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A predictive clinical model for moderate to severe intraventricular hemorrhage in very low birth weight infants

Journal of Perinatology volume 42, pages 1374–1379 (2022)Cite this article

Subjects

Abstract

Importance

Intraventricular hemorrhage (IVH) occurs in 15–45% of all very low birth weight (VLBW) preterm infants. Despite improvements in the perinatal care, the incidence of IVH remains high. As more preterm infants survive, there will be a larger burden of neurodevelopmental abnormalities borne by former preterm infants.

Objective

The objective of this study was to develop a predictive clinical model of IVH risk within the first few hours of life in an effort to augment perinatal counseling and guide the timing of future targeted therapies aimed at preventing or slowing the progression of disease.

Design

This is a prospective observational cohort study of VLBW infants born in the NICU at John’s Hopkins Children’s Center from 2011 to 2019. The presence and severity of IVH was defined on standard head ultrasound screening (HUS) using the modified Papile classification. Clinical variables were identified as significant using absolute risk regression from a general linear model. The model predictors included clinically meaningful variables that were not collinear.

Setting

This study took place at the Johns Hopkins Children’s Center Level IV NICU.

Participants

The study sample included VLBW infants treated in the neonatal intensive care unit (NICU) at John’s Hopkins Children’s Center from 2011 to 2019. A total of 683 infants included in the study had no or grade I IVH, and 115 infants had grades II through IV IVH. Exclusion criteria included admission to the JHH NICU after 24 h of age, BW > 1500 g, and failure to consent.

Main Outcome

The main outcome of this study was the presence of grades II-IV IVH on standard head ultrasound screening using the modified Papile classification [1].

Results

A total of 798 VLBW infants were studied in this cohort and 14.4% had moderate to severe IVH. Fifty four percent of the cohort was black, 33% white, and half of the cohort was male. A higher gestational age, 5-min Apgar score, hematocrit, and platelet count were significantly associated with decreased incidence of IVH in a multi-predictor model (ROC 0.826).

Conclusion and relevance

In the face of continued lack of treatments for IVH, prevention is still a primary goal to avoid long-term developmental sequela. This model can be used for perinatal counseling and may provide important information during the narrow therapeutic window for targeted prevention therapies.

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Fig. 1: ROC curves comparing the Lee model to the new proposed model [33, 34].

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Data availability

Request for data sharing should be submitted to the corresponding author for consideration.

References

  1. Volpe J. Volpe’s neurology of the newborn, 6th ed. Elsevier; Volpe’s neurology of the newborn; 2018.

  2. Pfahl S, Hoehn T, Lohmeier K, Richter-Werkle R, Babor F, Schramm D, et al. Long-term neurodevelopmental outcome following low grade intraventricular hemorrhage in premature infants. Early Hum Dev. 2018;117:62–67.

    Article  Google Scholar 

  3. Glass HC, Costarino AT, Stayer SA, Brett CM, Cladis F, Davis PJ. Outcomes for extremely premature infants. Anesth Analg. 2015;120:1337–51.

    Article  Google Scholar 

  4. Kobaly K, Schluchter M, Minich N, Friedman H, Taylor HG, Wilson-Costello D, et al. Outcomes of extremely low birth weight (<1 kg) and extremely low gestational age (<28 weeks) infants with bronchopulmonary dysplasia: effects of practice changes in 2000 to 2003. Pediatrics. 2008;121:73–81.

    Article  Google Scholar 

  5. Schmidhauser J, Caflisch J, Rousson V, Bucher HU, Largo RH, Latal B. Impaired motor performance and movement quality in very-low-birthweight children at 6 years of age. Dev Med Child Neurol. 2006;48:718–22.

    Article  Google Scholar 

  6. Mukerji A, Shah V, Shah PS. Periventricular/Intraventricular hemorrhage and neurodevelopmental outcomes: a meta-analysis. Pediatrics. 2015;136:1132–43.

    Article  Google Scholar 

  7. Kiechl-Kohlendorfer U, Ralser E, Pupp Peglow U, Pehboeck-Walser N, Fussenegger B. Early risk predictors for impaired numerical skills in 5-year-old children born before 32 weeks of gestation. Acta Paediatr. 2013;102:66–71.

