Supraventricular Tachycardia in the Setting of Neonatal COVID-19 Infection: A Case Report.

BACKGROUND: COVID-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may present with a wide range of clinical presentations and a variety of symptoms in neonates. The cardiovascular manifestations that have been described in the setting of COVID-19 infection in neonates are tachycardia and hypotension, but information regarding cardiac arrhythmias is scarce, while the effect of SARS-CoV-2 on myocardial function is still not well established. CLINICAL FINDINGS: We present a case of a neonate admitted with fever and nasal congestion. PRIMARY DIAGNOSIS: The neonate was tested positive for SARS-CoV-2. Supraventricular tachycardia (SVT) was diagnosed during his hospitalization in the neonatal intensive care unit. INTERVENTIONS: The neonate was under treatment with intravenous fluid repletion, intravenous broad-spectrum antibiotics, and continuous hemodynamic monitoring. SVT resolved spontaneously, while the team was preparing application of further supportive measures with a bag of ice on the infant's face. OUTCOMES: The neonate was discharged in good condition on day 14 post-admission, with no further recurrence of SVT. Follow-up visits were scheduled with the cardiologist. PRACTICE RECOMMENDATIONS: SVT in full-term or premature neonates can be a clinical manifestation of COVID-19 infection. Both neonatologists and neonatal nurse practitioners should be prepared to deal with cardiological manifestations of COVID-19 infection in neonates.

The Role of Substance P, Neurokinin A, Neuropeptide Y, and Cortisol in Assessing Neonatal Pain.

Introduction: Our aim was to investigate biomarkers of neonatal pain and their association with two pain scales. Methods: This prospective study included 54 full-term neonates. Levels of substance P (SubP), neurokinin A (NKA), neuropeptide Y (NPY), and cortisol were recorded and two pain scales (Premature Infant Pain Profile [PIPP] and Neonatal Infant Pain Scale [NIPS]) were used. Results: A statistically significant decrease in the levels of NPY (p = 0.02) and NKA (p = 0.03) was detected. A significant increase in NIPS scale (p < 0.001) and PIPP scale (p < 0.001) postpainful intervention was also detected. There was a positive correlation between cortisol and SubP (p = 0.01), NKA and NPY (p < 0.001) and between NIPS and PIPP (p < 0.001). A negative correlation was found for NPY with SubP (p = 0.004), cortisol (p = 0.02), NIPS (p = 0.001) and PIPP (p = 0.002). Conclusions: Novel biomarkers and pain scales may help in designing an objective tool for the quantification of neonatal pain in the everyday practice.

Gaucher Disease Type 2 Manifested as Hemophagocytic Lymphohistiocytosis in a Neonate in the COVID-19 Era.

BACKGROUND: A term neonate presented with persistent severe thrombocytopenia, elevated liver enzymes, conjugated hyperbilirubinemia, hepatosplenomegaly, and mild hypotonia. OBSERVATIONS: A thorough workup for infections, congenital thrombocytopenias, and neonatal malignancies was negative. Because of increased anti-SARS-CoV-2 IgG antibodies after maternal COVID-19, multisystem inflammatory syndrome of neonates was considered and intravenous immunoglobulin was administered. The clinical condition of the neonate deteriorated and due to laboratory evidence of hyperinflammation, hemophagocytic lymphohistiocytosis was suspected, and treatment with etoposide and dexamethasone was initiated with temporary stabilization. Gaucher disease type 2 was eventually diagnosed. CONCLUSION: Gaucher disease can rarely present in neonates as hemophagocytic lymphohistiocytosis.

Difference in Mortality and Morbidity Between Extremely and Very Low Birth Weight Neonates.

