Variability in Practice and Implementation of Oxygen Target Saturation Policies in United States' Neonatal Intensive Care Units.

OBJECTIVE: This study aimed to describe target oxygen saturation (SpO2) ranges used for premature infants in United States' neonatal intensive care units (NICUs) and to describe if these target SpO2 ranges have changed in recent years. STUDY DESIGN: A 29-question survey focused on target SpO2 practices and policies was distributed via the NICU medical directors listservs for the American Academy of Pediatrics Section of Neonatal-Perinatal Medicine and Pediatrix Medical Group between August and October of 2021. Results were collected via Research Electronic Data Capture (REDCap). RESULTS: We received responses representing 170 unique, levels 2, 3, and 4 NICUs from 36 states. Most NICUs (130, 78%) have recently changed their SpO2 targets in response to target SpO2 clinical trials. Over time, the most commonly reported target SpO2 range has shifted from 88-92% to 90-95%. Of NICUs that changed limits, the most common lower SpO2 limits increased from 88 to 90% and the upper SpO2 limits changed from 92 to 95%. The interquartile range for lower SpO2 limit shifted from 85-88% to 88-90% and the IQR for upper SpO2 limit decreased from 92-95% to 94-95%. Most NICUs had designated conditions that would allow for deviations from standard target SpO2 ranges. These most commonly include pulmonary hypertension (152, 95%), severe bronchopulmonary dysplasia (81, 51%), and retinopathy of prematurity (51, 32%). CONCLUSION: Oxygen saturation limits have changed over time with an overall increase in targeted SpO2. However, there remains considerable interunit variation in SpO2 policies. There is a need to achieve consensus to optimize clinical outcomes. KEY POINTS: · What are the SpO2 ranges in United States' NICUs?. · There is a shift in SpO2 ranges for preterm infants in NICUs across United States.. · Variability still persists in SpO2 ranges for preterm infants in United States' NICUs..

Neonatal Intensive Care Unit Resource Use for Infants at 22 Weeks' Gestation in the US, 2008-2021.

Importance: During the past decade, clinical guidance about the provision of intensive care for infants born at 22 weeks' gestation has changed. The impact of these changes on neonatal intensive care unit (NICU) resource utilization is unknown. Objective: To characterize recent trends in NICU resource utilization for infants born at 22 weeks' gestation compared with other extremely preterm infants (≤28 weeks' gestation) and other NICU-admitted infants. Design, Setting, and Participants: This is a serial cross-sectional study of 137 continuously participating NICUs in 29 US states from January 1, 2008, through December 31, 2021. Participants included infants admitted to the NICU. Data analysis was performed from October 2022 to August 2023. Exposures: Year and gestational age at birth. Main Outcomes and Measures: Measures of resource utilization included NICU admissions, NICU bed-days, and ventilator-days. Results: Of 825 112 infants admitted from 2008 to 2021, 60 944 were extremely preterm and 872 (466 [53.4%] male; 18 [2.1%] Asian; 318 [36.5%] Black non-Hispanic; 218 [25.0%] Hispanic; 232 [26.6%] White non-Hispanic; 86 [9.8%] other or unknown) were born at 22 weeks' gestation. NICU admissions at 22 weeks' gestation increased by 388%, from 5.7 per 1000 extremely preterm admissions in 2008 to 2009 to 27.8 per 1000 extremely preterm admissions in 2020 to 2021. The number of NICU admissions remained stable before the publication of updated clinical guidance in 2014 to 2016 and substantially increased thereafter. During the study period, bed-days for infants born at 22 weeks increased by 732%, from 2.5 per 1000 to 20.8 per 1000 extremely preterm NICU bed-days; ventilator-days increased by 946%, from 5.0 per 1000 to 52.3 per 1000 extremely preterm ventilator-days. The proportion of NICUs admitting infants born at 22 weeks increased from 22.6% to 45.3%. Increases in NICU resource utilization during the period were also observed for infants born at less than 22 and at 23 weeks but not for other gestational ages. In 2020 to 2021, infants born at less than or equal to 23 weeks' gestation comprised 1 in 117 NICU admissions, 1 in 34 of all NICU bed-days, and 1 in 6 of all ventilator-days. Conclusions and Relevance: In this serial cross-sectional study of 137 US NICUs from 2008 to 2021, an increasing share of resources in US NICUs was allocated to infants born at 22 weeks' gestation, corresponding with changes in national clinical guidance.

