Background: Cleft palate is a prevalent congenital condition globally, significantly impacting individuals' eating, speaking, and breathing abilities. It occurs due to incomplete fusion of the palate shelves in utero, leading to a gap that connects the oral and nasal cavities. 

Objectives: The current study aimed to assess whether administering vitamin B6 from day zero of pregnancy could decrease the occurrence of corticosteroid-induced cleft palate in a mouse model.

Method: Eighteen pregnant C57BL/6J mice were divided into three equal groups. In control group, six mice received daily injected of sterile physiological saline from the 11th through the 14th days of gestation. In group II, the mice were injected with 125 mg/kg hydrocortisone sodium succinate with 0.9% benzyl alcohol daily from the 11th through the 14th days of gestation. Mice of group III were injected with hydrocortisone sodium succinate as in group II and given drinking water containing 500 µg/ml of vitamin B6 from day zero of gestation until delivery, with a minimal daily intake of 5 ml. Two days after delivery, the offspring were counted, and their head circumferences were taken for analysis. The heads of the offspring were fixed in Bouin's solution, processed for paraffin sectioning, and stained with hematoxylin and eosin (H&E) for histological analysis. Cleft palate percentages of all groups were counted and statistically analyzed using ANOVA test to determine any significant relationships (P<0.05).

Results: Histological examination revealed that the control group had a normally developed palate, with only 3.22% (1/31 offspring) showing cleft palate. In contrast, the group II mice injected with hydrocortisone had a cleft palate percentage of 57.58% (19/33 offspring), mostly exhibiting bilateral cleft palate. In contrast, group III mice, which received vitamin B6 in their drinking water, showed a decreased incidence of cleft palate to 27.59% (8/29 offspring), with most cases being unilateral.

Conclusion: The results indicate that hydrocortisone injection during early pregnancy causes teratogenic effects on the palatine shelves, including the persistence of the midline epithelial seam. Administering vitamin B6 significantly reduces the incidence of cleft palate while promoting the growth of the palatal shelves.