Maternal Exposure to Antidepressants and Psychiatric Outcomes Among Offspring in a National Birth Cohort (Prenatal SSRIs and offspring Psychiatric Outcome)

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:
  (N06A) ANTIDEPRESSANTS

  ANTIDEPRESSANTS

  (N06AB) Selective serotonin reuptake inhibitors

  Selective serotonin reuptake inhibitors
• Medical condition to be studied:
  Childhood depression

  Pregnancy
• Additional medical condition(s):
  Antenatal depression, Offspring diagnoses of depression, anxiety, ADHD and autism spectrum disorders

Population studied

• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  242000

Study design details

• Main study objective:
  To investigate the impact of antenatal SSRI exposure on offspring psychiatric disorders into early adulthood in a national birth cohort
• Outcomes:
  Offspring diagnosis of depression. Offspring diagnoses ofAnxiety disorders Autism spectrum disorder (ASD) Attention deficit hyperactivity disorder (ADHD) Tourette syndrome (TS) Speech, motor, and scholastic disorders
• Data analysis plan:
  To determine whether the sharp rise in risk of depression observed in our previous research (defined as register diagnoses of major depressive disorder/other depressive disorders) among maternal SSRI-exposed subjects at 12-14 years of age continues into older age groups, we will first visually examine plots of cumulative incidence functions with confidence bands (based on Kaplan-Meier estimators), then we will fit Cox regression models. We will then add interaction terms for the product of maternal exposure category and age (or a more general function of age, for example, a dichotomous indicator of onset age, treated as a time-dependent covariate) to Cox models. Significant (p<0.05) p-values for these product terms will suggest that the risk of depression associated with prenatal SSRI exposure varies by offspring age. We will estimate separate HRs for the association of maternal SSRI exposure with depression diagnosed before and after the median age of diagnosis.