Trends in Procedural Closure of the Patent Ductus Arteriosus among Infants Born at 22 to 30 Weeks' Gestation.

OBJECTIVE: To describe recent trend in procedural closure of the patent ductus arteriosus (PDA) among premature infants and compare the clinical characteristics of infants receiving surgical vs transcatheter closure. STUDY DESIGN: We conducted a descriptive, retrospective cohort study of preterm infants born between 220/7 and 296/7 weeks' gestation from 2014 through 2021. Infants were identified from the Pediatrix Clinical Data Warehouse. We excluded infants with any major congenital anomaly. We identified all preterm infants with a PDA and all those who underwent procedural closure (surgical ligation or transcatheter occlusion) and compared changes over time using ANOVA for continuous variables and the Cochran-Armitage trend test to evaluate time-related changes in proportions. RESULTS: The study cohort included 64 580 infants, of whom 24 028 (37.2%) were diagnosed with a PDA. The number of infants receiving any procedural closure of the PDA decreased from 371 (4.4%) in 2014 to 144 (1.9%) in 2021. During the same period, number of surgical ligations decreased from 369 (4.36%) to 64 (0.84%), and the number of transcatheter occlusions increased from 2 (0.02%) to 80 (1.05% p for all < 0.001). The median age at time of surgical ligation increased from 25 days (10th and 90th percentile, 10, 61) to 31 days (10th and 90th percentile, 16, 66), and the median age of transcatheter occlusion decreased from 103 days (10th and 90th percentile, 32, 150) to 43 days (10th and 90th percentile, 22, 91). CONCLUSIONS: There was a decrease in surgical closure and an increase in transcatheter occlusion of the PDA in infants born at 22-30 weeks' gestation from 2014 to 2021. Despite the decline in overall procedural closure, the rate of transcatheter occlusion surpassed surgical ligation by 2021. Narrowing differences in the median age and weight at closure suggest increasing overlap in the types of infants who received each type of procedural closure.

Prevalence and Clinical Significance of Commonly Diagnosed Genetic Disorders in Preterm Infants.

Background and Objectives: Preterm infants (<34 weeks' gestation) experience high rates of morbidity and mortality before hospital discharge. Genetic disorders substantially contribute to morbidity and mortality in related populations. The prevalence and clinical impact of genetic disorders is unknown in this population. We sought to determine the prevalence of commonly diagnosed genetic disorders in preterm infants, and to determine the association of disorders with morbidity and mortality. Methods: This was a retrospective multicenter cohort study of infants born from 23 to 33 weeks' gestation between 2000 and 2020. Genetic disorders were abstracted from diagnoses present in electronic health records. We excluded infants transferred from or to other health care facilities prior to discharge or death when analyzing clinical outcomes. We determined the adjusted odds of pre-discharge morbidity or mortality after adjusting for known risk factors. Results: Of 320,582 infants, 4196 (1.3%) had genetic disorders. Infants with trisomy 13, 18, 21, or cystic fibrosis had greater adjusted odds of severe morbidity or mortality. Of the 17,427 infants who died, 566 (3.2%) had genetic disorders. Of the 65,968 infants with a severe morbidity, 1319 (2.0%) had genetic disorders.ConclusionsGenetic disorders are prevalent in preterm infants, especially those with life-threatening morbidities. Clinicians should consider genetic testing for preterm infants with severe morbidity and maintain a higher index of suspicion for life-threatening morbidities in preterm infants with genetic disorders. Prospective genomic research is needed to clarify the prevalence of genetic disorders in this population, and the contribution of genetic disorders to preterm birth and subsequent morbidity and mortality. Article Summary: Genetic disorders were found in 1.3% of preterm infants and at a higher rate (2.0%) in infants who died or developed severe morbidity. What's Known on This Subject: Previous research described the prevalence and associated short-term morbidity and mortality of trisomy 13, 18, and 21 in preterm infants. The prevalence of other commonly diagnosed genetic disorders and associated short-term morbidity and mortality in preterm infants is unknown. What This Study Adds: In a multicenter, retrospective cohort of 320,582 preterm (<34 weeks' gestation) infants, we found that 1.3% had genetic disorders diagnosed through standard care. Multiple disorders were associated with increased adjusted odds of morbidities or mortality prior to hospital discharge. Contributors Statement Page: Selin S. Everett conceptualized and designed the study, conducted analyses, drafted the initial manuscript, and critically reviewed and revised the manuscript.Dr. Thomas Hays conceptualized and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript.Miles Bomback conceptualized and designed the study and critically reviewed and revised the manuscript.Drs. Veeral N. Tolia and Reese H. Clark coordinated and supervised data collection and critically reviewed and revised the manuscript.Dr. Rakesh Sahni conceptualized and designed the study and critically reviewed and revised the manuscript.Dr. Alex Lyford conducted analyses and critically reviewed and revised the manuscript. Dr. Ronald J. Wapner reviewed and critically revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Congenital anomalies of the kidney and urinary tract (CAKUT) in critically ill infants: a multicenter cohort study.

