Ultrasound-guided diagnostic pericardiocentesis in preterm infants: a case report.

Pericardial effusion (PE) in pediatric population can be asymptomatic or a life-threatening event. Reports on neonates or preterm infants are scarce and generally related to pericardiocentesis of large amounts of PE in emergency situations.We describe a diagnostic pericardiocentesis in a preterm infant with small and loculated pericardial effusion and suspected cardiac mass. We used an ultrasound-guided long-axis in-plane pericardiocentesis technique, with a needle-cannula. The operator obtained a subxiphoid pericardial effusion view with a high frequency linear probe and entered the skin below the tip of the xiphoid process with a 20-gauge closed IV needle-cannula (ViaValve®). The needle was identified in its entirety as it courses through soft tissue up to pericardial sac. The main advantages of this approach are a continuous viewing and angulation of the needle through all planes of the tissue and the use of a small, practical, closed IV needle-cannula with blood control septum to prevent fluid exposure while disconnecting the syringe. This novel approach is easy and safe in neonatal population, for diagnostic or emergency drainages and can be performed at bedside in a neonatal intensive care unit.

COVID-19-Associated Multisystem Inflammatory Syndrome in a Neonate with Atypical Coronary Artery Involvement.

OBJECTIVE: The study aimed to report a novel coronavirus disease 2019 (COVID-19)-associated multisystem inflammatory syndrome in children (MIS-C) in a neonate found to have an atypical diffuse thickening in coronary artery walls whose diagnosis required a multi-imaging approach. STUDY DESIGN: A neonate presented at birth with multiple organ involvement and coronary artery anomalies. A diagnosis of MIS-C associated with COVID-19 was supported by maternal severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy, and by the presence of both immunoglobulin (Ig)-G against SARS-CoV-2 and spike-specific memory B-cells response in the neonatal blood. Other plausible causes of the multiple organ involvement were excluded. RESULT: At admission, a severe coronary artery dilatation was identified on echocardiography, supporting the diagnosis of the MIS-C Kawasaki-like disease; however, coronary artery internal diameters were found to be normal using cardiac computed tomography angiography. At discharge, comparing the two imaging techniques each other, the correct diagnosis resulted to be an abnormal thickening in coronary arterial walls. These findings suggest that the inflammatory process affecting the coronary arterial wall in MIS-C could result not only in typical coronary artery lesions such as dilatation of the lumen or aneurysms development but also in abnormal thickening of the coronary artery wall. CONCLUSION: Our case provides an alert for pediatric cardiologists about the complexity to assess coronary artery involvement in MIS-C and raises the question that whether an abnormal vascular remodeling, with normal inner diameters, is to be considered like coronary artery dilatation for risk stratification. KEY POINTS: · COVID-19 associated MIS-C can present in neonates with multiple organ involvement.. · Coronary artery assessment in neonatal MIS-C could be complex, and a multi-imaging approach could be required.. · Beside the typical coronary artery lesions, such as dilatation of the lumen or aneurysms, also abnormal thickening of the coronary artery wall can occur..

Lutein supplementation and retinopathy of prematurity: a meta-analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial retinal disorder characterized by an abnormal vascular development of the retina of the preterm infants. Carotenoids are natural pigments that are synthesized by all plants and some microorganisms where they play a role in photoprotection and coloration. Lutein and zeaxanthin (L/Z) are two carotenoids identified as the major components of the macular pigment. Recently it has been suggested that lutein and its isomer zeaxanthin may act as antioxidant agents and that they may prevent ROP. OBJECTIVE: The primary objective of this study is to assess the safety and effectiveness of oral lutein in the prevention of retinopathy of prematurity in preterm neonates. STUDY DESIGN: We conducted a systematic search for randomized or quasi-randomized controlled trials without any language or publication year restriction. The studies have to recruit preterm neonates ≤32 completed weeks of gestation and to compare the administration of oral L/Z at any dosage or duration, versus placebo in order to prevent ROP. RESULT: Data from three RCT with a total of 406 participants failed to show any reduction in ROP incidence nor the risk of BPD, sepsis, NEC and mortality. It may reduce the number of transfusions but this result has to be assessed in a separate ad hoc trial.

