Interaction between Thalassemia Minor and Anemia during the First Trimester on Neonatal Birth Weights: A Retrospective Cohort Study

Background The prevalence of mild thalassemia remains high among women of reproductive age in thalassemia-endemic areas, and the prevalence of anemia during pregnancy has significantly increased. Both conditions affect neonatal birth weight, but the existence of a synergistic interaction remains unclear. Objective This study was conducted to investigate the independent and combined effects of mild thalassemia genotypes and first-trimester anemia on neonatal birth weight and to assess their value in risk stratification. Methods A retrospective cohort study was conducted in which 3453 singleton pregnant women who delivered at Guangxi Zhuang Autonomous Region People's Hospital between 2019 and 2023 were included. Participants were categorized into four groups based on thalassemia genotype and first-trimester anemia status. Neonatal birth weight was the primary outcome. Multivariate linear regression and stratified analyses were performed to assess associations. Interaction was evaluated by introducing a product term and calculating the relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). Results Neonatal birth weight significantly differed among the four groups (P = 0.021), with the lowest weight observed in the thalassemia with anemia group (G3: 3148.99 ± 396.16 g). Stratified analysis revealed that among anemic women, those with thalassemia had significantly lower neonatal birth weights than those without thalassemia did (α-thalassemia: β = -82.26, P = 0.038; β-thalassemia: β = -81.19, P = 0.034). Among women with α-thalassemia, anemia was independently associated with reduced neonatal birth weight (β = -61.48, P = 0.027). Interaction analysis revealed a significant multiplicative interaction effect between thalassemia and anemia on neonatal birth weight (β = -69.14; P = 0.037), and the RERI indicated evidence of an additive interaction (β = -79.14; P = 0.042). Conclusions The interaction between mild thalassemia and first-trimester anemia may affect neonatal birth weight. The combination of thalassemia and anemia, particularly α-thalassemia, represents a noteworthy potential high-risk phenotype. This study provides targeted evidence to support neonatal weight management and risk stratification in pregnant women from thalassemia-endemic areas.