BACKGROUND: The aim of the study was to determine the prevalence of congenital anomalies of the kidney and urinary tract (CAKUT) in the neonatal intensive care unit (NICU) and to evaluate risk factors associated with worse outcomes. We hypothesized that infants with CAKUT with extra-renal manifestations have higher mortality. METHODS: This is a cohort study of all inborn infants who were diagnosed with any form of CAKUT discharged from NICUs managed by the Pediatrix Medical Group from 1997 to 2018. Logistic and linear regression models were used to analyze risk factors associated with in-hospital mortality. RESULTS: The prevalence of CAKUT was 1.5% among infants hospitalized in 419 NICUs. Among the 13,383 infants with CAKUT analyzed, median gestational age was 35 (interquartile range [IQR] 31-38) weeks and median birth weight was 2.34 (IQR 1.54-3.08) kg. Overall in-hospital mortality for infants with CAKUT was 6.8%. Oligohydramnios (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] 2.2-9.1, p < 0.001), extra-renal anomalies (aOR 2.5, 95% CI 2.0-3.1, p < 0.001), peak SCr (aOR 1.02, 95% CI 1.01-1.03, p < 0.001) and exposure to nephrotoxic medications (aOR 1.4, 95% CI 1.1-1.7, p = 0.01) were associated with increased mortality, while a history of urological surgery or intervention was associated with lower mortality (aOR 0.6, 95% CI 0.4-0.7, p < 0.001). CONCLUSIONS: Infants hospitalized in the NICU who have CAKUT and the independent risk factors for mortality (e.g., oligohydramnios and presence of extra-renal anomalies) require close monitoring, minimizing of exposure to nephrotoxic drugs, and timely urological surgery or intervention. A higher resolution version of the Graphical abstract is available as Supplementary information.

Iron supplementation and the risk of bronchopulmonary dysplasia in extremely low gestational age newborns.

BACKGROUND: The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD). METHODS: A secondary analysis of the PENUT Trial dataset was conducted. The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks' gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization. RESULTS: Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks' 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD. CONCLUSIONS: We find no support for an increased risk of BPD with iron supplementation. TRIAL REGISTRATION NUMBER: NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 IMPACT: Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants. For 24-27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.

The Prevalence and Clinical Significance of Congenital Anomalies of the Kidney and Urinary Tract in Preterm Infants.

Importance: The prevalence and importance of congenital anomalies of the kidney and urinary tract (CAKUT) in preterm infants is unknown. Objective: To determine the prevalence of CAKUT in preterm infants and association with in-hospital morbidity and mortality. Design, Setting, and Participants: This cohort study included infants cared for in neonatal intensive care units managed by a large US network of hospitals and doctors. Eligible participants were infants born at 23 to 33 weeks' gestation between 2000 and 2020. Infants transferred from or to other health care facilities prior to discharge or death were excluded in analysis of outcomes. Data were analyzed from December 2021 until May 2022. Exposures: The presence of anomalies of the kidneys, ureters, bladder, or urethra was assessed. Covariates were discharge year, exposure to antenatal steroids, sex, maternal race, gestational age, birthweight, mechanical ventilation in first 72 hours of life, genetic disorders, and extrarenal anomalies. Main Outcomes and Measures: Death or in-hospital severe illness (acute kidney injury, kidney failure, intracranial hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, bacterial sepsis, or administration of inotrope or vasopressor). Results: In this cohort of 409 704 infants, 191 105 (46.6%) were girls, mean (SD) gestational age was 30.1 (2.84) weeks, and mean (SD) birth weight was 1.49 (0.53) kg. A total of 8093 infants (2.0%) had CAKUT, with urinary tract dilation comprising the majority of cases (5669 [70.0%]). The presence of CAKUT correlated with earlier gestational age and was associated with genetic disorders and extrarenal anomalies. Analysis of 323 957 infants after exclusions demonstrated an adjusted odds ratio of 3.96 (95% CI, 3.70-4.24) of death or severe illness. This risk was found across all forms of CAKUT including isolated urinary tract dilation. Conclusions and Relevance: The findings of this cohort study suggest that clinicians caring for preterm infants should have higher suspicion for CAKUT and consider screening, particularly those with extrarenal anomalies or genetic disorders, as preterm infants with CAKUT appear to be at significantly higher risk of death or severe illness. Detection of CAKUT can inform risk stratification and clinical decision making, and should also prompt clinicians to consider a genetic evaluation.

