European survey showed wide variations in diagnostic procedures and management strategies for metabolic bone disease of prematurity in 22 countries.

AIM: The aim of this study was to evaluate the clinical relevance, diagnostic procedures and treatment strategies for metabolic bone disease in preterm infants across Europe. METHODS: An e-survey was distributed by email to 545 neonatal units in 38 European countries between July and October 2021. The protocol was based on the Checklist for Reporting Results of Internet E-Surveys. RESULTS: In total, 76 neonatal units (14%) from 22 European countries (58%) completed the e-survey. In the 12 months prior to the survey, 29% of 76 units reported at least one symptomatic case of fracture associated with metabolic bone disease of prematurity, and 18% of 76 units reported at least one case of craniofacial deformity. Most centres followed local guidelines for diagnosis (77% of 73 units) and treatment (63% of 72 units). Alkaline phosphatase was the blood marker most used for treatment indication (81% of 72 units), and phosphate supplementation was the treatment most used (82% of 71 units). CONCLUSION: Metabolic bone disease of prematurity remains clinically relevant. Wide variations in diagnostic procedures and management strategies were observed in European neonatal units. Evidence-based consensus guidelines appear urgently needed to reduce the number of symptomatic cases.

Parents' and neonatal healthcare professionals' views on barriers and facilitators to parental presence in the neonatal unit: a qualitative study.

BACKGROUND: Parent and infant separation in the neonatal unit is associated with adverse health outcomes. Family-integrated care has several advantages and the potential to reduce these adverse outcomes but requires parental presence. This study aimed to explore the views of parents and neonatal healthcare professionals (nHCPs) on barriers and facilitators to parental presence in a Swiss neonatal unit and to identify possible differences between nHCPs and parents, and between mothers and fathers. METHODS: Data were collected through semi-structured interviews with parents and focus group discussions with nHCPs. Inductive content analysis was used to identify barriers and facilitators to parental presence in the neonatal unit. RESULTS: Twenty parents (10 mothers and 10 fathers) and 21 nHCPs (10 nurses and 11 physicians) participated in the study. Parents and nHCPs experienced barriers and facilitators related to: (1) Structural factors of the institution, such as infrastructure or travel and distance to the neonatal unit. (2) Organization and time management of parental presence, daily activities, and work. (3) Resources, which include factors related to the legal situation, support services, family, and friends. (4) Physical and psychological aspects, such as pain, which mainly affected mothers, and aspects of emotional distress, which affected both parents. Self-care was an important physical and psychological facilitator. (5) Parent-professional interaction. Parental presence was influenced by communication, relationship, and interaction in infant care; and (6) Cultural aspects and language. Some perspectives differed between mothers and fathers, while the overall views of parents and nHCPs provided complementary rather than conflicting insights. Using visit plans to support the organization, educating nHCPs in knowledge skills and available resources to improve encouragement and information to parents, strengthening parent self-care, and improving nHCPs' attitudes towards parental presence were seen as possible improvements. CONCLUSIONS: Multifactorial barriers and facilitators determine parental presence and experience in the neonatal unit. Parents and nHCPs made specific recommendations to improve parental presence.

Optimistic vs Pessimistic Message Framing in Communicating Prognosis to Parents of Very Preterm Infants: The COPE Randomized Clinical Trial.

