EBM Review: Antidepressant use during pregnancy and asthma in the offspring.

Liu X, Olsen J, Pedersen LH, et al. Antidepressant use during pregnancy and asthma in the offspring. Pediatrics. 2015 Apr;135(4):e911-7.

BACKGROUND AND OBJECTIVES: It has been suggested that maternal depression during pregnancy is associated with asthma in the offspring, but the role of medical treatment of depression is not known. Our goal was to examine whether prenatal antidepressant use increases the risk of asthma in the offspring.

METHODS: A cohort study was performed among all live singletons born in Denmark between 1996 and 2007. Mothers who had a diagnosis of depressive disorder and/or who used antidepressants 1 year before or during the index pregnancy were identified. Using a Cox proportional hazards regression model, we estimated the hazard ratio (HR) forasthma in the offspring after antidepressant use during pregnancy.

RESULTS: Of the 733,685 children identified, 84,683 had a diagnosis of asthma. A total of 21,371 children were exposed to prenatal maternal depression (ie, a diagnosis of depressive disorder or use of antidepressants 1 year before or during pregnancy). Prenatal maternal depression was associated with childhood asthma (HR: 1.25 [95% confidence interval (CI): 1.20-1.30]). Overall, 8,895 children were exposed to antidepressants in utero. Compared with children born to mothers with prenatal depression and no antidepressant use during pregnancy, the HR for asthma after any antidepressant use during pregnancy was 1.00 (95% CI: 0.93-1.08). HRs after use of selective serotonin reuptake inhibitors only, newer antidepressants only, and older antidepressants only were 0.95 (95% CI: 0.88-1.03), 1.11 (95% CI: 0.89-1.39), and 1.26 (95% CI: 1.02-1.55), respectively.

CONCLUSIONS: Antidepressant use during pregnancy generally did not increase the risk of asthma. Only use of older antidepressants was associated with an increased risk of asthma.

Reviewed by:

Lauren Levy, MD Lauren Levy, MD PGY-3

Meral Patel, MD Meral Patel, MD PGY-3

Data on Depression:

  • Maternal and paternal diagnoses plus whether medications were prescribed
  • Used ICD-10 codes for depressive disorder
  • Searched both inpatient and outpatient systems, as well as prescription registry
  • Antidepressant use was based on Anatomical Therapeutic Chemical codes
  • Allowed for exposure to multiple medications
  • Data on timing of drug exposure gathered

Defining Asthma:

  • At least 2 prescriptions for anti-asthmatic medications or 1 asthma hospital contact after 3 years of age from 1999-2010
  • Hospital contact based on ICD-10 codes
  • Medications based on Anatomical Therapeutic Chemical codes

Covariates:

  • Adjusted for maternal country of origin, maternal parity, maternal age, social status, smoking history, gender of the child, calendar year at birth and maternal history of asthma

Statistics:

  • Hazard Ratios with 95% CI
  • 3 groups of mothers
  • Separated subtypes of antidepressants in 4 groups
  • Analyzed timing of exposure via 3 groups
  • Other potential confounding factors:
    • Environmental or genetic: paternal depression, paternal antidep use, paternal asthma?*, paternal age and maternal hx of depression/med use > 1 year prior to delivery

Results:

  • HR for asthma after antidepressant use was 1.0
  • Older antidepressants only had slightly higher HR (1.26)
  • No association based on time of drug use
  • Paternal depression and/or drug use also associated with increased risk of asthma

Limitations:

  • Unknown whether the prescribed drugs were actually taken
  • May miss mild asthma
  • Depression severity
  • Correlation vs causation? Observational data leaves you with correlation instead of causation. It is still helpful because it’s as close as you can get to drawing a conclusion – impossible to randomize depression or smoking, etc. due to ethical issues.

Discussion:

  • Both maternal and paternal depression are associated with moderately increased risk of asthma
  • Potential association between tricyclic antidepressants (TCAs) use and asthma incidence may be related to severity of maternal depression or other confounding factors

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