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Caffeine in premature infants

Cynthia M Amaro, Jose A Bello, Deepak Jain, Alexandra Ramnath, Carmen D'Ugard, Silvia Vanbuskirk, Eduardo Bancalari, Nelson Claure
OBJECTIVE: To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. STUDY DESIGN: Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation...
March 6, 2018: Journal of Pediatrics
Molly Potter, Ted Rosenkrantz, R Holly Fitch
The current study investigated behavioral and post mortem neuroanatomical outcomes in Wistar rats with a neonatal hypoxic-ischemic (HI) brain injury induced on postnatal day 6 (P6; Rice-Vannucci HI method; Rice et al., 1981). This preparation models brain injury seen in premature infants (gestational age (GA) 32-35 weeks) based on shared neurodevelopmental markers at time of insult, coupled with similar neuropathologic sequelae (Rice et al., 1981; Workman et al., 2013). Clinically, HI insult during this window is associated with poor outcomes that include attention deficit hyperactivity disorder (ADHD), motor coordination deficits, spatial memory deficits, and language/learning disabilities...
February 21, 2018: International Journal of Developmental Neuroscience
Roos Vliegenthart, Martijn Miedema, Gerard J Hutten, Anton H van Kaam, Wes Onland
BACKGROUND: Placebo-controlled trials have shown that caffeine is highly effective in treating apnoea of prematurity and reduces the risk of bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI). OBJECTIVE: To identify, appraise and summarise studies investigating the modulating effect of different caffeine dosages. METHODS: A systematic review identified all randomised controlled trials (RCTs) comparing a high versus a standard caffeine treatment regimen in infants with a gestational age <32 weeks, by searching the main electronic databases and abstracts of the Pediatric Academic Societies...
February 7, 2018: Archives of Disease in Childhood. Fetal and Neonatal Edition
Fatemeh Faramarzi, Mohammadreza Shiran, Mohammadreza Rafati, Roya Farhadi, Ebrahim Salehifar, Maryam Nakhshab
Background: Caffeine is widely used for prevention of apnea and helps successful extubation from mechanical ventilation. It facilitates the transition from invasive to noninvasive support and reduces duration of continuous positive airway pressure (CPAP) in preterm infants. The optimum caffeine dose in preterm infants has not been well-studied in terms of benefits and risks. We compared efficacy and safety of once versus twice-daily caffeine dose in premature infants. Methods: This study was a randomized clinical trial conducted in Bu-Ali Sina Teaching Hospital, Sari...
2018: Caspian Journal of Internal Medicine
Akane Nagasato, Masatoshi Nakamura, Hidetoshi Kamimura
 Methylxanthine is widely administered for the treatment of apnea of prematurity in many countries, and previous reports have clearly established that caffeine is effective for the treatment of apnea of prematurity. In Japan, caffeine has been available since December 2014. Thus, we compared the efficacy and safety of caffeine with that of aminophylline in our hospital. There was no significant difference between the caffeine group and aminophylline group regarding the characteristics of the study patients...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Ebtihal Ali, Cheryl Rockman-Greenberg, Michael Moffatt, Michael Narvey, Martin Reed, Depeng Jiang
BACKGROUND: Caffeine, the most commonly used medication in Neonatal Intensive Care Units, has calciuric and osteoclastogenic effects. METHODS: To examine the association between the cumulative dose and duration of therapy of caffeine and osteopenia of prematurity, a retrospective cohort study was conducted including premature infants less than 31 weeks and birth weight less than 1500 g. Osteopenia of prematurity was evaluated using chest X-rays on a biweekly basis over 12 weeks of hospitalization...
January 22, 2018: BMC Pediatrics
Samuel J Gentle, Colm P Travers, Waldemar A Carlo
PURPOSE OF REVIEW: Caffeine use in preterm infants has endured several paradigms: from standard of care to possible neurotoxin to one of the few medications for which there is evidence of bronchopulmonary dysplasia (BPD) risk reduction. The purpose of the review is to analyze this dynamic trajectory and discuss controversies that still remain after decades of caffeine use. RECENT FINDINGS: Following concerns for caffeine safety in preterm infants, a large randomized controlled trial demonstrated a reduction in BPD and treatment for patent ductus arteriosus...
