Autoantibodies to Folate Receptor α During Early Pregnancy and Risk of Oral Clefts in Denmark

The objective of this study was to determine whether IgG and IaM autoantibodies to folate receptor alpha (FR alpha) in pregnant women are associated with an increased risk of oral cleft-affected offspring. A case-control Study nested in the prospective Danish National Birth Cohort (100,418 pregnancies, enrolled during 1997-2003) was done. Hundred eighty-five children were born with an oral cleft. Maternal serum from their mothers (cases) was compared with maternal serum from 779 randomly selected mothers of nonmalformed children (controls). We found that the average level of FR alpha IgG autoantibodies did not differ significantly among cases and controls (p = 0.71). Slightly higher levels of FR alpha IgM autoantibodies were found among controls compared with cases. This was, however, not statistically significant (p = 0.06), except for mothers of children with isolated cleft lip (p = 004). Blocking of folate binding to FR was similar among cases and controls (p = 0.54). The results did not change when stratifying into the cleft subgroups, nor when only isolated oral cleft cases were considered. In conclusion, high maternal autoantibody levels and blocking of folate binding to FR alpha in maternal serum during pregnancy are not associated with an increased risk of oral clefts in the offspring in this population-based cohort. (Pediatr Res 67: 274-279, 2010)