Association Between Maternal Serum Zinc Level And Fetal Growth Restriction: A Population-based Birth Cohort Study

Objective The present study analyzed the association between maternal serum zinc level during pregnancy and the risks of low birth weight(LBW) and small for gestational age(SGA) infants in a large population-based birth cohort study.Methods Total 4358 pregnant women were recruited in a Hefei subsample of China-Anhui birth cohort study. According to the established standards, 3187 pregnant women were chosen. Maternal fasting blood during pregnancy were collected from pregnant women. Serum zinc concentration was determined by flame atomic absorption spectroscopy(FAAS). Logistic regression model was used to estimate OR with 95%confidence intervals(CI) with respect to LBW and SGA incidence, for adjustment of pre-pregnancy BMI, maternal age, time for collecting serum and average monthly income. A nested case-control study was also used in the current study. In the case-control study, 50 SGA cases and 100 controls were chosen. TNF-α, IL-8 and CRP in maternal serum were measured by enzyme-linked immunoassay. Serum zinc concentration of umbilical cord serum was determined by FAAS. The expression and distribution of placental NF-κ B p65 was detected by immunohistochemistry.Results The average serum zinc concentration was 91.0 μg/d L among 3187 pregnant women. According to the suggested lower cutoffs of serum zinc concentrations by NHANES II, 2 940 pregnant women were sufficient(≥56 μg/d L) and 247 deficient(<56μg/d L). Of interest, 2.2% newborns were with LBW among subjects with normal zinc level. Moreover, 7.3% newborns were with LBW among subjects with low zinc level(OR: 3.48; 95% CI: 2.03, 5.96; P < 0.001). Adjusted OR for LBW was 3.41(95% CI:1.97, 5.91; P < 0.001) among subjects with low zinc level. Moreover, 8.2% newborns were with SGA among subjects with normal zinc level. 15.0% newborns were with SGA among subjects with low zinc level(OR: 1.98; 95% CI: 1.36, 2.88; P < 0.001).Adjusted OR for SGA was 1.93(95% CI: 1.32, 2.82; P < 0.001) among subjects with low zinc level. 2.6% newborns were with LBW among subjects with normal zinc level during the first trimester. 6.5% newborns were with LBW among subjects with low zinc level during the first trimester(OR: 2.63; 95% CI: 0.58, 12.00; P = 0.211). Adjusted OR for LBW was 2.64(95% CI: 0.58, 12.05; P = 0.211)among subjects with low zinc level during the first trimester. 8.3% newborns were with SGA among subjects with normal zinc level during the first trimester. Of interest, 22.6% newborns were with SGA among subjects with low zinc level during the first trimester(OR: 3.23; 95% CI: 1.33, 7.84; P =0.009). Adjusted RR for SGA was 3.12(95% CI: 1.27, 7.66; P = 0.013) among subjects with low zinc level during the first trimester. 7.4% newborns were with LBW among subjects with low zinc level during the second and third trimesters(OR: 3.70; 95% CI:2.06, 6.62; P < 0.001). Adjusted OR for LBW was 3.81(95% CI: 2.12, 6.85; P < 0.001)among subjects with low zinc level during the second and third trimesters. 13.9%newborns were with SGA among subjects with low zinc level during the second and third trimesters(OR: 1.82; 95% CI: 1.21, 2.76; P = 0.004). Adjusted OR for SGA was1.82(95% CI: 1.20, 2.75; P = 0.005) among subjects with low zinc level during the second and third trimesters. A nested case-control study within above cohort showed that maternal serum zinc level was lower in SGA cases as compared with controls. By contrast, maternal serum C-reactive protein, TNF-α and IL-8 levels were significantly higher in SGA cases than that of controls. Moreover, nuclear NF-κB p65 was significantly up-regulated in placentas of SGA cases as compared with controls.Conclusion Maternal zinc deficiency during pregnancy elevates the risks of fetal growth restriction. Placental and maternal inflammation may have relationships with fetal growth restriction which caused by maternal zinc deficiency.