    Article  Google Scholar 

  8. van de Bor M, den Ouden L. School performance in adolescents with and without periventricular-intraventricular hemorrhage in the neonatal period. Semin Perinatol. 2004;28:295–303.

    Article  Google Scholar 

  9. Radic JAE, Vincer M, McNeely PD. Outcomes of intraventricular hemorrhage and posthemorrhagic hydrocephalus in a population-based cohort of very preterm infants born to residents of Nova Scotia from 1993 to 2010. J Neurosurg Pediatr. 2015;15:580–8.

  10. Bassan H. Neurodevelopmental outcome in survivors of periventricular hemorrhagic infarction. Pediatrics. 2007;10:785–92.

  11. Mirza H, Oh W, Laptook A, Vohr B, Tucker R, Stonestreet BS. Indomethacin prophylaxis to prevent intraventricular hemorrhage: association between incidence and timing of drug administration. J Pediatr. 2013;163:706–.e701.

    Article  CAS  Google Scholar 

  12. Ment LR, Oh W, Ehrenkranz RA, Philip AG, Schneider K, Katz KH, et al. Risk period for intraventricular hemorrhage of the preterm neonate is independent of gestational age. Semin Perinatol. 1993;17:338–41.

    CAS  PubMed  Google Scholar 

  13. Al-Abdi SY, Al-Aamri MA. A Systematic Review and Meta-analysis of the Timing of Early Intraventricular Hemorrhage in Preterm Neonates: Clinical and Research Implications. J Clin Neonatol. 2014;3:76–88.

    Article  Google Scholar 

  14. Hand IL, Shellhaas RA, Milla SS. Routine neuroimaging of the preterm brain. Pediatrics. 2020;146:e202002908.

  15. Robinson S, Conteh FS, Oppong AY, Yellowhair TR, Newville JC, El Demerdash N, et al. Extended combined neonatal treatment with erythropoietin plus melatonin prevents posthemorrhagic hydrocephalus of prematurity in rats. Front Cell Neurosci. 2018;12:322.

  16. Gram M, Ekstrom C, Holmqvist B, Carey G, Wang X, Vallius S, et al. Insulin-like growth factor 1 in the preterm rabbit pup: characterization of cerebrovascular maturation following administration of recombinant human insulin-like growth factor 1/insulin-like growth factor 1-binding protein 3. Dev Neurosci. 2021;43:281–95.

  17. Koschnitzky JE, Keep RF, Limbrick DD, McAllister JP, Morris JA, Strahle J, et al. Opportunities in posthemorrhagic hydrocephalus research: outcomes of the Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop. Fluids Barriers CNS. 2018;15:11.

    Article  Google Scholar 

  18. Kaur A, Luu T, Shah P, Ayoub A, Auger N. Neonatal intraventricular hemorrhage and hospitalization in childhood. Pediatr Neurol. 2020;103:35–42.

  19. Han R, McKinnon A, CreveCoeur T, Bash B, Mathur A, Smyser C, et al. Predictors of mortality for preterm infants with intraventricular hemorrhage: a population based study. Child’s Nerv Syst. 2018;34:2203–13.

  20. Pedroza C, Troung VT. Performance of models for estimating absolute risk difference in multicenter trials with binary outcome. BMC Med Res Methodol. 2016;16:113.

  21. Lee J, Hong M, Yum SK, Lee JH. Perinatal prediction model for severe intraventricular hemorrhage and the effect of early postnatal acidosis. Childs Nerv Syst. 2018;34:2215–22.

    Article  Google Scholar 

  22. Andrikopoulou M, Almalki A, Farzin A, Cordeiro CN, Johnston MV, Burd I. Perinatal biomarkers in prematurity: early identification of neurologic injury. Int J Dev Neurosci. 2014;36:25–31.

    Article  CAS  Google Scholar 

  23. Ballabh P. Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res. 2010;67:1–8.

    Article  Google Scholar 

  24. Robinson S. Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts. J Neurosurg Pediatr. 2012. https://doi.org/10.3171/2011.12.PEDS11136

  25. He L, Zhou W, Zhao X, Liu X, Rong X, Song Y. Development and validation of a novel scoring system to predict severe intraventricular hemorrhage in very low birth weight infants. Brain Dev. 2019;41:671–7.

