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.

Evaluation of Heparin Anti-Factor Xa Levels Following Antithrombin Supplementation in Pediatric Patients Supported With Extracorporeal Membrane Oxygenation.

OBJECTIVE: Thrombotic events are potential complications in patients receiving extracorporeal membrane oxygenation (ECMO) necessitating the use of systemic anticoagulation with heparin. Heparin works by potentiating the effects of antithrombin (AT), which may be deficient in critically ill patients and can be replaced. The clinical benefits and risks of AT replacement in children on ECMO remain incompletely understood. METHODS: This single-center, retrospective study reviewed 28 neonatal and pediatric patients supported on ECMO at a tertiary care hospital between April 1, 2013, and October 31, 2014, who received at least 1 dose of AT during their ECMO course. The primary outcome of the study was the change in anti-factor Xa levels after pooled human AT supplementation. Secondary outcomes included the percentage of anti-factor Xa levels within the therapeutic range surrounding AT administration; survival to decannulation; 30 days after cannulation and discharge; time to first circuit change; and incidence of bleeding and thrombotic events. RESULTS: A total of 78 doses of AT were administered during the study period. The mean increase in anti-factor Xa level following AT administration in patients without a ≥10% concurrent change in heparin was 0.075 ± 0.13 international units/mL. A greater percentage of anti-factor Xa levels were therapeutic for the 48 hours following AT administration (64.2% vs 38.6%). Survival and adverse events were similar to Extracorporeal Life Support Organization averages, with the exception of a higher incidence of intracranial hemorrhage. CONCLUSIONS: Patients experienced a small but significant increase in anti-factor Xa level and a greater percentage of therapeutic anti-factor Xa levels following AT supplementation.

Prevalence of Asthma and Allergies and Risk of Relapse in Childhood Nephrotic Syndrome: Insight into Nephrotic Syndrome Cohort.

OBJECTIVE: To determine the lifetime prevalence of allergies in childhood nephrotic syndrome, the seasonality of presentation and relapses, and the impact of allergies on subsequent relapses. STUDY DESIGN: In a longitudinal cohort of children with nephrotic syndrome (ages 1-18 years), assessment for allergic diseases was conducted using the validated and modified version of the International Study of Asthma and Allergies in Childhood questionnaire at enrollment. Outcomes included frequently relapsing nephrotic syndrome, relapse rates, and the relapse-free duration after initial steroid therapy. RESULTS: Among 277 participants, the majority were male (65%) with a median age of 3.7 years (IQR 2.8-5.8) at presentation. A total of 64% reported lifetime allergies with 20% having asthma, 33% wheezing, 27% eczema, and 24% rhinitis. Over 3.3 years of follow-up, presence of asthma and allergies was not associated with frequently relapsing nephrotic syndrome (OR 1.20; 95% CI 0.60, 2.40), higher relapse rates (relative risk 0.95; 95% CI 0.71, 1.27), or risk of first relapse (hazard ratio 1.10; 95% CI 0.83, 1.47) compared with those with no history of allergic diseases. There was also no seasonal variation evident at initial presentation or frequency of relapses. CONCLUSIONS: Two-thirds of children with nephrotic syndrome at presentation have allergic symptoms and asthma; however, neither are associated with an increased frequency of relapses.

Surfactant Administration in Preterm Infants: Drug Development Opportunities.

