Antipsychotics in pregnancy and the risk of adverse pregnancy outcomes - a nationwide study

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/1000000134
• EU PAS number:
  EUPAS1000000134
• Study ID:
  1000000134
• Official title and acronym:
  Antipsychotics in pregnancy and the risk of adverse pregnancy outcomes - a nationwide study
• DARWIN EU® study:
  No
• Study countries:
  Norway
• Study description:
  Maternal use of antipsychotics is increasing in recent years. Questions remain as to the risk of spontaneous abortion among women who use antipsychotics in early pregnancy, also due to the methodological challenges of studying spontaneous abortion as an outcome. Therefore, using a novel pregnancy algorithm that captures early non-live births, we aim to assess the association of second-generation antipsychotic use during pregnancy with spontaneous abortions. In addition, we will assess associations with the other maternal and pregnancy outcomes.; We will use Norwegian nationwide registry data, which consist of the Medical Birth Registry of Norway (MBRN), linked to the Norwegian Prescription Database (NorPD) covering all dispensed medications to outpatients, the Norwegian control and payment of health reimbursements (KUHR) covering primary care contacts, and the Norwegian Patient Registry (NPR) covering secondary care contacts, through the maternal personal identification number. Identification of pregnancy episodes and outcomes will be done using the pregnancy algorithm developed by PharmaSafe research group at the University of Oslo.; The primary exposure group is defined as second-generation antipsychotics during early pregnancy. Several comparison groups will be employed: 1. Unexposed, diseased comparison group 2. First-generation antipsychotics during pregnancy (Active comparator), 3. Exposed to second-generation antipsychotics only prior to pregnancy (Discontinuer). The primary outcome is defined as spontaneous abortions. We will estimate the hazard ratio with 95% CI with each comparator group, while controlling for measured confounders identified using Directed Acyclic Graphs. ; In the secondary analysis, we will restrict to pregnancies identified in the MBRN. We will assess the outcomes: preterm birth, small-for-gestational age (SGA), low Apgar score, transfer to NICU, congenital malformations, caesarean section, gestational diabetes, and preeclampsia.
• Study status:
  Planned

Research institution and networks

Institutions

Pharmacoepidemiology and Drug Safety Research Group (PharmaSafe), University of Oslo

Norway

Study timelines

Date when funding contract was signed

Planned: 08/04/2024

Study start date

Planned: 01/05/2024

Data analysis start date

Planned: 01/05/2024

Date of final study report

Planned: 28/02/2025

Sources of funding

Other public funding (e.g. hospital or university)

More details on funding

University of Oslo provided funds for data access and storage.
Dr. Sakai was funded International Alliance for PharmacoGenetic Epidemiology Excellence (iAPOGEE) visiting scholarship and Scandinavia-Japan Sasakawa Foundation for this project.

Study protocol

Initial protocol

Study protocol.pdf

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable