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Published on: November 20, 2015
Early postnatal dexamethasone treatment and increased incidence of cerebral palsy
E S Shinwell1, M Karplus, D Reich
1Kaplan Medical Center, Rechovot, Israel. shinwell@netvision.net.il
Insights
Early dexamethasone treatment in preterm infants with respiratory distress syndrome significantly increased the risk of cerebral palsy and developmental delay. This neurodevelopmental outcome study highlights potential long-term risks associated with this intervention.
Area of Science:
- Neonatal Medicine
- Pediatric Neurology
- Clinical Trials
Background:
- Early postnatal dexamethasone is used to prevent chronic lung disease in preterm infants.
- The long-term neurodevelopmental effects of this treatment require thorough investigation.
- Previous studies indicated potential risks alongside benefits.
Purpose of the Study:
- To evaluate the long-term neurodevelopmental outcomes in preterm infants receiving early postnatal dexamethasone.
- To assess the association between dexamethasone treatment and neurological sequelae, including cerebral palsy and developmental delay.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving preterm infants ventilated for respiratory distress syndrome.
- Comparison of a three-day course of dexamethasone versus placebo administered within 12 hours of birth.
- Follow-up assessment of neurodevelopmental outcomes at a mean age of 53 months for surviving infants.
Main Results:
- Dexamethasone-treated infants showed a significantly higher incidence of cerebral palsy (49% vs. 15%) and developmental delay (55% vs. 29%).
- Spastic diplegia was the most common form of cerebral palsy observed in the dexamethasone group.
- Periventricular leucomalacia and dexamethasone treatment were significant predictors of abnormal neurological outcomes.
Conclusions:
- A short course of early postnatal dexamethasone in preterm infants with respiratory distress syndrome is linked to increased rates of cerebral palsy and developmental delay.
- The findings suggest that the neurodevelopmental risks may outweigh the benefits for preventing chronic lung disease in this population.
Objective:
To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease.
Methods:
The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months.
Results:
No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome.
Conclusions:
A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.
