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Ig G treatment during pregnancy reduces severity of rare, recurring liver condition in newborns


Treatment with high-dose immunoglobulin G (IgG) during pregnancy lessens the severity of hemochromatosis (NH), a rare, devastating gestational disease with abnormal iron accumulation in the liver and severe liver injury that almost always results in fetal death or acute liver failure in newborns.

In an article in the Nov. 6 issue of The Lancet, researchers Peter F. Whitington, M.D., and Judith U. Hibbard, M.D., described the effectiveness of treating mothers with IgG in reducing liver injury in babies with recurrent NH. Whitington, a noted authority on liver disease, is professor of pediatrics at Northwestern University Feinberg School of Medicine, Children’s Memorial Hospital. Hibbard is professor of maternal-fetal medicine, University of Illinois – Chicago and held a similar position at the Pritzker School of Medicine, University of Chicago, during the course of he study.

One of the most devastating aspects of NH to affected families is that after a woman has had one baby with the disorder, her risk for recurrence of NH in another child is 80 percent. A woman may have unaffected children before having the first one with NH. After that, most or all pregnancies end with fetal death or a child born with NH. Currently, there is no test to determine if a pregnancy will be affected, and there is no effective approach to prenatal diagnosis of NH. The best advice available to date for such women is to avoid pregnancy.

Until now, the cause of NH has been unknown. Whitington hypothesized that it is an alloimmune disease based on its unusual pattern of recurrence, which is similar to the known alloimmune diseases hydrops fetalis due to Rh incompatibility and neonatal alloimmune thrombocytopenia. Treatment with IgG has been found effective in the treatment of these alloimmune blood disorders, so Whitington proposed its use in NH.

The positive results of the current study provide support for the theory that recurrent NH is an alloimmune disease. In the study, 15 women whose most recent pregnancy ended in documented NH were treated with intravenous IgG once a week from the 18th week of pregnancy until birth. One woman had two pregnancies.

All 16 pregnancies progressed uneventfully and resulted in live babies with normal physical examination findings and birth weights. Twelve babies showed evidence of liver involvement with NH, including four with significant liver injury, but all of the infants survived with medical or no treatment and are currently healthy, having fully recovered from NH that was blunted by gestational treatment.

In contrast, these women’s previously affected pregnancies almost always resulted in fetal death or a severely affected newborn that was unresponsive to medical treatment.

Whitington and his laboratory group are currently developing a test to detect alloimmune NH; specifically, they are purifying, identifying and cloning candidate fetal proteins for use in blood tests. Other future directions include other clinical trials and creating animal models of NH to further study the disease and perhaps improve postnatal therapy for NH.

Elizabeth Crown | EurekAlert!
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