Importance: In the neonatal intensive care unit, there is a lack of understanding about how best to communicate the prognosis of a serious complication to parents. Objective: To examine parental preferences and the effects of optimistic vs pessimistic message framing when providing prognostic information about a serious complication. Design, Setting, and Participants: This crossover randomized clinical trial was conducted at a single German university medical center between June and October 2021. Eligible participants were parents of surviving preterm infants with a birth weight under 1500 g. Data were analyzed between October 2021 and August 2022. Interventions: Alternating exposure to 2 scripted video vignettes showing a standardized conversation between a neonatologist and parents, portrayed by professional actors, about the prognosis of a hypothetical very preterm infant with severe intraventricular hemorrhage. The video vignettes differed in the framing of identical numerical outcome estimates as either probability of survival and probability of nonimpairment (optimistic framing) or a risk of death and impaired survival (pessimistic framing). Main Outcomes and Measures: The primary outcome was preference odds (ratio of preference for optimistic vs pessimistic framing). Secondary outcomes included state anxiety, perceptions of communication, and recall of numerical estimates. Results: Of 220 enrolled parents (142 [64.5%] mothers; mean [SD] age: mothers, 39.1 [5.6] years; fathers, 42.7 [6.9] years), 196 (89.1%) preferred optimistic and 24 (10.1%) preferred pessimistic framing (preference odds, 11.0; 95% CI, 6.28-19.10; P < .001). Preference for optimistic framing was more pronounced when presented second than when presented first (preference odds, 5.41; 95% CI, 1.77-16.48; P = .003). State anxiety scores were similar in both groups at baseline (mean difference, -0.34; -1.18 to 0.49; P = .42) and increased equally after the first video (mean difference, -0.55; 95% CI, -1.79 to 0.69; P = .39). After the second video, state anxiety scores decreased when optimistic framing followed pessimistic framing but remained unchanged when pessimistic framing followed optimistic framing (mean difference, 2.15; 95% CI, 0.91 to 3.39; P < .001). With optimistic framing, participants recalled numerical estimates more accurately for survival (odds ratio, 4.00; 95% CI, 1.64-9.79; P = .002) but not for impairment (odds ratio, 1.50; 95% CI, 0.85-2.63; P = .16). Conclusions and Relevance: When given prognostic information about a serious complication, parents of very preterm infants may prefer optimistic framing. Optimistic framing may lead to more realistic expectations for survival, but not for impairment. Trial Registration: German Clinical Trials Register (DRKS): DRKS00024466.

Attitudes and values towards decisions at the margin of viability among expectant mothers at risk for preterm birth.

AIM: To explore how expectant mothers at risk for preterm birth would like to be involved in decision-making at the margin of viability and what they would base their decisions on. METHODS: This cross-sectional observational study included a mixed-methods post-hoc analysis alongside a previously reported randomised clinical trial. Expectant mothers between 280/7 and 366/7 weeks' gestation who were hospitalised for risk of preterm birth responded to written case vignettes of an impending preterm birth at the margin of viability. Participants responded to closed and open-ended questions that were theoretically coded for attitudes and values towards shared decision-making. RESULTS: Sixty-four expectant mothers were included in the analysis, 36 provided written perspectives. Decision-making was perceived as an enormous burden and a potential source of guilt and regret. Weighing personal values in terms of 'fighting for the baby' and 'quality of life' were used to inform the decision-making process. Explicitly stating that any decision is a good decision, empowerment through co-constructing shared decisions rather than simply presenting choices, sharing the clinicians' personal views, and honest, and empathetic counselling were perceived as supportive. CONCLUSION: Mothers at risk for preterm birth provided specific insights into their decision-making patterns that may be helpful to clinicians.

Video versus direct laryngoscopy to improve the success rate of nasotracheal intubations in the neonatal intensive care setting: a randomised controlled trial.

OBJECTIVE: To assess whether video laryngoscopy (VL) for tracheal intubation of neonates results in a higher first-attempt success rate and fewer adverse tracheal intubation-associated events (TIAEs) when compared with direct laryngoscopy (DL). DESIGN: Single-centre, parallel group, randomised controlled trial. SETTING: University Medical Centre Mainz, Germany. PATIENTS: Neonates <440/7 weeks postmenstrual age in whom tracheal intubation was indicated either in the delivery room or in the neonatal intensive care unit. INTERVENTION: Intubation encounters were randomly assigned to either VL or DL at first attempt. PRIMARY OUTCOME: First-attempt success rate during tracheal intubation. RESULTS: Of 121 intubation encounters assessed for eligibility, 32 (26.4%) were either not randomised (acute emergencies (n=9), clinicians' preference for either VL (n=8) or DL (n=2)) or excluded from the analysis (declined parental consent (n=13)). Eighty-nine intubation encounters (41 in the VL and 48 in the DL group) in 63 patients were analysed. First-attempt success rate was 48.8% (20/41) in the VL group compared with 43.8% (21/48) in the DL group (OR 1.22, 95% CI 0.51 to 2.88).The frequency of adverse TIAEs was 43.9% (18/41) and 47.9% (23/48) in the VL and DL group, respectively (OR 0.85, 95% CI 0.37 to 1.97). Oesophageal intubation with concomitant desaturation never occurred in the VL group but in 18.8% (9/48) of intubation encounters in the DL group. CONCLUSION: This study provides effect sizes for first-attempt success rates and frequency of TIAEs with VL compared with DL in the neonatal emergency setting. This study was underpowered to detect small but clinically important differences between the two techniques. The results of this study may be useful in planning future trials.

