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.

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.

Transpyloric Feeding is Associated With Improved Oxygenation Compared With Gastric Feeding Among Nonintubated Extremely Low Birth Weight Infants.

OBJECTIVE: To study the impact of transpyloric (TP) feed initiation on short-term oxygenation and manual oxygen blender titration among extremely low birth weight infants. STUDY DESIGN: This retrospective study evaluated several measures of oxygenation among extremely low birth weight infants receiving positive pressure respiratory support for 96 hours before and after TP tube placement in a single neonatal intensive care unit during the years 2017- 2020. The measures included the achieved oxygen saturation (SpO2), the baseline fraction of inspired oxygen (FiO2), the SpO2/FiO2 ratio, the number and severity of hypoxemic episodes and the frequency of manual oxygen titrations (titration index) and were analyzed using an interrupted time series regression approach. RESULTS: A total of 56 infants were evaluated. No significant differences were observed in any oxygenation measures during TP vs gastric feeding among 14 intubated infants. However, among 42 nonintubated patients, significant improvements were observed in the median SpO2/FiO2 ratios (P = .001), median titration index (P = .05), median number of hypoxemic episodes (P = .02), and median severity of hypoxemic episodes (P = .008) after TP tube placement. CONCLUSIONS: The transition from gastric to TP tube feeding was temporally associated with acute improvement in oxygenation for nonintubated infants, but not for intubated infants.

Incidence of group B streptococcus early-onset sepsis in term neonates with second-line prophylaxis maternal intrapartum antibiotics: a multicenter retrospective study.

BACKGROUND: The difference in the incidence of early-onset sepsis caused by group B streptococcus among term neonates whose mothers received first-line vs second-line intrapartum prophylaxis is poorly described. OBJECTIVE: This study aimed to compare the incidence of group B streptococcus early-onset sepsis among term neonates born to mothers who receive first-line, second-line, or no intrapartum antibiotics and to describe the short-term and survival outcomes of neonates who developed group B streptococcus early-onset sepsis stratified by maternal antepartum prophylaxis. STUDY DESIGN: This was a retrospective review of electronic medical records. We queried the Pediatrix Medical Group Clinical Data Warehouse to evaluate the outcomes of term neonates born to group B streptococcus positive mothers between 2003 and 2020 and compared the incidence and outcomes of neonates with group B streptococcus early-onset sepsis whose mothers received first-line vs second-line or no intrapartum prophylaxis. RESULTS: Among the 496,180 neonates, 104,196 (21%) were born to mothers who were group B streptococcus positive. Of 97,983 mothers who were group B streptococcus positive with adequate prenatal antibiotic documentation, 49,234 (50%), 12,679 (13%), and 36,070 (37%) received first-line, second-line, and no intrapartum prophylaxis, respectively. The incidence of group B streptococcus early-onset sepsis among all neonates with maternal group B streptococcus carriage was 0.22% (231/104,196). Neonates whose mothers received second-line intrapartum antibiotics and no antibiotics had a higher risk for group B streptococcus early-onset sepsis infection than those whose mothers received first-line intrapartum antibiotics (adjusted odds ratio, 4.12; 95% confidence interval, 2.66-6.38 and adjusted odds ratio, 3.80; 95% confidence interval, 2.66-5.44, respectively). There was no statistically significant difference in the risk for group B streptococcus early-onset sepsis among neonates born to mothers who received second-line vs no antibiotics (adjusted odds ratio, 0.92; 95% confidence interval, 0.64-1.33). CONCLUSION: Neonates exposed to second-line maternal group B streptococcus prophylaxis had an increased risk for group B streptococcus early-onset sepsis when compared with those exposed to first-line maternal group B streptococcus prophylaxis. There was no statistically significant difference in group B streptococcus early-onset sepsis incidence between second-line antibiotic prophylaxis and no antibiotics in mothers with group B streptococcus carriage.

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.

Defining Body Mass Index Using Weight and Length for Gestational Age in the Growth Assessment of Preterm Infants at Birth.

