Prenatal Maternal Depression, Antidepressant Medication Use and Neonatal Outcomes

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• Prenatal Maternal Depression, Antidepressant
  Medication Use and Neonatal Outcomes
• Using Linked Population Health Data
• Tim F Oberlander MD, FRCPC
• Centre for Community Child Health Research
• Child Family Research Institute
• R Howard Webster Professorship in Early Child
  Development
• Human Early Learning Partnership (HELP)
• University of British Columbia

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Acknowledgements

• No conflicts of interest Off Label Drug Use
• CFRI UBC
• Ruth Grunau
• Shaila Misri
• Joanne Weinberg
• Wayne Riggs
• Dan Rurak Ken Lim
• Elizabeth Simpson
• Human Early Learning Partnership
• Clyde Hertzman Colleagues
• Child and Youth Development Trajectory
  Research Unit
• Bill Warburton
• Early Human Experience Unit
• Ursula Brain Mary Beckingham

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The Context Mothers Mood, Infant and Childhood
Development and Behavior
SRI use
Fetal SRI exposure serotonin
Emotional behaviour (Maternal-Infant Interaction)
Serotonin (5HT) related outcomes in childhood
Neonatal Withdrawal
HPA Stress Response
Arousal regulation (Habituation, attention,
Executive function)
Neonatal Pain Reactivity
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Medication vs. Depression effects Can they
be separated?

• in most instances, it is not possible to
  differentiate drug-induced adverse effects from
  those induced by the disease process itself.
• NTP-CERHR EXPERT PANEL REPORT on the REPRODUCTIVE
  and DEVELOPMENTAL TOXICITY of FLUOXETINE 2004

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Barriers to typical cohort research

• Sample size obstacles
• Space, s time
• Heterogeneity of population
• Unexpected variation in depression
  characteristics, treatment, pregnancy etc
• Randomized controlled trial design not available
• ethical, medical, logistical challenges

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Effects of Prenatal SRI exposure 3 key
(unanswered) questions

• Are the effects of depression different from
  medication-depression (SSRI-D) exposure?
• Does the timing of gestation exposure matter?
• Can risk for congenital anomalies be separated
  from the risks associated with illness itself?

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Linked Population-Health Data Studies
?
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Population Level Research

• Administrative health data on 119,547 live
  births over 39 months (1998-2001)
• Linked Health Data
• maternal prescriptions for SSRIs and other
  psychotropic medications
• maternal medical records
• birth outcome data
• demographic data

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1. Depression Vs SSRI effects (Oberlander,
Warburton et al 2006)

• Compared neonatal outcomes between three mutually
  exclusive with prenatal exposure groups
• SSRIs and Depression (SSRI-D)
• (n 1,451 )
• Depression only
• (n 14,234)
• Neither depression nor medication
• (n 92,192)

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Neonatal Outcomes Birth Weight
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Neonatal Outcomes Respiratory Distress
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Maternal CharacteristicsDiagnoses of depression
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Maternal CharacteristicsDiagnoses of depression
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Propensity Score Matching Outcomes Neonatal
Outcome Differences
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Propensity Score Matching Outcomes Neonatal
Outcome Differences
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Conclusions

• Exposure to depression mattered, but SSRI-D
  exposure mattered more
• Prenatal SSRI exposure (unmatched)
• Lower birth weight
• Shorten gestational age
• Longer hospital stays
• Increased incidence of respiratory distress
• Using linked population health data and
  propensity score matching, prenatal SE-D
  exposure
• increased risk for low birth weight and
  respiratory distress, even when accounting for
  maternal illness severity.

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2. Effects of Timing (Oberlander, Warburton,
Hertzman et al in press)

• Issues
• Effects related to first vs third trimester
  exposure
• Duration of exposure
• Maternal illness severity

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2. Effects of Timing (Oberlander et al in press)
1 P lt 0.05 for group differences
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2. Effects of Timing (Oberlander et al in press)
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2. Effects of Timing (Oberlander, Warburton,
Hertzman et al 2007)

• Findings
• Timing Controlling for maternal illness and
  duration of exposure
• neonatal outcomes did not differ between LE and
  EE (pgt.05).
• Length of Exposure Controlling for maternal
  illness characteristics
• increasing the length of prenatal SRI exposure
  increased the risk for lower birth weight,
  respiratory distress and reduced gestational age
  (plt 0.05).

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3. Risk for Congenital Anomalies (Oberlander,
Warburton, Hertzman et al 2007)

• Background issues
• Increased risk for major congenital anomalies and
  CHD
• Increased first trimester dose
• Conflicting evidence
• Numbers of anomalies small in huge populations
• Multiple confounding factors (age, smoking,
  parity, other teratogenic agents)

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3. Risk for Congenital Anomalies (Oberlander,
Warburton, Hertzman et al 2007)

• Polydrug exposure
• Prenatal exposure to SRIs benzodiazepine
  an anticonvulsants
• 2-fold to 4-fold increase in incidence of major
  congenital anomalies,
• major cardiac anomalies - 15-fold increase in
  incidence, even when controlling for maternal
  illness characteristics.
• Risk associated with SRI mono therapy did not
  increase over no exposure or no drug/no
  depression exposure.
• Risk not associated with increased 1st trimester
  dose/day
• Risks did not vary with maternal illness severity

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Cohort Characteristics
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Cohort Characteristics
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Cohort Characteristics
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Summary

• Population-level linked health data
• Summary of findings
• Effects of illness differs from impact of
  medication
• Duration of exposure gt influence than timing of
  exposure
• Congenital Anomalies
• Polydrug exposure differs from monodrug exposure
• Medication dose does not influence risk
• Addresses questions not easily answerable using
  cohort studies
• Account for unmeasured but possibly confounding
  variables, where randomization can not occur
• Highlight importance of SES and social context

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• To create, promote and apply new knowledge
  through leading interdisciplinary research to
  help children thrive.
• Please visit HELPs website
• www.earlylearning.ubc.ca
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Background

• Maternal depression
• 10-20 of pregnancies
• Serotonin Reuptake Inhibitor (SRI) antidepressant
  medication
• 5 of pregnancies (Oberlander, 2006)
• Prenatal exposure associated with
• reduced Apgar scores, reduced birth weight ,
  cluster of symptoms termed poor neonatal
  adaptation (PNA)
• respiratory distress, increased motor tone, and
  feeding difficulties
• 3rd trimester exposure gt 1st trimester exposure
• Increased risk for congenital anomalies
• FDA Health Canada warnings (2004)
• Why do some infants experience adverse outcomes
  following prenatal exposure to SRI ?