Search

Infants frequently receive metronidazole at variable doses and duration for surgical site infection prophylaxis and treatment of intra-abdominal infections. Seizures are a rare (but potentially devastating) side effect of metronidazole, yet the prevalence of seizures in infants, as well as the relationship with metronidazole dose and exposure, are unknown.We examined the Pediatrix Clinical Data Warehouse for infants in neonatal intensive care units from 1997 to 2018 who received at least 1 dose of metronidazole during their first 120 days of life. We used an existing population pharmacokinetic model to simulate exposure parameters, estimating multivariable associations between metronidazole dosing and exposure parameters, and the occurrence of seizure.There were 19,367 intravenous doses of metronidazole given to 1546 infants, and 31 experienced a seizure. Infants with a seizure had a longer median (interquartile values) duration of metronidazole exposure than those without (11 days [6, 15] vs. 7 [4, 11], P = 0.01). Each added day of metronidazole (OR = 1.06, 95% CI: 1.02-1.10), and each standard deviation increase in cumulative area under the plasma concentration-time curve (OR = 1.27, 95% CI: 1.11-1.45) were associated with increased odds of seizure. Higher simulated maximum plasma concentration was associated with lower odds of seizure (OR = 0.88, 95% CI: 0.81-0.96).Longer metronidazole exposure and higher cumulative exposure could be associated with increased odds of infant seizures. Using a large observational dataset allowed us to identify a rare adverse event, but prospective studies are needed to validate this finding and further characterize metronidazole dose- and exposure-safety relationships.

To assess the validity and utility of the bronchopulmonary dysplasia (BPD) outcome estimator developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).This retrospective study correlated the BPD and mortality outcomes of 23-28-week prematurely born infants with those predicted by the 2022 NICHD BPD outcome estimator. In addition, evidence-based recommended postnatal steroid administration using risk predictions by the BPD estimator was compared with actual postnatal steroid use.Among the 223 infants enrolled in the study, 139 did not develop BPD, 64 babies developed BPD, and 20 babies died. BPD estimator predicted outcomes correctly in 74% of cases who did not develop BPD, 48% of cases with Grade 1 BPD, and 35% of deaths. Only 6% of cases with Grade 2 BPD and none of the babies with Grade 3 BPD were identified correctly. The predicted and actual steroid use for BPD prevention/treatment were 37.2% and 29.6%, respectively (p = 0.18). The BPD estimator had a sensitivity of 72.7%, specificity of 77.7%, positive predictive value of 57.8%, and negative predictive value of 87.1% to predict actual postnatal steroid use.In this cohort, the 2022 NICHD BPD estimator underestimated probabilities for babies who did not develop BPD, may overestimate probabilities for babies who develop BPD and had low sensitivity to predict mortality. In addition, the application of the BPD estimator may result in an overestimation of postnatal steroid use.

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.

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

OBJECTIVE Characterize the use, efficacy, and safety of poractant alfa and calfactant surfactants compared to beractant in preterm infants receiving late surfactant. STUDY DESIGN We included infants

To characterize the association between hyperbilirubinemia and a failed newborn hearing screen in infants born at 22-32 weeks of gestation.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 at21 days postnatal age with failed hearing screen, adjusting for important demographic and clinical risk factors.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).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.

OBJECTIVE: The management of early hypotension in extremely low gestational age neonates (ELGANs) varies greatly between centers. The objective of this study was to provide updated data on the use of vasoactive medications in ELGANs during the first postnatal week. STUDY DESIGN: We identified ELGANs (22-27 weeks gestational age) cared for at Pediatrix neonatal intensive care units from 2009-2018. We evaluated the frequency of exposure to vasoactive medications by gestational age, and compared use of vasoactive medications between 2 epochs (2009-2013 and 2014-2018). RESULTS: A total of 10 070/34 234 (29%) ELGANs received ≥1 vasoactive medication. Dopamine was the most frequently used vasoactive medication. The majority (83%) of treated ELGANs initiated therapy on postnatal day 0-1. Overall use of vasoactive medications was slightly lower in 2014-2018 than 2009-2013 (28% vs 31%, p

