Maternal And Umbilical Cord Serum Cobalt Concentration And Preterm Birth:A Population-based Birth Cohort Study

Backgrounds and ObjectivesPreterm birth（PTB）,defined as birth before 37 weeks of gestation,is a significant risk factor associated with neonate death,illness,and children’s growth and development.Increasing evidence has shown that infants with PTB were at higher risk for respiratory morbidities,neurological morbidities,and long-term hospitalization.PTB could even affect children’s cognitive development.Nevertheless,the etiology for PTB has not been illuminated clearly,and environmental exposures,nutritional deficiencies during pregnancy,maternal obesity,maternal infections and inflammation.Cobalt（Co）is an essential trace nutrient for human,and plays a key role in a number of biochemical processes,including erythrocytes formation,amino acids synthesis,and nucleic acids synthesis.Besides,Co is a necessary metal component of vitamin B₁₂,also called cyanocobalamin.Another study also suggested that the low Co levels in pregnancy women could reflect decreased levels of maternal vitamin B₁₂during pregnancy.Deficiency of Co is strongly related to disturbances in vitamin B₁₂synthesis,so it might cause anaemia and thyroid hypofunction and increase the risk of developmental abnormalities and failure in infants.Study has shown that vitamin B₁₂deficiency may affect more than three-quarters of some pregnant populations.Therefore,the prevalence of vitamin B₁₂2 deficiency in pregnant populations also reflects the possibility of the high prevalence of Co deficiency in pregnant women.A meta-analysis has shown that the lower levels of maternal vitamin B₁₂2 were associated with an increased risk of PTB.However,few researches have paid attention to the association between serum Co levels during pregnancy and the risk of PTB.The purpose of this study was to determine the association between maternal and umbilical cord serum Co concentrations and the risk of PTB.MethodsOur participants were from the Ma’anshan Birth Cohort study conducted in the Maternal and Child Health（MCH）Center in Ma’anshan city,Anhui Province,China from May 2013 to September 2014.Information of demographic characteristics（maternal age,pre-pregnancy BMI,maternal education）,socioeconomic status,pregnancy history（gravidity,parity）,pregnancy complications,lifestyle factors and fetal birth outcome were collected.In total,3240 maternal-singleton pairs were obtained in this study.Additionally,we also excluded 289 without maternal serum sample in the first trimester,160 without maternal serum sample in the second trimester,and 542without umbilical cord serum samples.A total of 2951,3080,and 2698 serum samples were obtained from pregnant women in the first trimester,the second trimester,and the umbilical cord blood,respectively.The distribution for Co in maternal and umbilical cord serum was positively skewed,and it presented an approximating normal distribution after being natural log-transformed.The tertile levels of serum Co were defined as low,medium and high levels for Co,respectively.Mann-whitney U test and kruskal-wallis H test were used to examine the differences between the subgroups.Logistic regression models were used to examine the relationship between serum Co levels and the risk of PTB.Restricted cubic spline models were used to consider potential non-linear associations between ln-transformed Co and the risk of PTB.We performed all statistical analyses with SPSS（version 10.0）and STATA（version 11.0）.Two-tailed P values less than 0.05 were considered statistically significant.ResultsWe found that the concentrations of serum Co progressively elevated with duration of pregnancy:the median and the 2.5^thh to 97.5^thh percentile concentrations of serum Co were 169.90ng/L（83.73 to 637.19ng/L）in the first trimester of pregnancy,and390.57ng/L（123.43 to 975.29ng/L）in the second trimester of pregnancy,respectively.Besides,the median concentrations of umbilical cord serum Co were 301.09ng/L（146.04 to 611.83ng/L）.Compared with high Co levels,the adjusted OR for PTB was1.73（95%CI:1.07,2.80;P<0.05）among subjects with low Co levels and 1.44（95%CI:0.88,2.36;P>0.05）among subjects with medium Co levels in the first trimester of pregnancy.Similarly,the adjusted OR for PTB was 1.73（95%CI:1.10,2.71;P<0.05）among subjects with low Co levels and 1.22（95%CI:0.75,1.99;P>0.05）among subjects with medium Co levels in the second trimester of pregnancy.The adjusted OR for PTB was 2.65（95%CI:1.43,4.94;P<0.005）among subjects with low Co levels and2.36（95%CI:1.26,4.42;P<0.01）among subjects with medium Co levels in the umbilical cord serum.Restricted cubic spline models revealed that maternal and umbilical cord serum Co concentration is negatively associated with the risk of PTB.ConclusionOur findings demonstrated that the lower levels in maternal and umbilical cord serum Co were associated with the increased the risk of PTB.