Evaluation of pregnancy outcomes after maternal first trimester exposure to valproate and analysis of embryotoxic risks - Valproate during pregnancy

• Conditions: Q89.9; O03; P95; Congenital malformation, unspecified; Spontaneous abortion; Fetal death of unspecified cause

• Registration Number: DRKS00015636
• Lead Sponsor: Pharmakovigilanzzentrum Embryonaltoxikologie Charité-Universitätsmedizin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-10-23
• Study Completion: 2021-12-31
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: Female
• Target Recruitment: 484

Inclusion Criteria

For both cohorts: Enrollment of pregnancies, of which neither the outcome nor pathological results of prenatal diagnostics are known at the first contact. An analysis of these prospectively ascertained pregnancies can therefore be used for risk quantification of the defined endpoints.

Exclusion Criteria

Maternal malignancies in both cohorts. For the control cohort maternal exposure to substances considered as potent teratogens or fetotixicants, i.e. acenocoumarol, ACE-inhibitors and AT1-antagonists (exposure in 2nd and 3rd trimester), carbamazepine, lenalidomide, methotrexate, mycophenolate, phenobarbital, phenprocoumon, phenytoin, retinoids (acitretin, adapalen, isotretinoin, tazaroten, tretinoin), thalidomide, topimarat, valproate, warfarin.

Study & Design

• Study Type: observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Risk quantification of congenital major birth defects after maternal exposure to valproate during first trimester in comparison to a non-exposed control cohort. Is there an increased rate of spontaneous abortions and stillbirths after maternal exposure to valproate during first trimester in comparison to a non-exposed control cohort? The German Embryotox pharmacovigilance institute in Berlin counsels patients or their physicians about the risk of medication during pregnancy. This counselling mainly takes places in early pregnancy when outcome or pathological prenatal diagnosis is unknown. If the patient agrees, data are recorded by a structured questionnaire. Approximately eight weeks after the estimated date of birth another questionnaire is send to collect data about the pregnancy outcome.

Secondary Outcome Measures

Name	Time	Method
Is there a time-dependency on the risk of major congenital malformations and spontaneous abortions after in utero exposure to valproate? Is there an increased rate of elective terminations of pregnancy after maternal exposure to valproate during first trimester in comparison to a non-exposed control cohort? Is the risk for preterm delivery or low birthweight increased after maternal exposure to valproate during first trimester? If there are sufficient data of valproate dosage available, dose-dependent rates of major congenital malformations and spontaneous abortions will be analyzed. Moreover, differences between mono- and polytherapy on the primary endpoints will be evaluated as well as the influence of additional folic acid supplementation.