BACKGROUND Thrombosis in the neonatal population is rare, but increasing. Its incidence and management are not well understood. OBJECTIVES To investigate the incidence, associated factors, and management of thrombosis in the neonatal intensive care unit (NICU) population. PATIENTS/METHODS We performed a retrospective cohort study of infants admitted to a Pediatrix Medical Group-affiliated NICU from 1997 through 2015. We determined the prevalence of venous and arterial thrombosis, and assessed demographic characteristics and known risk factors. Categorical variables were compared with the Pearson χ2 test and continuous variables with Wilcoxon rank-sum tests. Stepwise logistic regression was used to identify associated factors. The primary outcome was incidence of thrombosis. Secondary analyses investigated correlations between clinical and demographic characteristics and thrombosis. RESULTS Among 1 158 755 infants, we identified 2367 (0.20%) diagnosed with thrombosis. In a multivariable regression analysis, prematurity, male sex, congenital heart disease, sepsis, ventilator support, vasopressor receipt, central venous catheter, invasive procedures, and receipt of erythropoietin were associated with increased risk of thrombosis, while Black race and Hispanic ethnicity were associated with reduced risk. The majority of infants diagnosed with thrombosis (73%) received no anticoagulation, but anticoagulant use in infants with thrombosis was higher than those without (27% versus 0.2%, P

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. We performed a retrospective cohort study of neonates who were born at 23 to 29 weeks' gestation and birth weight1,500 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. 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. 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.· 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..

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.

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.

Objectives: Investigate characteristics of term infants culture-evaluated for early-onset sepsis (EOS) in neonatal intensive care units (NICUs), frequencies of organisms causing EOS, and factors associated with EOS. Study design: Using a cohort design, we identified term infants evaluated for EOS with blood, cerebrospinal fluid, or urine cultures in 326 NICUs (2011–2016). Using multivariable logistic regression, we investigated the association between EOS and demographic characteristics. Results: Of 142,410 infants, 1197 (0.8%) had EOS, most commonly caused by group B Streptococcus (GBS; 40.6%). Lower EOS risk was associated with low Apgar score, Cesarean delivery, small for gestational age, prenatal antibiotic exposure, and positive or unknown maternal GBS screening result. Increased risk was associated with prolonged rupture of membranes, maternal age

Objective Determine the associations between neonatal intensive care unit (NICU) medication safety practices, laboratory-based adverse events (lab-AEs), and death. Study design We combined data from a 2016 survey of Pediatrix NICUs on use of medication safety practices with 2014-2016 infant data. We grouped NICUs based on the number of safety practices used (≤5, 6-7, and 8-10) and evaluated the association between the number of safety practices used and lab-AEs and deaths using logistic regressions. Results Of the 94 NICUs included, 17% used ≤5 medication safety practices, 51% used 6-7, and 32% used 8-10. NICUs with more safety practices did not have a difference in lab-AEs or death. Conclusion In this cohort, the use of more medication safety practices was not associated with fewer lab-AEs or decreased death.

Objectives To determine the relationship between the emergence of COVID-19 and neonatal intensive care unit (NICU) family presence as well as how NICU design affects these changes. Study design A cross-sectional survey from April 21 to 30, 2020. We queried sites regarding NICU demographics, NICU restrictions on parental presence, and changes in ancillary staff availability. Results Globally, 277 facilities responded to the survey. NICU policies preserving 24/7 parental presence decreased (83–53%, p

