Association between Newborn Sickle Cell Disease and Low Birth Weight Among Full-term Births: A Population-Based Study in the State of Virginia (2014- 2023)
Jyothi Sri Lokanadham, Parker Brodsky ParksAbstract
Background
Sickle cell disease (SCD) is an inherited hemoglobinopathy associated with maternal and neonatal morbidity. While maternal SCD has been linked to adverse birth outcomes, few studies have evaluated the association between newborn SCD status and low birth weight (LBW) among full-term births across SCD genotypes.
Methods
We conducted a retrospective population-based study of live births in Virginia from 2014 – 2023. Vital birth records were linked with Virginia newborn bloodspot screening data to identify infants with confirmed SCD. The analysis was restricted to singleton full-term births (≥ 37 weeks' gestation) with maternal age 15 to 49 years. Multivariable logistic regression was used to estimate adjusted odds ratio and 95% confidence intervals for LBW. To account for the relationship between race and SCD, a composite variable representing race and SCD was created and included in the model. Race-SCD categories with sparse data were excluded from the models to ensure stable estimation. A secondary analysis was performed to evaluate the phenotype-specific associations among sickle cell births and low birth weight.
Results
Among 871,647 births included in the study, 580 full-term infants had SCD, of which 541 were born to African American mothers. Compared to Non-Hispanic White infants without SCD, Non-Hispanic Black infants with SCD had nearly 3 times higher odds of LBW (OR = 2.97, 95%CI: 1.84-4.79), and Non-Hispanic Black infants without SCD had higher odds of LBW (OR = 2.36, 95%CI: 2.26-2.46). Among Non-Hispanic Black infants with SCD, FS (OR = 2.60, 95%CI: 1.33-5.01) and FSC (OR = 4.79, 95%CI: 2.41- 9.51) phenotypes were associated with increased odds of LBW. Maternal smoking (OR = 2.87,95%CI:2.69-3.06), eclampsia (OR = 3.30,95%CI: 2.84-3.84), and gestational hypertension (OR = 2.24,95%CI:2.13-2.36) were strongly associated with LBW. Female infants had higher odds of LBW than male infants (OR = 1.57, 95%CI:1.52-1.62). Unmarried mothers (OR = 1.32,95%CI:1.26-1.37) had higher odds of LBW, and lower maternal education was also associated with higher odds of LBW (OR = 1.11, 95%CI:1.05-1.16). Model discrimination was moderate (c-statistic = 0.66).
Conclusions
Maternal factors such as hypertensive disorders and smoking during pregnancy are associated with LBW. Newborn SCD is associated with increased odds of LBW among full-term Non-Hispanic Black infants and those with FS and FSC genotypes. These findings highlight the need for prenatal SCD diagnosis, targeted prenatal counseling and monitoring pregnancies at risk of SCD related complications. Early identification of high-risk populations can guide interventions to reduce LBW and improve neonatal outcomes among communities disproportionately affected by SCD.