OBJECTIVE:We implemented 5 potentially better practices to limit mechanical ventilation (MV), supplemental oxygen, and bronchopulmonary dysplasia in newborn infants born before 33 weeks' gestation. METHODS:The methods used in this study included (1) exclusive use of bubble continuous positive airway pressure (bCPAP), (2) provision of bCPAP in the delivery room, (3) strict intubation criteria, (4) strict extubation criteria, and (5) prolonged CPAP to avoid supplemental oxygen. We excluded outborn infants and those with major anomalies and obstetric complications from analysis. RESULTS:Demographics were similar in 61 infants born before and 60 born after implementation. For infants born at 26 to 32 6 ⁄ 7 weeks' gestation, intubation (first 72 hours) decreased from 52% to 11% (P Ͻ .0001) and surfactant use decreased from 48% to 14% (P ϭ .0001). In all infants, the mean Ϯ SD fraction of inspired oxygen requirement (first 24 hours) decreased from 0.27 Ϯ 0.08 to 0.24 Ϯ 0.05 (P ϭ .0005), days of oxygen decreased from 23.5 Ϯ 44.5 to 9.3 Ϯ 22.0 (P ϭ .04), and days of MV decreased from 8.8 Ϯ 27.8 to 2.2 Ϯ 6.2 (P ϭ .005). Hypotension decreased from 33% to 15% (P ϭ .03). The percentage of infants with bronchopulmonary dysplasia was 17% before and 8% after (P ϭ .27). Nurse staffing ratios remained unchanged. CONCLUSIONS:Implementation of these potentially better practices reduced the need for MV, surfactant, and supplemental oxygen as well as reduced hypotension among infants born before 33 weeks' gestation without adverse consequences. The costs for equipment and surfactant were lower. Pediatrics 2011;128:e218-e226 All the authors made substantive intellectual contributions to this report. Dr Levesque contributed to the conception and design of the study, implementation, data collection, analysis, and interpretation, drafted the article, and approved the version submitted; Dr Kalish contributed to the data analysis and interpretation and critical revising of the article for important intellectual content and approved the final version submitted; and Ms LaPierre, Ms Welch, and Ms Porter participated in the conception and design, implementation, data collection and interpretation, and revising of the article and approved the version submitted.www.pediatrics.org/cgi

Early gestation lung development is characterized by branching morphogenesis of the airways and basic lung structure formation. Androgens delay late-gestation lung development if the androgen exposure begins in early gestation. We hypothesized that there would be effects of early gestation androgens on lung development. Embryonic mouse lungs (d 11.5) were cultured with dihydrotestosterone (DHT), DHT plus flutamide, or with nothing as controls. Branching morphogenesis was significantly increased after 24, 48, and 72 h of culture. This effect was blocked by simultaneous flutamide treatment. Fetal sex did not influence the DHT response. DHT increased cell proliferation as measured by [3H]thymidine incorporation into DNA. Autoradiography showed prominent [3H]thymidine labeling of epithelia and mesenchyme in regions of new bud formation. DHT treatment significantly increased the thymidine-labeling index of fibroblasts and airway epithelial cells. Programmed cell death, which is found in developing organs in association with cell proliferation during structure formation and tissue remodeling, was studied using terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling assay. In control lungs, programmed cell death occurred in the peripheral mesenchyme surrounding newly forming buds and underlying airway branch points. DHT treatment increased programmed cell death in association with increased branching morphogenesis. Evaluation of near-adjacent sections (control and DHT-treated lungs) showed that apoptotic mesenchymal cells were flanked by [3H]thymidine-labeled fibroblasts and epithelial cells, suggesting a coordination of these processes in the progression of branching morphogenesis. We conclude that androgen enhances the process of early lung morphogenesis by increasing cell proliferation and programmed cell death and by promoting the structural progression of branching morphogenesis.

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Background: Organ-specific vascular endothelial growth factor (VEGF) expression is decreased during the pathogenesis of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) several weeks before either disease can be diagnosed. Early measurement of organ-specific tissue VEGF levels might allow identification of infants at high risk for these diseases, but is not clinically feasible. Urine VEGF is easily measured and useful in early diagnosis of several diseases. Objectives: Our aims were to assess the correlation of urine VEGF levels measured in the first postnatal month with subsequent BPD or ROP diagnosis and to determine whether various infant characteristics influence urine VEGF levels. Methods: 106 subjects born at <29 weeks' gestation and surviving to 36 weeks' postmenstrual age were selected from an existing database and biorepository. Urine VEGF and total protein were measured in 2-3 samples per subject. Results: Urine VEGF/protein levels increased by 72% per week (p < 0.0001) during the first postnatal month. In multivariable analysis controlling for postnatal age, lower VEGF/protein was associated with higher levels of mechanical respiratory support (p = 0.006), male gender (p = 0.001) and early sepsis (p = 0.003) but not with fraction of inspired oxygen. Lower urine VEGF/protein and mechanical ventilation were each associated with BPD and ROP. In analyses adjusted for respiratory support, lower urine VEGF/protein and ROP remained associated but urine VEGF/protein and BPD did not. Conclusions: Low urine VEGF/protein levels in the first postnatal month are associated with mechanical ventilation, BPD, and ROP.

