Pregnancy Outcomes in Patients with Sickle Cell Syndromes Managed Antenatally with Exchange Transfusions: A Single Centre Analysis
Authors: Vlachodimtropoulou Koumoutsea Evangelia , Nuntouchaporn Hutachok , Eleftheriou Perla , O'Brien Patrick , Porter John 
Published: October 2019

Abstract
Background/Objectives
The optimal management of pregnancy with sickle cell disease (SCD) is controversial (Cohen and O'Brien, Chapter 14, 2012). In particular, the value of prophylactic exchange transfusions in preventing complications from SCD and/or pregnancy itself is unclear. For the past decade at University College London Hospitals (UCLH), UK, we have undertaken prenatal exchange transfusions for most patients with sickle cell syndromes (SCS), HbSS, SC or Sb-thalassaemia. This is due to the poor outcomes we had experienced previously in a proportion of patients in whom prophylactic transfusion was not undertaken. We review the outcome over seven years in all such pregnancies managed at UCLH.
Methodology/Patients
We undertook a retrospective analysis of pregnancy outcomes of women with SCS delivering between 1 Jan 2011 and 31 Dec 2017. Data were collected from electronic hospital-held records. We recorded 50 pregnancies in 22 women, of which 25 resulted in live births. Most women had HbSS (82%), 14% had HbSC and 4% HbS-bthalassemia. The early pregnancy (<12 weeks) miscarriage rate of 28% was greater than the UK National Guidelines, 2012, which was 22% (Table 1). The median age (range) of our patients was 32 (19-40) years, which might contribute to the increased miscarriage rate. One woman sustained 6 of the 11 recorded miscarriages. Only 4% of pregnancies occurred in women >40, which is similar to national data for England (3.6%) (Centre for Maternal and Child Enquiries [CMACE], 2011). This age distribution is comparable to that in the population of Oteng-Ntim et al, 2015, who looked at pregnancy outcomes in a UK sickle population between 2010 and 2011. Patients were managed antenatally with exchange transfusions where there were no contraindications with respect to prior allo-immunisation, to reduce sickle related complications and improve pregnancy outcomes. Eight All patients were adequately hydrated antenatally. To gain insight into the effect of this management on maternal complications and fetal outcomes, these were compared with a recently reported cohort of SCS in London who did not receive exchange transfusions (Oteng-Ntim et al, 2015).
Results
Painful crises requiring admission antenatally were 9% compared with 17.6% reported by Oteng-Ntim et al, 2015. There were no admissions with sickle chest syndrome, either antenatally or postnatally, compared with 6.4% (Oteng-Ntim et al.). Preterm labour before 34 weeks' and 37 weeks' gestation occurred in one case (4.5%) and in 38% of cases, compared to 44.2% reported by Serjeant et al, 2004 and 47.1% reported by Oteng-Ntim et al before 37 weeks. There were no late miscarriages or stillbirths in our cohort. By contrast, in Oteng-Ntim et al, the stillbirth rate was 2.8% which is higher than the 0.92% reported in the general population (CMACE, 2011). The Caesarean section (CS) rate was 64%, which is higher than previously reported (39% in Barfield et al, 2010, 52.9% in Oteng-Ntim et al, 2015) (Table 3). One woman sustained a significant post-partum haemorrhage. The following complication rates were similar to those reported by Oteng-Ntim et al, 2015 (Table 3): postnatal pain: 18% vs 21.6%; pre-eclampsia 8% vs 7.8%; intrauterine growth restriction (IUGR): 22% vs 27.3% (Table 4). Four patients had pre-existing allo-antibodies, of whom three had two or more antibodies. No new allo-immunisations developed during pregnancy.
Conclusions
Although our cohort numbers are small, they suggest a lower rate of painful crisis/chest syndrome than reported in series of SCS in which prophylactic exchange transfusions were typically not practised. While the rate of IUGR was lower than in historic reports, the difference was less clear than for painful crisis. There were no stillbirths in our series, despite the previously documented high incidence in women with SCS. The high rate of CS reflects local practice by clinicians wishing to avoid prolonged labour in this patient population. No serious adverse reactions to transfusion in pregnancy were seen despite one patient having had a previous hyperhaemolytic episode outside pregnancy. This study shows that prophylactic antenatal exchange transfusion is well tolerated and associated with fewer veno-occlusive crisis complications than historically reported with sickle disorders. Randomised studies are indicated in a larger cohort of patients to determine whether other benefits or risks accrue from this approach.

Disclosures
Porter: Cerus: Honoraria; Novartis: Consultancy; Agios: Honoraria.