Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Infants Born Extremely Preterm.

OBJECTIVE: The objective of this study was to examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks of gestational age) on vs off invasive mechanical ventilation. STUDY DESIGN: This is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in 5 level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean gestational age: 26.4 weeks, SD 1.71). Monitoring data were available and analyzed for 719 infants (47 512 patient-days); of whom, 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72 hours after birth and ≥5-day antibiotics). RESULTS: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer events with oxygen saturation <80% (IH80) and more bradycardia events before sepsis. IH events were associated with higher sepsis risk but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model including postmenstrual age, cardiorespiratory variables (apnea, periodic breathing, IH80, and bradycardia), and ventilator status predicted sepsis with an area under the receiver operator characteristic curve of 0.783. CONCLUSION: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.

Patent Ductus Arteriosus and Development of Bronchopulmonary Dysplasia-associated Pulmonary Hypertension.

Rationale: Extremely preterm infants with evolving bronchopulmonary dysplasia (BPD) are at risk for development of BPD-associated pulmonary hypertension (BPD-PH). A patent ductus arteriosus (PDA) shunt may be a modifiable risk factor for BPD-PH development. Objective: To determine whether the presence and duration of ductus arteriosus patency differs between extremely preterm infants with and without BPD-PH. Methods: We conducted a retrospective case-control study among preterm infants of gestational age 22 weeks, 0 days, to 28 weeks, 6 days, who remained on respiratory support on postnatal day 28 at the University of Alabama at Birmingham from 2017 to 2020. Infants who were diagnosed with PH (cases) by echocardiography were compared with infants without PH (control subjects). Data from echocardiograms performed during the hospitalization after postnatal day 28 were included. Logistic regression adjusted for covariates that differed significantly between groups. A probit analysis related the duration of ductal patency to the development of BPD-PH. Measurements and Main Results: A total of 138 infants developed BPD alone, and 82 infants developed BPD-PH. After adjustment for differing covariates between groups, both PDA (adjusted odds ratio, 4.29; 95% confidence interval, 1.89-9.77) and moderate to large PDA (adjusted odds ratio, 4.15; 95% confidence interval, 1.78-9.64) remained significantly related to BPD-PH at discharge. By probit analysis, each additional month of PDA and hemodynamically significant PDA exposure was associated with an increased probability for the composite outcome of BPD-PH at discharge or death with coefficients of 0.40 (P < 0.001) and 0.45 (P < 0.001), respectively. Conclusions: In extremely preterm infants on respiratory support on postnatal day 28, both the presence of and a longer duration of ductus arteriosus patency were associated with the development of BPD-PH.

Intermittent Hypoxemia and Bronchopulmonary Dysplasia with Pulmonary Hypertension in Preterm Infants.

Rationale: Bedside biomarkers that allow early identification of infants with bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) are critically important, given the higher risk of death in these infants. Objectives: We hypothesized that infants with BPD-PH have patterns of intermittent hypoxemia (IH) that differ from infants with BPD without PH. Methods: We conducted a matched case-control study of extremely preterm infants from 22 weeks 0 days to 28 weeks 6 days born between 2018 and 2020 at the University of Alabama at Birmingham. BPD-PH status was determined using echocardiographic data performed after postnatal Day 28. Physiologic data were compared between infants with BPD-PH (cases) and BPD alone (control subjects). Receiver operating characteristic (ROC) analysis estimated the predictive ability of cumulative hypoxemia, desaturation frequency, and duration of intermittent hypoxemic events in the week preceding echocardiography to discriminate between cases and control subjects. Measurements and Main Results: Forty infants with BPD-PH were compared with 40 infants with BPD alone. Infants with and without PH had a similar frequency of IH events, but infants with PH had more prolonged hypoxemic events for desaturations below 80% (7 s vs. 6 s; P = 0.03) and 70% (105 s vs. 58 s; P = 0.008). Among infants with BPD-PH, infants who died had longer hypoxemic events below 70% (145 s vs. 72 s; P = 0.01). Using the duration of hypoxemic events below 70%, the areas under the ROC curves for diagnosis of BPD-PH and death in BPD-PH infants were 0.71 and 0.77, respectively. Conclusions: Longer duration of intermittent hypoxemic events was associated both with a diagnosis of BPD-PH and with death among infants with BPD-PH.

