Safety of the second generation antipsychotics during pregnancy (Second generation antipsychotics and pregnancy)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Population studied

• Short description of the study population:
  Exposed cohort:; The definition of exposure includes pregnancies where the woman has purchased second generation antipsychotics (4th level ATC code N05AE, N05AH, N05AL, N05AX) at any time during pregnancy and/ or one month before pregnancy. Major congenital anomalies will be analyzed in the cohort with purchase(s) during one month prior to pregnancy or during the first trimester ; The two unexposed reference groups consist of:; - 1. All pregnant women and their offspring not exposed to second generation antipsychotics during pregnancy and three months before pregnancy, but exposed to first generation antipsychotics (ATC codes N05AA, N05AB, N05AC, N05AD, N05AF) at any time during the period of three months before pregnancy until the end of pregnancy; - 2. Pregnant women and their offspring unexposed to second generation antipsychotics during the period of three months prior to pregnancy until the end of pregnancy
• Age groups:
  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  10000

Study design details

• Main study objective:
  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.
• Outcomes:
  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.
• Data analysis plan:
  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).

Documents

Study results

ABSTRACT_121019

SGA_malformations_Ellfolk et al.

Study publications

Ellfolk M, Leinonen MK, Gissler M, Lahesmaa-Korpinen AM, Saastamoinen L, Nurmin…

Ellfolk M, Leinonen MK, Gissler M, Kiuru-Kuhlefelt S, Saastamoinen L, Malm H. S…