Association between selected essential trace element concentrations in umbilical cord and risk for cleft lip with or without cleft palate: A case-control study

A deficiency or excess of zinc (Zn), selenium (Se), cobalt (Co), molybdenum (Mo), or manganese (Mn) may interfere with fetal organogenesis. However, the impact of these essential trace elements on the occurrence of cleft lip with or without cleft palate (CL ± P) remains to be elucidated. We aimed to investigate the associations between the amounts of Zn, Se, Co, Mo, and Mn in umbilical cord tissue and risk for CL ± P. This case-control study included 200 controls without congenital malformations and 88 CL ± P cases. Zn, Se, Co, Mo, and Mn concentrations in the umbilical cord were determined using inductively coupled plasma mass spectrometry. Information was collected on demographics, lifestyle behaviors, and dietary intake. The median concentrations of Zn in cases of CL ± P and cleft lip with cleft palate (CLP), of Se in cases of CL ± P and cleft lip only (CLO), and of Co in cases of CLO were lower than in the controls. In utero exposure to higher levels of Zn was associated with reduced risk for CL ± P (OR = 0.44, 95% CI, 0.20–0.93) and for CLP (OR = 0.35, 95% CI, 0.14–0.86), and a higher level of Se was associated with reduced risk for CL ± P and CLO, with ORs of 0.47 (95% CI, 0.23–0.95) and 0.22 (95% CI, 0.08–0.67), respectively. By contrast, higher levels of Mo in the umbilical cord were associated with 2.52-fold (95% CI, 1.23–5.20) and 2.59-fold (95% CI, 1.12–5.95) higher risk for CL ± P and CLP, respectively. No association was found between Co or Mn and risk for CL ± P. In conclusion, in utero exposure to higher levels of Zn and Se was associated with reduced risk for CL ± P, but higher levels of Mo were associated with increased risk for CL ± P.