Acute Respiratory Distress Syndrome in a Preterm Pregnant Patient With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Data suggest that pregnant women are not at elevated risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or developing severe disease compared with nonpregnant patients. However, management of pregnant patients who are critically ill with coronavirus disease 2019 (COVID-19) infection is complicated by physiologic changes and other pregnancy considerations and requires balancing maternal and fetal well-being. CASE: We report the case of a patient at 28 weeks of gestation with acute respiratory distress syndrome (ARDS) from COVID-19 infection, whose deteriorating respiratory condition prompted delivery. Our patient's oxygenation and respiratory mechanics improved within hours of delivery, though she required prolonged mechanical ventilation until postpartum day 10. Neonatal swabs for SARS-CoV-2 and COVID-19 immunoglobulin (Ig) G and IgM were negative. CONCLUSION: We describe our multidisciplinary management of a preterm pregnant patient with ARDS from COVID-19 infection and her neonate.

The neurointensive nursery: concept, development, and insights gained.

PURPOSE OF REVIEW: With the advent of therapeutic hypothermia for treatment of hypoxic ischemic encephalopathy, and improvements in neuroimaging and bedside neuromonitoring, a new era of neonatal brain-focused care has emerged in recent years. We describe the development of the first neurointensive care nursery (NICN) as a model for comanagement of neonates with identified neurologic risk factors by a multidisciplinary team constituted of neurologists, neonatologists, specialized nurses, and others with the goal of optimizing management, preventing secondary injury and maximizing long-term outcomes. RECENT FINDINGS: Optimizing brain metabolic environment and perfusion and preventing secondary brain injury are key to neurocritical care. This includes close management of temperature, blood pressure, oxygenation, carbon dioxide, and glucose levels. Early developmental interventions and involvement of physical and occupational therapy provide additional assessment information. Finally, long-term follow-up is essential for any neurocritical care program. SUMMARY: The NICN model aims to optimize evidence-based care of infants at risk for neurologic injury. Results from ongoing hypothermia and neuroprotective trials are likely to yield additional treatments. New technologies, such as functional MRI, continuous neurophysiological assessment, and whole genomic approaches to rapid diagnosis may further enhance clinical protocols and neonatal precision medicine. Importantly, advances in neurocritical care improve our ability to provide comprehensive information when counseling families. Long-term follow-up data will determine if the NICN/Neuro-NICU provides enduring benefit to infants at risk for neurologic injury.

Outcome After Therapeutic Hypothermia in Term Neonates With Encephalopathy and a Syndromic Diagnosis.

The large randomized, controlled trials of therapeutic hypothermia for hypoxic-ischemic encephalopathy excluded neonates with congenital disorders. The objective of this study was to report our experience using hypothermia in neonates with signs of hypoxic-ischemic encephalopathy and a syndromic disorder or brain anomaly. Subjects were identified from a database of neonates admitted to the Neuro-Intensive Care Nursery at University of California, San Francisco. Of 169 patients fulfilling criteria for hypothermia, 8 (5%) had a syndromic disorder and were cooled per guidelines for nonsyndromic neonates. Perinatal characteristics of infants with and without syndromic disorder were not significantly different. Overall outcome was poor: 38% had evidence of acute hypoxic-ischemic injury, 3 subjects died, and 2 survivors had low developmental quotient (ie, 25). The risk versus benefit of therapeutic hypothermia for hypoxic-ischemic encephalopathy among neonates with congenital brain malformations or syndromic diagnoses is uncertain.

A randomized clinical trial of therapeutic hypothermia mode during transport for neonatal encephalopathy.

OBJECTIVE: To determine if temperature regulation is improved during neonatal transport using a servo-regulated cooling device when compared with standard practice. STUDY DESIGN: We performed a multicenter, randomized, nonmasked clinical trial in newborns with neonatal encephalopathy cooled during transport to 9 neonatal intensive care units in California. Newborns who met institutional criteria for therapeutic hypothermia were randomly assigned to receive cooling according to usual center practices vs device servo-regulated cooling. The primary outcome was the percentage of temperatures in target range (33°-34°C) during transport. Secondary outcomes included percentage of newborns reaching target temperature any time during transport, time to target temperature, and percentage of newborns in target range 1 hour after cooling initiation. RESULTS: One hundred newborns were enrolled: 49 to control arm and 51 to device arm. Baseline demographics did not differ with the exception of cord pH. For each subject, the percentage of temperatures in the target range was calculated. Infants cooled using the device had a higher percentage of temperatures in target range compared with control infants (median 73% [IQR 17-88] vs 0% [IQR 0-52], P < .001). More subjects reached target temperature during transport using the servo-regulated device (80% vs 49%, P <.001), and in a shorter time period (44 ± 31 minutes vs 63 ± 37 minutes, P = .04). Device-cooled infants reached target temperature by 1 hour with greater frequency than control infants (71% vs 20%, P < .001). CONCLUSIONS: Cooling using a servo-regulated device provides more predictable temperature management during neonatal transport than does usual care for outborn newborns with neonatal encephalopathy.

