Inotrope Use and the Risk of Intraventricular Hemorrhage in Preterm Neonates: A Systematic Review and Meta Analysis

Anggita Dian Karera; Delta Iswara; Amanah Sekar Kinasih; Dyah Ati Sayuka; Din Alfina

doi:10.55227/ijhet.v4i4.458

Authors

Anggita Dian Karera An Ni’mah General Hospital
Delta Iswara An Ni’mah General Hospital, Wangon, Central Java, Indonesia
Amanah Sekar Kinasih An Ni’mah General Hospital, Wangon, Central Java, Indonesia
Dyah Ati Sayuka Faculty of Medicine, Diponegoro University, Semarang, Central Java, Indonesia
Din Alfina An Ni’mah General Hospital, Wangon, Central Java, Indonesia

DOI:

https://doi.org/10.55227/ijhet.v4i4.458

Keywords:

inotropes, preterm neonates, intraventricular hemorrhage, risk factors

Abstract

More than 40% of neonatal hypotension cases are managed with inotropes; however, recent evidence indicates that inotrope administration, rather than hypotension itself, is independently associated with an increased risk of intraventricular hemorrhage (IVH) after adjustment for confounding factors. This systematic review and meta-analysis aimed to evaluate the association between inotrope use and the occurrence of IVH among preterm neonates. The study followed PRISMA guidelines. A systematic literature search was conducted through PubMed, Scopus, ScienceDirect, and Google Scholar. The methodological quality of each study was assessed using the Newcastle-Ottawa Scale (NOS) for case-control and cohort designs. Relevant data were extracted for qualitative and quantitative synthesis. Meta-analysis was performed using a random-effects model based on adjusted odds ratios (aORs) reported in each study, and the results were presented as pooled aORs with 95% confidence intervals. Eight studies met the inclusion criteria. The meta-analysis showed that inotrope use was significantly associated with a higher risk of IVH in preterm neonates, including IVH of any grade (pooled OR 2.03, 95% CI 1.25-3.29) and severe IVH (pooled OR 2.00, 95% CI 1.33-3.02). Overall, inotrope use doubled the risk of IVH (pooled OR 2.00, 95% CI 1.48-2.70). These findings emphasize the need for cautious and strictly indicated inotrope administration along with standardized hemodynamic management.

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References

Al-Aweel, I., Pursley, D.M., Rubin, L.P., Shah, B., Weisberger, S., & Richardson, D.K. (2001). Variations In Prevalence Of Hypotension, Hypertension, And Vasopressor Use In NICUs. Journal of Perinatology. 21(5): 272-278.

Al-Mouqdad, M.M., Abdelrahim, A., Abdalgader, A.T., Alyaseen, N., Khalil, T.M., Taha, M.Y., et al. (2021). Risk Factors For Intraventricular Hemorrhage In Premature Infants In The Central Region Of Saudi Arabia. Int J Pediatr Adolesc Med. 8(2): 76-81.

Alotaibi, W.S.M., Alsaif, N.S., Ahmed, I.A., Mahmoud, A.F., Ali, K., Hammad, A., et al. (2020). Reduction Of Severe Intraventricular Hemorrhage, A Tertiary Single-Center Experience: Incidence Trends, Associated Risk Factors, And Hospital Policy. Child’s Nervous System. 36(12): 2971-2979.

Akuamoah-Boateng, G., Moon, T.D., Amorim, G., Bandini, R., & Ballot, D. (2025). Intraventricular Hemorrhage Among Very Low Birth Weight Infants In A South African Cohort: A Retrospective Study Of Trends And Short-Term Outcomes. BMC Pediatr. 25(1): 138.

Batton, B., Li, L., Newman, N.S., Eunice Kennedy Shriver National Institute Of Child Health And Human Development Research Network. (2013). Use Of Antihypotensive Therapies In Extremely Preterm Infants. Pediatrics. 131(6): e1865-e1873.

Bouyssi-Kobar, M., Murnick, J., Brossard-Racine, M., et al. (2018). Altered Cerebral Perfusion In Infants Born Preterm Compared With Infants Born Full Term. Journal of Pediatrics. 193: 54-61.e2.

