title: Early Caffeine Use in Very Low Birth Weight Infants and Neonatal Outcomes: A Systematic Review and Meta-Analysis.
abstract: The use of caffeine citrate for treatment of apnea in very low birth weight infants showed short-term and long-term benefits. A systematic review and meta-analysis of the literature was undertaken to document the effect providing caffeine early (0-2 days of life) compared to providing caffeine late (≥3 days of life) in very low birth weight infants on several neonatal outcomes, including bronchopulmonary dysplasia (BPD). We searched MEDLINE, the EMBASE database, the Cochrane Library, and KoreaMed for this meta-analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale and Jadad's scale. Studies were included if they examined the effect of the early use of caffeine compared with the late use of caffeine. Two reviewers screened the candidate articles and extracted the data from the full-text of all of the included studies. We included a total of 59,136 participants (range 58,997-59,136; variable in one study) from a total of 5 studies. The risk of death (odds ratio [OR], 0.902; 95% confidence interval [CI], 0.828 to 0.983; P=0.019), bronchopulmonary dysplasia (BPD) (OR, 0.507; 95% CI, 0.396 to 0.648; P<0.001), and BPD or death (OR, 0.526; 95% CI, 0.384 to 0.719; P<0.001) were lower in the early caffeine group. Early caffeine use was not associated with a risk of necrotizing enterocolitis (NEC) and NEC requiring surgery. This meta-analysis suggests that early caffeine use has beneficial effects on neonatal outcomes, including mortality and BPD, without increasing the risk of NEC.
authors.affiliation: Department of Pediatrics, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Hye Won
authors.identifier: 0000-0002-2669-3621
authors.initials: HW
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Gina
authors.identifier: 0000-0001-8996-2713
authors.initials: G
authors.lastname: Lim
authors.affiliation: Department of Pediatrics, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Sung-Hoon
authors.identifier: 0000-0002-0352-9722
authors.initials: SH
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Sochung
authors.identifier: 0000-0002-7655-2691
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Kyo Sun
authors.identifier: 0000-0001-9322-6508
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Soo-Nyung
authors.identifier: 0000-0003-4319-336X
authors.initials: SN
authors.lastname: Kim
mesh_terms: D001049:Apnea / Q000188:drug therapy*; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy; D002110:Caffeine / Q000008:administration & dosage* / Q000009:adverse effects; D002951:Citrates / Q000008:administration & dosage* / Q000009:adverse effects; D020345:Enterocolitis, Necrotizing / Q000209:etiology; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D002951:Citrates; D002110:Caffeine; C026189:caffeine citrate
keywords: Bronchopulmonary Dysplasia; Caffeine; Infant, Newborn; Outcome; Very Low Birth Weight