Maternal plasma folate, nutrients interactions, and the risk of orofacial clefts: A case–control study in a developing country setting

Background Orofacial clefts (OFCs) are complex congenital anomalies influenced by both genetic and environmental factors, with maternal folate long recognized as a modifiable risk factor. Aim This study investigated the association between maternal plasma folate levels and OFC risk and assessed contributions of other nutritional factors. Methods A case–control study was conducted in Kumasi, Ghana, involving 103 cases (children with OFCs) and controls (children without OFCs) (January to July 2024). Data were collected through interviewer-administered questionnaires and 24-h dietary recalls. Plasma folate was measured with a Human Folate ELISA kit, and BMI obtained by Bioelectrical Impedance Analysis device. Other variables included dietary intake of vitamin B 12 , B 6 , iron, zinc, BMI, and maternal age. Plasma folate was categorized as low (< 159.88 ng/mL), intermediate (159.88–293.06 ng/mL), and high (>293.06 ng/mL). Logistic regression assessed associations. Results Low plasma folate levels were observed in 52.4% of the case mothers versus 28.2% of controls ( p = 0.0004). In the unadjusted model, high folate was linked to increased OFC odds (odds ratio (OR) = 2.192, 95% confidence interval (CI): 1.081–4.447), while low folate showed non-significant elevated odds (OR = 1.229, 95% CI: 0.638–2.367). After adjustment, plasma folate was no longer significant. Independent predictors were dietary folate (OR = 1.009, 95% CI: 1.003–1.015), iron (OR = 0.871, 95% CI: 0.785–0.967), vitamin B 6 (OR = 0.335, 95% CI: 0.118–0.949), vitamin B 12 (OR = 0.751, 95% CI: 0.604–0.935), and maternal age (OR = 1.148, 95% CI: 1.012–1.302). Summary Plasma folate alone provides an incomplete assessment of OFC risk. Considering maternal nutritional profiles as a whole provides a more comprehensive understanding of risk.