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Are offspring of women with hereditary hematologic disorders at increased risk of congenital cardiovascular malformations?

Hereditary hematologic disorders (HHD) have been reported in excess among infants and families of infants with congenital cardiovascular malformations (CCM) compared with controls, suggesting possible common pathogenetic mechanisms. It is plausible that hemodynamic changes during pregnancy associated with HHD could affect cardiac morphogenesis. To investigate whether offspring of women with selected HHD have an excess risk of CCM, the authors examined data from a nationwide birth defects monitoring program (BDMP) covering about 2.9 million births in the United States between 1982 and 1988. The system ascertains major birth defects diagnosed in the newborn period. An anonymous linkage procedure linked maternal obstetric records with newborn records using demographic, diagnostic, and geographic variables. A total of 1,239 mothers were identified with selected HHD (47 hereditary spherocytosis, 575 thalassemias, 310 sickle cell anemia, 88 other hereditary hemolytic anemias, 159 von Willebrand disease, and 60 other congenital coagulapathies). In all, 14 infants received a newborn discharge diagnosis of CCM (expected number based on population rates of CCM from the same hospitals and time period is 7.74; P = 0.0268). No single CCM entity accounted for this excess. In contrast, 8 infants had major non‐CCM defects (expected number 7.46; P = 0.466). These data suggest an excess risk of CCM among offspring of women with selected HHD. Further studies are needed to explore these findings and to evaluate the pathogenetic significance of this association.