Practices and Outcomes from a Prospective, Multicenter Registry for Preterm Newborns with Pulmonary Hypertension.

OBJECTIVE: To describe current treatment practices of preterm infants with early hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH) and their association with patient outcomes. STUDY DESIGN: We developed a prospective, observational, multicenter clinical registry of preterm newborns <34 weeks' gestation with HRF and PH, based on either clinical or echocardiographic evidence during the first 72 hours of life, from 28 neonatal intensive care units in the US from 2017 through 2022. The primary end point was mortality among those who did or did not receive PH-targeted treatment, and the secondary end points included comparisons of major morbidities. Variables were compared using t tests, Wilcoxon rank-sum tests, Fisher exact tests, and χ² tests. RESULTS: We analyzed the results of 224 preterm infants enrolled in the registry. Of which, 84% (188/224) received PH-targeted treatment, most commonly inhaled nitric oxide (iNO). Early mortality in this cohort was high, as 33% (71/224) of this sample died in the first month of life, and 77% of survivors (105/137) developed bronchopulmonary dysplasia. Infants who received PH-targeted treatment had higher oxygenation indices at the time of enrollment (28.16 [IQR: 13.94, 42.5] vs 15.46 [IQR: 11.94, 26.15]; P = .0064). Patient outcomes did not differ between those who did or did not receive PH-targeted therapy. CONCLUSIONS: Early-onset HRF with PH in preterm infants is associated with a high early mortality and a high risk of developing bronchopulmonary dysplasia. iNO is commonly used to treat early-onset PH in preterm infants with HRF. In comparison with untreated infants with lower oxygenation indices, iNO treatment in severe PH may prevent poorer outcomes.

Success of blinding a procedural intervention in a randomised controlled trial in preterm infants receiving respiratory support.

BACKGROUND: Blinding of treatment allocation from treating clinicians in neonatal randomised controlled trials can minimise performance bias, but its effectiveness is rarely assessed. METHODS: To examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre randomised controlled trial of minimally invasive surfactant therapy versus sham treatment in preterm infants of gestation 25-28 weeks with respiratory distress syndrome. The intervention (minimally invasive surfactant therapy or sham) was performed behind a screen within the first 6 h of life by a 'study team' uninvolved in clinical care including decision-making. Procedure duration and the study team's words and actions during the sham treatment mimicked those of the minimally invasive surfactant therapy procedure. Post-intervention, three clinicians completed a questionnaire regarding perceived group allocation, with the responses matched against actual intervention and categorised as correct, incorrect, or unsure. Success of blinding was calculated using validated blinding indices applied to the data overall (James index, successful blinding defined as > 0.50), or to the two treatment allocation groups (Bang index, successful blinding: -0.30 to 0.30). Blinding success was measured within staff role, and the associations between blinding success and procedural duration and oxygenation improvement post-procedure were estimated. RESULTS: From 1345 questionnaires in relation to a procedural intervention in 485 participants, responses were categorised as correct in 441 (33%), incorrect in 142 (11%), and unsure in 762 (57%), with similar proportions for each of the response categories in the two treatment arms. The James index indicated successful blinding overall 0.67 (95% confidence interval (CI) 0.65-0.70). The Bang index was 0.28 (95% CI 0.23-0.32) in the minimally invasive surfactant therapy group and 0.17 (95% CI 0.12-0.21) in the sham arm. Neonatologists more frequently guessed the correct intervention (47%) than bedside nurses (36%), neonatal trainees (31%), and other nurses (24%). For the minimally invasive surfactant therapy intervention, the Bang index was linearly related to procedural duration and oxygenation improvement post-procedure. No evidence of such relationships was seen in the sham arm. CONCLUSION: Blinding of a procedural intervention from clinicians is both achievable and measurable in neonatal randomised controlled trials.

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Outcomes for Ectopia Cordis.

