ApneBoot: A Novel Device for Apnea Management in Premature Infants

Gastrointestinal prokinetic agents, such as cisapride, are commonly used in pediatric practice to improve gastric emptying, to decrease emesis, to improve lower esophageal sphincter tone, and to improve irritability and feeding aversion associated with gastroesophageal reflux (GER). Although cisapride seems to be effective in infants from 2 months to 14 years old, data for younger and preterm infants are not available. Whether reflux is a significant cause of reflex apnea or feeding intolerance in the preterm infant is controversial. The objective of this 1-year prospective study, started in 1998, was to determine the efficacy of cisapride for treatment of reflux and reflux-associated apnea (RAAP) in preterm infants. Before this study, the diagnosis of reflux was often made clinically and the effect of therapy on reflux or the decision to increase the dose of cisapride was made empirically. The clinical bias was that persistent apnea, not responding to caffeine, was caused by GER. We reasoned that a systematic approach to the diagnosis and treatment of reflux would improve the care of preterm infants and reduce the risk of toxicity, especially if an increased dose of cisapride showed no improvement in reflux or apnea. Twenty-four preterm infants (24-36 weeks' gestational age) had clinical apnea/pH studies when they were referred by the attending neonatologist for suspected GER. These infants were born at 28.8 +/- 3.1 weeks with birth weight of 1169 +/- 387 g (range: 631-2263 g). Each infant was studied before and 8 days after starting cisapride treatment. Cisapride dose was 0.09 to 0.25 mg/kg every 6 hours enterally. Treatment decisions regarding dose of cisapride were the responsibility of the attending neonatologist. The pH was recorded continuously for 24 hours at 0.25 Hz and was analyzed using EsopHogram software. A single sensor pH catheter was inserted to ~2 cm above the esophageal gastric junction. GER was defined as a drop in esophageal pH below 4.0 for a least 5 seconds, or pathologic GER was defined as a reflux index (RI) >2 standard deviation (SD) from the mean based on published norms for term infants. The following parameters were calculated from the pH recording: number of reflux events per 24 hours, duration of the longest episode, number of episodes >5 minutes per 24 hours, and RI, ie, percentage of time with pH <4.0. Each study had a combined time-lapse video recording and multichannel digital recording. Recorded parameters were: continuous pulse oximetry, electrocardiogram, respiratory effort (piezo sensor), and airflow (temperature sensor at nostrils and mouth). The recording was scored for central apneas of 10 to 14 seconds and >/=15 seconds (prolonged) and >/=10 seconds for obstructive and mixed apneas. RAAP was scored when an apnea (irrespective of the type) occurred within 1 minute of a GER event. Baseline, after cisapride, and follow-up electrocardiograms were performed because of concern about prolonged QTc and cardiac arrhythmias. The infants were 35.6 +/- 4.5 weeks postconceptional age when first studied. Twelve infants (mean birth weight: 1821 +/- 749 g; gestational age: 32 +/- 2 weeks; postconceptional age: 35.6 +/- 2.6 weeks) were identified retrospectively as controls because their baseline GER parameters were within the normal range using Vandenplas' criteria. Overall, cisapride treatment significantly improved the RI from 16.6 +/- 15.2 to 9.1 +/- 8.4 SD. The number of reflux episodes >/=5 minutes was reduced from 7.1 +/- 5.8 to 4.3 +/- 4.4 SD. No significant effect was seen on the total number of refluxes (/24 hours). Eight infants (33%) had no decrease in the RI after a week of treatment. Three of these infants improved after cisapride dose was increased from 0.09 to 0.25 mg/kg/dose every 6 hours. Although 0.09 mg/kg/day is the minimum effective dose, 67% of our infants did respond to this low dose. Cisapride was discontinued in 3 infants because of prolonged QTc >/=0.450 seconds (0.473 in 1 and 0.470 in 2). More data about the effect of cisapride on QTc interval are reported in Pediatrics in a separate article. Only 1 infant showed no improvement with increased dose. Caffeine treatment had no effect on the baseline or follow-up GER values. Although apnea indexes for central and obstructive apnea were similar before and after cisapride, mixed apnea was less during treatment. There was a significant decrease (0.32 +/- 0.40 to 0.12 +/- 0.17/hour) in RAAP when the one infant who had increased reflux on increased dose of cisapride was excluded as an outlier. The statistical difference, before and after cisapride, for the group is significant with the outlier omitted. The clinical significance is unclear because ~50% of the infants had minimal changes in their apnea indexes. Furthermore, ~40% of infants did not have RAAP. (ABSTRACT TRUNCATED)