Incidence and risk factors of retinopathy of prematurity in an Italian cohort of preterm infants.

OBJECTIVE: Non-negligible differences in retinopathy of prematurity (ROP) and its risk factors between different neonatal intensive care units (NICUs) are reported. Our aim was to assess the incidence and risk factors for ROP development in a large cohort of very preterm infants who were assisted in two Italian NICUs. METHODS: Preterm infants with gestational age between 23+ 0 and 29+ 6 weeks were stratified into subgroups of infants who developed ROP and those who did not; their clinical characteristics were compared with univariate and multivariable logistic regression analyses. RESULTS: We studied a total of 178 infants of whom 67 (38%) developed ROP (stage 1: n = 12; stage 2: n = 41; stage 3: n = 14). Regression analysis demonstrated that maternal milk (OR 0.979, 95% Cl 0.961-0.998) decreased the risk of developing ROP, while intraventricular hemorrhage (IVH) (OR 2.055, 95% Cl 1.120-3.772) increased it. Moreover, maternal milk was found to decrease (OR 0.981, 95% Cl 0.964-0.997) the risk of ROP at discharge, while RBC transfusion increased it (OR 1.522, 95% Cl 1.208-1.916). CONCLUSIONS: In our cohort the occurrence of ROP was similar to that previously reported. Strategies for promoting the use of mother's own milk, preventing IVH, and standardizing the approach to RBC transfusions could contribute to decreasing the risk of ROP in very preterm infants.

Allogeneic cord blood transfusions prevent fetal haemoglobin depletion in preterm neonates. Results of the CB-TrIP study.

Repeated red blood cell (RBC) transfusions in preterm neonates are associated with poor outcome and increased risk for prematurity-associated diseases. RBC transfusions cause the progressive replacement of fetal haemoglobin (HbF) by adult haemoglobin (HbA). We monitored HbF levels in 25 preterm neonates until 36 weeks of post-menstrual age (PMA); patients received RBC units from allogeneic cord blood (cord-RBCs) or from adult donors (adult-RBCs), depending on whether cord-RBCs were available. Primary outcome was HbF level at PMA of 32 weeks. Twenty-three neonates survived until this age: 14 received no transfusions, two only cord-RBCs, three only adult-RBCs and four both RBC types. HbF levels in neonates transfused with cord-RBCs were significantly higher than in neonates receiving adult-RBCs (P < 0·0001) or both RBC types (P < 0·0001). Superimposable results were obtained at PMA of 36 weeks. Every adult-RBCs transfusion increased the risk for an HbF in the lowest quartile by about 10-fold, whereas this effect was not evident if combined adult- and cord-RBCs were evaluated. Overall, these data show that transfusing cord-RBCs can limit the HbF depletion caused by conventional RBC transfusions. Transfusing cord blood warrants investigation in randomised trials as a strategy to mitigate the severity of retinopathy of prematurity (NCT03764813).

Rotating-disc micro-solid phase extraction of F2-isoprostanes from maternal and cord plasma by using oxidized buckypaper as sorbent membrane.

