Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

A risk prediction model for severe intraventricular hemorrhage in very low birth weight infants and the effect of prophylactic indomethacin

Journal of Perinatology volume 34, pages 43–48 (2014)Cite this article

Subjects

Abstract

Objective:

Develop a risk prediction model for severe intraventricular hemorrhage (IVH) in very low birth weight infants (VLBWI).

Study Design:

Prospectively collected data of infants with birth weight 500 to 1249 g born between 2001 and 2010 in centers from the Neocosur Network were used. Forward stepwise logistic regression model was employed. The model was tested in the 2011 cohort and then applied to the population of VLBWI that received prophylactic indomethacin to analyze its effect in the risk of severe IVH.

Result:

Data from 6538 VLBWI were analyzed. The area under ROC curve for the model was 0.79 and 0.76 when tested in the 2011 cohort. The prophylactic indomethacin group had lower incidence of severe IVH, especially in the highest-risk groups.

Conclusion:

A model for early severe IVH prediction was developed and tested in our population. Prophylactic indomethacin was associated with a lower risk-adjusted incidence of severe IVH.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Bassan H . Intracranial hemorrhage in the preterm infant: understanding it, preventing it. Clin Perinatol 2009; 36 (4): 737–762.

    Article  PubMed  Google Scholar 

  2. The Victorian Infant Collaborative Study Group. Improved outcome into the 1990s for infants weighing 500–999 g at birth. Arch Dis Child Fetal Neonatal Ed 1997; 77 (2): F91–F94.

    Article  Google Scholar 

  3. Sheth RD . Trends in incidence and severity of intraventricular hemorrhage. J Child Neurol 1998; 13 (6): 261–264.

    Article  CAS  PubMed  Google Scholar 

  4. Hintz SR, Kendrick DE, Vohr BR, Poole WK, Higgins RD . Changes in neurodevelopmental outcomes at 18 to 22 months corrected age among infants of less than 25 weeks gestational age born in 1993–1999. Pediatrics 2005; 115 (6): 1645–1651.

    Article  PubMed  Google Scholar 

  5. Philip AG, Allan WC, Tito AM, Wheeler LR . Intraventricular hemorrhage in preterm infants: declining incidence in the 1980’s. Pediatrics 1989; 84: 797–801.

    CAS  PubMed  Google Scholar 

  6. Horbar JD, Badger GJ, Carpenter JH, Fanaroff AA, Kilpatrick S, LaCorte M et al. Trends in mortality and morbidity for very low birth weight infants, 1991–1999. Pediatrics 2002; 110 (1 Pt 1): 143–151.

    Article  PubMed  Google Scholar 

  7. Hamrick SE, Miller SP, Leonard C, Glidden DV, Goldstein R, Ramaswamy V et al. Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: the role of cystic periventricular leukomalacia. J Pediatr 2004; 145 (5): 593–599.

    Article  PubMed  Google Scholar 

  8. Horbar JD, Onstad L, Wright E . Predicting mortality risk for infants weighing 501 to 1500 grams at birth: a National Institutes of Health Neonatal Research Network report. Crit Care Med 1993; 21 (1): 12–18.

    Article  CAS  PubMed  Google Scholar 

  9. McCrea HJ, Ment LR . The diagnosis, management, and postnatal prevention of intraventricular hemorrhage in the preterm neonate. Clin Perinatol 2008; 35 (4): 777–792.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 (3): 442–458.

    Article  Google Scholar 

  11. Crowley P . Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev 2007; 18 (3): CD000065.

    Google Scholar 

  12. Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY, Mercer BM et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008; 359 (9): 895–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Whitelaw A, Odd D . Postnatal phenobarbital for the prevention of intraventricular hemorrhage in preterm infants. Cochrane Database Syst Rev 2007; 4: CD001691.

    Google Scholar 

  14. Ment LR, Oh W, Ehrenkranz RA, Philip AG, Vohr B, Allan W et al. Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial. Pediatrics 1994; 93 (4): 543–550.

    CAS  PubMed  Google Scholar 

  15. Ment LR, Vohr B, Allan W, Westerveld M, Sparrow SS, Schneider KC et al. Outcome of children in the indomethacin intraventricular hemorrhage prevention trial. Pediatrics 2000; 105: 485–491.

    Article  CAS  PubMed  Google Scholar 

  16. Schmidt B, Davis P, Moddemann D, Ohlsson A, Roberts RS, Saigal S et al. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001; 344 (26): 1966–1972.

    Article  CAS  PubMed  Google Scholar 

  17. Fowlie PW, Davis PG . Prophylactic indomethacin for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal 2003; 88 (6): F464–F466.

