Effects of NSAID and metamizole exposure in the 1st trimester of pregnancy - An observational cohort study series
Organizational Data
- DRKS-ID:
- DRKS00011140
- Recruitment Status:
- Recruiting complete, study complete
- Date of registration in DRKS:
- 2016-10-11
- Last update in DRKS:
- 2018-12-11
- Registration type:
- Retrospective
Acronym/abbreviation of the study
NSAIDs and Metamizol during pregnancy
URL of the study
No Entry
Brief summary in lay language
Non-steroidal anti-inflammatory drugs (NSAID) are often used during 1st and 2nd trimester of pregnancy. Primary objectives of this study are risk estimation of major congenital birth defects and miscarriage (spontaneous abortion rate) after exposure to the study medication during 1st trimester. Data analysis will be based on cases which are prospectively ascertained and archived in the pharmacovigilance database of the German Embryotox Pharmacovigilance Centre.
Brief summary in scientific language
Due to the high prevalence of pain symptoms, analgesics are commonly used and needed in pregnancy. Paracetamol (acetaminophen) is considered safe in terms of teratogenicity and recommended as the analgesic of choice throughout pregnancy. During 1st and 2nd trimester ibuprofen as a well proven non-steroidal anti-inflammatory drug (NSAID) is another analgesic of first choice. However, various situations and reasons may lead to the use of not sufficiently explored analgesics in pregnancy. Therefore, different NSAIDs, coxibes, acetylsalicylic acid (ASA) and also metamizole may be used intentionally or inadvertently during pregnancy although sufficient data on prenatal risk and safety are still lacking. Therefore, it is urgently needed to improve the risk profile of these analgesics in pregnancy. This would support adequate counselling of pregnant women and their health care providers. Based on their different action mode the following analgesics will be studied separately: 1) NSAIDs, 2) selective cox inhibitors (coxibes), 3) acetylsalicylic acid (ASA) in analgesic doses (defined as > 300mg/d), 4) metamizole. Objectives are to estimate the risk of major birth defects and miscarriage (spontaneous abortion) after exposure to the study medication during 1st trimester The Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy counsels patients or their physicians about the risk of medication during pregnancy. This counselling mainly takes place in early pregnancy when outcome or prenatal diagnostic is not known. If the pregnant patient agrees, data are recorded by a structured questionnaire. Eight weeks after the estimated date of birth a further questionnaire is send to collect data about the pregnancy outcome. Analysis of those prospectively ascertained pregnancies can be used for risk assessment of pathologic pregnancy course including congenital malformations. Both exposed group and control group are recruited from the already collected and archived data.
Health condition or problem studied
- ICD10:
- Q89.9 - Congenital malformation, unspecified
- ICD10:
- O03 - Spontaneous abortion
- Healthy volunteers:
- No Entry
Interventions, Observational Groups
- Arm 1:
- Via questionnaire prospectively ascertained pregnancies with systemic NSAID/metamizole exposure during first trimester [1) NSAIDs, 2) selective cox inhibitors (coxibes), 3) acetylsalicylic acid (ASA) in analgesic doses (defined as > 300mg/d), 4) metamizole]. Exclusion criteria: exposure to a known teratogen or fetotoxicant; maternal malignancies. Data from our institute's patient registry.
- Arm 2:
- Control group: Via questionnaire prospectively ascertained pregnancies not exposed to a study medication [1) NSAIDs, 2) selective cox inhibitors (coxibes), 3) acetylsalicylic acid (ASA) in analgesic doses (defined as > 300mg/d), 4) metamizole], known teratogens or fetotoxicants; Exclusion criteria: maternal malignancies. Data from our institute's patient registry.
Endpoints
- Primary outcome:
- Is there an increased rate of major birth defects after systemic exposure to the study medication [1) NSAIDs, 2) selective cox inhibitors (coxibes), 3) acetylsalicylic acid (ASA) in analgesic doses (defined as > 300mg/d), 4) metamizole] during 1. trimester of pregnancy? Is there an increased rate of spontaneous abortion after systemic exposure to the study medication 1)-4) during 1. trimester of pregnancy? The Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy counsels patients or their physicians about the risk of medication during pregnancy. This counselling mainly takes place in early pregnancy when outcome or prenatal diagnostic is not known. If the pregnant patient agrees, data are recorded by a structured questionnaire. Eight weeks after the estimated date of birth a further questionnaire is send to collect data about the pregnancy outcome.
- Secondary outcome:
- Is the risk for preterm delivery or low birthweight increased after systemic exposure to study medication 1)-4) during 1. trimester of pregnancy? Is there evidence of an exposure time-dependence spontaneous abortion rate during the 1st trimester?
