Methotrexate (Post-conception) - Medication and Pregnancy KB

Methotrexate (Post-conception)

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Cooper (Controls exposed to other treatment, sick), 2014	USA 1995 - 2007	Women with inflammatory arthropathies, those with connective tissue disorders (systemic lupus erythematosus), and those with inflammatory bowel disease who filled prescriptions for immunosuppressive or corticosteroids during pregnancy.	Singleton birth in women with immune-mediated diseases treated with first-trimester exposure to methotrexate. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Singleton birth in women with immune-mediated diseases treated with first-trimester exposure to immunosuppressive medications.	23 / 379	Women receiving methotrexate may have filled prescriptions for other immunosuppressive medications. Immunosuppressive medications as Tumor necrosis factor inhibitors, Hydroxychloroquine, gold, sulfasalazine, leflunomide, azathioprine, and minocycline.
Cooper (Controls unexposed, sick), 2014	USA 1995 - 2007	Women with inflammatory arthropathies, those with connective tissue disorders (systemic lupus erythematosus), and those with inflammatory bowel disease who filled prescriptions for immunosuppressive or corticosteroids during pregnancy.	Singleton birth in women with immune-mediated diseases treated with first-trimester exposure to methotrexate. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Singleton birth in women with immune-mediated diseases treated with immunosuppressive medications in the 180 days before, but not during pregnancy.	23 / 171	Women receiving methotrexate may have filled prescriptions for other immunosuppressive medications.
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.
Viktil (Controls exposed to other treatment, sick), 2012	Norway 2004 - 2007	All singleton pregnancies registered in the Medical Birth Registry of Norway (MBRN) which contains all births including late abortion, from 12 weeks of gestation onwards during the study period.	Singleton pregnancies whose mothers were dispensed methotrexate from 3 months prior to conception until labour. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Singleton pregnancies whose mothers were dispensed other anti-rheumatic drugs (Prednisolone, NSAIDs, Sulfasalazine, Hydroxychloroquine, Azathioprine, Leflunomide, Etanercept, Adalumimab, or Anakinra) from 3 months prior to pregnancy to delivery.	8 / 1453	Only the first pregnancy for each parent during the study period was included. Some of the women received more than one of the drugs in the study period.
Viktil (Controls unexposed NOS), 2012	Norway 2004 - 2007	All singleton pregnancies registered in the Medical Birth Registry of Norway (MBRN) which contains all births including late abortion, from 12 weeks of gestation onwards during the study period.	Singleton pregnancies whose mothers were dispensed methotrexate from 3 months prior to conception until labour. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Singleton pregnancies whose mothers didn't received an anti-rheumatic drugs in the period 3 months prior to conception until labour.	8 / 154976	Only the first pregnancy for each parent during the study period was included. Some of the women received more than one of the drugs in the study period.
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.
Vinet, 2013	Canada 1996 - 2008	Women having an induced abortion (at the index date).	Age-matched controls selected at random from all subjects who entered the cohort on the same month and year as the case and who were born within 12 months of the case birthdate.	112 / 5855	Some women were also exposed to anti-TNF agents. Spontaneous abortions may be increased in women receiving MTX, consequently resulting in a lower induced abortion rate.

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