Combined antenatal vitamin K and phenobarbital therapy for preventing intracranial hemorrhage in newborns less than 34 weeks' gestation

doi:10.1016/0029-7844(95)00091-5

Obstetrics & Gynecology

Volume 86, Issue 1, July 1995, Pages 1-8

https://doi.org/10.1016/0029-7844(95)00091-5 Get rights and content

Objective

To determine whether maternal antenatal therapy with vitamin K and phenobarbital prevents intracranial hemorrhage in premature newborns.

Methods

Women at high risk for spontaneous or indicated premature delivery before 34 weeks' gestation were randomly assigned to receive either placebo or vitamin K and phenobarbital. All patients received betamethasone and antibiotics and were managed uniformly by a single perinatal group in one hospital. All newborns were managed uniformly in the same nursery by one neonatal group. Two independent interpretations of neonatal head ultrasound examinations were obtained.

Results

The duration of gestation at study entry and at delivery were similar in the placebo (181 mothers) and treatment (191) groups. With the hospital radiology group (the primary interpreter), the incidence rates of severe intracranial hemorrhage (8 versus 7%) and mild intracranial hemorrhage (38 versus 32%) were similar for both groups. With the secondary interpreter (a single pediatric radiologist), the incidence rates of severe intracranial hemorrhage (9 versus 7%) and mild intracranial hemorrhage (27 versus 26%) were also similar. Neonatal mortality was equivalent in both the placebo and treatment groups (8 versus 10%).

Conclusion

Combined antenatal therapy with vitamin K and phenobarbital does not reduce the frequency or severity of intracranial hemorrhage in premature newborns.

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Cited by (34)

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Germinal matrix hemorrhage–intraventricular hemorrhage (GMH-IVH) is the most common variety of neonatal intracranial hemorrhage and is characteristic of the premature infant. This form of brain injury affects around 25% of all very low birthweight (<1500 g) premature infants, resulting in an increased risk for neurodevelopmental disability. Its occurrence can lead to impact on subsequent brain development because of destruction of the immature germinal cerebral region resulting in loss of progenitor cells, acceleration of white matter injury via pressure and oxidative stress, and direct parenchymal injury. Finally, hydrocephalus can complicate IVH, resulting in a further increased risk of neurodevelopmental disability. In this chapter, the neuropathology, pathogenesis, clinical features, diagnosis, prognosis, and management of IVH, and its complications will be reviewed. The prominent position of this lesion in neonatal medicine has been accompanied by a large increase in work from several disciplines. This chapter attempts to integrate this information in a meaningful way without oversimplifying a clearly complex problem.
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Citation Excerpt :
Phenobarbital and vitamin K are important to mention here, as these medications attracted the attention of investigators. Initial studies showed some protective effect of phenobarbital; however, subsequent clinical trials failed to confirm the protective effect of phenobarbital in preventing IVH.89–93 Maternal treatment of vitamin K or magnesium sulfate to prevent IVH did not demonstrate any benefit either.64,94–96
Effects of phenobarbital and multiple-dose corticosteroids on developmental outcome at age 7 years
2003, Obstetrics and Gynecology
To determine the effects of phenobarbital and repeated antenatal steroid use on the primary outcome (intelligence and achievement) and secondary outcomes (behavior and head circumference) at age 7 years.
This study was a secondary analysis of a double-blind clinical trial (phenobarbital–vitamin K versus placebo). Intelligence (Wechsler Intelligence Scale for Children, third edition), achievement (Wide Range Achievement Test, third edition), and behavioral (Achenbach Teacher’s Report Form and the Child Behavioral Check List) testing and head circumference measurement were performed on 7-year-old children whose mothers participated in a trial to determine if antenatal phenobarbital and vitamin K prevented severe intracranial hemorrhage. Antenatal steroid therapy in these women was repeated weekly.
Two hundred ninety-nine of 372 newborns (80%) whose mothers participated in the trial were followed up at age 7 years. Comparing mean (± standard deviation [SD]) Wechsler Intelligence Scale for Children scores in the placebo versus treatment groups, there were no differences (P > .4) in Full Scale IQ (100.3 ± 14.2 versus 100.6 ± 14.2), Performance IQ (100.3 ± 14.6 versus 101.5 ± 15.6), and Verbal IQ (100.2 ± 14.9 versus 99.6 ± 13.7). Comparing mean (± SD) Wide Range Achievement Test standardized scores in the placebo versus treatment groups, there were no differences (P > .4) in Reading (97.3 ± 13.9 versus 98.0 ± 14.9), Spelling (95.8 ± 12.7 versus 95.3 ± 13.3), Mathematics (95.9 ± 13.8 versus 94.5 ± 14.5), or head circumference measurements (20.3 ± 0.6 cm versus 20.4 ± 0.6, P > .2). Similarly, there were no differences in the mean Achenbach Teacher’s Report Form and Child Behavioral Check List scores between the placebo and treatment groups.
Antenatal phenobarbital and repetitive antenatal corticosteroid therapy was not associated with adverse effects on intelligence, achievement, behavior, or head circumference at age 7 years.
Therapies administered to mothers at risk for preterm birth and neurodevelopmental outcome in their infants
2002, Clinics in Perinatology

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^**: This study was supported by the Mcllvain Fund and the Andrew Nicely Memorial Fund through the Saint Luke's Foundation, Kansas City, Missouri.

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Combined antenatal vitamin K and phenobarbital therapy for preventing intracranial hemorrhage in newborns less than 34 weeks' gestation**

Objective

Methods

Results

Conclusion

Am J Obstet Gynecol

J Pediatr

Am J Obstet Gynecol

Am J Obstet Gynecol

J Pediatr

J Pediatr

Pediatr Neurol

Am J Obstet Gynecol

Am J Obstet Gynecol

Prevention of intraventricular hemorrhage in very low birth weight infants by maternally administered phenobarbital

Obstet Gynecol

Antenatal phenobarbital in preventing intraventricular hemorrhage in premature newborns

Fetal Therapy

Maternally administered antenatal vitamin K1: Effect on neonatal prothrombin activity, partial thromboplastin time, and intraventricular hemorrhage

Obstet Gynecol

Maternal administration of vitamin K does not improve the coagulation profile of preterm infants

Pediatrics

Antenatal corticosteroids appear to reduce the risk of postnatal germinal matrix hemorrhage in intubated low birth weight new-borns

Pediatrics

Maternally administered antenatal vitamin K₁: Effect on neonatal prothrombin activity, partial thromboplastin time, and intraventricular hemorrhage