OBJECTIVES: To utilize a large multicenter neonatal cohort to describe survival and clinical outcomes of very low birth weight (VLBW) or preterm infants with ectopia cordis. STUDY DESIGN: Data were prospectively collected on 2 211 262 infants (born 2000-2017) from 845 US centers. Both VLBW (401-1500 g or 22-29 weeks of gestation) and non-VLBW (>1500 g and >29 weeks) infants had diagnoses or anatomic descriptors consistent with ectopia cordis and/or pentalogy of Cantrell. The primary outcome was neonatal survival, defined as hospital discharge or initial length of stay of ≥12 months. RESULTS: In total, 180 infants had ectopia cordis, 135 (76%) with findings of pentalogy of Cantrell. VLBW infants comprised 52% of the population. VLBW mortality was 96% with 79% dying within 12 hours, compared with 59% and 36%, respectively, for non-VLBW. One-third of VLBW infants received life support compared with 65% of non-VLBW. Surgery was reported for 34% of VLBW and 68% of non-VLBW infants. Congenital heart disease was reported in 8% of VLBW and 36% of non-VLBW, with conotruncal abnormalities most common. Survival exceeded 50% for infants >2500 g and >37 weeks of gestation. CONCLUSIONS: Survival of VLBW infants with ectopia cordis was poor and substantially worse compared with non-VLBW, with notable discrepancies in resuscitative efforts and surgical interventions. Although gestational age and weight strongly influence current survival, more detailed information regarding the severity of cardiac and noncardiac abnormalities is required to fully determine prognosis and inform counseling.

Contemporary Outcomes of Infants with Gastroschisis in North America: A Multicenter Cohort Study.

OBJECTIVE: To quantify outcomes and analyze factors predictive of morbidity and mortality in infants with gastroschisis. STUDY DESIGN: Clinical data regarding neonates with gastroschisis born between 2009 and 2014 were prospectively collected at 175 North American centers. Multivariate regression was used to assess risk factors for mortality and length of stay (LOS). RESULTS: Gastroschisis was diagnosed in 4420 neonates with median birth weight 2410 g (IQR 2105-2747). Survival (discharge home or alive in hospital at 1 year) was 97.8% with a 37 day median LOS (IQR 27-59). Sepsis, defined by positive blood or cerebrospinal fluid culture, was the only significant independent predictor of mortality (P = .04). Significant independent determinants of LOS and the percentage of neonates affected were as follows: bowel resection (9.8%, P < .0001), sepsis (8.6%, P < .0001), presence of other congenital anomalies (7.6%, including 5.8% with intestinal atresias, P < .0001), necrotizing enterocolitis (4.5%, P < .0001), and small for gestational age (37.3%, P = .0006). Abdominal surgery in addition to gastroschisis repair occurred in 22.3%, with 6.4% receiving gastrostomy or jejunostomy tubes and 6.3% requiring ostomy creation. At discharge, 57.0% were less than the 10th percentile weight for age. The mode of delivery (52.4% cesarean delivery) was not associated with any differences in outcome. CONCLUSIONS: Although neonates with gastroschisis have excellent overall survival they remain at risk for death from sepsis, prolonged hospitalization, multiple abdominal operations, and malnutrition at discharge. Outcomes appear unaffected by the use of cesarean delivery. Further opportunities for quality improvement include sepsis prevention and enhanced nutritional support.

Randomized trial of occlusive wrap for heat loss prevention in preterm infants.

OBJECTIVE: To determine whether the application of occlusive wrap applied immediately after birth will reduce mortality in very preterm infants. STUDY DESIGN: This was a prospective randomized controlled trial of infants born 24 0/7 to 27 6/7 weeks' gestation who were assigned randomly to occlusive wrap or no wrap. The primary outcome was all cause mortality at discharge or 6 months' corrected age. Secondary outcomes included temperature, Apgar scores, pH, base deficit, blood pressure and glucose, respiratory distress syndrome, bronchopulmonary dysplasia, seizures, patent ductus arteriosus, necrotizing enterocolitis, gastrointestinal perforation, intraventricular hemorrhage, cystic periventricular leukomalacia, pulmonary hemorrhage, retinopathy of prematurity, sepsis, hearing screen, and pneumothorax. RESULTS: Eight hundred one infants were enrolled. There was no difference in baseline population characteristics. There were no significant differences in mortality (OR 1.0, 95% CI 0.7-1.5). Wrap infants had statistically significant greater baseline temperatures (36.3°C wrap vs 35.7°C no wrap, P < .0001) and poststabilization temperatures (36.6°C vs 36.2°C, P < .001) than nonwrap infants. For the secondary outcomes, there was a significant decrease in pulmonary hemorrhage (OR 0.6, 95% CI 0.3-0.9) in the wrap group and a significant lower mean one minute Apgar score (P = .007) in the wrap group. The study was stopped early because continued enrollment would not result in the attainment of a significant difference in the primary outcome. CONCLUSION: Application of occlusive wrap to very preterm infants immediately after birth results in greater mean body temperature but does not reduce mortality.

Timing of cord clamping in very preterm infants: more evidence is needed.

