Long-term neurodevelopment outcome of caffeine versus aminophylline therapy for apnea of prematurity

Caffeine is one of the most commonly utilized medications in the NICU. In preterm infants, short-term and long-term pulmonary and neurodevelopmental benefits of therapy are well documented in the literature. While robust evidence supports the use of standard doses of caffeine for apnea of prematurity or to facilitate successful extubation, much remains unknown regarding the boundaries of efficacy and safety for this common therapeutic agent. Escalating dosing regimens seem to provide additional benefit in select infants, but grave toxicity has also been documented with early utilization of high-dose caffeine. Conflicting data exist surrounding the ideal timing of initiation of therapy. Even the widely adhered to discontinuation point has been challenged by data supporting continued use. Until robust data definitively support change, practice should align with current evidence defining clear, safe, and efficacious dosing and timing of caffeine therapy.

Download Full-text

Long-Term Effects of Caffeine Therapy for Apnea of Prematurity

New England Journal of Medicine ◽

10.1056/nejmoa073679 ◽

2007 ◽

Vol 357 (19) ◽

pp. 1893-1902 ◽

Cited By ~ 499

Author(s):

Barbara Schmidt ◽

Robin S. Roberts ◽

Peter Davis ◽

Lex W. Doyle ◽

Keith J. Barrington ◽

...

Keyword(s):

Long Term Effects ◽

Apnea Of Prematurity

Download Full-text

Reply: Caffeine Therapy for Apnea of Prematurity: Long-Term Effect on Sleep by Actigraphy and Polysomnography

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.201410-1887le ◽

2014 ◽

Vol 190 (12) ◽

pp. 1457-1458

Author(s):

Lisa J. Meltzer ◽

Carole L. Marcus

Keyword(s):

Term Effect ◽

Long Term Effect ◽

Apnea Of Prematurity

Download Full-text

Long-term facilitation of catecholamine secretion from adrenal chromaffin cells of neonatal rats by chronic intermittent hypoxia

Journal of Neurophysiology ◽

10.1152/jn.00435.2019 ◽

2019 ◽

Vol 122 (5) ◽

pp. 1874-1883

Author(s):

Vladislav V. Makarenko ◽

Ying-Jie Peng ◽

Shakil A. Khan ◽

Jayasri Nanduri ◽

Aaron P. Fox ◽

...

Keyword(s):

Intermittent Hypoxia ◽

Chromaffin Cells ◽

Neonatal Rat ◽

Catecholamine Secretion ◽

Chronic Intermittent Hypoxia ◽

Neonatal Rats ◽

Adrenal Chromaffin ◽

Apnea Of Prematurity ◽

Long Term Facilitation

In neonates, catecholamine (CA) secretion from adrenal medullary chromaffin cells (AMC) is an important mechanism for maintaining homeostasis during hypoxia. Nearly 90% of premature infants experience chronic intermittent hypoxia (IH) because of high incidence of apnea of prematurity, which is characterized by periodic stoppage of breathing. The present study examined the effects of repetitive hypoxia, designed to mimic apnea of prematurity, on CA release from AMC of neonatal rats. Neonatal rats were exposed to either control conditions or chronic intermittent hypoxia (IH) from ages postnatal days 0–5 (P0–P5), and CA release from adrenal medullary slices was measured after challenge with repetitive hypoxia (5 episodes of 30-s hypoxia, Po2 ~35 mmHg). In response to repetitive hypoxia, chronic IH-treated AMC exhibited sustained CA release, and this phenotype was not seen in control AMC. The sustained CA release was associated with long-lasting elevation of intracellular Ca2+ concentration ([Ca2+]i), which was due to store-operated Ca2+ entry (SOCE). 2-Aminoethoxydiphenyl borate, an inhibitor of SOCE, prevented the long-lasting [Ca2+]i elevation and CA release. Repetitive hypoxia increased H2O2 abundance, and polyethylene glycol (PEG)-catalase, a scavenger of H2O2 blocked this effect. PEG-catalase also prevented repetitive hypoxia-induced SOCE activation, sustained [Ca2+]i elevation, and CA release. These results demonstrate that repetitive hypoxia induces long-term facilitation of CA release in chronic IH-treated neonatal rat AMC through sustained Ca2+ influx mediated by SOCE. NEW & NOTEWORTHY Apnea of prematurity and the resulting chronic intermittent hypoxia are major clinical problems in neonates born preterm. Catecholamine release from adrenal medullary chromaffin cells maintains homeostasis during hypoxia in neonates. Our results demonstrate that chronic intermittent hypoxia induces a hitherto uncharacterized long-term facilitation of catecholamine secretion from neonatal rat chromaffin cells in response to repetitive hypoxia, simulating hypoxic episodes encountered during apnea of prematurity. The sustained catecholamine secretion might contribute to cardiovascular morbidities in infants with apnea of prematurity.

Download Full-text

Long-Term Effects of Caffeine Therapy for Apnea of Prematurity

Survey of Anesthesiology ◽

10.1097/sa.0b013e318179f0cc ◽

2008 ◽

Vol 52 (3) ◽

pp. 125-126

Author(s):

&NA;

Keyword(s):

Long Term Effects ◽

Apnea Of Prematurity

Download Full-text

Apnea within the first year of life in premature infants with bronchopulmonary displasia and pulmonary hypertension

Pediatrician (St Petersburg) ◽

10.17816/ped9316-23 ◽

2018 ◽

Vol 9 (3) ◽

pp. 16-23

Author(s):

Anna Yu. Solomakha ◽

Natalia A. Petrova ◽

Dmitry O. Ivanov ◽

Yurii V. Sviryaev

Keyword(s):

Pulmonary Hypertension ◽

Premature Infants ◽

Intermittent Hypoxia ◽

Apnea Hypopnea Index ◽

First Year ◽

Different Types ◽

First Year Of Life ◽

Apnea Of Prematurity ◽

The Relationship

Infants with severe and moderate bronchopulmonary dysplasia (BPD) are characterized by long-term persistence of apnea of prematurity and often have a pulmonary hypertension (PH). Respiratory pauses, accompanied by intermittent hypoxia, do not clinically manifest themselves, therefore cardiorespiratory monitoring (CRM) is required. We hypothesized that the persistent of apnea, as the cause of hypoxemia episodes, may be associated with the persistence of PH in infants with BPD. The aim of the study was to evaluate the dynamics of cardiorespiratory parameters and to study the relationship between obstructive apnea and PH during the first year of life of premature infants with BPD + PH. Materials and methods. CRM was performed in 58 infants were born at 26 0/7-31 0/7 weeks gestation and with birth weight less than 1500 grams, before discharge from the hospital (35-44 weeks of post menstrual age). 14 infants did not have BPD (group without BPD). 44 infants had BPD and 17 of them had a complication of this disease PH (BLD + PH group). Other infants with BPD did not have PH (BLD-PH group). Eight infants with BPD also underwent a study at home (aged 9 to 10 months of life). Results. Preterm infants with BPD + PH were more significant decrease in the average SpO2, higher desaturation index and more a number of desaturation episodes of <10% compared to infants with BPD-PH and without BPD. There was no difference in the apnea/hypopnea index and frequency of occurrence of different types of apnea between groups. There was no difference in cardiorespiratory performance in infants with BPD+PH compared to infants with BPD-PH in 9-10 months of life. Conclusions. There was a positive dynamics of cardiorespiratory parameters in infants with BPD+PH in 9-10 months after discharge from the hospital. The number of infants with an index of OA> 1/hour is higher in the group BPD+LH.

Download Full-text