Infant and childhood neurodevelopmental outcomes following prenatal exposure to selective serotonin reuptake inhibitors: overview and design of a Finnish Register-Based Study (FinESSI)

Study type

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

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (N06AB) Selective serotonin reuptake inhibitors

  Selective serotonin reuptake inhibitors
• Medical condition to be studied:
  Neurodevelopmental disorder

Population studied

• Age groups:
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  64000

Study design details

• Main study objective:
  The objective of the FinESSI study is to investigate if prenatal SSRI exposure increases the risk of adverse psychiatric or neurodevelopmental outcome until age 14, controlling for maternal depression.
• Outcomes:
  The specific outcomes under study include: offspring depression, anxiety, autism spectrum disorders (ASD), and attention-deficit hyperkinetic disorders (ADHD).
• Data analysis plan:
  Clinically relevant and plausible covariates were first tested and included in the models if associated with both exposure and outcome at P<0.1. To take into account the fact that children born from 1996-2010 were aged 0-14 years at the end of the follow-up in 2010, we use survival methods. Events in the survival analysis were defined as age at the first diagnosis of the studied outcome. Separate survival analyses were conducted for each of the four outcomes. We plotted the cumulative incidence of offspring diagnoses among the SSRI exposed, the Psychiatric disorder, no medication group, the SSRI discontinued group and the Unexposed group. To compare offspring psychiatric diagnoses between these four groups, Cox proportional hazards models were used. Each outcome was analyzed separately by fitting two models: a crude model adjusted only for sex, and a model adjusted for additional covariates associated with the exposure and each specific outcome.