Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective study

Abstract Background Caffeine is a routinely prescribed pharmacological active compound in neonatal intensive care units (NICU) for treating apnea of prematurity (AOP), which also decreases the risk of bronchopulmonary dysplasia and cerebral palsy in neonates. Caffeine-induced excessive calcium loss...

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Main Authors: Manoj Kumar, Amin Ali, Muhammad Azeem Khan, Sadia Sohail, Syed Muzafar Saleem, Midhat Khan, Fizzah Naz, Wasif Ahmed Khan, Muhammad Sohail Salat, Kashif Hussain, Gul Ambreen
Format: Article
Language:English
Published: BMC 2022-07-01
Series:BMC Pediatrics
Subjects:
Online Access:https://doi.org/10.1186/s12887-022-03493-x
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author Manoj Kumar
Amin Ali
Muhammad Azeem Khan
Sadia Sohail
Syed Muzafar Saleem
Midhat Khan
Fizzah Naz
Wasif Ahmed Khan
Muhammad Sohail Salat
Kashif Hussain
Gul Ambreen
author_facet Manoj Kumar
Amin Ali
Muhammad Azeem Khan
Sadia Sohail
Syed Muzafar Saleem
Midhat Khan
Fizzah Naz
Wasif Ahmed Khan
Muhammad Sohail Salat
Kashif Hussain
Gul Ambreen
author_sort Manoj Kumar
collection DOAJ
description Abstract Background Caffeine is a routinely prescribed pharmacological active compound in neonatal intensive care units (NICU) for treating apnea of prematurity (AOP), which also decreases the risk of bronchopulmonary dysplasia and cerebral palsy in neonates. Caffeine-induced excessive calcium loss can promote the development of metabolic bone disease (MBD) in preterm neonates. This study aimed to evaluate the effect of the caffeine regimen on the development of osteopenia of prematurity (OOP), using serum alkaline phosphatase (serum-ALP) concentrations as a surrogate marker at the 4th week of life. Methods This retrospective cohort study was conducted including neonates of < 32 weeks gestational age (GA) and birth weight < 1500 g, admitted to NICU from April-2017 to December-2018 and received caffeine therapy till 28 days of life for AOP. Based on serum-ALP levels, formed the high and low-ALP groups. Neonatal characteristics, caffeine regimen, risk factors for OOP, including duration of parenteral nutrition (PN), exposure to medicines associated with MBD, and intake of essential vitamins and minerals, were compared in both groups. Predictors of OOP were analyzed through logistic regression. Results From the total of 268 participants, 52 (19%) developed OOP, mostly female (61.5%). In the high ALP group, the serum-ALP levels were significantly higher than in the low-ALP group (725.0 ± 143.8 vs 273.6 ± 55.0 units/L, p < 0.001). The high-ALP group received significantly (p < 0.001) higher daily and cumulative caffeine doses and were associated with a higher likelihood of developing OOP in this study cohort [cumulative dose (mg) (AOR = 1.082 95% CI 1.011 to 1.157) and daily dose (mg/kg/day) (AOR = 2.892 95% CI 1.392 to 6.007)]. Smaller GA was found directly related to OOP. Among the other medical risk factors, phosphorus intake was significantly low in the high-ALP group. No, significant relationship between duration of PN and use of steroids and diuretics, and intake of vitamins and minerals were identified. Conclusion The daily and cumulative doses of caffeine and smaller GA are associated with the development of OOP in this study cohort. Clinical randomized control studies are needed to validate the outcomes and determine the range of safest and most effective caffeine doses for treating AOP in preterm neonates.
