Establish the feasibility of optimizing PEEP (PEEPOPT) using ventilator software in infants receiving prolonged invasive mechanical ventilation. A retrospective review of infants who underwent PEEPOPT studies. Paired-t test was used to compare dynamic lung compliance (Cdyn), tidal volume (VT), and oxygen saturation (SpO2) before and after PEEPOPT studies. Fifteen infants with bronchopulmonary dysplasia and/or receiving prolonged invasive mechanical ventilation were included with a median gestational age of 24 4/7 weeks and postmenstrual age of 40 1/7 weeks at the time of the PEEPOPT study. PEEPOPT was different from clinically set PEEP (PEEPSET) in 14/15 infants; PEEPOPT was higher in 27% and lower in 67% of infants (–2 to +5cmH2O). Cdyn improved for most infants by 0.23 (0.01–0.60) mL/H2O (p < 0.001). VT increased for most infants by 1.5 (–0.5 to 3.4) mL/kg (p < 0.001), and SpO2 increased by 2% (–1 to 12%). Assessment of PEEPOPT using our standardized protocol is feasible, non-invasive, and provides a low-cost bedside tool. PEEPOPT differed from PEEPSET in most subjects, highlighting the importance of evaluating PEEPOPT.

This perspective work by academic neonatal providers is written specifically for the audience of newborn care providers and neonatologists involved in neonatal hypoglycemia screening. Herein, we propose adding a screen for congenital hyperinsulinism (CHI) by measuring glucose and ketone (i.e., β-hydroxybutyrate (BOHB)) concentrations just prior to newborn hospital discharge and as close to 48 h after birth as possible, at the same time that the mandated state Newborn Dried Blood Spot Screen is obtained. In the proposed protocol, we do not recommend specific metabolite cutoffs, as our primary objective is to simply highlight the concept of screening for CHI in newborns to newborn caregivers. The premise for our proposed screen is based on the known effect of hyperinsulinism in suppressing ketogenesis, thereby limiting ketone production. We will briefly discuss genetic CHI, other forms of neonatal hypoglycemia, and their shared mechanisms; the mechanism of insulin regulation by functional pancreatic islet cell membrane KATP channels; adverse neurodevelopmental sequelae and brain injury due to missing or delaying the CHI diagnosis; the principles of a good screening test; how current neonatal hypoglycemia screening programs do not fulfill the criteria for being effective screening tests; and our proposed algorithm for screening for CHI in newborns.

Objective This study aimed to evaluate if early (within the first 3 hours after birth) transient neonatal hypoglycemia (TNH) is associated with poor academic performance in infants at-risk for hypoglycemia. Study Design This was a retrospective cohort study of at risk-infants (late preterm infants, small and large for gestational age infants, and infants of diabetic mothers [IDMs]) who were born in 1998 and 1999 at the University of Arkansas for Medical Sciences and had >= 1 recorded glucose concentration. The outcome measure was proficiency on 4th grade literacy and mathematics achievement tests. Three glucose concentration cutoffs for defining hypoglycemia (<35, <40, and <45 mg/dL) were investigated. Logistic regression models were developed to examine the association between early TNH and achievement test proficiency based on perinatal factors. Results Among 726 infants, 472 had one, 233 had two, and 21 had three risk factor(s). Early TNH (glucose concentration <35, <40, and <45 mg/dL) was observed in 6.3, 11.6, and 20.5% of the study cohort, respectively. Irrespective of the cutoff used, the frequency of early TNH (number of patients with early TNH in a risk category divided by the total number of patients in that category) was significantly greater among infants with multiple risk factors. After controlling for perinatal factors, early TNH (cutoffs <35 and <40 mg/dL) was significantly associated with decreased probability of proficiency in literacy but not mathematics. Despite that early TNH was more common in IDMs and infants with three risk factors, the category or number of risk factors did not impact academic proficiency. Conclusion Early TNH (<35 and <40 mg/dL) was associated with lower adjusted probability of proficiency on 4th grade literacy achievement tests in at-risk infants. The impact of early TNH on academic performance was similar irrespective of category or number of risk factors.

