Apnea and intermittent hypoxemia (IH) are common developmental disorders in infants born earlier than 37 weeks' gestation. Caffeine administration has been shown to lower the incidence of these disorders in preterm infants. Cessation of caffeine treatment is based on different post-menstrual ages (PMA) and resolution of symptoms. There is uncertainty about the best timing for caffeine discontinuation.

To evaluate the effects of early versus late discontinuation of caffeine administration in preterm infants.

We searched CENTRAL, PubMed, Embase, and three trial registries in August 2023; we applied no date limits. We checked the references of included studies and related systematic reviews.

We included randomized controlled trials (RCTs) in preterm infants born earlier than 37 weeks' gestation, up to a PMA of 44 weeks and 0 days, who received caffeine for any indication for at least seven days. We compared three different strategies for caffeine cessation: 1. at different PMAs, 2. before or after five days without symptoms, and 3. at a predetermined PMA versus at the resolution of symptoms.

We used standard Cochrane methods. Primary outcomes were: restarting caffeine therapy, intubation within one week of treatment discontinuation, and the need for non-invasive respiratory support within one week of treatment discontinuation. Secondary outcomes were: number of episodes of apnea in the seven days after treatment discontinuation, number of infants with at least one episode of apnea in the seven days after treatment discontinuation, number of episodes of intermittent hypoxemia (IH) within seven days of treatment discontinuation, number of infants with at least one episode of IH in the seven days after of treatment discontinuation, all-cause mortality prior to hospital discharge, major neurodevelopmental disability, number of days of respiratory support after treatment discontinuation, duration of hospital stay, and cost of neonatal care. We used GRADE to assess the certainty of evidence for each outcome.

We included three RCTs (392 preterm infants). Discontinuation of caffeine at PMA less than 35 weeks' gestation versus PMA equal to or longer than 35 weeks' gestation This comparison included one single completed RCT with 98 premature infants with a gestational age between 25 + 0 and 32 + 0 weeks at birth. All infants had discontinued caffeine treatment for five days at randomization. The infants received either an oral loading dose of caffeine citrate (20 mg/kg) at randomization followed by oral maintenance dosage (6 mg/kg/day) until 40 weeks PMA, or usual care (controls), during which caffeine was stopped before 37 weeks PMA. Early cessation of caffeine administration in preterm infants at PMA less than 35 weeks' gestation may result in an increase in the number of IH episodes in the seven days after discontinuation of treatment, compared to prolonged caffeine treatment beyond 35 weeks' gestation (mean difference [MD] 4.80, 95% confidence interval [CI] 2.21 to 7.39; 1 RCT, 98 infants; low-certainty evidence). Early cessation may result in little to no difference in all-cause mortality prior to hospital discharge compared to late discontinuation after 35 weeks PMA (risk ratio [RR] not estimable; 98 infants; low-certainty evidence). No data were available for the following outcomes: restarting caffeine therapy, intubation within one week of treatment discontinuation, need for non-invasive respiratory support within one week of treatment discontinuation, number of episodes of apnea, number of infants with at least one episode of apnea in the seven days after discontinuation of treatment, or number of infants with at least one episode of IH in the seven days after discontinuation of treatment. Discontinuation based on PMA versus resolution of symptoms This comparison included two RCTs with a total of 294 preterm infants. Discontinuing caffeine at the resolution of symptoms compared to discontinuing treatment at a predetermined PMA may result in little to no difference in all-cause mortality prior to hospital discharge (RR 1.00, 95% CI 0.14 to 7.03; 2 studies, 294 participants; low-certainty evidence), or in the number of infants with at least one episode of apnea within the seven days after discontinuing treatment (RR 0.60, 95% CI 0.31 to 1.18; 2 studies; 294 infants; low-certainty evidence). Discontinuing caffeine based on the resolution of symptoms probably results in more infants with IH in the seven days after discontinuation of treatment (RR 0.38, 95% CI 0.20 to 0.75; 1 study; 174 participants; moderate-certainty evidence). No data were available for the following outcomes: restarting caffeine therapy, intubation within one week of treatment discontinuation, need for non-invasive respiratory support within one week of treatment discontinuation, or number of episodes of IH in the seven days after treatment discontinuation. Adverse effects In the Rhein 2014 study, five of the infants randomized to caffeine had the caffeine treatment discontinued at the discretion of the clinical team, because of tachycardia. The Pradhap 2023 study reported adverse events, including recurrence of apnea of prematurity (15% in the short and 13% in the regular course caffeine therapy group), varying severities of bronchopulmonary dysplasia, hyperglycemia, extrauterine growth restriction, retinopathy of prematurity requiring laser treatment, feeding intolerance, osteopenia, and tachycardia, with no significant differences between the groups. The Prakash 2021 study reported that adverse effects of caffeine therapy for apnea of prematurity included tachycardia, feeding intolerance, and potential neurodevelopmental impacts, though most were mild and transient. We identified three ongoing studies.

There may be little or no difference in the incidence of all-cause mortality and apnea in infants who were randomized to later discontinuation of caffeine treatment. However, the number of infants with at least one episode of IH was probably reduced with later cessation. No data were found to evaluate the benefits and harms of later caffeine discontinuation for: restarting caffeine therapy, intubation within one week of treatment discontinuation, or need for non-invasive respiratory support within one week of treatment discontinuation. Further studies are needed to evaluate the short-term and long-term effects of different caffeine cessation strategies in premature infants.

Cardiopulmonary events (CPE) have a central, obstructive, or mixed etiology. Lack of standardized diagnosis and management of CPE may prolong the length of stay (LOS).

To increase the accuracy of CPE diagnosis and decrease LOS by 10% for preterm infants over a 12-month period.

Develop an evidence-based algorithm to identify type of CPE, determine management approach, and evaluate cardio-respiratory monitors output. Apply model for improvement and statistical process control charts to determine special cause variation.

Identification of central apnea increased from 15 to 39% (p < 0.01). LOS decreased 26% from 52.6 days to 39.2 days, with an estimated cost savings of $13,119 per each of the 225 infants in the initiative.

After implementing an evidence-based algorithm for management of neonatal CPE, a significant increase in the accuracy of the diagnosis of central apnea and cost savings associated with a decrease in LOS were observed.

To evaluate a precise definition of a clinically significant cardiopulmonary event (CSCPE) on the hospital length of stay (LOS), medical provider satisfaction, and discharge complications.

