Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury

Mosarrat Qureshi; Prakesh S. Shah; Dalal Abdelgadir; Xiang Y. Ye; Jehier Afifi; Ryan Yuen; Sara Calderon Crossman; Barbara Taylor; Khorshid Mohammad; Bruno Piedboeuf; Khalid Aziz; Marc Beltempo; Jaideep Kanungo; Joseph Ting; Zenon Cieslak; Rebecca Sherlock; Ayman Abou Mehrem; Jennifer Toye; Carlos Fajardo; Zarin Kalapesi; Jaya Bodani; Koravangattu Sankaran; Lannae Strueby; Mary Seshia; Deepak Louis; Ruben Alvaro; Amit Mukerji; Orlando Da Silva; Mohammad Adie; Kyong Soon Lee; Eugene Ng; Brigitte Lemyre; Faiza Khurshid; Ermelinda Pelausa; Keith Barrington; Anie Lapoint; Guillaume Ethier; Christine Drolet; Martine Claveau; Valerie Bertelle; Edith Masse; Roderick Canning; Hala Makary; Cecil Ojah; Luis Monterrosa; Julie Emberley; Andrzej Kajetanowicz; Shoo K. Lee

doi:10.1016/j.jpeds.2021.02.073

Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury

Mosarrat Qureshi, Prakesh S. Shah, Dalal Abdelgadir, Xiang Y. Ye, Jehier Afifi, Ryan Yuen, Sara Calderon Crossman, Barbara Taylor, Khorshid Mohammad, Bruno Piedboeuf, Khalid Aziz, Marc Beltempo, Jaideep Kanungo, Joseph Ting, Zenon Cieslak, Rebecca Sherlock, Ayman Abou Mehrem, Jennifer Toye, Carlos Fajardo, Zarin KalapesiJaya Bodani, Koravangattu Sankaran, Lannae Strueby, Mary Seshia, Deepak Louis, Ruben Alvaro, Amit Mukerji, Orlando Da Silva, Mohammad Adie, Kyong Soon Lee, Eugene Ng, Brigitte Lemyre, Faiza Khurshid, Ermelinda Pelausa, Keith Barrington, Anie Lapoint, Guillaume Ethier, Christine Drolet, Martine Claveau, Valerie Bertelle, Edith Masse, Roderick Canning, Hala Makary, Cecil Ojah, Luis Monterrosa, Julie Emberley, Andrzej Kajetanowicz, Shoo K. Lee

Medicine

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

Objective: To evaluate the impact of prophylactic indomethacin on early death (<10 days after birth) or severe neurologic injury and on early death or spontaneous intestinal perforation by completed weeks of gestational age in neonates born <29 weeks of gestation. Study design: This was a multicenter, retrospective cohort study of neonates (n = 12 515) born at 23^6/7 weeks of gestational age, admitted to neonatal intensive care units participating in the Canadian Neonatal Network who received prophylactic indomethacin started within the first 12 hours after birth. Univariate and multivariate analysis compared the composite outcomes of early death or severe neurologic injury and early death or spontaneous intestinal perforation. Results: Of 12 515 eligible neonates, 1435 (11.5%) were exposed to prophylactic indomethacin; recipients were of lower gestational age and birth weight and had greater severity of illness (Score of Neonatal Acute Physiology with Perinatal Extension) on admission compared with nonrecipients. After we adjusted for confounders, prophylactic indomethacin was associated with reduced odds of early death or severe neurologic injury and early death or spontaneous intestinal perforation in neonates born at 23-24 weeks of gestational age. However, prophylactic indomethacin was associated with increased odds of early mortality or spontaneous intestinal perforation for neonates born at 26-28 weeks of gestational age. Conclusions: Prophylactic indomethacin use was associated with benefit in neonates born at 23-24 weeks of gestational age, but with harm at 26-28 weeks of gestational age. Given the observation of significantly improved survival, a randomized controlled trial is needed to investigate the effect of prophylactic indomethacin in babies born at 23-25 weeks of gestational age.