Introduction: Episodes of apnoea are common in extremely preterm infants (EPIs) and usually treated with caffeine and respiratory support. Understanding differences in apnoea definitions, monitoring practices, and use of respiratory stimulants is essential to improve future treatment. Methods: Between March and July 2024, one lead consultant at European tertiary neonatal intensive care units (NICUs) was invited to complete a web-based survey on respiratory practices in EPIs. We sought information how they defined apnoea and monitored for it, and how they treated it with caffeine, doxapram, and non-invasive respiratory support. Results: We received replies from 447/721 (62%) NICUs across 24 European countries. Most NICUs (74%) use both electrocardiogram electrodes and pulse oximetry for apnoea monitoring. All NICUs reported using caffeine citrate, with 102 centres (23%) starting it in the delivery room. The median loading, maintenance and maximum maintenance doses used are 20 mg/kg, 5 and 10 mg/kg/day, respectively. Caffeine is occasionally given twice daily in some NICUs (30%) and stopped at 34–35 weeks of postmenstrual age at most of them (74%). Doxapram is used at 111 (25%) NICUs, with geographical differences. Strategies for the use and escalation of non-invasive respiratory support in case of persistent apnoea are not clearly defined. Automatic closed-loop oxygen delivery is used at 25% of NICUs. Conclusion: Despite consistency in the dosing and weaning of caffeine, there is much variation in the management of apnoea in preterm infants across Europe. Future research should focus on timing and dosage of caffeine, the use of doxapram, and strategies for optimising non-invasive respiratory support.

The purpose of this research was to determine the effects of mothers' singing on their adjustment to and bonding with their new infants as well as use of music in the home environment in the first 2 weeks after their infants' birth. Preterm mothers were assessed for coping with their infants' NICU stay, and premature infants' length of hospitalization was evaluated. Fifty-four full-term infants and mothers and 20 premature infants and 16 mothers were randomly assigned to experimental or control conditions. Mothers in both experimental groups were recorded singing songs of their choice for use at home. Recordings of each preterm mother's voice were played 20 minutes per day, 3 to 5 times per week, at a time when she was not able to visit her infant in the NICU. All full-term and preterm mothers in experimental and control groups completed a posttest survey 2 weeks after infants were discharged. Comparisons revealed that experimental preterm and full-term mothers indicated less adjustment to their baby and lifestyle changes and less bonding compared to control mothers, though this difference was not significant. Preterm and full-term experimental mothers reported the greatest number of postpartum medical complications, which might explain their poor adjustment and bonding scores. There was a significant difference between mothers' value of music, with preterm experimental valuing music more. Preterm and full-term experimental mothers used music with and sang to infants more compared to preterm and full-term control mothers, but not to a significant degree. Preterm mothers reported a mean score of 4.75 (with a 5 indicating that they strongly agreed) for the following item: knowing my infant listened to my singing helped me to cope with my infant's stay in the NICU. Furthermore, preterm infants who listened to the CD recording of their mothers' singing left the hospital an average of 2 days sooner than those in the control group, though this difference was not significant.

Recent scientific studies have added more and more consistent evidence that the newborn, even if preterm, is very sensitive to the nociceptive stimulus. The baby responds with a well known physiological, metabolic and hormonal reaction, that, if repeated, may lead to short and medium term negative effects on the newborn. This vulnerability to painful stimulus, especially in preterm infants, can be explained by neurophysiological mechanisms. In spite of a well developed sensory apparatus for nociception, the descending inhibitory systems and their neurotransmitters responsible for nociceptive afferents, are deficient and immature until after the term birth. Behavioral changes and reductions in the volume of some sensitive brain areas were observed in ex preterm infants admitted to the neonatal intensive care unit; the modifications were very similar to those seen in experimental model of rat with same gestational age, exposed to early and repeated painful stimulus [1]. We consider as environmental interventions all steps that can reduce stress in the baby during a painful procedure. A variety of non pharmacologic pain-prevention and relief techniques have been shown to effectively reduce pain from minor procedures in neonates. These include use of oral sucrose/glucose, breastfeeding, non-nutritive sucking, kangaroo care, facilitated touch (holding the arms and legs in a flexed position), swaddling, and developmental care [2]. The involvement of the mother is recommended through skin-to-skin or breast-feeding during a single sampling. Several studies have shown how breastfeeding during a painful procedure reduces the stress in newborn [3]. The prevention of pain in neonates should be the goal of all caregivers, because repeated painful exposures can have deleterious consequences. Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth are also those most likely to be exposed to the greatest number of painful stimulus in the NICU. We have to improve strategies for routinely assessing pain, minimizing the number of painful procedures performed, using pharmacologic and non pharmacologic therapies for the prevention of pain associated with routine minor procedures, and eliminating pain associated with major procedures.