April 2018: Current Opinion in Pediatrics
Mehmet Deliktaş, Hacer Ergin, Aydın Demiray, Hakan Akça, Özmert M A Özdemir, Mehmet Bülent Özdemir
OBJECTIVE: Unconjugated bilirubin (UCB) may cause neurotoxicity in preterm neonates due to immaturity of UGT1A1 leading to bilirubin accumulation in the brain. Caffeine used in the treatment of apnea of prematurity was reported to decrease mechanical ventilation requirement, the frequencies of bronchopulmonary dysplasia, patent ductus arteriosus, cerebral palsy and neurodevelopmental disorders in very low birth weight infants. However, the effect of caffeine on hyperbilirubinemia was not yet clarified...
January 2, 2018: Journal of Maternal-fetal & Neonatal Medicine
S Khurana, M Shivakumar, G V Sujith Kumar Reddy, P Jayashree, Y Ramesh Bhat, L E S Lewis
OBJECTIVE: Methylxanthines are the most commonly prescribed drug in neonatal setups. However, Clinicians show indecision in choosing the right agent for Apnea of Prematurity in most of the developing countries. Present study aimed to compare rate of mortality and survival with normal neurodevelopment outcome at 18 to 24 months of corrected age, between Caffeine- and Aminophylline-treated infants for apnea of prematurity. METHODS: 240 infants were randomly allocated to caffeine and aminophylline for apnea of prematurity during February 2012 to January 2015...
2017: Journal of Neonatal-perinatal Medicine
Maria Katarzyna Borszewska-Kornacka, Roman Hożejowski, Magdalena Rutkowska, Ryszard Lauterbach
BACKGROUND: There is growing evidence that supports the benefits of early use of caffeine in preterm neonates with RDS; however, no formal recommendations specifying the exact timing of therapy initiation have been provided. OBJECTIVES: We compared neonatal outcomes in infants receiving early (initial dose on the 1st day of life) and late (initial dose on day 2+ of life) caffeine therapy. METHODS: Using data from a prospective, cohort study, we identified 986 infants ≤32 weeks' gestation with RDS and assessed the timing of caffeine therapy initiation, need for ventilatory support, mortality and incidence of typical complications of prematurity...
2017: PloS One
Christa R Tabacaru, Suk Young Jang, Manisha Patel, Faranek Davalian, Santina Zanelli, Karen D Fairchild
Background: Apnea of prematurity often occurs during and following caffeine therapy. We hypothesized that number of apnea events would be impacted by adjustments in caffeine therapy. Materials and Methods: An automated algorithm was used in all infants ≤32 weeks gestation admitted to a level IV Neonatal Intensive Care Unit from 2009 to 2014 to analyze chest impedance, electrocardiogram, and oxygen saturation data around the time of serum caffeine levels, caffeine boluses while on maintenance therapy, and caffeine discontinuation...
September 1, 2017: Journal of Caffeine Research
K Vongbhavit, M A Underwood
OBJECTIVE: To compare demographic data, prenatal and postnatal characteristics, laboratory data, and outcomes in a cohort of premature infants with spontaneous ileal perforation (SIP), surgical necrotizing enterocolitis (sNEC) and matched controls. METHODS: A retrospective case-control study of infants with intestinal perforation with a birth weight (BW) less than 2,000 grams and gestational age (GA) less than 34 weeks and infants without perforation matched for BW (±150 grams) and GA (±1week)...
2017: Journal of Neonatal-perinatal Medicine
Deepak Jain, Eduardo Bancalari
Bronchopulmonary dysplasia (BPD) is one of the few diseases affecting premature infants that have continued to evolve since its first description about half a century ago. The current form of BPD, a more benign and protracted respiratory failure in extremely preterm infants, is in contrast to the original presentation of severe respiratory failure with high mortality in larger premature infants. This new BPD is end result of complex interplay of various antenatal and postnatal factors causing lung injury and subsequent abnormal repair leading to altered alveolar and vascular development...
August 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Shilpa Vyas-Read, Usama Kanaan, Prabhu Shankar, Jane Stremming, Curtis Travers, David P Carlton, Anne Fitzpatrick
BACKGROUND: Approximately 8-23% of premature infants develop pulmonary hypertension (PH), and this diagnosis confers a higher possibility of mortality. As a result, professional societies recommend PH screening in premature infants. However, the risk factors for and the outcomes of PH may differ depending on the timing of its diagnosis, and little evidence is available to determine at-risk infants in the referral neonatal population. The objective of this study was to define clinical and echocardiographic characteristics of infants with pulmonary hypertension during the neonatal hospital course and at or near-term...