Palivizumab Use in the NICU: 1999-2020.

OBJECTIVE: To examine the relationship between changes in American Academy of Pediatrics (AAP) guidance and palivizumab use for infants admitted to the NICU. We hypothesized that each change in guidance would be associated with a change in palivizumab usage. METHODS: This is a retrospective repeated cross-sectional study of palivizumab usage in defined subgroups of infants discharged between 1999 and 2020 using the Pediatrix Clinical Data Warehouse. RESULTS: Palivizumab utilization increased in all groups between 1999 and 2003 and remained stable until 2013. Large changes in palivizumab use occurred between 2013 and 2015 followed by slower changes from 2016 to 2020. The largest decrease was in infants born between 29 0/7 and 31 6/7 weeks' gestational age without chronic lung disease (decreased from 87% to 21%; P < .001). The second largest absolute decrease was infants born at 32 0/7 to 34 6/7 weeks' gestational age without chronic lung disease and no major anomalies (decreased from 52% to 6%; P < .001). The decrease in term infants with major congenital heart problem was smaller (25 to 17%; P < .001). Even in the most vulnerable infants born between 22 0/7 and 28 6/7 estimated gestational age, palivizumab use declined (88% in 2013 to 74% in 2020; P < .001). CONCLUSIONS: Early AAP guidelines had minor impacts on palivizumab use in infants discharged from the hospital from the NICU. The 2014 guidelines resulted in major changes in palivizumab use and extended into populations for which the AAP guidance remained unchanged.

Association between postmenstrual age and furosemide dosing practices in very preterm infants.

OBJECTIVE: Furosemide renal clearance is slow after very preterm (VP) birth and increases with postnatal maturation. We compared furosemide dose frequency and total daily dose between postmenstrual age (PMA) groups in VP infants. STUDY DESIGN: Observational cohort study of VP infants exposed to a repeated-dose course of furosemide in Pediatrix neonatal intensive care units (NICU) from 1997 to 2016. RESULTS: We identified 6565 furosemide courses among 4638 infants. There were no statistically significant differences between PMA groups on the odds of receiving more frequent furosemide dosing. Furosemide courses initiated at <28 weeks PMA were associated with a higher total daily dose than those initiated at a later PMA. CONCLUSIONS: Furosemide dosing practices in the NICU are similar across PMA groups, despite maturational changes in drug disposition. Research is needed to identify and test rational dosing strategies across the PMA spectrum for this commonly used but unproven pharmacotherapy.

Changing Tocolytic Exposures among Neonatal Intensive Care Unit Admitted Preterm Infants.

