The impact of increased serum ferritin levels in late pregnancy on pregnancy outcomes: a multi-center cohort study in China.

objectivesWe aimed to explore the association between third trimester maternal serum ferritin (TT-SF) and adverse pregnancy outcomes.

methodsA prospective cohort study was conducted at 6 hospitals in China from May to December 2019, including 4003 pregnant women, to investigate the associations between TT-SF and obstetric complications, as well as maternal and neonatal perinatal outcomes. Logistic regression was used to screen for complications and outcomes associated with TT-SF. Mixed-effects models and interaction analyses were applied to control for the effects of center and population heterogeneity. The Youden index was used to determine the optimal TT-SF threshold for distinguishing outcomes.

resultsLongitudinal data indicate that the serum ferritin (SF) level in pregnant women decreases as pregnancy progresses, physiologically dropping from 75 ng/ml in the first trimester and 28.9 ng/ml in the second trimester to 21 ng/ml. Univariate logistic regression analysis shows that TT - SF is associated with low birth weight (LBW), preterm birth (PTB), and intrahepatic cholestasis of pregnancy (ICP). After adjusting for center effects and population heterogeneity, TT - SF remains independently associated with LBW and PTB (adjusted P < 0.05). The optimal cut - off value determined by the Youden index is 18.28 ng/ml, and density analysis confirms that this threshold can clearly divide pregnant women into two heterogeneous groups. Among them, the incidence of preterm birth in pregnant women with TT - SF higher than this threshold is 1.59 times that of those with TT - SF lower than the threshold, and the incidence of low birth weight is 4.5 times that of the latter. However, there is no statistically significant difference in the level of third trimester white blood cells (TT-WBC) in the third trimester between the two groups. Stratified analyses indicated that increases in TT-SF levels were significantly associated with an increased risk of LBW among women who initiated iron supplementation during mid-pregnancy and among those with supplementation durations longer than one month, whereas no significant association was observed with the daily dose of iron supplementation.

conclusionOur research findings highlight an often-overlooked aspect in clinical practice. Excessively high TT-SF levels may be associated with preterm birth and low-birth-weight infants, potentially indicating an increase in subclinical inflammation. At this stage, there is no observable difference in third trimester blood white blood cell (TT-WBC) levels. These findings suggest that TT-SF could serve as a marker for assessing the risk of preterm birth or low-birth-weight infants. Iron supplementation during pregnancy may exhibit distinct time-window effects and cumulative dose effects, and these findings provide insights for further optimization of iron supplementation strategies during pregnancy.