OBJECTIVE: To evaluate how frequently surfactant is used off-label in preterm infants. STUDY DESIGN: We conducted a retrospective cohort analysis of prospectively collected administrative data for 2005-2015 from 348 neonatal intensive care units in the US. We quantified off-label administration of poractant alfa, calfactant, or beractant in inborn infants born at <37 weeks of gestational age (GA). Off-label surfactant administration was defined according to the Food and Drug Administration (FDA) label. RESULTS: Of a total of 110 822 preterm infants who received surfactant, 68 226 (62%) received the surfactant off-label. The majority of infants who received surfactant off-label had a higher birth weight than those who received surfactant on-label (40 716 [37%]), had an older GA than those who received surfactant on-label (35 191 [32%]), or were treated with intubation and surfactant administration followed by immediate extubation (INSURE) (32 310 [29%]). Poractant alfa was administered via INSURE more frequently than beractant or calfactant (16 688 [38%], 7137 [20%], and 8485 [27%], respectively). An increasing number of infants received surfactant via INSURE from 2005 to 2015 (from 1697 [19%] to 3368 [36%]). CONCLUSIONS: The majority of surfactant given to preterm infants is administered off-label. The uptrend in administration via INSURE coincides with increased supporting evidence. The gap between FDA labeling and current clinic practice exemplifies an opportunity for label expansion, which may require additional prospective or retrospective safety and/or effectiveness data for infants of older GA and higher birth weight.

Association of Atrial Septal Defects and Bronchopulmonary Dysplasia in Premature Infants.

OBJECTIVE: To evaluate the association between the presence of an atrial septal defect (ASD) and the odds of developing bronchopulmonary dysplasia (BPD) in premature infants. STUDY DESIGN: We identified a cohort of infants that underwent at least one echocardiogram assessment, birth weight 501-1249 g, and gestational age 23-30 weeks discharged from the neonatal intensive care unit from 2004 to 2016. We used a BPD risk estimator to calculate the predicted risk of developing BPD at 6 postnatal ages within the first 28 days of life. We examined the association between the presence of an ASD and the development of BPD using 2 multivariable logistic regression models for each BPD risk severity on each postnatal day. The first model adjusted for predicted BPD risk and the second added therapeutic interventions for BPD. RESULTS: Of 20 496 infants from 228 NICUs who met inclusion criteria, 8892 (43%) were diagnosed with BPD and 1314 (6%) had an ASD. BPD was present in 48% of infants with an ASD and 43% of infants without an ASD. In infants with an ASD, the OR of developing BPD was higher after adjusting for predicted risk of BPD plus therapeutic interventions, regardless of postnatal age or predicted BPD risk severity. CONCLUSIONS: The presence of an ASD was associated with an increased odds of BPD in this cohort. Future trials should consider ASD as a potentially modifiable risk factor in this vulnerable population.

Evaluation of Gentamicin Exposure in the Neonatal Intensive Care Unit and Hearing Function at Discharge.

OBJECTIVE: To characterize the association between gentamicin dosing, duration of treatment, and ototoxicity in hospitalized infants. STUDY DESIGN: This retrospective cohort study conducted at 330 neonatal intensive care units (2002-2014) included inborn infants exposed to gentamicin with available hearing screen results, and excluded infants with incomplete dosing data and major congenital anomalies. Our primary outcome was the final hearing screen result performed during hospitalization: abnormal (failed or referred for further testing in one or both ears) or normal (bilateral passed). The 4 measures of gentamicin exposure were highest daily dose, average daily dose, cumulative dose, and cumulative duration of exposure. We fitted separate multivariable logistic regression models adjusted for demographics, comorbidities, and other clinical events. RESULTS: A total of 84 808 infants met inclusion/exclusion criteria; median (25th, 75th percentile) gestational age and birth weight were 35 weeks (33, 38) and 2480 g (1890, 3184), respectively. Failed hearing screens occurred in 3238 (3.8%) infants; failed screens were more likely in infants of lower gestational age and birth weight, who had longer hospital lengths of stay, higher rates of morbidities, and were small for gestational age. Median highest daily dose, average daily dose, and cumulative dose were 4.0 mg/kg/day (3.0, 4.0), 3.8 mg/kg/day (3.0, 4.0), and 12.1 mg/kg (9.1, 20.5), respectively. Median cumulative duration of exposure was 3 days (3, 6). In adjusted analysis, gentamicin dose and duration of therapy were not associated with hearing screen failure. CONCLUSIONS: Gentamicin dosing and duration of treatment were not associated with increased odds of failed hearing screen at the time of discharge from initial neonatal intensive care unit stay.