    Article  CAS  Google Scholar 

  18. Papile L, Bursten J . Incidence and evolution of subependimal and intraventricular hemorrhage. A study of infants with birth weights less than 1500g. J Pediatr 1978; 92: 529–534.

    Article  CAS  PubMed  Google Scholar 

  19. Ancel P-Y, Marret S, Larroque B, Arnaud C, Zupan-Simunek V, Voyer M et al. Are maternal hypertension and small-for-gestational age risk factors for severe intraventricular hemorrhage and cystic periventricular leukomalacia? Results of the EPIPAGE cohort study. Am J Obstet Gynecol 2005; 193: 178.

    Article  PubMed  Google Scholar 

  20. Hall RW, Kronsberg SS, Barton BA, Kaiser JR, Anand KJ NEOPAIN Trial Investigators Group. Morphine, hypotension, and adverse outcomes among preterm neonates: who’s to blame? Secondary results from the NEOPAIN Trial. Pediatrics 2005; 115: 1351.

    Article  PubMed  Google Scholar 

  21. Kaiser JR, Gauss CH, Pont MM, Williams DK . Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants. J Perinatol 2006; 26 (5): 279–285.

    Article  CAS  PubMed  Google Scholar 

  22. Kluckow M . Low systemic blood flow and pathophysiology of the preterm transitional circulation. Early Hum Dev 2005; 81: 429.

    Article  PubMed  Google Scholar 

  23. Linder N, Haskin O, Levit O, Klinger G, Prince T, Naor N . Risk factors for intraventricular hemorrhage in very low birth weight premature infants: a retrospective case-control study. Pediatrics 2003; 111: e590–e595.

    Article  PubMed  Google Scholar 

  24. Whitelaw A . Intraventricular haemorrhage and posthaemorrhagic hydrocephalus: pathogenesis, prevention and future interventions. Semin Neonatol 2001; 6: 135.

    Article  CAS  PubMed  Google Scholar 

  25. Heuchan AM, Evans N, Henderson Smart DJ, Simpson JM . Perinatal risk factors for major intraventricular haemorrhage in the Australian and New Zealand Neonatal Network, 1995–97. Arch Dis Child Fetal Neonatal Ed 2002; 86: F86–F90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ryckman KK, Dagle JM, Kelsey K, Momany AM, Murray JC . Replication of genetic associations in the inflammation, complement and coagulation pathways with intraventricular hemorrhage in low birth weight preterm neonates. Pediatr Res 2011; 70 (1): 90–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Shankaran S, Bauer CR, Bain R, Wright LL, Zachary J . Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage. Arch Pediatr Adolesc Med 1996; 150: 491–497.

    Article  CAS  PubMed  Google Scholar 

  28. Beverley DW, Chance GW, Coates CF . Intraventricular haemorrhage: timing of occurrence and relation to perinatal events. Br J Obstet Gynecol 1984; 91: 1007–1013.

    Article  CAS  Google Scholar 

  29. Ment LR, Oh W, Philip AGS, Ehrenkranz RA, Duncan CC, Allan W et al. Risk factors for early intraventricular haemorrhage in low birth weight infants. J Pediatr 1992; 121: 776–783.

    Article  CAS  PubMed  Google Scholar 

  30. Kluckow M, Evans N . Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed 2000; 82: F188–F194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Van de Bor M, Verloove-Vanhorick SP, Brand R, Keirse MJ, Ruys JH . Incidence and prediction of periventricular—intraventricular hemorrhage in very preterm infants. J Perinat Med 1987; 15 (4): 333–339.

    Article  CAS  PubMed  Google Scholar 

  32. Vogtmann C, Koch R, Gmyrek D, Kaiser A, Friedrich A . Risk-adjusted intraventricular hemorrhage rates in very premature infants. Dtsch Arztebl Int 2012; 109 (31–32): 527–533.

    PubMed  PubMed Central  Google Scholar 

  33. Guzman JM, Parraga MJ, Del Prado N, Ruíz MD, García Del Río M, Benito Zaballo F et al. Usefulness of Clinical Risk Index for Babies based on birth weight in predicting hospital death and severe intraventicular hemorrhage in the SEN 1500 Spanish neonatal network. An Pediatr (Barc) 2009; 71 (2): 117–127.

    Article  Google Scholar 

  34. Chien L, White R, Thiessen P, Walker R, Brabyn D, Lee SK et al. SNAP-II predicts severe intraventricular hemorrhage and chronic lung disease in the neonatal intensive care unit. J Perinatol 2002; 22: 26–30.

