Paternal methotrexate exposure not tied to adverse pregnancy outcomes

Reuters Health Information: Paternal methotrexate exposure not tied to adverse pregnancy outcomes

Paternal methotrexate exposure not tied to adverse pregnancy outcomes

Last Updated: 2017-03-17

By Scott Baltic

NEW YORK (Reuters Health) - A father’s exposure to methotrexate 90 days or less before conception “should not be of major concern,” researchers say.

Prepregnancy paternal methotrexate exposure appears to confer no increased risk of major or minor congenital malformation, stillbirth, or preterm birth in his offspring, their study found.

Methotrexate is a first-line therapy for rheumatoid arthritis and is also used to treat inflammatory bowel disease, psoriasis, and several cancers. Current multinational recommendations indicate that both men and women should discontinue methotrexate at least three months before a planned pregnancy, the report noted.

The nationwide register study examined records of all 849,676 live births in Denmark between 1997 and 2011, including 127 in which the fathers had been exposed to methotrexate within 90 days of pregnancy.

Among those 127 live births, there were four major malformations (3.2%), versus 28,814 in the rest of the cohort (3.4%). There were no stillbirths and no increased risk of preterm birth in the methotrexate-exposed group.

This was the case despite the fact that compared to the majority of fathers, methotrexate-exposed men had more chronic illnesses and were more likely to be exposed to other medications, too, including antirheumatic drugs, antipsoriatic drugs, intestinal anti-inflammatory agents, and corticosteroids.

The authors noted, however, that limitations in the Danish birth registry made it impossible to determine whether paternal methotrexate is associated with miscarriage.

The report was released online March 6 in Obstetrics and Gynecology.

“Several decades ago, researchers suggested that men using methotrexate could have their semen damaged and thereby harm a future child,” senior author Dr. Jon Traerup Andersen, of Copenhagen University Hospital, told Reuters Health by email. “This theoretic risk resulted in recommendations of discontinuation of the drug in men at least three months before a pregnancy.”

Only a few very small studies had previously investigated this topic, finding no evidence of any harmful effects on the fetus, he added. Thus, “without any evidence, men have either been unable to adhere to their methotrexate treatment or unable to have children.”

His group’s results, Andersen concluded, “support that men can continue their treatment before pregnancy” and argue for a reconsideration of current guidelines.

“This new study is important and reassuring for prospective fathers who are taking methotrexate,” Dr. Robert H. Shmerling, of Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, told Reuters Health in an email. “Its results should become a part of the conversation between doctors prescribing methotrexate to men considering fatherhood.”

Shmerling, who was not involved in the new research, pointed out, however, that “this single study is unlikely to be the last word on the matter,” given its small size, the lack of information about methotrexate dose (higher doses could come with more risk), and the lack of confirmation that the men actually took methotrexate, only that they filled prescriptions for it.

He also noted that because information on pregnancy termination and miscarriage was not available, if methotrexate caused fetal malformations that led to these events, the study would have missed them.

“Therefore, it may be premature to conclude with confidence that methotrexate taken by men has no impact on fetal health if their partners become pregnant,” Shmerling said. “However, guidelines could and should acknowledge the reassuring data to date and the remaining uncertainties.”


Obstet Gynecol 2017.

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