Published December 4, 2025
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Maternal plasma folate, nutrients interactions, and the risk of orofacial clefts: A case-control study in a developing country setting.

  • 1. Department of Biochemistry and Biotechnology, College of Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
  • 2. School of Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
  • 3. Cleft-Craniofacial Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana.

Description

BackgroundOrofacial clefts (OFCs) are complex congenital anomalies influenced by both genetic and environmental factors, with maternal folate long recognized as a modifiable risk factor.AimThis study investigated the association between maternal plasma folate levels and OFC risk and assessed contributions of other nutritional factors.MethodsA 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 B12, B6, iron, zinc, BMI, and maternal age. Plasma folate was categorized as low (293.06 ng/mL). Logistic regression assessed associations.ResultsLow 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 B6 (OR = 0.335, 95% CI: 0.118-0.949), vitamin B12 (OR = 0.751, 95% CI: 0.604-0.935), and maternal age (OR = 1.148, 95% CI: 1.012-1.302).SummaryPlasma folate alone provides an incomplete assessment of OFC risk. Considering maternal nutritional profiles as a whole provides a more comprehensive understanding of risk.
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