Original language	English
Pages (from-to)	26-33.e2
Journal	Journal of Pediatrics
Volume	235
DOIs	https://doi.org/10.1016/j.jpeds.2021.02.073
Publication status	Published - Aug 2021

Bibliographical note

Funding Information:
Supported by the Canadian Neonatal Network was provided by the Maternal-infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by the Canadian Institutes of Health Research (CIHR) (CTP 87518), the Ontario Ministry of Health and Long-Term Care, and the participating hospitals. P.S. holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research from the CIHR (APR-126340). The funding agencies had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The authors declare no conflicts of interest.

Funding Information:
Supported by the Canadian Neonatal Network was provided by the Maternal-infant Care Research Centre ( MiCare ) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by the Canadian Institutes of Health Research (CIHR) (CTP 87518), the Ontario Ministry of Health and Long-Term Care, and the participating hospitals. P.S. holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research from the CIHR (APR-126340). The funding agencies had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The authors declare no conflicts of interest.

Publisher Copyright:
© 2021 Elsevier Inc.

ASJC Scopus Subject Areas

Pediatrics, Perinatology, and Child Health

PubMed: MeSH publication types

Journal Article
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Qureshi, M., Shah, P. S., Abdelgadir, D., Ye, X. Y., Afifi, J., Yuen, R., Crossman, S. C., Taylor, B., Mohammad, K., Piedboeuf, B., Aziz, K., Beltempo, M., Kanungo, J., Ting, J., Cieslak, Z., Sherlock, R., Mehrem, A. A., Toye, J., Fajardo, C., ... Lee, S. K. (2021). Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury. Journal of Pediatrics, 235, 26-33.e2. https://doi.org/10.1016/j.jpeds.2021.02.073

Qureshi, M, Shah, PS, Abdelgadir, D, Ye, XY, Afifi, J, Yuen, R, Crossman, SC, Taylor, B, Mohammad, K, Piedboeuf, B, Aziz, K, Beltempo, M, Kanungo, J, Ting, J, Cieslak, Z, Sherlock, R, Mehrem, AA, Toye, J, Fajardo, C, Kalapesi, Z, Bodani, J, Sankaran, K, Strueby, L, Seshia, M, Louis, D, Alvaro, R, Mukerji, A, Da Silva, O, Adie, M, Lee, KS, Ng, E, Lemyre, B, Khurshid, F, Pelausa, E, Barrington, K, Lapoint, A, Ethier, G, Drolet, C, Claveau, M, Bertelle, V, Masse, E, Canning, R, Makary, H, Ojah, C, Monterrosa, L, Emberley, J, Kajetanowicz, A & Lee, SK 2021, 'Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury', Journal of Pediatrics, vol. 235, pp. 26-33.e2. https://doi.org/10.1016/j.jpeds.2021.02.073

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title = "Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury",

abstract = "Objective: To evaluate the impact of prophylactic indomethacin on early death (<10 days after birth) or severe neurologic injury and on early death or spontaneous intestinal perforation by completed weeks of gestational age in neonates born <29 weeks of gestation. Study design: This was a multicenter, retrospective cohort study of neonates (n = 12 515) born at 236/7 weeks of gestational age, admitted to neonatal intensive care units participating in the Canadian Neonatal Network who received prophylactic indomethacin started within the first 12 hours after birth. Univariate and multivariate analysis compared the composite outcomes of early death or severe neurologic injury and early death or spontaneous intestinal perforation. Results: Of 12 515 eligible neonates, 1435 (11.5%) were exposed to prophylactic indomethacin; recipients were of lower gestational age and birth weight and had greater severity of illness (Score of Neonatal Acute Physiology with Perinatal Extension) on admission compared with nonrecipients. After we adjusted for confounders, prophylactic indomethacin was associated with reduced odds of early death or severe neurologic injury and early death or spontaneous intestinal perforation in neonates born at 23-24 weeks of gestational age. However, prophylactic indomethacin was associated with increased odds of early mortality or spontaneous intestinal perforation for neonates born at 26-28 weeks of gestational age. Conclusions: Prophylactic indomethacin use was associated with benefit in neonates born at 23-24 weeks of gestational age, but with harm at 26-28 weeks of gestational age. Given the observation of significantly improved survival, a randomized controlled trial is needed to investigate the effect of prophylactic indomethacin in babies born at 23-25 weeks of gestational age.",

