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.

An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication.

Anti-hypotensive treatment, which includes dopamine, dobutamine, epinephrine, norepinephrine, milrinone, vasopressin, terlipressin, levosimendan, and glucocorticoids, is a long-established intervention in neonates with arterial hypotension (AH). However, there are still gaps in knowledge and issues that need clarification. The main questions and challenges that neonatologists face relate to the reference ranges of arterial blood pressure in presumably healthy neonates in relation to gestational and postnatal age; the arterial blood pressure level that potentially affects perfusion of critical organs; the incorporation of targeted echocardiography and near-infrared spectroscopy for assessing heart function and cerebral perfusion in clinical practice; the indication, timing, and choice of medication for each individual patient; the limited randomized clinical trials in neonates with sometimes conflicting results; and the sparse data regarding the potential effect of early hypotension or anti-hypotensive medications on long-term neurodevelopment. In this review, after a short review of AH definitions used in neonates and existing data on pathophysiology of AH, we discuss currently available data on pharmacokinetic and hemodynamic effects, as well as the effectiveness and safety of anti-hypotensive medications in neonates. In addition, data on the comparisons between anti-hypotensive medications and current suggestions for the main indications of each medication are discussed.

Intertemporal Improvement in Physicians' Perceptions of the Short-Term Adverse Outcomes of Neonatal Pain: Results of a Two-Time-Point National Survey.

Pain in early life may seriously impact neonatal outcomes. This study aimed to evaluate whether the perceptions of physicians working in neonatal intensive care units (NICUs) of the short-term adverse outcomes associated with neonatal pain have changed over a 20-year period. Self-administered questionnaires were distributed to 117 and 145 neonatologists, pediatricians, and fellows working in level III NICUs in 2000 (T1) and 2019 (T2), respectively. The questionnaire consisted of four domains, including the central nervous, cardiovascular, and respiratory systems, as well as "other systems" (metabolic/endocrine system, growth, and general condition), with 21 total items overall. Although the proportion of positive (correct) responses to the total and system-specific domain scores was significantly higher at T2 than T1, the knowledge of certain short-term adverse outcomes was suboptimal even at T2. Adjustment for cofactors confirmed the independent association of the survey time-point with the total and system-specific domain scores. Moreover, NICU type was an independent significant factor associated with the adjusted total and central nervous system scores, while young doctors had a better knowledge of adverse cardiovascular effects. Conclusions: The perceptions of NICU physicians concerning the short-term outcomes associated with neonatal pain have significantly improved over the past 20 years, although remaining knowledge gaps mandate ongoing efforts to achieve an improvement in neonatal care.

Strong Association between Inotrope Administration and Intraventricular Hemorrhage, Gestational Age, and the Use of Fentanyl in Very Low Gestational Age Infants: A Retrospective Study.

This was a single center, retrospective cohort study designed to evaluate the association between the administration of inotropes to hypotensive very low gestational age infants (VLGAI) and prenatal and neonatal risk factors. Inpatient medical records were reviewed to identify neonates treated with inotropes (treated group) and a control group for comparison. Two hundred and twenty two (222) VLGAI (less than 32 weeks' gestation) were included in the final analysis and were stratified based on timing of treatment with 83 infants (37.4%) and 139 infants (62.6%) in the treated and control groups, respectively. A total of 56/83 (67%) received inotropes for arterial hypotension during the first 3 days (early treatment subgroup) and 27/83 (32.5%) after 3 days of life (late-treated subgroup). Fentanyl, severe intraventricular hemorrhage (IVH), and gestational age (GA) were the risk factors most significantly associated with the need for inotrope use both during the first 3 days of life and the whole NICU stay, before and after adjustment for confounders. In conclusion, fentanyl, severe IVH, and GA are the risk factors most strongly associated with the need for inotrope treatment in VLGAI. Measures to modify these risk factors may decrease the need for cardiovascular medications and improve outcomes.

Changes in Physicians' Perceptions and Practices on Neonatal Pain Management Over the Past 20 Years. A Survey Conducted at Two Time-Points.

Intense research for more than three decades expelled the view that neonates do not experience pain. The aim of this survey was to investigate whether the Greek physicians involved in neonatal intensive care have changed their perceptions regarding neonatal pain, adapting their management practices to the knowledge that have emerged in the past 20-years. This study is a survey conducted at two time-points, 20 years apart. Anonymous questionnaires were distributed to 117 and 145 physicians working in neonatal intensive care units (NICUs) all over Greece in years 2000 and 2019, respectively. The response rate was 90.6 and 80.7% in 2000 and 2019, respectively. All respondents, at both time-points, believed that neonates experience pain, which has serious acute and long-term consequences, while the vast majority considered analgesia-sedation (A-S) during painful interventions as obligatory. Utilization of NICU protocols and pain assessment tools remained low although increased significantly between 2000 and 2019. The use of systemic A-S postoperatively was high at both time-points, while its implementation in infants subjected to prolonged pain, specifically mechanical ventilation, increased significantly by 2019. Systemic or local analgesia for acute procedural pain was used by lower proportions of physicians in 2019, except for the tracheal intubation. In contrast, the use of sweet solutions and non-pharmacological measures prior to or during bedside procedures significantly increased over time. Opioid administration significantly increased, while a shift from morphine to fentanyl was observed. International literature and perinatal-neonatal congresses were stated as the main sources of updating physicians' knowledge and improving management practice on neonatal pain prevention and treatment. In conclusion, Greek NICU-physicians' perceptions that neonates can experience pain with potentially serious acute and long-term consequences remained strong over the past 20 years. Although physicians' practices on neonatal pain management improved, they are still suboptimal, while significant differences exist among centers. Continuing education, globally accepted management protocols, and readily applied pain assessment tools would further improve the management of procedural pain and stress in neonates.

Clara cell secretory protein (CC16) as a peripheral blood biomarker of lung injury in ventilated preterm neonates.

The aim of this study was to assess the serum concentrations of Clara cell secretory protein (CC16) in association with acute and chronic lung injury in mechanically ventilated preterm neonates. Thirty-five preterm neonates (gestational age [GA]