Parental perceptions of informed consent in a study of tracheal intubations in neonatal intensive care.

Background and objective: Obtaining informed consent in neonatal emergency research is challenging. The aim of this study was to assess parental perceptions of informed consent following participation in a clinical trial in neonatal emergency care. Methods: This was a supplementary analysis of a randomised controlled trial comparing video and direct laryngoscopy for neonatal endotracheal intubation in the delivery room and neonatal intensive care unit. After obtaining informed consent for the clinical trial, parents were asked to answer a series of self-administered questions about their perceptions of clinical trial participation and the consent process. Informed consent had been given either before birth, after birth but before inclusion in the trial, or after inclusion in the trial. Results: We received responses from 33 mothers and 27 fathers (n = 60) of the 63 preterm and term infants who participated in the study. Fifty-three (89.8%, n = 59) parents agreed that infants should participate in clinical trials, and 51 (85%, n = 60) parents agreed that parents should be asked for informed consent. Fifty-three (89.8%, n = 59) parents felt that their infant's participation in this particular trial would be beneficial. Fifty-two (86.7%, n = 60) parents felt that the informed consent process was satisfactory. One parent (100%, n = 1) approached before birth, 23 parents (82.1%, n = 28) approached after birth but before enrolment and 26 (83.9%, n = 31) parents approached after enrolment were satisfied with the timing of the consent process. Eight (13.3%, n = 60) parents felt some pressure to provide informed consent. Of these, two (25%) were approached before enrolment and six (75%) were approached after enrolment. Conclusion: Parents valued their infant's participation in an emergency neonatal clinical trial and considered it important to be asked for consent. In this study, it seemed less important whether consent was obtained before or after the intervention. Future studies may need to investigate which form of consent is most acceptable to parents for the individual study in question.

Ethics education in pediatrics: Implementation and evaluation of an interactive online course for medical students.

Introduction: The COVID-19 pandemic has catalyzed the development of online learning formats in virtually all areas of medical education. In pediatric ethics, online learning may not only substitute but also offer specific advantages over traditional classroom teaching. Many pediatricians rate their ethics education as poor and medical ethics education lacks evaluation, especially regarding the students' needs. The aim of this project was to implement and evaluate a novel interactive distance learning approach to engage medical students in pediatric ethics education. Methods: An online ethics course was designed and delivered between May and June 2020. Core item of this course was a moderated, written forum discussion spanning several days. Evaluation was mixed methods. We evaluated the effectiveness of the course in terms of quality of the learning environment with a particular focus on relevance to students as well as interactive learning and reflective thinking. The Constructivist On-Line Learning Environment Survey (COLLES) was used to evaluate six different domains of the course. Data are presented as mean (standard deviation [SD]). The respective score range is 1-5, whereby a score of 4 or 5 means that the participants indicated the corresponding item as frequently or almost always present. Results: Responses were available from 104 (78.3%) of the 133 participating students. "Relevance" yielded a score of 4.17 (0.83), "reflective thinking" a score of 4.22 (0.83). "Interactivity" was scored 3.76 (0.99) and "tutor support" 4.72 (0.53). "Peer support" and "interpretation" scored 3.87 (0.98) and 4.49 (0.60), respectively. In qualitative analysis, students particularly valued the structure of the course, the relevance for their professional practice, their active participation and the incentive to reflective thinking. Students also indicated that this was an innovative and exciting format, which fills a current educational gap and should hence be continued beyond the pandemic. Conclusion: In conclusion, students actively engaged in online learning and perceived this ethics course as highly relevant for their professional practice.

A single center experience in 90 cases with nonimmune hydrops fetalis: diagnostic categories ‒ mostly aneuploidy and still often idiopathic.