This is a single-center, observational study that included 139 infants before and 134 infants after the new definition was implemented in December 2017. Retrospective data collected November 2015 to November 2017 (before) was compared with prospective data from June 2018 to July 2020 (after). Outcome measures were the proportion of infants waiting to outgrow CSCPE, LOS, provider satisfaction with the definition, and discharge complications. Multivariate regression modeling was used to evaluate variables on LOS and postmenstrual age at discharge.

The proportion waiting to outgrow CSCPE decreased from 68.4% to 31.7% (P < .0001). The LOS was similar between groups; however, multivariate analysis correcting for gestational age and reason awaiting discharge estimated 3.5 days (95% CI, 1.4-5.8 days; P = .0017) decrease in LOS, and 0.92 weeks (95% CI, 0.29-1.56; P = .005) younger postmenstrual age at discharge in the after group. There was no difference in the number of readmissions or emergency room visits for apnea or deaths. Provider satisfaction improved with discharge planning after the implementation of the definition.

We developed an alternate definition for a CSCPE that decreased the proportion of infants waiting to outgrow a CSCPE but not LOS. There was no difference in the number of readmissions or emergency room visits for apnea or deaths, and provider satisfaction in management and discharge planning was greater.

This study was registered under the ClinicalTrial.gov Protocol ID: 5892S-15. "The effect of standardizing the definition and approach to a clinically significant cardiopulmonary event in infants less than 30 weeks on length of stay." Recorded Nov 2017.

Apnea of prematurity is a developmental disorder affecting most extremely preterm infants. The consequences of apnea of prematurity on neurodevelopment are not well established, but several reports suggest that apnea and hypoxemia episodes may be associated with worse neurological outcome. Caffeine is the only FDA-approved drug for the prevention and treatment of apnea of prematurity. Besides its clear effectiveness to reduce apnea, the use of caffeine appears to have a wide margin of safety and has been associated with possible beneficial effects on later neurodevelopmental outcome. At the same time, there are also many studies in experimental animals and some in preterm infants suggesting potential serious adverse effects from caffeine administration, especially when using higher doses. Because of these uncertainties, there is a wide variation in caffeine use across institutions. This review summarizes some of the available evidence on caffeine use in this population, its indications and best timing of initiation and discontinuation, appropriate dosing, and some of the possible adverse effects of caffeine administration. Because of the many gaps in knowledge, especially as it relates to efficacy and safety, we encourage further basic and clinical studies to provide stronger evidence, not only on its potential beneficial effects but also its side effects.

To study the clinical features and outcome of very preterm infants withdrawn from caffeine citrate at different time points.

A retrospective analysis was performed on the medical data of the preterm infants with a gestational age of <32 weeks, who were hospitalized in the Division of Neonatology, the Second Xiangya Hospital of Central South University, from January 1, 2016 to November 30, 2020. According to the time of withdrawal from caffeine citrate, the infants who met the study criteria were divided into the group with withdrawal before the last week of hospitalization and the group with withdrawal within the last week of hospitalization. The two groups were compared in terms of clinical features, features of citric caffeine use, length of hospital stay and hospital costs, change in the intensity of respiratory support, and preterm complications.

A total of 403 preterm infants were enrolled, with 285 infants in the group with withdrawal before the last week of hospitalization and 118 infants in the group with withdrawal within the last week of hospitalization. There were no significant differences in clinical features between the two groups (P>0.05). Compared with the group with withdrawal before the last week of hospitalization, the group with withdrawal within the last week of hospitalization had a significantly longer duration of the use of caffeine citrate, a significantly shorter length of hospital stay, a significantly lower rate of increased intensity of respiratory support after withdrawal, and a significantly lower incidence rate of moderate or severe bronchopulmonary dysplasia (P<0.05).

A relatively long course of caffeine citrate treatment is more beneficial to the short-term clinical outcome of very preterm infants.

There is sufficient evidence to support use of caffeine therapy for apnea of prematurity, but practices vary widely when it comes to discontinuing therapy. This study was planned to compare 'recurrence of apnea of prematurity' (RAP); when 2 protocols were used to stop caffeine therapy.

Neonates delivered at 26-32 wk gestation on caffeine therapy for apnea of prematurity were randomized into 2 groups: Group 1-caffeine stopped at 7 d apnea-free period, and Group 2-continued for a prefixed period till at least 34 wk postmenstrual age (PMA). Proportion of infants in each group with RAP were analyzed.

Each group consisted of 60 infants. Proportion of infants in each group with RAP, were not different (15% vs 13%); odds ratio (OR) 0.87; 95% confidence interval (CI) (0.31-2.43). Caffeine could be stopped earlier (33 vs 34 wk PMA); and cumulative duration of therapy was lesser (19.5 vs 33 d) when stopped at 7 d apnea-free period. Other studied outcomes were similar between the two groups.

Mandatorily continuing caffeine therapy up to 34 wk PMA in select preterm groups does not seem to decrease risk of recurrence of apnea. Larger trials that specifically study extremely preterm infants are required to make robust recommendations on when to stop therapy.

CTRI/2016/12/007559. http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=14195&EncHid=&modid=&compid=%27,%2714195det%27.

A novel home monitoring program, in which premature infants are cared for at home with a nasogastric tube in place prior to achievement of full oral feeding, was evaluated. The program combines a digital, fully EMR-integrated, virtual daily rounding platform with direct provider video and telephone contact.

A case-control study was performed evaluating infants <  34 weeks' gestation who were followed in our program. A historical control group, was created by matching 2 : 1 based on gestational age±6 days, retroactively.

15 patients discharged in the program were compared with 30 controls. The home cohort gained an average of 30 g/day compared with the in-hospital group at 27g/day (p = 0.325). The home group required a mean of 5.9±2.9 days to full oral feeding once discharged, not different from the control group at 5.4±3.7 days (p = 0.606). The percentage of oral feeds for the home cohort, however, increased at a rate of 12.2%before discharge compared to rising 57%at home (p <  0.001). The control group spent an additional 8.1±3.9 days in the hospital after reaching criteria. There were no reported adverse events or readmissions.

Premature infants can safely advance oral feeds using a home monitoring program. While at home, infants gained weight similarly to their inpatient controls inpatient, yet gained full oral skills at a significantly faster rate compared to when they were in the hospital.