OBJECTIVE: Since 2010, the American College of Obstetrics and Gynecology have released three committee opinions to recommend and reaffirm the utility of magnesium sulfate for neuroprotection and later for tocolysis to achieve antenatal steroid course completion in preterm labor. We sought to determine changes in antenatal magnesium sulfate exposure and other tocolytic agents for pregnancies resulting in neonatal intensive care unit (NICU)-admitted preterm infants. STUDY DESIGN: Using the Pediatrix Clinical Data Warehouse, we evaluated all inborn infants delivered between 22 and 33 weeks' gestation and admitted to the intensive care units from 2009 to 2018. We classified patients based on antenatal exposure to tocolytic medications: calcium channel blockers (nifedipine and amlodipine), betamimetics (terbutaline, theophylline, and ritodrine), prostaglandin inhibitors (indomethacin), and magnesium sulfate. RESULTS: A total of 229,781 patients met inclusion criteria. During the study period, magnesium sulfate exposure increased from 27.6 to 57.7% of births while betamimetic exposure decreased from 10.2 to 5.2%. Increasing magnesium sulfate exposure over time was seen at all gestational ages examined and magnesium exposure was most common between 23 and 31 weeks' gestation. By 2017 to 2018, 70.5% of 24 to 29 weeks' gestation NICU infants received exposure to at least one tocolytic agent while this remained at 53.7% of 32 to 33 weeks' NICU admitted infants. Antenatal steroid exposure increased from 74.8 to 87.4% during the study period. CONCLUSION: For NICU-admitted preterm infants, prenatal exposure patterns to tocolytic agents has shifted since 2009 with prenatal magnesium sulfate exposure increasing significantly. Antenatal steroid exposure has risen concurrently. Exposure to tocolytic agents is the highest among preterm infants born between 24 and 29 weeks' gestation. KEY POINTS: · Exposure to magnesium sulfate significantly increased from 2009 to 2018 for NICU admitted infants.. · Concurrently, the use of other tocolytics decreased significantly.. · The use of antenatal steroids has been rising over time..

Association between anti-seizure medication and outcomes in infants.

OBJECTIVE: To compare treatment failure between: (1) infants treated with phenobarbital versus levetiracetam for first-line treatment and (2) infants treated with phenytoin versus levetiracetam for second-line treatment following phenobarbital. STUDY DESIGN: This retrospective cohort study included infants with seizures receiving phenobarbital or levetiracetam as the initial anti-seizure medication. Treatment failure was defined as the need for additional anti-seizure medication within 24-72 h and compared using mixed-effect logistic regression after adjustment for confounding factors, including center. RESULTS: In this cohort of 6842 infants, the incidence of treatment failure was 31% vs. 38% in infants receiving first-line phenobarbital versus levetiracetam (adjusted OR: 0.70; 95% CI 0.58-0.84). There was no significant difference in second-line treatment failure (adjusted OR: 1.31; 95% CI 0.92-1.86). CONCLUSIONS: First-line treatment of neonatal seizures with phenobarbital is associated with a lower rate of treatment failure than levetiracetam. There was no significant difference in second-line treatment failure.

Low Rate of Spontaneous Closure in Premature Infants Discharged with a Patent Ductus Arteriosus: A Multicenter Prospective Study.

OBJECTIVES: To assess the rate of spontaneous closure and the incidence of adverse events in infants discharged home with a patent ductus arteriosus. STUDY DESIGN: In a prospective multicenter study, we enrolled 201 premature infants (gestational age of 23-32 weeks at birth) discharged home with a persistently patent ductus arteriosus (PDA) and followed their PDA status at 6-month intervals through 18 months of age. The primary study outcome was the rate and timing of spontaneous ductal closure. Secondary outcomes included rate of assisted closure and the incidence of serious adverse events. RESULTS: Spontaneous ductal closure occurred in 95 infants (47%) at 12 months and 117 infants (58%) by 18 months. Seventeen infants (8.4%) received assisted closure with surgical ligation or device assisted occlusion. Three infants died (1.5%). Although infants with spontaneous closure had a higher mean birth weight and gestational age compared with infants with a persistent PDA or assisted closure, we did not identify other factors predictive of spontaneous closure. CONCLUSIONS: Spontaneous closure of the PDA occurred in slightly less than one-half of premature infants discharged with a patent ductus by 1 year, lower than prior published reports. The high rate of assisted closure and/or adverse events in this population warrants close surveillance following discharge. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02750228.

Factors Associated with Outpatient Therapy Utilization in Extremely Preterm Infants.

