1. In a Danish cohort, maternal genitourinary tract infection during pregnancy was associated with an increased risk of childhood leukemia in offspring
Evidence Rating Level: 2 (Good)
Little is known about the etiology of leukemia. Previous studies have reported that childhood leukemia may originate in utero, with cytokine levels at birth different for healthy children compared to those who developed leukemia in childhood. It is thought that maternal infection can lead to chromosomal and immunological alterations which could be a risk factor for childhood leukemia. Previous systematic reviews and meta-analyses have found that maternal influenza, rubella, and varicella during pregnancy were associated with a higher risk of childhood leukemia, but the evidence from these studies originated predominantly from case-control studies. This population-based cohort study used data from all live births in Denmark between 1978 and 2015, including a total of 222,277 children. Maternal infection was identified using the Danish National Patient Registry based on inpatient and outpatient diagnoses and these infections were characterized by site. The primary outcome of the study was a diagnosis of leukemia in the children and secondary outcomes of acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Compared to children born to mothers without infection (adjusted hazard ratio [HR], 1.35 [95% CI, 1.04-1.77]), children born to mother with infection during pregnancy had a 35% increased risk of leukemia, with maternal genital and urinary tract infections associated with a 142% and 65% increased risk respectively (HRs of 2.42 (95% CI, 1.50-3.92) and 1.65 (95% CI, 1.15-2.36). Associations were not observed for other infections such as respiratory tract and digestive infections. This study has limitations including that data was extracted from hospital diagnoses, potentially missing milder infections and infections not treated in healthcare facilities. Additionally, outpatient infection data was only available from 1995 onwards. Overall, this study suggests that maternal urinary and genital tract infections during pregnancy are associated with a higher risk of childhood leukemia. Future studies on the etiology of childhood leukemia, and those examining mild infections and other factors are needed, with additional studies aimed at developing preventive measures.
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