July 11, 2017: BMC Pediatrics
Aleksandra Goryniak, Angelika Szczęśniak, Daria Śleboda, Barbara Dołęgowska
Apnea of prematurity (AOP) can affect even 85-100% of premature newborns and is related to lack of full maturity of organs. AOP is manifesting by 15-20 seconds cessations of breathing accompanied by bradycardia and oxygen desaturation, what can lead to hypoxia or death. Therefore it is very important to implement the effective and safe treatment immediately after birth. Widely used caffeine citrate, which stimulates the respiratory system, improving the working of the respiratory muscles. However the metabolism of caffeine citrate is difficult in preterm infants due to the immaturity of the hepatic enzyme system, what can lead to the occurrence of side effects and toxicity...
2017: Postepy Biochemii
M Shivakumar, P Jayashree, Muhammad Najih, Leslie Edward Simon Lewis, Ramesh Bhat Y, Asha Kamath, - Shashikala
OBJECTIVE: To compare the efficacy and safety of standard doses of Caffeine and Aminophylline for Apnea of prematurity. STUDY DESIGN: Randomized controlled trial. SETTING: Tertiary-care referral centre and a teaching institution in Southern India. Trial was conducted from February 2012 to January 2015. PARTICIPANTS: 240 preterm (≤34 wk) neonates with apnea of prematurity. INTERVENTIONS: Neonates randomized into two groups: Caffeine group received loading dose of caffeine citrate (20 mg/kg) followed by 5 mg/kg/day maintenance dose every 24 hour...
April 15, 2017: Indian Pediatrics
Shuya Zhang, Rong Zhou, Bo Li, Haiyan Li, Yanyan Wang, Xuejiao Gu, Lingyun Tang, Cun Wang, Dingjuan Zhong, Yuanyuan Ge, Yuqing Huo, Jing Lin, Xiao-Ling Liu, Jiang-Fan Chen
Retinopathy of prematurity (ROP) is the leading cause of childhood blindness, but current anti-VEGF therapy is concerned with delayed retinal vasculature, eye, and brain development of preterm infants. The clinical observation of reduced ROP severity in premature infants after caffeine treatment for apnea suggests that caffeine may protect against ROP. Here, we demonstrate that caffeine did not interfere with normal retinal vascularization development but selectively protected against oxygen-induced retinopathy (OIR) in mice...
August 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Xigang Jing, Yi-Wen Huang, Jason Jarzembowski, Yang Shi, Girija G Konduri, Ru-Jeng Teng
BackgroundBronchopulmonary dysplasia (BPD) is a major morbidity in premature infants, and impaired angiogenesis is considered a major contributor to BPD. Early caffeine treatment decreases the incidence of BPD; the mechanism remains incompletely understood.MethodsSprague-Dawley rat pups exposed to normoxia or hyperoxia since birth were treated daily with either 20 mg/kg caffeine or normal saline by an intraperitoneal injection from day 2 of life. The lungs were obtained for studies at days 10 and 21.ResultsHyperoxia impaired somatic growth and lung growth in the rat pups...
September 2017: Pediatric Research
Ru-Jeng Teng, Xigang Jing, Teresa Michalkiewicz, Adeleye J Afolayan, Tzong-Jin Wu, Girija G Konduri
Rodent pups exposed to hyperoxia develop lung changes similar to bronchopulmonary dysplasia (BPD) in extremely premature infants. Oxidative stress from hyperoxia can injure developing lungs through endoplasmic reticulum (ER) stress. Early caffeine treatment decreases the rate of BPD, but the mechanisms remain unclear. We hypothesized that caffeine attenuates hyperoxia-induced lung injury through its chemical chaperone property. Sprague-Dawley rat pups were raised either in 90 (hyperoxia) or 21% (normoxia) oxygen from postnatal day 1 (P1) to postnatal day 10 (P10) and then recovered in 21% oxygen until P21...
May 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
Stefanie Endesfelder, Ulrike Weichelt, Evelyn Strauß, Anja Schlör, Marco Sifringer, Till Scheuer, Christoph Bührer, Thomas Schmitz
Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term "oxygen radical disease of prematurity". Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats...
January 18, 2017: International Journal of Molecular Sciences
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