OBJECTIVE: Factors influencing utilization of outpatient interventional therapies for extremely low gestational age newborns (ELGANs) after discharge remain poorly characterized, despite a significant risk of neurodevelopmental impairment. We sought to assess the effects of maternal, infant, and environmental characteristics on outpatient therapy utilization in the first 2 years after discharge using data from the Preterm Erythropoietin Neuroprotection (PENUT) Trial. STUDY DESIGN: This is a secondary analysis of 818, 24 to 27 weeks gestation infants enrolled in the PENUT trial who survived through discharge and completed at least one follow-up call or in-person visit between 4 and 24 months of age. Utilization of a state early intervention (EI) program, physical therapy (PT), occupational therapy (OT), and speech therapy (ST) was recorded. Odds ratios and cumulative frequency curves for resource utilization were calculated for patient characteristics adjusting for gestational age, treatment group, and birth weight. RESULTS: EI was not accessed by 37% of infants, and 18% did not use any service (PT/OT/ST/EI). Infants diagnosed with severe morbidities (intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis), discharged with home oxygen, or with gastrostomy placement experienced increased utilization of PT, OT, and ST compared with peers. However, substantial variation in service utilization occurred by the state of enrollment and selected maternal characteristics. CONCLUSIONS: ELGANs with severe medical comorbidities are more likely to utilize services after discharge. Therapy utilization may be impacted by maternal characteristics and state of enrollment. Outpatient therapy services remain significantly underutilized in this high-risk cohort. Further research is required to characterize and optimize the utilization of therapy services following NICU discharge of ELGANs. KEY POINTS: · Outpatient therapy is underutilized in ELGANs.. · Medical comorbidities may impact therapy use.. · Maternal characteristics may impact therapy use.. · State of enrollment may impact therapy use..

Covariation of changing patent ductus arteriosus management and preterm infant outcomes in Pediatrix neonatal intensive care units.

OBJECTIVE: To test the hypothesis that NICU-specific preterm infant outcomes co-vary with changes in local patent ductus arteriosus (PDA) management. STUDY DESIGN: This retrospective multicenter study examined NICU-specific aggregated data for infants born 400-1499 g (VLBW) in the Pediatrix Clinical Data Warehouse. For each NICU and each year 2006-2016 we calculated proportion of infants receiving cyclooxygenase inhibitor (COXI) and/or PDA ligation and determined NICU-specific changes in these therapies between consecutive years. We examined relationships between NICU-specific changes in COXI/ligation and concurrent changes in local adjusted in-hospital outcomes. RESULTS: In 5678 observations of change at 259 NICUs summarizing 78,105 infants, between-year decreases in NICU-specific proportion treated with COXI/ligation were associated with concurrent increases in local mortality and decreases in BPD among infants 400-749 g, and with decreased pulmonary hemorrhage in larger infants. CONCLUSIONS: NICU-specific adjusted mortality, BPD, and pulmonary hemorrhage rates co-vary with changes in local COXI/ligation rates in some VLBW infant subgroups.

Hydrops fetalis-trends in associated diagnoses and mortality from 1997-2018.

OBJECTIVES: To describe and evaluate trends in the etiology and mortality risk in neonates admitted for neonatal intensive care with hydrops fetalis. STUDY DESIGN: A retrospective review of de-identified patient data in the Pediatrix Clinical Data Warehouse from 1997 to 2018. RESULTS: We identified 2144 infants diagnosed with hydrops fetalis. The most common diagnoses were congenital heart disease (n = 325, 15.2%), genetic diagnoses (n = 269, 12.5%) and cardiac arrhythmia (n = 176, 8.2%). Of 2144 neonates, 988 (46%) survived to hospital discharge and 775 (36%) died prior to discharge. Mortality rate was highly variable across diagnoses, ranging from 90% in infants with congenital diaphragmatic hernia to 0% in infants with atrial flutter. Over the study period, more infants were diagnosed with trisomies and fewer with twin-to-twin transfusion. Mortality decreased by 5% from 1997-2007 to 2008-2018. CONCLUSIONS: The risk of death among neonates with hydrops fetalis is highly dependent on the underlying cause, with increasing risk of mortality at lower gestational ages.

The use of supplemental hydrocortisone in the management of persistent pulmonary hypertension of the newborn.

OBJECTIVE: Characterize association between hydrocortisone receipt and hospital outcomes of infants with persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: Cohort study of infants ≥34 weeks with PPHN who received inhaled nitric oxide at <7 days of age (2010-2016). We generated propensity scores, and performed inverse probability-weighted regression to estimate hydrocortisone effect on outcomes: death, chronic lung disease (CLD), oxygen at discharge. RESULTS: Of 2743 infants, 30% received hydrocortisone, which was associated with exposure to mechanical ventilation, sedatives, paralytics, or vasopressors (p < 0.001). There was no difference in death, CLD, or oxygen at discharge. In infants with meconium aspiration syndrome, hydrocortisone was associated with decreased oxygen at discharge (odds ratio 0.56; 95% confidence interval 0.21, 0.91). CONCLUSIONS: There was no association between hydrocortisone receipt and death, CLD, or oxygen at discharge in our cohort. Prospective studies are needed to evaluate the effectiveness of hydrocortisone in infants with PPHN.

