Pulmonary injury is associated with the disruption of alveologenesis in the developing lung and causes bronchopulmonary dysplasia (BPD) in prematurely born infants. Transforming growth factor (TGF)-beta is an important regulator of cellular differentiation and early lung development, and its levels are increased in newborn lung injury. Although overexpression of TGF-beta in the lungs of newborn animals causes pathological features that are consistent with BPD, the role of endogenous TGF-beta in the inhibition of the terminal stage of lung development is incompletely understood. In this investigation, the hypothesis that O(2)-induced injury of the maturing lung is associated with TGF-beta-mediated disruption of alveologenesis and microvascular development was tested using a murine model of BPD. Here we report that treatment of developing mouse lungs with TGF-beta-neutralizing antibodies attenuates the increase in pulmonary cell phospho-Smad2 nuclear localization, which is indicative of augmented TGF-beta signaling, associated with pulmonary injury induced by chronic inhalation of 85% oxygen. Importantly, the neutralization of the abnormal TGF-beta activity improves quantitative morphometric indicators of alveologenesis, extracellular matrix assembly, and microvascular development in the injured developing lung. Furthermore, exposure to anti-TGF-beta antibodies is associated with improved somatic growth in hyperoxic mouse pups and not with an increase in pulmonary inflammation. These studies indicate that excessive pulmonary TGF-beta signaling in the injured newborn lung has an important role in the disruption of the terminal stage of lung development. In addition, they suggest that anti-TGF-beta antibodies may be an effective therapy for preventing some important developmental diseases of the newborn lung.

Objectives:To evaluate the impact of pulmonary hypertension (PH) on long-term growth and neurodevelopmental outcomes of extremely preterm infants with bronchopulmonary dysplasia (BPD).Study Design:A single-center retrospective cohort of preterm infants born at <28 weeks gestational age from 2000 to 2011 was evaluated at 3 years of age. Growth and neurodevelopmental outcomes were compared among 3 groups: non-BPD, BPD without PH and BPD with PH. BPD was defined according to oxygen demand at 36 weeks postmenstrual age. PH was diagnosed by echocardiography during the neonatal intensive care unit stay.Results:Sixty-two infants without BPD, 60 with BPD without PH and 20 with BPD with PH were analyzed. Regardless of PH status, somatic growth was smaller in both BPD groups of infants than in non-BPD infants, with further reduction in the group having BPD with PH. Furthermore, a developmental quotient of <70 was more prevalent in the BPD infants with PH than in the BPD infants without PH (odds ratio (OR): 4.37; 95% confidence interval, CI: 1.16 to 16.5). Multivariate analysis demonstrated that BPD with PH was one of the independent perinatal risk factors for developmental quotient <70 at 3 years of age (OR: 4.94, 95% confidence interval: 1.06 to 24.1).Conclusion:PH had an additional negative effect on long-term growth and neurodevelopmental outcomes of extremely preterm infants with BPD.

Background Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. Methods We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. Findings On July 1, 2019, 26% of infants (580/2,265; range, 0–100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were “rule-out” sepsis (32%) and “culture-negative” sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and “culture-negative” infections was 12 days (median; IQR, 8–14) and 7 days (median; IQR, 5–10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization ( p = 0·02). Interpretation Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. Funding Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship

Objective:To characterize the risk factors for late-onset circulatory collapse (LCC) in preterm infants responsive to corticosteroid therapy and evaluate the long-term neurological prognosis.Study Design:A retrospective case–control study for preterm infants (⩽32 weeks' gestation) admitted to our neonatal intensive care unit from 1994 through 2002.Result:Sixty-five infants (11%) were diagnosed with LCC. Infants with a shorter gestation and lower birth weight had a higher incidence of LCC. LCC infants had a significantly lower 1-min Apgar score, significantly higher incidence of severe intraventricular hemorrhage, chronic lung disease, and postnatal periventricular leukomalacia, and significantly longer duration of ventilation use, oxygen use, and hospital stay. Somatic growth at 36 weeks' postmenstrual age was poorer in infants with LCC than without LCC (controls). LCC infants were significantly more likely than controls to have cerebral palsy at 3 years.Conclusion:LCC is associated with poor neurodevelopmental outcomes. Prevention of LCC can lead to improved neurological prognoses.