Early-Life Outcomes in Relation to Social Determinants of Health for Children Born Extremely Preterm.

OBJECTIVE: To characterize the relationships between social determinants of health (SDOH) and outcomes for children born extremely preterm. STUDY DESIGN: This is a cohort study of infants born at 22-26 weeks of gestation in National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2017) who survived to discharge. Infants were classified by 3 maternal SDOH: education, insurance, and race. Outcomes included postmenstrual age (PMA) at discharge, readmission, neurodevelopmental impairment (NDI), and death postdischarge. Regression analyses adjusted for center, perinatal characteristics, neonatal morbidity, ethnicity, and 2 SDOH (eg, group comparisons by education adjusted for insurance and race). RESULTS: Of 7438 children, 5442 (73%) had at least 1 risk-associated SDOH. PMA at discharge was older (adjusted mean difference 0.37 weeks, 95% CL 0.06, 0.68) and readmission more likely (aOR 1.27, 95% CL 1.12, 1.43) for infants whose mothers had public/no insurance vs private. Neither PMA at discharge nor readmission varied by education or race. NDI was twice as likely (aOR 2.36, 95% CL 1.86, 3.00) and death 5 times as likely (aOR 5.22, 95% CL 2.54, 10.73) for infants with 3 risk-associated SDOH compared with those with none. CONCLUSIONS: Children born to mothers with public/no insurance were older at discharge and more likely to be readmitted than those born to privately insured mothers. NDI and death postdischarge were more common among children exposed to multiple risk-associated SDOH at birth compared with those not exposed. Addressing disparities due to maternal education, insurance coverage, and systemic racism are potential intervention targets to improve outcomes for children born preterm.

Neonatal fluid overload-ignorance is no longer bliss.

Excessive accumulation of fluid may result in interstitial edema and multiorgan dysfunction. Over the past few decades, the detrimental impact of fluid overload has been further defined in adult and pediatric populations. Growing evidence highlights the importance of monitoring, preventing, managing, and treating fluid overload appropriately. Translating this knowledge to neonates is difficult as they have different disease pathophysiologies, and because neonatal physiology changes rapidly postnatally in many of the organ systems (i.e., skin, kidneys, and cardiovascular, pulmonary, and gastrointestinal). Thus, evaluations of the optimal targets for fluid balance need to consider the disease state as well as the gestational and postmenstrual age of the infant. Integration of what is known about neonatal fluid overload with individual alterations in physiology is imperative in clinical management. This comprehensive review will address what is known about the epidemiology and pathophysiology of neonatal fluid overload and highlight the known knowledge gaps. Finally, we provide clinical recommendations for monitoring, prevention, and treatment of fluid overload.

Potential missed opportunities for antenatal corticosteroid exposure and outcomes among periviable births: observational cohort study.

OBJECTIVE: Test the hypothesis potential missed opportunities for antenatal corticosteroids increase as gestational age decreases and are associated with adverse outcomes. DESIGN: Observational cohort study. SETTING: 24 US centers in the Neonatal Research Network. POPULATION: Actively treated infants 22-25 weeks' gestation and birth weight 401-1000 grams, without major birth defects, born 2006-2018. METHODS: Potential missed opportunity was defined as no antenatal corticosteroids but did have prenatal antibiotics, and/or magnesium sulfate, and/or prolonged rupture of membranes. Poisson regression models adjusted for baseline characteristics. MAIN OUTCOME MEASURES: Antenatal corticosteroid exposure, mortality, and severe intracranial hemorrhage or periventricular leukomalacia. RESULTS: 6966 (87.5%) were exposed to antenatal corticosteroids, 454 (5.7%) had no exposure but potential missed opportunities for antenatal corticosteroid exposure, and 537 (6.7%) had no exposure and no evidence of potential missed opportunities. Compared with infants born at 25 weeks, potential missed opportunities for antenatal corticosteroid exposure were more likely at 22 weeks (adjusted relative risk (aRR) [95% CI] 11.06 [7.52-16.27]) and 23 weeks (3.24 [2.44-4.29]) but did not differ at 24 weeks (1.08 [0.82-1.42]). Potential missed opportunities for antenatal corticosteroids decreased over time at 22-23 weeks' gestation. Antenatal corticosteroid exposed infants had lower risk of death (31.0% vs 54.8%; 0.77 [0.70-0.84]) and survivors had lower risk of severe brain injury (25.0% v 44.5%; 0.64 [0.55-0.73]) compared with infants with potential missed opportunities. CONCLUSION: Potential missed opportunities for antenatal corticosteroid exposure increased with decreasing gestational age and were associated with higher rates of death and severe brain injury among actively treated periviable births.

