Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage

Vitamin K given to women before a very preterm birth does not decrease the risk of bleeding in the brain and associated neurological injury in babies born very preterm.

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 neurological disabilities including cerebral palsy. Preterm infants have reduced levels of clotting factors, some of which require vitamin K for activation. Vitamin K may therefore help the blood to clot in preterm babies and so decrease this risk of haemorrhage. The review of trials did not find vitamin K, given as an injection to women immediately prior to a very preterm birth, decreased the risk of periventricular haemorrhage in their babies. There were too few data on children at follow up to assess the effects of vitamin K given immediately before very preterm birth on child development. Eight trials were included but only seven contributed data to the results. These seven trials involved 843 women. The trials were of variable quality and only two trials used a placebo.

In four trials that did not use placebo, more women were treated with vitamin K also received corticosteroids before giving birth compared to those not receiving vitamin K. Prenatal corticosteroids are known to reduce the rate of haemorrhage. Women receiving vitamin K were also more likely to be treated with phenobarbital in one trial.

Women given vitamin K reported a rash in two trials.

Authors' conclusions: 

Vitamin K administered to women prior to very preterm birth has not been shown to significantly prevent PVH in preterm infants or improve neurodevelopmental outcomes in childhood.

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Background: 

Preterm infants are at risk of periventricular haemorrhage (PVH). This can be a sign of brain damage that might lead to neurodevelopmental abnormalities, including cerebral palsy. It has been suggested that vitamin K might improve coagulation in preterm infants and thereby decrease the risk of PVH.

Objectives: 

To assess the effects of vitamin K administered to women at risk of imminent very preterm birth to prevent PVH and associated neurological injury in the infant.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 December 2010).

Selection criteria: 

Randomised or quasi-randomised trials of vitamin K administered parenterally or orally to women at risk of imminent preterm birth. The primary outcomes were neonatal mortality, neonatal neurological morbidity, as measured by the presence of PVH on ultrasound during the first week of life, and long-term neurodevelopment. Secondary outcomes included other neonatal morbidity and any maternal side effects.

Data collection and analysis: 

Two review authors independently assessed eligibility, trial quality and extracted data.

Main results: 

Eight trials were included but only seven (843 women) contributed data to the results. The trials were of variable quality. Antenatal vitamin K was associated with a non-significant reduction in all grades of PVH (risk ratio (RR) 0.76; 95% confidence interval (CI) 0.54 to 1.06) and a significant reduction in severe PVH (grades 3 and 4) (RR 0.58; 95% CI 0.37 to 0.91) for babies receiving prenatal vitamin K compared with control babies. When the two quasi-randomised trials were excluded, antenatal vitamin K was associated with a non-significant reduction in all grades of PVH (RR 0.87; 95% CI 0.60 to 1.26) and a non-significant reduction in severe PVH (RR 0.82; 95% CI 0.49 to 1.36).

Treatment with vitamin K resulted in a significant reduction in the Bayley Mental Development Index at two years of age (mean difference (MD) -9.00; 95% CI -16.66 to -1.34, one trial, 121 children); however, these results are derived from one trial with many participants lost to follow up. No difference was found in the incidence of other neurodevelopmental abnormalities at paediatric follow up at 18 to 24 months or seven years of age between children born to mothers given vitamin K and children not so exposed.

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