Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal.

BACKGROUND: Although clinicians have traditionally used the Finnegan Neonatal Abstinence Scoring Tool to assess the severity of neonatal opioid withdrawal, a newer function-based approach - the Eat, Sleep, Console care approach - is increasing in use. Whether the new approach can safely reduce the time until infants are medically ready for discharge when it is applied broadly across diverse sites is unknown. METHODS: In this cluster-randomized, controlled trial at 26 U.S. hospitals, we enrolled infants with neonatal opioid withdrawal syndrome who had been born at 36 weeks' gestation or more. At a randomly assigned time, hospitals transitioned from usual care that used the Finnegan tool to the Eat, Sleep, Console approach. During a 3-month transition period, staff members at each hospital were trained to use the new approach. The primary outcome was the time from birth until medical readiness for discharge as defined by the trial. Composite safety outcomes that were assessed during the first 3 months of postnatal age included in-hospital safety, unscheduled health care visits, and nonaccidental trauma or death. RESULTS: A total of 1305 infants were enrolled. In an intention-to-treat analysis that included 837 infants who met the trial definition for medical readiness for discharge, the number of days from birth until readiness for hospital discharge was 8.2 in the Eat, Sleep, Console group and 14.9 in the usual-care group (adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7 to 8.8), for a rate ratio of 0.55 (95% CI, 0.46 to 0.65; P<0.001). The incidence of adverse outcomes was similar in the two groups. CONCLUSIONS: As compared with usual care, use of the Eat, Sleep, Console care approach significantly decreased the number of days until infants with neonatal opioid withdrawal syndrome were medically ready for discharge, without increasing specified adverse outcomes. (Funded by the Helping End Addiction Long-term (HEAL) Initiative of the National Institutes of Health; ESC-NOW ClinicalTrials.gov number, NCT04057820.).

Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole.

Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN_METRO, NCT01222585) study. First, we used linear correlation to compare 42 paired DBS and plasma metronidazole concentrations from 21 preterm infants [mean (SD): post natal age 28.0 (21.7) days, GA 26.3 (2.4) weeks]. Using the resulting predictive equation, we estimated plasma metronidazole concentrations (ePlasma) from 399 DBS collected from 122 preterm and term infants [mean (SD): post natal age 16.7 (15.8) days, GA 31.4 (5.1) weeks] from the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP, NCT01994993) trial. When evaluating the PTN_METRO model using ePlasma from the SCAMP trial, we found that the model generally predicted ePlasma well in preterm infants with GA ≤31 weeks. When including ePlasma from term and preterm infants with GA >31 weeks, the model was optimized using a sigmoidal Emax maturation function of postmenstrual age on clearance and estimated the exponent of weight on volume of distribution. The optimized model supports existing dosing guidelines and adds new data to support a 6-hour dosing interval for infants with postmenstrual age >40 weeks. Using an opportunistic DBS to externally validate and optimize a metronidazole population pharmacokinetic model was feasible and useful in this vulnerable population.

Generalizability of the Necrotizing Enterocolitis Surgery Trial to the Target Population of Eligible Infants.

OBJECTIVE: The objective of this study was to evaluate whether infants randomized in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Necrotizing Enterocolitis Surgery Trial differed from eligible infants and whether differences affected the generalizability of trial results. STUDY DESIGN: Secondary analysis of infants enrolled in Necrotizing Enterocolitis Surgery Trial (born 2010-2017, with follow-up through 2019) at 20 US academic medical centers and an observational data set of eligible infants through 2013. Infants born ≤1000 g and diagnosed with necrotizing enterocolitis or spontaneous intestinal perforation requiring surgical intervention at ≤8 weeks were eligible. The target population included trial-eligible infants (randomized and nonrandomized) born during the first half of the study with available detailed preoperative data. Using model-based weighting methods, we estimated the effect of initial laparotomy vs peritoneal drain had the target population been randomized. RESULTS: The trial included 308 randomized infants. The target population included 382 (156 randomized and 226 eligible, non-randomized) infants. Compared with the target population, fewer randomized infants had necrotizing enterocolitis (31% vs 47%) or died before discharge (27% vs 41%). However, incidence of the primary composite outcome, death or neurodevelopmental impairment, was similar (69% vs 72%). Effect estimates for initial laparotomy vs drain weighted to the target population were largely unchanged from the original trial after accounting for preoperative diagnosis of necrotizing enterocolitis (adjusted relative risk [95% CI]: 0.85 [0.71-1.03] in target population vs 0.81 [0.64-1.04] in trial) or spontaneous intestinal perforation (1.02 [0.79-1.30] vs 1.11 [0.95-1.31]). CONCLUSION: Despite differences between randomized and eligible infants, estimated treatment effects in the trial and target population were similar, supporting the generalizability of trial results. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01029353.