OBJECTIVES: The prognosis of nonimmune hydrops fetalis (NIHF) is still poor with a high mortality and morbidity rate despite progress in perinatal care. This study was designed to investigate etiology and outcome of NIHF. METHODS: A retrospective review of 90 NIHF cases from 2007 to 2019 was conducted at University Medical Center of the Johannes Gutenberg University, Mainz, Germany. Demographics, genetic results, prenatal and postnatal outcomes including one year survival as well as autopsy data were extracted. Etiology of hydrops was classified using 13 previously established categories. In 4 patients observed between 2016 and 2019, we used a next-generation-sequencing (NGS) panel for genetic evaluation. RESULTS: Ninety NIHF cases were identified, with a median gestational age (GA) at diagnosis of 14 weeks. There were 25 live-born infants with a median GA of 34 weeks at birth, 15 patients survived to one year. There was aneuploidy in more than one third of the cases. All 90 cases were subclassified into etiologic categories with chromosomal 35, idiopathic 15, syndromic 11, cardiovascular 9, inborn errors of metabolism 6, lymphatic dysplasia 3, thoracic 3, infections 3, gastrointestinal 3 and hematologic 2. The NGS panel was used in 4 cases and 4 diagnoses were made. CONCLUSIONS: In 90 cases with NIHF we identified an aneuploidy in more than one third of the cases. Improved techniques, such as possibly specific genetic analysis, could reduce the high rate of unexplained cases of NIHF.

Characteristics of neonatal herpes simplex virus infections in Germany: results of a 2-year prospective nationwide surveillance study.

OBJECTIVE: To assess incidence and burden of neonatal herpes simplex virus (HSV) infections and to explore possible transmission routes. METHODS: A 2-year prospective nationwide surveillance study performed in 2017 and 2018. All German paediatric departments (n=464 in 2017, n=441 in 2018) were contacted on a monthly basis to report potential cases of neonatal HSV infections. Infants with a postnatal age of ≤60 days and a positive HSV PCR or HSV culture from skin, mucous membrane, vesicles or conjunctival smear, blood or cerebrospinal fluid were included in the study. RESULTS: 37 cases were analysed. 29 patients who exhibited no or only mild clinical symptoms were discharged home without organ damage or neurological abnormalities. Four patients showed significant neurological impairment, one patient required liver transplantation and two patients died during in-patient treatment. The 2-year incidence of neonatal HSV infections was 2.35 per 100 000 live births (95% CI 1.69 to 3.02) and disease-specific mortality was 0.13 per 100 000 live births (95% CI 0.04 to 0.21). Data on possible transmission routes were available in 23 cases. In 20 cases, an orofacial HSV infection was present in one or more family members. An active maternal genital HSV infection was reported in 3 cases. CONCLUSION: Neonatal HSV infections are rare in Germany. Most infants have a benign clinical course, but some infants are severely affected. Postnatal HSV exposure may account for a considerable number of neonatal HSV infections.

The COPE-Trial-Communicating prognosis to parents in the neonatal ICU: Optimistic vs. PEssimistic: study protocol for a randomized controlled crossover trial using two different scripted video vignettes to explore communication preferences of parents of preterm infants.

BACKGROUND: One of the numerous challenges preterm birth poses for parents and physicians is prognostic disclosure. Prognoses are based on scientific evidence and medical experience. They are subject to individual assessment and will generally remain uncertain with regard to the individual. This can result in differences in prognostic framing and thus affect the recipients' perception. In neonatology, data on the effects of prognostic framing are scarce. In particular, it is unclear whether parents prefer a more optimistic or a more pessimistic prognostic framing. OBJECTIVE: To explore parents' preferences concerning prognostic framing and its effects on parent-reported outcomes and experiences. To identify predictors (demographic, psychological) of parents' communication preferences. DESIGN, SETTING, PARTICIPANTS: Unblinded, randomized controlled crossover trial (RCT) at the Division of Neonatology of the University Medical Center Mainz, Germany, including German-speaking parents or guardians of infants born preterm between 2010 and 2019 with a birth weight < 1500 g. Inclusion of up to 204 families is planned, with possible revision according to a blinded sample size reassessment. INTERVENTION: Embedded in an online survey and in pre-specified order, participants will watch two video vignettes depicting a more optimistic vs. a more pessimistic framing in prognostic disclosure to parents of a preterm infant. Apart from prognostic framing, all other aspects of physician-parent communication are standardized in both videos. MAIN OUTCOMES AND MEASURES: At baseline and after each video, participants complete a two-part online questionnaire (baseline and post-intervention). Primary outcome is the preference for either a more optimistic or a more pessimistic prognostic framing. Secondary outcomes include changes in state-anxiety (STAI-SKD), satisfaction with prognostic framing, evaluation of prognosis, future optimism and hope, preparedness for shared decision-making (each assessed using customized questions), and general impression (customized question), professionalism (adapted from GMC Patient Questionnaire) and compassion (Physician Compassion Questionnaire) of the consulting physician. DISCUSSION: This RCT will explore parents' preferences concerning prognostic framing and its effects on physician-parent communication. Results may contribute to a better understanding of parental needs in prognostic disclosure and will be instrumental for a broad audience of clinicians, scientists, and ethicists. TRIAL REGISTRATION: German Clinical Trials Register DRKS00024466 . Registered on April 16, 2021.

