The Ethics and Practice of Periviability Care.

Since the 1960s, the gestational age at which premature infants typically survive has decreased by approximately one week per decade [...].

Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial.

OBJECTIVES: To determine whether rate of severe intraventricular hemorrhage (IVH) or death among preterm infants receiving placental transfusion with UCM is noninferior to delayed cord clamping (DCC). METHODS: Noninferiority randomized controlled trial comparing UCM versus DCC in preterm infants born 28 to 32 weeks recruited between June 2017 through September 2022 from 19 university and private medical centers in 4 countries. The primary outcome was Grade III/IV IVH or death evaluated at a 1% noninferiority margin. RESULTS: Among 1019 infants (UCM n = 511 and DCC n = 508), all completed the trial from birth through initial hospitalization (mean gestational age 31 weeks, 44% female). For the primary outcome, 7 of 511 (1.4%) infants randomized to UCM developed severe IVH or died compared to 7 of 508 (1.4%) infants randomized to DCC (rate difference 0.01%, 95% confidence interval: (-1.4% to 1.4%), P = .99). CONCLUSIONS: In this randomized controlled trial of UCM versus DCC among preterm infants born between 28 and 32 weeks' gestation, there was no difference in the rates of severe IVH or death. UCM may be a safe alternative to DCC in premature infants born at 28 to 32 weeks who require resuscitation.

Overdiagnosis of Newborn Hyperbilirubinemia: A Natural Experiment in Quality Improvement Fundamentals.

Two hospitals noted increased newborn hyperbilirubinemia coinciding with an undisclosed total serum bilirubin (TSB) assay change. Clinicians rapidly applied quality improvement methodologies to ascertain increased jaundice evaluations, readmissions, and possible safety issues. Methods: In January 2020, 2 hospitals (A and B) transitioned to a new method of measuring TSB using a new clinical chemistry analyzer (Siemens Atellica CH), which measured TSB by vanadate oxidase assay instead of the previous diazo assay. Five affiliated hospitals (C-G) continued to utilize the diazo assay. This natural experiment led to a comparison of data across the 7 hospitals. We analyzed: (1) TSB levels, (2) hospital hyperbilirubinemia readmissions, and (3) paired TSB measurements comparing the diazo assay and vanadate oxidase method. Results: Compared to the 2019 baseline, Hospitals A and B had a significant increase in TSBs ≥17.0 mg/dl and TSBs ≥20 mg/dl in 2020; Hospitals C-G did not. Readmissions for phototherapy significantly increased in hospitals A and B in 2020 compared to 2019. Paired blood samples showed bias-elevated TSBs by vanadate assay compared to the diazo method. By 2021, the laboratory resumed processing TSB samples by diazo assay, and the frequency of elevated TSBs and hyperbilirubinemia readmissions returned to 2019 levels. Conclusions: Factitious TSB elevation related to an assay change significantly increased newborn hyperbilirubinemia evaluations and phototherapy readmissions. Imbedded quality improvement methodologies of careful structure, process, and outcomes review hastened resolution.

Promoting children's rights to health and well-being in the United States.

The United States has a highly sophisticated pediatric healthcare system and spends more than any other country per capita on children's healthcare. However, not all children have access to needed and affordable health care and the life expectancy and health outcomes of children in the country are worse than in any other industrialized nation. These nations typically offer universal healthcare for children as part of a robust recognition of a children's rights framework. In 1989 the United Nations adopted the Convention on the Rights of the Child that recognizes the right of the child to the highest attainable standard of health and to facilities for the treatment of illness and rehabilitation of health. Currently the United States is the only United Nations member country that has not ratified the Convention on the Rights of the Child. This paper outlines the potential benefits of adopting a child rights approach based on the principles and provisions of the Convention on the Rights of the Child. The fact that countries who invest much less in healthcare compared to the United States can achieve better health outcomes provides the certainty that a solution is possible and within reach.

Discontinuation of Car Seat Tolerance Screening and Postdischarge Adverse Outcomes in Infants Born Preterm.

