Is it possible to prevent cleft palate by prenatal administration of folic acid? An experimental study

Abstract

Objective: In this study, folic acid was tested for its antiteratogenic effects on experimentally induced cleft palate in animals.

Design: Eleven pregnant Lew 1 A dams (75 fetuses) received 200 mg/kg procarbazine via gastric tubing on postconception (p.c.) day 14 to induce a cleft palate (CP); seven of the pregnant dams (45 fetuses) were additionally given 4 mg/kg folic acid subcutaneously from the 14th to the 17th day p.c. As a control group, three more pregnant dams (24 fetuses) were not treated with the drugs mentioned above. All fetuses were delivered by Caesarian section on day 20 p.c.

Outcomes measured: All fetuses were weighed and examined macroscopically with a stereomicroscope. Each fetal head was cut into 35 frontal sections and scrutinized histologically.

Results: None of the control fetuses (n = 24) exhibited a cleft. Without folate administration, 90% of the fetuses (27 of 30) that received procarbazine exhibited a CP. After additional prenatal folate administration, this rate remained virtually unchanged (91%; 41 of 45). However, the proportion of complete (total) CP (4%) was significantly (p <.0001) lower than in the group without folate (53%). Cleft-associated microgenia and microglossia were also significantly less frequent when folate was administered prenatally: microgenia was reduced by 22% (p =.029) and microglossia by 24% (p =.032).

Conclusions: On the basis of these results, folate has a partial ameliorating effect on the teratogenicity of procarbazine given to pregnant rats. Additional studies are necessary on the effect of folate in different species, also taking cleft lip and CP into consideration.