This paper describes the development of an original micro-solid phase extraction device and its evaluation for the isolation of F2-isoprostanes (F2-IsoPs) from cord and maternal plasma samples. The unit is very simple and consists in a rotating disc (1.8 cm diameter) of oxidized buckypaper (BP), enwrapped in a polypropylene mesh pouch. Even if the selected F2-IsoPs have logP and pKa values that make them suitable candidates for their sorption on BP, several parameters were optimized to maximize recoveries: time of adsorption and desorption; stirring speed; volume, pH and ionic strength of the sample; type, volume, and fractions of the elution solvent; oxidation grade of BP. Among all, the last one was crucial in affecting extraction yields because of the analyte interactions with polar functionalities, introduced by a preliminary oxidative acid treatment. The investigation established the optimal oxidation time and highlighted the pros and cons of the acid activation step. All extracts were analyzed by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Validation was performed according to the main FDA guidelines for bioanalytical methods. Depending on the spike level and analyte, recoveries ranged between 30 and 120% with precision and accuracy values lower than 20%. Quantitative analysis was accomplished by matrix-matched calibration curves whose determination coefficients were higher than 0.95. Lower limit of quantitation (LLOQ) spanned the range 2.45-6.77 µg L-1. The validated method was applied to the analysis of eight pairs of mother/child plasma samples, revealing the presence of 8-iso-15-keto-PGF2α and 8-iso-PGE2 at a concentration of about 10 µg L-1 in most cord plasma samples of preterm newborns.

Extubation from high-frequency oscillatory ventilation in extremely low birth weight infants: a prospective observational study.

OBJECTIVE: To evaluate if weaning from high-frequency oscillatory ventilation (HFOV) directly to a non-invasive mode of respiratory support is feasible and results in successful extubation in extremely low birth weight (ELBW) infants. DESIGN: Prospective observational study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: One hundred and eight ELBW infants of 26.2±1.4 weeks of gestational age (GA) directly extubated from HFOV. INTERVENTIONS: All infants were managed with elective HFOV and received surfactant after a recruitment HFOV manoeuvre. Extubation was attempted at mean airways pressure (MAP) ≤6 cm H2O with FiO2 ≤0.25. After extubation, all infants were supported by nasal continuous positive airway pressure (6-8 cm H2O). MAIN OUTCOME MEASURES: Extubation failure (clinical deterioration requiring reintubation) was defined as shorter than 7 days. RESULTS: Ninety patients (83%) were successfully extubated and 18 (17%) required reintubation. No significant differences were found between the two groups in terms of birth weight, day of life and weight at the time of extubation. Multivariable analysis showed that GA (OR 1.71; 95% CI 1.04, 2.08) and higher MAP prior to surfactant (OR 1.51; 95% CI 1.06, 2.15) were associated with successful extubation. CONCLUSIONS: In ELBW infants, direct extubation from HFOV at MAP ≤6 cm H2O with FiO2 ≤0.25 is feasible. Our extubation success rate (83%) is higher than conventional mechanical ventilation in this very vulnerable class of infants.

Nasal high-frequency oscillatory ventilation and CO2 removal: A randomized controlled crossover trial.

OBJECTIVE: To compare short-term application of nasal high-frequency oscillatory ventilation (nHFOV) with nasal continuous positive airway pressure (nCPAP). WORKING HYPOTHESIS: nHFOV improves CO2 removal with respect to nCPAP in preterm infants needing noninvasive respiratory support and persistent oxygen supply after the first 72 h of life. STUDY DESIGN: Multicenter non-blinded prospective randomized crossover study. PATIENT SELECTION: Thirty premature infants from eight tertiary neonatal intensive care units, of mean ± SD 26.4 ± 1.8 weeks of gestational age and 921 ± 177 g of birth weight. METHODOLOGY: Infants were randomly allocated in a 1:1 ratio to receive a starting treatment mode of either nCPAP or nHFOV delivered by the ventilator CNO (Medin, Germany), using short binasal prongs of appropriate size. A crossover design with four 1-h treatment periods was used, such that each infant received both treatments twice. The primary outcome was the mean transcutaneous partial pressure of CO2 (TcCO2 ) value during the 2-h cumulative period of nHFOV compared with the 2-h cumulative period of nCPAP. RESULTS: Significantly lower TcCO2 values were observed during nHFOV compared with nCPAP: 47.5 ± 7.6 versus 49.9 ± 7.2 mmHg, respectively, P = 0.0007. A different TcCO2 behavior was found according to the random sequence: in patients starting on nCPAP, TcCO2 significantly decreased from 50.0 ± 8.0 to 46.6 ± 7.5 mmHg during nHFOV (P = 0.001). In patients starting on nHFOV, TcCO2 slightly increased from 48.5 ± 7.8 to 49.9 ± 6.7 mmHg during nCPAP (P = 0.13). CONCLUSIONS: nHFOV delivered through nasal prongs is more effective than nCPAP in improving the elimination of CO2 .

Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings.

PURPOSE: To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). DESIGN: Single randomized controlled trial. PARTICIPANTS: All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. METHODS: Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. MAIN OUTCOME MEASURES: Presence of retinal and choroidal abnormalities on FA at 9 months. RESULTS: Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. CONCLUSIONS: This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied.

Fluorescein angiography and retinal vascular development in premature infants.

OBJECTIVE: To investigate the role of fluorescein angiography (FA) in the management of retinopathy of prematurity (ROP) in preterm newborns. METHODS: An observational case series of 13 extremely low birth weight infants. From September 2009 to March 2010, 13 newborn infants with a gestational age <29 weeks end/or birth weight <1000 g underwent serial fluorescein angiography with RetCam (Clarity, Pleasanton, CA) every 2 weeks. The fluorescein angiograms were examined to optimize the timing of diagnosis of ROP and to investigate development of retinal and choroidal vascularization. RESULTS: There were no side effects related to FA. Variable features of retinal and choroidal circulation in preterm infants with a high risk of developing ROP were noted. FA allows vessels branching at the junction between vascular and avascular retina (V-Av junction) to be viewed easily and shows the ROP findings that sometimes cannot be seen by indirect ophthalmoscopy. Dye leakage is the most significant sign of progression to severe ROP or the need for surgery in newborn babies with ROP. CONCLUSIONS: RetCam-assisted intravenous FA is safe and allows a more objective assessment of the ROP stage and zone.

Neonatal tuberculosis: an experience that teaches.

OBJECTIVE: This study reports on an experience following contact by a large number of newborn babies with a nurse infected by active tuberculosis (TB). METHODS: A large number of newborn babies were checked for possible contact with Mycobacterium tuberculosis (MTB) using interferon-gamma tests (IGTs) to determine specific treatment. RESULTS: One hundred and seven infants showed a positive IGT positive and were not affected by active TB. All were treated with anti-tubercular drugs and were followed-up for 1 year. None of the infants developed active TB and all infants showed normal tuberculin skin tests and chest-x-rays, as well as IGT results at the end of treatment. CONCLUSIONS: Our experience suggests that newborns are at low risk of infection after contact with a nurse with active TB. IGTs can be used to assess possible contact with MTB and to determine a reduced number of infants to treat.

Analysis of risk factors for progression to treatment-requiring ROP in a single neonatal intensive care unit: is the exposure time relevant?

OBJECTIVE: Retinopathy of prematurity (ROP) is a multifactorial disease whose pathogenesis is organized in two phases. We hypothesized that postnatal risk factors may differently exert their effect in a phase dependent way. METHODS: Data obtained from medical records of 93 very low birth weight neonates with stage ≥ 3 ROP were analyzed. Perinatal ROP risk factors were compared between infants with stage 3 ROP not requiring surgery and infants with treatment-requiring ROP with relation to newborn's lifetime exposure. RESULTS: In the first two weeks and in the whole first month of life length of oxygen administration was an independent risk factor for treatment-requiring ROP. In the first month of life also sepsis was identified as independent risk factor for surgical ROP. Sepsis and Candida pneumonia in the time frame from birth to ROP diagnosis and prolonged mechanical ventilation from diagnosis to prethreshold ROP were associated to treatment-requiring ROP. Blood transfusions are the only risk factor for treatment-requiring ROP identified in all the periods analyzed. CONCLUSION: Risk factors for ROP play their role since birth. Beside scrupulous oxygen-administration monitoring and prevention of infections, blood transfusions are of primary importance in the development of treatment-requiring ROP.

A prospective, randomized, double blind study comparing lutein to placebo for reducing occurrence and severity of retinopathy of prematurity.

