Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic-ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with ...high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate-to-severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third-level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic-ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life.
Background
JAM3
gene, located on human chromosome 11q25, encodes a member of the junctional adhesion molecule (JAM) family. Mutations of this gene are associated with hemorrhagic destruction of the ...brain, subependymal calcification, and congenital cataracts (HDBSCC).
Case report
Herein, we present a newborn male with a prenatal suspicion of bilateral cataracts but without fetal ultrasound findings of cortical malformations. He was postnatally diagnosed with a clinical picture of HDBSCC and Early-onset Developmental and Epileptic Encephalopathy (DEE), associated to a homozygous variant of
JAM3
gene.
Conclusion
Identification of this variant in affected individuals has implications for perinatal and postnatal management and genetic counseling. To the best of our knowledge, this is the first case reported of a child with a
JAM3
variant in Italy, from a different ethnic background than the other reported children until now (Saudi Arabian, Turkish, Afghani, and Moroccan origin). JAM3 screening could be requested in prenatal diagnosis of fetal congenital cataracts and included in Next-Generation DNA Sequencing panels.
We describe the case of a male newborn presenting with a prenatal diagnosis of persistent hyperextension of the fetal neck and severe hypotonia and respiratory insufficiency at birth. Facial ...weakness, increased serum creatine kinase levels, and abnormal feeding, together with other signs, such as severe contractures, also classically associated with congenital myopathies prompted to perform a muscle biopsy showing internal rods suggestive of a possible nemaline myopathy. These findings suggest that a careful neurological examination should be performed in infants with persistent hyperextension of the fetal neck to exclude weakness and a possible underlying muscle disorder.
Continuous glucose monitoring using subcutaneous sensors is useful in the management of glucose control in neonatal intensive care. We evaluated feasibility and reliability of a continuous glucose ...monitoring system in a population of very low birth weight neonates needing parenteral nutrition. Moreover, we presented percentiles of glycemia of the studied population.
Very low birth weight neonates were enrolled within 24 h from birth. An ENLITE sensor connected to a continuous glucose monitoring system was inserted and maintained for at least 72 h. Data obtained with the continuous glucose monitoring system and with a glucometer were compared. Calibration was performed every 12 h.
Twenty-three patients (9 males) were included. Median gestational age was 28 weeks (range 23-30) and median birth weight was 860 g (range 500-1092). A total of 299 paired glucose values were obtained. Modified Clarke Error Grid criteria for clinical significance were met. 74 and 33 episodes of hypoglycemia and hyperglycemia were detected, respectively. 31,329 values of glycemia were analyzed and the percentiles calculated.
This continuous glucose monitoring system is safe and accurate. It allows increasing the detection of hypo- and hyper-glycaemia episodes and it could be routinely used in the management of glucose infusion in very low birth weight neonates under total parenteral nutrition.
The incidence of sensorineural hearing loss (SNHL) is still high in very low birth weight (VLBW) infants. The purpose of our study was to provide the prevalence rates of SNHL and to analyze the risk ...factors of hearing impairment and changes in hearing thresholds in a cohort of VLBW infants. A retrospective observational study was conducted in our neonatal intensive care unit (NICU) from 2012 to 2016. All VLBW infants included were screened by transient evoked otoacoustic emissions (TEOAEs) and diagnostic auditory brainstem response (ABR). In total, we enrolled 316 infants and SNHL was diagnosed in 68, leading to an early incidence of 21.5% as 36 infants out of 68 improved. Finally, SNHL was confirmed in 20 patients (6.3%) who needed hearing aids. They were significantly smaller, sicker, had longer hospitalizations, and received more ototoxic therapies. Logistic regression analysis showed that gestational age (GA) influenced the association between drugs and SNHL. The results underlined how the total exposure to antibiotics is significantly associated with SNHL, even after GA correction. In conclusion, GA, birth weight and, above all, the length and complexity of NICU stay quantify the risk of SNHL and should be considered at the individual level for parent counseling.
Background: The present study was designed to assess the feasibility and reliability of a Continuous Glucose Monitoring System (CGMS) in a population of asphyxiated neonates during therapeutic ...hypothermia. Methods: This non-randomized feasibility study was conducted in the Neonatal Intensive Care Unit (NICU) facilities of Fondazione Policlinico A. Gemelli IRCSS. Infants matching the criteria for hypothermic treatment were included in this study and were connected to the CGMS (Medtronic, Northridge, CA, USA) within the first 12 h of life. Hypoglycemia was defined as a glucose value ≤ 47 mg/dL, and hyperglycemia was defined as a glucose value ≥ 180 mg/dL. Data obtained via the CGMS were compared with those obtained via a point-of-care blood glucometer (GTX). Results: The two measuring techniques were compared using the Modified Clarke Error Grid (MCEG). Sixteen infants were enrolled. The sensor had an average (standard deviation) duration of 93 (38) h. We collected 119 pairs of glycemia values (CGMVs) from the CGMS vs. GTX measurements. The CGMS detected twenty-five episodes of hypoglycemia and three episodes of hyperglycemia. All the CGMVs indicating hyperglycemia matched with the blood sample taken via the point-of-care glucometer. Conclusions: The use of a CGMS would be useful as it could detect more episodes of disglycemia than standard care. Our data show poor results in terms of the accuracy of the CGMS in this particular setting.