We launched a well-received pilot ROR program in the NICU and reached our goal of ≥50% infants being read to by their parents. Further study is needed to assess the impact of reading in the NICU on parents and infants.

Drosophila trachealess (Trl ), master regulator of tracheogenesis, has no known functional mammalian homolog. We hypothesized that genes similar to trachealess regulate lung development. Quantitative (Q)RT-PCR and immunostaining were used to determine spatial and temporal patterns of npas1 gene expression in developing murine lung. Immunostaining for ␣-smooth muscle actin demonstrated myofibroblasts, and protein gene product (PGP)9.5 identified neuroendocrine cells. Branching morphogenesis of embryonic lung buds was analyzed in the presence of antisense or sense oligodeoxynucleotides (ODN). Microarray analyses were performed to screen for changes in gene expression in antisense-treated lungs. QRT-PCR was used to validate the altered expression of key genes identified on the microarrays. We demonstrate that npas1 is expressed in murine embryonic lung. npas1 mRNA peaks early at Embryonic Day (E)10.5-E11.5, then drops to low levels. Sequencing verifies the identity of npas1 transcripts in embryonic lung. NPAS1 immunostaining occurs in nuclei of parabronchial mesenchymal cells, especially at the tracheal bifurcation. Arnt, the murine homolog of Tango (the heterodimerization partner for Trl) is also expressed in developing lung but at constant levels. npas1-or arnt-antisense ODN inhibit lung branching morphogenesis, with altered myofibroblast development and increased pulmonary neuroendocrine cells. On microarrays, we identify Ͼ 50 known genes down-regulated by npas1-antisense, including multiple genes regulating cell migration and cell differentiation. QRT-PCR confirms significantly decreased expression of the neurogenic genes RBP-Jk and Tle, and three genes involved in muscle development: ␤Ϫig-h3, claudin-11, and myocardin. Npas1 can regulate myofibroblast distribution, branching morphogenesis, and neuroendocrine cell differentiation in murine embryonic lung. Keywords: branching morphogenesis; myofibroblasts; smooth muscle actin; cell migration; neuroendocrine cells Lung morphogenesis is the result of complex interactions among multiple transcription factors, growth factors, and signaling pathways (1-4). Tracheal development in Drosophila melanogaster provides a simple model for investigating analogous genes involved in respiratory system development (5). Trachealess (trl) is the master regulatory gene because null mutation of trl leads to complete absence of the fly respiratory system (6). Trl also regulates downstream branching morphogenesis of the devel-

Objective This study aimed to describe maternal characteristics and clinical outcomes of infants born to mothers with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests during pregnancy at an urban, safety-net hospital in Boston. Study Design We abstracted electronic chart data from 75 pregnant women with positive SARS-CoV-2 tests at any stage of gestation until 72 hours after birth who delivered consecutively between March 31 and August 6, 2020 at our center. We collected clinical data on maternal and infant characteristics, including testing, signs, and symptoms of coronavirus disease 2019 (COVID-19), delivery outcomes, newborn care practices (skin-to-skin care, location of care, and breastfeeding) and 30-day postdischarge infant emergency room visits and readmissions. We described categorical characteristics as percentages for this case series. Results Among 75 pregnant women, 47 (63%) were Hispanic, 10 (13%) had hypertension, 23 (30%) had prepregnancy obesity, and 57 (76%) had symptomatic SARS-CoV-2 infection. Regarding birth outcomes, 32 (41%) had cesarean delivery and 14 (19%) had preterm birth. Among 75 infants, 5 (7%) had positive SARS-CoV-2 polymerase chain reaction tests in the first week of life, all of whom were born to Hispanic mothers with symptomatic SARS-CoV-2 infection and had clinical courses consistent with gestational age. Six (8%) infants visited the emergency department within 30 days of discharge; one was admitted with a non-COVID-19 diagnosis. Conclusion At our urban, safety-net hospital among pregnant women with positive SARS-CoV-2 tests, 41% had a cesarean delivery and 19% had a preterm birth. Seven percent of infants had one or more positive SARS-CoV-2 tests and all infants had clinical courses expected for gestational age. Key Points