Association between Furosemide Exposure and Patent Ductus Arteriosus in Hospitalized Infants of Very Low Birth Weight.

OBJECTIVE: To evaluate the association between furosemide exposure and patent ductus arteriosus (PDA) in a large, contemporary cohort of hospitalized infants with very low birth weight (VLBW). STUDY DESIGN: Using the Pediatrix Medical Group Clinical Data Warehouse, we identified all inborn infants of VLBW <37 weeks of gestation discharged from the neonatal intensive care unit after the first postnatal week from 2011 to 2015. We defined PDA as any medical (ibuprofen or indomethacin) or surgical PDA therapy. We collected data up to the day of PDA treatment or postnatal day 18 for infants not diagnosed with PDA. We performed multivariable logistic regression to evaluate the association between PDA and exposure to furosemide. RESULTS: We included 43 576 infants from 337 neonatal intensive care units, of whom 6675 (15%) underwent PDA treatment. Infants with PDA were more premature and more often exposed to mechanical ventilation and inotropes. Furosemide was prescribed to 4055 (9%) infants. On multivariable regression, exposure to furosemide was associated with decreased odds of PDA treatment (OR 0.72; 95% CI 0.65-0.79). Increasing percentage of days with furosemide exposure was not associated with PDA treatment (OR 1.01; 95% CI 0.97-1.06). CONCLUSIONS: Furosemide exposure was not associated with increased odds of PDA treatment in hospitalized infants of VLBW. Further studies are needed to characterize the efficacy and safety of furosemide in premature infants.

Early lumbar puncture and risk of intraventricular hemorrhage in very low birth weight infants.

BACKGROUND: Lumbar puncture (LP) is the gold standard for diagnosing meningitis; however it is unknown whether early LP (≤3days of life) is associated with increased risk of intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants. OBJECTIVE: To determine whether early LP in VLBW infants is associated with severe IVH. METHODS: VLBW infants from a cohort of 1,158,789 infants discharged from 382 neonatal intensive care units (1997-2015) were enrolled. EXCLUSION CRITERIA: infants with major congenital anomalies, outborns, died/transferred prior to day of life 3, and those who had an LP performed only after day of life 3. Logistic regression was used to determine the association between early LP and the incidence of severe IVH (IVH grades 3/4) by 28days of life for each day of life from day 0 (birth) to day 3, adjusting for clinical covariates. RESULTS: 106,461 infants were included: 754 received an LP on Day-0, 640 on Day-1, 559 on Day-2 and 483 on Day-3. Severe IVH occurred in 4% (4130/104,025) of the infants in the no LP group and 9% (217/2436) of the LP group. Severe IVH was higher for infants with early LP: adjusted OR (95% confidence interval)=2.64 (1.96-3.54) on Day-0; 2.21 (1.61-3.04) on Day-1; 1.55 (1.03-2.34) on Day-2; and 2.25 (1.50-3.38) on Day-3. CONCLUSIONS: Early LP was associated with severe IVH in VLBW infants by 28days of life. LP is either a surrogate for an unrecognized factor or is itself associated with an increased risk of IVH.

The Use of Echocardiography for Pediatric Patients Presenting with Syncope.