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.

Endotoxin content in neonatal formulas, fortification, and lactoferrin products: association with outcomes and guidance on acceptable limits.

While endotoxin (lipopolysaccharide) can be harmful and contribute to morbidity and mortality with Gram-negative sepsis or necrotizing enterocolitis in preterm infants, non-toxic amounts are produced as part of the neonatal microbiome and may be present in enteral nutrition and medications administered. The United States Food and Drug Administration has given guidance for endotoxin concentration limits for intravenous medications and fluids of 5 endotoxin units/kg/hour (120 endotoxin units/kg/day), but no guidance for amounts of endotoxin in enteral products. To determine baseline exposure to infants in the neonatal intensive care unit, we examined endotoxin content of enteral formulas and fortification used for preterm infants, as well as bovine lactoferrin products. We also examined endotoxin exposure and outcomes in very low birth weight infants. Endotoxin content was measured using kinetic chromogenic limulus amebocyte lysate analysis. Daily endotoxin exposure from enteral formulas ranged between < 75 to 7110 endotoxin units/kg and from lactoferrin products from 7 to 3720 endotoxin units/kg. In examining neonatal outcomes from a bovine lactoferrin product studied at three different escalating doses (100, 200, and 300 mg/kg/day), we measured endotoxin in the lactoferrin product and daily exposure was 1089 (N = 10), 2178 (N = 10) and 3287 (N = 11) endotoxin units/kg, respectively. There were no cases of necrotizing enterocolitis or mortality and no lactoferrin-related adverse effects in these patients. Enteral endotoxin daily exposures from lactoferrin products are similar to amounts in preterm enteral nutrition and appear safe and not associated with patient harm. Testing enteral products and establishing safety limits may improve care of high risk patients.

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.

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..

Safety and Pharmacokinetics of Exebacase in an Infant With Disseminated Staphylococcus aureus Infection.

Exebacase, an antistaphylococcal lysin produced from a bacteriophage-encoded gene, is a promising adjunctive therapy for severe methicillin-resistant Staphylococcus aureus infections. We describe the first infant to receive exebacase, dosing, and pharmacokinetics. Exebacase may be safe and efficacious in children; however, further clinical trials are needed to optimize dosing.

Group B Streptococcus Infection in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years.

BACKGROUND: This study was performed to determine the incidence of group B Streptococcus (GBS) disease among extremely preterm infants and assess to risk of death or neurodevelopmental impairment (NDI) at a corrected age of 18-26 months. METHODS: In this observational cohort study of infants enrolled in a multicenter registry, the incidence of GBS disease was assessed in infants born in 1998-2016 at 22-28 weeks' gestation and surviving for >12 hours. The composite outcome, death or NDI, was assessed in infants born in 1998-2014 at 22-26 weeks' gestation. Infection was defined as GBS isolation in blood or cerebrospinal fluid culture at ≤72 hours (early-onset disease [EOD]) or >72 hours (late-onset disease [LOD]) after birth. Using Poisson regression models, the outcome was compared in infants with GBS disease, infants infected with other pathogens, and uninfected infants. RESULTS: The incidence of GBS EOD (2.70/1000 births [95% confidence interval (CI), 2.15-3.36]) and LOD (8.47/1000 infants [7.45-9.59]) did not change significantly over time. The adjusted relative risk of death/NDI was higher among infants with GBS EOD than in those with other infections (adjusted relative risk, 1.22 [95% CI, 1.02-1.45]) and uninfected infants (1.44 [1.23-1.69]). Risk of death/NDI did not differ between infants with GBS LOD and comparator groups. GBS LOD occurred at a significantly later age than non-GBS late-onset infection. Among infants surviving >30 days, the risk of death was higher with GBS LOD (adjusted relative risk, 1.90 [95% CI, 1.36-2.67]), compared with uninfected infants. CONCLUSIONS: In a cohort of extremely preterm infants, the incidence of GBS disease did not change during the study period. The increased risk of death or NDI with GBS EOD, and of death among some infants with GBS LOD, supports the need for novel preventive strategies for disease reduction. CLINICAL TRIALS REGISTRATION: NCT00063063.