author = "Mosarrat Qureshi and Shah, {Prakesh S.} and Dalal Abdelgadir and Ye, {Xiang Y.} and Jehier Afifi and Ryan Yuen and Crossman, {Sara Calderon} and Barbara Taylor and Khorshid Mohammad and Bruno Piedboeuf and Khalid Aziz and Marc Beltempo and Jaideep Kanungo and Joseph Ting and Zenon Cieslak and Rebecca Sherlock and Mehrem, {Ayman Abou} and Jennifer Toye and Carlos Fajardo and Zarin Kalapesi and Jaya Bodani and Koravangattu Sankaran and Lannae Strueby and Mary Seshia and Deepak Louis and Ruben Alvaro and Amit Mukerji and {Da Silva}, Orlando and Mohammad Adie and Lee, {Kyong Soon} and Eugene Ng and Brigitte Lemyre and Faiza Khurshid and Ermelinda Pelausa and Keith Barrington and Anie Lapoint and Guillaume Ethier and Christine Drolet and Martine Claveau and Valerie Bertelle and Edith Masse and Roderick Canning and Hala Makary and Cecil Ojah and Luis Monterrosa and Julie Emberley and Andrzej Kajetanowicz and Lee, {Shoo K.}",

note = "Funding Information: Supported by the Canadian Neonatal Network was provided by the Maternal-infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by the Canadian Institutes of Health Research (CIHR) (CTP 87518), the Ontario Ministry of Health and Long-Term Care, and the participating hospitals. P.S. holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research from the CIHR (APR-126340). The funding agencies had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The authors declare no conflicts of interest. Funding Information: Supported by the Canadian Neonatal Network was provided by the Maternal-infant Care Research Centre ( MiCare ) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by the Canadian Institutes of Health Research (CIHR) (CTP 87518), the Ontario Ministry of Health and Long-Term Care, and the participating hospitals. P.S. holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research from the CIHR (APR-126340). The funding agencies had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = aug,

doi = "10.1016/j.jpeds.2021.02.073",

language = "English",

volume = "235",

pages = "26--33.e2",

journal = "Journal of Pediatrics",

issn = "0022-3476",

publisher = "Mosby Inc.",

}

TY - JOUR

T1 - Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury

AU - Qureshi, Mosarrat

AU - Shah, Prakesh S.

AU - Abdelgadir, Dalal

AU - Ye, Xiang Y.

AU - Afifi, Jehier

AU - Yuen, Ryan

AU - Crossman, Sara Calderon

AU - Taylor, Barbara

AU - Mohammad, Khorshid

AU - Piedboeuf, Bruno

AU - Aziz, Khalid

AU - Beltempo, Marc

AU - Kanungo, Jaideep

AU - Ting, Joseph

AU - Cieslak, Zenon

AU - Sherlock, Rebecca

AU - Mehrem, Ayman Abou

AU - Toye, Jennifer

AU - Fajardo, Carlos

AU - Kalapesi, Zarin

AU - Bodani, Jaya

AU - Sankaran, Koravangattu

AU - Strueby, Lannae

AU - Seshia, Mary

AU - Louis, Deepak

AU - Alvaro, Ruben

AU - Mukerji, Amit

AU - Da Silva, Orlando

AU - Adie, Mohammad

AU - Lee, Kyong Soon

AU - Ng, Eugene

AU - Lemyre, Brigitte

AU - Khurshid, Faiza

AU - Pelausa, Ermelinda

AU - Barrington, Keith

AU - Lapoint, Anie

AU - Ethier, Guillaume

AU - Drolet, Christine

AU - Claveau, Martine

AU - Bertelle, Valerie

AU - Masse, Edith

AU - Canning, Roderick

AU - Makary, Hala

AU - Ojah, Cecil

AU - Monterrosa, Luis

AU - Emberley, Julie

AU - Kajetanowicz, Andrzej

AU - Lee, Shoo K.