What is the central question of this study? The respiratory centres in the brainstem that control respiration receive inputs from various sources, including proprioceptors in muscles and joints and suprapontine centres, which all affect limb movements. What is the effect of spontaneous movement on respiration in preterm infants? What is the main finding and its importance? Apnoeic events tend to be preceded by movements. These activity bursts can cause respiratory instability that leads to an apnoeic event. These findings show promise that infant movements might serve as potential predictors of life-threatening apnoeic episodes, but more research is required.

A common condition in preterm infants (<37 weeks' gestational age) is apnoea resulting from immaturity and instability of the respiratory system. As apnoeas are implicated in several acute and long-term complications, prediction of apnoeas may preempt their onset and subsequent complications. This study tests the hypothesis that infant movements are a predictive marker for apnoeic episodes and examines the relation between movement and respiration. Movement was detected using a wavelet algorithm applied to the photoplethysmographic signal. Respiratory activity was measured in nine infants using respiratory inductance plethysmography; in an additional eight infants, respiration and partial pressure of airway carbon dioxide ( P C O 2 ) were measured by a nasal cannula with side-stream capnometry. In the first cohort, the distribution of movements before and after the onset of 370 apnoeic events was compared. Results showed that apnoeic events were associated with longer movement duration occurring before apnoea onsets compared to after. In the second cohort, respiration was analysed in relation to movement, comparing standard deviation of inter-breath intervals (IBI) before and after apnoeas. Poincaré maps of the respiratory activity quantified variability of airway P C O 2 in phase space. Movement significantly increased the variability of IBI and P C O 2 . Moreover, destabilization of respiration was dependent on the duration of movement. These findings support that bodily movements of the infants precede respiratory instability. Further research is warranted to explore the predictive value of movement for life-threatening events, useful for clinical management and risk stratification.

Very low birth weight (VLBW) infants must achieve several maturational milestones to be discharged home from the NICU.

Describe the timing of maturational milestones in VLBW infants and the impact of clinical variables and milestone achievement on postmenstrual age (PMA) at discharge.

For VLBW infants without severe lung disease discharged home from a level IV NICU, we assessed PMA at the achievement of thermoregulation, cardiorespiratory stability, feeding, and discharge.

In 400 infants (median GA 28.4 weeks), lower birth weight, white race, and having multiple comorbidities of prematurity predicted later discharge PMA. The most common milestone sequence was CPAP discontinuation, caffeine discontinuation, thermoregulation, apnea resolution, and full oral feeds. PMA at apnea resolution and full oral feeds correlated highly with discharge PMA.

In a single-center VLBW cohort, comorbidities of prematurity impacted the timing of NICU discharge through delay in oral feeding and cardiorespiratory stability.

A complex set of medical, social, and financial factors underlie decisions to discharge very preterm infants. As care practices change, whether postmenstrual age and weight at discharge have changed is unknown.

Between 2005 and 2018, 824 US Vermont Oxford Network member hospitals reported 314 811 infants 24 to 29 weeks' gestational age at birth without major congenital abnormalities who survived to discharge from the hospital. Using quantile regression, adjusting for infant characteristics and complexity of hospital course, we estimated differences in median age, weight, and discharge weight z score at discharge stratified by gestational age at birth and by NICU type.

From 2005 to 2018, postmenstrual age at discharge increased an estimated 8 (compatibility interval [CI]: 8 to 9) days for all infants. For infants initially discharged from the hospital, discharge weight increased an estimated 316 (CI: 308 to 324) grams, and median discharge weight z score increased an estimated 0.19 (CI: 0.18 to 0.20) standard units. Increases occurred within all birth gestational ages and across all NICU types. The proportion of infants discharged home from the hospital on human milk increased, and the proportions of infants discharged home from the hospital on oxygen or a cardiorespiratory monitor decreased.

Gestational age and weight at discharge increased steadily from 2005 to 2018 for survivors 24 to 29 weeks' gestation with undetermined causes, benefits, and costs.

The families of hospitalised preterm infants risk depression and post-traumatic stress and the preterm infants risk re-hospitalisation. The French neonatal society's aim was to review the literature on how the transition from hospital to home could limit these risks and to produce a position paper.

A systematic literature review was performed covering 1 January 2000 to 1 January 2018, and multidisciplinary experts examined the scientific evidence.

We identified 939 English and French papers and 169 are quoted in the position paper. Most studies stressed the importance of early, personalised and progressive involvement of the family. Healthcare staff and families should assess discharge preparations jointly. This evaluation should assess the capacities of the newborn infant, with regard to its physiological maturity. It should also assess the family's ability to supply the medical, psychological and social assistance required before and after discharge. There should be a structured follow-up process that includes effective communication, various tools, interventions, networks, health and social professionals.

Discharge preparations may improve the transition from hospital to home and the outcomes for the parents and newborn preterm infant. This early family-centred approach should be structured, coordinated and based on individual needs and circumstances.

Preterm infants and term infants with complex medical conditions are often discharged home with technological support. There is a scarcity of evidence-based guidelines for post-discharge management of these infants at high risk. Common diagnoses necessitating the need for respiratory support and/or monitoring devices include apnea of prematurity and bronchopulmonary dysplasia for preterm infants, and upper airway anomalies, central nervous system disorders, and neuromuscular disorders for term infants. Some infants who are unable to receive complete oral feeds for various reasons are sometimes discharged home with nasogastric or gastrostomy tube feeds. For safe patient care at home and reduction of emergency department visits, there should be proper transition of care from hospital to primary care provider, and appropriate instruction of caregivers for care of the infant including teaching about medications, feeding, and management of medical devices. Primary care providers should be aware of these common supportive devices and their complications to provide timely intervention if needed. [Pediatr Ann. 2020;49(2):e88-e92.].

To assess site variability and concomitant respiratory support related to the timing of caffeine discontinuation, and compare clinical characteristics of infants who discontinued caffeine before vs. within the last week of hospitalization.

Cohort study of 81,110 infants <35 weeks gestational age and <1500 g birth weight discharged from 304 neonatal intensive care units from 2001-2016.

The mean postmenstrual age at caffeine discontinuation ranged from 32 to 37 weeks among sites. Respiratory support at the time of discontinuation was common, but variable, with 0-57% of infants receiving positive airway pressure at caffeine discontinuation by site. Infants who discontinued caffeine within the last week of hospitalization had longer total duration of caffeine, but were discharged from the hospital at an earlier postmenstrual age.

There was substantial variability among sites in the timing of caffeine discontinuation before discharge and respiratory support at the time of caffeine discontinuation.