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.

Insulin for Treatment of Neonatal Hyperglycemia in Premature Infants: Prevalence over Time and Association with Outcomes.

OBJECTIVE: Our objective was to determine the prevalence of insulin treatment in premature infants with hyperglycemia and evaluate the association of length of treatment with outcomes. STUDY DESIGN: The study included cohort of 29,974 infants 22 to 32 weeks gestational age (GA) admitted to over 300 neonatal intensive care unit (NICU) from 1997 to 2018 and diagnosed with hyperglycemia. RESULTS: Use of insulin significantly decreased during the study period (p = 0.002) among studied NICUs. The percentage of hyperglycemic infants exposed to insulin ranged from 0 to 81%. Infants who received insulin were more likely to have lower GA, birth weight, 5-minute Apgar score, longer duration of stay, and require mechanical ventilation. After adjustment for GA, infants requiring insulin for >14 days were more likely to have treated retinopathy of prematurity (ROP) and develop chronic lung disease (CLD). Insulin treatment of 1 to 7 days had increased odds of death, death/ROP, and death/CLD compared with no exposure. CONCLUSION: Insulin use decreased over time, and differing durations of use were associated with adverse outcomes. KEY POINTS: · Insulin use decreased over time.. · There is a temporal relation between the duration of treatment and adverse outcomes.. · Further studies are needed to determine the efficacy and safety of insulin use..

Outcomes of Moderately Preterm Infants of Insulin-Dependent Diabetic Mothers.

OBJECTIVE: Little is known about the hospital outcomes of moderately preterm (MPT; 29 0/7-33 6/7 weeks gestational age) infants born to insulin-dependent diabetic mothers (IDDMs). We evaluated characteristics and outcomes of MPT infants born to IDDMs compared with those without IDDM (non-IDDM). STUDY DESIGN: Cohort study of infants from 18 centers included in the MPT infant database from 2012 to 2013. We compared characteristics and outcomes of infants born to IDDMs and non-IDDMs. RESULTS: Of 7,036 infants, 527 (7.5%) were born to IDDMs. Infants of IDDMs were larger at birth, more often received continuous positive pressure ventilation in the delivery room, and had higher risk of patent ductus arteriosus (adjusted relative risk or aRR: 1.49, 95% confidence interval [CI]: 1.20-1.85) and continued hospitalization at 40 weeks postmenstrual age (aRR: 1.55, 95% CI: 1.18-2.05). CONCLUSION: MPT infants of IDDM received more respiratory support and prolonged hospitalizations, providing further evidence of the important neonatal health consequences of maternal diabetes. KEY POINTS: · Little data are available on moderate preterm infants of IDDMs.. · MPT infants of IDDMs need more respiratory support.. · Longer neonatal intensive care unit stays among MPT infants of IDDMs..

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..

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.

Should Vitamin A Injections to Prevent Bronchopulmonary Dysplasia or Death Be Reserved for High-Risk Infants? Reanalysis of the National Institute of Child Health and Human Development Neonatal Research Network Randomized Trial.

OBJECTIVE: To determine whether infants at higher risk of bronchopulmonary dysplasia (BPD) or death benefit more from vitamin A therapy than those at lower risk. STUDY DESIGN: We conducted a post hoc reanalysis of a landmark phase III randomized controlled trial conducted from January 1996 to July 1997 at 14 university-affiliated neonatal intensive care units in the US. Data analysis was performed from October 2019 to October 2020. Infants born weighing 401-1000 g and receiving respiratory support at 24 hours of age were assigned to intramuscular vitamin A 5000 IU or sham procedure 3 times weekly for 4 weeks. The primary outcome was BPD, defined as use of supplemental oxygen, or death at 36 weeks postmenstrual age. An externally validated model for predicting BPD or death was used to estimate the risk of these outcomes for each infant. RESULTS: As previously reported, 222 of 405 infants (54.8%) assigned vitamin A therapy and 248 of 402 infants (61.7%) in the control group developed BPD or died (relative risk [RR], 0.89 [95% CI, 0.80-0.99]; risk difference [RD], -6.9% [95% CI, -13.0 to -0.7]). The predicted individual risks of BPD or death ranged from 7.1% to 98.6% (median, 61.5%; mean, 60.9%). The effect of vitamin A therapy on BPD or death depended on infants' risk of the primary outcome (P = .03 for interaction): for example, a RR of 0.73 (RD, -14.5%) for infants with a 25% predicted risk and a RR of 0.96 (RD, -1.0%) for infants with a 75% risk. There was no difference in the decrease in vitamin A deficiency across risk groups. CONCLUSIONS: Contrary to expectations, the effect of vitamin A therapy on BPD or death was greater for lower risk than higher risk infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT01203488.

