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 (RA) 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 notes.
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 outcome was the case despite the fact that, compared with the majority of fathers, methotrexate-exposed men had more chronic illnesses and were more likely to be exposed to other medications, as well as anti-rheumatic drugs, antipsoriatic drugs, intestinal anti-inflammatory agents and corticosteroids.
The authors notes, 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 on March 6 in Obstetrics and Gynecology.1
“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 tells Reuters Health. “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 adds. 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 concludes, “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, tells 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, points 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 notes 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 says. “However, guidelines could and should acknowledge the reassuring data to date and the remaining uncertainties.”
- Eck LK, Jensen TB, Mastrogiannis D, et al. Risk of adverse pregnancy outcome after paternal exposure to methotrexate within 90 days before pregnancy. Obstet Gynecol. 2017 Mar 6. doi: 10.1097/AOG.0000000000001936. [Epub ahead of print]