High doses of ampicillin are often used to achieve therapeutic drug concentrations in infants. A paradoxical antibiotic effect, often called the Eagle effect, occurs when increasing concentrations of antibiotic above a threshold results in decreased efficacy. It is unknown if infants treated with ampicillin are at risk for this paradoxical effect.We identified infants28 days of age with Escherichia coli, Enterococcus or Streptococcus agalactiae (group B streptococcus) bloodstream infections from 1997 to 2012 and previously included in an ampicillin pharmacokinetic (PK) modeling study. We compared the odds of death for ampicillin dose, estimated time above the minimum inhibitory concentration (TMIC) and PK parameters using separate logistic regression models. Adjusted logistic regression and Poisson models were used to calculate the odds of prolonged bacteremia ≥3 days and the duration of bacteremia, respectively, for dose, TMIC and multiple PK parameters.Among 1272 infants meeting inclusion criteria, odds of death 7 or 30 days after the positive blood culture were not consistent with a paradoxical effect across any of the dosing regimens or PK parameters evaluated. The odds of prolonged bacteremia was lowest at the lowest dose category and the lowest daily dose category but not associated with the area-under-the-concentration time curve from 0 to 24 hours, or the maximum or minimum concentrations at steady state. TMIC of ≥50% of the dosing interval was associated with decreased duration of bacteremia and odds of prolonged bacteremia.It is unlikely that a paradoxical antibiotic effect will have a clinical correlate when ampicillin is used for neonatal bacteremia. A TMIC ≥50% decreased both duration of bacteremia and odds of prolonged bacteremia.

To identify patterns of neuroimaging (NI), including cranial ultrasounds (CUS) and magnetic resonance imaging (MRI), among a large cohort of United States NICU infants. The retrospective cohort study of the Pediatrix Clinical Data Warehouse for infants discharged between 2008 and 2017. From the 863,863 infants during the study period, 204,197 (24%) had at least one NI study. CUS was the most common study (n = 189,190, 22%) followed by MRI (n = 37,107, 4%). From 2008 to 2017, the percentage of infants who underwent any NI decreased from 28 to 21% (p

BACKGROUND We sought to compare meropenem and fluconazole dosing in the neonatal intensive care unit with recommendations based on published pharmacokinetic (PK) studies in infants. METHODS We performed an observational cohort study of infants

Background Despite the absence of adequate safety or efficacy data, clindamycin is widely prescribed in the neonatal intensive care unit. We evaluated the association between clindamycin exposure and adverse events, as well as antibiotic effectiveness in infants. Methods This was a retrospective cohort study of infants receiving clindamycin before postnatal day 121 who were discharged from a Pediatrix Medical Group neonatal intensive care unit (1997-2015). Using a previously developed pharmacokinetic model, we performed simulations to predict clindamycin exposure based on available dosing data. We used multivariable logistic regression to evaluate the association between clindamycin exposure and safety outcomes during and after clindamycin therapy. We reported the proportion of infants with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and clearance of MRSA bacteremia. Results A total of 4089 infants received clindamycin at a median (25th-75th percentile) dose of 15 mg/kg/d (12-16). Clearance increased with older gestational age. Infants with the highest total clindamycin exposure had marginally increased odds of necrotizing enterocolitis within 7 days (adjusted odds ratio = 1.95 [1.04-3.63]), but exposure was not associated with death, sepsis, seizures, intestinal perforation or intestinal strictures. Of 25 infants who had MRSA bacteremia, 19 (76%) cleared the infection by the end of the clindamycin course. Conclusions Higher clindamycin exposure was not associated with increased odds of death or nonlaboratory adverse events. The use of pharmacokinetic models combined with available electronic health record data offers a valuable, cost-effective approach to analyzing the safety and effectiveness of drugs in infants when large-scale trials are not feasible.

OBJECTIVE: Examine the effect of off-label surfactant on mortality and morbidity in more mature and larger premature infants diagnosed with respiratory distress syndrome (RDS). STUDY DESIGN: Cohort study of premature infants born at 30–36 weeks, birth weight > 2 kg, and a diagnosis of RDS. We compared the odds of mortality and morbidity between infants who were exposed vs unexposed to surfactant. We used a treatment effects model to balance covariates between groups. RESULTS: Of 54,964 included infants, 25,278 (46%) were exposed to surfactant. The frequency of mortality and morbidities were higher in the exposed group in unadjusted analyses. Following adjustment with a doubly robust treatment effects model, we found no significant treatment effect of surfactant on mortality or morbidity. CONCLUSION: Surfactant exposure is not associated with reduced or increased mortality or morbidity in more mature premature infants with RDS.