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.

Neurosurgical procedures for children with myelomeningocele after fetal or postnatal surgery: a comparative effectiveness study.

AIM: To compare the frequencies of neurosurgical procedures to treat comorbid conditions of myelomeningocele in patients who underwent fetal surgery versus postnatal surgery for closure of the placode. METHOD: By utilizing the National Spina Bifida Patient Registry in a comparative effectiveness study, 298 fetal surgery patients were matched by birthdate (±3mo) and spina bifida clinic site with one to three postnatal surgery patients (n=648). Histories were obtained by record review on enrollment and yearly subsequently. Multivariable Poisson regression was used to compare frequencies of procedures between cohorts, with adjustments for sex, ethnicity, insurance status, spinal segmental level of motor function, age at last visit recorded in the Registry, and, for shunt revision in shunted patients, age at cerebrospinal fluid (CSF) diversion. RESULTS: The median age at last visit was 4 years. In fully adjusted analyses in patients aged at least 12 months old, fetal surgery was associated with decreased frequency of CSF diversion for hydrocephalus by ventriculoperitoneal shunt insertion or endoscopic third ventriculostomy compared with postnatal surgery (46% vs 79%; incidence rate ratio=0.61; 95% confidence interval [CI] 0.53-0.71; p<0.01). Over all ages, fetal surgery was associated with decreased frequency of Chiari decompression for brainstem dysfunction (3% vs 7%; incidence rate ratio=0.41; 95% CI 0.19-0.88; p=0.02). Also over all ages, differences were not significant in frequencies of shunt revision in shunted patients (53% vs 55%; incidence rate ratio=0.87; 95% CI 0.69-1.11; p=0.27), nor tethered cord release for acquired spinal cord dysfunction (18% vs 16%; incidence rate ratio=1.11; 95% CI 0.84-1.47; p=0.46). INTERPRETATION: Even with the variations inherent in clinical practice, fetal surgery was associated with lower frequencies of CSF diversion and of Chiari decompression, independent of covariates. What this paper adds Fetal surgery was associated with lower frequencies of cerebrospinal fluid diversion and decompression of Chiari II malformation than postnatal surgery. Frequencies of ventriculoperitoneal shunt revision and tethered cord release were not significantly different between cohorts.

Discharging Medically Complex Infants with Supplemental Nasogastric Tube Feeds: Impact on Neonatal Intensive Care Unit Length of Stay and Prevention of Gastrostomy Tubes.

OBJECTIVE: The aim of this study is to evaluate the feasibility, safety, and efficacy of discharge with supplemental nasogastric tube (NGT) feeds in medically complex infants. STUDY DESIGN: Cohort study of 400 infants enrolled in the Transitional Medical Home (TMH) program at Duke University Level IV neonatal intensive care unit from January 2013 to 2017. RESULTS: Among 400 infants enrolled in the TMH, 57 infants were discharged with an NGT. A total of 45 infants with a variety of diagnoses and comorbidities were included in final analysis. Among 45 infants, 5 obtained a gastrostomy tube (GT) postdischarge. Median (25-75th percentile) length of use of NGT in 40 infants was 12 days (4-37). Excluding four outliers who used NGT for ≥140 days, the median length of use was 8 days (3-24). This extrapolates to a median of 288 hospital days saved for the remaining 36 infants. There were only three emergency room visits related to parental concern for incorrect NGT placement. There was no statistically significant difference in percent oral feeding predischarge or growth in first month postdischarge between infants who orally fed versus those who obtained GTs. CONCLUSION: Discharge with supplemental NGT feeds is safe and feasible utilizing a standardized protocol and close postdischarge follow-up. This practice can decrease length of stay and prevent need for GT. KEY POINTS: · Discharge with nasogastric tube (NGT) supplementation is safe.. · Discharge with NGT supplementation decreases cost.. · Discharge with NGT can decrease neonatal intensive care unit length of stay.. · Medical home model facilitates safe discharge..