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Status: Finalised

First registered on: 23/09/2013

Last updated on: 10/12/2019

1. Study identification

EU PAS Register NumberEUPAS4799

Official titleSafety of the second generation antipsychotics during pregnancy

Study title acronymSecond generation antipsychotics and pregnancy

Study typeObservational study

Brief description of the studySecond generation antipsychotics have largely replaced first generation antipsychotics but little is known about their safety during pregnancy. This is a population based study based on national register data in Finland. Data from the National Birth Register, the Register of Congenital Malformations, and the Drug Prescription Register have been linked through years 1996-2012 in the Drugs and Pregnancy project, and data in this study are extracted from the Drugs and Pregnancy project database. The data include all births (live and still births), pregnancy terminations due to major congenital anomaly, and information on drug purchases during pregnancy and 3 months before pregnancy. There are appr. 55,000-60,000 births per year in Finland, and we expect to have a baseline study population with appr. 1 mil. pregnancies. Appr. 0.2-0.6% of pregnant women during the study period used antipsychotics and we expect to include appr.2,000 pregnancies exposed to second generation antipsychotics. The primary aims of the study are i.) to assess the risk of major congenital anomalies after first trimester exposure to second generation antipsychotics and ii.) to investigate the prevalence of other perinatal outcomes, including large for gestational age, preterm birth, low birth weight, and perinatal mortality after continuous exposure. The exposed group is compared i) to women and their offspring exposed to first generation antipsychotics during the period of theree months prior to pregnancy until the end of pregnancy (to control for maternal illness), and ii) to unexposed women. Logistic regression is used to evaluate associations between exposure and outcome, and covariates to be considered include year of birth, mother's age, parity, tobacco use, prepregnancy diabetes, use of other psychiatric drugs and use of drugs classified as potentially harmful. The results will provide important information on the safety of second generation antipsychotics during pregnancy.

Was this study requested by a regulator?No

Is the study required by a Risk Management Plan (RMP)? Not applicable

Regulatory procedure number (RMP Category 1 and 2 studies only)

Other study registration identification numbers and URLs as applicable

2. Research centres and Investigator details

Coordinating study entity

Centre to which the investigator belongsDrugs and Pregnancy

Department/Research groupDrugs and Pregnancy -research

Organisation/affiliationNational Institute for Health and Welfare, THL

Website/Homepagehttp://www.thl.fi/en_US/web/en/research/projects/drugs_and_pregnancy

Details of (Primary) lead investigator

Title Dr

Last name Malm

First name Heli

Is this study being carried out with the collaboration of a research network?

Other centres where this study is being conducted

Not applicable (single centre)

Countries in which this study is being conducted

National study

Finland

3. Study timelines: initial administrative steps, progress reports and final report

PlannedActual

Date when funding contract was signed01/01/201201/01/2012

Start date of data collection15/05/201415/05/2014

Start date of data analysis15/09/201401/09/2016

Date of interim report, if expected31/10/2018

Date of final study report01/09/201903/11/2019

4. Sources of funding

Please provide estimates of the percentage of funding by source for this study

Names(s)Approximate % funding

Pharmaceutical companies

Charities

Government bodyFinnish Medicines Agency100

Research councils

EU funding scheme

5. Contact details for enquiries

Scientific Enquiries

Title Dr

Last name Malm

First name Heli

Address line 1P.O. BOX 790

Address line 2HUS

Address line 3

CityHelsinki

Postcode00290

CountryFinland

Phone number (incl. country code)358947176589

Alternative phone number

Fax number (incl. country code)

Email address heli.malm@hus.fi

Public Enquiries

Title Dr

Last name Malm

First name Heli

Address line 1P.O. BOX 790

Address line 2HUS

Address line 3

CityHelsinki

Postcode00290

CountryFinland

Phone number (incl. country code)358947176589

Alternative phone number

Fax number (incl. country code)

Email address heli.malm@hus.fi

11. Scope of the study

What is the scope of the study?

Risk assessment

Primary scope : Risk assessment

12. Main objective(s)

What is the main objective of the study?

To assess pregnancy-related risks associated with the use of second generation antipsychotics. These include major congenital anomalies and perinatal outcomes including preterm birth, birth weight, perinatal death etc.

Are there primary outcomes?Yes

Major congenital anomalies, perinatal outcomes including preterm birth>37 weeks and very preterm birth (<32 weeks), low birth weight (<2500g) and very low birth weight (<1500g), perinatal death, mode of delivery, neonatal outcome (Apgar score, hypoxia, need for treatment in neonatal care unit, etc.

Are there secondary outcomes?No

13. Study design

What is the design of the study?

Cohort study

14. Follow-up of patients

Will patients be followed up?Not applicable/no follow-up

15. Data analysis plan

Please provide a brief summary of the analysis method

All data are anonymized and coded prior to statistical analysis. The prevalence of specific outcomes is compared between exposed and unexposed pregnant women and their offspring. Univariate analyses are used to study demographic differences between the study cohorts, and logistic regression to assess the association between new generation antipsychotic use during pregnancy and major congenital anomalies (MCA) and perinatal outcomes. With an estimated of 2,000 exposed births and fetuses from elective terminations of pregnancy due to fetal anomaly, the study has a 98.3% power to detect a 60% relative increase (1.8% absolute increase) in the prevalence of MCAs presuming a baseline prevalence of 3% in the control cohort (alpha = 0.05, two-sided), and for perinatal complications that have a prevalence of 6% (as preterm birth) we have a 98.3% power to detect a 40% relative risk increase (2.4% absolute risk increase).