Gestational treatment to prevent recurrent lethal neonatal hemochromatosis
Neonatal hemochromatosis (NH) is characterized as a condition in which fetuses and infants under one month of age have accumulation of iron in the liver and other tissues in a pattern similar to that seen in hereditary hemochromatosis. Most cases result in stillbirths, and the average life expectancy of children born with this disease is less than a few days. Death results mainly from liver failure. However, some affected babies have been successfully treated by medical means (with survival reported to be less than 20%) and by liver transplantation (survival reported to be less than 50%).
It has become very clear that NH causes damage to the fetal liver, which usually starts at 20-24 weeks of pregnancy. Considering all known causes of fetal disease, NH has been thought to possibly be the result of a genetic disease (gene defect). However, some curious findings in NH are hard to explain in this way. A mother may have one or more unaffected children before having the first affected child. Thereafter, the following pregnancies may end in either a late stillbirth or a child born with NH. Also, mothers have given birth to affected children with different fathers. The point is: there is no concrete evidence that NH is inherited through genes.
Treatment
We have developed a theory concerning the cause of NH upon which we have based the treatment of prospective mothers who have had children with NH. We believe that the cause of recurrent NH involves certain women developing an abnormal immune response to their unborn babies (called alloimmunity). According to this theory, the mother's immune system mounts an attack against a fetal liver protein and results in liver damage and a direct or indirect effect on fetal iron storage.
Several years ago we began to treat pregnant women on a research protocol. The purpose of treatment is to limit the elaboration of immunoglobulin (mother's immune attack) directed against the fetus (baby). The results of treatments performed as of August 2005 are: 26 women have been treated though 29 pregnancies, all of which ended in a live and reasonably healthy baby. About 75% of the babies showed some evidence of being affected, but only about 15% had significant liver disease. All 29 babies survived with medical care alone (no liver transplant). This is significantly different from these same women's prior affected pregnancies when treatment was not given in which there was only about 10% survival with medical therapy.
Long-term outlook
The results suggest that the course of the pregnancies was altered by the treatment to permit the birth of children with much milder NH and no pregnancy or newborn deaths. These findings suggest that a simple therapy might prevent this devastating disease. Further study is underway to confirm these results.
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