    Article  PubMed  Google Scholar 

  35. Wells JT, Ment LR . Prevention of intraventricular hemorrhage in preterm infants. Ear Hum Develop 1995; 42: 209–233.

    Article  CAS  Google Scholar 

  36. Leviton A, Fenton T, Kuban KC, Pagano M . Labor and delivery characteristics and the risk of germinal matrix hemorrhage in low birth weight infants. J Child Neurol 1991; 6 (1): 35–40.

    Article  CAS  PubMed  Google Scholar 

  37. Anderson GD, Bada HS, Sibai BM, Harvey C, Korones SB, Magill HL et al. The relationship between labor and route of delivery in the preterm infant. Am J Obstet Gynecol 1988; 158: 1382–1390.

    Article  CAS  PubMed  Google Scholar 

  38. Anderson GD, Bada HS, Shaver DC, Harvey CJ, Korones SB, Wong SP et al. The effect of cesarean section on intraventricular hemorrhage in the preterm infant. Am J Obstet Gynecol 1992; 166: 1091–1101.

    Article  CAS  PubMed  Google Scholar 

  39. Hoegberg U, Holmgren PA . Infant mortality of very preterm infants by mode of delivery, institutional policies and maternal diagnosis. Acta Obstet Gynecol Scand 2007; 86: 693–700.

    Article  Google Scholar 

  40. Qiu H, Paneth N, Lorenz JM, Collins M . Labor and delivery factors in brain damage, disabling cerebral palsy and neonatal death in lowbirth-weight infants. Am J Obstet Gynecol 2003; 189: 1143–1149.

    Article  PubMed  Google Scholar 

  41. Meidell MC, Marinelli P, Pettett G . Perinatal factors associated with early-onset intracranial hemorrhage in premature infants, a prospective study. Am J Dis Child 1985; 129: 160–163.

    Article  Google Scholar 

  42. Beeby PJ, Elliot EJ, Henderson-Smart DJ, Rieger ID . Predictive value of umbilical artery pH in preterm infants. Arch Dis Child Fetal Neonatal Ed 1994; 71: F93–F96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gaudier FL, Goldenberg RL, Nelson KG, Peralta-Carcelen M, DuBard MB, Hauth JC . Influence of acid-base status at birth and Apgar scores on survival in 500–1000-g infants. Obstet Gynecol 1996; 87: 175–180.

    Article  CAS  PubMed  Google Scholar 

  44. Szymonowicz W, Yu VYH, Wilson FE . Antecedents of periventricular haemorrhage in infants weighing 1250 g or less at birth. Arch Dis Child 1984; 59: 13–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mohamed MA, Aly H . Male gender is associated with intraventricular hemorrhage. J Pediatrics 2010; 125: e333–e339.

    Article  Google Scholar 

  46. Fowlie PW, Davis PG, McGuire W . Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants (Review). Cochrane Database of Syst Rev 2010; 7: CD000174.

    Google Scholar 

  47. Yanowitz TD, Baker RW, Brozanski BS . Prophylactic indomethacin reduces grades III and IV intraventricular hemorrhages when compared to early indomethacin treatment of a patent ductus arteriosus. J Perinatol 2003; 23: 317–322.

    Article  PubMed  Google Scholar 

  48. Bandstra ES, Montalvo BM, Goldberg RN . Prophylactic indomethacin for prevention of intraventricular hemorrhage in premature infants. Pediatrics 1988; 82: 533.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the Neocosur centers that participated in this study.

Author information

Author notes

  1. The members in the Neocosur Neonatal Network are listed in the Appendix.

Authors and Affiliations

  1. Division de Pediatria, Hospital Clinico Pontificia Universidad Catolica de Chile, Santiago, Chile

    M J Luque

  2. Seccion de Neonatologia, Hospital Clinico Pontificia Universidad Catolica de Chile, Santiago, Chile

    J L Tapia & J Kattan

  3. Departamento Salud Publica, Pontificia Universidad Catolica, Santiago, Chile

    L Villarroel

  4. Facultad de Matematicas, Pontificia Universidad Catolica, Santiago, Chile

    G Marshall

  5. Servicio de Neonatologia, Hospital Universitario Austral, Pilar, Argentina

    G Musante

  6. Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL, USA

    W Carlo

Authors
  1. M J Luque
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J L Tapia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Villarroel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Marshall
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G Musante
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. W Carlo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Kattan
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Neocosur Neonatal Network

Corresponding author

Correspondence to M J Luque.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Appendix