OBJECTIVE: To study the association between discontinuing predischarge car seat tolerance screening (CSTS) with 30-day postdischarge adverse outcomes in infants born preterm. STUDY DESIGN: Retrospective cohort study involving all infants born preterm from 2010 through 2021 who survived to discharge to home in a 14-hospital integrated health care system. The exposure was discontinuation of CSTS. The primary outcome was a composite rate of death, 911 call-triggered transports, or readmissions associated with diagnostic codes of respiratory disorders, apnea, apparent life-threatening event, or brief resolved unexplained events within 30 days of discharge. Outcomes of infants born in the periods of CSTS and after discontinuation were compared. RESULTS: Twelve of 14 hospitals initially utilized CSTS and contributed patients to the CSTS period; 71.4% of neonatal intensive care unit (NICU) patients and 26.9% of non-NICU infants were screened. All hospitals participated in the discontinuation period; 0.1% was screened. Rates of the unadjusted primary outcome were 1.02% in infants in the CSTS period (n = 21 122) and 1.06% after discontinuation (n = 20 142) (P = .76). The aOR (95% CI) was 0.95 (0.75, 1.19). Statistically insignificant differences between periods were observed in components of the primary outcome, gestational age strata, NICU admission status groups, and other secondary analyses. CONCLUSIONS: Discontinuation of CSTS in a large integrated health care network was not associated with a change in 30-day postdischarge adverse outcomes. CSTS's value as a standard predischarge assessment deserves further evaluation.

Extremely premature birth bioethical decision-making supported by dialogics and pragmatism.

Moral values in healthcare range widely between interest groups and are principally subjective. Disagreements diminish dialogue and marginalize alternative viewpoints. Extremely premature births exemplify how discord becomes unproductive when conflicts of interest, cultural misunderstanding, constrained evidence review, and peculiar hierarchy compete without the balance of objective standards of reason. Accepting uncertainty, distributing risk fairly, and humbly acknowledging therapeutic limits are honorable traits, not relativism, and especially crucial in our world of constrained resources. We think dialogics engender a mutual understanding that: i) transitions beliefs beyond bias, ii) moves conflict toward pragmatism (i.e., the truth of any position is verified by subsequent experience), and iii) recognizes value pluralism (i.e., human values are irreducibly diverse, conflicting, and ultimately incommensurable). This article provides a clear and useful Point-Counterpoint of extreme prematurity controversies, an objective neurodevelopmental outcomes table, and a dialogics exemplar to cultivate shared empathetic comprehension, not to create sides from which to choose. It is our goal to bridge the understanding gap within and between physicians and bioethicists. Dialogics accept competing relational interests as human nature, recognizing that ultimate solutions satisfactory to all are illusory, because every choice has downside. Nurturing a collective consciousness via dialogics and pragmatism is congenial to integrating objective evidence review and subjective moral-cultural sentiments, and is that rarest of ethical constructs, a means and an end.

The Triple Aim Quality Improvement Gold Standard Illustrated as Extremely Premature Infant Care.

OBJECTIVES: The Triple Aim is widely regarded as the quality improvement gold standard that enhances population health, lowers costs, and betters individual care. There have been no large-scale, sustained demonstrations of such improvement in healthcare. Illustrating the Triple Aim using relevant extremely premature infant outcomes might highlight interwoven proficiency and efficiency complexities that impede sustained value progress. STUDY DESIGN: Ten long-term collaborating neonatal intensive care units (NICU) in the Vermont Oxford Network calculated the Triple Aim in 230/7 to 276/7-week infants using three surrogate measures: (1) population health/x-axis-eight major morbidity rates as a composite, risk-adjusted metric; (2) cost/y-axis-total hospital length of stay; and (3) individual care/z-axis-mortality, then illustrated this relationship as a sphere within a three-dimensional cube. RESULTS: Three thousand seven hundred six infants born between January 1, 2014 and December 31, 2019, with mean (standard deviation) gestational age of 25.7 (1.4) weeks and birth weight of 803 (208) grams were analyzed. Triple Aim three-axis cube positions varied inconsistently comparing NICUs. Each NICUs' sphere illustrated mixed x- and z-axis movement (clinical proficiency), and y-axis movement (cost efficiency). No NICU demonstrated the theoretically ideal Triple Aim improvement in all three axes. Backward movement in at least one axis occurred in eight NICUs. The whole-group Triple Aim sphere moved forward along the x-axis (better morbidities metric), but moved backward in the y-axis length of stay and z-axis mortality measurements. CONCLUSION: Illustrating the Triple Aim gold standard as extreme prematurity outcomes reveals complexities inherent to simultaneous attempts at improving interwoven quality and cost outcomes. Lack of progress using relevant Triple Aim parameters from our well-established collaboration highlights the difficulties prioritizing competing outcomes, variable potentially-better-practice applications amongst NICUs, unmeasured biologic interactions, and obscured cultural-environmental contexts that all likely affect care. Triple Aim excellence, if even remotely possible, will necessitate scalable, evidence-based methodologies, pragmatism regarding inevitable trade-offs, and wise constrained-resource decisions. KEY POINTS: · The Triple Aim gold standard is elusive. There is no demonstration of sustained, large-scale success in healthcare and our quality improvement network has previously published benchmark extreme prematuritymorbidity improvements.. · Extreme prematurity outcomes illustrated as the Triple Aim show uneven results in relevant surrogate parameters and Triple Aim achievement, if even possible, will necessitate evidence-based methodologies that are scalable.. · Pragmatism, inevitable trade-offs, and wise constrained-resource decisions are required for Triple Aim success..

