# Presentation: 493984

## 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

- 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*

## 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

## Neurobehavioral OutcomesSSRI-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***

## Neurodevelopmental EffectsSSRI-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)

## 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

## 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

## 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.

## 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.