Background There are no guidelines regarding enteral feeding (EF) of infants with hypoxic-ischemic encephalopathy (HIE) during and shortly after therapeutic hypothermia; consequently, clinical ...practice is, to date, still variable. The objective of this study is to assess whether a minimal EF strategy during therapeutic hypothermia may be associated with a shorter time to full EF of infants with HIE and to identify the clinical variables that independently affect the time to full EF. Methods A retrospective study, covering the period from 1 January 2015 to 30 June 2022 was performed at the Neonatal Intensive Care Unit of the Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, which compared infants with HIE who received minimal EF during therapeutic hypothermia with those who did not. Results Seventy-eight infants received minimal EF during therapeutic hypothermia, while 75 did not. Infants who were fed reached full EF significantly faster than those who were not. Moreover, they received parenteral nutrition and maintained central venous lines for a shorter time. A multivariate analysis, taking into account the variable of clinical severity, confirmed that minimal EF is an independent beneficial factor for reaching full EF in a shorter time and mechanical ventilation and seizures are independent factors for a longer time to full EF. Conclusions Minimal EF during therapeutic hypothermia is associated with a shorter time to full EF in stable infants with HIE. Further prospective studies are needed to better define the enteral nutrition strategy for infants during therapeutic hypothermia, regardless of the severity of clinical conditions.
To evaluate the effect of volume guarantee (VG) combined with high-frequency oscillatory ventilation (HFOV) on respiratory and other physiological parameters immediately after lung recruitment and ...surfactant administration in HFOV elective ventilated extremely low gestational age newborns (ELGAN) with respiratory distress syndrome (RDS).
Observational study.
Tertiary neonatal intensive care unit.
Twenty-two ELGANs of 25.5 ± 1.1 weeks of gestational age requiring invasive mechanical ventilation and surfactant administration for RDS during the first 6 h of life.
All infants intubated in delivery room, were managed with elective HFOV and received surfactant after a lung recruitment manoeuver. Eleven infants received HFOV + VG and were compared with a control group of 11 infants receiving HFOV alone. HFOV was delivered in both groups by Dräger Babylog VN500 ventilator (Dräger, Lubeck, Germany).
Variations and fluctuations of delivered high-frequency tidal volume (VT
), fluctuation of pressure amplitude (ΔP) and partial pressure of CO
(pCO
) levels after recruitment manoeuver and immediately after surfactant administration, in HFOV + VG vs. HFOV ventilated infants.
There were no significant differences in the two groups at starting ventilation with or without VG. The mean applied VT
per kg was 1.7 ± 0.3 ml/kg in the HFOV group and 1.7 ± 0.1 ml/kg in the HFOV + VG group. Thirty minutes after surfactant administration, HFOV group had a significant higher VT
/Kg than HFOV + VG (2.1 ± 0.3 vs. 1.6 ± 0.1 ml/kg,
< 0.0001) with significantly lower pCO
levels (43.1 ± 3.8 vs. 46.8 ± 1.5 mmHg,
= 0.01), 54.4% of patients having pCO
below 45 mmHg. Measured post-surfactant ΔP values were higher in HFOV group (17 ± 3 cmH
O) than in HFOV + VG group (13 ± 3 cmH
O,
= 0.01).
HFOV + VG maintains pCO
levels within target range and reduces VT
delivered variations more consistently than HFOV alone after surfactant administration.
Hypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can ...affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants.
This is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO
± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system.
A total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO
comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively,
0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively,
0.522). Mean pH, pH standard deviation, mean pO
, pO
standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069-2.117).
Infants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.
The growing phenomenon of antibiotic resistance and the presence of limited data concerning the pediatric area prompted us to focus on Staphylococcus aureus infection in this study, its antibiotic ...resistance profile, and the therapeutic management of affected children. We conducted a retrospective study by collecting clinical data on infants and children with antibiogram-associated S. aureus infection. We enrolled 1210 patients with a mean age of 0.9 years. We analyzed the resistance patterns and found 61.5% resistance to oxacillin, 58.4% resistance to cephalosporins, 41.6% resistance to aminoglycosides, and 38.3% resistance to fluoroquinolones. Importantly, we found no resistance to glycopeptides, a key antibiotic for MRSA infections whose resistance is increasing worldwide. We also found that the main risk factors associated with antibiotic resistance are being aged between 0 and 28 days, the presence of devices, and comorbidities. Antibiotic resistance is a growing concern; knowing the resistance profiles makes it possible to better target the therapy; however, it is important to use antibiotics according to the principles of antibiotic stewardship to limit their spread.
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