Change in neurodevelopmental outcomes for extremely premature infants over time: a systematic review and meta-analysis.

OBJECTIVE: Survival rates of extremely premature infants are rising, but changes in neurodevelopmental impairment (NDI) rates are unclear. Our objective was to perform a systematic review of intrainstitutional variability of NDI over time. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid MEDLINE, Embase, PubMed, Cochrane Library and Google Scholar. STUDY SELECTION: Study eligibility: (1) at least two discrete cohorts of infants born <27 weeks' gestation or <1000 g birth weight, (2) one cohort born after 1990 and at least one subsequent cohort of similar gestational age, (3) all cohorts cared for within the same Neonatal Intensive Care Unit(s) (NICU) and (4) neurodevelopmental outcomes at 18-36 months corrected age. MAIN OUTCOME: Change in NDI rates. Quality, validity and bias were assessed using Grading of Recommendations, Assessment, Development, and Evaluation and Quality in Prognosis Studies guidelines. RESULTS: Of 203 publications, 15 were eligible, including 13 229 infants. At the first time point, average NDI rate across study groups weighted by sample size was 41.0% (95% CI 34.0% to 48.0%). The average change in NDI between time points was -3.3% (95% CI -8·8% to 2.2%). For each added week of gestation at birth, the rate of NDI declined by 9.7% (95% CI 6.2% to 13.3%). Most studies exhibited moderate-severe bias in at least one domain, especially attrition rates. CONCLUSIONS: When comparing discrete same-centre cohorts over time, there was no significant change in NDI rates in infants born <27 weeks' gestation or <1000 g. Higher survival rates unaccompanied by improvement in neurodevelopment highlight urgency for renewed focus on the causes of NDI and evidence-based strategies to reduce brain injury.

Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.

BACKGROUND: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

Perinatal Outcomes of Subjects Enrolled in a Multicenter Trial with a Waiver of Antenatal Consent.

OBJECTIVE: This study aimed to determine whether outcomes differed between infants enrolled in the PREMOD2 trial and those otherwise eligible but not enrolled, and whether the use of waiver effected these differences. STUDY DESIGN: The multicenter PREMOD2 (PREmature infants receiving Milking Or Delayed cord clamping) trial was approved for waiver of antenatal consent by six of the nine sites institutional review boards, while three sites exclusively used antenatal consent. Every randomized subject delivered at a site with a waiver of consent was approached for postnatal consent to allow for data collection. Four of those six sites IRBs required the study team to attempt antenatal consent when possible. Three sites exclusively used antenatal consent. RESULTS: Enrolled subjects had higher Apgar scores, less use of positive pressure ventilation, a lower rate of bronchopulmonary dysplasia, and a less frequent occurrence of the combined outcome of severe intraventricular hemorrhage or death. A significantly greater number of infants were enrolled at sites with an option of waiver of consent (66 vs. 26%, risk ratio = 2.54, p < 0.001). At sites with an option of either approaching families before delivery or after delivery with a waiver of antenatal consent, those approached prior to delivery refused consent 40% (range 15-74% across six sites) of the time. CONCLUSION: PREMOD2 trial demonstrated analytical validity limitations because of the variable mix of antenatal consent and waiver of consent. A waiver of antenatal consent for minimal risk interventional trials conducted during the intrapartum period will be more successful in enrolling a representative sample of low and high-risk infants if investigators are able to enroll all eligible subjects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03019367. KEY POINTS: · Waiver of consent is when informed consent cannot be obtained prior to delivery.. · Cord milking is a procedure in which blood is pushed (stripped) two to four times towards the newborn.. · Delayed clamping means the umbilical cord is not clamped immediately after birth..

