Low Body Mass Index in Pregnant Women with Sickle Cell Disease Is Associated with Premature Delivery in Sub- Saharan Africa

Background: Sickle cell disease (SCD) is one of the most common genetic disorders in the world, and is a public health problem in sub-Saharan Africa. Nearly 30% of Ghanaians have sickle cell trait and about 2% (15,000) of babies are born with SCD every year. Pregnant women living with SCD, particularly in low-income countries have increased risk of maternal and perinatal complications (BJOG: An International Journal of Obstetrics & Gynaecology. 2016 Apr;123(5), 691-698.). Fetal complications include premature delivery, intrauterine growth restriction, low birthweight, perinatal fetal distress, and a high rate of perinatal mortality. In 2015, we established a multidisciplinary SCD obstetric (SCOB) team, including both local and international experts, at the Obstetrics Department, Korle- Bu Teaching Hospital (KBTH), Accra, Ghana. In a before-and-after study, we showed that a multidisciplinary obstetric care including haematologists, compared to obstetric care alone, resulted in an 89% relative risk reduction in the maternal death rate in women with SCD (Am J Hematol: An International Journal of Hematology. 2017 May 16. doi: [Epub ahead of print]). Prior studies have indicated that individuals with SCD have a lower body mass index (BMI) when compared to individuals without SCD, due to increased resting metabolic rate (proposed mechanism includes: hypermetabolism, increased hemolysis, red cell turnover and cardiac demand). We tested the hypothesis that low baseline BMI is associated with increased risk of premature birth in pregnant women with SCD.

Methods: In a prospective pregnancy cohort study over a total of 20 months, we followed 149 women with SCD from baseline (irrespective of gestational age at enrollment during pregnancy) till six weeks postpartum. Height and weight were used to calculate BMI at study entry. Premature/preterm birth was defined as births that occured before 37 weeks of gestation; and low and very low birthweight defined as birthweights below 2,500 and 1,500gram respectively. Acute pain was defined as acute pain episodes leading to a clinic visit or hospitalization that required oral or intravenous opioid pain management. Acute chest syndrome (ACS) was defined as the presence of at least 2 of the following criteria: fever >38⁰ Celcius, increased respiratory rate > 20 breaths per minute, presence of chest pain or pulmonary ausculatory findings, increased O₂ requirement (evidenced by a decrease in SpO₂ > 3% below the baseline) or new radiodensity on chest roentgenogram (x-ray) or pneumonia. Prospective rate of acute pain and ACS episodes per year during follow-up was limited to participants with at least 8 weeks of follow-up time. The team members reviewed all acute pain and ACS episodes.

Results: A total of 149 pregnant women with SCD (HbSS: 54; HbSC: 95) between the ages of 18 - 41 years (mean 29.2years; standard deviation (SD) 4.9) were included in the analysis. The mean gestational age at enrollment was 24.4 weeks with a mean total follow-up time of 18.7 weeks (SD 7.8). The mean BMI at enrollment (n=139) was 25.5 kg/m² (HbSS: 24.1 versus HbSC: 26.3; p=0.005). Out of 148 births, there were 26.4% premature births with more occurrence in women with HbSS phenotype compared to HbSC (40.7% versus 18.1%; p= 0.003). Approximately 25.2% of the infants had low birthweight (<2,500gram), with a subset of them (5.6%) having a very low birthweight (<1,500gram). There was a significant difference in the number of low birthweight infants between HbSS and HbSC (39.6% versus 15.6%; p= 0.002). In a multivariable model, phenotype (HbSS), pre-eclampsia and low BMI were associated with increased risk of premature birth. HbSS and pre-eclampsia were associated with increased risks of 2.343 (95% CI 1.004 - 5.469; p<0.05) and 4.034 (95% CI 1.320 - 12.331; p=0.014) respectively. For every one-unit increase in BMI, there was a decreased risk of premature birth by 0.888 (95% CI 0.799 - 0.986; p= 0.027). Prospective mean rates of acute pain and ACS episodes per year during follow-up in pregnancy (n= 141) were 1.80 and 0.40, respectively.

Conclusion: In a large prospective pregnancy cohort of women with SCD, we demonstrated that low BMI, phenotype HbSS, and pre-eclampsia increase the risk of premature birth. Understanding the mechanism for low BMI in women with SCD and improving the preconception BMI may result in a targeted intervention for decreasing premature births and low infant birthweight in SCD.

View largeDownload slide

View largeDownload slide

Close modal