Percent Body Fat Content Measured by Plethysmography in Infants Randomized to High- or Usual-Volume Feeding after Very Preterm Birth.

We measured percent body fat by air-displacement plethysmography in 86 infants born at <32 weeks of gestation randomized to receive either high-volume (180-200 mL/kg/day) or usual volume feeding (140-160 mL/kg/day). High-volume feeding increased percent body fat by ≤2% at 36 weeks of postmenstrual age (within a predefined range of equivalence). TRIAL REGISTRATION: ClincialTrials.gov: NCT02377050.

Early Skin-to-Skin Care with a Polyethylene Bag for Neonatal Hypothermia: A Randomized Clinical Trial.

OBJECTIVE: To determine whether early polyethylene bag use with skin-to-skin care compared with skin-to skin care alone reduce hypothermia among infants born at term in resource-limited settings. STUDY DESIGN: Infants born at term in the tertiary referral center in Lusaka, Zambia, were randomized using sequentially numbered sealed opaque envelopes in 2 phases: after birth (phase 1) and at 1 hour after birth (phase 2) to either skin-to-skin care with polyethylene bags or skin-to-skin care alone. Infant and maternal temperatures were recorded at birth, 1 hour, and every 4 hours until discharge or 24 hours. RESULTS: We enrolled 423 infants from May 2017 to August 2017. The rate of moderate-severe hypothermia (temperature <36.0°C) at 1 hour was 72 of 208 (34.6%) in the skin-to-skin care with a polyethylene bag group compared with 101 of 213 (47.4%) in the skin-to-skin care alone group (relative risk, 0.71; 95% CI 0.56-0.90; P < .01; number needed to treat = 8). phase 1 treatment assignment significantly modified the effect of phase 2 treatment (P = .02 for interaction effect). Among infants randomized to skin-to-skin care with a polyethylene bag in phase 1, the risk of moderate-severe hypothermia was decreased in infants randomized to continue this intervention until discharge compared with infants randomized to skin-to-skin care alone. The rates of severe hypothermia, hyperthermia, and other adverse events did not differ significantly between groups. CONCLUSIONS: Low-cost polyethylene bags started after birth in combination with skin-to-skin care reduced moderate or severe hypothermia at 1 hour and at discharge among infants born at term in a resource-limited setting compared with skin-to-skin care alone. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03141723.

Higher- or Usual-Volume Feedings in Infants Born Very Preterm: A Randomized Clinical Trial.