OBJECTIVE: The objectives of this study were to describe (1) body mass indexes (BMIs) using weight and length for gestational age (GA) classifications, and (2) the additional information BMI, as a measure of body proportionality, provides for preterm infant growth assessment and care plans at birth. STUDY DESIGN: Birth weight, length, and BMI of 188,646 preterm infants (24-36 weeks gestation) admitted to U.S. neonatal intensive care units (Pediatrix Clinical Data Warehouse, 2013-2018) were classified (Olsen curves) as small, appropriate, or large for GA (SGA < 10th, AGA 10-90th, LGA > 90th percentile for GA, respectively). The distribution for the 27 weight-length-BMI combinations was described. RESULTS: At birth, most infants were appropriate for weight (80.0%), length (82.2%), head circumference (82.9%), and BMI (79.9%) for GA. Birth weight for GA identified approximately 20% of infants as SGA or LGA. Infants born SGA (or LGA) for both weight and length ("proportionate" in size) were usually appropriate for BMI (59.0% and 75.6%). BMI distinguished disproportionate weight for length in infants with SGA or LGA weight at birth (58.3%, 49.9%). BMI also identified 11.4% of AGA weight infants as small or large for BMI ("disproportionate" in size) at birth; only using weight for GA missed these underweight/overweight for length infants. CONCLUSION: The unique, additional information provided by birth BMI further informs individualized preterm infant growth assessment by providing an assessment of an infant's body proportionality (weight relative to its length) in addition to the routine assessment of weight, length, and head circumference for GA and may better inform care plans and impact outcomes. KEY POINTS: · Most preterm infants were born AGA for all growth measures.. · AGA weight infants may be under- or overweight for length.. · BMI distinguished body disproportionality in SGA/LGA infants.. · Recommend BMI assessed along with weight, length and head.. · Further research on BMI in preterm infants is needed..

Urinary Tract Infection Epidemiology in NICUs in the United States.

OBJECTIVE: Our objective was to characterize the incidence, associated clinical factors, timing of infection, microbiology, and incidence of concordant blood culture of urinary tract infections (UTIs) in very low birth weight (VLBW <1,500g) infants. STUDY DESIGN: Multicenter observational cohort study of VLBW infants with gestational age (GA) ≤32 weeks, still hospitalized on postnatal day 7, and discharged 2010 to 2018 from Pediatrix Medical Group neonatal intensive care units. Demographic and clinical characteristics of infants with and without UTI were compared. Multivariable logistic regression evaluated adjusted odds of UTI diagnosis. RESULTS: Of 86,492 included infants, 5,988 (7%) had a UTI. The most common pathogen was Enterococcus spp. (20%), followed by Escherichia coli (19%) and Klebsiella spp. (18%). Candida spp. (6%) was the most common nonbacterial pathogen. Concordant-positive blood culture was present in 8% of infants with UTI diagnoses. UTI was associated with lower GA, male sex, vaginal delivery, prenatal steroid exposure, and longer duration of hospitalization. CONCLUSION: UTI is a common cause of infection in VLBW infants, especially among the smallest, most premature, male infants, and those with a longer duration of hospitalization. Neonatal clinicians should consider obtaining urine culture in the setting of late-onset sepsis evaluations in VLBW infants. KEY POINTS: · UTI is a common cause of LOS in VLBW infants.. · The most common pathogens are Enterococcus spp. and E. coli.. · UTI risk varies among different VLBW infant populations.. · Next steps should include evaluation of preventative measures..

Oxygenation Factors Associated with Retinopathy of Prematurity in Infants of Extremely Low Birth Weight.

OBJECTIVE: To study characteristics of oxygenation during the first 2 postnatal months and correlation with the occurrence and severity of retinopathy of prematurity (ROP) among infants of extremely low birth weight. STUDY DESIGN: This retrospective study analyzed the incidence and severity of hyperoxemia and hypoxemia while on respiratory support with or without supplemental oxygen among infants of extremely low birth weight (birth weight <1000 g) admitted to the neonatal intensive care unit during 2016-2020. The findings were correlated with the occurrence and severity of ROP after adjusting for baseline covariates. RESULTS: After adjusting for differences in baseline demographic and clinical features, the group with severe ROP was exposed to greater fraction of inspired oxygen (FiO2) (P = .001) and experienced more frequent FiO2 titration adjustments (P = .001) compared with the group without ROP. Ambient air hyperoxemia occurred more frequently in the group without ROP (P = .003), and iatrogenic hyperoxemia occurred more frequently in the group with severe ROP (P = .046). There were no differences in the severity of ambient and iatrogenic hyperoxemia in the study population. The group with severe ROP demonstrated more hypoxemic episodes (P = .01) and longer time spent in the severe hypoxemic range (P = .005) compared with the group without ROP. CONCLUSIONS: Severe ROP is associated with greater FiO2 exposure, increased iatrogenic hyperoxemia, decreased ambient air hyperoxemia, and increased hypoxemia in infants of extremely low birth weight despite a greater frequency of FiO2 titration. This study illustrates the need for automated closed loop FiO2 delivery systems to further optimize oxygen saturation targeting in this high-risk population.