Purpose: The aim of the present study was to evaluate the mortality and morbidity of extremely low (ELBW < 1,000 g) and very low birth weight neonates (VLBW: 1,000-1,500 g) hospitalized in a referral NICU of a Children's hospital. Design: A retrospective study was conducted in records of the Neonatal Unit of a tertiary care Children's hospital in Greece from January 2009 to March 2019. Sample: All neonates with birth weight ≤1,500 grams, who were all outborn, were reviewed. Main Outcome Variable: Mortality and morbidity, including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, early onset sepsis, late onset sepsis, retinopathy of prematurity (ROP), ROP treated with laser and neurological findings were investigated. Results: A total of 444 neonates (52 percent males) were analyzed. Among them, 187 (42 percent) were ELBW and 257 (58 percent) were VLBW. The mean gestational age was lower in ELBW neonates compared to VLBW (26.3 ± 2.3 vs. 29.7 ± 2.4 weeks, respectively; p < .001). Mortality was significantly higher in ELBW compared to VLBW neonates (26.7 percent vs. 7.0 percent, p < .001). Morbidity was significantly higher in ELBW compared to VLBW for respiratory distress syndrome (p < .001), bronchopulmonary dysplasia (p < .001), intraventricular hemorrhage (p < .001), periventricular leukomalacia (p < .001), necrotizing enterocolitis (p = .05), early onset sepsis (p < .001) and late onset sepsis (p = 0.001). Similarly, the incidence of ROP and ROP treated with laser was higher in ELBW compared to VLBW neonates (p < .001). Severe neurological findings during follow-up were more prevalent in ELBW compared to VLBW neonates. Finally, the incidence of eye disorders was higher in ELBW compared to VLBW (p = .05). Conclusion: Our results confirmed that ELBW have higher mortality and morbidity than VLBW neonates. Efforts should be made in order to ameliorate perinatal and neonatal care to reduce the burden of prematurity.

Validation of Greek Versions of the Neonatal Infant Pain Scale and Premature Infant Pain Profile in Neonatal Intensive Care Unit.

BACKGROUND: The Neonatal Infant Pain Scale and the Premature Infant Pain Profile have been used widely in neonatal intensive care units for pain assessment. AIM: This study reports the evaluation and validation of these scales in full-term newborns who were hospitalized in two Greek neonatal intensive care units. Evaluation and validation of the Neonatal Infant Pain Scale and the Premature Infant Pain Profile in full-term newborns who were hospitalized in two Greek neonatal intensive care units. MATERIALS AND METHODS: This is a cross-sectional study. Two neonatal intensive care units at a large General Children's Hospital in Greece. A total of 81 full-term newborns. This cross-sectional study was conducted in two neonatal intensive care units at a large General Children's Hospital in Greece. We studied 81 full-term newborns, who were exposed to various painful routine procedures. A single measurement was taken from each neonate. Two observers were present during each procedure and evaluated pain using both the Neonatal Infant Pain Scale and Premature Infant Pain Profile. Internal consistency coefficient Cronbach's α, internal class agreement coefficient, and κ factor were appropriately measured. RESULTS: The weighting of the Neonatal Infant Pain Scale and Premature Infant Pain Profile pointed out an excellent coherence between the two scales and agreement among the researchers. The internal consistency coefficient Cronbach's α was >.8 and the internal class agreement coefficient was >.98 for both scales, which indicates an excellent consistency between scales. The κ factor for Neonatal Infant Pain Scale was >.73 and for the Premature Infant Pain Profile it was >.6, which indicates a significant agreement among investigators. CONCLUSIONS: The Neonatal Infant Pain Scale and Premature Infant Pain Profile were successfully adjusted in Greek standards with reliability between the scales and among the researchers. Moreover, they constitute reliable tools for the evaluation of neonatal procedural pain in full-term newborns in Greece.

Expression of leukotriene biosynthetic enzymes in tonsillar tissue of children with obstructive sleep apnea: a prospective nonrandomized study.

