Methotrexate (Pre-conception only) - Medication and Pregnancy KB

Methotrexate (Pre-conception only)

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Howren, 2020	Canada 2002 - 2012	Women with pregnancies ending in delivery (live-births and stillbirths) between the study period. And an Rheumatic diseases (RD) pregnancy cohort was created from the source population.	Pregnant women with rheumatic diseases who filled at least one prescription of methotrexate in preconception (90 days prior to the date of conception) or during pregnancy (i.e., from conception to delivery). (This is a subgroup of exposure among the one considered).	unexposed, sick Pregnancies in women with rheumatic diseases without filled prescriptions for conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) during aforementioned perinatal windows of interest.	24 / 6064	Each pregnancy can be exposed to more than one category of csDMARDs.
Matsui, 2003	Japan 1974 - 2000	First pregnancies in patients who achieved remission from gestational trophoblastic tumor (GTT) after receiving methotrexate (MTX), actinomycin-D (Act-D), or etoposide (including those switched to other regimens), or combination therapy.	Pregnancies in women initially treated with methotrexate for gestational trophoblastic tumor who conceived less than 6 months after completion of chemotherapy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnancies in women initially treated with chemotherapy for gestational trophoblastic tumor who conceived more than 6 months after completion of chemotherapy.	4 / 115	17 (30.4%) of 56 patients initially given MTX had to be switched to other single-agent regimens due to the development of drug resistance and/or toxicity. Drug resistance was defined after at least three consecutive cycles of chemotherapy.
Svirsky, 2017	Israel 2004 - 2014	All women who conceived after methotrexate treatment for ectopic pregnancy between the study period.	Women treated with methotrexate injection(s) for ectopic pregnancy who subsequently conceived less than 6 months after treatment.	unexposed, sick Women treated with methotrexate injection(s) for ectopic pregnancy who subsequently conceived more than 7 months after treatment (between 7 to ≥24 months).	93 / 133	There is a two years overlap between this study and an earlier published study by the same author: Svirsky et al., 2009.
Svirsky, 2009	Israel 2000 - 2006	Women who were treated with intramuscular injection of methotrexate (MTX) for ectopic pregnancy between the study period.	Women treated with intramuscular injection of methotrexate (MTX) 50mg/m2 in a single dose for ectopic pregnancy who conceived within 6 months from the last methotrexate (MTX) injection.	unexposed, sick Women treated with intramuscular injection of methotrexate (MTX) 50mg/m2 in a single dose) for ectopic pregnancy who postponed conception for more than 6 months after the last methotrexate (MTX) injection.	45 / 80	Index pregnancy is the one following MTX treatment. In two cases of twin pregnancy only the outcome of the first newborn was considered for statistical analysis.
Weber-Schoendorfer (Controls exposed to other treatment, sick), 2014	Worldwide (9 countries) 1994 - 2011	Pregnant women enrolled at teratology information service centers between the study period that met MTX-exposure criteria.	Pregnant women who were exposed to MTX only before conception (i.e., between 10 weeks prior to the last menstrual period and no more than 1 week plus 6 days after the last menstrual period) or after conception (i.e., ≥1 dose 2 weeks after the first day of the last menstrual period).	exposed to other treatment, sick Pregnant women with rheumatic/inflammatory diseases who did not take MTX during pregnancy or during the 12 weeks before conception. These women had either been treated with other immunomodulatory drugs or the physician had decided not to prescribe any of these drugs.	324 / 459	Number of total assessed post-conception MTX-exposed infants not reported for genetic birth defects (so not reported here).
Weber-Schoendorfer (Controls unexposed, disease free), 2014	Worldwide (9 countries) 1994 - 2011	Pregnant women enrolled at teratology information service centers between the study period that met MTX-exposure criteria.	Pregnant women who were exposed to MTX only before conception (i.e., between 10 weeks prior to the last menstrual period and no more than 1 week plus 6 days after the last menstrual period) or after conception (i.e., ≥1 dose 2 weeks after the first day of the last menstrual period).	unexposed, disease free Pregnant women identified through teratology information service centers during spontaneous consultations for other conditions or exposures. Not affected by rheumatic/inflammatory diseases and were not taking any immunomodulatory drugs during pregnancy.	324 / 1107	Number of total assessed post-conception MTX-exposed infants not reported for genetic birth defects (so not reported here).

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
Dawson, 2014	USA 1997 - 2009	Infants with major birth defects identified through population-based surveillance systems.	Live-born infants with no major birth defects selected at random from the same ascertainment area as case infants.	27623 / 10113	Infants with birth defects with a known etiology, including those with recognized chromosomal syndromes or single-gene disorders, are excluded. The indication for methotrexate use was not reported in most cases.

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