OBJECTIVE: To determine whether higher-volume feedings improve postnatal growth among infants born very preterm. STUDY DESIGN: Randomized clinical trial with 1:1 parallel allocation conducted from January 2015 to June 2018 in a single academic medical center in the US. In total, 224 infants with a birth weight 1001-2500 g born at <32 weeks of gestation were randomized to higher-volume (180-200 mL/kg/d) or usual-volume (140-160 mL/kg/d) feedings after establishing full enteral feedings (≥120 mL/kg/d). The primary outcome was growth velocity (g/kg/d) from randomization to study completion at 36 weeks of postmenstrual age or hospital discharge if earlier. RESULTS: Growth velocity increased among infants in the higher-volume group compared with the usual-volume group (mean [SD], 20.5 [4.5] vs 17.9 [4.5] g/kg/d; P < .001). At study completion, all measurements were higher among infants in the higher-volume group compared with the usual-volume group: weight (2365 [324] g, z score -0.60 [0.73] vs 2200 [308] g, z score -0.94 [0.71]; P < .001); head circumference (31.9 [1.3] cm, z score -0.30 [0.91] vs 31.4 [1.3] cm, z score -0.53 [0.84]; P = .01); length (44.9 [2.1] cm, z score -0.68 [0.88] vs 44.4 [2.0], z score -0.83 [0.84]; P = .04); and mid-arm circumference (8.8 [0.8] cm vs 8.4 [0.8] cm; P = .002). Bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, or other adverse outcomes did not differ between groups. CONCLUSIONS: In infants born very preterm weighing 1001-2500 g at birth, higher-volume feedings increased growth velocity, weight, head circumference, length, and mid-arm circumference compared with usual-volume feedings without adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02377050.

Non-invasive forced oscillometry to quantify respiratory mechanics in term neonates.

BACKGROUND: To determine normative data by forced oscillation technique (FOT) in non-sedated normal term neonates and test the hypothesis that infants with transient tachypnea of the newborn (TTN) have higher resistance (R) and lower reactance (X) on day 1. METHODS: Healthy term infants (n = 138) and infants with TTN (n = 17) were evaluated on postnatal days 1 through 3 (NCT03346343). FOT was measured with a mask using a TremoFlo C-100 Airwave System™. R, X, and area under the reactance curve (AX) were measured at prime frequencies 7-41 Hz for 8 s. RESULTS: In all, 86% of control infants had adequate measurements (coherence >0.8, CV < 0.25) on day 1. Infants with TTN had higher resistance at 13 Hz (TTN 32.5 cm H2O·s/L [95% CI 25.5-39.4]; controls 23.8 cm H2O·s/L [95% CI 22.2 to 25.3], P = 0.007) and lower reactance from 17 to 37 Hz (TTN -35.1 to -10.5; controls -26.3 to -6.1, P < 0.05). In healthy controls, lung mechanics were unchanged from days 1 to 3. In TTN, lung mechanics normalized on days 2 and 3. CONCLUSIONS: FOT is feasible in neonates and distinguishes normal control infants from those with TTN on postnatal day 1. Oscillometry offers a non-invasive, longitudinal technique to assess lung mechanics in newborns.

Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort.

Adams-Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data on the frequency and distribution of mutations in large cohorts are currently limited. The purpose of this study was therefore to comprehensively examine the genetic architecture of AOS in an extensive cohort. Molecular diagnostic screening of 194 AOS/ACC/TTLD probands/families was conducted using next-generation and/or capillary sequencing analyses. In total, we identified 63 (likely) pathogenic mutations, comprising 56 distinct and 22 novel mutations, providing a molecular diagnosis in 30% of patients. Taken together with previous reports, these findings bring the total number of reported disease variants to 63, with a diagnostic yield of 36% in familial cases. NOTCH1 is the major contributor, underlying 10% of AOS/ACC/TTLD cases, with DLL4 (6%), DOCK6 (6%), ARHGAP31 (3%), EOGT (3%), and RBPJ (2%) representing additional causality in this cohort. We confirm the relevance of genetic screening across the AOS/ACC/TTLD spectrum, highlighting preliminary but important genotype-phenotype correlations. This cohort offers potential for further gene identification to address missing heritability.

Environmental or Nasal Cannula Supplemental Oxygen for Preterm Infants: A Randomized Cross-Over Trial.

