MTHFR and isolated spina bifida: In addition, the MTHFR C677T mutation, accompanied by increased blood homocysteine concentrations, results in a higher risk of various adverse pregnancy outcomes and offspring with congenital cardiovascular disease, neural tube defects (NTDs), or cleft lip and palate (Van Der Put et al., 2001; Wilcken et al., 2003; Pan et al., 2015; Zhang et al., 2018).