    Article  Google Scholar 

  26. Poryo M, Boeckh JC, Gortner L, Zemlin M, Duppré P, Ebrahimi-Fakhari D, et al. Ante-, peri- and postnatal factors associated with intraventricular hemorrhage in very premature infants. Early Hum Dev. 2018;116:1–8.

    Article  Google Scholar 

  27. Singh R, Gorstein SV, Bednarek F, Chou JH, McGowan EC, Visintainer PF. A predictive model for SIVH risk in preterm infants and targeted indomethacin therapy for prevention. Sci Rep. 2013;3:2539.

    Article  Google Scholar 

  28. Luque MJ, Tapia JL, Villarroel L, Marshall G, Musante G, Carlo W, et al. A risk prediction model for severe intraventricular hemorrhage in very low birth weight infants and the effect of prophylactic indomethacin. J Perinatol. 2014;34:43–48.

    Article  CAS  Google Scholar 

  29. Dekom S, Vachhani A, Patel K, Barton L, Ramanathan R, Noori S. Initial hematocrit values after birth and peri/intraventricular hemorrhage in extremely low birth weight infants. J Perinatol. 2018;38:1471–5.

    Article  Google Scholar 

  30. Grevsen AK, Hviid CVB, Hansen AK, Hvas AM. The role of platelets in premature neonates with intraventricular hemorrhage: a systematic review and meta-analysis. Semin Thromb Hemost. 2020;46:366–78.

    Article  Google Scholar 

  31. Dormann C, Elith J, Buchmann C, Gudrun C, Carre G, Garcia Marquez JR, et al. Collinearity: a review of methods to deal with it and a simulation study evaluating their performance. Ecography. 2013;36:027–46.

  32. Curley A, Stanworth S, Phil D, Willoughby K, Fustolo-Gunnik F, Venkatesh V, et al. Randomized trial of platelet-transfusion thresholds in neonates. N Engl J Med. 2019;380:242–51.

  33. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics; 1988;44:837–45.

  34. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36.

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Acknowledgements

This work is dedicated to Phoebe Marie Teng, Eli Joseph Teng, and Caleb Edward Teng who passed from IVH.

Funding

Grant funding for this project-(R01HD086058) (ADE, EMG, FJN, DV).

Author information

Author notes

  1. These authors contributed equally: Dhananjay Vaidya, Frances J. Northington.

Authors and Affiliations

  1. Division of Neonatal-Perinatal Medicine, Northwestern University, Chicago, IL, USA

    Rachel M. Weinstein

  2. Division of Pediatrics, Johns Hopkins University, Baltimore, MD, USA

    Rachel M. Weinstein

  3. Division of Neonatal-Perinatal Medicine, Johns Hopkins University, Baltimore, MD, USA

    Charlamaine Parkinson & Frances J. Northington

  4. Blalock-Taussig-Thomas Congenital Heart Center, Johns Hopkins University, Baltimore, MD, USA

    Allen D. Everett

  5. Department of Obstetrics and Gynecology, Johns Hopkins Hospital, Baltimore, MD, USA

    Ernest M. Graham

  6. Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA

    Dhananjay Vaidya

Authors
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  4. Ernest M. Graham
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Contributions

FJN had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. RMW and FJN developed the study design, assisted with the data analysis, and interpreted the data. RMW created the tables and wrote the manuscript with support from FJN, EMG, ADE, and DV. CP assisted with data collection and ensured accuracy of the data. DV performed the data analysis and revised the manuscript.

Corresponding author

Correspondence to Frances J. Northington.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study was approved by Johns Hopkins University IRB. Information was collected under IRB 00026068 for the duration of the study. In 2018, the IRB began requiring consent from parent/guardian for inclusion in the study, and consent in both English and Spanish were obtained forthwith.

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Weinstein, R.M., Parkinson, C., Everett, A.D. et al. A predictive clinical model for moderate to severe intraventricular hemorrhage in very low birth weight infants. J Perinatol 42, 1374–1379 (2022). https://doi.org/10.1038/s41372-022-01435-0

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