Effect of an Alternate Definition for a Clinically Significant Cardiopulmonary Event on Discharge.

OBJECTIVE: To evaluate a precise definition of a clinically significant cardiopulmonary event (CSCPE) on the hospital length of stay (LOS), medical provider satisfaction, and discharge complications. STUDY DESIGN: This is a single-center, observational study that included 139 infants before and 134 infants after the new definition was implemented in December 2017. Retrospective data collected November 2015 to November 2017 (before) was compared with prospective data from June 2018 to July 2020 (after). Outcome measures were the proportion of infants waiting to outgrow CSCPE, LOS, provider satisfaction with the definition, and discharge complications. Multivariate regression modeling was used to evaluate variables on LOS and postmenstrual age at discharge. RESULTS: The proportion waiting to outgrow CSCPE decreased from 68.4% to 31.7% (P < .0001). The LOS was similar between groups; however, multivariate analysis correcting for gestational age and reason awaiting discharge estimated 3.5 days (95% CI, 1.4-5.8 days; P = .0017) decrease in LOS, and 0.92 weeks (95% CI, 0.29-1.56; P = .005) younger postmenstrual age at discharge in the after group. There was no difference in the number of readmissions or emergency room visits for apnea or deaths. Provider satisfaction improved with discharge planning after the implementation of the definition. CONCLUSIONS: We developed an alternate definition for a CSCPE that decreased the proportion of infants waiting to outgrow a CSCPE but not LOS. There was no difference in the number of readmissions or emergency room visits for apnea or deaths, and provider satisfaction in management and discharge planning was greater. CLINICAL TRIAL REGISTRATION INFORMATION: This study was registered under the ClinicalTrial.gov Protocol ID: 5892S-15. "The effect of standardizing the definition and approach to a clinically significant cardiopulmonary event in infants less than 30 weeks on length of stay." Recorded Nov 2017.

Medication Use in the Neonatal Intensive Care Unit and Changes from 2010 to 2018.

OBJECTIVE: To provide up-to-date medication prescribing patterns in US neonatal intensive care units (NICUs) and to examine trends in prescribing patterns over time. STUDY DESIGN: We performed a cohort study of 799 016 infants treated in NICUs managed by the Pediatrix Medical Group from 2010 to 2018. We used 3 different methods to report counts of medication: exposure, courses, and days of use. We defined the change in frequency of medication administration by absolute change and relative change. We examined the Food and Drug Administration (FDA) package insert for each medication to determine whether a medication was labeled for use in infants and used PubMed to search for pharmacokinetics (PK) studies. RESULTS: The most frequently prescribed medications included ampicillin, gentamicin, caffeine citrate, poractant alfa, morphine, vancomycin, furosemide, fentanyl, midazolam, and acetaminophen. Of the top 50 medications used in infants with extremely low birth weight, only 20 (40%) are FDA-labeled for use in infants; of the 30 that are not labeled for use in infants, 13 (43%) had at least 2 published PK studies. The medications with the greatest relative increase in use from 2010 to 2018 included dexmedetomidine, clonidine, rocuronium, levetiracetam, atropine, and diazoxide. The medications with the greatest relative decrease in use included tromethamine acetate, pancuronium, chloral hydrate, imipenem + cilastatin, and amikacin. CONCLUSION: Trends of medication use in the NICU change substantially over time. It is imperative to identify changes in medication use in the NICU to better inform further prospective studies.

Mortality Risk Factors among Infants Receiving Dialysis in the Neonatal Intensive Care Unit.