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OBJECTIVE:To compare third grade literacy and mathematics test proficiency among children born with gastroschisis vs unaffected controls and identify predictors of academic proficiency among these children.STUDY DESIGN:Infants born with gastroschisis (2000-2005) were identified from the Arkansas Reproductive Health Monitoring System. For each case, 2 controls were selected at random from birth certificates and matched for hospital and month of birth, sex, and race/ethnicity. Data on rehospitalization within the first 6 years and payer data were abstracted from the Arkansas Hospital Inpatient Discharge database. Surviving cases and controls were linked to the Arkansas Department of Education database containing achievement test scores. The primary outcome was proficiency, defined as performance at or above grade level, on third grade achievement tests. Cases and controls who did not attend public schools could not be linked to education records. Multivariable logistic regression models evaluated the association between study characteristics and academic proficiency.RESULTS:The final study cohort included 47 cases and 63 controls. There was no statistically significant difference in the rate of literacy (68% vs 81%; P = .65) or mathematics proficiency (89% vs 87%; P = .15) between cases and controls. On multivariable analysis, a complex gastroschisis (defined as atresia, volvulus, necrosis, or perforation of the bowel) was associated with lower proficiency in literacy (aOR, 0.1; 95% CI, 0.02-0.58; P = .01). No neonatal or maternal characteristics predictive of lower proficiency in mathematics were identified.CONCLUSIONS:Among children born with gastroschisis, the presence of a complex gastroschisis was associated with lower proficiency on third grade literacy achievement tests.

Background:The American Academy of Pediatrics and Pediatric Endocrine Society neonatal hypoglycemia guidelines based their glucose concentration treatment thresholds on studies that predominantly used Beckman and Yellow Springs Glucose Oxidase Analyzers. Currently, a majority (76%) of U.S. hospital laboratories utilizing glucose oxidase methodology use Vitros® Glucose Analyzers. However, a bias of ~+5% between glucose concentrations from Beckman vs. Vitros Glucose Analyzers has been reported; this could have a clinically significant effect when using published guideline treatment thresholds.Methods:To determine if there is similar instrument bias between Beckman and Vitros Analyzers in reported glucose concentrations from term newborns, we compared plasma glucose concentrations measured within the first 3 h after birth by Beckman vs. Vitros Analyzers in a total of 1,987 newborns (Beckman n = 904, Vitros n = 1,083). Data were fit using nonlinear cubic spline models between collection time and glucose concentration.Results:The non-linear patterns of initial glucose concentrations (during the first 3 h after birth) as measured by Beckman and Vitros Analyzers paralleled each other with no overlap of the fit spline curve 95% confidence intervals, with an approximate +5 mg/dL constant bias. Additionally, in method comparison studies performed in the Chemistry Laboratory on adult samples, there was a +4.2-7.4 mg/dL measured glucose bias for the Beckman vs. Vitros Analyzer.Conclusion:Glucose concentrations from term, appropriate size for gestational age newborns were about 5 mg/dL higher when measured by Beckman vs. Vitros Analyzers. Perhaps, concentrations of 45 mg/dL reported from Beckman Analyzers may be equivalent to 40 mg/dL from Vitros Analyzers. When managing neonatal hypoglycemia, it is important to know which analyzer was used and whether adjusting for potential instrument bias is necessary when following published guidelines.