IMPORTANCE: Cysteinyl leukotrienes (CysLTs) potentially promote adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). Previous studies have identified CysLTs and their receptors in tonsillar tissue from children with OSA. OBJECTIVE: To demonstrate expression of the leukotriene biosynthetic enzymes 5-lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP), leukotriene A(4) hydrolase (LTA(4)H), and leukotriene C(4) synthase (LTC(4)S) in T and B tonsillar lymphocytes from pediatric patients with OSA. It was hypothesized that children with OSA have greater expression of biosynthetic enzymes for CysLTs (5-LO, FLAP, and LTC(4)S) in their tonsillar tissue than do children with recurrent tonsillitis (RT), who were enrolled as controls. DESIGN, SETTING, AND PARTICIPANTS: This prospective, nonrandomized study was performed at a tertiary care university hospital on 13 children with OSA and adenotonsillar hypertrophy undergoing adenotonsillectomy and 12 children without OSA also undergoing tonsillectomy for RT. Tonsillar tissue from children with OSA or RT was examined for 5-LO, FLAP, LTA(4)H, and LTC(4)S expression under real time-quantitative polymerase chain reaction (RT-qPCR), flow cytometry (FC), and confocal laser scanning microscopy (CM). MAIN OUTCOMES AND MEASURES: Expression of biosynthetic enzymes for CysLTs (5-LO, FLAP, and LTC(4)S) was the main outcome measure. Patients with OSA and control patients with RT were compared for numbers of copies of 5-LO, FLAP, and LTC(4)S messenger RNA (by RT-qPCR) in T or B tonsillar lymphocytes and proportions of CD3(+) or CD19(+) tonsillar lymphocytes that expressed 5-LO, FLAP, and LTC(4)S (by FC). RESULTS: Messenger RNA for all 4 enzymes was detected in T and B lymphocytes from both study groups, and expression of all biosynthetic enzymes was demonstrated in participants with OSA and RT by FC. Patients with OSA differed from controls in the proportions (median [10th-90th percentile]) of LTC(4)S(+) CD3(+) T lymphocytes (23.31% [8.64%-50.07%] vs 10.81% [3.48%-23.32%], respectively) (P = .01) and LTC(4)S(+) CD19(+) B lymphocytes (20.66% [14.62%-65.77%] vs 12.53% [2.87%-36.64%], respectively) (P = .01) detected by FC. Immunoreactivity for the 4 enzymes was detected by CM in B lymphocytes of mantle zones and T lymphocytes of extrafollicular areas. CONCLUSIONS AND RELEVANCE: Leukotriene biosynthetic enzymes are expressed in tonsillar lymphocytes, and the previously reported detection of CysLTs in tonsillar tissue from children with OSA may be attributed to endogenous synthesis. Enhanced expression of LTC(4)S is a potential target for pharmacologic interventions in OSA.

Poincaré plot width, morning urine norepinephrine levels, and autonomic imbalance in children with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) in childhood is accompanied by sympathetic overflow unopposed by the parasympathetic tone. Complex methods like power spectral analysis of heart rate variability have been applied to study this imbalance. In this report, width of Poincaré scattergram of the R-R interval (parasympathetic tone) and morning urine norepinephrine concentration (sympathetic activity) were used to assess autonomic imbalance. METHODS: Poincaré plot was obtained from the electrocardiographic channel of nocturnal polysomnography and its width was measured, and norepinephrine-to-creatinine concentration ratio was calculated in morning urine specimen. RESULTS: Twenty children with obstructive sleep apnea and moderate-to-severe nocturnal hypoxemia (oxygen saturation of hemoglobin [SpO(2)] nadir <90%), 24 subjects with mild hypoxemia (SpO(2) nadir ≥90%), and 11 control subjects were recruited. Children with obstructive sleep apnea and moderate-to-severe hypoxemia had significantly narrower Poincaré plot width (318.7 ± 139.3 ms) and higher ln-transformed urine norepinephrine-to-creatinine ratio (4.5 ± 0.6) than control subjects (484.2 ± 104.4 ms and 3.8 ± 0.4, respectively; P < 0.05). Ln-transformed urine norepinephrine levels were inversely related to Poincaré plot width (P = 0.02). CONCLUSIONS: Subjects with obstructive sleep apnea and moderate-to-severe nocturnal hypoxemia have enhanced sympathetic activity and reduced parasympathetic drive. Poincaré plot width and urine norepinephrine levels are simple measures of autonomic imbalance in pediatric obstructive sleep apnea.

Cysteinyl leukotriene receptors in tonsillar B- and T-lymphocytes from children with obstructive sleep apnea.

