Maternal serum ferritin across gestation and risk of small-for-gestational-age: a longitudinal cohort study

Iron supplementation is essential for maintaining maternal-fetal health during pregnancy. However, research on the relationship between serum ferritin (SF) and small-for-gestational-age (SGA) births remains limited and inconclusive.

This study aimed to investigate the association between maternal SF levels and SGA during pregnancy.

We utilized electronic medical records from women who delivered at Shanghai First Maternity and Infant Hospital between 2018 and 2020. Maternal SF levels were measured at 8.0-13.6 weeks' gestation (GW) and 29.0-31.6 GW. Based on these measurements, participants were categorized into three groups according to SF concentration percentiles: low (< 25th), medium (25th to < 75th), and high (≥75th). The association between maternal SF levels and SGA was evaluated using binary logistic regression. Additionally, a restricted cubic spline model was employed to explore potential nonlinear relationships between SF levels and the risk of SGA.

A total of 17,451 pregnant women were included. At 29.0-31.6 weeks of gestation, women with elevated serum ferritin (SF) (≥18.1 ng/mL, ≥75th percentile) had a significantly higher incidence of SGA than those with lower levels [4.4% vs. 2.4%; adjusted odds ratio (aOR) = 1.418, 95% CI: 1.089-1.846, P = 0.009]. A significant positive dose-response relationship between SF levels and SGA risk was observed (P for trend < 0.0001), with a threshold of 12.1 ng/ml. Compared with women with consistently low SF levels in both trimesters, the risk of SGA was significantly increased in two groups: 1) those with medium first-trimester SF (31.5 to < 81.9 ng/ml) and high third-trimester SF (≥18.1 ng/ml) (aOR = 1.712, 95% CI: 1.138-2.576, P = 0.01); and 2) those with high SF in both trimesters (first: ≥81.9 ng/ml; third: ≥18.1 ng/ml) (aOR = 1.676, 95% CI: 1.118-2.513, P = 0.012). However, SF levels dropping from high to medium between trimesters was not associated with an increased risk of SGA (aOR = 0.951, 95% CI: 0.614-1.472).

Our findings demonstrate an independent and positive association between elevated maternal serum ferritin levels during the third trimester of pregnancy and increased risk of SGA. These results challenge the current practice of routine iron supplementation in pregnant women with normal iron levels.