What are Selective Serotonin Reuptake Inhibitors (SSRIs) in pregnancy associated with in terms of neonatal outcome?

Neonatal Outcomes Associated with SSRI Use During Pregnancy

SSRI use during pregnancy is associated with a constellation of neonatal symptoms including crying, irritability, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia, and seizures that typically resolve within 1-4 weeks after birth. 1

Neonatal Adaptation Syndrome

SSRI exposure during the third trimester can lead to what is known as neonatal adaptation syndrome, characterized by:

• Continuous crying and irritability
• Jitteriness and restlessness
• Shivering and fever
• Tremors
• Hypertonia or rigidity
• Tachypnea or respiratory distress
• Feeding difficulties
• Sleep disturbance
• Hypoglycemia
• Seizures (in severe cases) 1, 2

These symptoms typically:

• Begin several hours to days after birth
• Usually resolve within 1-2 weeks
• May persist up to 4 weeks in some cases (particularly with paroxetine) 1

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• Late pregnancy SSRI exposure is associated with PPHN
• Number needed to harm: 286-351 2
• This represents a small but clinically significant absolute risk 3

Other Perinatal Complications

SSRI exposure during pregnancy has been associated with:

• Increased risk of preterm delivery 4
• Respiratory distress syndrome (particularly with third-trimester exposure) 4
• Endocrine and metabolic disturbances 4
• Temperature regulation disorders 4
• Convulsions 4

Mechanism of Neonatal Effects

The neonatal effects may be explained by either:

1. Serotonin syndrome: Due to increased serotonin concentration in the intersynaptic cleft
2. SSRI withdrawal: Due to a relative hypo-serotonergic state after birth 1

In adults, serotonin syndrome typically presents with:

• Mental status changes (agitation, confusion)
• Autonomic hyperactivity (fever, tachycardia, tachypnea)
• Neuromuscular abnormalities (tremor, hyperreflexia, hypertonia)

While withdrawal symptoms include anxiety, headache, nausea, and occasionally extrapyramidal signs 1

Management Considerations

For infants exposed to SSRIs during pregnancy:

• Monitor for signs of drug toxicity or withdrawal during the first week of life 1, 2
• Arrange early follow-up after initial hospital discharge 1, 2
• In severely affected infants, a short-term course of chlorpromazine may provide symptom relief 1

Long-term Outcomes

• Several reviews have not identified adverse neurodevelopmental outcomes among infants born to women treated with SSRIs during pregnancy 1
• Data on long-term effects on psychomotor and behavioral development remain limited 5

Important Caveats

1. Risk-benefit assessment: The risk of untreated maternal depression (which can lead to premature birth, decreased breastfeeding initiation, and increased risk of relapse) often outweighs the potential risks of SSRI treatment 2, 6

2. Individual SSRI considerations:

   • Paroxetine has the lowest ratio of infant to maternal plasma concentrations (<0.10) 1
   • Sertraline and fluvoxamine are minimally excreted in human milk (<10% of maternal daily dose) 1, 2
   • Sertraline is often recommended as first-line during pregnancy due to its established safety profile 2

3. Medication management: Use the lowest effective dose during pregnancy to minimize neonatal effects while maintaining maternal mental health 2, 7

By understanding these associations, clinicians can better monitor and manage neonates exposed to SSRIs during pregnancy, while providing appropriate support for maternal mental health needs.