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.

Folic acid and orofacial clefts: A review of the evidence

“…Hernandez-Diaz et al (2000) reported that exposure to folic acid antagonists early doubled the risks of OFC. Animal studies also provide support for anti-teratogenic effects of folic acid supplementation and dietary folate on OFC including studies in mice, rats and dogs (Peer et al,1958;Reynolds et al, 2003;Bienengraber et al, 2001;Malek et al, 2003;2004, Paros andBeck, 1999;Fu et al, 1996;Burgoon et al, 2002;Elwood and Colquhoun, 1997). These studies also provide suggestive results for a potential role of folic acid and possibly other micronutrients in OFC etiology/prevention.…”

Effect of folic acid on animal models, cell cultures, and human oral clefts: a literature review

“…The animal model studies analyzed demonstrated the protective effect of FA against CP [7,8,[24][25][26][27][28] (Table 2). The experimental design utilized varies among studies: in two of the studies, FA supplementation was enabled via feeding of female mice prior to mating [7,29].…”

“…The experimental design utilized varies among studies: in two of the studies, FA supplementation was enabled via feeding of female mice prior to mating [7,29]. In certain other studies, FA was administered through injections, either intraperitoneally [8], subcutaneously during pregnancy [24], or intravenously [30]. In a few more studies, cultured ex vivo mouse embryos were treated with FA and retinoic acid [25,26].…”

Folic acid and orofacial clefts: a review of the evidence

“…Hernandez‐Diaz et al (2000) reported that exposure to folic acid antagonists doubled the risks of OFCs. Animal studies also provide support for anti‐teratogenic effects of folic acid supplementation and dietary folate on OFCs including studies in mice, rats and dogs (Peer et al , 1958; Fu et al , 1996; Elwood and Colquhoun, 1997; Paros and Beck, 1999; Bienengraber et al , 2001; Burgoon et al , 2002; Malek et al , 2003, 2004; Reynolds et al , 2003). These studies also provide suggestive results for a potential role of folic acid and possibly other micronutrients in OFCs etiology/prevention.…”