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Background Issues

Maternal SSRI-Use During Pregnancy and Neonatal Neurobehavioral Outcome Philip Sanford Zeskind, Ph.D. Director, Neurodevelopmental Research Department of Pediatrics Carolinas Medical Center - Charlotte and University of North Carolina – Chapel Hill. Background Issues.

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Background Issues

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  1. Maternal SSRI-Use During Pregnancy and Neonatal Neurobehavioral OutcomePhilip Sanford Zeskind, Ph.D.Director, Neurodevelopmental ResearchDepartment of PediatricsCarolinas Medical Center - CharlotteandUniversity of North Carolina – Chapel Hill

  2. Background Issues • High rates of maternal depression and SSRI-use among women of child-bearing age • Serotonin levels, affected by maternal SSRI-use, has fundamental role in cell development and brain function • Determining whether this neurotransmitter has adverse effects on development has been based on studies mostly using measures of birthweight, preterm birth and physical anomalies

  3. Methodological Issues • All infants full birthweight, in term nursery a. no abnormal signs on routine physical and neurological examinations • 17 SSRI-exposed and 17 non-exposed • matched on maternal age, cigarette-use and SES • no differences in demographic characteristics • Studied via direct, blinded observation and measurement a. not based on medical record review

  4. Neurobehavioral OutcomesSSRI-exposed infants: • Greater tremulousness • Increased startles (arousals) • Greater generalized motor activity • Disrupted Sleep-State Architecture a. Increased REM Sleep b. More rigid state organization c. Depressed range of states • Disrupted autonomic organization (HRV) All measures previously used to detect effects of prenatal drug exposure and/or to differentiate high risk infants

  5. Neurodevelopmental EffectsSSRI-exposed Infants: • Lower gestational age by 1 week • Within a full birthweight sample in term nursery • Similar to previous findings • A symptom of other developmental problems affecting maturation rate and maternal-fetus interactions • Often interpreted as the problem or complication • Associated with development of autonomic regulation (HRV and startles)

  6. Effects on Further Development • Developmental and drug-toxicology literatures have clearly shown these neurobehaviors to be related to subsequent development • Emphasis on measures of autonomic and behavioral regulation • Less emphasis on standardized tests (e.g., IQ, language) • Unsolicited letters and email describing observable motor effects still evident at 2 years • Supports the one long-term effect documented on motor development from 6-24 month year-olds

  7. Withdrawal Syndrome? • Withdrawal Syndrome • Neurobehaviors may reflect effects of sudden withdrawal from medication • Some suggest providing additional SSRIs in neonatal period to help adaptation • Serotonin Syndrome • Fetus bathed in serotonin during development of nervous system • Direct neurotoxic effects • Effects on synaptic development, adaptation and function • Provision of additional SSRIs to ease withdrawal may be contraindicated

  8. Conclusions • Maternal use of SSRIs during pregnancy may disrupt neurobehavioral development of newborn infant. • Birthweight, preterm birth and physical anomalies are insufficient measures of effects of prenatal SSRI-exposure. • Neurobehavioral effects may be evidence of direct neurotoxic effects on development of nervous system, as well as a withdrawal syndrome. • Effects of exposure during nervous system development different than withdrawal after nervous system developed in adults.

  9. A Question of Balance A careful cost-benefit analysis should be discussed by physician and patient when considering to use SSRIs during pregnancy to treat maternal depression.

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