With commentary by Erik Alexander, MD, chief, thyroid section, Brigham and Women's Hospital and associate professor of medicine, Harvard Medical School, member and former board of directors for American Thyroid Association, and Michael Kuzniewicz, MD, MPH, director of the Perinatal Research Unit, Kaiser Permanente Northern California Division of Research, and assistant professor in neonatology, University of California, San Francisco.
When thyroid problems develop or worsen during pregnancy, women understandably worry about the effects of the thyroid treatments on the baby.
Now, a large study from Denmark found that exposure to levothyroxine, used to help a sluggish thyroid (hypothyroidism), had no impact on birth weight and other factors. However, treatment with anti-thyroid medications for overactive thyroid (hyperthyroidism) was linked with a higher risk of preterm births, low birth weights and infant death.
The new study ''adds to a growing body of literature that raises concerns about anti-thyroid drug use and its effect on the developing fetus," says Erik Alexander, MD, chief of the thyroid section at Brigham and Women's Hospital and associate professor of medicine at Harvard Medical School. He reviewed the new study, published in Early Human Development.
"The study reconfirms the finding of previous studies that women with hyperthyroidism are at greater risk of delivery preterm and to have an infant that is small for gestational age," says Michael Kuzniewicz, MD, MPH, director of the Perinatal Research Unit, Kaiser Permanente Northern California Division of Research and assistant professor in neonatology, University of California, San Francisco. He has published on the topic and also reviewed the new findings.
While the news is better for those with low thyroid function, they need to be carefully monitored from early in pregnancy to be sure they are taking enough levothyroxine to keep the thyroid working well, says Dr. Alexander, a member of the American Thyroid Association and formerly on its board of directors.
The researchers drew data from Danish registries from 1995 through 2010, examining the records of nearly a million pregnancies. Of those, about 6,500 women took levothyroxine for underactive thyroid and about 1,800 took anti-thyroid medicine for overactive thyroid. The anti-thyroid medicines were methimazole/carbimazole and propylthiaouracil (PTU). Overactive thyroid is much less common in pregnancy than sluggish thyroid, experts know.
Compared to the babies whose mothers did not have thyroid problems, babies of mothers treated with levothyroxine were no more likely to be born early, at low birth weight or below-average length or to die in the first year.
However, the babies of mothers who took anti-thyroid medications were more than twice as likely as babies of mothers without thyroid issues to be born early, more than twice as likely to die in the first year and somewhat more likely to be low birth weight and length. The number of babies who died within the first year among those whose mothers had hyperthyroidism was .9 percent of about 1,700 babies, or 15.
The new study looked more broadly at a variety of newborn outcomes, compared to previous research, says Dr. Alexander.
The study confirms some previous research. But despite the large size of the study, says Dr. Kuzniewicz, it is still not possible to say with certainty which antithyroid drug is best to reduce risks such as birth defects. That's partly because the use of antithyroid drugs is rare, less than .2 percent, and many of the birth defects linked with the drugs are rare, he says.
Even so, more research is needed, he says, especially on the cognitive development of the babies.
Fortunately, the percent of pregnant women who have hyperthyroidism that must be managed is small, Dr. Alexander says. Yet, the new research, and previous studies, should raise awareness. According to the American Thyroid Association (ATA), pregnant women with only mild hyperthyroidism may do OK with close monitoring, without treatment. If the condition becomes severe, it may be necessary to treat with anti-thyroid drugs and in that case PTU is the drug of choice, the ATA says. If that does not work, surgery is acceptable, the ATA says, but it's not without risks.
Ideally, some experts say, women with hyperthyroidism should be treated either with ablative therapy (iodine radiation or surgery) or medical therapy and achieve normal thyroid functioning before becoming pregnant.
Radioiodine is not advisable to treat hyperthyroidism during pregnancy, according to the American Thyroid Association, since it crosses the placenta and is taken up by the baby's thyroid gland. That could result in permanent hypothyroidism.
While the new study did not find that levothyroxine was linked with adverse outcomes, in general, Dr. Alexander says women with low thyroid function must be aware that the dose of levothyroxine needs to be monitored often during pregnancy so it can be adjusted if necessary.
Women who already know they have hypothyroidism and become pregnant should notify their doctor right away, Dr. Alexander says.