Objectives The aim of the study is to (1) determine the incidence of developmental dysplasia of the hip (DDH) in preterm infants born prior to 35 completed weeks' gestation in a breech presentation, and (2) evaluate if the association between breech presentation and DDH in full-term infants holds for premature infants. Study Design This study design comprises retrospective review of infants born between January 1, 2008, and December 31, 2017, at <35 weeks' gestation and admitted to the NICU. Infants had hip ultrasounds at 4 to 6 weeks' corrected age if they were born in a breech presentation with a stable hip examination. We excluded infants born in a presentation other than breech or vertex, had no documentation of presentation at birth, or if they died within the first year. Results We included 1,533 infants. Preterm infants <35 weeks' gestation born in the breech versus vertex position had an incidence of DDH of 0.47% (2/428) and 0.36% (4/1,105), respectively. There was no significant difference in the incidence of DDH between infants born in the breech versus vertex position (Chi-square and Fisher's exact tests). The sensitivity, specificity, and positive and negative predictive values of breech presentation in detecting DDH were 33, 72, 0.47, and 99.6%, respectively. Conclusion There is no association between breech presentation and DDH in preterm infants <35 weeks' gestation. Obtaining hip ultrasounds on preterm infants <35 weeks' gestation born in the breech presentation with a normal hip examination is not recommended.

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.

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.

AbstractThis review presents the effects of delayed umbilical cord clamping on neonatal transitional physiology. The effects of delayed cord clamping on short- and long-term neonatal outcomes are then discussed. There is ample evidence over the last 50 years that delayed cord clamping in preterm infants is beneficial for both short-term and long-term outcomes. Providing ventilation in the initial steps of neonatal resuscitation prior to clamping of the umbilical cord has a physiologic basis and results in better outcomes for newborns. The challenge now is to design equipment and strategies that can allow initial resuscitation very close to the mother while the umbilical cord is still attached to the placenta.

BACKGROUND AND OBJECTIVES:Unplanned extubation can be a significant event that places the patient at risk for adverse events. Our goal was to reduce unplanned extubations to <1 unplanned extubation per 100 patient-intubated days.METHODS:All unplanned extubations in the NICU beginning in October 2009 were audited. Data collected included time of day, patient weight, and patient care activity at the time of the event. Bundles of potentially better practices were implemented in sequential Plan-Do-Study-Act cycles. Rates of unplanned extubation (number per patient-intubated day) for each month were analyzed by using control charts, and causes of unplanned extubation were analyzed by using Pareto charts.RESULTS:We found a significant decrease in the unplanned extubation rate after implementation of the first bundle of potentially better practices in May 2010 (2.38 to 0.41 per 100 patient-intubated days). Several more Plan-Do-Study-Act cycles were conducted to sustain this improvement. A persistent reduction in the unplanned extubation rate (0.58 per 100 patient-intubated days) began in February 2013. Causes included dislodgement during care and procedures and variation in the fixation of the endotracheal tube. The majority of events occurred in very low birth weight infants during the daytime shift.CONCLUSIONS:Unplanned extubations in the NICU can be reduced by education of staff and by implementing standard practices of care. Sustainability of any practice change to improve quality is critically dependent on culture change within the NICU. We suggest that the benchmark for unplanned extubation should be a rate <1 per 100 patient-intubated days.

Mucosal immunity is an important mechanism in the response to injury. Our hypothesis is that surfactant protein A (SP-A) is an autocrine factor that stimulates alveolar type II epithelial cell release of neutrophil chemotactic factors by binding to the SP-A receptor expressed by these cells. We examined (1) the effect of SP-A (20 μg/ml) or IL-1β (10 ng/ml) on release of neutrophil chemotactic factors by primary cultures of type II cells or alveolar macrophages, and (2) the effect of intratracheal instillation of the blocking antibody to the SP-A receptor on the response to oleic acid-induced lung injury in vivo. All media and cell culture supernates were assayed for neutrophil chemotactic activity, and bronchoalveolar lavage fluid from the in vivo experiments was analyzed for inflammatory cell counts. While SP-A and media used for the cell cultures has no intrinsic neutrophil chemotactic activity, supernates from primary cultures of type II cells incubated in either SP-A or IL-1β had twofold higher neutrophil chemotactic factor activity compared to supernates from controls. SP-A had no effect on release of neutrophil chemotactic factor by alveolar macrophages. Oleic acid-induced lung injury resulted in a marked influx of neutrophils into BAL, and this influx was reduced by 70% by pretreatment with the antibody to SP-A receptor. We conclude that SP-A stimulates the release of neutrophil chemotactic factor by alveolar type II cells, and this effect is mediated by the receptor for SP-A specifically expressed by these cells.