Our meta-analysis of nine studies shows that sustained lung inflation without chest compression was not better than intermittent ventilation for reducing mortality in the delivery room (low-quality evidence ‒ GRADE) or during hospitalisation (moderate-quality evidence ‒ GRADE), which were the primary outcomes of this review. However, the single largest study, which was well conducted and had the greatest number of enrolled infants, was stopped early for higher mortality rate in the sustained inflation group. When considering secondary outcomes, such as rate of intubation, rate or duration of respiratory support, or bronchopulmonary dysplasia, we found no benefit of sustained inflation over intermittent ventilation (moderate-quality evidence ‒ GRADE). Duration of mechanical ventilation was shortened in the SLI group (low-quality evidence ‒ GRADE); this result should be interpreted cautiously, however, as it might have been influenced by study characteristics other than the intervention. There is no evidence to support the use of sustained inflation based on evidence from our review.

Management of apnoea and bradycardia in the newborn

Methylxanthine therapy reduces the frequency of apnea and the need for mechanical ventilation. Recent research has raised concerns about the safety of methylxanthines in very preterm infants. Possible adverse effects include poor growth, worsening of hypoxic-ischemic brain damage and abnormal childhood behavior. Over 2,000 infants with birth weights 500–1,250 g have been randomized in the international placebo-controlled Caffeine for Apnea of Prematurity (CAP) trial to examine the long-term efficacy and safety of methylxanthine therapy for the management of apnea of prematurity. Additional therapies such as continuous positive airway pressure were used as necessary to control apneic attacks. At 18 months we measure the combined rate of death or survival with one or more of the following impairments: cerebral palsy, cognitive deficit, blindness and deafness. This outcome was chosen because of the need to evaluate the impact of common neonatal therapies beyond discharge from the intensive care unit. However, several potential long-term consequences of methylxanthine therapy may not become apparent until the study cohort reaches pre-school age. We will therefore extend the follow-up to age 5 years. The main outcome at 5 years will be a composite of death or survival with severe disability in at least one of six domains: cognition, neuromotor function, vision, hearing, behavior, and general health. Once this project is completed, caffeine will be one of the most rigorously evaluated neonatal therapies.

Apnea, especially in preterm newborns (AoP) is one of the common problems encountered at neonatal units. Numerous factors are likely to play a role in the etiology of apnea. Recent data sugest a role for genetic predisposition of AoP. It seems, that physiological rather than pathological immaturity of the respiratory, or cardiorespiratory control, play a major part in the pathophysiology of AoP. Immaturity of the brainstem, cerebral cortex, receptors of the lungs and the airways as well as of the chemoreceptors contribute to the development of apnea in preterm newborns. Several neurotransmitters (GABA, adenosin, endorphins) and their maturational changes are including in pathogenesis of apnea, too. The instability of the upper airway in preterm infants, asynchrony of musculature of the upper airway and diaphragm, pathological changes in the upper airway and malformations of the central nervous system might also contribute to the occurrence and severity of AoP. In newborns, apnea occurs more frequently in active sleep than in quiet sleep and the frequency of apnea in active sleep is higher in the warm conditions. Durations of apnea correlate with the body heat loss. Cardiovascular changes during apnea - bradycardia, peripheral vasoconstriction and various changes in peripheral blood flow and pressure occur together with changes in ECG. The standard clinical management of apnea includes non-pharmacological treatment (eliciting arousal reactions and reflex breathing by mechanical skin, or mucosa stimulations), pharmacological treatment (methylxanthines are preferred) and application of continuous positive airway pressure (CPAP) or in severe apnea - mechanical ventilation.