Appendix

The present study included the following collaborators from the Neocosur Network: Argentina: Guillermo Colantonio, Jorge Zapata, Gaston Perez, Susana Garcia Ana Pedraza (Clinica y Maternidad Suizo Argentina, Buenos Aires); Isabel Kurlat, Oscar Di Siervi, Adriana Escarate (Hospital de Clinicas Jose de San Martin); Gonzalo Mariani, Jose Maria Ceriani, Silvia Fernandez, Carlos Fustiñana, Pablo Brener, Eleonora Edwards (Hospital Italiano, Buenos Aires); Jorge Tavosnaska, Liliana Roldan, Hector Sexer, Gladys Saa, Debora Sabatelli, Maria Laura Gendra, Maria Fernanda Buraschi, Paula Molina (Hospital Juan Fernandez, Buenos Aires); Daniel Agost, Federico Morganti, Adriana Fontana, Daniela Chandias, Monica Rinaldi (Hospital Lagomaggiore, Mendoza); Carlos Grandi, Elio Rojas, Claudio Solana, Ricardo Nieto, Javier Meritano, Miguel Larguia, Laura Kasten, Lucrecia Cuneo (Maternidad Sarda, Buenos Aires); Marcelo Decaro, Lionel Cracco, Gustavo Bassi, Noemi Jacobi, Andrea Brum, Nestor Vain (Sanatorio de la Trinidad, Buenos Aires); Adriana Aguilar, Miriam Guerrero, Edgardo Szyld, Alcira Escandar (Hospital Dr Diego Paroissien, Buenos Aires); Daniel Abdala, Martin Guida, Lucila Ferrin, Horacio Roge (Hospital Español de Mendoza); Gabriel Musante, Maria C. Capelli, Juan Pablo Berazategui, Magdalena de Elizalde, Juan Ignacio Fraga, Rodolfo Keller (Hospital Universitario Austral, Buenos Aires); Luis Ahumada, Mirta Ferreyra (Hospital Nuestra Señora de la Misericordia, Cordoba). Brasil: Vanda Ferreira, Roberta Borges, Marynea Do Vale, Silvia Cavalcante, Joama Gusmão, Patricia Franco, Maria Jose Silva (Hospital Universidad Federal de Maranhão, Sao Luis). Chile: Jorge Fabres, Alberto Estay, Alvaro Gonzalez, Jose Luis Tapia, Javier Kattan, Mariela Quezada, Soledad Urzua (Hospital Clinico Universidad Catolica de Chile, Santiago); Rodrigo Ramirez, Maria Eugenia Hübner, Jaime Burgos, Jorge Catalan (Hospital Clinico Universidad de Chile, Santiago); Lilia Campos, Lilian Cifuentes, Jorge Leon, Roxana Aguilar, Sergio Treuer, Jimena Giaconi, Aldo Bancalari (Hospital Guillermo Grant, Concepcion); Jane Standen, Marisol Escobar, Viviana Veas, Daniela Sandino (Hospital Gustavo Fricke, Viña del Mar); Agustina Gonzalez, Claudia Avila, Carla Guzman (Hospital San Jose, Santiago); Claudia Toro, Patricia Mena, Beatriz Milet, Enrica Pittaluga (Hospital Dr Sotero del Rio, Santiago); Veronica Peña, Rafael Mendizabal, Dagoberto Pizarro (Hospital San Borja Arriaran, Santiago); Ivonne D’Apremont, Guillermo Marshall, Luis Villarroel, Mariela Quezada, Angelica Dominguez (Unidad Base de Datos, Pontificia Universidad Catolica, Santiago). Paraguay: Jose Lacarruba, Elizabeth Cespedes, Ramon Mir, Elvira Mendieta, Larissa Genes, Carlos Caballero (Departamento de Hospital de Clinicas de Asuncion). Peru: Veronica Webb, Fabiola Rivera, Margarita Llontop, Sicilia Bellomo, Jaime Zegarra (Hospital Cayetano Heredia, Lima); Oscar Chumbes, Anne Castañeda, Walter Cabrera, Raul Llanos, Jorge Mucha, Gustavo Garcia (Hospital Guillermo Almenara, Lima). Uruguay: Beatriz Ceruti, Daniel Borbonet, Sandra Gugliucci, Ana Lain, Mariza Martinez, Gabriela Bazan, Susana Piffaretti, Isabel Cuña, Patricia Bermudez (Facultad de Medicina Servicio de Recien Nacidos, Montevideo).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luque, M., Tapia, J., Villarroel, L. et al. A risk prediction model for severe intraventricular hemorrhage in very low birth weight infants and the effect of prophylactic indomethacin. J Perinatol 34, 43–48 (2014). https://doi.org/10.1038/jp.2013.127

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2013.127

Keywords

This article is cited by

Search

Advanced search

Quick links