Clinical Implications of Sickle Cell Thalassemia on Pregnancy Outcomes: A Systematic Review

Background/Objectives: Sickle cell thalassemia (HbSβ-thal) and related sickle cell disease (SCD) genotypes are associated with substantial maternal, fetal, and neonatal morbidity during pregnancy. This systematic review aimed to summarize pregnancy outcomes and clinical management strategies in women with HbSβ-thal and related hemoglobinopathies, with an additional narrative comparison to sickle cell trait (SCT)-a distinct, heterozygous, and generally benign carrier state that is not a form of SCD. Methods: A systematic literature search was conducted in PubMed, MEDLINE, Web of Science, EMBASE, and Scopus for studies published between 2016 and 2026 using terms related to sickle cell anemia, sickle cell disease, sickle cell thalassemia, HbS/beta-thalassemia, sickle cell trait, pregnancy outcomes, maternal complications, neonatal outcomes, fetal outcomes, and clinical/obstetric management. Studies reporting maternal, fetal, or neonatal outcomes were included, while letters, commentaries, conference abstracts, and presentations were excluded. Study selection followed PRISMA principles. Risk of bias was assessed using appropriate tools according to study design, including the Newcastle-Ottawa Scale (NOS), AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews), SANRA (Scale for the Assessment of Narrative Review Articles), and CARE (CAse REport) guidelines. SCT terms were included in the same search strategy, so that SCT studies were retrieved and screened through the same PRISMA process and are reported as a prespecified comparator subgroup. Results: Fourteen studies met the inclusion criteria: ten reporting outcomes in HbSβ-thal and related SCD genotypes and four reporting outcomes in SCT. The most frequently reported maternal complications were severe anemia, vaso-occlusive crises (VOCs), preeclampsia, thromboembolic events, infections, acute chest syndrome, cesarean delivery, and postpartum complications, which led to a significant increase in hospitalization rates. Fetal and neonatal outcomes were also unfavorable, with increased rates of preterm birth, low birth weight, intrauterine growth restriction, placental insufficiency, and neonatal intensive care admission. Placental vascular malperfusion and low maternal hemoglobin were important mechanisms underlying fetal growth restriction. By contrast, the included SCT literature suggested outcomes generally closer to the general obstetric population, with a smaller number of specific associations (e.g., preeclampsia, intrauterine fetal death) reported inconsistently across studies. Conclusions: Pregnancies complicated by HbSβ-thal and related hemoglobinopathies remain high-risk and require early identification, preconception counseling, multidisciplinary care, close antenatal surveillance, individualized transfusion strategies, and postpartum thromboprophylaxis when indicated. Prospective genotype-specific studies, particularly isolating HbSβ-thal from broader SCD cohorts, are needed to optimize evidence-based management.