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Background: Data on clinical outcomes of infants with birthweights less than 501 g (ELBW <501 ) are limited., Objective: To evaluate management strategies and clinical outcomes of ELBW <501 infants compared to infants weighing 501-750 g (ELBW 501-750 )., Methods: A retrospective study of all ELBW <501 and ELBW 501-750 infants born between 2012 and 2022 at a center utilizing first intention high frequency jet ventilation was performed. Patient characteristics, clinical and outcome data were compared between the two groups., Results: A total of 358 infants (92 ELBW <501 infants and 266 ELBW 501-750 ) were included. The survival rate for the ELBW <501 group was 60.9% compared to 86.5% for ELBW 501-750 . ELBW <501 infants required more frequent use of 2.0 mm endotracheal tubes, required higher FiO 2 and longer duration of mechanical ventilation. Compared to ELBW 501-750 group, the ELBW <501 group were more likely to be SGA (68.2% vs. 16.5%) and more premature (23.2 vs. 24.3 weeks) with lower survival, longer length of stay, higher incidence of ROP and lower weight at discharge but comparable rates of IVH, grade 3 BPD, discharged on supplemental oxygen, and tracheostomy., Conclusion: ELBW <501 infants are at risk for significant morbidity and mortality. However, with specialized obstetric and neonatal care, survival rates of 60% are possible with respiratory outcomes comparable to ELBW 501-750 infants. However, the increased risk of severe ROP for ELBW <501 requiring either surgical or medical intervention is concerning and warrants optimal surveillance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Elgin, Berger, Kaluarachchi, Dagle, Thomas, Colaizy and Klein.)

Neonatal capillary leak syndrome (CLS) is a rare, but life-threatening condition following neonatal sepsis or inflammatory injury. The objective of this study was to describe a standardized treatment approach for CLS that improves mortality and neonatal outcomes. A retrospective cohort study of 10 infants born at 22 to 26 weeks of gestation who developed CLS following a significant inflammatory insult was performed. Time to diagnosis and treatment approaches over 2 epochs were recorded and described. In epoch 2, with increased clinical awareness of CLS and implementation of a standardized treatment approach, there was a non-statistically significant decrease in the time to treatment with a significant decrease in mortality. An early targeted treatment approach for neonatal CLS can decrease mortality rates in this highly morbid condition., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Advances in ventilation strategies for infants in the NICU have led to increased survival of extremely preterm infants. More than 75% of infants born at less than or equal to 27 weeks' gestation require initial mechanical ventilation for survival due to developmental immaturity of their lungs and respiratory drive. Various ventilators using different technologies and involving multiple management strategies are available for use in this population. Centers across the world have successfully used conventional, high-frequency oscillatory and high-frequency jet ventilation to manage respiratory failure in extremely preterm infants. This review explores the existing evidence for each mode of ventilation and the importance of individualizing ventilator management strategies when caring for extremely preterm infants., (Copyright © 2022 by the American Academy of Pediatrics.)

Information regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in premature infants remains limited. Early in the pandemic, several studies reported that the risk of infection in infants was relatively small and that affected infants had a milder disease than what was seen in adults. Since the increase of the delta variant (SARS-CoV-2 B.1.617.2) within the population, there have been increased reports of more severe disease in infants. We present 3 cases of premature, very low birth weight infants with confirmed SARS-CoV-2 infection who presented with significant hyperglycemia and bone marrow dysfunction. Two infants had presumed vertical transmission, and 1 infant was infected by respiratory transmission. Despite the mode of transmission, symptom onset and duration were similar in all infants. All resolved with symptomatic management. In the context of the continuing pandemic, evaluation for SARS-CoV-2 infection should be considered in premature very low birth weight infants who demonstrate certain patterns of acute metabolic and hematologic abnormalities., (Copyright © 2022 by the American Academy of Pediatrics.)