OBJECTIVES: To assess the frequency, yield, and cost of echocardiograms meeting "rarely appropriate" criteria. STUDY DESIGN: Retrospective, single-center study of pediatric patients presenting with syncope. Patients were categorized according to the appropriate use criteria and based upon location of care (emergency department only, primary care setting only, or referred to a pediatric cardiologist). Multivariable regression was used to determine factors associated with performance of a "rarely appropriate" echocardiogram. Costs were calculated using fair market values from the Healthcare Bluebook. RESULTS: The cohort included 637 patients presenting with syncope during the 1-year study. Echocardiograms were ordered for 127 of 637 (20.1%) including 0 of 328 emergency department patients, 1 of 66 (1.5%) primary care setting patients, and 127 of 243 (52.3%) patients evaluated by a pediatric cardiologist. Use of echocardiography by pediatric cardiologists was categorized as "appropriate" in 92 of 127 (72.4%), "maybe appropriate" in 6 of 127 (4.7%), and "rarely appropriate" in 29 of 127 (22.8%). Abnormal findings were seen in 6 of 127 (4.7%) echocardiograms but in none of the "rarely appropriate" studies. In multivariable analysis, female sex and younger age were the only factors associated with performance of a "rarely appropriate" echocardiogram. "Rarely appropriate" echocardiograms cost an estimated $16 704.00 ($576.00 per patient) in the 1-year study. CONCLUSIONS: "Rarely appropriate" echocardiograms performed for syncope do not contribute management changing diagnostic information. However, they burden patients with additional cost and perhaps contribute to increased need for follow-up.

Respiratory Support for Very Low Birth Weight Infants Receiving Dexamethasone.

OBJECTIVE: To assess how neonatal intensive care units followed the American Academy of Pediatrics guidelines for use of dexamethasone in preterm infants by evaluating respiratory support at the time of dexamethasone administration. STUDY DESIGN: This is an observational study of infants discharged from one of 290 neonatal intensive care units from 2003 to 2010. The cohort included very low birth weight (<1500 g birth weight) infants born at ≤32 weeks gestational age. The main outcome was respiratory support at time of exposure to dexamethasone. Significant respiratory support was defined as invasive respiratory support (conventional or high-frequency ventilation) with a fraction of inspired oxygen (FiO2) > 0.3. RESULTS: Of 81 292 infants; 7093 (9%) received dexamethasone. At the time that dexamethasone was initiated, 4604 (65%) of infants were on significant respiratory support. CONCLUSIONS: In accordance with the American Academy of Pediatrics recommendations, a majority of infants were on significant respiratory support when receiving dexamethasone, yet a substantial number of infants still received dexamethasone on less than significant respiratory support. Further research on reducing dexamethasone use in premature infants is required to decrease the risk of neurodevelopmental impairment.

Congenital Heart Disease in Premature Infants 25-32 Weeks' Gestational Age.

OBJECTIVE: To determine the birth prevalence of congenital heart defects (CHDs) across the spectrum of common defects in very/extremely premature infants and to compare mortality rates between premature infants with and without CHDs. STUDY DESIGN: The Kids' Inpatient Databases (2003-2012) were used to estimate the birth prevalence of CHDs (excluding patent ductus arteriosus) in very/extremely premature infants born between 25 and 32 weeks' gestational age. Birth prevalence was compared with term infants for a subset of "severe" defects expected to be near universally diagnosed in the neonatal period. Weighted multivariable logistic regression was used to calculate aORs of mortality comparing very and extremely premature infants with vs without CHDs. RESULTS: We identified 249 011 very/extremely premature infants, including 28 806 with CHDs. The overall birth prevalence of CHDs was 116 per 1000 very/extremely premature births. Severe CHDs had significantly higher birth prevalence in very/extremely premature infants when compared with term infants (7.4 per 1000 very/premature births vs 1.5 per 1000 term births; P < .001). Very/extremely premature infants with severe CHDs had an overall 26.3% in-hospital mortality and a 7.5-fold increased adjusted odds of death compared with those without CHDs. Mortality varied widely by defect in very/extremely premature infants, ranging from 12% for interrupted aortic arch to 67% for truncus arteriosus. CONCLUSIONS: Given the increased birth prevalence of severe CHDs in very/extremely premature infants, and significantly higher mortality, there is justification for intensive interventions aimed at decreasing the likelihood of premature delivery for patients where CHD is diagnosed in utero.

Sedation, Analgesia, and Paralysis during Mechanical Ventilation of Premature Infants.

