Maternal Vitamin B₁₂ Status and Risk of Cleft Lip and Cleft Palate Birth Defects in Tamil Nadu State, India

Abstract

Background and Objective: The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL±P) in a case–control study in Tamil Nadu state, India. Methods: Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B12, methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case–control status. Results: Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B12 status (OR = 3.65 95% CI, 1.21-11.05). Case–control status was not consistently associated with folate or tHcy levels. Low vitamin B12 status, when defined by a combination of both plasma vitamin B12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09). Conclusions: Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B12 or folate levels or their interactions are causally related to CL±P.

Differences in Folate and Vitamin B12 Serum Levels Between Mothers Whose Children were Diagnosed with Non-syndromic Cleft Lip and Cleft Lip with Palate

“…with the incidence of CL and or CLP (12). The study stated that a person deficient in vitamin B12 had a 6.…”

“…Elevated homocysteine is a strong risk factor for embryonic toxicity and the development of congenital defects, especially in the form of CL and/or CLP (11). A research conducted by Munger (2021) stated that there was a close difference between deficiency or low levels of vitamin B12…”

The effect of living environment on developmental disorders in cold regions

“…Tana et al reported that compared with the control group, exercise reduced the prevalence of the DDs in the offspring of GBD mice by 34.5% [80] . Addition to exercise, intaking trace elements is also one of the available approaches to prevent DDs [81][82][83] . This is owing to the pivotal role of trace elements in retaining redox homeostasis and regulating signal transduction pathways and immune function in healthy growth and development of body [84] .…”

Nitrous oxide–induced reproductive risks: Should recreational nitrous oxide users worry?

“…It is generally known that folate deficiency results in pregnancy-related complications and abnormal embryonic development with congenital defects, like neural tube defects (NTDs). However, low vitamin B 12 status was also found to be associated with the risk of NTDs (Molloy et al, 2009), cleft lip/palate (Munger et al, 2021), early recurrent abortion (Reznikoff-Etiévant et al, 2002), preterm birth and low birth weight (Rogne et al, 2017). For review of vitamin B 12 deficiency in pregnancy, see Van Sande et al (2013).…”