To compare parental reports of recent diagnoses of anxiety, depression, and/or behavioral/conduct disorder among former preterm (PT) and term adolescents by race/ethnicity and evaluate receipt of mental healthcare within the past year among those adolescents with any of these conditions. A total of 20,871 Non-Hispanic white (NHW), Non-Hispanic black (NHB), and Hispanic adolescents were evaluated using data from the 2017/2018 National Survey of Children’s Health. PT birth and race/ethnicity disparity in the diagnosis of these emotional/behavioral problems and receipt of mental healthcare among adolescents with any of these diagnoses were analyzed using logistic regression. The unadjusted prevalence (95% CI) of these diagnoses was significantly higher among former PT (0.19 [0.17–0.22]) compared to term (0.15 [0.14–0.16]) adolescents. Despite having higher rates of adverse socioeconomic measures, former PT and term NHBs and Hispanics had lower unadjusted prevalence of these diagnoses in comparison to NHWs. After adjusting for differences in demographic, clinical, and socioeconomic characteristics, NHBs (0.47 [0.36–0.64]) and Hispanics (0.40 [0.30–0.54]) remain at lower odds of the composite measure of the emotional and/or behavioral problems compared to NHWs, while PT birth did not have a significant impact on this outcome measure. Only 53% of adolescents with these diagnoses received recent mental healthcare. No significant differences in the adjusted odds of receipt of mental healthcare were noted across the groups based on PT birth or race/ethnicity. In contrast to PT birth, race/ethnicity had a significant impact on the adjusted odds of emotional/behavioral disorders during adolescence. Among adolescents with these diagnoses, PT birth and race/ethnicity did not significantly influence the adjusted odds of receipt of mental healthcare.

OBJECTIVES:Although epinephrine is used in the neonatal intensive care unit, few data exist on efficacy of doses <0.05 mcg/kg/min. This study evaluates the efficacy and safety of low-dose epinephrine continuous infusion at doses <0.05 mcg/kg/min in infants. METHODS:Single-center, retrospective review of hypotensive infants from 2011-2018. Charts were reviewed for initial and maximum epinephrine doses, additional vasoactive agents, short-term efficacy, and adverse effects. The primary outcome was percentage of patients initiated on low-dose epinephrine whose dose did not require titration to ≥0.05 mcg/kg/min. RESULTS:A total of 115 patients met study criteria with 131 distinct occurrences of low-dose epinephrine initiation. Most patients were unresponsive to other vasopressors at the time of epinephrine initiation. The median (IQR) starting dose of low-dose epinephrine was 0.01 (0.01-0.04) mcg/kg/min and median (IQR) maximum dose was 0.04 (0.02-0.08) mcg/kg/min. Fifty-five percent were responders. Patients in this cohort demonstrated significant improvement of blood pressure and urine output (p < 0.001) without adverse effects. CONCLUSIONS:Low-dose epinephrine infusion may be considered as an alternative treatment to standard starting doses in hypotensive neonatal intensive care unit patients.

Background Neonatal hypoglycemia may affect long-term neurodevelopment. Methods Quality improvement (QI) initiative for Mother-Baby-Unit (MBU) admissions (birthweight ≥ 2100 g; ≥35 weeks’ gestation) over two epochs from 2016–2019 to reduce the frequency of early (≤3 h) neonatal hypoglycemia in small and large newborns. Intervention New algorithm using Olsen’s growth curves, hypoglycemia thresholds of <2.22 mmol/L [40 mg/dL] (0–3 h) and <2.61 mmol/L [47 mg/dL] (>3 to 24 h), feeding optimization and 24-hour glucose checks for small for gestational age and preterm newborns. Results Among 39,460 newborns, using subsets with identical screening criteria, early hypoglycemia decreased significantly after QI implementation among large for gestational age newborns with birthweight >3850 g (66%) and small for gestational age newborns with birthweight <2500 g (70%). Among all MBU admissions, the adjusted odds of any hypoglycemia in 24 h decreased ( P < 0.001). Conclusions Feeding optimization may decrease early hypoglycemia frequency in large and small newborns.

