Medication Summary

Pharmacologic intervention in the prevention and treatment of germinal matrix/intraventricular hemorrhage (GM/IVH) and posthemorrhagic hydrocephalus remains controversial.

Class Summary

Prostaglandin inhibitors are postulated to perform prostaglandin synthesis inhibition. They inhibit free radical formation and accelerate maturation of germinal matrix vasculature. Indomethacin has been shown to decrease the risk of high-grade PVH-IVH. However, developmental outcomes have not been shown to be improved with the use of indomethacin prophylaxis. For this reason, the role of indomethacin in the prevention of IVH remains uncertain. Analysis of patients enrolled in a multicenter trial of indomethacin prophylaxis suggests that prophylaxis is effective in male infants but not in female infants. This remains to be confirmed through prospective evaluations.

Other members of this class of drugs have not been demonstrated to be of value in reducing the incidence of PVH-IVH.

Indomethacin (Indocin)

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Indomethacin use is controversial but possibly indicated in patients at risk for GM/IVH, including those younger than 32 weeks' gestation or those who weigh less than 1250 g at birth. Among its actions, indomethacin inhibits the formation of prostaglandins by decreasing the activity of cyclooxygenase. Additionally, through poorly understood mechanisms, indomethacin causes maturation of the germinal matrix microvasculature. It is also associated with decreased cerebral blood flow, cerebral blood flow velocity, and cerebral blood volume, especially when administered rapidly. Alterations of oxidative metabolism are also suggested. Unfortunately, there are conflicting data regarding long-term improvement in outcomes.

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Media Gallery

Coronal midline ultrasonographic appearance of a normal neonatal brain.
Normal neonatal brain shown with a left sagittal ultrasonographic scan.
Normal neonatal brain shown with midline sagittal ultrasonographic scan.
Grade I hemorrhage minimal or grade I periventricular hemorrhage (PVH).
Moderate or grade II hemorrhage (subependymal, with no or little ventricular enlargement).
Severe or grade III hemorrhage (subependymal, with significant ventricular enlargement).
Intraventricular hemorrhage (IVH) with periventricular hemorrhagic infarction (PVHI).
Periventricular hemorrhagic infarction (PVHI) with porencephalic cyst formation.
Periventricular hemorrhagic infarction (PVHI) on magnetic resonance imaging (MRI).
Ultrasonogram revealing hydrocephalus.

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Author

David J Annibale, MD Professor of Pediatrics, Medical University of South Carolina College of Medicine; Director of Neonatology, Director of Fellowship Training Program in Neonatal-Perinatal Medicine, Department of Pediatrics, Division of Neonatology, MUSC Children's Hospital

David J Annibale, MD is a member of the following medical societies: American Academy of Pediatrics, National Perinatal Association

Disclosure: Editorial staff for AAP NeoREVIEWS PLUS (includes reimbursement for meeting expecnses and $300 honorarium; Advisory meetings for the National Certification Corp. development of a QI certification test. (includes all expenses without honorarium) for: American Academy of Pediatrics, National Certification Corp.

Coauthor(s)

Jeanne G Hill, MD Professor of Radiology and Pediatrics, Division Director, Pediatric Radiology, Director of Medical Student Education, Department of Radiology and Radiologic Science, Medical University of South Carolina College of Medicine

Jeanne G Hill, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Radiology, American Roentgen Ray Society, Association of Program Directors in Radiology, Association of University Radiologists, Charleston County Medical Association, Radiological Society of North America, Society for Pediatric Radiology, Southern Pediatric Radiology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Brian S Carter, MD, FAAP Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Attending Physician, Division of Neonatology, Children's Mercy Hospital and Clinics; Faculty, Children's Mercy Bioethics Center

Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Pediatric Society, American Society for Bioethics and Humanities, American Society of Law, Medicine & Ethics, Society for Pediatric Research, National Hospice and Palliative Care Organization

Disclosure: Nothing to disclose.

Chief Editor

Santina A Zanelli, MD Associate Professor, Department of Pediatrics, Division of Neonatology, University of Virginia Health System

Santina A Zanelli, MD is a member of the following medical societies: American Academy of Pediatrics, American Epilepsy Society, Society for Neuroscience, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Scott S MacGilvray, MD Clinical Professor, Department of Pediatrics, Division of Neonatology, The Brody School of Medicine at East Carolina University

Scott S MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Acknowledgements

Jeanne Hill, MD Radiology Program Director, Associate Professor, Departments of Radiology and Pediatrics, Medical University of South Carolina

Jeanne Hill, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Radiology, Association of Program Directors in Radiology, Association of University Radiologists, Radiological Society of North America, and Society for Pediatric Radiology

Disclosure: Nothing to disclose.