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spelling doaj.art-3ed4821964d8419e9548d5907fd9b1642022-12-22T03:04:47ZengBMCBMC Pediatrics1471-24312022-07-0122111010.1186/s12887-022-03493-xRelationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective studyManoj Kumar0Amin Ali1Muhammad Azeem Khan2Sadia Sohail3Syed Muzafar Saleem4Midhat Khan5Fizzah Naz6Wasif Ahmed Khan7Muhammad Sohail Salat8Kashif Hussain9Gul Ambreen10Department of Paediatrics & Child Health, Aga Khan UniversityDepartment of Neonatology & Paediatrics, Dow University of Health SciencesDepartment of Neonatology & Paediatrics, Medicare HospitalDepartment of Paediatrics, Fatimiyah Hospital PaediatricsDepartment of Paediatrics & Child Health, Aga Khan UniversityDepartment of Paediatrics & Child Health, Aga Khan UniversityDepartment of Paediatrics & Child Health, Aga Khan UniversityDepartment of Paediatrics & Child Health, Aga Khan UniversityDepartment of Paediatrics & Child Health, Aga Khan UniversityDepartment of Pharmacy, Aga Khan University HospitalDepartment of Pharmacy, Aga Khan University HospitalAbstract Background Caffeine is a routinely prescribed pharmacological active compound in neonatal intensive care units (NICU) for treating apnea of prematurity (AOP), which also decreases the risk of bronchopulmonary dysplasia and cerebral palsy in neonates. Caffeine-induced excessive calcium loss can promote the development of metabolic bone disease (MBD) in preterm neonates. This study aimed to evaluate the effect of the caffeine regimen on the development of osteopenia of prematurity (OOP), using serum alkaline phosphatase (serum-ALP) concentrations as a surrogate marker at the 4th week of life. Methods This retrospective cohort study was conducted including neonates of < 32 weeks gestational age (GA) and birth weight < 1500 g, admitted to NICU from April-2017 to December-2018 and received caffeine therapy till 28 days of life for AOP. Based on serum-ALP levels, formed the high and low-ALP groups. Neonatal characteristics, caffeine regimen, risk factors for OOP, including duration of parenteral nutrition (PN), exposure to medicines associated with MBD, and intake of essential vitamins and minerals, were compared in both groups. Predictors of OOP were analyzed through logistic regression. Results From the total of 268 participants, 52 (19%) developed OOP, mostly female (61.5%). In the high ALP group, the serum-ALP levels were significantly higher than in the low-ALP group (725.0 ± 143.8 vs 273.6 ± 55.0 units/L, p < 0.001). The high-ALP group received significantly (p < 0.001) higher daily and cumulative caffeine doses and were associated with a higher likelihood of developing OOP in this study cohort [cumulative dose (mg) (AOR = 1.082 95% CI 1.011 to 1.157) and daily dose (mg/kg/day) (AOR = 2.892 95% CI 1.392 to 6.007)]. Smaller GA was found directly related to OOP. Among the other medical risk factors, phosphorus intake was significantly low in the high-ALP group. No, significant relationship between duration of PN and use of steroids and diuretics, and intake of vitamins and minerals were identified. Conclusion The daily and cumulative doses of caffeine and smaller GA are associated with the development of OOP in this study cohort. Clinical randomized control studies are needed to validate the outcomes and determine the range of safest and most effective caffeine doses for treating AOP in preterm neonates.https://doi.org/10.1186/s12887-022-03493-xCaffeineApnea of prematurityMetabolic bone diseaseOsteopenia of prematurityPreterm neonatesNICU
spellingShingle Manoj Kumar
Amin Ali
Muhammad Azeem Khan
Sadia Sohail
Syed Muzafar Saleem
Midhat Khan
Fizzah Naz
Wasif Ahmed Khan
Muhammad Sohail Salat
Kashif Hussain
Gul Ambreen
Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective study
BMC Pediatrics
Caffeine
Apnea of prematurity
Metabolic bone disease
Osteopenia of prematurity
Preterm neonates
NICU
title Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective study
title_full Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective study
title_fullStr Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective study
title_full_unstemmed Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective study
title_short Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective study
title_sort relationship of caffeine regimen with osteopenia of prematurity in preterm neonates a cohort retrospective study
topic Caffeine
Apnea of prematurity
Metabolic bone disease
Osteopenia of prematurity
Preterm neonates
NICU
url https://doi.org/10.1186/s12887-022-03493-x
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