Extensive subcutaneous fat necrosis of the newborn associated with therapeutic hypothermia.

Subcutaneous fat necrosis of the newborn is a form of panniculitis that most often occurs in full-term infants with predisposing risk factors. Three neonates with hypoxic ischemic encephalopathy were treated with therapeutic hypothermia and developed extensive subcutaneous fat necrosis. All three infants developed extensive subcutaneous fat necrosis, involving the back, scalp, and arms. Mild, asymptomatic hypercalcemia was noted in one infant in the weeks following the subcutaneous fat necrosis. Hypothermia as a risk factor for subcutaneous fat necrosis is reviewed. Clinicians should be aware of subcutaneous fat necrosis as a possible risk factor and complication associated with asphyxiated newborns who may undergo therapeutic hypothermia. Future studies for therapeutic hypothermia should evaluate neonates for the development of subcutaneous fat necrosis.

Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary lipidosis.

We show that mice lacking the ATP-binding cassette transmembrane transporter ABCG1 show progressive and age-dependent severe pulmonary lipidosis that recapitulates the phenotypes of different respiratory syndromes in both humans and mice. The lungs of chow-fed Abcg1(-/-) mice, >6-months old, exhibit extensive subpleural cellular accumulation, macrophage, and pneumocyte type 2 hypertrophy, massive lipid deposition in both macrophages and pneumocytes and increased levels of surfactant. No such abnormalities are observed at 3 months of age. However, gene expression profiling reveals significant changes in the levels of mRNAs encoding key genes involved in lipid metabolism in both 3- and 8-month-old Abcg1(-/-) mice. These data suggest that the lungs of young Abcg1(-/-) mice maintain normal lipid levels by repressing lipid biosynthetic pathways and that such compensation is inadequate as the mice mature. Studies with A-549 cells, a model for pneumocytes type 2, demonstrate that overexpression of ABCG1 specifically stimulates the efflux of cellular cholesterol by a process that is dependent upon phospholipid secretion. In addition, we demonstrate that Abcg1(-/-), but not wild-type macrophages, accumulate cholesterol ester droplets when incubated with surfactant. Together, these data provide a mechanism to explain the lipid accumulation in the lungs of Abcg1(-/-)mice. In summary, our results demonstrate that ABCG1 plays essential roles in pulmonary lipid homeostasis.

Interleukin (IL)-1 beta in tracheal aspirates from premature infants induces airway epithelial cell IL-8 expression via an NF-kappa B dependent pathway.

Tracheal aspirate IL-8 concentration and airway epithelial cell IL-8 expression are each increased in premature infants undergoing mechanical ventilation. We sought to determine the cytokines responsible for IL-8 expression in this context. Tracheal aspirates were collected from 18 mechanically ventilated premature infants. IL-8 protein abundance was high in tracheal aspirates from ventilated premature infants (mean, 5806 +/- 4923 pg/mL). IL-1 alpha (mean, 20 +/- 6 pg/mL), IL-1 beta (mean 67 +/- 46 pg/mL), and tumor necrosis factor (TNF)-alpha (mean, 8 +/- 2 pg/mL) were also found. Incubation of tracheal aspirates with 16HBE14o- human bronchial epithelial cells increased IL-8 protein in both cell lysates and supernatants, as well as transcription from the IL-8 promoter. Aspirates also induced nuclear factor (NF)-kappa B activation. Mutation of the IL-8 promoter NF-kappa B site abolished aspirate-induced IL-8 transcription. Endotoxin concentrations in the tracheal aspirates were negligible and incapable of inducing IL-8 promoter activity. Finally, incubation of tracheal aspirates with a neutralizing antibody against IL-1 beta reduced epithelial cell IL-8 production, whereas neutralizing antibodies against IL-1 alpha and TNF-alpha had no effect. We conclude that airway fluid from mechanically ventilated premature infants contains soluble factors capable of inducing airway epithelial cell IL-8 expression via a NF-kappa B-dependent pathway, and that IL-1 beta plays a specific role in this process.