Developmental Regulation of the SP-A Receptor (SP-AR) by Bombesin and Trans-retinoic Acid (tRA) in Rat Lung

Apoptosis has been shown to be involved in several processes during embryogenesis, but the ontogeny of apoptosis during lung development has not been studied. The goals of the current study were to determine if apoptosis occurs during lung development, and to determine the ontogeny of the changes in apoptosis that occur. We studied the ontogeny of apoptosis in vivo using lungs from 14-18-d gestation fetal rats, newborn rats, and 1-d-, 2-d-, 5-d-, and 10-d-old rat pups. Apoptosis was assessed by electron microscopy and the terminal deoxyribonucleotidyl transferase dUTP nick end-labeling assay. We compared the in vivo results with explants of 14-d gestation fetal rat lung placed in culture for 1-4 d because the biochemical development of the lung in organ culture has been shown to closely parallel the development of the lung in vivo. We found apoptosis of mesenchymal cells at the periphery of distal lung buds in early fetal lung(14-16-d gestation). Apoptosis of both mesenchyme and epithelium was present in later fetal lung (18-d gestation). There were no qualitative differences in apoptosis between in vivo fetal lung and explant cultures of fetal lung. There was a 14-fold increase in apoptosis at birth and in the first postnatal day of life (9-12% of cells) compared with fetal lung (0.6-1% of cells). This was followed by a rapid decline in the percentage of apoptotic cells to fetal levels at postnatal d 2-10. We conclude that apoptosis occurs in a spatially, temporally, and cell-specific manner during lung development. The number of cells undergoing apoptosis increases dramatically in the first day after birth.

There are no reliable predictors of gentamicin (G) levels in premature infants. As G is excreted by the kidneys, we hypothesized G levels can be predicted by urine output. We conducted a retrospective study of neonates(gestational age (GA)=30-36wks, n=18) who received G therapy (3 mg/kg/day). Infants with a diagnosis of acute tubular necrosis, asphyxia, hypotension or who received vasopressor support or indomethacin were excluded. We collected data on GA, body weight, urine output (UOP, cc/m2/hr), fluid intake and output(I/O), G intervals/route, body surface area, G levels and day of life G levels drawn. Data were analyzed by student's test, chi square test, correlation coefficient as appropriate. Results showed urine output ≥2 and ≤4.0 cc/k/hr predicted therapeutic G levels (peak= 5-10 mcg/mL) in premature infants (sensitivity 0.69, specificity 1 and positive predictive value 1). Urine output >4 cc/k/hr resulted in levels < 5 mcg/mL. There were significant inverse correlations between peak G levels and UOP (Fig 1) and balance of I/O (Fig 2). We conclude that urine output, 24hrs prior to G level measurement, is a non-invasive, highly predictive parameter of adequacy of dose. We also conclude that the inverse correlation of peak G levels with urine output reflects the change in volume of distribution (balance of I/O).

Oleic acid (OA) causes reversible lung injury which resolves in 5-7 days. This injury is characterized by inflammatory cell infiltration, changes in surfactant phospholipids and derangements in pulmonary function which peaks at 4-24 h after injury and begins to resolve by 72 h without permanent damage to alveolar epithelium. Surfactant protein A (SP-A) has been shown to be involved in pulmonary defense during lung inflammation, and SP-A may also be a proinflammatory mediator. Our hypothesis is that OA causes a reversible change in SP-A production and/or release and that SP-A may be involved in the reversible injury that occurs after OA administration. Adult rats were treated with either saline or OA i.v. after which lung lavage was collected at 1, 4, 24, 72h and 120h. Lungs were also removed. Lavage samples were centrifuged, to remove debris and cells, and then concentrated 15-fold. Lungs were homogenized and protein content was measured. Equivalent amounts of lung lavage and lung homogenates were separated by SDS-PAGE. Immunoblots were processed using polyclonal anti-rat SP-A antibody, and SP-A bands were analyzed by densitometry. There was a decrease in SP-A protein levels in lavage at 1, 4, and 24 hours after OA injury. Levels returned to normal by 72 h after injury. In contrast there was an increase in SP-A protein levels in lung homogenates at 1, 4, 24 and 72 hours after OA injury. The peak response was a 2-fold increase over controls at 4-24 h. We conclude that OA injury inhibits release of SP-A during the acute injury phase which resolves as the injury heals. It is possible that OA directly inhibits secretion of SP-A by type II cells and Clara cells. Alternatively, OA may cause release of both proinflammatory and antiinflammatory cytokines which in turn affect SP-A release. We speculate that the decreased release of SP-A (with known inflammatory actions) into the alveolus may be involved in the reversibilty of the OA injury. Funded in part by NIH grant HL-49099 (MJK).