Patterns of Safety Incidents in a Neonatal Intensive Care Unit.

Introduction: Safety incidents preceding manifest adverse events are barely evaluated in neonatal intensive care units (NICUs). This study aimed at identifying frequency and patterns of safety incidents in our NICU. Methods: A 6-month prospective clinical study was performed from May to October 2019 in a German 10-bed level III NICU. A voluntary, anonymous reporting system was introduced, and all neonatal team members were invited to complete paper-based questionnaires following each particular safety incident. Safety incidents were defined as safety-related events that were considered by the reporting team member as a "threat to the patient's well-being" which "should ideally not occur again." Results: In total, 198 safety incidents were analyzed. With 179 patients admitted, the incident/admission ratio was 1.11. Medication errors (n = 94, 47%) and equipment problems (n = 54, 27%) were most commonly reported. Diagnostic errors (n = 19, 10%), communication problems (n = 12, 6%), errors in documentation (n = 9, 5%) and hygiene problems (n = 10, 5%) were less frequent. Most safety incidents were noticed after 4-12 (n = 52, 26%) and 12-24 h (n = 47, 24%), respectively. Actual harm to the patient was reported in 17 cases (9%) but no life-threatening or serious events occurred. Of all safety incidents, 184 (93%) were considered to have been preventable or likely preventable. Suggestions for improvement were made in 132 cases (67%). Most often, implementation of computer-assisted tools and processes were proposed. Conclusion: This study confirms the occurrence of various safety incidents in the NICU. To improve quality of care, a graduated approach tailored to the specific problems appears to be prudent.

Adverse Events and Unsuccessful Intubation Attempts Are Frequent During Neonatal Nasotracheal Intubations.

Background: Intubation of neonates is difficult and hazardous. Factors associated with procedure-related adverse events and unsuccessful intubation attempts are insufficiently evaluated, especially during neonatal nasotracheal intubations. Objective: Aim of this study was to determine the frequency of tracheal intubation-associated events (TIAEs) during neonatal nasotracheal intubations and to identify factors associated with TIAEs and unsuccessful intubation attempts in our neonatal unit. Methods: This was a prospective, single-site, observational study from May 2017 to November 2019, performed at a tertiary care neonatal intensive care unit in a German academic teaching hospital. All endotracheal intubation encounters performed by the neonatal team were recorded. Results: Two hundred and fifty-eight consecutive intubation encounters in 197 patients were analyzed. One hundred and forty-eight (57.4%) intubation encounters were associated with at least one TIAE. Intubation inexperience (<10 intubation encounters) (OR = 2.15; 95% CI, 1.257-3.685) and equipment problems (OR = 3.43; 95% CI, 1.12-10.52) were predictive of TIAEs. Intubation at first attempt (OR = 0.10; 95% CI, 0.06-0.19) and videolaryngoscopy (OR = 0.47; 96% CI, 0.25-0.860) were predictive of intubation encounters without TIAEs. The first intubation attempt was commonly done by pediatric residents (67.8%). A median of two attempts were performed until successful intubation. Restricted laryngoscopic view (OR = 3.07; 95% CI, 2.08-4.53; Cormack-Lehane grade 2 vs. grade 1), intubation by pediatric residents when compared to neonatologists (OR = 1.74; 95% CI, 1.265-2.41) and support by less experienced neonatal nurses (OR = 1.60; 95% CI, 1.04-2.46) were associated with unsuccessful intubation attempts. Conclusions: In our unit, TIAEs and unsuccessful intubation attempts occurred frequently during neonatal nasotracheal intubations. To improve success rates, quality improvement und further research should target interprofessional education and training, equipment problems and videolaryngoscopy.

Low Frequency of Viral Respiratory Tract Infections During Family-Centered Neonatal Intensive Care: Results of a Prospective Surveillance Study.