Do small baby units improve extremely premature infant outcomes?

Increasing numbers of neonatal intensive care units have formed small baby units or small baby teams with the intention to optimize care of extremely premature infants. Considerable time, energy, and resources are required to develop and sustain complex quality improvement constructs, so legitimate questions about effectiveness, unintended consequences, and lost opportunity costs warrant scrutiny. The small baby unit literature is diminutive. Errors of chance, bias, and confounding secondary to insufficient definitions of process and outcome metrics, overlapping quality improvement projects, and limited cost analyses restrict firm conclusions. Well-established quality improvement methodologies such as evidence-based guidelines, standardized variability reduction using measurement-and-adjust techniques, family-integrated focus, and developmentally sensitive care, reliably improve outcomes for all-sized premature infants. There is not compelling published evidence that adding specialized small baby units or designated teams for extremely premature infants further enhances short- or long-term health if robust quality improvement fundamentals are already imbedded within local culture.

Continued improvement in morbidity reduction in extremely premature infants.

OBJECTIVE: Provide a progress report updating our long-term quality improvement collaboration focused on major morbidity reduction in extremely premature infants 23-27 weeks. METHODS: 10 Vermont Oxford Network (VON) neonatal intensive care units (NICUs) (the POD) sustained a structured alliance: (A) face-to-face meetings, site visits and teleconferences, (B) transparent process and outcomes sharing, (C) utilisation of evidence-based potentially better practice toolkits, (D) family integration and (E) benchmarking via a composite mortality-morbidity score (Benefit Metric). Morbidity-specific toolkits were employed variably by each NICU according to local priorities. The eight major VON morbidities and the risk-adjusted Benefit Metric were compared in two epochs 2010-2013 versus 2014-2018. RESULTS: 5888 infants, mean (SD) gestational age 25.8 (1.4) weeks, were tracked. The POD Benefit Metric significantly improved (p=0.03) and remained superior to the aggregate VON both epochs (p<0.001). Four POD morbidities significantly improved through 2018 - chronic lung disease (48%-40%), discharge weight <10th percentile (32%-22%), any late infection (19%-17%) and periventricular leukomalacia (4%-2%). In epoch 2, 34% of survivors had none of the eight major morbidities, while 36% had just one. Mortality did not change. CONCLUSIONS: Inter-NICU collaboration, process and outcomes sharing and potentially better practice toolkits sustain improvement in 23-27 week morbidity rates, notably chronic lung disease, extrauterine growth restriction and the lowest zero-or-one major morbidity rate reported by a quality improvement collaboration. Unrevealed biological and cultural variables affect morbidity rates, countless remain unmeasured, thus duplication to other quality improvement groups is challenging. Understanding intensive care as innumerable interactions and constant flux that defy convenient linear constructs is fundamental.

Prolonged Tracheal Intubation and the Association Between Patent Ductus Arteriosus and Bronchopulmonary Dysplasia: A Secondary Analysis of the PDA-TOLERATE trial.

In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required <10 days of intubation. However, in infants requiring intubation for ≥10 days, prolonged PDA exposure (≥11 days) was associated with an increased risk of moderate/severe BPD.

Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants.