In December 2012, the American College of Obstetricians and Gynecologists published a Committee Opinion entitled "Timing of umbilical cord clamping after birth." It stated that "evidence exists to support delayed cord clamping in preterm infants, when feasible. The single most important benefit for preterm infants is the possibility for a nearly 50% reduction in IVH." However, the Committee Opinion added that the ideal timing of umbilical cord clamping has yet to be determined and recommended that large clinical trials be conducted in the most preterm infants. Published randomized controlled trials include <200 infants of <30 weeks' gestation, with assessments of neurodevelopmental outcome in less than one-half of the children. This is a major gap in the evidence. Without reliable data from randomized controlled trials that optimally include childhood follow-up evaluations, we will not know whether delayed cord clamping may do more overall harm than good. Ongoing trials of delayed cord clamping plan to report childhood outcomes in >2000 additional very preterm infants. Current recommendations may need to change when these results become available. Greater international collaboration could accelerate resolution of whether this promising intervention will improve disability-free survival in about 1 million infants who will be born very preterm globally each year.

The OPTIMIST-A trial: evaluation of minimally-invasive surfactant therapy in preterm infants 25-28 weeks gestation.

BACKGROUND: It is now recognized that preterm infants ≤28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplasia and other morbidities. In an effort to circumvent this problem, techniques of minimally-invasive surfactant therapy have been developed, in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure. A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea (the "Hobart method") has been shown to be feasible and potentially effective, and now requires evaluation in a randomised controlled trial. METHODS/DESIGN: This is a multicentre, randomised, masked, controlled trial in preterm infants 25-28 weeks gestation. Infants are eligible if managed on continuous positive airway pressure without prior intubation, and requiring FiO2 ≥ 0.30 at an age ≤6 hours. Randomisation will be to receive exogenous surfactant (200 mg/kg poractant alfa) via the Hobart method, or sham treatment. Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached (FiO2 ≥ 0.45, unremitting apnoea or persistent acidosis). Primary outcome is the composite of death or physiological bronchopulmonary dysplasia, with secondary outcomes including incidence of death; major neonatal morbidities; durations of all modes of respiratory support and hospitalisation; safety of the Hobart method; and outcome at 2 years. A total of 606 infants will be enrolled. The trial will be conducted in >30 centres worldwide, and is expected to be completed by end-2017. DISCUSSION: Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants. The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25-28 weeks gestation. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry: ACTRN12611000916943; ClinicalTrials.gov: NCT02140580.

Association between neurodevelopmental outcomes and concomitant presence of NEC and IVH in extremely low birth weight infants.

OBJECTIVE: To quantify the association between necrotizing enterocolitis (NEC) and neurodevelopmental disability (NDI) in extremely low birth weight (ELBW) infants with intraventricular hemorrhage (IVH). STUDY DESIGN: ELBW survivors born 2011-2017 and evaluated at 16-26 months corrected age in the Vermont Oxford Network (VON) ELBW Follow-Up Project were included. Logistic regression determined the adjusted relative risk (aRR) of severe NDI in medical or surgical NEC compared to no NEC, stratified by severity of IVH. RESULTS: Follow-up evaluation occurred in 5870 ELBW survivors. Compared to no NEC, medical NEC had no impact on NDI, regardless of IVH status. Surgical NEC increased risk of NDI in patients with no IVH (aRR 1.69; 95% CI 1.36-2.09), mild IVH (aRR 1.36;0.97-1.92), and severe IVH (aRR 1.35;1.13-1.60). CONCLUSIONS: ELBW infants with surgical NEC carry increased risk of neurodevelopmental disability within each IVH severity stratum. These data describe the additive insult of surgical NEC and IVH on neurodevelopment, informing prognostic discussions and highlighting the need for preventative interventions.

Trends in Mortality and Morbidities for Infants Born 24 to 28 Weeks in the US: 1997-2021.