Objective: Ensuring cardiorespiratory (CR) stability is essential for a safe discharge. The aim of this study was to assess the impact of a new pre-discharge protocol named CORE on the risk of hospital readmission (RHR). Methods: Preterm infants admitted in our NICU between 2015 and 2018 were randomly assigned to CORE (exposed) or to standard (not-exposed) discharge protocol. CORE included 24 h-clinical observation, followed by 24 h-instrumental CR monitoring only for high-risk infants. RHR 12 months after discharge and length of stay represent the primary and secondary outcomes, respectively. Results: Three hundred and twenty three preterm infants were enrolled. Exposed infants had a lower RHR (log-rank p < 0.05). The difference was especially marked 3 months after discharge (9.09 vs. 21.6%; p = 0.004). The hospital length of stay in exposed and not-exposed infants was 39(26-58) and 43(26-68) days, respectively (p = 0.16). Conclusions: The CORE protocol could help neonatologists to define the best timing for discharge reducing RHR without lengthening hospital stay.

To characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants.

We used electronic health records (2010-2013) from 4 neonatal intensive care units to identify infants of ≤28 weeks of gestational age exposed to caffeine citrate. Safety outcomes included death, bronchopulmonary dysplasia, necrotizing enterocolitis, spontaneous intestinal perforation, intraventricular hemorrhage, patent ductus arteriosus ligation, seizures, and arrhythmias. We used multivariable logistic regression to evaluate the association of caffeine citrate exposure with clinical events.

Of 410 infants with a median (IQR) gestational age of 26 (24-27) weeks, 95% received caffeine citrate for >0 days. Infants received a median (IQR) daily dose of 8 (5-10) mg/kg/day. Incidences of clinical events on day of caffeine citrate exposure were death 2%, patent ductus arteriosus ligation 12%, and medical and surgical necrotizing enterocolitis 5% and 4%, respectively. Bronchopulmonary dysplasia occurred in 37% of infants and was not associated with caffeine dose. Increased caffeine citrate dose was associated with lower odds of patent ductus arteriosus ligation and necrotizing enterocolitis.

Caffeine citrate was used in extremely premature infants at younger gestation, at higher doses, and for longer durations than recommended on the drug label. Increased caffeine citrate exposure, dose, or therapy duration was not associated with increased risk of necrotizing enterocolitis.

This study sought to characterize trends in the diagnosis of apnea, associated comorbidities and complications, and 30-day readmission rates in preterm singleton infants.

The study design was a retrospective, longitudinal, observational study. 2003-2014 New York State Statewide Planning and Research Cooperative System and New York City Vital Statistics databases were merged identifying preterm live singleton births. Hospitalizations of preterm newborns with and without apnea were compared; multivariable logistic regression and log-linear Poisson regression models applied.

Of 1,384,013 singleton births, 7.5% were identified as preterm. While relative risk of preterm birth rates declined (RR = 0.987, 95% CI = 0.982-0.991), the diagnosis of apnea increased significantly (RR = 1.069, 95% CI = 1.049-1.089). Multivariable analysis identified two apnea predictors, gastric reflux (OR = 3.19, 95% CI = 2.80-3.63) and early gestational age (OR = 0.83 for 1 week GA increase, 95% CI = 0.82-0.84). Preterm newborns with apnea were more likely to be readmitted within the first 30 days and total charges were 5.4 times higher.

While the preterm birth rate has declined the rate of diagnosis of apnea with associated comorbidities and complications has increased. Given the additional findings of higher 30-day readmission rates and charges, more multidisciplinary research appears warranted to identify ways to optimize the quality of high risk newborn care.

To study the impact of implementing a protocol to standardize the duration of observation in preterm infants with apnea/bradycardia/desaturation spells before hospital discharge on length of stay (LOS) and readmission rates.

A protocol to standardize the duration of in-hospital observation for preterm infants with apnea, bradycardia and desaturation spells who were otherwise ready for discharge was implemented in December 2013. We evaluated the impact of this protocol on the LOS and readmission rates of very low birth weight infants (VLBW). Data on readmission for apnea and an apparent life-threatening event (ALTE) within 30 days of discharge were collected. The pre-implementation epoch (2011 to 2013) was compared to the post-implementation period (2014 to 2016).

There were 426 and 368 VLBW discharges before and after initiation of the protocol during 2011 to 2013 and 2014 to 2016, respectively. The LOS did not change with protocol implementation (66±42 vs 64±42 days before and after implementation of the protocol, respectively). Interprovider variability on the duration of observation for apneic spells (F-8.8, P=0.04) and bradycardia spells (F-17.4, P<0.001) decreased after implementation of the protocol. The readmission rate for apnea/ALTE after the protocol decreased from 12.1 to 3.4% (P=0.01).

Implementing an institutional protocol for VLBW infants to determine the duration of apnea/bradycardia/ desaturation spell-free observation period as recommended by the American Academy of Pediatrics clinical report did not prolong the LOS but effectively reduced interprovider variability and readmission rates.

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. Episodes of central apnea/bradycardia/desaturation (ABDs), and percent time with SpO₂ <88% and <75% were measured. Results: ABDs were analyzed in 302 preterm infants (mean gestational age 27.6 weeks) around the time of 485 serum caffeine levels, 90 caffeine boluses, and 273 episodes of caffeine discontinuation. Higher serum caffeine levels were not associated with fewer ABDs or higher heart rate. For caffeine boluses given due to clinically recognized spells, hypoxemia and algorithm-detected ABDs decreased day 1-2 after the bolus compared to the day before and day of the bolus (mean 4.4 events/day after vs. 6.6 before, p = 0.004). After caffeine discontinuation, there was no change in hypoxemia and a small increase in ABDs (2 events/day 3-5 days after discontinuation vs. 1 event/day before and >5 days after, p < 0.01). This increase in ABDs occurred irrespective of gestational age, respiratory support, or postmenstrual age at the time caffeine was stopped. Conclusions: In this retrospective analysis, caffeine boluses and caffeine discontinuation were associated with a small change in the number of ABD events in preterm infants.