OBJECTIVE: To test the hypothesis that environmental compared with nasal cannula oxygen decreases episodes of intermittent hypoxemia (oxygen saturations <85% for ≥10 seconds) in preterm infants on supplemental oxygen by providing a more stable hypopharyngeal oxygen concentration. STUDY DESIGN: This was a single center randomized crossover trial with a 1:1 parallel allocation to order of testing. Preterm infants on supplemental oxygen via oxygen environment maintained by a servo-controlled system or nasal cannula with flow rates ≤1.0 L per kg per minute were crossed over every 24 hours for 96 hours. Data were collected electronically to capture real time numeric and waveform data from patient monitors. RESULTS: Twenty-five infants with gestational age of 27 ± 2 weeks (mean ± SD) and a birth weight of 933 ± 328 g were studied at postnatal day 36 ± 26. The number of episodes of intermittent hypoxemia per 24 hours was 117 ± 77 (median, 98; range, 4-335) with oxygen environment vs 130 ± 63 (median, 136; range, 16-252) with nasal cannula (P = .002). Infants on oxygen environment compared with nasal cannula also had decreased episodes of severe intermittent hypoxemia (P = .005). Infants on oxygen environment compared with nasal cannula had a lower proportion of time with oxygen saturations <85% (.05 ± .03 vs .06 ± .03, P < .001), and a lower coefficient of variation of oxygen saturation (P = .02). CONCLUSIONS: In preterm infants receiving supplemental oxygen, servo-controlled oxygen environment decreases hypoxemia compared with nasal cannula. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02794662.

Mortality and pulmonary outcomes of extremely preterm infants exposed to antenatal corticosteroids.

BACKGROUND: Antenatal corticosteroids are given primarily to induce fetal lung maturation but results from meta-analyses of randomized controlled trials have not shown mortality or pulmonary benefits for extremely preterm infants although these are the infants most at risk of mortality and pulmonary disease. OBJECTIVE: We sought to determine if exposure to antenatal corticosteroids is associated with a lower rate of death and pulmonary morbidities by 36 weeks' postmenstrual age. STUDY DESIGN: Prospectively collected data on 11,022 infants 22 0/7 to 28 6/7 weeks' gestational age with a birthweight of ≥401 g born from Jan. 1, 2006, through Dec. 31, 2014, were analyzed. The rate of death and the rate of physiologic bronchopulmonary dysplasia by 36 weeks' postmenstrual age were analyzed by level of exposure to antenatal corticosteroids using models adjusted for maternal variables, infant variables, center, and epoch. RESULTS: Infants exposed to any antenatal corticosteroids had a lower rate of death (2193/9670 [22.7%]) compared to infants without exposure (540/1302 [41.5%]) (adjusted relative risk, 0.71; 95% confidence interval, 0.65-0.76; P < .0001). Infants exposed to a partial course of antenatal corticosteroids also had a lower rate of death (654/2520 [26.0%]) compared to infants without exposure (540/1302 [41.5%]); (adjusted relative risk, 0.77; 95% confidence interval, 0.70-0.85; P < .0001). In an analysis by each week of gestation, infants exposed to a complete course of antenatal corticosteroids had lower mortality before discharge compared to infants without exposure at each week from 23-27 weeks' gestation and infants exposed to a partial course of antenatal corticosteroids had lower mortality at 23, 24, and 26 weeks' gestation. Rates of bronchopulmonary dysplasia in survivors did not differ by antenatal corticosteroid exposure. The rate of death due to respiratory distress syndrome, the rate of surfactant use, and the rate of mechanical ventilation were lower in infants exposed to any antenatal corticosteroids compared to infants without exposure. CONCLUSION: Among infants 22-28 weeks' gestational age, any or partial antenatal exposure to corticosteroids compared to no exposure is associated with a lower rate of death while the rate of bronchopulmonary dysplasia in survivors did not differ.

Caffeine controversies.

PURPOSE OF REVIEW: Caffeine use in preterm infants has endured several paradigms: from standard of care to possible neurotoxin to one of the few medications for which there is evidence of bronchopulmonary dysplasia (BPD) risk reduction. The purpose of the review is to analyze this dynamic trajectory and discuss controversies that still remain after decades of caffeine use. RECENT FINDINGS: Following concerns for caffeine safety in preterm infants, a large randomized controlled trial demonstrated a reduction in BPD and treatment for patent ductus arteriosus. The lower rate of death or neurodevelopmental impairment noted at 18-21 months was not statistically different at later timepoints; however, infants in the caffeine group had lower rates of motor impairment at 11-year follow-up. The time of caffeine therapy initiation is now substantially earlier, and doses used are sometimes higher that previously used, but there are limited data to support these practices. SUMMARY: Caffeine therapy for apnea of prematurity (AOP) remains one of the pillars of neonatal care, although more evidence to support dosing and timing of initiation and discontinuation are needed.