BACKGROUND: Mortality and morbidity for very preterm infants in the United States decreased for years. The current study describes recent changes to assess whether the pace of improvement has changed. METHODS: Vermont Oxford Network members contributed data on infants born at 24 to 28 weeks' gestation from 1997 to 2021. We modeled mortality, late-onset sepsis, necrotizing enterocolitis, chronic lung disease, severe intraventricular hemorrhage, severe retinopathy of prematurity, and death or morbidity by year of birth using segmented relative risk regression, reporting risk-adjusted annual percentage changes with 95% confidence intervals overall and by gestational age week. RESULTS: Analyses of data for 447 396 infants at 888 hospitals identified 3 time point segments for mortality, late onset sepsis, chronic lung disease, severe intraventricular hemorrhage, severe retinopathy of prematurity, and death or morbidity, and 4 for necrotizing enterocolitis. Mortality decreased from 2005 to 2021, but more slowly since 2012. Late-onset sepsis decreased from 1997 to 2021, but more slowly since 2012. Severe retinopathy of prematurity decreased from 2002 to 2021, but more slowly since 2011. Necrotizing enterocolitis, severe intraventricular hemorrhage, and death or morbidity were stable since 2015. Chronic lung disease has increased since 2012. Trends by gestational age generally mirror those for the overall cohort. CONCLUSIONS: Improvements in mortality and morbidity have slowed, stalled, or reversed in recent years. We propose a 3-part strategy to regain the pace of improvement: research; quality improvement; and follow through, practicing social as well as technical medicine to improve the health and well-being of infants and families.

Predictors of Mortality in Very Low Birth Weight Neonates With Congenital Diaphragmatic Hernia.

BACKGROUND: Limited data exists regarding the mortality of very low birth weight (VLBW) neonates with congenital diaphragmatic hernia (CDH). This study aims to quantify and determine predictors of mortality in VLBW neonates with CDH. METHODS: This analysis of 829 U.S. NICUs included VLBW [birth weight ≤1500g] neonates, born 2011-2021 with and without CDH. The primary outcome was in-hospital mortality. A generalized estimating equation regression model determined the adjusted risk ratio (ARR) of mortality. RESULTS: Of 426,140 VLBW neonates, 535 had CDH. In neonates with CDH, 48.4% had an additional congenital anomaly vs 5.5% without. In-hospital mortality for neonates with CDH was 70.4% vs 12.6% without. Of those with CDH, 73.3% died by day of life 3. Of VLBW neonates with CDH, 38% were repaired. A subgroup analysis was performed on 60% of VLBW neonates who underwent delivery room intubation or mechanical ventilation, as an indicator of active treatment. Mortality in this group was 62.7% for neonates with CDH vs 16.4% without. Higher Apgars at 1 min and repair of CDH were associated with lower mortality (ARR 0.91; 95%CI 0.87,0.96 and ARR 0.28; 0.21,0.39). The presence of additional congenital anomalies was associated with higher mortality (ARR 1.14; 1.01,1.30). CONCLUSION: These benchmark data reveal that VLBW neonates with CDH have an extremely high mortality. Almost half of the cohort have an additional congenital anomaly which significantly increases the risk of death. This study may be utilized by providers and families to better understand the guarded prognosis of VLBW neonates with CDH. TYPE OF STUDY: Level II. LEVEL OF EVIDENCE: Level II.

Comparing Healthcare Needs in Extremely Low Birth Weight Infants With NEC and Spontaneous Intestinal Perforation.

BACKGROUND: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) affect 6-8% of extremely low birth weight (ELBW) infants. SIP has lower mortality than NEC, but with similar short-term morbidity in length of stay, growth failure, and supplemental oxygen requirements. Comparative long-term neurodevelopmental outcomes have not been clarified. METHODS: Data were prospectively collected from 59 North American neonatal units, regarding ELBW infants (401-1000 g or 22-27 weeks gestational age) born between 2011 and 2018 and evaluated again at 16-26 months corrected age. Outcomes were collected from infants with laparotomy-confirmed NEC, laparotomy-confirmed SIP, and those without NEC or SIP. The primary outcome was severe neurodevelopmental disability. Secondary outcomes were weight <10th percentile, medical readmission, post-discharge surgery and medical support at home. Adjusted risk ratios (ARR) were calculated. RESULTS: Of 13,673 ELBW infants, 6391 (47%) were followed including 93 of 232 (40%) with NEC and 100 of 235 (42%) with SIP. There were no statistically significant differences in adjusted risk of any outcomes when directly comparing NEC to SIP (ARR 2.35; 95% CI 0.89, 6.26). However, infants with NEC had greater risk of severe neurodevelopmental disability (ARR 1.43; 1.09-1.86), rehospitalization (ARR 1.46; 1.17-1.82), and post-discharge surgery (ARR 1.82; 1.48-2.23) compared to infants without NEC or SIP. Infants with SIP only had greater risk of post-discharge surgery (ARR 1.64; 1.34-2.00) compared to infants without NEC or SIP. CONCLUSIONS: ELBW infants with NEC had significantly increased risk of severe neurodevelopmental disability and post-discharge healthcare needs, consistent with prior literature. We now know infants with SIP also have increased healthcare needs. LEVELS OF EVIDENCE: Level II.