Home cardiorespiratory monitoring has changed significantly since it was first introduced in the 1970s. It has improved from a simple alarm system to a sophisticated piece of equipment capable of monitoring the patient's electrocardiogram, respiratory effort, and oxygen saturations. In addition, the indications for using a monitor have also changed. The home monitor was initially used to reduce the incidence of sudden infant death syndrome (SIDS). Although there were several studies demonstrating the reduction of SIDS rates in communities where apnea programs existed, none was a prospective, double-blinded study or had adequate numbers to be clinically significant. Therefore, the American Academy of Pediatrics took the stance that monitors were not an effective way to reduce SIDS. However, when used appropriately, as part of a complete program (ie, the monitor is just one of many clinically based modalities), by a clinician with expertise in interpreting download tracings, home cardiorespiratory monitoring can be a useful, lifesaving, and economical tool to observe infants who are at increased risk of sudden death or increased morbidity secondary to intermittent hypoxia. [Pediatr Ann. 2017;46(8):e303-e308.].

To describe the prevalence of apnea in otherwise healthy term newborns, identify attributable length of stay (LOS) and healthcare utilization (cost) of apnea, and measure hospital variation in attributable LOS and cost of apnea in this population.

We conducted a secondary analysis of a national administrative dataset, the 2012 Kids' Inpatient Database, which included 3.4 million newborn discharges in the US. The birth hospitalizations of approximately 2.6 million otherwise healthy, full-term newborns were included for analysis. Attributable LOS and cost of apnea were calculated using multivariate analyses.

Apnea was diagnosed in 1 in 1000 healthy full-term newborns. Multivariate analyses showed that newborns with apnea had 0.6 days longer LOS (P < .001) and $483 greater costs (P < .001) compared with healthy term newborns, per birth hospitalization. Newborns diagnosed with apnea plus hypoxia and/or bradycardia had 1.4 days longer LOS (P < .001) and $653 greater costs (P < .001). The attributable LOS and cost attributable to apnea varied between individual hospitals and differed by hospital region.

Apnea is associated with higher LOS and cost in the newborn hospitalization, with variation in hospital practice. This suggests the need for better comprehension of the underlying physiology and standardization of practice in its management in the term newborn.

To assess comorbid conditions and clinical outcomes among late preterm and low birth weight term infants (<2.5 kg) who failed the Infant Car Seat Challenge (ICSC) on the Mother-Baby Unit.

This was a retrospective chart review of consecutive infants who failed ICSC on the Mother-Baby Unit and were subsequently admitted to the neonatal intensive care unit at Prentice Women's Hospital between January 1, 2009, and December 31, 2015. Regression models were used to estimate risk differences (RDs) with 95% CIs for factors related to length of stay.

A total of 148 infants were studied (43% male; 37% delivered via cesarean). ICSC failure in the Mother-Baby Unit was due to desaturation, bradycardia, and tachypnea in 59%, 37%, and 4% of infants, respectively. During monitoring on the neonatal intensive care unit, 39% of infants experienced apnea (48% in preterm vs 17% in term infants) in the supine position, 19% received phototherapy, and 2% and 6.8% received nasogastric and thermoregulatory support, respectively. Univariate predictors of increased duration of stay (days) were younger gestational age, apnea, nasogastric support, intravenous fluids, and antibiotics (all P < .05). In multivariable analysis adjusted for gestational age and discharge weight, only apnea (RD, 4.87; 95% CI, 2.99-6.74; P < .001), administration of antibiotics (RD, 3.25; 95% CI, 0.29-6.21; P < .032), and intravenous fluid support (RD, 4.87; 95% CI, 0.076-9.66; P < .047) remained independent predictors of a longer duration of stay.

Infants who failed ICSC were at risk for comorbid conditions that prolonged hospital stay beyond the neonatal intensive care unit observation period. Almost one-half of late preterm infants who failed ICSC had apnea events in the supine position.

Apnea, bradycardia, and oxygen desaturation events are a common in neonatal intensive care units, with relevant literature to date largely focusing on very low birth weight and extremely low birth weight infants. We conducted a retrospective review of infants born at ≥34 weeks gestational age at 2 tertiary neonatal intensive care units in Boston, MA, between January 2009 and December 2013. Our objectives included (1) describing the diagnostic evaluations performed in late preterm to term infants with discharge-delaying apnea, bradycardia, or oxygen desaturation events and (2) identifying variables associated with home monitor use. Of the 741 eligible infants identified, diagnostic evaluations were variable and infrequent with blood culture, blood glucose, and head ultrasound performed most commonly. The likelihood of home monitor use was greater in infants with either a prolonged inpatient stay or greater gestational age at birth.

Apnea of prematurity (AOP) is nearly universal among very preterm infants, but neither the apnea burden nor its clinical associations have been systematically studied in a large consecutive cohort.

We analyzed continuous bedside monitor chest impedance and electrocardiographic waveforms and oxygen saturation data collected on all neonatal intensive care unit (NICU) patients <35 wk gestation from 2009 to 2014 (n = 1,211; >50 infant-years of data). Apneas, with bradycardia and desaturation (ABDs), defined as central apnea ≥10 s associated with both bradycardia <100 bpm and oxygen desaturation <80%, were identified using a validated automated algorithm.

Number and duration of apnea events decreased with increasing gestational age (GA) and postmenstrual age (PMA). ABDs were more frequent in infants <31 wk GA at birth but were not more frequent in those with severe retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), or severe intraventricular hemorrhage (IVH) after accounting for GA. In the day before diagnosis of late-onset septicemia and necrotizing enterocolitis, ABD events were increased in some infants. Many infants continued to experience short ABD events in the week prior to discharge home.

Frequency of apnea events is a function of GA and PMA in infants born preterm, and increased apnea is associated with acute but not with chronic pathologic conditions.

Apnea of Prematurity (AOP) is common, affecting the majority of infants born at <34 weeks gestational age. Apnea and periodic breathing are accompanied by intermittent hypoxia (IH). Animal and human studies demonstrate that IH exposure contributes to multiple pathologies, including retinopathy of prematurity (ROP), injury to sympathetic ganglia regulating cardiovascular action, impaired pancreatic islet cell and bone development, cerebellar injury, and neurodevelopmental disabilities. Current standard of care for AOP/IH includes prone positioning, positive pressure ventilation, and methylxanthine therapy; these interventions are inadequate, and not optimal for early development.

The objective is to support breathing in premature infants by using a simple, non-invasive vibratory device placed over limb proprioceptor fibers, an intervention using the principle that limb movements trigger reflexive facilitation of breathing.

Premature infants (23-34 wks gestational age), with clinical evidence of AOP/IH episodes were enrolled 1 week after birth. Caffeine treatment was not a reason for exclusion. Small vibration devices were placed on one hand and one foot and activated in 6 hour ON/OFF sequences for a total of 24 hours. Heart rate, respiratory rate, oxygen saturation (SpO2), and breathing pauses were continuously collected.

