Abstract: Out of six relevant reports identified by the search strategy, one trial involving 72 women with sickle cell anaemia (HbSS) met our inclusion criteria. The trial was at unclear risk of bias. Overall, there were few events for most of the reported outcomes and the results were generally imprecise. The included trial reported no maternal mortality occurring in women who received either prophylactic or selective blood transfusion. Very low-quality evidence indicated no clear differences in maternal mortality, perinatal mortality (risk ratio (RR) 2.85, 95% confidence interval (CI) 0.61 to 13.22; very low-quality evidence) or markers of severe maternal morbidity (pulmonary embolism (no events); congestive cardiac failure (RR 1.00, 95% CI 0.07 to 15.38; very low-quality evidence); acute chest syndrome (RR 0.67, 95% CI 0.12 to 3.75)) between the treatment groups (prophylactic blood transfusion versus selective blood transfusion). Low-quality evidence indicated that prophylactic blood transfusion reduced the risk of pain crisis compared with selective blood transfusion (RR 0.28, 95% CI 0.12 to 0.67, one trial, 72 women; low-quality evidence), and no differences in the occurrence of acute splenic sequestration (RR 0.33, 95% CI 0.01 to 7.92; low-quality evidence), haemolytic crises (RR 0.33, 95% CI 0.04 to 3.06) or delayed blood transfusion reaction (RR 2.00, 95% CI 0.54 to 7.39; very low-quality evidence) between the comparison groups. Other relevant maternal outcomes pre-specified for this review such as cumulative duration of hospital stay, postpartum haemorrhage and iron overload, and infant outcomes, admission to neonatal intensive care unit (NICU) and haemolytic disease of the newborn, were not reported by the trial. Evidence from one small trial of very low quality suggests that prophylactic blood transfusion to pregnant women with sickle cell anaemia (HbSS) confers no clear clinical benefits when compared with selective transfusion. Currently, there is no evidence from randomised or quasi-randomised trials to provide reliable advice on the optimal blood transfusion policy for women with other variants of sickle cell disease (i.e. HbSC and HbSβThal). The available data and quality of evidence on this subject are insufficient to advocate for a change in existing clinical practice and policy.

Plain-language summary: We searched for evidence on 30 May 2016 and identified one controlled trial, with an unclear risk of bias, that randomised 72 women with sickle cell anaemia (haemoglobin SS) before 28 weeks of gestation to one of the two blood transfusion policies. The trial indicated no difference in severe ill health and death of the mother or newborn. There was no difference in the risk of delayed blood transfusion reaction. The trial suggested giving blood at frequent intervals reduced the risk of pain crisis, with a large degree of uncertainty about the size of the effect, compared with giving blood only when medically indicated. Blood transfusion was delivered at a ratio of four to one for prophylactic versus selective blood transfusion, respectively. Overall, the quality of evidence for outcomes that are important to the woman is very low. The available evidence on this subject is insufficient to advocate for a change in clinical practice and policy. More research needs to be conducted.