OBJECTIVES: To identify risk factors associated with mortality for infants receiving dialysis in the neonatal intensive care unit (NICU). STUDY DESIGN: In this retrospective cohort study, we extracted data from the Pediatrix Clinical Data Warehouse on all infants who received dialysis in the NICU from 1999 to 2018. Using a Cox proportional hazards model with robust SEs we estimated the mortality hazard ratios associated with demographics, birth details, medical complications, and treatment exposures. RESULTS: We identified 273 infants who received dialysis. Median gestational age at birth was 35 weeks (interquartile values 33-37), median birth weight was 2570 g (2000-3084), 8% were small for gestational age, 41% white, and 72% male. Over one-half of the infants (59%) had a kidney anomaly; 71 (26%) infants died before NICU hospital discharge. Factors associated with increased risk of dying after dialysis initiation included lack of kidney anomalies, Black race, gestational age of <32 weeks, necrotizing enterocolitis, dialysis within 7 days of life, and receipt of paralytics or vasopressors (all P < .05). CONCLUSION: In this cohort of infants who received dialysis in the NICU over 2 decades, more than 70% of infants survived. The probability of death was greater among infants without a history of a kidney anomaly and those with risk factors consistent with greater severity of illness at dialysis initiation.

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.

Long QT and Hearing Loss in High-Risk Infants Prospective Study Registry.

The objective of this study is to determine the prevalence of an abnormal electrocardiogram showing a prolonged QTc greater than 450 ms in infants with unilateral or bilateral sensorineural hearing loss. We conducted a prospective study of healthy term infants (≥37 weeks gestational age) who failed their newborn auditory brainstem response hearing screen, were seen by an audiologist and diagnosed as having sensorineural hearing loss during follow-up to 1 year of age. In infants with a diagnosis of hearing loss, we collected a detailed family history and performed an ECG between 2 and 6 months of age. We obtained follow-up for 1 year by calling the parent requesting the hearing and cardiac status of their child. Two of the 40 infants with sensorineural hearing loss (5%) had a QTc greater than 450 ms. Both had mild bilateral hearing loss and genetic testing did not identify a known mutation for long QT syndrome. The remaining 38 infants had QTc intervals of ≤ 450 ms. One patient diagnosed with bilateral severe sensorineural hearing loss had a normal ECG (QTc = 417 ms). Several months after the ECG was performed, the infant's mother contacted the study cardiologist after she learned that the infant's maternal grandmother was diagnosed with a cardiomyopathy and arrhythmias. Genetic testing was recommended even though the child was asymptomatic and was positive for a pathogenic mutation in the KCNQ1 gene. We speculate that molecular genetic testing in infants with hearing loss may become the standard of care rather than targeted electrocardiograms.Clinical Trial Registration NCT02082431 https://www.clinicaltrials.gov/ct2/show/NCT02692521?cond=NCT02692521&rank=1 .

Necrotizing Enterocolitis in Very Low Birth Weight Neonates: A Natural History Study.

OBJECTIVE: We characterize the most recent natural history of necrotizing enterocolitis (NEC), as this is an essential first step in guiding the prevention and treatment of this disease in the present day. STUDY DESIGN: We performed a retrospective cohort study of neonates who were born at 23 to 29 weeks' gestation and birth weight <1,500 g who received care from the Pediatrix Medical Group between 2004 and 2019. We assessed the incidence of medical and surgical NEC and the patterns of initial antibiotic treatment to develop a contemporary cohort for further analysis. Among patients discharged between 2015 and 2019, we characterized the stage-specific risk factors for patients diagnosed with medical or surgical NEC, as well as patterns of disease onset, progression, biomarkers, and outcomes. We used the same approach to characterize patients diagnosed with suspected NEC. RESULTS: Among 34,032 patients in the contemporary cohort, 1,150 (3.4%) were diagnosed with medical NEC and 543 (1.6%) were diagnosed with surgical NEC. The temporal pattern of disease onset was different for medical and surgical NEC, with gestational age- and birth weight-specific risk disparities emerging earlier in surgical NEC. Thirty-day mortality was much greater among surgical NEC patients (medical NEC 16.4% vs. surgical NEC 43.0%), as were rates of various in-hospital and long-term outcomes. Suspected NEC was diagnosed in 1,256 (3.7%) patients, among whom risk factors and disease onset, progression, and outcomes closely resembled those of medical NEC. CONCLUSION: Analyzing data from a contemporary cohort enabled us to characterize the current, stage-specific natural history of NEC, including novel insights into suspected NEC. Future studies could leverage this cohort to characterize how specific patient characteristics, care processes, or biomarkers may influence or predict disease outcomes. KEY POINTS: · The incidence of NEC has reached a stable baseline in recent years.. · Risk factors for NEC vary in a stage-specific manner.. · The stage-specific onset and progression of NEC differ by gestational age and birth weight..