Clinical prediction models for bronchopulmonary dysplasia: a systematic review and external validation study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Very different models using clinical parameters at an early postnatal age to predict BPD have been developed with little extensive quantitative validation. The objective of this study is to review and validate clinical prediction models for BPD. METHODS: We searched the main electronic databases and abstracts from annual meetings. The STROBE instrument was used to assess the methodological quality. External validation of the retrieved models was performed using an individual patient dataset of 3229 patients at risk for BPD. Receiver operating characteristic curves were used to assess discrimination for each model by calculating the area under the curve (AUC). Calibration was assessed for the best discriminating models by visually comparing predicted and observed BPD probabilities. RESULTS: We identified 26 clinical prediction models for BPD. Although the STROBE instrument judged the quality from moderate to excellent, only four models utilised external validation and none presented calibration of the predictive value. For 19 prediction models with variables matched to our dataset, the AUCs ranged from 0.50 to 0.76 for the outcome BPD. Only two of the five best discriminating models showed good calibration. CONCLUSIONS: External validation demonstrates that, except for two promising models, most existing clinical prediction models are poor to moderate predictors for BPD. To improve the predictive accuracy and identify preterm infants for future intervention studies aiming to reduce the risk of BPD, additional variables are required. Subsequently, that model should be externally validated using a proper impact analysis before its clinical implementation.

Neonatal surfactant therapy beyond respiratory distress syndrome.

Whilst exogenous surfactant therapy is central to the management of newborn infants with respiratory distress syndrome, its use in other neonatal lung diseases remains inconsistent and controversial. Here we discuss the evidence and experience in relation to surfactant therapy in newborns with other lung conditions in which surfactant may be deficient or dysfunctional, including meconium aspiration syndrome, pneumonia, congenital diaphragmatic hernia and pulmonary haemorrhage. We find that, for all of these diseases, administration of exogenous surfactant as bolus therapy is frequently associated with transient improvement in oxygenation, likely related to temporary mitigation of surfactant inhibition in the airspaces. However, for none of them is there a lasting clinical benefit of surfactant therapy. By virtue of interrupting disease pathogenesis, lavage therapy with dilute surfactant in MAS offers the greatest possibility of a more pronounced therapeutic effect, but this has yet to be definitively proven. Lavage therapy also involves a greater degree of procedural risk.

Association of Hospital Adoption of Probiotics With Outcomes Among Neonates With Very Low Birth Weight.

Importance: For neonates with very low birth weight (VLBW), randomized clinical trials (RCTs) indicate that probiotic treatment decreases the risk of necrotizing enterocolitis (NEC), with smaller decreases in the risk of sepsis and death. There is little evidence on the rate of probiotic adoption in US neonatal intensive care units (NICUs) and whether the benefits seen in trials have materialized in practice. Objective: To estimate changes in probiotic use among neonates with VLBW and to test whether neonates with VLBW treated at NICUs adopting routine probiotic use experience better outcomes compared with neonates treated at nonadopting NICUs. Design, Setting, and Participants: This cohort study used Vermont Oxford Network data on neonates with VLBW in US NICUs from January 1, 2012, to December 31, 2019. Data were analyzed from January 2022 through February 2023. Exposure: Probiotics adoption vs nonadoption. Adopting NICUs were defined as those that currently or previously treated at least 20% of neonates with VLBW with probiotics. Main Outcomes: The primary outcomes were rates of NEC, in-hospital mortality, and sepsis, defined as bacterial or fungal infection occurring after day 3 from birth. A difference-in-differences analysis compared changes in VLBW infant outcomes between adopting and nonadopting NICUs before and after hospital-level adoption of probiotics. Additional analyses used the proportion of neonates treated with probiotics in each neonate's birth NICU and year. Results: The analysis included 307 905 neonates with VLBW (mean [SD] gestational age, 28.4 [2.9] weeks; 50.0% male) at 807 US hospitals. The rate of probiotic treatment of neonates with VLBW rose from 1572 of 38 296 neonates (4.1%) in 2012 to 4788 of 37 910 (12.6%) in 2019. Only 123 of 745 NICUs (16.5%) adopted probiotics by 2019, with 4591 of 6017 neonates with VLBW (76.3%) receiving probiotics in 2019 at adopting NICUs. Incidence of NEC declined by 18% at adopting NICUs (odds ratio [OR], 0.82; 95% CI, 0.70-0.95; P = .10) compared with nonadopting NICUs. Probiotic adoption was not associated with a significant reduction in sepsis (OR, 1.11; 95% CI, 0.98-1.25; P = .09) or mortality (OR, 0.93; 95% CI, 0.80-1.08; P = .33). Conclusion and Relevance: In this cohort study, adoption of routine use of probiotics increased slowly in US NICUs and was associated with lower NEC risk but not with sepsis or mortality among neonates with VLBW. The findings for probiotic adoption and NEC, sepsis, and mortality were smaller than would have been predicted by the totality of RCT evidence but are consistent with a meta-analysis restricted to studies at low risk of bias.