De Backer, D., Aldecoa, C., Njimi, H., & Vincent, J.L. (2012). Dopamine Versus Norepinephrine In The Treatment Of Septic Shock: A Meta-Analysis. Crit Care Med. 40: 725-730.

Garvey, A.A., Kooi, E.M.W., & Dempsey, E.M. (2018). Inotropes For Preterm Infants: 50 Years On Are We Any Wiser. Front Pediatr. 6: 88.

Golder, V., Hepponstall, M., Yiallourou, S.R., Odoi, A., & Horne, R.S. (2013). Autonomic Cardiovascular Control In Hypotensive Critically Ill Preterm Infants Is Impaired During The First Days Of Life. Early Hum Dev. 89(6): 419-423.

Hedia, S.M., Hamza, M.B., Elsharkawy, H.M., Badawy, M.E., & Elashry, S.M. (2025). Evaluation Of Inotrope Use As A Risk Factor In Occurrence Of Intraventricular Hemorrhage In Preterm Neonates. Egypt J Hosp Med. 98: 977-984.

Kuint, J., Barak, M., Morag, I., et al. (2009). Early Treated Hypotension And Outcome In Very Low Birth Weight Infants. Neonatology. 95(4): 311-316.

Lai, G.Y., Shlobin, N., & Garcia, R.M. (2022). Global Incidence Proportion Of Intraventricular Haemorrhage Of Prematurity: A Meta-Analysis Of Studies Published 2010-2020. Arch Dis Child Fetal Neonatal Ed. 107(5): 513-519.

Noori, S., McCoy, M., Anderson, M.P., Ramji, F., & Seri, I. (2014). Changes In Cardiac Function And Cerebral Blood Flow In Relation To Peri/Intraventricular Hemorrhage In Extremely Preterm Infants. J Pediatr. 164: 264-270.e3.

Rees, P., Gale, C., Battersby, C., Williams, C., Carter, B., & Sutcliffe, A. (2025). Intraventricular Hemorrhage And Survival, Multimorbidity, And Neurodevelopment. JAMA Netw Open. 8(1): e2452883-e2452883.

St. Peter, D., Gandy, C., & Hoffman, S.B. (2017). Hypotension And Adverse Outcomes In Prematurity: Comparing Definitions. Neonatology. 111(3): 228-233.

Tsao, P.C. (2023). Pathogenesis And Prevention Of Intraventricular Hemorrhage In Preterm Infants. J Korean Neurosurg Soc. 66(3): 228-238.

Ventura, A.M., Shieh, H.H., Bousso, A., Goes, P.F., Fernandes, I.F.O., de Souza, D.C., et al. (2015). Double-Blind Prospective Randomized Controlled Trial Of Dopamine Versus Epinephrine As First-Line Vasoactive Drugs In Pediatric Septic Shock. Crit Care Med. 43: 2292-2302.

Verma, R.P., Dasnadi, S., Zhao, Y., & Chen, H.H. (2019). Complications Associated With The Current Sequential Pharmacological Management Of Early Postnatal Hypotension In Extremely Premature Infants. Baylor University Medical Center Proceedings. 32(3): 355-360.

Vesoulis, Z.A., Flower, A.A., Zanelli, S., Rambhia, A., Abubakar, M., Whitehead, H.V., et al. (2020). Blood Pressure Extremes And Severe IVH In Preterm Infants. Pediatr Res. 87(1): 69-73.

Wong, J., Shah, P.S., & Yoon, E.W. (2015). Inotrope Use Among Extremely Preterm Infants In Canadian Neonatal Intensive Care Units: Variation And Outcomes. Am J Perinatol. 32(1): 9-14.

Xiao, T., Hu, L., Chen, H., Gu, X., Zhou, J., Zhu, Y., et al. (2024). The Performance Of The Practices Associated With The Occurrence Of Severe Intraventricular Hemorrhage In The Very Premature Infants: Data Analysis From The Chinese Neonatal Network. BMC Pediatr. 24(1): 394.

Zhou, M., Wang, S., Zhang, T., Duan, S., & Wang, H. (2024). Neurodevelopmental Outcomes In Preterm Or Low Birth Weight Infants With Germinal Matrix Intraventricular Hemorrhage: A Meta-Analysis. Pediatr Res. 95(3): 625-633.