To study the impact of transpyloric feed initiation on short-term oxygenation and manual oxygen blender titration among extremely low birth weight (ELBW) infants.This retrospective study evaluated several measures of oxygenation among ELBW infants receiving positive pressure respiratory support for 96 hours before and after TP tube placement in a single NICU during the years 2017- 2020. The measures included the achieved oxygen saturation (SpOA total of 56 infants were evaluated. No significant differences were observed in any oxygenation measures during transpyloric vs. gastric feeding among 14 intubated infants. However, among 42 non-intubated patients, significant improvements were observed in the median SpOThe transition from gastric to transpyloric tube feeding was temporally associated with acute improvement in oxygenation for non-intubated infants, but not for intubated infants.

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. 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. 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. 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.· 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..

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.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.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).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.

OBJECTIVE Obstetric studies often report neonatal morbidity as a composite score. Composite scores can simplify data analysis when multiple outcomes of interest are present and allows researchers to conduct smaller, more manageable trials. The Hassan scale is a neonatal morbidity composite scale that assigns high scores to infants with multiple morbidities and low scores to infants without or with single morbidities. The objective of this study was to validate the association between scores on the Hassan scale and neonatal intensive care unit (NICU) length of stay STUDY DESIGN: We conducted a cohort study of all infants born between 22 and 366/7 weeks' gestation and cared for within 419 neonatal units in the Pediatrix Medical Group between 1997 and 2018. Each infant was assigned a Hassan's score based on the number of neonatal morbidity events that occurred during the delivery hospitalization. The association between Hassan's scores and neonatal length of stay was evaluated using linear regression. Multivariable models were constructed to determine if the Hassan score was independently associated with neonatal length of stay. RESULTS There were 760,037 infants included. The median (interquartile range [IQR]) gestational age of delivery was 34 (31, 35) weeks and the median (IQR) birth weight at delivery was 2,000 (1,503, 2,430) g. The median length of stay for infants discharged home was 17 (10-33) days. A Hassan's score was able to be assigned to 699,206 (92%) patients. Neonatal morbidities included in the Hassan scale were more common among infants born earlier in gestation. On adjusted analysis, the Hassan scale was found to be independently associated with neonatal length of stay (p

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=NCT02692521rank=1 .

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 1999–2018. Using a Cox proportional hazards model with robust standard errors 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 (IQV) 33–37), and median birth weight was 2570 grams (2000–3084), 8% were small for gestational age, 41% white, and 72% male. Over 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

Define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates.We simulated ampicillin concentrations in newborns (birthweight 1500 g; gestational age 22-27 weeks), summarizing three 48 h regimens: high 100 mg/kg Q8hr, medium 100 mg/kg Q12hr, and standard 50 mg/kg Q12hr. Concentration data were analyzed for concentration above minimum inhibitory concentration (MIC), below neurotoxicity threshold (CAmong 34,689 newborns, all dosing regimens provided concentrations above MIC through 48 h, but CFor EOS in preterm infants, two ampicillin doses (50 mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.

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.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.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 at28 weeks PMA were associated with a higher total daily dose than those initiated at a later PMA.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.

Background: Furosemide is commonly used off-label in the neonatal intensive care unit (NICU), but current dosing practices vary widely. Objectives: To describe dosing practices including route, dose, and duration of exposure to furosemide in a large number of community and tertiary NICUs across North America. Method: Using the Pediatrix Medical Group Clinical Data Warehouse, we identified infants who received ≥1 dose of furosemide between 1997 and 2016. We excluded infants with incomplete dosing data. We calculated average daily furosemide dose, cumulative dose, total days of exposure, and maximum daily dose. We compared dosing between infants born at Results: A total of 18,572 infants had complete dosing data. The median (interquartile value) postnatal age at first exposure was 11 days (4, 26), the median maximum daily dose was 1.0 mg/kg (0.97, 1.6), the median average daily dose was 1.0 mg/kg (0.88, 1.1), and the median cumulative dose was 2.0 mg/kg (1.0, 4.5). The median total duration of exposure was 2 days (1, 4). A total of 177 (1%) infants received ≥4 mg/kg/day of furosemide. Infants born p < 0.001. Conclusions: Most infants received short courses of furosemide within the labeled dosing parameters. Further studies are needed to assess the safety and efficacy of furosemide in the NICU.