Utilization of Erythropoietin within the United States Neonatal Intensive Care Units from 2008 to 2017.

OBJECTIVE: Little data are available regarding erythropoietin (Epo) utilization patterns within neonatal intensive care units (NICUs). We sought to describe the trends in Epo utilization across a large cohort of U.S. NICUs. STUDY DESIGN: This is a retrospective cohort study of infants discharged from 2008 to 2017 using the Pediatrix Clinical Data Warehouse. RESULTS: We identified 704,159 eligible infants from 358 sites, of whom 9,749 (1.4%) had Epo exposure. For extremely low gestational age newborns (ELGANs), Epo exposure ranged from 7.6 to 13.5%. We found significant site variability in Epo utilization in ELGANs. Among the 299 NICUs caring for ELGANs during the study period, 184 (61.5%) never used Epo for this population, whereas 21 (7%) utilized Epo in 50% or more of eligible infants. Epo was initiated at a median of 25 days in ELGANs. For infants with hypoxic-ischemic encephalopathy (HIE), Epo exposure remained ≤1% through 2014 then increased fourfold to 3.4% by 2017. The median day of Epo initiation was the day of birth for infants diagnosed with HIE. CONCLUSION: Epo is utilized in ELGANs more commonly than for other NICU populations. Utilization patterns appear to indicate the treatment of established anemia for ELGANs and more recently for neuroprotection in patients diagnosed with HIE.

Longitudinal Survey of COVID-19 Burden and Related Policies in U.S. Neonatal Intensive Care Units.

OBJECTIVE: This study aimed to determine the prevalence of confirmed novel coronavirus disease 2019 (COVID-19) disease or infants under investigation among a cohort of U.S. neonatal intensive care units (NICUs). Secondarily, to evaluate hospital policies regarding maternal COVID-19 screening and related to those infants born to mothers under investigation or confirmed to have COVID-19. STUDY DESIGN: Serial cross-sectional surveys of MEDNAX-affiliated NICUs from March 26 to April 3, April 8 to April 19, May 4 to May 22, and July 13 to August 2, 2020. The surveys included questions regarding COVID-19 patient burden and policies regarding infant separation, feeding practices, and universal maternal screening. RESULTS: Among 386 MEDNAX-affiliated NICUs, responses were received from 153 (42%), 160 (44%), 165 (45%), 148 (38%) across four rounds representing an active patient census of 3,465, 3,486, 3,452, and 3,442 NICU admitted patients on the day of survey completion. Confirmed COVID-19 disease in NICU admitted infants was rare, with the prevalence rising from 0.03 (1 patient) to 0.44% (15 patients) across the four survey rounds, while the prevalence of patients under investigation increased from 0.8 to 2.6%. Hospitals isolating infants from COVID-19-positive mothers fell from 46 to 20% between the second and fourth surveys, while centers permitting direct maternal breastfeeding increased 17 to 47% over the same period. Centers reporting universal severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) screening for all expectant mothers increased from 52 to 69%. CONCLUSION: Among a large cohort of NICU infants, the prevalence of infants under investigation or with confirmed neonatal COVID-19 disease was low. Policies regarding universal maternal screening for SARS-CoV-2, infant isolation from positive mothers, and direct maternal breastfeeding for infants born to positive mothers are rapidly evolving. As universal maternal screening for SARS-CoV-2 becomes more common, the impact of these policies requires further investigation. KEY POINTS: · In this cohort, neonatal COVID-19 is rare.. · Policies regarding isolation and breastfeeding for infants are rapidly evolving.. · Most hospitals are now providing universal screening for expectant mothers for SARS-CoV-2..

The Denominator Matters! Lessons from Large Database Research in Neonatology.

Observational studies from large datasets are becoming more common in neonatology. In this review, we highlight the importance of the denominator in study design and interpretation including examples of bias from source data, weight-based categories, age-related bias, and diagnosis-based denominators.