Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage

[Intervention Review]
Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage

Caroline A Crowther1, Danielle D Crosby2, David J Henderson-Smart3

1ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, Australia. 2School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, Australia. 3NSW Centre for Perinatal Health Services Research, Queen Elizabeth II Research Institute, Sydney, Australia

Contact address: Caroline A Crowther, ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, 72 King William Road, Adelaide, South Australia, 5006, Australia. caroline.crowther@adelaide.edu.au. (Editorial group: Cochrane Pregnancy and Childbirth Group.)

Cochrane Database of Systematic Reviews, Issue 2, 2009 (Status in this issue: New search for studies completed, conclusions not changed)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DOI: 10.1002/14651858.CD000164
This version first published online: 21 July 2003 in Issue 3, 2003. Last assessed as up-to-date: 30 March 2008. (Help document - Dates and Statuses explained).

This record should be cited as: Crowther CA, Crosby DD, Henderson-Smart DJ. Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No.: CD000164. DOI: 10.1002/14651858.CD000164.
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Abstract


Background
Preterm infants are at risk of periventricular haemorrhage. Phenobarbital might prevent ischaemic injury or reduce fluctuations in blood pressure and blood flow in the brain.


Objectives
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.


Search strategy
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2008).


Selection criteria
Randomised trials with reported data that compared neonatal and maternal outcomes following prenatal exposure to phenobarbital, with outcomes in controls with or without placebo.


Data collection and analysis
We independently assessed trial eligibility and quality and extracted data. We included eligible trials in the initial analysis and prespecified sensitivity analyses to evaluate the effect of trial quality.


Main results
Nine trials (1752 women) were included. Analyses of all included trials showed a significant reduction in the rates of all grades of periventricular haemorrhage (PVH) (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.50 to 0.83; nine trials; 1591 women) and severe grades PVH (3 and 4) (RR 0.41, 95% CI 0.20 to 0.85; eight trials; 1527 women) in infants whose mothers had been given prenatal phenobarbital. These results were influenced by trials of poor quality which contributed excessive weight in the analysis due to their higher rates of severe PVH. When only the two higher quality trials were included, these beneficial effects disappeared for all grades of PVH (RR 0.90, 95% CI 0.75 to 1.08; two trials; 945 women), and severe grades of PVH (RR 1.05, 95% CI 0.60 to 1.83; two trials; 945 women).

No difference was found in the incidence of neurodevelopmental abnormalities at paediatric follow up at 18 to 24 months or seven years of age between children born to mothers given prenatal phenobarbital and children not so exposed.

Maternal sedation was more likely in women receiving phenobarbital (RR 2.06, 95% CI 1.79 to 2.37; one trial; 576 women).


Authors' conclusions
The evidence in this review does not support the use of prophylactic maternal phenobarbital administration to prevent periventricular haemorrhage in preterm infants or to protect them from neurological disability in childhood. Phenobarbital administration may lead to maternal sedation. If any future trials are carried out, they should measure neurodevelopmental status at follow up.


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Plain language summary

Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage
Evidence does not support phenobarbital treatment to women giving birth before 34 weeks to decrease the risk of bleeding into the babies' brains.

Babies born very early (before 34 weeks) are at risk of bleeding in the brain (periventricular haemorrhage). This can be a cause of brain damage that might lead to disability including cerebral palsy. Phenobarbital may prevent injury to the brain by stabilising blood pressure and blood flow in the brain. Possible adverse effects of phenobarbital for the women include drowsiness, gastrointestinal upset and development of a rash.

Nine trials involving 1752 women were included in the review. The trials with low risk of bias found that phenobarbital given to women immediately prior to a very preterm birth did not decrease the risk of bleeding in the brains of the babies. No differences in child development were found on follow up at 18 to 24 months or at seven years.

Maternal sedation was more likely in women receiving phenobarbital. The use of prenatal corticosteroids, known to reduce rates of periventricular haemorrhage, varied between trials and may have influenced findings.






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