Purpose of Review: Ventilation of periviable infants born at 22-23 weeks gestation remains a challenge in neonatology. This review highlights the evidence surrounding the use of first intention high-frequency jet ventilation (HFJV) in infants born near the limits of viability with a review of pulmonary fetal development and a focused overview of HFJV strategies including an in-depth analysis of the management strategies used in the initial randomized trials., Recent Findings: A paucity of recent trials exists, with no randomized control trials assessing the use of first intention HFJV performed in the last 25 years. A retrospective observational cohort trial of the use of HFJV for infants born at less than 750 g has been recently published demonstrating the efficacy of HFJV for this population even with 2.0-mm endotracheal tubes., Summary: The lack of recent randomized trials contributes to the controversy surrounding the use of first intention HFJV. Although new research is needed in the area, this review includes the ventilation strategy of an experienced center with a focus on the use of first intention HFJV for the care of premature infants born less than 24 weeks gestation., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The approach to clinical care of infants born at 22 weeks' gestation must be consistent and well-designed if optimal results are to be expected. Publications from several international centers have demonstrated that, although there may be variance in aspects of care in this vulnerable population, treatment should be neither random nor inconsistent. In designing a standardized approach, careful attention should be paid to the unique anatomy, physiology, and biochemistry of this vulnerable patient population. Emerging evidence, suggesting a link between cardiopulmonary health and longer-term sequela, highlights the importance of understanding the relationship between cardiorespiratory illnesses of the 22-week infant, treatments provided, and subsequent cardiopulmonary development. In this review we will provide an overview to our approach to cardiopulmonary assessment and treatment, with a particular emphasis on the importance of early recognition of atypical phenotypes, timely interventions with evidence-based treatments, and longitudinal monitoring., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To compare survival and short-term respiratory outcomes of infants weighing <750 g initially intubated with 2.0 mm versus 2.5 mm endotracheal tube (ETT)., Study Design: Retrospective, observational cohort study., Results: Of 149 inborn infants weighing <750 g admitted to the NICU, 69 (46%) were intubated with 2.0 mm ETT, 78 with 2.5 mm ETT (53%), and 2 infants never required intubation. Infants intubated with 2.0 mm ETT were more premature (median gestational age (GA) 23 weeks (22, 24) vs. 24 weeks (24, 25) p < 0.0001), smaller (median birth weight 545 g (450, 616) vs. 648 g (579, 700), p < 0.0001), and more frequently intubated at delivery (96% vs. 68%, p < 0.00001). Survival to discharge was similar 77%, 53/69 and 87%, 68/78 (p = 0.09). Adjusted for GA, there were no significant differences in ventilator days (p = 0.7338) or Grade 3 BPD., Conclusions: Premature infants born at a median GA of 23 weeks and median birth weight of 545 g can be successfully managed with 2.0 mm ETT., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Chorioamnionitis is a common precipitant of preterm birth and is associated with many of the morbidities of prematurity, including necrotizing enterocolitis (NEC). However, a mechanistic link between these two conditions remains yet to be discovered. We have adopted a murine model of chorioamnionitis involving lipopolysaccharide (LPS)-induced fetal exposure to maternal inflammation (FEMI). This model of FEMI induces a sterile maternal, placental, and fetal inflammatory cascade, which is also present in many cases of clinical chorioamnionitis. Although models exist that utilize live bacteria and more accurately mimic the pathophysiology of an ascending infection resulting in chorioamnionitis, these methods may cause indirect effects on development of the immature intestinal tract and the associated developing microbiome. Using this protocol, we have demonstrated that LPS-induced FEMI results in a dose-dependent increase in pregnancy loss and preterm birth, as well as disruption of normal intestinal development in offspring. Further, we have demonstrated that FEMI significantly increases intestinal injury and serum cytokines in offspring, while simultaneously decreasing goblet and Paneth cells, both of which provide a first line of innate immunity against intestinal inflammation. Although a similar model of LPS-induced FEMI has been used to model the association between chorioamnionitis and subsequent abnormalities of the central nervous system, to our knowledge, this protocol is the first to attempt to elucidate a mechanistic link between chorioamnionitis and later perturbations in intestinal development as a potential link between chorioamnionitis and NEC.

The COVID-19 pandemic represents the greatest challenge to date faced by the medical community in the 21st century. The rate of rapid dissemination, magnitude of viral contagiousness, person to person transmission at an asymptomatic phase of illness pose a unique and dangerous challenge for all patients, including neonatal and obstetric patients. Although scientific understanding of the pathophysiology of the disease, nature of transmission, and efficacy of mitigation strategies is growing, neither a cure or vaccine have been developed. While COVID-19 is primarily a disease of older patients, infection is now seen across all age demographics with reports of illness in pregnant patients and infants. Altered hormone status and predominance of Th-2 immune helper cells may result in increased predisposition to SARS-CoV-2. Case reports of pregnant patients demonstrate a clinical presentation comparable to non-pregnant adults, but evidence of vertical transmission to the fetus is controversial. Neonatal reports demonstrate an inconsistent and non-specific phenotype, and it is often difficult to separate COVID-19 from the underlying conditions of prematurity or bacterial infection. The development of international registries to enable risk profiling of COVID-19 positive pregnant mothers and/or their offspring may facilitate the development of enhanced mitigation strategies, medical treatments and effective vaccinations.