The type II alveolar epithelial cell synthesizes and secretes pulmonary surfactant. Terbutaline enhances phospholipid release from adult and fetal type II cells. Our hypothesis is that the actin network of microfilaments regulates the secretory activity of the type II cell. To examine the developmental regulation of the changes in actin subfractions associated with secretory activity, cultures of type II cells derived from adult and 19-d fetal rat lung were incubated with or without 10 μM terbutaline for 1, 30, and 60 min. Dose-response effects of terbutaline were examined in adult type II cells. Effects of phorbol ester were also examined. Globular (G-actin) and filamentous (F-actin) fractions were extracted from the cells and analyzed separately. Specified cellular equivalent volumes of each subfraction were analyzed by Western blotting, visualized by a color reaction, and quantified by densitometry. There was a decrease in the cytoskeletal F-actin pool along with an increase in the G-actin fraction within 1 min in adult type II cells exposed to terbutaline, indicating that depolymerization of F-actin occurs. Values returned to control levels by 60 min. In contrast, the decrease in F-actin, with a concomitant increase in G-actin, was maximal at 60 min in fetal cells exposed to terbutaline. There was a dose-dependent increase in actin depolymerization with maximal effects at 10 μM terbutaline. Phorbol ester also caused an increase in actin depolymerization. Depolymerization of the actin microfilament network may regulate transport and exocytosis of lamellar bodies in type II cells. We speculate that there is an early secretory mechanism that involves depolymerization of actin microfilaments and a late, actin-independent secretory mechanism present in adult type II cells. The timing of the response of the actin-dependent pathway is developmentally regulated. This may explain the developmental differences in the secretion of surfactant that we have previously shown.

The lectin, Maclura pomifera agglutinin (MPA), binds to alpha-galactose residues of glycoproteins on the apical surface of type II alveolar cells. It has recently been shown to bind to macrophages. We isolated the cell surface glycoprotein, which binds the MPA lectin, from fetal and adult rat whole lung to determine if changes in this glycoprotein occur during development from fetal to adult life. The glycoprotein was purified from whole lung cell membranes by lectin affinity chromatography that resulted in 10(5)-fold enrichment. The MPA binding glycoproteins from both fetal and adult lung had the same apparent molecular weight of 170 kD as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Amino acid analysis revealed similar composition of the fetal and adult proteins. Two-dimensional peptide maps of the 170 kD proteins isolated from fetal and adult lung were also similar. These data indicate that the glycoprotein that binds MPA to lung cell membranes does not change during this stage of development. Our method for the isolation of this glycoprotein can be used for the generation of antibodies or other molecular probes for further study of this protein.

Several studies have shown a lack of effect of indomethacin therapy for the closure of a patent ductus arteriosus (PDA) in premature infants over 14 days of postnatal age. In this report we describe two cases in which a hemodynamically significant PDA was closed with indomethacin in preterm infants over 20 days of age. The response to indomethacin may be more related to postconceptual age than to actual postnatal age. We suggest that intravenous indomethacin therapy should be attempted before surgical ligation is performed in those premature infants under 34 weeks postconceptual age who have a hemodynamically significant patent ductus arteriosus.

D'apres cette etude sur 108 enfants a l'aide d'un thermometre a mercure, la temperature de la peau axillaire est variable. La specificite de la temperature prise a ce niveau est de 97,7% mais la sensibilite de cette mesure pour la detection d'une fievre est faible, la valeur predictive est pauvre et cette technique n'est pas recommandee en consultation

Bronchopulmonary dysplasia (BPD) is a prevalent morbidity associated with prematurity. In 2005, the incidence of BPD in VLBW infants our NICU was 61%, greater than the 75th %ile for the Vermont-Oxford Network (VON). A QI project was initiated in 2006, with an aim to develop a bundle of potentially better practices to reduce the incidence of BPD by 50%. At this time, our project continues, with a current goal of further reducing the incidence of BPD in our NICU, so that we perform in the 10th25th %ile within the VON.