Antenatal medication management for women with sickle-cell disease: A systematic review

Improvements in sickle-cell disease (SCD) treatment have led to an increasing number of individuals surviving to reproductive age. However, pregnancy in women with SCD carries a heightened risk of maternal and fetal complications.

To evaluate the effectiveness and safety of commonly used antenatal medications and transfusion strategies on maternal and neonatal outcomes in pregnant women with SCD.

A systematic review was conducted using a pre-registered protocol (PROSPERO: CRD42023484839). Comprehensive literature searches were performed in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Embase, and CINAHL from their inception to November 24, 2023. Eligible studies included randomized controlled trials (RCTs), cluster RCTs, quasi-experimental studies, prospective and retrospective cohort studies, case-control studies, interrupted time series, and controlled before-and-after studies. Included studies examined antenatal medication or transfusion strategies for pregnant women with SCD, including any genotype. Risk of bias was assessed using RoB 2 for RCTs and ROBINS-I for non-randomized studies (NRSIs). Certainty of RCT evidence was evaluated using GRADE criteria. Data were synthesized using narrative synthesis due to study heterogeneity.

A total of 23 studies were included, of which two were RCTs and 21 were NSRIs. The RCTs investigated prophylactic transfusion and iron supplementation. Prophylactic transfusion may reduce the risk of sickle-cell crisis but the effect on other maternal or neonatal outcomes is unclear due to very low-certainty evidence. The effect of iron supplementation on maternal and neonatal outcomes is also of very low certainty. The observational studies carried a high risk of bias preventing meta-analysis and limiting the ability to draw conclusions.

There is a limited body of evidence on antenatal medication and transfusion management strategies for pregnant women with SCD. High-quality studies are needed to inform evidence-based antenatal care for this population.

PROSPERO: CRD 42023484839.