Maternal Folic Acid, B12, and Zinc Serum Levels and Risk of Orofacial Cleft in Offspring in Tabriz

Orofacial clefts (OFCs) are prevalent congenital malformations affecting approximately 1 in 700 live births. The etiology of OFCs is multifactorial, encompassing both genetic predispositions and environmental factors, with maternal nutritional status, particularly folic acid, vitamin B12, and zinc levels, playing a crucial role in fetal development. This study investigates the association between maternal serum micronutrient levels and the risk of OFCs in Tabriz.

A case-control study was conducted over six months at the Children's Hospital of Tabriz University of Medical Sciences, enrolling mothers aged 18-40 with children diagnosed with cleft lip and palate. A total of 66 mothers in the case group and 108 in the control group were assessed. Blood samples were collected to measure serum levels of folic acid, vitamin B12, and zinc using established laboratory techniques. Statistical analyses were performed with SPSS version 21.0, applying appropriate tests(Kolmogorov-Smirnov test, Pearson correlation coefficient, non-parametric tests) to determine significant associations.

The case group exhibited a significantly lower mean Body Mass Index (BMI) (P<0.001) and weight (P<0.001), while no significant differences in height (P=0.102) or age (P=0.489) were observed. Notably, serum folic acid levels were significantly lower in the case group (P<0.001), whereas no significant differences were found for serum zinc (P=0.252) and vitamin B12 levels (P=0.763). Logistic regression analysis indicated that prenatal supplement use was protective against orofacial clefts (OR=0.062, P=0.002), while a positive family history (OR=11.473, P=0.023) and proximity to high voltage power lines (OR=20.085, P=0.001) were associated with increased risk. Furthermore, lower BMI (OR=0.859, P=0.016) and folic acid levels (OR=0.819, P=0.006) correlated with a higher risk of clefts.

This study highlights that low serum folic acid levels in pregnant women significantly correlate with non-syndromic cleft lip and palate in offspring. Additionally, associations with low BMI, pregnancy supplements, and environmental exposures underscore the importance of comprehensive preventive strategies to improve pregnancy outcomes and reduce congenital anomalies.