Background: Viral respiratory tract infections (VRTI) may cause severe respiratory and sepsis-like symptoms in infants hospitalized in the neonatal intensive care unit (NICU). Little is known about the frequencies of VRTI in relation to visiting policies in the NICU. Objective: Aim of this study was to evaluate the frequency of symptomatic and asymptomatic VRTI in our family-centered NICU. Methods: This was a 12-month, prospective, observational study from February 2018 to January 2019. Infants hospitalized ≥72 h were eligible for the study. To determine the frequency of VRTI, multiplexed point-of-care testing (mPOCT) of symptomatic infants was combined with a weekly screening of all infants. Our 10-bed NICU is 24/7 open to families and visitors. The number of simultaneous visitors is restricted to two per patient. Parents and visitors are instructed in hand hygiene and advised to avoid visits in cases of respiratory illness. Siblings irrespective of age may visit the NICU following a physical check-up. Results Multiplexed point-of-care testing (71 symptomatic episodes) combined with the weekly screening (272 episodes) yielded in 21 positive samples from 2 of the 67 infants enrolled in the study. Both infants were first detected during symptomatic episodes. Rhino-/enterovirus were detected in all cases. Conclusion: Respiratory viruses were detected during symptomatic and asymptomatic episodes but affected <3% of infants enrolled in the study. In our unit, a low frequency of VRTI was attained despite adherence to family integrated care including liberal visiting policies for younger siblings.

The clinical impact of PCR-based point-of-care diagnostic in respiratory tract infections in children.

BACKGROUND: Children are commonly affected by respiratory tract infections. Based on clinical symptoms, laboratory evaluation, and imaging, the causative pathogen often cannot be delineated. Point-of-care-testing systems that provide an opportunity for fast detection of common viruses and some bacteria can therefore influence treatment's options. We aimed to examine whether the Biofire® FilmArray® has an effect on antibiotic treatment, duration of antibiotic therapy, and length of hospital stay within a pediatric cohort. METHODS: We included children who were admitted to inpatient treatment with an acute respiratory tract infection from 02/2017 to 04/2018 using the FA respiratory panel for pathogen detection. The study group data were compared to the retrospective data of children admitted from 02/2016 to 02/2017, using a proprietary multiplex RT-PCR. RESULTS: A total of 322 children of the study group and 464 children of the control group were analyzed for clinical symptoms, laboratory findings, antibiotic treatment, and length of hospital stay. There was no significant reduction (P < .05) of antibiotic treatment and length of hospital stay. CRP, prehospital antibiotic treatment, antibiotic treatment, past medical history, age, and further pathogen detection showed a significant impact on antibiotic therapy, duration of antibiotic treatment, and length of hospital stay. CONCLUSION: The use of the FA did not result in a significant reduction of antibiotic treatment or in length of hospital stay. Other parameters had a more significant impact. Therefore, we suggest that standard operation procedures with therapy guidelines are necessary to provide an effective application of POCT systems.

Is faster better? A randomised crossover study comparing algorithms for closed-loop automatic oxygen control.

OBJECTIVE: Closed-loop automatic control (CLAC) of the fractional inspired oxygen (FiO2) improved oxygen administration to preterm infants on respiratory support. We investigated whether a revised CLAC algorithm (CLACfast, ≤2 FiO2 adjustments/min), compared with routine manual control (RMConly), increased the proportion of time with arterial haemoglobin oxygen saturation measured by pulse oximetry within prespecified target ranges (Target%) while not being inferior to the original algorithm (CLACslow: ≤0.3 FiO2 adjustments/min). DESIGN: Unblinded randomised controlled crossover study comparing three modes of FiO2 control in random order for 8 hours each: RMC supported by CLACfast was compared with RMConly and RMC supported by CLACslow. A computer-generated list of random numbers using a block size of six was used for the allocation sequence. SETTING: Two German tertiary university neonatal intensive care units. PATIENTS: Of 23 randomised patients, 19 were analysed (mean±SD gestational age 27±2 weeks; age at randomisation 24±10 days) on non-invasive (n=18) or invasive (n=1) respiratory support at FiO2 >0.21. MAIN OUTCOME MEASURE: Target%. RESULTS: Mean±SD [95% CI] Target% was 68%±11% [65% to 71%] for CLACfast versus 65%±11% [61% to 68%] for CLACslow versus 58%±11% [55% to 62%] for RMConly. Prespecified hypothesis tests of: (A) superiority of CLACfast versus RMConly and (B) non-inferiority of CLACfast versus CLACslow with margin of 5% yielded one-sided p values of <0.001 for both comparisons. CONCLUSIONS: This revised and faster CLAC algorithm was still superior to routine care in infants on respiratory support and not inferior to a previously tested slower algorithm. TRIAL REGISTRATION NUMBER: NCT03163108.