EFFECTS OF HYPERHAEMOLYSIS ON FETOMATERNAL OUTCOMES IN PREGNANT WOMEN WITH SICKLE CELL DISEASE

Abstract

Background: Sickle cell disease (SCD) is a public health problem in sub-Saharan Africa. Recent improvement in healthcare has ensured significant increase in survival and increased chance of getting pregnant. Chronic haemolysis is a feature of SCD; haemolysis has been linked to chronic uncompensated anaemia, pulmonary hypertension, chronic leg ulcers, priapism, renal impairment, acute vaso-occlusion, venous thromboembolism and death in SCD. Hyperhaemolysis occurs in stressful conditions, and pregnancy can be stressful. Pregnancy in SCD, can be life-threatening and may be associated with poor fetomaternal outcome. Few studies, have looked at hyperhaemolysis during pregnancy and its association with fetomaternal outcome.

Methodology: A prospective cohort study with 25 pregnant women with SCD, and their 2 sets of matched controls (23 pregnant women without SCD; 25 non-pregnant women with SCD) was conducted at the Obstetrics department, Korle-Bu Teaching Hospital, and the adult sickle cell clinic, Ghana Institute of Clinical Genetics, Korle-Bu. The pregnant women with and without SCD were matched for gestational age (±2weeks) and enrolled during the second trimester. Most pregnant women presenting to the clinic for their booking visit are unsure of the date of their last menstrual period. As such, the gestational age is determined by an obstetrics scan. During the second trimester an obstetrics scan gives an error margin of 10 to 14 days; hence there will be no difference in the gestational age match using ±2weeks. The SCD group (pregnant/non-pregnant) were matched for age (±2years) and phenotype. The age match was based on convenience. All pregnant women with and without SCD were followed up prospectively till six weeks postpartum. The non-pregnant women with SCD had only baseline samples drawn. The primary outcome of the study was to determine the association between hyperhaemolysis and fetomaternal outcome in pregnant women with SCD using selected markers of haemolysis- haemoglobin, absolute reticulocyte count, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), serum bilirubin and urobilinogen. The maternal outcomes were acute pain, ACS and anaemia. The fetal outcomes were spontaneous abortion, intrauterine fetal death (IUFD), preterm birth and low birthweight. Data was extracted using Excel and analysed by the use of means, standard deviation, analysis of variance and logistic regression using STATA corps version 14.

Results: The mean age of the study participants was 30.3 ± 5.3 years. The mean gestational age at enrollment for the pregnant women with and without SCD was 19.4 ± 3.7 weeks. There were 13 acute pain episodes in nine pregnant women with SCD with a pain incidence rate of 1.23 events per patient- years. There was no admission for ACS during the study period. Using the criteria for defining

hyperhaemolysis, only one patient each had a drop in Hb ≥20% from baseline at 28 and 36 weeks’ gestation and six weeks postpartum; with no corresponding 25% increase in reticulocyte count and an increase in LDH, indirect bilirubin and AST. There were no significant differences in the concentrations of the haemolytic markers during study follow-up. Compared to the pregnant women without SCD, the pregnant women with SCD had more caesarean deliveries [4(19.0%) vrs 18(72.0%);p=0.01]; preterm births [5(27.8%) vrs 10(41.7%);p=0.35], low birthweight babies [3(16.7%) vrs 7(29.2%); p=0.74] and IUFD [0 (0.0%) vrs 2 (8.0%)] respectively.

Conclusion: This study did not demonstrate hyperhaemolysis in pregnant women with SCD; hence no association between hyperhaemolysis and fetomaternal outcome could be determined. There was no difference in steady state laboratory parameters of the selected markers of haemolysis between the SCD cohorts (both pregnant and non-pregnant).