The Relationship Between Pre-Pregnancy Sickle Cell Disease-Specific Complications and Maternal and Fetal Outcomes in Sickle Cell Disease Pregnancies

Patients with sickle cell disease (SCD) have worse maternal and fetal outcomes compared to the general population, and experience antepartum complications unique to SCD patients, including painful vasoocclusive crises (VOC), acute chest syndrome (ACS), stroke and symptomatic anemia. The relationship between pre-pregnancy SCD-specific complications and maternal/fetal outcomes and antepartum complications has not been explored. We hypothesize that increased rates of SCD-specific complications are associated with increased rates of antepartum SCD-specific complications and worsened maternal and fetal outcomes. We further hypothesize that elevation in fetal hemoglobin is associated with improved maternal/fetal outcomes.

We conducted a retrospective review of patients with SCD (SS, SC, S/beta-thalassemia) whose pregnancies were managed at the Mount Sinai Hospital (MSH), a high risk obstetrics care institution in Ontario, Canada, between January 1st, 1999 and June 30th, 2009 based on the institution's electronic and paper-based medical records. Patients were jointly managed by a hematologist specialized in hemoglobinopathies and an obstetrician specialized in high risk obstetric care. We compared the pre-pregnancy and antepartum rates of SCD-specific complications (painful VOC, ACS, stroke, and on-demand transfusion requirements). Pre-pregnancy fetal hemoglobin level was analyzed according to the presence or absence of maternal/fetal complications (expressed as an aggregate of preterm delivery, placental insufficiency, low birth weight (<2500 g), the need of emergent Caesarian section, fetal anomalies and fetal death). The t-test was used to compare means of the two groups. Fisher's exact test was used to compare categorical frequency data. An alpha value of 0.05 was chosen as the level of significance.

We identified 22 pregnancies in 22 patients with SCD, 4 patients had not delivered at the time of censor. Fourteen patients were HbSS, 7 were HbSC, 1 was HbS/beta-thalassemia. Mean maternal age was 31.1 years. Mean gestational age at delivery was 37 weeks (95% CI 36 to 38 weeks) and 5 (23%) were preterm (< 37 weeks). Eleven of the 18 deliveries (61%) were by Caesarian section and 7 were performed on an emergent basis (4 due to fetal distress and 3 due to failure to progress). Three (17%) were low birth weight (< 2500 g) and 2 (11%) were intrauterine growth restricted. Maternal and fetal outcomes and rates of antepartum complications were similar to the existing literature. There was no association between prior history of ACS and having an episode of ACS during pregnancy. A history of painful VOC was associated with having at least one episode of painful VOC during pregnancy (P = 0.0433). Pre-pregnancy history of on-demand red cell transfusion was also associated with the need of at least one unit of transfusion during pregnancy (P = 0.0048). However, the frequency and time of first painful VOC during pregnancy were not associated with worsened maternal/fetal outcome. There was no association between fetal hemoglobin level and antepartum rates of painful VOC (P = 0.4867), ACS (P = 0.3702), and maternal/fetal complications (P = 0.2489). The results suggest that patients with a history of painful VOC may be predisposed to having painful VOC during pregnancy. Similarly, patients with a history of on-demand transfusion may need transfusion during pregnancy. The present study is limited by small sample size and its single-centered and retrospective nature. Further observation studies with larger sample size are required to prospectively validate these results.

Kuo:Novartis Canada: Research Funding.