Lutein has been shown to have antioxidant functions in newborns and with zeaxantin selectively taken up into the macula of the eye. We hypothesize that lutein administration may contribute to reducing the incidence of Retinopathy of Prematurity (ROP). This was a single center, double-blind randomized controlled study. Preterm infants with gestational age (GA) ≤ 32 weeks able to tolerate minimal enteral feeding before the seventh day of life (DOL) were enrolled; lutein and zeaxantin plasma concentrations and ROP occurrence and severity were evaluated. Sixty-three newborns were enrolled, 31 in the lutein group and 32 in the placebo group (one died before ROP assessment). The mean GA was 29.9 (± 1.9) weeks and the mean birth weight was 1331 (± 415) grams. There were no differences in the incidence of ROP at any stage between groups. Oxidative injury is probably an additional mechanism of damage of the developing retinal vessels, and it probably plays only a minor role in the pathogenesis of ROP. Supplementation with antioxidant substances might have beneficial effects noticeable only on larger samples of high risk neonates or at very high dosage. Further investigations would be needed to evaluate whether lutein supplementation can influence functional rather than anatomical outcomes in preterm infants.

Effectiveness of ketorolac tromethamine in prevention of severe retinopathy of prematurity.

PURPOSE: This study assessed the effectiveness of the use of ketorolac tromethamine to reduce retinopathy of prematurity (ROP) incidence and its progression to more severe forms. METHODS: Forty-seven preterm newborn infants with a birth weight (BW) of 1,000 grams or less and/or a gestational age (GA) of 29 weeks or less were enrolled in the study when avascular retina zone I or ROP any stage were diagnosed at screening. Studied infants were randomized to receive ketorolac tromethamine ophthalmic solution in one eye and a drop of placebo in the other eye, until ROP requiring treatment or full retinal vascularization was diagnosed. RESULTS: Only 2 newborn infants did not develop ROP. Among 45 newborn infants who developed ROP, 6 showed different ROP staging between the two eyes, 4 of which had a better outcome in the eye receiving ketorolac tromethamine. The differences between ROP stagings were not significant even when analyzed by GA and BW subgroups. No significant treatment-related side effects occurred. CONCLUSION: This report suggests that ketorolac tromethamine ophthalmic solution cannot reduce the risk of developing severe ROP in preterm infants.

Chest physiotherapy in preterm infants with lung diseases.

BACKGROUND: In neonatology the role of chest physiotherapy is still uncertain because of the controversial outcomes. METHODS: The aim of this study was to test the applicability in preterm infants of 'reflex rolling', from the Vojta method, in preterm neonates with lung pathology, with particular attention to the effects on blood gases and oxygen saturation, on the spontaneous breathing, on the onset of stress or pain. The study included 34 preterm newborns with mean gestational age of 30.5 (1.6) weeks - mean (DS) - and birth weight of 1430 (423) g - mean (DS) -, who suffered from hyaline membrane disease, under treatment with nasal CPAP (continuous positive airways pressure), or from pneumonia, under treatment with oxygen-therapy. The neonates underwent phase 1 of 'reflex rolling' according to Vojta method three times daily. Respiratory rate, SatO2, transcutaneous PtcCO2 e PtcO2 were monitored; in order to evaluate the onset of stress or pain following the stimulations, the NIPS score and the PIPP score were recorded; cerebral ultrasound scans were performed on postnatal days 1-3-5-7, and then weekly. RESULTS: In this population the first phase of Vojta's 'reflex rolling' caused an increase of PtcO2 and SatO2 values. No negative effects on PtcCO2 and respiratory rate were observed, NIPS and PIPP stress scores remained unmodified during the treatment; in no patient the intraventricular haemorrhage worsened in time and none of the infants developed periventricular leucomalacia. CONCLUSIONS: Our experience, using the Vojta method, allows to affirm that this method is safe for preterm neonates, but further investigations are necessary to confirm its positive effects and to evaluate long-term respiratory outcomes.