Caffeine, a widely used central nervous system stimulant, has emerged as the most commonly used therapeutic agent for managing apnea of prematurity in neonates over the last decade. Despite the evidence favoring caffeine, there are several controversies with the use of caffeine in neonates. Several studies have shown that caffeine significantly decreases cerebral blood flow velocity, impacting cerebral oxygenation and tissue oxygenation index. Higher doses of caffeine have raised safety concerns, with reports of increased incidence of cerebellar hemorrhage and adverse neurological outcomes in preterm infants. The duration of caffeine therapy remains a conundrum, with no consensus guidelines available. Neonatal units differ in their approaches to discontinuing caffeine therapy and discharging babies based on apnea-free intervals. The documentation and monitoring protocols for apnea vary across units, raising concerns about the accuracy of clinical recommendations. This article aims to unfold the complexities surrounding caffeine therapy in neonatal care, highlighting the potential concerns of using caffeine, especially in higher doses, while acknowledging the existing benefits for managing apnea of prematurity. We call on medical professionals to conduct more thorough research and controlled trials to understand better how to use caffeine effectively for premature babies for improving neonatal outcomes.

Keywords: Continuous Positive Airway Pressure(CPAP) 1, Sleep Apnea 2, Neonatal 3, Respiratory Distress Syndrome (RDS) 4, Premature baby 5, Transpiration medical device 6, Internet of Things 7 CPAP, a non-invasive ventilation method crucial in neonatal care, has significant implications for the survival of very low birth weight preterm infants. However, its widespread adoption is hindered by cost constraints and the need for additional features like Apnea Hypopnea Index (AHI) monitoring. This study seeks to overcome these challenges by developing an affordable CPAP device for Neonatal Intensive Care Units (NICUs). By incorporating sensors for data collection and a microcontroller-based control system, this device aims to optimize CPAP function while minimizing energy consumption. Furthermore, the collected data will be securely stored on a cloud platform, potentially benefiting both neonatal care and sleep apnea management. Recognizing the vital role of sleep in human health, this innovation underscores the importance of restorative rest for physical and mental well-being. Highlights: · Web-integrated CPAP devices often come with remote monitoring capabilities. This allows healthcare providers to remotely monitor patients' CPAP usage data, including compliance and efficacy metrics, without requiring in-person visits. This feature facilitates better patient management and allows for timely intervention if issues arise. · These devices typically track and record various parameters such as usage hours, mask leaks, apnea-hypopnea index (AHI), and pressure settings. The data can be accessed by both patients and healthcare providers, providing insights into treatment progress and effectiveness over time. · Many web-integrated CPAP devices offer cloud connectivity, allowing users to sync their data to secure online platforms. This feature enables seamless access to CPAP usage data from multiple devices, such as smartphones, tablets, or computers, enhancing convenience and flexibility for users. · Some modern CPAP machines offer wireless connectivity options, such as Bluetooth or Wi-Fi, enabling users to connect their devices to compatible accessories or smartphone apps. This connectivity allows for features like remote control of device settings, automatic software updates, and integration with health tracking apps for a more comprehensive health management experience. · The integration of web-based CPAP platforms with telemedicine services allows for virtual consultations between patients and healthcare providers. This feature enhances access to care, particularly for patients in remote or underserved areas, and enables real-time adjustments to CPAP settings based on patient feedback and data analysis.

Nonpharmacological Management of Idiopathic Apnea of the Premature Infant

ObjectivesThe primary objective of this study is to determine the current level of patient medication exposure in Level 3 Neonatal Wards (L3NW). The secondary objective is to evaluate in the first month of life the rate of medication prescription not cited in the Summary of Product Characteristics (SmPC). A database containing all the medication prescriptions is collected as part of a prescription benchmarking program in the L3NW.Material and methodsThe research is a two-year observational cohort study (2017–2018) with retrospective analysis of medications prescribed in 29 French L3NW. Seventeen L3NW are present since the beginning of the study and 12 have been progressively included. All neonatal units used the same computerized system of prescription, and all prescription data were completely de-identified within each hospital before being stored in a common data warehouse.ResultsThe study population includes 27,382 newborns. Two hundred and sixty-one different medications (International Nonproprietary Names, INN) were prescribed. Twelve INN (including paracetamol) were prescribed for at least 10% of patients, 55 for less than 10% but at least 1% and 194 to less than 1%. The lowest gestational ages (GA) were exposed to the greatest number of medications (18.0 below 28 weeks of gestation (WG) to 4.1 above 36 WG) (p<0.0001). In addition, 69.2% of the 351 different combinations of an medication INN and a route of administration have no indication for the first month of life according to the French SmPC. Ninety-five percent of premature infants with GA less than 32 weeks received at least one medication not cited in SmPC.ConclusionNeonates remain therapeutic orphans. The consequences of polypharmacy in L3NW should be quickly assessed, especially in the most immature infants.