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.

To determine if administering IV contrast for CT abdomen and pelvis improves detection of urgent and clinically important non-urgent pathology in patients with urgent clinical symptoms compared to patients not receiving IV contrast, and in turn to determine whether repeat CT exams on the same patient within 72 h were of low diagnostic benefit if the first CT was performed with IV contrast. We evaluated 400 consecutive patients who had CT abdomen and pelvis (CT AP) examinations repeated within 72 h. For each patient, demographic data, reason for examination, examination time stamps, and examination technique were documented. CT AP radiology reports were reviewed and both urgent and non-urgent pathology was extracted. Of 400 patients, 63% had their initial CT AP without contrast. Administration of IV contrast for the first CT AP was associated with increased detection of urgent findings compared with non-contrast CT (p = 0.004) and a contrast-enhanced CT AP following an initial non-contrast CT AP examination better characterized both urgent (p = 0.002) and non-urgent findings (p

The prevalence and importance of congenital anomalies of the kidney and urinary tract (CAKUT) in preterm infants is unknown.To determine the prevalence of CAKUT in preterm infants and association with in-hospital morbidity and mortality.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.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.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).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.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.

Objective: To assess the longitudinal metabolic patterns during the evolution of bronchopulmonary dysplasia (BPD) development. Methods: A case-control dataset of preterm infants (

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.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 weight1000 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.After adjusting for differences in baseline demographic and clinical features, the group with severe ROP was exposed to greater fraction of inspired oxygen (FiOSevere ROP is associated with greater FiO

Recent data have revealed declines in the prevalence rates of NEC over the last decade in premature infants. In contrast, SIP has either remained steady or risen during the same epoch. These trends are consistent with our knowledge of the clinical arena. The ability to discern SIP contamination within NEC datasets has slowly improved. Additionally, quality improvement efforts are being utilized to reduce NEC through stewardship of antibiotics, acid inhibitors, central lines and blood products, as well as optimization of human milk diets. These forces are moving us to a new era, where NEC will no longer be the dominant surgical intestinal disease of the extremely preterm neonate. Indeed, in the extremely low birth weight (ELBW) population, SIP may already be the most prevalent reason for abdominal surgery. In this perspective, the reader will find supporting data and references for these assertions as well as predictions for the future.

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.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.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.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.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.

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.

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 .

Objective To compare the risk of in-hospital mortality and morbidity between outborn and inborn neonates treated with whole body hypothermia. Methods The association of outborn birth status with in-hospital mortality and morbidity, prior to NICU discharge or transfer, was assessed in a large historical cohort of neonates who had therapeutic hypothermia initiated on the day of birth. The cohort was restricted to neonates born at ≥35 weeks gestational age from 2007 to 2018. Since the sample was non-random, inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalance in baseline maternal and neonatal characteristics between outborn and inborn neonates. Cox proportional hazards regression was used to assess the association between outborn status and in-hospital mortality. Results There were 4447 neonates included in the study (2463 outborn). Outborn status was not significantly associated with an increased risk of in-hospital mortality in the unadjusted cohort (HR = 1.17, 95% CI 0.97–1.42, p = 0.10) or IPW cohort (HR = 1.09, 95% CI 0.95–1.26, p = 0.22). However, in the IPW cohort, outborn neonates were significantly more likely to have seizures (28% vs 24%, p = 0.006), anticonvulsant exposure (46% vs 41%, p = 0.002), and gastrostomy tube placement (5.8% vs 3.8%, p = 0.009) during their newborn hospitalization. Conclusion Outborn status was not significantly associated with increased in-hospital mortality among neonates treated with whole body hypothermia. However, outborn neonates were more likely to have seizures, receive anticonvulsant treatment, and undergo gastrostomy tube placement. Further study is needed to better understand the etiologies of these outcome disparities and potential implications for long-term neurodevelopmental outcomes.