OBJECTIVES: Cysteinyl leukotrienes have been implicated in the pathogenesis of adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). This study aimed to quantify the expression of cysteinyl leukotriene receptors (CysLT(1), CysLT(2)) by tonsillar lymphocyte subpopulations from children with OSA and to make comparisons to lymphocyte subpopulations from control subjects with recurrent tonsillitis (RT). METHODS: Tonsillar tissue from children with OSA or RT was studied for CysLT(1) and CysLT(2) expression by RT-PCR, flow cytometry (FC), and immunofluorescence. RESULTS: Ten children with OSA and 10 control subjects were recruited. In OSA participants, CysLT(1)+ fraction of small-size CD19+ B-lymphocytes was similar to the CysLT(1)+ CD3+ T-lymphocytes fraction (FC: 36.5 [16.5-55.4] vs. 14 [2.8-22.1]) (p>0.05) and higher than the CysLT(1)+ moderate/large-size CD19+ B-lymphocytes fraction (6.6 [1.5-14.4]) (p<0.01). Similar trends were recognized for CysLT(2). CysLT(1) and CysLT(2) immunoreactivity was detected by immunofluorescence in the tonsillar mantle zones (small B-lymphocytes) and the extrafollicular areas (T-lymphocytes). Compared to subjects with RT, children with OSA had significantly higher expression of CysLT(1) in small-size CD19+ B-lymphocytes (FC) and in CD3+ T-lymphocytes (RT-PCR and FC) (p<0.05). CONCLUSIONS: Increased expression of leukotriene receptors by immunologically active tonsillar areas in children with OSA is a potential therapeutic target for pediatric sleep apnea.

Associations of tonsillar hypertrophy and snoring with history of wheezing in childhood.

BACKGROUND: Reports in adults and children have correlated history of wheezing or asthma with the presence of obstructive sleep-disordered breathing but the mechanism of this epidemiologic association is unknown. The goal of the present study was to examine whether tonsillar hypertophy can explain this association. METHODS: Children were recruited from the Emergency Department and the Pediatric Pulmonology Clinic. History of wheezing requiring treatment (explanatory variable) and snoring > or = 1 night/week (outcome) were recorded and presence of tonsillar hypertrophy (outcome) was assessed. RESULTS: Four hundred forty-two children were recruited (mean age: 7.6 + or - 3.6 years) and 210 of them had history of wheezing. History of wheezing was significantly associated with the presence of tonsillar hypertrophy and snoring even after adjustment for age, gender, obesity, and passive smoking [odds ratio (95% confidence interval): 2.23 (1.37-3.63); P = 0.001 and 1.73 (1.12-2.67); P = 0.013, respectively]. When only children with tonsillar hypertrophy were considered (n = 92), history of wheezing was significantly related to the presence of snoring, whereas in subjects without tonsillar hypertrophy (n = 350) wheezing did not affect snoring [odds ratio: 2.76 (1.10-6.93); P = 0.031 and 1.49 (0.92-2.43); P = 0.107, respectively]. CONCLUSIONS: Children with history of wheezing have more frequently tonsillar hypertrophy than those without wheezing. Tonsillar hypertrophy may mediate at least in part the reported association between asthma and obstructive sleep-disordered breathing in childhood.

Tonsillar size in 2- to 14-year-old children with and without snoring.

BACKGROUND: Few investigations have assessed tonsillar size in children of variable age, sleep-disordered breathing (SDB) status and degree of adiposity. This study evaluated the size of tonsils in young and older, lean and obese children, without or with snoring. METHODS: Children attending the Emergency Department or Pulmonology Clinic were recruited and tonsillar size was scored 1-4. Snoring >or=1 night/week was considered diagnostic of SDB and body mass index z-score >or=1.645 was defined as obesity. Age was analyzed as dichotomous variable (7 years old). RESULTS: 362 children (2-14 years old) were recruited; 78 (21.5%) were obese and 108 (29.8%) had SDB. SDB-but not age or obesity-was significantly related to tonsillar size (P = 0.001). There was not enough evidence to support the presence of interactions between SDB and age or obesity regarding the size of tonsils (P = 0.157 and P = 0.978, respectively). Young subjects without SDB had larger tonsils than older subjects without SDB (1.9 +/- 0.7 vs. 1.7 +/- 0.8; P = 0.017), whereas age did not affect tonsillar size in children with SDB (P = 0.78). CONCLUSIONS: Young and older children with SDB have similar tonsillar size. In contrast, older subjects without snoring have smaller tonsils than young subjects without snoring. Tonsillar enlargement in children with SDB probably occurs in early childhood without change in older age.