The Long-Term Effect of Maternal Iron Levels in the Second Trimester on Mild Thinness among Preschoolers: The Modifying Effect of Small for Gestational Age

Abstract

The supplementation of multiple micronutrients throughout pregnancy can reduce the risk of adverse birth outcomes and various diseases in children. However, the long-term effect of maternal multiple micronutrient levels in the second trimester on the overall development of preschoolers remains unknown. Therefore, 1017 singleton mother-infant pairs and 6-year-old preschoolers were recruited based on the China-Wuxi Birth Cohort Study. Meanwhile, information on the demographic characteristics of pregnant women and preschoolers, maternal copper, calcium, iron, magnesium, and zinc levels in whole blood during the second trimester, and neonatal outcomes, were collected. We aimed to investigate the long-term impact of maternal copper, calcium, iron, magnesium, and zinc levels in the second trimester on mild thinness among 6-year-old preschoolers, and the modifying effect of small for gestational age (SGA), within the Chinese population. Multiple logistic regression models revealed that high-level maternal iron in the second trimester reduced the risk of mild thinness [adjusted OR: 0.46 (95% CI: 0.26, 0.80)] among 6-year-old preschoolers. However, no significant association was found for the remaining four maternal essential metal elements. Additionally, the restricted cubic spline function showed that the risk of mild thinness decreased when maternal iron concentration exceeded 7.47 mmol/L in whole blood during the second trimester. Furthermore, subgroup analysis indicated that the long-term protective effect of high-level maternal iron on mild thinness was only observed in SGA infants. Summarily, high-level maternal iron in the second trimester distinctly lowers the risk of mild thinness among 6-year-old preschoolers, especially in preschoolers with birth outcomes of SGA. Our findings offer evidence for the implementation of iron supplementation in the second trimester as a preventive measure against mild thinness in children.

Keywords: iron; micronutrients; mild thinness; pregnancy; preschoolers; small for gestational age.

Figure 1

Flow chart of the inclusion of participants in the China-Wuxi Birth Cohort Study (C-WBCS).

Figure 2

Spearman correlations among multiple indexes. The color depth and the size of the pie indicate the Spearman correlation coefficients. A blank grid presents a p-value of more than 0.05. Notes: BMI, body mass index; Cu, copper; Ca, calcium; Fe, iron; Mg, magnesium; Zn, zinc.

Figure 3

Mild thinness of preschoolers in relation to five maternal essential metal elements levels in the second trimester in the logistic regression model. The odds ratios (OR) and 95% confidence intervals (CIs) were presented for each tertile compared with the third tertile (T1). Notes: Cu, copper; Ca, calcium; Fe, iron; Mg, magnesium; Zn, zinc; T1, 1st tertile; T2, 2nd tertile; T3, 3rd tertile; CI, confidence interval. ^a Crude model. ^b Adjusted model 1: adjusted for maternal age, pre-pregnancy BMI, parity, gravidity, newborn gender, and gestation age. ^c Adjusted model 2: adjusted for variables in model 1 and the other four maternal essential metal elements. ^d Mild thinness is defined as body mass index z-score < −1 for 6-year-old preschoolers of different genders. ^e p trend was the p value for the trend. ** p <0.01.

Figure 4

Dose–response relationship between maternal iron concentrations in the second trimester and mild thinness of 6-year-old preschoolers. The associations were estimated using restricted cubic spline functions with three knots. Models were adjusted for maternal age, pre-pregnancy BMI, parity, gravidity, newborn gender, gestation age, and the other four maternal essential metal elements. The light grey area represents the 95% CIs. Two vertical black lines represent iron concentrations when the OR for mild thinness of 6-year-old preschoolers was 1.0. The horizontal black line represents when the OR for mild thinness of 6-year-old preschoolers was 1.0. The abscissa of the intersection of the red line (the curve of RCS function) and the horizontal black line were written in red. Notes: OR, odds ratios; Fe, iron. ^a Mild thinness is defined as body mass index z-score < −1 for 6-year-old preschoolers of a different gender.

Figure 5

Small for gestational age in relation to five maternal essential metal elements levels in the second trimester using logistic regression analysis. The odds ratios (OR) and 95% confidence intervals (CIs) were presented for each tertile compared with the third tertile (T1). Notes: Cu, copper; Ca, calcium; Fe, iron; Mg, magnesium; Zn, zinc; T1, 1st tertile; T2, 2nd tertile; T3, 3rd tertile; SGA, small for gestational age; CI, confidence interval. ^a Crude model. ^b Adjusted model 1: adjusted for maternal age, pre-pregnancy BMI, parity, gravidity, newborn gender, and gestation age. ^c Adjusted model 2: adjusted for variables in model 1 and the other four maternal essential metal elements. ^d p trend was the p value for the trend. ** p <0.01, * p <0.05.