Importance: Umbilical cord milking as an alternative to delayed umbilical cord clamping may provide equivalent benefits to preterm infants, but without delaying resuscitation. Objective: To determine whether the rates of death or severe intraventricular hemorrhage differ among preterm infants receiving placental transfusion with umbilical cord milking vs delayed umbilical cord clamping. Design, Setting, and Participants: Noninferiority randomized clinical trial of preterm infants (born at 23-31 weeks' gestation) from 9 university and private medical centers in 4 countries were recruited and enrolled between June 2017 and September 2018. Planned enrollment was 750 per group. However, a safety signal comprising an imbalance in the number of severe intraventricular hemorrhage events by study group was observed at the first interim analysis; enrollment was stopped based on recommendations from the data and safety monitoring board. The planned noninferiority analysis could not be conducted and a post hoc comparison was performed instead. Final date of follow-up was December 2018. Interventions: Participants were randomized to umbilical cord milking (n = 236) or delayed umbilical cord clamping (n = 238). Main Outcomes and Measures: The primary outcome was a composite of death or severe intraventricular hemorrhage to determine noninferiority of umbilical cord milking with a 1% noninferiority margin. Results: Among 540 infants randomized, 474 (88%) were enrolled and completed the trial (mean gestational age of 28 weeks; 46% female). Twelve percent (29/236) of the umbilical cord milking group died or developed severe intraventricular hemorrhage compared with 8% (20/238) of the delayed umbilical cord clamping group (risk difference, 4% [95% CI, -2% to 9%]; P = .16). Although there was no statistically significant difference in death, severe intraventricular hemorrhage was statistically significantly higher in the umbilical cord milking group than in the delayed umbilical cord clamping group (8% [20/236] vs 3% [8/238], respectively; risk difference, 5% [95% CI, 1% to 9%]; P = .02). The test for interaction between gestational age strata and treatment group was significant for severe intraventricular hemorrhage only (P = .003); among infants born at 23 to 27 weeks' gestation, severe intraventricular hemorrhage was statistically significantly higher with umbilical cord milking than with delayed umbilical cord clamping (22% [20/93] vs 6% [5/89], respectively; risk difference, 16% [95% CI, 6% to 26%]; P = .002). Conclusions and Relevance: In this post hoc analysis of a prematurely terminated randomized clinical trial of umbilical cord milking vs delayed umbilical cord clamping among preterm infants born at less than 32 weeks' gestation, there was no statistically significant difference in the rate of a composite outcome of death or severe intraventricular hemorrhage, but there was a statistically significantly higher rate of severe intraventricular hemorrhage in the umbilical cord milking group. The early study termination and resulting post hoc nature of the analyses preclude definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT03019367.

Lack of Equipoise in the PDA-TOLERATE Trial: A Comparison of Eligible Infants Enrolled in the Trial and Those Treated Outside the Trial.

The PDA: TO LEave it alone or Respond And Treat Early trial compared the effects of 2 strategies for treatment of patent ductus arteriosus (PDA) in infants <280/7 weeks of gestation; however 137 potentially eligible infants were not recruited and received treatment of their PDA outside the PDA-TOLERATE trial due to "lack-of-physician-equipoise" (LPE). Despite being less mature and needing more respiratory support, infants with LPE had lower rates of mortality than enrolled infants. Infants with LPE treated before day 6 had lower rates of late respiratory morbidity than infants with LPE treated ≥day 6. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.

Sustained quality improvement collaboration and composite morbidity reduction in extremely low gestational age newborns.

AIM: Continuous quality improvement has failed to consistently reduce morbidities in extremely low gestational age newborns 23-27 weeks. 10 Vermont Oxford Network NICUs describe a novel, sustained collaboration for progress. METHODS: We emphasised a) commitment to inter-NICU trust with face-to-face meetings, site visits, teleconferences, scrutiny of quality improvement methodology, b) transparent process and outcomes sharing, c) evidence-based formulation of an orchestrated testing matrix to select potentially better practices, d) family integration, e) benchmarking with a composite mortality-morbidity score (Benefit Metric). RESULTS: A total of 4709 infants, mean (SD) gestational age 25.8 (1.4) weeks, admitted to 10 NICUs 1.01.2010 to 12.31.2016. The orchestrated matrix offered 45 potentially better practices; NICUs implemented mean 29 (range 19-40). There was widespread adoption of delivery room, respiratory care and infection prevention practices, but no uniform pattern. Our Benefit Metric was significantly greater than the Vermont Oxford Network all seven years (p < 0.001). Six major morbidities decreased, two significantly (p < 0.05), mortality unchanged (14%). 34% of survivors had no morbidities, 35% just one. CONCLUSION: Cultivating trust, transparent outcomes sharing, and tailored, potentially better practice selection is associated with encouraging improvement in 23- to 27-week survival without morbidity. Our outcomes are objective but the optimal implementation pathway to sustain progress remains murky, reflective of NICUs as complex adaptive networks.