Maternal and Fetal Outcomes in Sickle Cell Disease: Single Center Review

Background:

Pregnancy related maternal complications in sickle cell disease (SCD) have been previously described including recurrent vaso-occlusive crisis (VOC), pre-eclampsia, eclampsia, postpartum hemorrhage (PPH) and venous thromboembolism (VTE). Fetal/neonatal complications have also been described including prematurity, intra-uterine growth restriction (IUGR), congenital heart disease (CHD) and low birth weight. Some of these complications could be related to low hemoglobin (Hb) levels and high percent HbS during pregnancy. Our study describes the rate of maternal and fetal/neonatal complications in our patients with SCD and outline factors that could be related to these complications.

Methods:

A retrospective study was done at the Georgia Comprehensive Sickle Cell Center and included patients with SCD, > 18 years who were pregnant and had delivered between 2022 to 2024. Patients with HbSS/HbSB0 were grouped together while patients with HbSB+/HbSC/HbSHPFH were grouped separately. We collected maternal variables (SCD related acute visit, morphine milligram equivalent per day [MME/day], average Hb during pregnancy, gestational age), obstetric complications (pre-eclampsia, eclampsia, VOC, HELLP syndrome, PPH, intraamniotic infection, VTE), fetal/neonatal complications (IUGR, CHD, oligohydramnios, respiratory failure, hydrops fetalis). Patients with HbSS not on scheduled red blood cell (RBC) transfusion were referred as NT-HbSS while those on scheduled RBC transfusion were referred as T-HbSS. Paired T test, unpaired T test and Chi-Square test were used to analyze data. Statistical significance was defined as p-value ≤ 0.05.

Results:

24 Pregnancies were identified in patients with SCD (HbSS=14, HbSB0=1, HbSC=6, HbSB+=1, HbSHPFH=2) with a total of 26 neonates identified. 3 patients with T-HbSS were identified. There was an increase in SCD related acute visit per month in all patients from 0.30 pre-pregnancy to 0.63 during pregnancy (P 0.009). When separated by genotype/transfusion status, the NT-HbSS/SB0 group increased from 0.34 to 0.92 (P 0.010). No change was noted in the other groups.

The average percentage increase in acute visit per month in the HbSS/SB0 vs HbSC/SHPFH/SB+ group was 153.39% vs 35.80% respectively (P 0.036). The average percentage increase in MME/day in the HbSS/SB0 vs HbSC/SHPFH/SB+ group was 149.33% vs 34.63% respectively (P 0.047). Although a 37.44% increase in MME/day was noted in the T-HbSS group, this was not statistically significant when compared to other groups.

The rate of maternal/fetal/neonatal complication in all patients was 56%. In the HbSS/SB0 group, the rate of maternal/fetal/neonatal complication in patients with Hb <8 vs >8 was 78.57% vs 44.44% respectively (P 0.051). The rate of eclampsia/pre-eclampsia in all patients was 29.17%. In the HbSS/SB0 group, the rate of eclampsia/pre-eclampsia in patients with Hb <8 vs >8 was 66.70% vs 11% respectively (P 0.025). The average gestational age (weeks) for all patients was 36.5. The average gestational age in the HbSS/SB0 group with Hb <8 vs >8 was 33.83 vs 37.89 respectively (P 0.030). The average weight (lbs) for all neonates was 5.54. The average neonatal weight in the NT-HbSS/SB0 vs T-HbSS group was 4.85 vs 6.77 respectively (P 0.034). The average neonatal weight in the HbSS/HbSB0 group with Hb <8 vs >8 was 4.11 vs 6.16 respectively (P 0.004).

Conclusion:

Our study shows a high rate of maternal and fetal/neonatal complications across all patients with SCD. In addition, we noted a statistically significant higher rate of prematurity and low birth weight in neonates born to mothers with HbSS/SB0 who had an average Hb <8 during pregnancy. We also noted a statistically significant increase in the rate of pre-eclampsia/eclampsia in this group. The incidence of maternal and fetal/neonatal complications in the HbSS/HbSB0 group with average Hb <8 was higher compared to the subset with average Hb >8 and approached statistical significance. Although there was no statistically significant decrease in maternal and fetal/neonatal complications in the T-HbSS group, likely related to small sample size, we observed less increase in MME/day, less increase in SCD related acute visits and a decrease in the rate of prematurity. Given these findings, we are starting a larger randomized controlled study in pregnant patients with SCD to determine the impact of scheduled RBC transfusion on maternal and fetal outcome.