OBJECTIVE: To characterize administration of sedatives, analgesics, and paralytics in a large cohort of mechanically ventilated premature infants. STUDY DESIGN: Retrospective cohort study including all infants <1500 g birth weight and <32 weeks gestational age (GA) mechanically ventilated at 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. The primary outcome is the proportion of mechanically ventilated days in which infants were administered drugs of interest. Multivariable logistic regression was used to evaluate the predictors of administration of drugs of interest. RESULTS: We identified 85 911 mechanically ventilated infants. Infants received a drug of interest (opioids, benzodiazepines, other sedatives, and paralytics) on 433 587/1 305 413 (33%) of mechanically ventilated infant days. The administration of opioids increased during the study period from 5% of infant days in 1997 to 32% in 2012. The administration of benzodiazepines increased during the study period from 5% of infant days in 1997 to 24% in 2012. Use of paralytics and other drugs remained ≤1% throughout the study period. Predictors of drug administration included younger GA, small for GA status, male sex, presence of a major congenital anomaly, older postnatal age at intubation, exposure to high-frequency ventilation, exposure to inotropes, more recent year of discharge, and neonatal intensive care unit site. CONCLUSIONS: Administration of opioids and benzodiazepines in mechanically ventilated premature infants increased over time. Because infant characteristics were unchanged, site-specific differences in practice likely explain our observations. Increased administration over time is concerning given limited evidence of benefit and potential for harm.

Electronic Health Records and Pharmacokinetic Modeling to Assess the Relationship between Ampicillin Exposure and Seizure Risk in Neonates.

OBJECTIVE: To evaluate the relationship between ampicillin dosing, exposure, and seizures. STUDY DESIGN: This was a retrospective observational cohort study of electronic health record (EHR) data combined with pharmacokinetic model derived drug exposure predictions. We used the EHR from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. We included all infants 24-41 weeks gestational age, 500-5400 g birth weight, first exposed to ampicillin prior to 25 days postnatal age. Using a 1-compartment pharmacokinetic model and EHR data, we simulated maximum ampicillin concentration at steady state (Cmaxss, µg/mL) and area under the concentration time curve from 0 to 24 hours (AUC24, µg*h/dL). Using multivariable logistic regression, we evaluated association between ampicillin dosing, exposure, and seizures as documented in the EHR. RESULTS: We identified 131 723 infants receiving 134 041 courses of ampicillin for 653 506 infant-days of exposure. The median daily dose was 200 mg/kg/d (25th, 75th percentile; 100, 200). Median Cmaxss and AUC24 were 256.6 µg/mL (164.3, 291.5) and 2593 µg*h/dL (1917, 3334). On multivariable analysis, dosing was not associated with seizures. However increasing Cmaxss (OR = 1.10, 95% CI 1.03, 1.17) and AUC24 (OR 1.11, 95% CI 1.05, 1.18) were associated with increased odds of seizures. CONCLUSIONS: In this cohort of hospitalized infants, higher ampicillin exposure was associated with seizures as documented in the EHR.

Risk Factors and In-Hospital Outcomes following Tracheostomy in Infants.

OBJECTIVE: To describe the epidemiology, risk factors, and in-hospital outcomes of tracheostomy in infants in the neonatal intensive care unit. STUDY DESIGN: We analyzed electronic medical records from 348 neonatal intensive care units for the period 1997 to 2012, and evaluated the associations among infant demographics, diagnoses, and pretracheostomy cardiopulmonary support with in-hospital mortality. We also determined the trends in use of infant tracheostomy over time. RESULTS: We identified 885 of 887 910 infants (0.1%) who underwent tracheostomy at a median postnatal age of 72 days (IQR, 27-119 days) and a median postmenstrual age of 42 weeks (IQR, 39-46 weeks). The most common diagnoses associated with tracheostomy were bronchopulmonary dysplasia (396 of 885; 45%), other upper airway anomalies (202 of 885; 23%), and laryngeal anomalies (115 of 885; 13%). In-hospital mortality after tracheostomy was 14% (125 of 885). On adjusted analysis, near-term gestational age (GA), small for GA status, pulmonary diagnoses, number of days of forced fraction of inspired oxygen >0.4, and inotropic support before tracheostomy were associated with increased in-hospital mortality. The proportion of infants requiring tracheostomy increased from 0.01% in 1997 to 0.1% in 2005 (P < .001), but has remained stable since. CONCLUSION: Tracheostomy is not commonly performed in hospitalized infants, but the associated mortality is high. Risk factors for increased in-hospital mortality after tracheostomy include near-term GA, small for GA status, and pulmonary diagnoses.