Fewer respiratory pauses occurred during vibration periods, relative to baseline (p<0.005). Significantly fewer SpO2 declines occurred with vibration (p<0.05), relative to control periods. Significantly fewer bradycardic events occurred during vibration periods, relative to no vibration periods (p<0.05).

In premature neonates, limb proprioceptive stimulation, simulating limb movement, reduces breathing pauses and IH episodes, and lowers the number of bradycardic events that accompany aberrant breathing episodes. This low-cost neuromodulatory procedure has the potential to provide a non-invasive intervention to reduce apnea, bradycardia and intermittent hypoxia in premature neonates.

ClinicalTrials.gov NCT02641249.

To determine the predictive value of (1) maternal, (2) maturational, (3) comorbid and (4) discharge domains associated with preterm infant rehospitalization.

Retrospective, cohort study of preterm infants discharged home from a level IV neonatal intensive care unit. Rates of unplanned and planned 6-month readmissions were assessed. The four domains were modeled incrementally and separately to predict relative and combined contributions to the readmission risk.

Out of 504 infants, 5% had 30-day readmissions (22 unplanned, three planned). By 6 months, 13% were rehospitalized (52 unplanned, 15 planned). Sixty-seven infants had 96 readmission events with 30% of readmission events elective. The four domains together predicted 78% of total 1-month, all 6-month and unplanned 6-month readmissions. Discharge complexity was as predictive as comorbidity in all models.

These four-domain models were more predictive than single domains. Many total readmission events were planned, suggesting parsing planned and unplanned rehospitalizations may benefit quality-improvement efforts.

The aim of the study was to survey level 2 and 3 neonatal units in Australasia to determine the prevalence of oximetry studies at discharge for preterm infants, how these oximetry studies are performed, and which measures are included in an oximetry report.

A 10-question online survey was created using Survey Monkey regarding use of predischarge oximetry and e-mailed to 46 neonatal units (all level 2 and three units in NZ and all level 3 units in Australia).

The response rate was 59% (27/46) with a NZ response rate of 78% (18/23). There was variation in the groups of infants receiving predischarge oximetry studies, with one fifth of responding neonatal units never performing oximetry at discharge. Of the units using predischarge oximetry screening, infants being discharged home on supplemental oxygen were the only group for which all units perform predischarge oximetry. Masimo (Masimo, Irvine, California, USA) is the most common oximeter brand and profox Associates, Inc. (PROFOX Associates, Inc., Escondido, CA 92025, USA) the most common analysis software used. Measures included in oximetry reports vary between units, with profox Associates, Inc.'s default event definition of 'a drop in saturation by four or more' being the most commonly reported desaturation definition.

These findings indicate a need for guidelines to standardise preterm infant oximetry monitoring at neonatal discharge. Further research is required to determine the utility of predischarge oximetry and to establish which infants should be screened.

To determine the half-life of serum caffeine concentrations and its relation to apnea of prematurity (AOP) after caffeine is discontinued in preparation for hospital discharge.

Prospective cohort study involving preterm infants with gestational ages ⩽33 weeks at birth. After caffeine was discontinued, serum caffeine concentrations and electronic detection of pathologic apnea, defined a priori, were obtained at 24 and 168 h, respectively.

Caffeine levels decreased from 13.3±3.8 to 4.3±2 mg l(-1) (n=50, mean±s.d.) at 24 and 168 h, respectively (P<0.01). The mean caffeine half-life was 87±25 h at 35±1 weeks postmenstrual age. Seven days after discontinuation of caffeine, 64% of the infants had pathologic apnea.

Hospital discharge planning for preterm infants with a history of AOP should be carefully considered after discontinuing caffeine. This study showed that caffeine may not reach subtherapeutic levels until around 11-12 days.

Apnea of prematurity is one of the most common diagnoses in the NICU. Despite the frequency of apnea of prematurity, it is unknown whether recurrent apnea, bradycardia, and hypoxemia in preterm infants are harmful. Research into the development of respiratory control in immature animals and preterm infants has facilitated our understanding of the pathogenesis and treatment of apnea of prematurity. However, the lack of consistent definitions, monitoring practices, and consensus about clinical significance leads to significant variation in practice. The purpose of this clinical report is to review the evidence basis for the definition, epidemiology, and treatment of apnea of prematurity as well as discharge recommendations for preterm infants diagnosed with recurrent apneic events.

To discover a predictor, that could be used at least 3 to 4 weeks' before discharge, to identify infants who would need home oxygen therapy. We hypothesized that infants requiring a high level of respiratory support at 34 weeks' postmenstrual age (PMA) would require home oxygen.

Single center retrospective study of 143 infants less than 28 weeks' gestation. We determined when infants weaned from each level of respiratory support (mechanical ventilation, nasal continuous airway pressure [nCPAP] or biphasic positive pressure, nasal cannula flow ≥ 2 L/min, nasal cannula flow < 2 L/min or no respiratory support). Our primary outcome was need for home oxygen.

Infants who required nCPAP at 34 weeks' PMA had a 100% positive predictive value for home oxygen therapy.

Higher levels of respiratory support at 34 weeks' PMA can predict the need for home oxygen and is useful in preparing patients and families for discharge.

To examine the success rate of our current practice of discontinuing caffeine at 33 0/7-35 6/7 weeks post menstrual age (PMA), as well as factors that predict the success or failure of discontinuation.

A retrospective chart review of infants born before 34 weeks gestational age between 2006-2012. Data collected included demographics, and other comorbidities mainly complications of prematurity.

647 treated infants had caffeine discontinued at 33-35 PMA before discharge or transfer. 64 (10% ) infants failed discontinuation and had caffeine restarted. Most (77% ) of those who failed started having monitor alarms within 7 days of discontinuation. BPD and Hispanic ethnicity were predictive of weaning failure (p <  0.05).

Caffeine can be discontinued at 33-35 weeks PMA with a failure rate of 10% . BPD and Hispanic ethnicity are predictive of failure. It is generally safe to discharge infants seven days after the caffeine was discontinued if no significant monitor events occur during that time.

