Population-based study of serum ferritin in early pregnancy and adverse perinatal outcomes

Abstract

Background: Chronic placental inflammation is associated with preterm birth (PTB) and perinatal mortality. Ferritin is often elevated in chronic inflammatory conditions, but prior studies of its relation to PTB were restricted to ferritin measurement within pregnancy, were underpowered to detect rarer outcomes, and did not account for pre-existing maternal inflammatory conditions, such as inflammatory bowel or rheumatological disease.

Objectives: To evaluate whether an elevated ferritin level prior to pregnancy is associated with major adverse pregnancy outcomes.

Methods: A population-based cohort study was completed using Ontario, Canada. Included were all Ontarian women with a hospital livebirth or stillbirth at ≥20 weeks' gestation, 2007-2018, and serum haemoglobin and ferritin measured as an outpatient within 120 days before conception. Excluded were women with a diagnosed iron overload disorder or a ferritin concentration <15 µg/L. The main exposure was a pre-pregnancy serum ferritin ≥95th percentile. Study outcomes included PTB < 37 weeks' gestation, including clinician-initiated and spontaneous PTB; PTB < 32 weeks; chorioamnionitis; and perinatal death. Relative risks (RR) and 95% confidence intervals (CI) were calculated for each study outcome, comparing a serum ferritin concentration ≥95th vs <5th percentile (the referent), while adjusting maternal age, residence, haemoglobin concentration, diabetes mellitus, inflammatory bowel disease, illicit drug/tobacco use, chronic kidney disease, chronic hypertension, sickle-cell disease or thalassaemia, and rheumatological conditions.

Results: Among 89 847 births, a preconceptional maternal serum ferritin ≥95th (112.0 μg/L) vs <5th (16.9 μg/L) percentile was associated with an adjusted relative risk (aRR) of 1.34 (95% CI 1.15, 1.57) for PTB, including spontaneous and clinician-initiated PTB. Results were equivocal for chorioamnionitis (aRR 1.23, 95% CI 0.81, 1.86), and there was no association with perinatal mortality (aRR 0.94, 95% CI 0.55, 1.61).

Conclusion: A high preconceptional ferritin concentration is associated with some adverse perinatal outcomes.

Keywords: chorioamnionitis; ferritin; inflammation; iron; perinatal mortality; preterm birth.