Fetal exposure to chorioamnionitis can impact the outcomes of the developing fetus both at the time of birth and in the subsequent neonatal period. Infants exposed to chorioamnionitis have a higher incidence of gastrointestinal (GI) pathology, including necrotizing enterocolitis (NEC); however, the mechanism remains undefined. To simulate the fetal exposure to maternal inflammation (FEMI) induced by chorioamnionitis, pregnant mice (C57BL/6J, IL-6 -/- , RAG -/- or TNFR1 -/- ) were injected intraperitoneally on embryonic day (E)15.5 with lipopolysaccharide (LPS; 100 µg/kg body weight). Pups were delivered at term, and reared to postnatal day (P)0, P7, P14, P28 or P56. Serum and intestinal tissue samples were collected to quantify growth, inflammatory markers, histological intestinal injury, and goblet and Paneth cells. To determine whether FEMI increased subsequent susceptibility to intestinal injury, a secondary dose of LPS (100 µg/kg body weight) was given on P5, prior to tissue harvesting on P7. FEMI had no effect on growth of the offspring or their small intestine. FEMI significantly decreased both goblet and Paneth cell numbers while simultaneously increasing serum levels of IL-1β, IL-10, KC/GRO (CXCL1 and CXCL2), TNF and IL-6. These alterations were IL-6 dependent and, importantly, increased susceptibility to LPS-induced intestinal injury later in life. Our data show that FEMI impairs normal intestinal development by decreasing components of innate immunity and simultaneously increasing markers of inflammation. These changes increase susceptibility to intestinal injury later in life and provide novel mechanistic data to potentially explain why preterm infants exposed to chorioamnionitis prior to birth have a higher incidence of NEC and other GI disorders., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature host-microbial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the bloom of Enterobacteriaceae species that occurs is phenotypically similar to what is seen in human NEC. This further strengthens our understanding of the importance of Paneth cells to intestinal homeostasis in the immature intestine., Competing Interests: The authors have declared that no competing interests exist.

Problem: Premature birth complicates 10%-12% of deliveries. Infection and inflammation are the most common etiologies and are associated with increased offspring morbidity and mortality. We hypothesize that lipopolysaccharide (LPS)-induced maternal inflammation causes direct placenta injury and subsequent injury to the fetal intestine., Method of Study: Pregnant C57Bl6 mice were injected intraperitoneally on day 15.5 with 100 μg/kg LPS or saline. Maternal serum, amniotic fluid, placental samples, and ileal samples of offspring were obtained assessed for inflammation and/or injury. Maternal placental ultrasounds were performed. Placental DNA was isolated for microbiome analysis., Results: Maternal injection with LPS caused elevated IL-1β, IL-10, IL-6, KC-GRO, and TNF. Placental tissue showed increased IL-1β, IL-6, and KC-GRO and decreased IL-10, but no changes were observed in amniotic fluid. Placental histology demonstrated LPS-induced increases in mineralization and necrosis, but no difference in placental blood flow. Most placentas had no detectable microbiome. Exposure to maternal LPS induced significant injury to the ilea of the offspring., Conclusion: Lipopolysaccharide causes a maternal inflammatory response that is mirrored in the placenta. Placental histology demonstrates structural changes; however, placental blood flow is preserved. LPS also induces an indirect intestinal injury in the offspring that lasts beyond the neonatal period., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Neonatal necrotizing enterocolitis (NEC) remains the most devastating gastrointestinal disease for premature infants. In the United States alone, NEC affects >4000 premature infants yearly, has a mortality rate of nearly 33%, and costs the health care system >$1 billion annually. Although NEC has been actively researched for several decades, its pathophysiology remains elusive. One potential mechanism suggests that disruption of the normal neonatal intestinal bacterial flora induces a proinflammatory state, allowing translocation of pathogens across the intestinal epithelia. Disruption of the normal intestinal flora (dysbiosis) is associated with many human diseases. Thus, it is a reasonable hypothesis that dysbiosis may play an important role in the development of NEC. This hypothesis is supported by evidence that probiotic use in premature infants can prevent the development of NEC. Although the role of probiotics and NEC is covered in other reviews, this review instead focuses on normal bacterial colonization in both term and preterm infants and on the association of dysbiosis and the development of NEC., Methods: PubMed was queried with the use of the following key search terms: NEC, neonatal microbiome, fetal microbiome, maternal microbiome, neonatal dysbiosis, and microbiome ontogeny. Relevant literature was reviewed and selected for inclusion in accordance with the objectives of the article according to the authors' discretion. Articles that made key salient points in review articles were further pulled from PubMed., Findings: Although the onset of NEC is thought to involve bacteria, the mechanisms behind their involvement remain unclear. Research to date has failed to identify a single causative organism, and current theories and data now indicate that a disruption of the host intestinal flora is associated with the onset of disease. Recent reports have found that a bloom of Proteobacteria, specifically Enterobacteriacae species, occurs just before the diagnosis of NEC. Whether this is a causative event or merely a marker of intestinal disease is still unclear., Implications: Because of the complexity of these interactions, it is vital that we continue to investigate the host-bacterial axis in the developing intestine in both humans and in animal models., (Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.)