Introduction: Although patent ductus arteriosus (PDA) has been implicated to play a role in the development of cerebral ischemia and intraventricular hemorrhage (IVH) through a cerebral steal phenomenon, there is conflicting data on the impact of PDA size on cerebral blood flow (CBF). Cerebral autoregulation is the brain’s innate protective mechanism to maintain constant CBF despite changes in blood pressure, and it is unclear if it is influenced by PDA hemodynamics. Objective: To delineate the relationship between PDA size and CBF velocity (CBFv) in premature infants. Methods: 113 premature infants born at 23–29 weeks’ gestation had echocardiograms performed during the first week after birth to evaluate for PDA. The infants were divided into 3 groups according to PDA size: none-to-small, moderate, or large. All infants had continuous recordings of umbilical artery blood pressure (ABP) and CBFv during the first week after birth. Critical closing pressure (CrCP) was calculated from ABP and CBFv tracings. Diastolic closing margin (DCM), defined as diastolic blood pressure minus CrCP, was calculated as a marker for the risk of developing IVH. Results: Infants with a large PDA (n = 16) had the lowest ABP across all phases of the cardiac cycle (systole [p = 0.003], mean [p = 0.005], and diastole [p = 0.012]) compared to infants with a moderate (n = 19) or none-to-small PDA (n = 78). Despite blood pressure being different, systolic, mean, and diastolic CBFv were not different across groups. Cerebral autoregulation, as measured during systole, was intact regardless of the PDA size. CrCP and DCM were also not different across groups. Conclusions: In this cohort, CBFv and cerebral autoregulation during systole were not influenced by PDA size. Intact cerebral autoregulation may play a role in maintaining CBFv regardless of PDA size and differences in ABP.

There is limited information about newborns with confirmed or suspected COVID-19. Particularly in the hospital after delivery, clinicians have refined practices in order to prevent secondary infection. While guidance from international associations is continuously being updated, all facets of care of neonates born to women with confirmed or suspected COVID-19 are center-specific, given local customs, building infrastructure constraints, and availability of protective equipment. Based on anecdotal reports from institutions in the epicenter of the COVID-19 pandemic close to our hospital, together with our limited experience, in anticipation of increasing numbers of exposed newborns, we have developed a triage algorithm at the Penn State Hospital at Milton S. Hershey Medical Center that may be useful for other centers anticipating a similar surge. We discuss several care practices that have changed in the COVID-19 era including the use of antenatal steroids, delayed cord clamping (DCC), mother-newborn separation, and breastfeeding. Moreover, this paper provides comprehensive guidance on the most suitable respiratory support for newborns during the COVID-19 pandemic. We also present detailed recommendations about the discharge process and beyond, including providing scales and home phototherapy to families, parental teaching via telehealth and in-person education at the doors of the hospital, and telehealth newborn follow-up.

Children with congenital heart defects (CHD) have impaired cognitive development. The objective was to determine if children with CHDs differed in academic performance during elementary and middle school years from children without CHDs. Data from the state birth defects registry, Arkansas Reproductive Health Monitoring System (ARHMS), birth certificate records, and achievement test-scores (grades 3-8) from the Arkansas Department of Education were linked using unique identifiers for children born between 2000-2011 in Arkansas. Cases were identified using 6-digit British Paediatric Association codes and matched controls were assigned from birth certificate data. Proficiency (yes/no) on achievement tests was determined using standard thresholds per grade. Data were stratified based on sex, gestational age, and birth weight. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from multivariate logistic regression adjusting for maternal education level and age, race/ethnicity, and infant sex. A total of 3,730 children with CHDs and 7,385 children without CHDs were evaluated. Children with CHD were less likely to be proficient in early elementary school grades for mathematics (3rd: OR=0.72, 95% CI: 0.59, 0.87; 4th: OR=0.77, 95% CI: 0.62, 0.95) and literacy (3rd: OR=0.75, 95% CI: 0.63, 0.89; 4th: OR=0.72, 95% CI: 0.58, 0.90). The trend of being less proficient associated with CHD remained mostly consistent with sex, gestational age, and birth weight. In multivariate analysis, CHD was negatively associated with being proficient in mathematics and literacy. Maternal education (1-3 years beyond high school) was positively associated with test proficiency. Additionally, non-Hispanic (NH) black children had lower odds of being proficient compared to NH white children. Educational performance was negatively associated with CHD in early elementary grades; there was no difference in later grades. However, larger sample sizes in later grades are necessary for reliable estimates. Maternal education and race/ethnicity were significant factors associated with childhood educational performance.

