Association of Serum Ferritin With Hypertensive Disorders of Pregnancy: A Longitudinal Analysis From a Large Retrospective Cohort

Background: Serum ferritin (SF) varies across gestation and reflects iron stores. Evidence on whether trimester-specific SF relates to the risk and severity of hypertensive disorders of pregnancy (HDP) remains limited, and clinicians lack gestational reference intervals to guide interpretation. Objective: To investigate trimester-specific changes in SF levels during pregnancy, evaluate the association between abnormal SF concentrations and the risk and severity of HDP, and establish gestational reference intervals to inform clinical interpretation. Methods: This retrospective cohort study included 28,607 pregnant women who received prenatal care at a single medical institution, of whom 2,501 developed HDP. Longitudinal changes of SF were analyzed using nonlinear mixed-effects (NLME) models. Multivariable logistic regression estimated adjusted odds ratios (aORs) for HDP across trimester-specific SF categories. Associations with severity were examined for gestational hypertension (GH) and severe preeclampsia (SPE). Trimester-specific SF reference intervals were derived in a healthy subgroup using the Hoffman method. Results: Compared with the CON group, women with HDP had higher SF, most notably in the second and third trimesters. In the first trimester, both low and high SF were associated with higher HDP risk, although only low SF remained after adjustment (aOR 1.389, 95% CIs 1.027–1.879). Elevated SF showed stronger associations with HDP in the second (aOR 1.655, 95% CIs 1.401–1.956) and third trimesters (aOR 2.077, 95% CIs 1.565–2.756). The highest SF category was further associated with GH (aOR 1.786, 95% CIs 1.177–2.709) and SPE (aOR 3.672, 95% CIs 2.456–5.490), suggesting a dose–response pattern. Trimester-specific reference intervals were: first 14.97–215.83 μg/L; second 6.67–63.17 μg/L; third 5.92–52.40 μg/L. Conclusion: SF demonstrates trimester-specific associations with the risk and severity of HDP. Low first-trimester SF aligns with iron deficiency signals, whereas higher SF in mid-to-late pregnancy marks higher HDP risk. These results support individualized interpretation and monitoring of SF rather than routine one-size-fits-all supplementation.