Association of sickle cell trait with adverse pregnancy outcomes in a population‐based cohort

• Published in: Acta obstetricia et gynecologica Scandinavica Vol. 102; no. 8; pp. 1100 - 1105
• Main Authors: Hulsizer, Joseph, Rifkin, Andrew S., Shi, Zhuqing, Wei, Jun, Zheng, S. Lilly, Helfand, Brian T., Morgan, Jessica, Ouyang, David W., Caplan, Michael S., Xu, Jianfeng
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.08.2023; John Wiley and Sons Inc
• Subjects: Bacteriuria; Black people; Clinical outcomes; common diseases; complications; Diabetes; Female; Health risks; Hispanic people; Humans; hypertension; Infant, Newborn; Original; Postpartum period; Pre-Eclampsia; Preeclampsia; Pregnancy; Pregnancy Outcome; Retrospective Studies; Risk Factors; Sickle cell disease; sickle cell trait; Sickle Cell Trait - complications; Sickle Cell Trait - epidemiology; Sickle Cell Trait - genetics; Womens health; United Kingdom > UK; common diseases; complications; sickle cell trait; diabetes; hypertension
• ISSN: 0001-6349; 1600-0412
• DOI: 10.1111/aogs.14622

Introduction Sickle cell trait (SCT) is common in African descendants. Its association with several adverse pregnancy outcomes (APOs) has been reported but remains inconsistent. The objectives of this study are to test associations of SCT with APOs in non‐Hispanic Black women, including (1) validate the associations of SCT with previously reported APOs, (2) test novel associations of SCT with broad spectrum of APOs, and (3) estimate the attributable risk of SCT for implicated APOs. Material and methods This is a retrospective analysis of a prospectively designed population‐based cohort. Women/participants were self‐reported non‐Hispanic Black women from the UK Biobank (UKB). SCT status was determined based on heterozygous Glu6Val in the HBB gene. Several APOs were studied, including four previously reported SCT‐associated APOs (preeclampsia, bacteriuria, pregnancy loss, and preterm delivery), and broad conditions related to pregnancy, childbirth, and the puerperium. APOs were curated by experts’ peer review and consensus processes. Associations of SCT with APOs were tested by estimating its relative risk and 95% confidence interval (95% CI), adjusting for number of live births and age at first birth. Attributable risk proportion (ARP) and population attributable risk proportion (PARP) of SCT to APOs were estimated. Results Among the 4057 self‐reported non‐Hispanic Black women with pregnancy records in the UKB, 581 (14.32%) were SCT carriers. For four previously reported SCT‐associated APOs, two were confirmed at a nominal P < 0.05; relative risk (RR) was 2.39 (95% CI 1.09–5.23) for preeclampsia, and 4.85 (95% CI 1.77–13.27) for bacteriuria. SCT contributed substantially to these two APOs among SCT carriers, with attributable risk proportion estimated at 61.00% and 68.96% for preeclampsia and bacteriuria, respectively. SCT also contributed substantially to these two APOs in the population (self‐reported Black UK women), with population attributable risk proportion estimated at 18.30% and 24.14% for preeclampsia and bacteriuria, respectively. In addition, novel associations were found for seven other APOs (nominal P < 0.05). Conclusions SCT is significantly associated with APOs in this study and contributes substantially to APOs among self‐reported Black women in the UK. Confirmation of these findings in independent study populations is required. In this population‐based cohort, sickle cell trait is significantly associated with adverse pregnancy outcomes (APOs), including previously known sickle cell trait‐associated APOs (preeclampsia and bacteriuria) and seven other APOs to be confirmed in future studies. Sickle cell trait contributes substantially to APOs among self‐reported Black women in the UK.