title: Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage.
abstract: BACKGROUND
  Preterm infants are at risk of periventricular haemorrhage. This can damage the brain and lead to neurodevelopmental abnormalities, including cerebral palsy. Phenobarbital might prevent ischaemic injury or reduce fluctuations in blood pressure and blood flow in the brain.
  
  
  OBJECTIVE
  The objective of this review was to assess the benefits and harms of giving phenobarbital to women at risk of imminent very preterm birth with the primary aim of preventing periventricular haemorrhage in the infant.
  
  
  METHODS
  We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies. Date of last search: December 1998.
  
  
  METHODS
  Randomised trials with reported data which compare outcomes, such as neonatal mortality, neonatal neurological and other morbidity, longterm neurodevelopment and maternal morbidity, following prenatal exposure to phenobarbital, with outcomes in controls with or without placebo.
  
  
  METHODS
  Assessments of trial eligibility, quality and data extractions were done by the two authors independently. Eligible trials were included in the initial analysis and prespecified sensitivity analyses done to evaluate the effect of trial quality.
  
  
  RESULTS
  Over 1600 women were entered into the eight trials included. Analyses showed a significant reduction in the rates of all grades of periventricular haemorrhage (PVH) (relative risk 0.75, 95% confidence interval 0.65 to 0.88) and severe grades PVH (3 and 4) (relative risk 0.49, 95% confidence interval 0.32 to 0.74) in infants whose mothers had been given prenatal phenobarbital. These results were influenced by the earlier trials which were of poorer quality and contributed excessive weight in the analysis due to their higher rates of severe PVH. Over time, and with improved trial quality, these beneficial effects disappeared. No difference was found in the incidence of neurodevelopmental abnormalities at paediatric follow-up assessed between 18-36 months of age. Maternal sedation was more likely in women receiving phenobarbital.
  
  
  CONCLUSIONS
  Phenobarbital administration to women prior to preterm birth cannot be recommended for routine clinical practice. Any future trials should examine the effects of phenobarbital prior to preterm birth at gestational ages with a high risk of PVH, stratify for gestational age and ensure minimal exclusions after randomisation. Neurodevelopmental status at follow-up should be measured as the most important outcome.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Adelaide, Women's and Children's Hospital, King William Road, Adelaide, South Australia, Australia, SA 5006. ccrowthe@medicine.adelaide.edu.au
authors.forename: C A
authors.initials: CA
authors.lastname: Crowther
authors.forename: D J
authors.initials: DJ
authors.lastname: Henderson-Smart
mesh_terms: D002491:Central Nervous System Agents / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000517:prevention & control*; D007969:Leukomalacia, Periventricular / Q000517:prevention & control*; D007752:Obstetric Labor, Premature; D010634:Phenobarbital / Q000627:therapeutic use*; D011247:Pregnancy
chemical_list: D002491:Central Nervous System Agents; D010634:Phenobarbital