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..

Indomethacin Prophylaxis in Preterm Infants: Changes over Time.

OBJECTIVE: Our objective was to examine changes in the use of indomethacin prophylaxis in the neonatal intensive care unit (NICU) between 2008 and 2018. STUDY DESIGN: The design of the study included cohort of 19,715 infants born between 220/7 and 266/7 weeks' gestation from 213 NICUs. A nonparametric trend test evaluated indomethacin prophylaxis and the percentage of sites using any prophylaxis over time. We evaluated the prevalence of indomethacin prophylaxis by the center and the correlation between indomethacin prophylaxis and severe intraventricular hemorrhage prevalence among 12 centers with the largest relative change in indomethacin prophylaxis prevalence. RESULTS: In total, 16% of infants received indomethacin prophylaxis. The use of indomethacin prophylaxis did not significantly decrease between 2008 and 2018 but it significantly decreased between 2014 and 2018 (p = 0.046). Among 74 centers with ≥10 infants included, 20% increased the use of indomethacin prophylaxis, while 57% decreased the use over the study period. Of the 12 centers with the largest relative change in indomethacin prophylaxis prevalence, 50% showed an inverse correlation between indomethacin prophylaxis prevalence and severe intraventricular hemorrhage, while 50% showed a positive correlation. CONCLUSION: Receipt of indomethacin prophylaxis remained similar until 2014, decreased from 2014 to 2018, and varied by the center.Key Points · The receipt of indomethacin prophylaxis decreased over time.. · Center change in the use of indomethacin prophylaxis does not correlate with the center prevalence of IVH.. · Variability in the use of indomethacin prophylaxis across centers persists..

Indomethacin Prophylaxis in Preterm Infants: Changes over Time.

OBJECTIVE: Our objective was to examine changes in the use of indomethacin prophylaxis in the neonatal intensive care unit (NICU) between 2008 and 2018. STUDY DESIGN: The design of the study included cohort of 19,715 infants born between 220/7 and 266/7 weeks' gestation from 213 NICUs. A nonparametric trend test evaluated indomethacin prophylaxis and the percentage of sites using any prophylaxis over time. We evaluated the prevalence of indomethacin prophylaxis by the center and the correlation between indomethacin prophylaxis and severe intraventricular hemorrhage prevalence among 12 centers with the largest relative change in indomethacin prophylaxis prevalence. RESULTS: In total, 16% of infants received indomethacin prophylaxis. The use of indomethacin prophylaxis did not significantly decrease between 2008 and 2018 but it significantly decreased between 2014 and 2018 (p = 0.046). Among 74 centers with ≥10 infants included, 20% increased the use of indomethacin prophylaxis, while 57% decreased the use over the study period. Of the 12 centers with the largest relative change in indomethacin prophylaxis prevalence, 50% showed an inverse correlation between indomethacin prophylaxis prevalence and severe intraventricular hemorrhage, while 50% showed a positive correlation. CONCLUSION: Receipt of indomethacin prophylaxis remained similar until 2014, decreased from 2014 to 2018, and varied by the center.Key Points · The receipt of indomethacin prophylaxis decreased over time.. · Center change in the use of indomethacin prophylaxis does not correlate with the center prevalence of IVH.. · Variability in the use of indomethacin prophylaxis across centers persists..

Effect of a Novel Oxygen Saturation Targeting Strategy on Mortality, Retinopathy of Prematurity, and Bronchopulmonary Dysplasia in Neonates Born Extremely Preterm.

