micrograms of folic
acid daily (and their surprisingly elevated adjusted odds ratio of 1.17!)
with the group taking no folic acid at all, and contrasting this to the
group using 400 micrograms or more.

Surprisingly, the editorial by Bille et al (2) critiquelessly accepts
this, resulting in a plea for strategies to implement worldwide
implementation. In our view, the results of this study are flawed by data-
driven post-hoc choices which do not allow such firm conclusions.

1. Wilcox AJ, Lie RT, Solvoll K, et al. Folic acid supplements and
risk of facial clefts: national population based case-control study. BMJ
2007; 334: 464-7.

2. Bille C, Murray JC, Olsen SF. Folic acid and birth malformations. BMJ
2007; 334: 433-4.

Competing interests:
None declared