Optimization of Iron Deficiency Screening, Diagnosis, and Treatment in Pregnancy

Background

Prenatal iron deficiency is underrecognized and undertreated. Despite the universally recognized role of iron in maternal health as well as fetal and placental development, US national screening guidelines for prenatal iron deficiency are non-existent.

Study Design/Methods

A review of published literature pertaining to prenatal iron deficiency was performed; these data were summarized and synthesized to construct an algorithm for the diagnosis and treatment of prenatal iron deficiency.

Results

Iron deficiency is the most common etiology of anemia in pregnancy and affects over 50% of pregnancies; however, the lack of universal screening undoubtedly underestimates its true prevalence. A ferritin < 30 μg/dL has a 92% sensitivity and 98% specificity for the diagnosis of iron deficiency; remarkably, maternal ferritin < 13.4 μg/dL compromises fetal iron stores. Prenatal iron deficiency invokes significant maternal-fetal consequences: prenatal anemia doubles maternal mortality and is associated with higher rates of preeclampsia, cesarean sections, peripartum hemorrhage, and maternal transfusions; fetal iron deficiency is associated with a higher incidence of intrauterine growth restriction, preterm birth, low birth weight, and unfavorable long-term cognitive and behavioral sequelae (including autism and schizophrenia), the latter persisting despite iron repletion. Optimal iron repletion routes of administration vary by gestational age, with oral iron utilized in the first and second trimesters and the option for intravenous supplementation reserved for the second and third trimesters. While the gastrointestinal tract absorbs a maximum of 5mg of iron per day, the iron requirements in pregnancy are 800mg per day, highlighting the critical role of intravenous supplementation. The 2023 International Federation of Gynecology and Obstetrics (FIGO) guidelines recommend screening all women for iron deficiency starting from menarche, irrespective of anemia, including prior to planned pregnancy and at the end of the second trimester. The 2024 European Hematology Association (EHA) emphasizes and recommends identification of pre-conceptual iron deficiency and normalization of iron stores before conception, along with effective treatment of iron deficiency anemia in pregnancy or postpartum. Unfortunately, the American College of Obstetrics and Gynecology (ACOG) has yet to endorse comparable screening guidance for prenatal iron deficiency. We constructed an algorithm to facilitate early screening, diagnosis, and treatment of iron deficiency in pregnancy that utilizes ferritin as an initial test to screen for iron deficiency, instructions on how to replete iron and when to refer a patient to hematologist. Although our algorithm utilizes ferritin as the principal screening test, transferrin saturation <20% is diagnostic of iron deficiency in the context of inflammation.

Conclusion

The absence of a United States national recommendation to screen, diagnose, and treat prenatal iron deficiency compromises maternal-fetal outcomes. The adoption of universal iron deficiency screening in all women at first confirmation of pregnancy would lead to earlier recognition and treatment of iron deficiency and improve maternal-fetal outcomes.

Tomasulo:AstraZeneca: Consultancy; Sanofi: Consultancy; Abbvie: Consultancy.