Enteral Feeding with Human Milk Decreases Time to Discharge in Infants following Gastroschisis Repair.

OBJECTIVE: To assess the effect of enteral feeding with human milk on the time from initiation of feeds to discharge after gastroschisis repair through review of a multi-institutional database. STUDY DESIGN: Infants who underwent gastroschisis repair between 1997 and 2012 with data recorded in the Pediatrix Medical Group Clinical Data Warehouse were categorized into 4 groups based on the percentage of days fed human milk out of the number of days fed enterally. Cox proportional hazards regression modeling was performed to determine the adjusted effect of human milk on the time from initiation of feeds to discharge. RESULTS: Among 3082 infants, 659 (21%) were fed human milk on 0% of enteral feeding days, 766 (25%) were fed human milk on 1%-50% of enteral feeding days, 725 (24%) were fed human milk on 51%-99% of enteral feeding days, and 932 (30%) were fed human milk on 100% of enteral feeding days. Following adjustment, being fed human milk on 0% of enteral feeding days was associated with a significantly increased time to discharge compared with being fed human milk on 100% of enteral feeding days (hazard ratio [HR] for discharge per day, 0.46; 95% CI, 0.40-0.52). The same was found for infants fed human milk on 1%-50% of enteral feeding days (HR, 0.37; 95% CI, 0.32-0.41) and for infants fed human milk on 51%-99% of enteral feeding days (HR, 0.51; 95% CI, 0.46-0.57). CONCLUSION: The use of human milk for enteral feeding of infants following repair of gastroschisis significantly reduces the time to discharge from initiation of feeds.

Sedatives and Analgesics Given to Infants in Neonatal Intensive Care Units at the End of Life.

OBJECTIVE: To describe the administration of sedatives and analgesics at the end of life in a large cohort of infants in North American neonatal intensive care units. STUDY DESIGN: Data on mortality and sedative and analgesic administration were from infants who died from 1997-2012 in 348 neonatal intensive care units managed by the Pediatrix Medical Group. Sedatives and analgesics of interest included opioids (fentanyl, methadone, morphine), benzodiazepines (clonazepam, diazepam, lorazepam, midazolam), central alpha-2 agonists (clonidine, dexmedetomidine), ketamine, and pentobarbital. We used multivariable logistic regression to evaluate the association between administration of these drugs on the day of death and infant demographics and illness severity. RESULTS: We identified 19 726 infants who died. Of these, 6188 (31%) received a sedative or analgesic on the day of death; opioids were most frequently administered, 5366/19 726 (27%). Administration of opioids and benzodiazepines increased during the study period, from 16/283 (6%) for both in 1997 to 523/1465 (36%) and 295/1465 (20%) in 2012, respectively. Increasing gestational age, increasing postnatal age, invasive procedure within 2 days of death, more recent year of death, mechanical ventilation, inotropic support, and antibiotics on the day of death were associated with exposure to sedatives or analgesics. CONCLUSIONS: Administration of sedatives and analgesics increased over time. Infants of older gestational age and those more critically ill were more likely to receive these drugs on the day of death. These findings suggest that drug administration may be driven by severity of illness.

Safety of octreotide in hospitalized infants.