Shift-to-shift handoffs in the NICU: lessons learned from a large scale audit.

OBJECTIVE: Describe the frequency of best practice behaviors during NICU provider and nursing shift-to-shift handoffs and identify strengths and opportunities for improvement. STUDY DESIGN: Observational study of handoff characteristics among 40 centers participating in a learning collaborative over a 10-month period. Data were gathered using a handoff audit tool that outlined best practices. Comparisons of behaviors between nurse-to-nurse and provider-to-provider handoffs were made where appropriate. RESULTS: Overall, 946 audits of shift-to-shift handoffs were analyzed. While many behaviors were demonstrated reliably, differences between nurse-to-nurse vs provider-to-provider handoffs were noted. Families were present for 5.9% of handoffs and, among those who were present, 48.2% participated by contributing information, asking questions, and sharing goals. CONCLUSIONS: Observation and measurement of handoff behaviors can be used to identify opportunities to improve handoff communication, family participation, and human factors that support handoff. Auditing handoffs is feasible and necessary to improve these critical transitions in infants' care.

Racial Inequity in High-Risk Infant Follow-Up Among Extremely Low Birth Weight Infants.

BACKGROUND AND OBJECTIVES: High-risk infant follow-up programs (HRIFs) are a recommended standard of care for all extremely low birth weight (ELBW) infants to help mitigate known risks to long-term health and development. However, participation is variable, with known racial and ethnic inequities, though hospital-level drivers of inequity remain unknown. We conducted a study using a large, multicenter cohort of ELBW infants to explore within- and between-hospital inequities in HRIF participation. METHODS: Vermont Oxford Network collected data on 19 503 ELBW infants born between 2006 and 2017 at 58 US hospitals participating in the ELBW Follow-up Project. Primary outcome was evaluation in HRIF at 18 to 24 months' corrected age. The primary predictor was infant race and ethnicity, defined as maternal race (non-Hispanic white, non-Hispanic Black, Hispanic, Asian American, Native American, other). We used generalized linear mixed models to test within- and between-hospital variation and inequities in HRIF participation. RESULTS: Among the 19 503 infants, 44.7% (interquartile range 31.1-63.3) were seen in HRIF. Twenty six percent of the total variation in HRIF participation rates was due to between-hospital variation. In adjusted models, Black infants had significantly lower odds of HRIF participation compared with white infants (adjusted odds ratio, 0.73; 95% confidence interval, 0.64-0.83). The within-hospital effect of race varied significantly between hospitals. CONCLUSIONS: There are significant racial inequities in HRIF participation, with notable variation within and between hospitals. Further study is needed to identify potential hospital-level targets for interventions to reduce this inequity.

Impact of concomitant necrotizing enterocolitis on mortality in very low birth weight infants with intraventricular hemorrhage.

OBJECTIVE: To evaluate the impact of necrotizing enterocolitis (NEC) on mortality in very low birth weight (VLBW) infants with intraventricular hemorrhage (IVH). STUDY DESIGN: Data were collected on VLBW infants born 2014-2018 at Vermont Oxford Network (VON) centers. NEC and IVH were categorized by severity. Adjusted risk ratios (ARR) for in-hospital mortality were calculated. RESULTS: This study included 187 187 VLBW infants. Both medical and surgical NEC increased mortality risk compared to those without NEC. Stratification by IVH severity modified this effect (no IVH: ARR 3.04 (95%CI 2.74-3.38) for medical NEC and 4.17 (3.84-4.52) for surgical NEC; mild IVH: ARR 2.14 (1.88-2.44) for medical NEC and 2.49 (2.24-2.78) for surgical NEC; severe IVH: ARR 1.14 (1.03-1.26) for medical NEC and 1.10 (1.02-1.18) for surgical NEC). CONCLUSION: The relative impact of NEC on mortality decreased as IVH severity increased. Given the frequent coexistence of NEC and IVH, these data inform multidisciplinary management of these complex patients.