OBJECTIVE: To study the impact of an oxygen management strategy incorporating oxygen saturation (SpO2) targeting and fraction of inspired oxygen monitoring on the incidence of retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and mortality. STUDY DESIGN: This retrospective cohort study analyzed the incidence of any ROP, severe ROP, ROP requiring treatment (surgery and/or bevacizumab), BPD, and mortality among 23-28 weeks of gestational age infants admitted to the neonatal intensive care unit in 3 epochs: Epoch 1 (2007-2010) before implementation of SpO2 histograms; Epoch 2 (2012-2014), with development of a software tool capable of generating automatic bedside SpO2 histograms; and Epoch 3 (2016-2019), with further software enhancements, incorporating simultaneous SpO2 and fraction of inspired oxygen measurements. RESULTS: During Epochs 1, 2, and 3, there were 601, 381, and 550 eligible infants, respectively, for a total of 1532 eligible infants. Mortality, any ROP, severe ROP, ROP needing treatment, and BPD all showed significant downward trends across the 3 epochs. The aOR of mortality was significantly lower in Epoch 3 compared with Epoch 1 (aOR 0.48). The aORs of any ROP and of BPD were significantly lower in Epochs 2 and 3 compared with Epoch 1 (respectively, ROP aORs 0.53 and 0.38; BPD aOR 0.43 and 0.43). The aOR of ROP needing treatment was significantly lower in Epoch 3 compared with Epoch 1 (aOR 0.43). CONCLUSIONS: We have demonstrated improvement in rates of mortality, any ROP, ROP requiring treatment, and BPD after implementation of a novel oxygen management strategy.

Association between Hyperbilirubinemia and Hearing Screen Failure in the Neonatal Intensive Care Unit in Infants Born Preterm.

OBJECTIVE: To characterize the association between hyperbilirubinemia and a failed newborn hearing screen in infants born at 22-32 weeks of gestation. STUDY DESIGN: We included infants with gestational ages of 22-32 weeks who were discharged from neonatal intensive care units in the US from 2002 to 2017 with available newborn hearing screen results obtained after 34 weeks postmenstrual age. We excluded infants with severe birth asphyxia or craniofacial abnormalities. We identified 95 672 infants from 313 neonatal intensive care units. We used multivariable logistic regression to examine the association between maximum total bilirubin at <21 days postnatal age with failed hearing screen, adjusting for important demographic and clinical risk factors. RESULTS: The median gestational age and birth weight were 30 weeks (IQR, 28-32 weeks) and 1330 g (IQR, 1010-1630 g), respectively. The median maximum total bilirubin was 8.3 mg/dL (IQR, 6.7-10.0 mg/dL), and 5275 infants (6%) failed their newborn hearing screen. On adjusted analysis, each 1 mg/dL increase in maximum total bilirubin was associated with a small, but significant, increase in odds of a failed hearing screen (OR, 1.03; 95% CI, 1.02-1.04). CONCLUSIONS: An increased maximum total bilirubin level was independently associated with hearing screen failure. Further prospective studies are needed to understand whether this increased risk of hearing screen failure translates to increased risk of hearing loss.

Association between Nephrotoxic Drug Combinations and Acute Kidney Injury in the Neonatal Intensive Care Unit.

OBJECTIVE: To determine the incidence of acute kidney injury (AKI) in infants exposed to nephrotoxic drug combinations admitted to 268 neonatal intensive care units managed by the Pediatrix Medical Group. STUDY DESIGN: We included infants born at 22-36 weeks gestational age, ≤120 days postnatal age, exposed to nephrotoxic drug combinations, with serum creatinine measurements available, and discharged between 2007 and 2016. To identify risk factors associated with a serum creatinine definition of AKI based on the Kidney Disease: Improving Global Outcomes criteria, we performed multivariable logistic and Cox regression adjusting for gestational age, sex, birth weight, postnatal age, race/ethnicity, sepsis, respiratory distress syndrome, baseline serum creatinine, and duration of combination drug exposure. The adjusted odds of AKI were determined relative to gentamicin + indomethacin for the following nephrotoxic drug combinations: chlorothiazide + ibuprofen; chlorothiazide + indomethacin; furosemide + gentamicin; furosemide + ibuprofen; furosemide + tobramycin; ibuprofen + spironolactone; and vancomycin + piperacillin-tazobactam. RESULTS: Among 8286 included infants, 1384 (17%) experienced AKI. On multivariable analysis, sepsis, lower baseline creatinine, and duration of combination therapy were associated with increased odds of AKI. Furosemide + tobramycin and vancomycin + piperacillin-tazobactam were associated with a decreased risk of AKI relative to gentamicin + indomethacin in both the multivariable and Cox regression models. CONCLUSIONS: In this cohort, infants receiving longer durations of nephrotoxic combination therapy had an increased odds of developing AKI.