Whitington and Kelly (2008) stated that neonatal hemochromatosis (NH) is the result of severe fetal liver injury that seems to result from maternal-fetal alloimmunity. Women who have had an infant affected with NH are at high-risk in subsequent pregnancies for having another affected infant. This study was designed to examine if therapy directed at limiting the severity of gestational alloimmunity can reduce the occurrence of severe NH in infants of women at risk. A secondary objective was to use a prospectively collected data set to examine questions of vital interest about NH. Women with a history of pregnancy ending in documented NH were treated with IVIG at 1 g/kg of body weight weekly from the 18th week until the end of gestation. Extensive data were prospectively collected regarding the gestational histories of the subjects. The outcomes of treated pregnancies were compared with those of previous affected pregnancies, which were used as historical controls. A total of 48 women were enrolled to be treated during 53 pregnancies. The gestational histories of these women demonstrated the high-risk of occurrence of NH: 92 % of pregnancies at risk resulted in intrauterine fetal demise, neonatal death, or liver failure necessitating transplant. In contrast, with gestational therapy, the 53 at-risk gestations resulted in 3 failures and 52 infants who survived intact with medical therapy alone. When compared on a per-woman or per-infant basis, the outcome of gestation at risk for NH was improved by gestational therapy. The authors concluded that NH seems to be the result of a gestational alloimmune disease, and occurrence of severe NH in at-risk pregnancies can be significantly reduced by treatment with high-dose IVIG during gestation.