Maternal serum level of manganese, single nucleotide polymorphisms, and risk of spontaneous preterm birth: A nested case-control study in China

Manganese (Mn) is an essential trace element, but an excess or accumulation can be toxic. Until now, few studies have examined the effects of maternal Mn level on the risk of spontaneous preterm birth (SPB). The aims of this study were to examine the association between maternal Mn level and the risk of SPB at the early stage of pregnancy, and investigate whether this association was modified by single nucleotide polymorphisms (SNPs) in genes of superoxide dismutase (SOD) and catalase (CAT). We conducted a nested case-control study in three maternal and child health care hospitals in Shanxi province, China, from December 2009 to December 2013. From an overall cohort of 4229 women, 528 were included in our study, including 147 cases of SPB and 381 controls. Maternal blood samples were collected during 4–22 gestational weeks. The maternal serum concentrations of Mn was measured using inductively coupled plasma–mass spectrometry. We found the maternal Mn concentration in the case group (median: 1.55 ng/mL) was significantly higher than that in the control group (median: 1.27 ng/mL). Compared to the lowest level, the SPB risk was significantly increased to 1.44 (95%CI: 0.60–3.43), 2.42 (95%CI: 1.06–5.55) and 2.46 (95%CI: 1.08–5.62) respectively for the second, third and fourth quartiles in first trimester, but not significant in second trimester or overall. When exposure to a high Mn level, women who with AA (6.36, 95%CI: 1.57–25.71) and AG (3.04, 95%CI: 1.59–5.80) of rs2758352, with CC (2.34, 95%CI: 1.31–4.18) of rs699473, and with GG (2.26, 95%CI: 1.22–4.16) of rs769214 were more likely to develop a SPB, but not among women with other genotypes. In conclusion, high maternal serum Mn level is associated with the increased SPB risk in first trimester, and the association is modified by maternal SNPs of SOD2, SOD3 and CAT.