Prolonged sedation and/or analgesia and 5-year neurodevelopment outcome in very preterm infants: results from the EPIPAGE cohort

Arch Pediatr Adolesc Med. 2008 Aug;162(8):728-33. doi: 10.1001/archpedi.162.8.728.


Objective: To describe the long-term outcome of very preterm infants receiving prolonged sedation and/or analgesia and examine the relationship between prolonged sedation and/or analgesia and this long-term outcome.

Design: A prospective population-based study (Etude EPIdémiologique sur les Petits Ages GEstationnels [EPIPAGE]). To reduce bias, the propensity score method was used.

Setting: Nine regions of France.

Participants: The study population included very preterm infants of fewer than 33 weeks' gestational age, born in 1997, who received mechanical ventilation and/or surgery. Main Exposure Prolonged exposure to sedative and/or analgesic drugs in the neonatal period, defined as exposure of more than 7 days to sedative and/or opioid drugs.

Main outcome measure: Presence of moderate or severe disability at 5 years of age.

Results: The analysis concerns 1572 premature infants who received mechanical ventilation for whom information about exposure to prolonged sedation and/or analgesia in the neonatal period was available. A total of 115 were exposed and 1457 were not exposed. There was no significant difference between the number of patients lost to follow-up from the group of very preterm infants who were exposed to prolonged sedation and/or analgesia and the group who were not. Exposed very preterm infants had severe or moderate disability at 5 years (41/97; 42%) more often than those who were not exposed (324/1248; 26%). After adjustment for gestational age and propensity score, this association was no longer statistically significant (adjusted relative risk, 1.0; 95% confidence interval, 0.8-1.2).

Conclusion: Prolonged sedation and/or analgesia is not associated with a poor 5-year neurological outcome after adjustment for the propensity score.

Publication types

  • Comparative Study

MeSH terms

  • Age Distribution
  • Analgesia / adverse effects*
  • Analgesia / methods
  • Case-Control Studies
  • Child, Preschool
  • Confidence Intervals
  • Conscious Sedation / adverse effects*
  • Conscious Sedation / methods
  • Developmental Disabilities / epidemiology
  • Developmental Disabilities / etiology
  • Disability Evaluation
  • Female
  • Follow-Up Studies
  • France / epidemiology
  • Gestational Age
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Infant, Premature*
  • Intellectual Disability / epidemiology*
  • Intellectual Disability / etiology
  • Intensive Care Units, Neonatal
  • Male
  • Multicenter Studies as Topic
  • Probability
  • Reference Values
  • Respiration, Artificial / methods
  • Respiratory Distress Syndrome, Newborn / diagnosis
  • Respiratory Distress Syndrome, Newborn / therapy*
  • Retrospective Studies
  • Risk Assessment
  • Sex Distribution
  • Time Factors