BACKGROUND: Octreotide is used off-label in infants for treatment of chylothorax, congenital hyperinsulinism, and gastrointestinal bleeding. The safety profile of octreotide in hospitalized infants has not been described; we sought to fill this information gap. METHODS: We identified all infants exposed to at least 1 dose of octreotide from a cohort of 887,855 infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012. We collected laboratory and clinical information while infants were exposed to octreotide and described the frequency of baseline diagnoses, laboratory abnormalities, and clinical adverse events (AEs). RESULTS: A total of 428 infants received 490 courses of octreotide. The diagnoses most commonly associated with octreotide use were chylothorax (50%), pleural effusion (32%), and hypoglycemia (22%). The most common laboratory AEs that occurred during exposure to octreotide were thrombocytopenia (47/1000 infant-days), hyperkalemia (21/1000 infant-days), and leukocytosis (20/1000 infant-days). Hyperglycemia occurred in 1/1000 infant-days and hypoglycemia in 3/1000 infant-days. Hypotension requiring pressors (12%) was the most common clinical AE that occurred during exposure to octreotide. Necrotizing enterocolitis was observed in 9/490 (2%) courses, and death occurred in 11 (3%) infants during octreotide administration. CONCLUSION: Relatively few AEs occurred during off-label use of octreotide in this cohort of infants. Additional studies are needed to further evaluate the safety, dosing, and efficacy of this medication in infants.

Retinopathy of prematurity risk prediction for infants with birth weight less than 1251 grams.

OBJECTIVE: To predict retinopathy of prematurity (ROP) exam findings among infants with birth weight <1251 g from 32-40 weeks postmenstrual age (PMA). STUDY DESIGN: Secondary analysis of 3714 eye exams from 1239 infants. RESULTS: The likelihood of developing type 1 ROP by 40 weeks PMA varied by gestational age (GA) (P < .001), from 33% for ≤25 weeks, 10% for 26 or 27 weeks, 4% for 28 or 29 weeks, and none for ≥30 weeks. By 40 weeks PMA, 51% with GA ≤27 weeks still needed subsequent exams. Previous exam findings, GA, and PMA were predictive of the development of type 1 ROP (area under the curve, 0.78) or mature retina (area under the curve, 0.85). CONCLUSIONS: This analysis provides the opportunity for development of an ROP approach to estimate resource needs in the neonatal intensive care unit and to facilitate communication with families when planning discharge or transfer.

Comparative effectiveness of surfactant preparations in premature infants.

OBJECTIVE: To compare effectiveness of 3 surfactant preparations (beractant, calfactant, and poractant alfa) in premature infants for preventing 3 outcomes: (1) air leak syndromes; (2) death; and (3) bronchopulmonary dysplasia (BPD) or death (composite outcome). STUDY DESIGN: We conducted a comparative effectiveness study of premature infants admitted to 322 neonatal intensive care units in the US from 2005-2010 who were treated with beractant, calfactant, or poractant alfa. We compared the incidence of air leak syndromes, death, and BPD or death, adjusting for gestational age (GA), antenatal steroids, discharge year, and small for GA status. RESULTS: A total of 51282 infants received surfactant; 40% received beractant, 30% calfactant, and 30% poractant alfa. Median birth weight was 1435 g (IQR 966-2065); median GA was 30 weeks (27-33). On adjusted analysis, we observed a similar risk of air leak syndromes (calfactant vs beractant OR = 1.17 [95% CI: 0.95, 1.43]; calfactant vs poractant OR = 1.23 [0.98, 1.56]; beractant vs poractant OR = 1.06 [0.87, 1.29]), death (calfactant vs beractant OR = 1.14 [0.93, 1.39]; calfactant vs poractant OR = 0.98 [0.78, 1.23]; beractant vs poractant OR = 0.86 [0.72, 1.04]), and BPD or death (calfactant vs beractant OR = 1.08 [0.93, 1.26]; calfactant vs poractant OR = 1.19 [1.00, 1.41]; beractant vs poractant OR = 1.10 [0.96, 1.27]). CONCLUSIONS: Beractant, calfactant, and poractant alfa demonstrated similar effectiveness in prevention of air leak syndromes, death, and BPD or death in premature infants when adjusted for site. Previously described differences in mortality between surfactants likely do not represent true differences in effectiveness but may relate to site variation in outcomes.