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SAN JUAN -- Two of the most commonly used drugs for treating hyperthyroidism were linked to birth defects when used in early pregnancy, though they have differing effects, researchers reported here.

In an analysis of Danish national data, infants born to mothers taking propylthiouracil (PTU) early in pregnancy had about a 50% higher risk of birth defects, and those taking methimazole (MMI) had a 75% greater risk than children born to women in the general population not taking the drug, , of Aalborg University Hospital in Denmark, and colleagues reported at the Amerian Thyroid Association meeting.

The two drugs were tied to very different birth defects: MMI was associated with more musculoskeletal problems, while PTU was tied to face and neck defects.

"We should restrict the use of anti-thyroid drugs in early pregnancy," Laurberg said, adding that it would "be nice to have some anti-thyroid drugs with fewer side effects."

, of the University of Michigan in Ann Arbor, who was not involved in the study, said that birth defects in this population have been "sufficiently uncommon" so it's been difficult to "get a precise handle on the similarities and differences between these drugs, the level of risk, and whether the birth defects are truly caused by these drugs."

"This uncertainty has resulted in controversy and debate as to the optimal ways to prescribe anti-thyroid drugs to hyperthyroid pregnant women," he said.

Laurberg and colleagues looked at Danish national data to find fetuses that were exposed to either drug in early pregnancy, and compared them with children born to mothers who received thyroid drugs but not during pregnancy, and those who never had thyroid drugs at all.

The analysis included 849,416 births from Danish Civil Registration System from 1996 to 2008, as well as Danish National Hospital Registry data on birth defects that had been registered before the child was 2-years-old.

A total of 564 infants had been exposed to PTU, 1,097 were exposed to MMI, and 159 had been exposed to MMI but were then switched to PTU. Also, 3,543 women had used thyroid drugs but not in pregnancy and 811,730 never used thyroid drugs in their lifetime.

Overall, the researchers found that the risk of birth defects was significant among newborns exposed to both drugs in utero compared with the general population, with an excess of 2% to 4% of exposed children having birth defects.

MMI appeared to be worse than PTU, Laurberg said, with a higher risk of birth defects than PTU (odds ratio 1.75 versus OR 1.5).

There were no significant risks for infants born to mothers who had used thyroid drugs but not during pregnancy, the researchers added.

The researchers also found that birth defects differed by drug. MMI conferred more musculoskeletal risks, which Laurberg said was driven largely by abdominal wall defects. These infants also had higher rates of integumentary, digestive, eye, and urinary defects, followed by respiratory and circulatory defects. Face and neck defects did not appear to be common in these children.

On the other hand, PTU was associated with a high risk of face and neck defects, followed by urinary defects. There were no significantly increased risks of any other defects, including respiratory, circulatory, digestive, or integumentary defects. There were no cases of eye or musculoskeletal problems.

Some research has suggested that switching from MMI to PTU in early pregnancy may help diminish birth defects. But among the 149 patients in the cohort who had received this therapeutic strategy, there was still a higher risk of birth defects in the infants compared with the general population (OR 1.82, 95% CI 1.08 to 3.07).

Laurberg recommended that clinicians restrict the use of any thyroid drug in early pregnancy, but if thyroid treatment is absolutely necessary, clinicians should probably use PTU.

He also advised that fertile women should be told to stop their thyroid drug within a week after the first day of missing a period if pregnancy is possible. And if they are planning to become pregnant, they should switch to PTU.

Koenig said the study "makes an important contribution to this field," particularly with regard to the idea of sequential therapy, giving PTU early in pregnancy and eventually switching to MMI, since these infants "did not appear to have a decreased risk of birth defects."

"The important points from this study are that an anti-thyroid drug with absolutely no increased rate of birth defects would be a welcome addition," Koenig said, "and that more data are needed to evaluate the sequential use of PTU and MMI."

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