Achieved oxygen saturations and risk for bronchopulmonary dysplasia with pulmonary hypertension in preterm infants.

OBJECTIVE: Characterisation of oxygen saturation (SpO2)-related predictors that correspond with both bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) development and survival status in infants with BPD-PH may improve patient outcomes. This investigation assessed whether (1) infants with BPD-PH compared with infants with BPD alone, and (2) BPD-PH non-survivors compared with BPD-PH survivors would (a) achieve lower SpO2 distributions, (b) have a higher fraction of inspired oxygen (FiO2) exposure and (c) have a higher oxygen saturation index (OSI). DESIGN: Case-control study between infants with BPD-PH (cases) and BPD alone (controls) and by survival status within cases. SETTING: Single-centre study in the USA. PATIENTS: Infants born at <29 weeks' gestation and on respiratory support at 36 weeks' postmenstrual age. EXPOSURES: FiO2 exposure, SpO2 distributions and OSI were analysed over the week preceding BPD-PH diagnosis. MAIN OUTCOMES AND MEASURES: BPD-PH, BPD alone and survival status in infants with BPD-PH. RESULTS: 40 infants with BPD-PH were compared with 40 infants with BPD alone. Infants who developed BPD-PH achieved lower SpO2 compared with infants with BPD (p<0.001), were exposed to a higher FiO2 (0.50 vs 0.34; p=0.02) and had a higher OSI (4.3 vs 2.6; p=0.03). Compared with survivors, infants with BPD-PH who died achieved a lower SpO2 (p<0.001) and were exposed to a higher FiO2 (0.70 vs 0.42; p=0.049). CONCLUSIONS: SpO2-related predictors differed between infants with BPD-PH and BPD alone and among infants with BPD-PH by survival status. The OSI may provide a non-invasive predictor for BPD-PH in preterm infants.

Extended CPAP or low-flow nasal cannula for intermittent hypoxaemia in preterm infants: a 24-hour randomised clinical trial.

OBJECTIVE: Optimal timing of continuous positive airway pressure (CPAP) cessation in preterm infants remains undetermined. We hypothesised that CPAP extension compared with weaning to low-flow nasal cannula (NC) reduces intermittent hypoxaemia (IH) and respiratory instability in preterm infants meeting criteria to discontinue CPAP. DESIGN: Single-centre randomised clinical trial. SETTING: Level 4 neonatal intensive care unit. PATIENTS: 36 infants <34 weeks' gestation receiving CPAP≤5 cmH2O and fraction of inspired oxygen (FiO2) ≤0.30 and meeting respiratory stability criteria. INTERVENTIONS: Extended CPAP was compared with weaning to low-flow NC (0.5 L/kg/min with a limit of 1.0 L/min) for 24 hours. OUTCOMES: The primary outcome was IH (number of episodes with SpO2<85% lasting ≥10 s). Secondary outcomes included: coefficient of variability of SpO2, proportion of time in various SpO2 ranges, episodes (≥10 s) with SpO2<80%, median cerebral and renal oxygenation, median effective FiO2, median transcutaneous carbon dioxide and bradycardia (<100/min for≥10 s). RESULTS: The median (IQR) episodes of IH per 24-hour period was 20 (6-48) in the CPAP group and 76 (18-101) in the NC group (p=0.03). Infants continued on CPAP had less bradycardia, time with SpO2 <91% and <85%, and lower FiO2 (all p<0.05). There were no statistically significant differences in IH<80%, median transcutaneous carbon dioxide or median cerebral or renal oxygenation. CONCLUSION: In preterm infants meeting respiratory stability criteria for CPAP cessation, extended CPAP decreased IH, bradycardia and other hypoxaemia measures compared with weaning to low-flow NC during the 24-hour intervention. TRIAL REGISTRATION NUMBER: NCT04792099.