Apnea of prematurity is very frequent in premature newborns (PNB). If the apnea episode is not interrupted in time, it can cause several damages to the newborn's central nervous system. In this paper, we introduce a novel technology for detecting apnea of prematurity episodes, based on cardiac pulse frequency (PF) and arterial oxygen saturation (SpO2) simultaneously, and using vibrotactile stimulation to interrupt such episodes. The thresholds of the newborns' PF and SpO2 had been established to identify the apnea episode automatically through the proposed system: for babies ≤ 35 weeks gestation, PF is ≤ 100 bpm and SpO2 ≤ 80%; for babies > 35 weeks gestation, PF is ≤ 80 bpm and SpO2 ≤ 80%. The system used vibrotactile stimuli at 250 Hz for 4 s. To manage the system that activates the vibratory device automatically and registers those parameters, a program had been developed. It registers apnea occurrence, period of manual stimulation and vibratory stimulation duration. This technique was tested on 4 PNB. It was observed 10 apnea episodes and the device was successful in the detection of all of them. The vibrotactile stimulation was capable of promoting the return of respiratory movements in 9 of the 10 detected events of apnea and seemed to be a promising means of handling them.

Compare how NICUs within academic centers in Canada, France, and the United States make discharge decisions regarding cardiorespiratory recordings and home use of apnea monitors, oximeters and caffeine.

An anonymous survey was sent to neonatologists through the member listserv of the American Academy of Pediatrics Section on Perinatal Pediatrics, the Canadian Fellowship Program Directory, and to Level 3 NICUs in France.

The response rates were 89% , 83% , and 79% for US, Canada and France respectively. In Canada, 45% perform pre-discharge recordings vs. 38% in France and 24% in the US. Apnea free days prior to discharge were required in 100% of centers in Canada, 96% in France, and 92% in the US. In Canada and France, 65% and 68% of units discharge patients on monitors vs. 99% in the US. 64% of the US centers sometimes use home caffeine compared to 40% in Canada and 34% in France. Over 60% of the centers in Canada and France wait until at least 40 weeks post menstrual age to discharge patients, whereas only about 33% of the US wait that late to discharge patients.

Discharge practices from NICUs are not well standardized across institutions or countries. Canada and France keep infants in the hospital longer and are less likely than the US to use home monitoring and home caffeine.

Apnea is nearly universal among very low birth weight (VLBW) infants, and the associated bradycardia and desaturation may have detrimental consequences. We describe here very long (>60 s) central apnea events (VLAs) with bradycardia and desaturation, discovered using a computerized detection system applied to our database of over 100 infant years of electronic signals. Eighty-six VLAs occurred in 29 out of 335 VLBW infants. Eighteen of the 29 infants had a clinical event or condition possibly related to the VLA. Most VLAs occurred while infants were on nasal continuous positive airway pressure, supplemental oxygen, and caffeine. Apnea alarms on the bedside monitor activated in 66% of events, on average 28 s after cessation of breathing. Bradycardia alarms activated late, on average 64 s after cessation of breathing. Before VLAs oxygen saturation was unusually high, and during VLAs oxygen saturation and heart rate fell unusually slowly. We give measures of the relative severity of VLAs and theoretical calculations that describe the rate of decrease of oxygen saturation. A clinical conclusion is that very long apnea (VLA) events with bradycardia and desaturation are not rare. Apnea alarms failed to activate for about one-third of VLAs. It appears that neonatal intensive care unit (NICU) personnel respond quickly to bradycardia alarms but not consistently to apnea alarms. We speculate that more reliable apnea detection systems would improve patient safety in the NICU. A physiological conclusion is that the slow decrease of oxygen saturation is consistent with a physiological model based on assumed high values of initial oxygen saturation.

Apnea of prematurity, a common disorder, can severely compromise an infant's condition unless correctly diagnosed and treated. Infants with a history of apnea of prematurity can be discharged home but then be rehospitalized for an apneic event, an apparent life-threatening event, or sudden infant death syndrome. The definition of a clinically significant cardiopulmonary event, such events' documentation, and the treatment approach were standardized, and discharge criteria were refined.

A prospective, single-center comparison was conducted between a group of premature infants before and after implementation of the standard approach. Data were collected prospectively from August 1, 2005, through July 21, 2006, for the prestandard-approach group and from August 1, 2006, through September 16, 2007, for the standard-approach group.

Twenty-two (35%) of the 63 infants in the prestandard-approach group experienced discharge delays because of poor documentation, whereby the clinician could not determine the safety of discharge. This resulted in 59 additional hospital days (mean length-of-stay [LOS] increase, 5.7 days). The standard-approach group of 72 infants experienced no discharge delays and no additional hospital days, and LOS decreased (all p < .0001). Annual charges were reduced by more than $58,000 in avoiding unnecessary hospital days. Readmission to the hospital for apnea of prematurity occurred for 5 (7.9%) of the prestandard-approach group but none of the standard-approach group (p = .0203). Overall compliance with the standardization process has been maintained at > or = 96%.

Implementation of a standard approach to the definition of apnea of prematurity and its treatment and documentation decreases LOS and reduces cost.

Maturational changes of breathing during sleep contribute to the unique features of childhood sleep disorders. The clinician's ability to evaluate common disorders related to sleep in children relies on an understanding of normal patterns of breathing during sleep across the ages. This article reviews respiratory physiology during sleep throughout childhood. Specific topics include an overview of respiration during sleep, normal parameters through childhood including respiratory rate, oxygen saturation, and measures of carbon dioxide, normal patterns of apneas throughout childhood, and features of breathing during sleep seen in term and preterm infants.

We conducted a randomized trial to test the hypothesis that mother's voice played through a pacifier-activated music player (PAM) during nonnutritive sucking would improve the development of sucking ability and promote more effective oral feeding in preterm infants.

Preterm infants between 34 0/7 and 35 6/7 weeks' postmenstrual age, including those with brain injury, who were taking at least half their feedings enterally and less than half orally, were randomly assigned to receive 5 daily 15-minute sessions of either PAM with mother's recorded voice or no PAM, along with routine nonnutritive sucking and maternal care in both groups. Assignment was masked to the clinical team.

Ninety-four infants (46 and 48 in the PAM intervention and control groups, respectively) completed the study. The intervention group had significantly increased oral feeding rate (2.0 vs. 0.9 mL/min, P < .001), oral volume intake (91.1 vs. 48.1 mL/kg/d, P = .001), oral feeds/day (6.5 vs. 4.0, P < .001), and faster time-to-full oral feedings (31 vs. 38 d, P = .04) compared with controls. Weight gain and cortisol levels during the 5-day protocol were not different between groups. Average hospital stays were 20% shorter in the PAM group, but the difference was not significant (P = .07).

