Lethal COG6-CDG in neonatal patient with arachnodactyly, joint contractures, and skin manifestations: Founder mutation in the Southeastern European population?

Herein, we report a lethal case of the ultra-rare COG6-congenital disorder of glycosylation (CDG) presenting with skin manifestations (scaling and erosions) and joint contractures in a neonate of Albanian origin. The patient was homozygous for a COG6 pathogenic variant, previously reported in another three individuals of Greek, Bulgarian and Turkish descent. The presence of a founder mutation in the geographical area is possible. The index case emphasizes the need to consider CDGs in neonatal patients with skin manifestations and joint contractures, particularly patients of Southeastern European or West Asian origin.

Systematic Review and Meta-Analysis of Cardiovascular Medications in Neonatal Hypotension.

Background: Comparative studies among the various cardiovascular medications used for the treatment of neonatal hypotension are lacking. Methods: This systematic review and pairwise meta-analysis of the anti-hypotensive treatments in preterm and term infants was conducted to evaluate efficacy and impact on outcome. Electronic databases were searched up to February 2021 for relevant articles. As an extension of the current approach for study selection, a machine learning technique was used. Only randomized controlled trials (RCTs) of inotropes, pressors, volume therapy, and corticosteroids were included. Response to treatment was the primary outcome while secondary outcomes included mortality and common morbidities. Results: Nineteen RCTs involving 758 preterm and term neonates were found, and 8 treatments were evaluated. Most studies involved subjects with early hypotension associated with prematurity. Pairwise meta-analysis among treatments showed that dopamine was more effective than dobutamine regarding the response to treatment (restoration of normotension or normalization of blood pressure) (7 trials, 286 neonates, odds ratio, 3.06 [95% CI = 1.06-8.87]; I2 = 49%, very low quality of the evidence per GRADE). Comparisons of other treatments were not significant. No differences were found among regimens regarding survival and other secondary outcomes. Conclusion: In this systematic review and pairwise meta-analysis, only the comparison of dopamine versus dobutamine provided evidence for efficacy of treatment and favored dopamine. No safe conclusions could be reached in regard to other treatments. Data regarding the management of arterial hypotension in conditions other than transition after birth in preterm newborns are sparse both in preterm and term infants.

Plasma Lipidomic and Metabolomic Profiling after Birth in Neonates Born to SARS-CoV-19 Infected and Non-Infected Mothers at Delivery: Preliminary Results.

Pregnant women are among the high-risk populations for COVID-19, whereas the risk of vertical transmission to the fetus is very low. Nevertheless, metabolic alternations described in COVID-19 patients may also occur in pregnant women and their offspring. We prospectively evaluated the plasma lipidomic and metabolomic profiles, soon after birth, in neonates born to infected mothers (cases, n = 10) and in the offspring of uninfected ones at delivery (controls, n = 10). All cases had two negative tests for SARS-CoV-2 (nasopharyngeal swabs) performed 72 h apart. Blood samples were obtained within the first hours after birth. Liquid chromatography-high resolution mass spectrometry (UHPLC-TOF/MS) and gas chromatography-mass spectrometry (GC-MS) were applied for the analyses. Multivariate statistical analysis was performed for data evaluation. Changes in several plasma lipid species-classes (long-chain fatty acids phosphatidylcholines, triglycerides), and amino-acids were identified that allowed for clear discrimination between the study groups. The results of this preliminary investigation suggest that neonates born to Sars-Cov-19 positive mothers, without evidence of viral infection at birth, have a distinct plasma lipidomic and metabolomic profile compared to those of uninfected mothers. Whether these findings are reflective of maternal metabolic alternations due to the virus or a metabolic response following an unidentified neonatal infection warrants further investigation.

Use of Ceftazidime-avibactam for the Treatment of Extensively drug-resistant or Pan drug-resistant Klebsiella pneumoniae in Neonates and Children <5 Years of Age.

BACKGROUND: Emergence of extensively drug-resistant (XDR) or pan drug-resistant (PDR) Enterobacteriaceae is a major public threat especially for young patients. Treatment options for these bacteria are extremely limited with no safety data existing for neonates and children. Ceftazidime-avibactam has activity against Gram-negative bacteria producing Klebsiella pneumoniae carbapenemase, but virtually no data exist on its use in neonatal and pediatric patients. METHODS: We present a single-center case series of neonates and children <5 years treated with ceftazidime-avibactam for XDR or PDR K. pneumoniae infections until August 2018. Medical records of patients who received ceftazidime-avibactam for at least 2 days (6 doses) were reviewed. Clinical, laboratory and microbiologic data were collected using a prestructured form. Adverse events and clinical/microbiologic responses and 15- and 30-day outcome were assessed. RESULTS: In our case series, 8 patients (median age 53 days, range from 13 days to 4.5 years) received 9 courses of ceftazidime-avibactam at a dose of 62.5 mg/kg q8h for suspected or proven XDR/PDR K. pneumoniae infections including bloodstream infections (8 courses), central nervous system infections (2 courses) and urinary tract infection (1 course). All patients were critically ill and received other antibiotics prior and concomitantly with the administration of ceftazidime-avibactam. There was no treatment discontinuation due to adverse events. Clinical and microbiologic responses occurred in all patients, and no patient died by day 30. CONCLUSIONS: Administration of ceftazidime-avibactam appears to be well tolerated and efficacious against in vitro susceptible XDR or PDR Enterobacteriaceae without being associated with significant adverse events.