Neonatal Hemochromatosis

The Stanford Medicine Children’s Health Fetal and Pregnancy Health Program provides multidisciplinary prenatal evaluation and management of neonatal hemochromatosis (NH). Our maternal-fetal medicine and obstetrics specialists partner with our perinatal genetics, pediatric gastroenterology, and neonatology to deliver comprehensive prenatal management of subsequent pregnancies of women who previously had a baby diagnosed with neonatal hemochromatosis or who have lost a fetus or newborn to NH, as a result of gestational alloimmune liver disease (GALD).

What is neonatal hemochromatosis?

Neonatal hemochromatosis is an extremely rare condition that results in injury to the liver of a developing fetus. The disease is characterized by abnormal amount of iron that accumulates in the liver. However, the mechanism of NH is different from hemochromatosis seen in adults. Effects of neonatal hemochromatosis range from mild to severe, possibly resulting in fetal or neonatal death.

What causes NH?

Current research strongly suggests that the vast majority of NH cases are caused when a mother’s body creates antibodies directed against cells of the developing fetal liver. Those antibodies cross the placenta and cause injury to the fetal liver, which may lead to severe fetal and neonatal complications, including hydrops, growth restriction, and liver failure. An estimated 95% of cases of unborn babies developing NH are linked to this specific response, called gestational alloimmune liver disease (GALD). It is important to understand that nothing the mother did caused GALD, and the details of the cause are not yet clear. However, there is a very high risk for subsequent pregnancies to be affected by this problem. Fortunately, prenatal treatment is available for this condition, so if you had a past pregnancy that ended in NH due to GALD, you can deliver a healthy baby with prenatal treatment (described below) in a future pregnancy.

How common is it?

Estimates indicate that fewer than one in a million pregnancies worldwide results in neonatal hemochromatosis, but exact numbers are unknown because NH is believed to be underdiagnosed. Since there is no gene yet identified related to NH, the condition is not thought to be hereditary, but it can run in families. Therefore, if you have an immediate family member who was affected by NH, you should seek care from a fetal center or a genetic counselor if you are considering getting pregnant or you are already pregnant.

Are all cases of fetal liver disease a result of NH?

No. There are several possible causes of liver disease in a developing fetus. However, if you had a stillborn baby and an autopsy showed isolated liver failure or significant iron deposits in the liver, your fetus or baby may have died of NH. If you suspect a history of NH, we urge you to consult with a fetal and pregnancy specialized center so that you can be counseled about prenatal treatment to avoid losing another pregnancy or newborn to NH.

Does having a baby with NH mean that all my future pregnancies will result in a baby with NH?

Once a woman has a pregnancy that results in a baby with NH due to GALD, she has an approximately 90% chance of the same outcome in subsequent pregnancies, according to research. A woman can have healthy babies before losing one to NH, but after she does, almost all subsequent fetuses will be affected by NH. It’s important to seek care early during your next pregnancy.

When do you suspect NH?

NH may be suspected in cases of stillbirth in the late second or third trimester, or a neonatal demise within a few hours or days after birth—especially if laboratory investigations or autopsy found the fetus or baby to have liver abnormalities, hydrops or ascites, hypoglycemia, or blood clotting problems (coagulopathy). Also, NH may be suspected in neonates with prenatal or postnatal signs of severe liver disease and in women with a history of pregnancies affected by GALD. Women who are at risk for GALD of the fetus or neonate may be at risk for preeclampsia, so they should be closely monitored. We welcome the chance to provide you with a consultation or to partner with your obstetrician or maternal-fetal medicine specialist to guide IVIG treatment, which can help women with a history of NH have a healthy baby.

How do you treat me during pregnancy to avoid my unborn baby developing NH?    

GALD, like many other maternal-fetal alloimmune diseases, can be treated by intravenous immunoglobulin (IVIG) infusions during pregnancy. While it’s not fully understood how these high-dose IVIG treatments work, it’s believed that IVIG infusions may dilute maternal antibodies or directly block maternal antibodies from getting to the fetus, or they may pass into the fetal circulation and block maternal antibodies from damaging the fetal liver cells. Results of this treatment are outstanding. With IVIG infusions started early in pregnancy, your baby has a nearly 100% chance of being born completely healthy. If your provider suspects a history of GALD, or if you have had a fetus die for unexplained reasons during late pregnancy or as a newborn due to liver injury, tell your doctor. We advise that you seek care from a maternal-fetal medicine specialist who specializes in high-risk pregnancies, or with a fetal center that provides comprehensive care for expectant mothers and babies.

What can I expect with IVIG infusions?

We offer IVIG infusions at our infusion center, and we can also arrange treatment at an ambulatory infusion center in your area. If you meet criteria for therapy, your IVIG infusions may begin as early as week 14 of your pregnancy, with a second infusion at week 16 and then weekly until the end of your pregnancy. Infusion sessions last generally six to eight hours each. You may experience a headache or fatigue afterward, but hydrating beforehand helps avoid these symptoms. Additional hydration during the infusion may also alleviate much of the symptoms. 

Why should I choose Stanford Medicine Children’s Health for prenatal treatment for NH?

We have expertise in successfully identifying and treating women who have lost babies due to NH—something that isn’t common, even among fetal and pregnancy specialized centers. It’s best to identify the possibility of NH early, and we are well equipped to do so. Our Johnson Center for Pregnancy and Newborn Services, ranked third in the nation for neonatology care by U.S. News & World Report, offers multidisciplinary care from a team of maternal-fetal medicine and obstetrics specialists and neonatology experts who have the understanding, knowledge, and compassion to support you and your unborn baby. These specialists, along with other medical and surgical experts, provide coordinated, multidisciplinary diagnostic care in our Fetal and Pregnancy Health Program. Also, some babies born with NH require the highest level of care, including exchange transfusions or liver transplant, to survive when they are very young, and our neonatal intensive care, gastroenterology, and liver transplant teams are some of the best in the nation.   

If I don’t live near Stanford Medicine Children’s Health, can I receive treatment for NH elsewhere?

Yes, if you are out of the region, we can partner with a local maternal-fetal medicine specialist who can guide prenatal IVIG treatment. Since NH is very rare, we are happy to extend our Stanford expertise to co-manage your care with your chosen physician or independently. We can provide telehealth visits and help you arrange infusions from a nearby infusion center. Our Stanford Medicine Children’s Health Perinatal Diagnostic Centers are located across the Bay Area, Central Coast, and Central Valley and provide a wide range of diagnostic services and treatments to pregnant women.