A PAM using mother's voice improves oral feeding skills in preterm infants without adverse effects on hormonal stress or growth.

In 2006 the apnea of prematurity (AOP) consensus group identified inaccurate counting of apnea episodes as a major barrier to progress in AOP research. We compare nursing records of AOP to events detected by a clinically validated computer algorithm that detects apnea from standard bedside monitors.

Waveform, vital sign, and alarm data were collected continuously from all very low-birth-weight infants admitted over a 25-month period, analyzed for central apnea, bradycardia, and desaturation (ABD) events, and compared with nursing documentation collected from charts. Our algorithm defined apnea as > 10 seconds if accompanied by bradycardia and desaturation.

Of the 3,019 nurse-recorded events, only 68% had any algorithm-detected ABD event. Of the 5,275 algorithm-detected prolonged apnea events > 30 seconds, only 26% had nurse-recorded documentation within 1 hour. Monitor alarms sounded in only 74% of events of algorithm-detected prolonged apnea events > 10 seconds. There were 8,190,418 monitor alarms of any description throughout the neonatal intensive care unit during the 747 days analyzed, or one alarm every 2 to 3 minutes per nurse.

An automated computer algorithm for continuous ABD quantitation is a far more reliable tool than the medical record to address the important research questions identified by the 2006 AOP consensus group.

To compare apnea events recorded by bedside cardiorespiratory monitor and nursing documentation with those detected by visual inspection of continuous electronic cardiorespiratory waveform.

In a prospective observational study, 20 nonventilated infants of 28 to 33 weeks' gestational age were monitored for apnea during the first 2 postnatal weeks. Apnea was defined as a respiratory pause > 20 seconds or > 15 seconds if associated with a heart rate < 80/min or oxygen saturation < 85%. True apnea was defined as one for which visual inspection of continuous electronic cardiorespiratory waveform on the central monitor verified apnea.

The number of apnea episodes recorded by nursing documentation and bedside monitors were 207 and 418, respectively. Only 7.7% of apnea events recorded by nursing documentation were confirmed as true apnea compared with 50.4% of apnea recorded by bedside monitors and the difference was statistically significant. Of true apnea (n = 211) episodes recorded on central monitors, 99% were recorded by bedside monitors but only 7.6% of apnea occurrences were recorded by nursing personnel.

Nursing documentation does not provide accurate monitoring of apnea. Although bedside monitors have better sensitivity and specificity than nursing documentation, future research should be directed to improve the specificity of bedside monitoring.

Late preterm infants are infants who are premature, but often mature enough to be managed in settings and with treatment plans appropriate for term newborns. They are arbitrarily defined as infants born at gestational ages of 34, 35 and 36 weeks. Late preterm infants have more problems with adaptation than term infants, and may require neonatal intensive care and prolonged admission. However, those who do not may, appropriately, be triaged to mother-baby care in a low-risk nursery setting. Special attention must be offered to the late preterm infant in ensuring adequate thermal homeostasis and the establishment of successful feeding before discharge. In particular, care must be taken to ensure that these babies do not experience severe late hyperbilirubinemia, which characteristically occurs in the breastfeeding late preterm infant at four to five days of age and is not always predictable by routine bilirubin screening before 48 h of age. Discharge of a late preterm infant places particular demands on the community; accessible facilities for retesting, re-evaluation and readmission must be made available by the discharging institution.

Late and moderate preterm infants form the majority of admissions for prematurity to special care neonatal nurseries. Although at risk for acute disorders of prematurity, they do not suffer the serious long term risks and chronic illnesses of the extremely premature. The special challenges addressed here are of transition and of thermal adaptation, nutritional compensation for postnatal growth restriction, the establishment of early feeding, and the avoidance of post-discharge jaundice or apnea. These 'healthy' premature infants provide challenges for discharge planning, in that opportunities may be available for discharge well before the expected date of delivery, which should be pursued. Barriers to early discharge are rigid conservative protocols and unwarranted investigations; facilitators of discharge are individualized care by nurses expert in cue-based feeding, early management of the thermal environment, support of family preferences and encouragement of mother-baby interactions. Safe discharge depends on recognizing these opportunities and applying strategies to address them.

In healthy neonates, connections between the heart and lungs through brain stem chemosensory pathways and the autonomic nervous system result in cardiorespiratory synchronization. This interdependence between cardiac and respiratory dynamics can be difficult to measure because of intermittent signal quality in intensive care settings and variability of heart and breathing rates. We employed a phase-based measure suggested by Schäfer and coworkers (Schäfer C, Rosenblum MG, Kurths J, Abel HH. Nature 392: 239-240, 1998) to obtain a breath-by-breath analysis of cardiorespiratory interaction. This measure of cardiorespiratory interaction does not distinguish between cardiac control of respiration associated with cardioventilatory coupling and respiratory influences on the heart rate associated with respiratory sinus arrhythmia. We calculated, in sliding 4-min windows, the probability density of heartbeats as a function of the concurrent phase of the respiratory cycle. Probability density functions whose Shannon entropy had a <0.1% chance of occurring from random numbers were classified as exhibiting interaction. In this way, we analyzed 18 infant-years of data from 1,202 patients in the Neonatal Intensive Care Unit at University of Virginia. We found evidence of interaction in 3.3 patient-years of data (18%). Cardiorespiratory interaction increased several-fold with postnatal development, but, surprisingly, the rate of increase was not affected by gestational age at birth. We find evidence for moderate correspondence between this measure of cardiorespiratory interaction and cardioventilatory coupling and no evidence for respiratory sinus arrhythmia, leading to the need for further investigation of the underlying mechanism. Such continuous measures of physiological interaction may serve to gauge developmental maturity in neonatal intensive care patients and prove useful in decisions about incipient illness and about hospital discharge.

Apnea of prematurity is an important and common clinical problem, and is often the rate-limiting process in NICU discharge. Accurate detection of episodes of clinically important neonatal apnea using existing chest impedance (CI) monitoring is a clinical imperative. The technique relies on changes in impedance as the lungs fill with air, a high impedance substance. A potential confounder, however, is blood coursing through the heart. Thus, the cardiac signal during apnea might be mistaken for breathing. We report here a new filter to remove the cardiac signal from the CI that employs a novel resampling technique optimally suited to remove the heart rate signal, allowing improved apnea detection. We also develop an apnea detection method that employs the CI after cardiac filtering. The method has been applied to a large database of physiological signals, and we prove that, compared to the presently used monitors, the new method gives substantial improvement in apnea detection.