Study Design
- Purpose:
- Other
- Retrospective/prospective:
- No Entry
- Study type:
- Non-interventional
- Longitudinal/cross-sectional:
- No Entry
- Study type non-interventional:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting complete, study complete
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
-
- University medical center Berlin
Recruitment period and number of participants
- Planned study start date:
- No Entry
- Actual study start date:
- 2016-05-01
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- 2017-10-09
- Target Sample Size:
- 8000
- Final Sample Size:
- 7184
Inclusion Criteria
- Sex:
- Female
- Minimum Age:
- no minimum age
- Maximum Age:
- no maximum age
- Additional Inclusion Criteria:
- Prospectively ascertained pregnancies, i.e. neither the outcome of pregnancy nor results of prenatal diagnostics are primarily known, but are ascertained at a later stage
Exclusion Criteria
Exclusion of cases with maternal malignancies or maternal exposure considered as potent teratogens or fetotoxicants: i.e. acenocoumarol, ACE-inhibitors and ARBs (AT1-Antagonists), carbamazepine, lenalidomide, methotrexate, mycophenolate, phenobarbital, phenprocoumon, phenytoin, retinoids (acitretin, adapalen, isotretinoin, tazaroten, tretinoin), thalidomide, topimarat, valproic acid, warfarin.
Addresses
Primary Sponsor
- Address:
- Pharmakovigilanzzentrum Embryonaltoxikologie Charité-UniversitätsmedizinProf. Dr. med. Christof SchaeferAugustenburger Platz113353 BerlinGermany
- Telephone:
- +49-30-3450525702
- Fax:
- +49-30-450525902
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.embryotox.de
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Pharmakovigilanzzentrum Embryonaltoxikologie Charité-UniversitätsmedizinDr. med. Katarina DatheAugustenburger Platz 113353 BerlinGermany
- Telephone:
- +49-30-450525743
- Fax:
- +49-30-450525902
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.embryotox.de
Contact for Public Queries
- Address:
- Pharmakovigilanzzentrum Embryonaltoxikologie Charité-UniversitätsmedizinDr. med. Katarina DatheAugustenburger Platz 113353 BerlinGermany
- Telephone:
- +49-30-450525743
- Fax:
- +49-30-450525902
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.embryotox.de
Principal Investigator
- Address:
- Pharmakovigilanzzentrum Embryonaltoxikologie Charité-UniversitätsmedizinDr. med. Katarina DatheAugustenburger Platz 113353 BerlinGermany
- Telephone:
- +49-30-450525743
- Fax:
- +49-30-450525902
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.embryotox.de
Sources of Monetary or Material Support
Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)
- Address:
- Bundesinstitut für Arzneimittel und MedizinprodukteKurt-Georg-Kiesinger-Allee 353175 BonnGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.bfarm.de/cln_103/DE/Home/home_node.html
Ethics Committee
Address Ethics Committee
- Address:
- Ethikkommission der Charité – Universitätsmedizin BerlinCharitéplatz 110117 BerlinGermany
- Telephone:
- (+49)30-450517222
- Fax:
- (+49)30-450517952
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2016-02-23
- Ethics committee number:
- EA4/029/16
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2016-03-23
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No Entry
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- Dathe K, Padberg S, Hultzsch S, Meixner K, Tissen-Diabaté T, Meister R, Beck E, Schaefer C. Metamizole use during first trimester - A prospective observational cohort study on pregnancy outcome. Pharmacoepidemiol Drug Saf 2017 August 3.
- Dathe K, Padberg S, Hultzsch S, Köhler LM, Meixner K, Fietz AK, Tissen-Diabaté T, Meister R, Schaefer C. Exposure to cox-2 inhibitors (coxibs) during the first trimester and pregnancy outcome: a prospective observational cohort study. Eur J Clin Pharmacol 2017 Dec 7.
- Padberg S, Tissen-Diabaté T, Dathe K, Hultzsch S, Meixner K, Linsenmeier V, Meister R, Schaefer C. Safety of diclofenac use during early pregnancy: A prospective observational cohort study. Reprod Toxicol 2018; 77: 122-9.
- Dathe K, Fietz AK, Pritchard LW, Padberg S, Hultzsch S, Meixner K, Meister R, Schaefer C. No evidence of adverse pregnancy outcome after exposure to ibuprofen in the first trimester – Evaluation of the national Embryotox cohort. Reprod Toxicol. 2018;79:32-8.
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry