Clinical Characteristics of Necrotizing Enterocolitis Diagnosed by Independent Adjudication of Abdominal Radiographs, Laparotomy, or Autopsy in Preterm Infants in the "Connection Trial".

OBJECTIVE: Necrotizing enterocolitis (NEC) classically is diagnosed by radiographic demonstration of pneumatosis intestinalis/portal venous gas (PI/PVG). This study examines clinical characteristics of NEC confirmed by independent evaluation of abdominal radiographs, taken for clinical signs of NEC, or by pathologic findings at laparotomy or autopsy (confirmed NEC [cNEC]). STUDY DESIGN: The investigated cohort included 1,382 extremely low birth weight (BW) infants (BW range: 500-1,000 g) with median 27 weeks (range: 23-32) gestational age (GA) at birth. They were randomized into the placebo-controlled "Connection Trial" of the new biological drug candidate IBP-9414 with cNEC as one primary endpoint. RESULTS: Total 119 infants (8.6%) had cNEC diagnosed at median 14 days of age by confirming PI/PVG at X-ray adjudication (n = 111) and/or by surgery/autopsy (n = 21). Sixteen percent of cNEC cases died. Adverse events of NEC were reported in 8.5% of infants and 4.1% had NEC diagnosed by radiology and surgery/autopsy at the participating centers. Regression analyses showed that the risk of cNEC decreased by 11 to 30% for every 100-g increment in BW and single-week increment in GA and associated cNEC with odds ratios (ORs) > 2.0 for gastrointestinal (GI) perforation and obstruction, hypotension, hypokalemia, hypophosphatemia, and death. Comparing risks of cNEC in infants below and above 750-g BW showed higher ORs (2.7-4.3) for GI perforation, hypotension, hypokalemia, and renal complications in the smaller infants, whereas the bigger infants had higher ORs (1.9-3.2) for serious non-GI events, late-onset sepsis (LOS), and death. Predictors of cNEC (hazard ratio, HR > 1.5) included serious non-GI events (mainly infections), hyponatremia, and hyperglycemia, whereas the HR was 0.52 for intravenous antibiotics. After cNEC diagnosis, there were higher rates of GI perforation and obstruction, hypotension, hypokalemia, and LOS. CONCLUSION: Independent adjudication of abdominal radiographs increased radiological recognition of NEC and proved to be feasible in a multicenter study setting as well as able to diagnose clinically relevant NEC. KEY POINTS: · Independent adjudication of abdominal radiographs in ELBW infants increased NEC recognition.. · Risk of NEC decreased by 11 to 30% with every 100-g increment in BW and GA week.. · In infants with BW 750 to 1,000 g, the risk of death from NEC was almost twice that in infants with BW 500 to 749 g. · Infants with NEC received antibiotics during one-third and parenteral nutrition during half of the first 7 postnatal weeks..

Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants.

BACKGROUND: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. METHODS: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. RESULTS: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. CONCLUSIONS: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).

Using the Neonatal Intensive Care Unit Wisely: A National Survey of Clinicians Regarding Practices for Lower-Acuity Care.

OBJECTIVE: The objective of this study was to document the practices and preferences of neonatal care stakeholders regarding location and duration of care for newborns with low illness acuity. STUDY DESIGN: We developed a survey instrument that comprised 14 questions across 2 global scenarios and 7 specific clinical conditions. The latter included apnea of prematurity, gestational age for neonatal intensive care unit admission, jaundice, neonatal opioid withdrawal, thermoregulation, and sepsis evaluation. Respondents reported their current practice and preferences for an alternative approach. We administered the survey to individuals in the membership email distribution lists of the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine, the National Association of Neonatal Nurses, and the Vermont Oxford Network. RESULTS: Of 2284 respondents, 53% believed that infants were, in general, admitted to a higher level of care than was required, and only 13% reported that the level of care was too low. Length of stay was perceived to be generally too long by 46% of respondents and too short by 21%. Across 10 specific clinical questions, there was substantial variability in current practice and up to 35% of respondents reported discordance between current and preferred practice. These respondents preferred a lower level of care in 8 of 10 scenarios. CONCLUSIONS: A multidisciplinary sample of US clinicians reported significant variation in the level and duration of care for infants with low illness acuity. Among individuals reporting discordance between current and preferred practice, a majority believed that current management could be accomplished in a lower level of care location.

The Trend in Costs of Tertiary-Level Neonatal Intensive Care for Neonates Born Preterm at 220/7-286/7 Weeks of Gestation from 2010 to 2019 in Canada.

OBJECTIVE: To describe the trend in costs over 10 years for tertiary-level neonatal care of infants born 220/7-286/7 weeks of gestation during an ongoing Canadian national quality improvement project. STUDY DESIGN: Clinical characteristics, outcomes, and third-party payor costs for the tertiary neonatal care of infants born 220/7-286/7 weeks of gestation between the years 2010 and 2019 were analyzed from the Canadian Neonatal Network database. Costs were estimated using resource use data from the Canadian Neonatal Network and cost inputs from hospitals, physician billing, and administrative databases in Ontario, Canada. Cost estimates were adjusted to 2017 Canadian dollars (CAD). A generalized linear mixed-effects model with gamma regression was used to estimate trends in costs. RESULTS: Between 2010 and 2019, the number of infants born <24 weeks of gestation increased from 4.4% to 7.7%. The average length of stay increased from 68 days to 75 days. Unadjusted average ± SD total costs per neonate were $120 717 ± $93 062 CAD in 2010 and $132 774 ± $93 161 CAD in 2019. After adjustment for year, center, and gestation, total costs and length of stay increased significantly, by $13 612 CAD (P < .01) and 8.1 days (P < .01) over 10 years, respectively; whereas costs accounting for LOS remained stable. CONCLUSIONS: The total costs and length of stay for infants 220/7-286/7 weeks of gestation have increased over the past decade in Canada during an ongoing national quality improvement initiative; however, there was an increase in the number and survival of neonates at the age of periviability.

Study protocol for reducing disparity in receipt of mother's own milk in very low birth weight infants (ReDiMOM): a randomized trial to improve adherence to sustained maternal breast pump use.

BACKGROUND: Black very low birth weight (VLBW; < 1500 g birth weight) and very preterm (VP, < 32 weeks gestational age, inclusive of extremely preterm, < 28 weeks gestational age) infants are significantly less likely than other VLBW and VP infants to receive mother's own milk (MOM) through to discharge from the neonatal intensive care unit (NICU). The costs associated with adhering to pumping maternal breast milk are borne by mothers and contribute to this disparity. This randomized controlled trial tests the effectiveness and cost-effectiveness of an intervention to offset maternal costs associated with pumping. METHODS: This randomized control trial will enroll 284 mothers and their VP infants to test an intervention (NICU acquires MOM) developed to facilitate maternal adherence to breast pump use by offsetting maternal costs that serve as barriers to sustaining MOM feedings and the receipt of MOM at NICU discharge. Compared to current standard of care (mother provides MOM), the intervention bundle includes three components: a) free hospital-grade electric breast pump, b) pickup of MOM, and c) payment for opportunity costs. The primary outcome is infant receipt of MOM at the time of NICU discharge, and secondary outcomes include infant receipt of any MOM during the NICU hospitalization, duration of MOM feedings (days), and cumulative dose of MOM feedings (total mL/kg of MOM) received by the infant during the NICU hospitalization; maternal duration of MOM pumping (days) and volume of MOM pumped (mLs); and total cost of NICU care. Additionally, we will compare the cost of the NICU acquiring MOM versus NICU acquiring donor human milk if MOM is not available and the cost-effectiveness of the intervention (NICU acquires MOM) versus standard of care (mother provides MOM). DISCUSSION: This trial will determine the effectiveness of an economic intervention that transfers the costs of feeding VLBWand VP infants from mothers to the NICU to address the disparity in the receipt of MOM feedings at NICU discharge by Black infants. The cost-effectiveness analysis will provide data that inform the adoption and scalability of this intervention. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04540575 , registered September 7, 2020.

A Graded Approach to Intravenous Dextrose for Neonatal Hypoglycemia Decreases Blood Glucose Variability, Time in the Neonatal Intensive Care Unit, and Cost of Stay.

OBJECTIVE: To determine associations between a graded approach to intravenous (IV) dextrose treatment for neonatal hypoglycemia and changes in blood glucose (BG), length of stay (LOS), and cost of care. STUDY DESIGN: Retrospective cohort study of 277 infants born at ≥35 weeks of gestation in an urban academic delivery hospital, comparing the change in BG after IV dextrose initiation, neonatal intensive care unit (NICU) LOS, and cost of care in epochs before and after a hospital protocol change. During epoch 1, all infants who needed IV dextrose for hypoglycemia were given a bolus and started on IV dextrose at 60 mL/kg/day. During epoch 2, infants received IV dextrose at 30 or 60 mL/kg/day based on the degree of hypoglycemia. Differences in BG outcomes, LOS, and cost of hospital care between epochs were compared using adjusted median regression. RESULTS: In epoch 2, the median (IQR) rise in BG after initiating IV dextrose (19 [10, 31] mg/dL) was significantly lower than in epoch 1 (24 [14,37] mg/dL; adjusted ß = -6.0 mg/dL, 95% CI -11.2, -0.8). Time to normoglycemia did not differ significantly between epochs. NICU days decreased from a median (IQR) of 4.5 (2.1, 11.0) to 3.0 (1.5, 6.5) (adjusted ß = -1.9, 95% CI -3.0, -0.7). Costs associated with NICU hospitalization decreased from a median (IQR) $14 030 ($5847, $30 753) to $8470 ($5650, $19 019) (adjusted ß = -$4417, 95% CI -$571, -$8263) after guideline implementation. CONCLUSIONS: A graded approach to IV dextrose was associated with decreased BG lability and length and cost of NICU stay for infants with neonatal hypoglycemia.

International comparison of guidelines for managing neonates at the early phase of the SARS-CoV-2 pandemic.

BACKGROUND: The COVID-19 pandemic threatens global newborn health. We describe the current state of national and local protocols for managing neonates born to SARS-CoV-2-positive mothers. METHODS: Care providers from neonatal intensive care units on six continents exchanged and compared protocols on the management of neonates born to SARS-CoV-2-positive mothers. Data collection was between March 14 and 21, 2020. We focused on central protocol components, including triaging, hygiene precautions, management at delivery, feeding protocols, and visiting policies. RESULTS: Data from 20 countries were available. Disease burden varied between countries at the time of analysis. In most countries, asymptomatic infants were allowed to stay with the mother and breastfeed with hygiene precautions. We detected discrepancies between national guidance in particular regarding triaging, use of personal protection equipment, viral testing, and visitor policies. Local protocols deviated from national guidance. CONCLUSIONS: At the start of the pandemic, lack of evidence-based guidance on the management of neonates born to SARS-CoV-2-positive mothers has led to ad hoc creation of national and local guidance. Compliance between collaborators to share and discuss protocols was excellent and may lead to more consensus on management, but future guidance should be built on high-level evidence, rather than expert consensus. IMPACT: At the rapid onset of the COVID19 pandemic, all countries presented protocols in place for managing infants at risk of COVID19, with a certain degree of variations among regions. A detailed review of ad hoc guidelines is presented, similarities and differences are highlighted. We provide a broad overview of currently applied recommendations highlighting the need for international context-relevant coordination.

Predicting Successful Neonatal Retro-Transfer to a Lower Level of Care.

Up to 20% of newborn infants retro-transferred to a lower level of care require readmission to a higher-level facility. In this study, we developed and validated a prediction rule (The Rule for Elective Transfer between Units for Recovering Neonates [RETURN]) to identify clinical characteristics of infants at risk for failing retro-transfer.

Measuring practice preference variation for quality improvement in neonatal respiratory care.

OBJECTIVES: The authors sought to measure and compare practice preference variation in neonatal respiratory care within and between neonatal intensive care units (NICUs) using the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool (NSIGHT). STUDY DESIGN: Eleven NICUs completed the NSIGHT between 2019 and 2021. Net preference was measured by mean response; agreement was ranked by standard distribution of response values. Heat maps showed comparisons between NICUs and disciplines. RESULTS: NICUs and individuals agreed most often on use of pressure support with mandatory ventilation and on use of non-invasive positive pressure ventilation for apnea. High preference variation surrounded decisions for invasive ventilation versus continuous positive airway pressure for extremely low birth weight infants. Preference difference was most frequent between neonatologists and nurses. CONCLUSIONS: Patterns of practice preference variation in neonatal respiratory care are specific to clinical scenario. Measuring preference variation may inform psychology of change and strengthen quality improvement efforts.

Variations in definitions of mortality have little influence on neonatal intensive care unit performance ratings.

OBJECTIVE: To measure the influence of varying mortality time frames on performance rankings among regional neonatal intensive care units (NICUs) in a large state. STUDY DESIGN: We performed a cross-sectional data analysis of very low birth weight infants receiving care at 24 level 3 NICUs. We tested the effect of 4 definitions of mortality: (1) death between admission and end of birth hospitalization or up to 366 days; (2) death between 12 hours of age and the end of birth hospitalization or up to 366 days; (3) death between admission and 28 days; and (4) death between 12 hours of age and 28 days. NICUs were ranked by quantifying their deviation from risk-adjusted expected mortality and dividing them into 3 tiers: top 6, bottom 6, and in between. RESULTS: There was wide interinstitutional variation in risk-adjusted mortality for each definition (observed minus expected z-score range, -6.08 to 3.75). However, mortality-based NICU rankings and classification into performance tiers were very similar for all institutions in each of our time frames. Among all 4 definitions, NICU rank correlations were high (>0.91). Few NICUs changed relative to a neighboring tier with changes in definitions, and none changed by more than one tier. CONCLUSION: The time frame used to ascertain mortality had little effect on comparative NICU performance.

Prospective economic evaluation of a peer support intervention for prevention of postpartum depression among high-risk women in Ontario, Canada.

OBJECTIVE: A previous multisite, randomized, controlled trial of peer support compared with usual care for prevention of postpartum depression demonstrated a reduction in depression symptoms at 12 weeks postbirth. Our objective was to determine the cost-effectiveness of this intervention. STUDY DESIGN: Prospectively planned economic evaluation alongside the clinical trial to determine the cost per case of postpartum depression averted, using individual patient data (n = 610) and societal perspective. All costs were expressed in 2011 Canadian dollars. RESULTS: The mean cost per woman was $4,497 in the peer support group and $3,380 in the usual care group (difference of $1,117, p < 0.0001). There was a 95% probability that the program would cost less than $20,196 per case of postpartum depression averted. CONCLUSIONS: Although this is a volunteer-based program, it results in a net cost to the health care system and society. However, this cost is within the range for other accepted interventions for this population.

Economic considerations for resuscitative interventions in the immediate newborn period.

We present a systematic scoping review of the literature, which documents that only a very small number of interventions related to delivery room stabilization and resuscitation have been studied for their economic impact. Published analyses are mostly of programmatic interventions such as resuscitation training programs, are mostly in low-resource settings, and are of variable methodological quality. Investigators who are conducting clinical studies of delivery room interventions can address these deficiencies in the literature by engaging with health services researchers to assess economic outcomes alongside those studies. We provide a framework of five questions that clinical researchers may use to decide on when such an ancillary study is indicated, and to provide them with the necessary language to discuss the methodological details of potential evaluations with their health services colleagues. Emphasis should be given to interventions that are targeted to high volumes of patients, are expensive, or are likely to lead to changes in costly chronic outcomes.

Prediction and Prevention of Preterm Birth: Secondary Analysis of a Randomized Intervention Trial.

Our objective was to evaluate whether pregnancy is prolonged by the use of a proteomics-based maternal serum screening test followed by treatment interventions. This is a secondary analysis of the PREVENT-PTB randomized trial comparing screening with the PreTRM test versus no screening. The primary trial analysis found no significant between-group difference in the preterm birth rate. Rather than considering a dichotomous outcome (preterm versus term), we treated gestational age at birth as a continuous variable using survival analysis. We also evaluated between-group difference in NICU length of stay and duration of respiratory support. Results indicated that pregnancy was significantly prolonged in subjects screened with the PreTRM test compared to controls (adjusted hazard ratio 0.53, 95% confidence interval 0.36-0.78, p < 0.01). Newborns of screened subjects had significantly shorter NICU stays but no significant decrease in duration of respiratory support. In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We conclude that screening with the PreTRM test followed by interventions for screen-positive pregnancies may prolong pregnancy and reduce NICU LOS, but these observations need to be confirmed by additional research.

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.

Development and pretesting of a decision-aid to use when counseling parents facing imminent extreme premature delivery.

OBJECTIVE: To develop and pretest a decision-aid to help parents facing extreme premature delivery during antenatal counseling regarding delivery room resuscitation. STUDY DESIGN: Semistructured interviews with 31 clinicians and with 30 parents of children born <26 weeks' gestation were conducted following standard methods of qualitative research. These characterized perceptions of prenatal counseling to identify information that parents value when making decisions regarding delivery room resuscitation. These parental needs were formatted into a decision-aid. We assessed the primary outcome of how effectively the decision-aid improved knowledge during a simulated counseling session. Two groups of women were studied: parents with a history of prematurity ("experienced") and healthy women without prior knowledge of prematurity ("naïve"). RESULTS: Interviewees thought that visual formats to present survival and short- and long-term outcome information facilitated their own preparation, recall, and understanding. Accordingly, we designed a decision-aid as a set of cards with pictures and pictographs to show survival rates and complications. There was significant improvement in knowledge in 13 "experienced" parents (P = .04) and 11 "naïve" women (P < .0001). Participants found the cards useful and easy to understand. CONCLUSIONS: A decision-aid for parents facing extreme premature delivery may improve their understanding of complicated information during antenatal counseling.