Folinic acid reduces cleft lip [CL(P)] in A/WySn mice

The A/WySnBk strain of mice displays 25-35% spontaneous CL(P). Pregnant mic e were treated with folinic acid continuously delivered via osmotic minipum ps at the rate of 7.6 +/- 0.2 mu l/ hr (12 mg/ 24 hr) for the period coveri ng gestation day (gd) 8.5-9.5, early in the critical period for formation o f the face. Untreated and osmotic minipump-delivered, saline-treated groups served as controls. Individual fetuses were examined for CL(P) and other a bnormalities on gd 18. The treatment resulted in a decrease in the frequenc y of CL(P) from 40.0 +/- 7.0% among untreated to 10.2 +/- 3.3% in the folin ic acid group (P < .001). The difference between the folinic-exposed group and the saline-filled minipump and surgical control was also significant (P < .029). With respect to mortality, litter size, and fetal weight, the two minipump groups did not differ significantly, nor did they differ from the untreated group. Thus the reduction in CL(P) frequency was due to the pres ence of folinic acid and not to effects of the surgical procedures. This st udy provides evidence that administration of folinic acid during pregnancy has an important ameliorating effect on genetically predisposed CL(P). (C) 1999 Wiley-Liss, Inc.