N1 - Funding Information: Supported by the Canadian Neonatal Network was provided by the Maternal-infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by the Canadian Institutes of Health Research (CIHR) (CTP 87518), the Ontario Ministry of Health and Long-Term Care, and the participating hospitals. P.S. holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research from the CIHR (APR-126340). The funding agencies had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The authors declare no conflicts of interest. Funding Information: Supported by the Canadian Neonatal Network was provided by the Maternal-infant Care Research Centre ( MiCare ) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by the Canadian Institutes of Health Research (CIHR) (CTP 87518), the Ontario Ministry of Health and Long-Term Care, and the participating hospitals. P.S. holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research from the CIHR (APR-126340). The funding agencies had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The authors declare no conflicts of interest. Publisher Copyright: © 2021 Elsevier Inc.

PY - 2021/8

Y1 - 2021/8

N2 - Objective: To evaluate the impact of prophylactic indomethacin on early death (<10 days after birth) or severe neurologic injury and on early death or spontaneous intestinal perforation by completed weeks of gestational age in neonates born <29 weeks of gestation. Study design: This was a multicenter, retrospective cohort study of neonates (n = 12 515) born at 236/7 weeks of gestational age, admitted to neonatal intensive care units participating in the Canadian Neonatal Network who received prophylactic indomethacin started within the first 12 hours after birth. Univariate and multivariate analysis compared the composite outcomes of early death or severe neurologic injury and early death or spontaneous intestinal perforation. Results: Of 12 515 eligible neonates, 1435 (11.5%) were exposed to prophylactic indomethacin; recipients were of lower gestational age and birth weight and had greater severity of illness (Score of Neonatal Acute Physiology with Perinatal Extension) on admission compared with nonrecipients. After we adjusted for confounders, prophylactic indomethacin was associated with reduced odds of early death or severe neurologic injury and early death or spontaneous intestinal perforation in neonates born at 23-24 weeks of gestational age. However, prophylactic indomethacin was associated with increased odds of early mortality or spontaneous intestinal perforation for neonates born at 26-28 weeks of gestational age. Conclusions: Prophylactic indomethacin use was associated with benefit in neonates born at 23-24 weeks of gestational age, but with harm at 26-28 weeks of gestational age. Given the observation of significantly improved survival, a randomized controlled trial is needed to investigate the effect of prophylactic indomethacin in babies born at 23-25 weeks of gestational age.

AB - Objective: To evaluate the impact of prophylactic indomethacin on early death (<10 days after birth) or severe neurologic injury and on early death or spontaneous intestinal perforation by completed weeks of gestational age in neonates born <29 weeks of gestation. Study design: This was a multicenter, retrospective cohort study of neonates (n = 12 515) born at 236/7 weeks of gestational age, admitted to neonatal intensive care units participating in the Canadian Neonatal Network who received prophylactic indomethacin started within the first 12 hours after birth. Univariate and multivariate analysis compared the composite outcomes of early death or severe neurologic injury and early death or spontaneous intestinal perforation. Results: Of 12 515 eligible neonates, 1435 (11.5%) were exposed to prophylactic indomethacin; recipients were of lower gestational age and birth weight and had greater severity of illness (Score of Neonatal Acute Physiology with Perinatal Extension) on admission compared with nonrecipients. After we adjusted for confounders, prophylactic indomethacin was associated with reduced odds of early death or severe neurologic injury and early death or spontaneous intestinal perforation in neonates born at 23-24 weeks of gestational age. However, prophylactic indomethacin was associated with increased odds of early mortality or spontaneous intestinal perforation for neonates born at 26-28 weeks of gestational age. Conclusions: Prophylactic indomethacin use was associated with benefit in neonates born at 23-24 weeks of gestational age, but with harm at 26-28 weeks of gestational age. Given the observation of significantly improved survival, a randomized controlled trial is needed to investigate the effect of prophylactic indomethacin in babies born at 23-25 weeks of gestational age.

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Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury

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