Is there an increased risk for adverse pregnancy outcome after exposure to low-dose methotrexate (MTX) during early pregnancy? A prospective multicenter cohort study.
- Conditions
- foetal methotrexate syndrome, congenital malformations, spontaneous abortions after intrauterine methotrexate exposure.MedDRA - 10071184 (LLT, 14.1): Foetal methotrexate syndromeQ86.8Other congenital malformation syndromes due to known exogenous causes
- Registration Number
- DRKS00003328
- Lead Sponsor
- Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie; Charité Universitätsmedizin
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Female
- Target Recruitment
- 1890
For all 3 cohorts: prospectively ascertained pregnancies, i.e. neither the outcome of pregnancy nor the results of prenatal diagnostics are primarily known, but are ascertained at a later stage.
Study group
Includes cases with low dose MTX, <=30 mg/week. Cases with more than 30 mg/week will be evaluated separately. MTX exposure time meets the period from 3 months pre-conception until week 12 after LMP. Exposure time may have started before 3 months preconception and continued beyond week 12.There is no limit of treatment duration during pregnancy. (Usually the treatment is stopped after recognition of pregnancy, which e.g. could be in week 20). A single dose of MTX is sufficient for study inclusion, as long as the single dose was not received earlier than one month before conception (in the preconception subgroup).
Control group 1 (Disease group”)
Includes cases with rheumatoid arthritis or other autoimmune diseases either without medication or with other immunomodulatory/immunosuppressive drugs than MTX. (e.g. MedDRA HLT code 10039078: rheumatoid arthropathies, HLT-code 10025135: lupus erythematosus (incl. subtypes), PT-code 10002817: antiphospholipid-syndrome, HLT-code 10065874: psoriatic conditions, PT-code 10011401: Crohn ‘s disease, PT 10047115: Vasculitis; ICD-10 (2010: http://www.lumrix.de/icd.php): D68.6, K50; M05-M09; M32-36). Matched with study group for year of counseling and treatment indication (disease) and recruiting country.
Control group 2 (General controls”)
Matched with study group for year of counseling and recruiting country.
For all three cohorts:
Excludes cases with exposure to following medication that is considered as major teratogen or major fetotoxicant:Acitretin, Isotretinoin,
Mycophenolate,Thalidomide, Valproic acid,
Angiotensin-II receptor blockers (sartanes) (only when used in 2nd or 3rd trimester) and
ACE inhibitors (only when used in 2nd or 3rd trimester)
Excludes cases with the following treatment indication: Malignancies (MedDRA code: Malignant or unspecified tumors (SMQ 20000091) ), ICD-10: C00-D09). Malignancy related conditions (MedDRA: SMQ 20000092), ICD-10: C00-D09)
Control group 1 (Disease group”):
Excludes cases with exposure to MTX
Control group 2 (General controls):
Excludes cases with exposure to MTX and cases with exposure to Immunomodulatory/immunosuppressive drugs (Exception: corticosteroids).
Study & Design
- Study Type
- observational
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Rate of major birth defects, rate of specific MTX embryopathy (time frame up to approximately 8 weeks after birth), rate of spontaneous abortion, intrauterine growth retardation (IUGR) in malformed and non malformed newborns (criterion: birth weigth), rate of prematurity.
- Secondary Outcome Measures
Name Time Method Definition of a teratogenic time window”. Evaluation of teratogenic dose-effect relationship. Rate of elective terminations of pregnancies (ETOPs). Postnatal symptoms and infant’s development are not subject to statistical analysis because there is no common tool for infant exam and data ascertainment for this study. However, individual observations will be analyzed and discussed.