Prenatal exposure to maternal β-thalassemia minor and the risk for long-term hematologic morbidity in the offspring: A population-based cohort study

Objective: β-Thalassemia has been shown to be associated with adverse short-term perinatal outcomes including low birth weight and preterm labor. The aim of this study was to assess whether in-utero exposure of maternal β-thalassemia minor is a risk factor for offspring hematological morbidity. Study design: A population-based retrospective cohort study was conducted, including all infants born between the years 1991–2014 at a tertiary medical center. Long-term hospitalizations with hematologic morbidities were compared between offspring of mothers with or without β-thalassemia minor. Multiple gestations, perinatal mortality, chromosomal disorders and congenital malformations were excluded. Both study groups were followed until 18 years of age for hospitalization with hematological morbidities. Kaplan-Meier survival curve was used to compare the cumulative hematological morbidity incidence between both groups, and a Cox proportional hazard model was used to control for confounders. Results: During the study period, 243,682 deliveries met the inclusion criteria, of them 0.3% (n = 677) were of mothers with β-thalassemia minor. Among offspring to thalassemic versus non-thalassemic mothers, hospitalization rates involving hematological morbidity, were higher (3.3% vs. 0.7%, p < 0.001) a finding that was consistent with the Kaplan-Meier survival curve (log rank p < 0.001). Using Cox regression model, which adjusted for maternal age, SGA, gestational age and birth weight, maternal β-thalassemia minor was found to be an independent risk factor for long-term offspring hematological (aHR = 5.54; 95% CI 3.63–8.44, p < 0.001, 5.56; 95% CI 3.65–8.47, p < 0.001, and 5.49; 95% CI 3.60–8.36, p < 0.001, respectively). Conclusion: Prenatal maternal β-thalassemia minor is independently associated with offspring long-term hematological morbidity.