Timing and mode of birth for women with sickle cell disease: A systematic review.

Introduction: Sickle cell disease (SCD) is a significant global health issue. Pregnant women with SCD are at high risk of maternal and fetal morbidity and mortality. Among considerations in the management of women with SCD during pregnancy is the increased risk of placental insufficiency and the potential need for induction of labor or cesarean section to reduce risks to the woman and baby. In two separate reviews, we aimed to evaluate the effect of timing of birth (induction of labor at early term [37-38 weeks' gestation] or term [39-40 weeks' gestation] vs. spontaneous labor or induction of labor at 41-42 weeks' gestation) and the impact of mode of birth (cesarean section or vaginal birth) among women with SCD on neonatal and maternal outcomes. Methods: We systematically searched for relevant studies in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and CINAHL. We searched without language restriction from inception to July 29, 2023. We planned to include randomized controlled trials and cohort studies and to use standard methodological procedures as described in the Cochrane Handbook for Systematic Reviews of Interventions. Primary review outcomes included maternal death, pre-eclampsia, stillbirth and neonatal death. Secondary outcomes included maternal outcomes, for example, thromboembolic events, and fetal outcomes, for example, admission to neonatal intensive care. Results: No studies on timing of birth met the eligibility criteria. One retrospective, cross-sectional study, which included 255 pregnant women with SCD, was eligible for inclusion in the mode of birth review. Due to high risk of bias and imprecision in the study, we have very little confidence that the effect estimates represent the true effect. Compared to vaginal birth, cesarean birth may be associated with a reduction in risk of stillbirth (OR 0.03, 95% CI 0.00 to 0.45; 1 study, 255 women) and neonatal death (OR 0.31, 95% CI 0.11 to 0.84; 1 study, 255 women) in women with SCD, but the evidence is very uncertain. Conversely, cesarean birth may be associated with an increase in risk of pre-eclampsia (OR 2.32, 95% CI 1.17 to 4.58; 1 study, 255 women), postnatal infection (OR 1.86, 95% CI 1.07 to 3.23; 1 study, 255 women), and the need for blood transfusion (OR 2.67, 95% CI 1.38 to 5.14; 1 study, 255 women) in this population but, again, the evidence is very uncertain. Conclusions: As no studies relevant to timing of birth met our eligibility criteria, we are unable to comment on the optimal timing of birth for women with SCD. Based on a single observational study, we remain uncertain about whether vaginal or cesarean birth is more appropriate for women with SCD. Further research is necessary to thoroughly evaluate the effect of timing and mode of birth on maternal and fetal outcomes in this population. PROSPEERO Registrations: CRD 42023461767; CRD 4202346175.