Pregnancy in Wilson disease safer with treatment

Last Updated: 2017-09-11

By Scott Baltic

NEW YORK (Reuters Health) - Continuing anti-copper therapy in pregnant women with Wilson disease (WD) is safer than stopping it, although they should be closely monitored for hepatic and neurological symptoms, according to a report by researchers in Germany and Austria.

The multicenter study, retrospectively analyzing data from 1965 to 2015, found that despite concerns about potential teratogenicity of copper chelators, rates of spontaneous abortions and birth defects were low in women with WD.

"Our data confirm that patients with WD with adequate copper control have better chances of successful pregnancies than untreated WD patients," the reseachers write.

They call their study "the largest collection of data on pregnancies in WD patients to date." It was published online August 31 in Hepatology.

WD is a rare, autosomal recessive inherited disorder of copper metabolism causing toxic hepatic and neural copper accumulation, according to the article. Treatment includes chelating agents D-penicillamine and trientine, as well as zinc salts that inhibit copper uptake. Earlier reports had suggested that the chelators might be teratogenic.

WD has an estimated prevalence of 1 in 30,000 and "can manifest as hepatic, neurologic, hematologic, or psychiatric disturbances, or a combination of these, in individuals ranging in age from three years to older than 60 years," corresponding author Dr. Karl H. Weiss, of University Hospital Heidelberg, Germany, told Reuters Health by email.

He noted that "phenotypic expression varies even within families" and that molecular genetic testing has identified more than 350 different disease-causing mutations. "The highly variable phenotype and diverse clinical presentation, as well as the diverse genotype pattern, pose a challenge to studying these patients," Dr. Weiss said.

In addition, Dr. Weiss explained, WD has distinct clinical subgroups, such as liver patients, neurologic patients, and asymptomatic siblings. Patients with neurologic symptoms usually carry a higher disease burden than patients with only liver symptoms.

Of the 136 women with WD in the study (282 pregnancies), clinical manifestations were hepatic in 54%, neurologic in 32%, and mixed in 9%. Five percent of the women were asymptomatic. Most patients were receiving a chelator or combination therapy, but in 31% of the pregnancies, WD had not been diagnosed at the time of conception.

After their pregnancies, 93% of patients had unchanged status, 6% experienced only hepatic deterioration, and 1% experienced neurologic deterioration.

About a quarter of the pregnancies ended in spontaneous abortion. This outcome was significantly more likely in patients who had neurologic manifestations at the time of WD diagnosis than in other clinical subgroups.

Spontaneous abortions occurred in 41% of cases not diagnosed with WD before conception and in 36% of cases where therapy was discontinued during pregnancy.

The lowest spontaneous abortion rates occurred in pregnancies where zinc or D-penicillamine therapy was used (10% and 17%, respectively). In a finding the authors call "unexpected," the spontaneous abortion occurred in 27.7% of trientine users, statistically similar to the rate in therapy-naive patients.

The overall rate of birth defects was comparable to the expected rate in the general population.

This report is "a comprehensive review of the topic, with the main conclusion being that pregnancy in Wilson's disease is relatively safe," Dr. George J. Brewer, of the University of Michigan, told Reuters Health by email. He agrees with the authors' recommendation to try to avoid overtreatment, "which can lead to copper deficiency in the fetus and birth defects."

"This study serves as reinforcement of the safety of pregnancy in people with Wilson disease who wish to get pregnant and do not have excessively severe liver or neurologic disease," Dr. Fred Askari, director of the Wilson Disease Center of Excellence at the University of Michigan, Ann Arbor, told Reuters Health by email. "Patients may find this study quite reassuring, as the overall rate of birth defects was similar to the general population."

While there appeared to be fewer spontaneous abortions in patients on zinc than in those receiving trientine, he added, retrospective studies have limitations, and issues such as use of prenatal vitamins with or without copper, as well as variable adherence with copper-reduction therapy during pregnancy, might have influenced the outcomes.

Finally, Dr. Askari noted, "children of people with Wilson disease are, at a minimum, obligate carriers for Wilson disease, so increased vigilance in descendants of people with Wilson disease is warranted."

Neither Dr. Brewer nor Dr. Askari was involved with the study.

SOURCE: http://bit.ly/2xUSDzd

Hepatology 2017.