Elsevier

Clinics in Perinatology

Volume 35, Issue 4, December 2008, Pages 777-792
Clinics in Perinatology

Pharmacologic Methods of Neuroprotection
The Diagnosis, Management, and Postnatal Prevention of Intraventricular Hemorrhage in the Preterm Neonate

https://doi.org/10.1016/j.clp.2008.07.014Get rights and content

Intraventricular hemorrhage (IVH) occurs in 20% to 25% of very low birthweight preterm neonates and may be associated with significant sequelae. Infants who have IVH are at risk for posthemorrhagic hydrocephalus and periventricular leukomalacia; as many as 75% of those who have parenchymal involvement of hemorrhage suffer significant neurodevelopmental disability. Because of the prevalence of IVH and the medical and societal impact of this disease, many postnatal pharmacologic prevention strategies have been explored. Randomized clinical prevention trials should provide long-term neurodevelopmental follow-up to assess the impact of preterm birth, injury, and pharmacologic intervention on the developing brain.

Section snippets

Intraventricular hemorrhage is an important predictor of adverse neurodevelopmental outcome

Although several early studies reported that cognitive outcome may be directly related to gestational age at birth,1, 2 recent data suggest that medical risk factors may be equally important predictors of neurologic outcome.3, 4, 5, 6, 7, 8, 9 Chief among these is Gr 3–4 IVH.7

IVH occurs in infants of 32 weeks' gestation or less, and the overall incidence of IVH is inversely related to gestational age. For the purposes of this article, IVH is described by the following classification: grade

Risk Factor Studies

Studies addressing the etiology of Gr 3−4 IVH have identified many environmental and medical risk factors, including low gestational age, absence of antenatal steroid exposure, antenatal maternal hemorrhage, maternal chorioamnionitis/infection/inflammation, maternal fertility treatment, outborn status (ie, neonatal transport), early sepsis, hypotension requiring therapeutic intervention, hypoxemia, hypercapnia, pneumothorax, pulmonary hemorrhage, respiratory distress syndrome, severity of

The risk period for intraventricular hemorrhage is independent of gestational age

To prevent injury, knowledge of the risk period is critical for success. IVH is encountered most commonly within the first 24 hours after birth, and hemorrhages can progress over 48 hours or more. By the end of the first postnatal week, 90% of the hemorrhages can be detected at their full extent, and this risk period for IVH is independent of gestational age.

Screening for Intraventricular Hemorrhage in Very Low Birthweight Preterm Neonates

Management of IVH typically is confined to screening for sequelae of IVH and managing systemic issues of the neonate, such as blood pressure and respiratory status, which might influence progression of IVH. The American Academy of Neurology “Practice parameter: neuroimaging of the neonate” suggests that screening ultrasonography should be performed on all preterm neonates of less than 30 weeks' gestation at two time points.16 The first ultrasound is recommended between 7 and 14 days of age to

Rationale for prevention strategies

As support in the neonatal period has improved, more low birthweight infants are surviving, and it has become increasingly clear that certain newborns seem to do better than their similarly premature counterparts. Differences even are noted in rates of IVH at different neonatal intensive care units, with those treating higher patient volumes and with a higher neonatologist-to-housestaff ratio having lower rates of IVH.75 It is uncertain what accounts for this difference, but there is

Postnatal pharmacologic preventions strategies for intraventricular hemorrhage

The well-known sequelae of IVH have prompted the development of pharmacologic prevention strategies for this injury to developing brain for almost 4 decades (Table 2). These interventions have included phenobarbital, pavulon, vitamin E, ethamsylate, indomethacin, ibuprofen, and recombinant activated factor VIIa. Because the preclinical and clinical trials for pavulon, vitamin E, and ethamsylate took place many years ago and these agents currently are not in wide use, these studies are reviewed

Summary

IVH remains a common problem of VLBW preterm neonates and may be associated with significant neurodevelopmental disability. Prevention strategies must address the environmental and genetic causes of this injury to developing brain. The effect of gender on the efficacy of indomethacin treatment and of genetics on the cognitive outcome of preterm neonates argues that as new interventions are developed, their effect on specific subgroups of neonates must be considered in addition to their overall

Acknowledgments

The authors thank Deborah Hirtz, MD, and Charles C. Duncan, MD, for scientific advice and Ms. Marjorene Ainley for administrative assistance.

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    This work was supported by grants number NS 27116 and NS 53865 from the National Institutes of Health.

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