Placental concentrations of manganese and the risk of fetal neural tube defects

Abstract

Manganese (Mn) is an essential trace element required for normal growth, development, and cellular homeostasis, but excess Mn is toxic to the central nervous system. The present pilot study examined whether the level of Mn in the placenta was associated with the risk of fetal neural tube defects (NTDs). A case-control study was conducted. Cases were 80 fetuses or newborns with NTDs, and controls were 50 healthy, nonmalformed newborns. Placental Mn, zinc, copper, iron, and selenium were determined with inductively coupled plasma-mass spectrometry. The median Mn concentration was significantly higher in case placentas than in controls: cases, 131.60 ng/g (95% confidence interval [CI], 99.25-166.76); controls, 101.54 ng/g (95% CI, 80.14-119.79). Mn concentrations above the median were associated with a 4-fold (95% CI, 1.23-14.79) increased risk for any NTDs and a 7-fold (95% CI, 1.52-39.64) increased risk for spina bifida after other confounding factors were controlled. Elevated Mn levels were associated with an increased risk of anencephaly, although the adjusted odds ratio did not reach statistical significance. The association between higher Mn concentrations and risk of NTDs showed a clear dose-response relationship. Risk of NTDs increased to 1.51 (95% CI, 0.65-3.52) and 5.03 (95% CI, 1.89-13.33) for those whose placental Mn level was in the second and third tertiles, respectively, compared with the lowest tertile. Elevated placental concentrations of Mn may be associated with increased risks of NTDs in this population.

Keywords: DMT-1; Iron; Manganese; Mn-SOD; NTD; Neural tube defect; Placenta; Zinc; manganese-superoxide dismutase; metal transporter 1; neural tube defect.