Contact information
Type
Scientific
Primary contact
Dr F.F.T. (Tessa) Ververs
ORCID ID
Contact details
University Medical Center Utrecht
Division of Perinatology and Gynaecology/Division of Laboratory and Pharmacy
Room D.00.218
P.O. Box 85500
Utrecht
3508 GA
Netherlands
+31 (0)30 250 7190
f.f.t.ververs@apoth.azu.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
CCMO P03.0335, UMC U 03-024; NTR346
Study information
Scientific title
Acronym
OAZE (Dutch: Onderzoek Antidepressiva tijdens Zwangerschap, een Evaluatie)
Study hypothesis
The use of modern antidepressants during pregnancy is associated with changes in foetal movement and development and can lead to serious withdrawal syndromes after birth. Antidepressant use as well as discontinuation of medication during pregnancy will have an effect on the mental development of the child.
Ethics approval
Received from the local medical ethics committee
Study design
Multicentre, non-randomised, two armed, parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Quality of life
Patient information sheet
Condition
Depression and pregnancy
Intervention
The study is a prospective observational study and therefore there are no interventions. Subjects enter the study as antidepressant user (group A) or as having stopped taking medication (group B).
Intervention type
Drug
Phase
Not Specified
Drug names
Antidepressants
Primary outcome measures
The effects of antidepressants are evaluated through measurements of foetal movement and development, registration of withdrawal syndromes after birth and measurement of child behaviour and development until the age of 2 years. Of 200 women who are on antidepressants during pregnancy (group A) and 200 women who stopped medication in the first trimester (group B) the social-economical status, smoking/drinking habits, co-medication, mental status (Edinburgh Depression Scale and State Trait Anxiety Inventory), specific pregnancy anxiety and blood level of the antidepressant are registered at 17, 28 and 37 weeks of pregnancy. Ultrasound recording of the foetal movements is also planned around these three time points. after delivery pregnancy outcome and observations of the baby during the first 10 days after birth are registered using the Finnigan score on withdrawal symptoms. Foetal drug exposure and neonatal drug elimination kinetics are estimated using umbilical cord blood and a blood sample of the child several hours after birth.
At 3 months, 8 months and 2 years after birth, behaviour and mental development are tested using the CBCL, child behaviour list and the IBQ infant behaviour questionnaire. The results of the two study groups A and B are compared. Dose-effect relations and level of exposure-effect relations are evaluated in relation to the severity of the withdrawal symptoms.
Secondary outcome measures
1. The positive effects of antidepressant use on the mental state of the mother during pregnancy and delivery versus the effects of discontinuation of pharmacotherapy
2. Pharmacokinetic changes of the different antidepressants in the three phases of pregnancy
Overall trial start date
12/07/2003
Overall trial end date
23/12/2006
Reason abandoned
Eligibility
Participant inclusion criteria
Women who are pregnant and use one of the modern antidepressants (selective serotonin re-uptake inhibitor [SSRI] and non-SSRI) are included at 16 weeks of pregnancy, group A. Women who stopped taking antidepressants in the first trimester or just before pregnancy are included in group B. Women must be willing and give informed consent and must be able to read in Dutch in order to fill in the questionnaires.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
400
Participant exclusion criteria
1. Co-medication with a similar or higher pregnancy risk factor
2. Alcohol or drug addiction
Recruitment start date
12/07/2003
Recruitment end date
23/12/2006
Locations
Countries of recruitment
Netherlands
Trial participating centre
University Medical Center Utrecht
Utrecht
3508 GA
Netherlands
Sponsor information
Organisation
University Medical Centre Utrecht (UMCU) (Netherlands)
Sponsor details
PO Box 85500
Utrecht
3508 GA
Netherlands
Sponsor type
University/education
Website
Funders
Funder type
Industry
Funder name
Eli Lilly Nederland BV (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Pfizer Netherlands (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Netherlands Brain Foundation (Hersenstichting Nederland) (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Stichting Doelmatig Geneesmiddelengebruik Midden Nederland (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Arijan Porsius Fonds (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19743889
Publication citations
-
Results
Ververs FF, Voorbij HA, Zwarts P, Belitser SV, Egberts TC, Visser GH, Schobben AF, Effect of cytochrome P450 2D6 genotype on maternal paroxetine plasma concentrations during pregnancy., Clin Pharmacokinet, 2009, 48, 10, 677-683, doi: 10.2165/11318050-000000000-00000.