Purpose. To study the effect of bright sunlight on immature retina of a premature baby at different periods of solar activity.Material and methods. The study involved two groups of premature babies: 32 babies (64 eyes) in 2016 and 50 babies (100 eyes) in 2017. Both groups were tested using a retinal camera (RetCam Shuttle, USA) on the 3rd or 4th week after birth. In cases of threshold stages of retinopathy of prematurity (ROP) binocular ophthalmoscopy were performed. In such cases, laser coagulation of the retina was performed using "ALOD 01" (ALCOM Medica, Russia).Results. The greatest number of ROP with the greatest number of surgical interventions and adverse outcomes that required vitreoretinal surgery were revealed in the second seasonal period (May — August), which experienced the highest solar activity. In 2016, the amount of ROP cases diagnosed in this period amounted to 59 %, which is comparable with the corresponding amount revealed in 2017 (61.1 %).Conclusions. Stronger solar activity and its longer periods increase the risk of ROP; consequently, to prevent this pathology, the eyes of the newborn should be protected from the negative effects of daylight and artificial light, including that emitted by diagnostic equipment.

The administration of anaesthesia is an extremely safe procedure today. Data published by the American Society of Anesthesiology tell us that the risk of anaesthesia-related death has decreased 25-fold since 1970, from 1 in 10 000 to 1 in 250 000. In the USA, this risk reduction has closely followed a second trend, namely, a doubling of the number of working anaesthesiologists. All this has occurred during a time when the youngest of premature infants in neonatal units survives intricate, lifesaving procedures and 100-year-old patients undergo and recover from major surgeries that were once thought to be impossible. Today, safety in anaesthesia is comparable to safety in aviation, i.e. the risk of an aviation accident per departure is 0.96 in 1 000 000 for scheduled passenger operations (about 145 million departures during the last 10 years) and 2.64 in 1 000 000 for other operations (charter, cargo, demonstration, etc — about 25 million departures during the last ten years) [1]. Considering the greater number of deaths involved in a passenger aircraft crash, undergoing anaesthesia is actually safer than flying!

Apnea of prematurity (AOP) is frequently managed with nasal continuous positive airway pressure (NCPAP). Nasal cannula (NC) are used at low flows (<0.5 L/min) to deliver supplemental oxygen to neonates. A number of centers use high-flow nasal cannula (HFNC) in the management of AOP without measuring the positive distending pressure (PDP) generated. Objective. To determine the NC flow required to generate PDP equal to that provided by NCPAP at 6 cm H(2)O and to assess the effectiveness of HFNC as compared NCPAP in the management of AOP. Method. Forty premature infants, gestation 28.7 +/- 0.4 weeks (mean +/- standard error of mean), postconceptual age at study 30.3 +/- 0.6 weeks, birth weight 1256 +/- 66 g, study weight 1260 +/- 63 g who were being managed with conventional NCPAP for at least 24 hours for clinically significant apnea of prematurity, were enrolled in a trial of ventilator-generated conventional NCPAP versus infant NC at flows of up to 2.5 L/min. End expiratory esophageal pressure was measured on NCPAP and on NC, and the gas flow on NC was adjusted to generate an end expiratory esophageal pressure equal to that measured on NCPAP. Two 6-hour periods were continuously recorded and the data were stored on computer. Results. The flow required to generate a comparable PDP with NC varied with the infant's weight and was represented by the equation: flow (L/min) = 0.92 + 0.68x, x = weight in kg, R = 0.72. There was no difference in the frequency and duration of apnea, bradycardia or desaturation per recording between the 2 systems. Conclusion. NC at flows of 1 to 2.5 L/min can deliver PDP in premature neonates. HFNC is as effective as NCPAP in the management of AOP.