We tested the hypothesis that Modified Finnegan Neonatal Scoring System (MFNSS) scores can guide early discharge at 72 hours for newborns at risk for neonatal abstinence syndrome (NAS). A retrospective cohort study with a primary outcome of early discharge of newborns at risk for NAS using mean MFNSS scores recorded before pharmacologic treatment was performed. Quantile regression was used to develop percentile curves of mean MFNSS scores. A total of 202 term newborns at risk for NAS with 5066 mean MFNSS scores recorded before pharmacologic treatment were studied. Sixty-eight of 121 (56%) newborns not treated at 72 hours had mean MFNSS scores <50th percentile and only 1 was ultimately treated (1.5%, 95% confidence interval: 0% to 8%). No newborns with mean MFNSS scores <25th percentile at 72 hours were treated. Newborns at risk for NAS with mean MFNSS scores <50th percentile can be safely discharged by 72 hours if families can assure close outpatient follow-up.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) affects 1-3/1,000 newborns. Intestinal ischemia during the perinatal hypoxic event is associated with enteral feeding intolerance and potentially an increased risk of gastrointestinal morbidities such as necrotizing enterocolitis (NEC). Therapeutic Hypothermia (TH) is the standard-of-care treatment for newborns with moderate-to-severe HIE and is believed to decrease gastrointestinal morbidity. Optimal introduction and advancement of enteral nutrition post-TH is unknown. Moreover, it is also unknown if HIE severity affects tolerance of enteral nutrition and risk for adverse gastrointestinal …

While intercenter variation (ICV) in anti-epileptic drug (AED) use in neonates with seizures has been previously reported, variation in AED practices across regional NICUs has not been specifically and systematically evaluated. This is important as these centers typically have multidisciplinary neonatal neurocritical care teams and protocolized approaches to treating conditions such as hypoxic ischemic encephalopathy (HIE), a population at high risk for neonatal seizures. To identify opportunities for quality improvement (QI), we evaluated ICV in AED utilization for neonates with HIE treated with therapeutic hypothermia (TH) across regional NICUs in the US. Children’s Hospital Neonatal Database and Pediatric Health Information Systems data were linked for 1658 neonates ≥36 weeks’ gestation, > 1800 g birthweight, with HIE treated with TH, from 20 NICUs, between 2010 and 2016. ICV in AED use was evaluated using a mixed-effect regression model. Rates of AED exposure, duration, prescription at discharge and standardized AED costs per patient were calculated as different measures of utilization. Ninety-five percent (range: 83–100%) of patients with electrographic seizures, and 26% (0–81%) without electrographic seizures, received AEDs. Phenobarbital was most frequently used (97.6%), followed by levetiracetam (16.9%), phenytoin/fosphenytoin (15.6%) and others (2.4%; oxcarbazepine, topiramate and valproate). There was significant ICV in all measures of AED utilization. Median cost of AEDs per patient was $89.90 (IQR $24.52,$258.58). Amongst Children’s Hospitals, there is marked ICV in AED utilization for neonatal HIE. Variation was particularly notable for HIE patients without electrographic seizures, indicating that this population may be an appropriate target for QI processes to harmonize neuromonitoring and AED practices across centers.

Therapeutic hypothermia is the standard-of-care treatment for infants diagnosed with moderate-to-severe hypoxic–ischemic encephalopathy (HIE). MRI for assessing brain injury is usually performed after hypothermia because of logistical challenges in bringing acutely sick infants receiving hypothermia from the neonatal intensive care unit (NICU) to the MRI suite. Perhaps examining and comparing early cerebral oxygen metabolism disturbances to those after rewarming will lead to a better understanding of the mechanisms of brain injury in HIE and the effects of therapeutic hypothermia.