Hemodynamic evaluation in preterm infants using ultrasonic cardiac output monitor (USCOM).

We aimed to establish reference ranges for USCOM parameters in preterm infants, determine factors that affect cardiac output, and evaluate the measurement repeatability. This retro-prospective study was performed at Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. We included infants below 32 weeks of gestational age (GA) and/or 1500 g of birth weight (BW). We excluded infants with congenital heart diseases or hemodynamic instability. Measurements were performed at 3 ± 1, 7 ± 2, and 14 ± 2 postnatal days. We analyzed 204 measurements from 92 patients (median GA = 30.57 weeks, BW = 1360 g). The mean (SD) cardiac output (CO) was 278 (55) ml/min/kg, cardiac index (CI) was 3.1 (0.5) L/min/m2, and systemic vascular resistance (SVRI) was 1292 (294) d*s*cm-5/m2. CO presented a negative correlation with postmenstrual age (PMA), while SVRI presented a positive correlation with PMA. The repeatability coefficient was 31 ml/kg/min (12%).  Conclusion: This is the first study describing reference values for USCOM parameters in hemodynamically stable preterm infants and factors affecting their variability. Further studies to investigate the usefulness of USCOM for the longitudinal assessment of patients at risk for cardiovascular instability or monitoring the response to therapies are warranted. What is Known: • The ultrasonic cardiac output monitoring (USCOM) has been widely used on adult and pediatric patients and reference ranges for cardiac output (CO) by USCOM have been established in term infants. What is New: • We established reference values for USCOM parameters in very preterm and very-low-birth-weight infants; the reference ranges for CO by USCOM in the study population were 198-405 ml/kg/min. • CO normalized by body weight presented a significant negative correlation with postmenstrual age (PMA); systemic vascular resistance index presented a significant positive correlation with PMA.

Mucopolysaccharidosis-Plus Syndrome, a Rapidly Progressive Disease: Favorable Impact of a Very Prolonged Steroid Treatment on the Clinical Course in a Child.

Mucopolysaccharidosis-plus syndrome (MPS-PS) is a novel autosomal recessive disorder caused by a mutation in the VPS33A gene. This syndrome presents with typical symptoms of mucopolysaccharidosis, as well as congenital heart defects, renal, and hematopoietic system disorders. To date, twenty-four patients have been described. There is no specific therapy for MPS-PS; clinical management is therefore limited to symptoms management. The clinical course is rapidly progressive, and most patients die before 1-2 years of age. We describe a currently 6-year-old male patient with MPS-PS presenting with multiorgan involvement. Symptoms started at four months of age when he progressively suffered from numerous acute and potentially life-threatening events. When he was two years old, he developed secondary hemophagocytic lymphohistiocytosis (HLH), which was successfully treated with steroids. To date, this child represents the oldest patient affected by MPS-PS described in the literature and the first one presenting with a life-threatening secondary HLH. The prolonged steroid treatment allowed a stabilization of his general and hematological conditions and probably determined an improvement of his psychomotor milestones and new neurological acquisitions with an improvement of quality of life. HLH should be suspected and adequately treated in MPS-PS patients presenting with suggestive symptoms of the disease. The usefulness of a prolonged steroid treatment to improve the clinical course of children with MPS-PS deserves further investigation.

The care of critically ill infants and toddlers in neonatal intensive care units across Italy and Europe: our proposal for healthcare organization.

Numerous studies have shown that critically ill infants and toddlers admitted to paediatric intensive care units (PICUs) have a lower mortality than those admitted to adult ICUs. In 2014, there were only 23 registered PICUs in Italy, most of which were located in the north. For this reason, in Italy and elsewhere in Europe, some neonatal ICUs (NICUs) have begun managing critically ill infants and toddlers. Our proposal for healthcare organization is to establish "extended NICUs" in areas where paediatric intensive care beds are lacking. While some countries have opted for a strict division between neonatal and paediatric intensive care units, the model of "extended NICUs" has already been set up in Italy and in Europe. In this instance, the management of critically ill infants and toddlers undoubtedly falls upon neonatologists, who, however, must gain specific knowledge and technical skills in paediatric critical care medicine (PCCM). Postgraduate residencies in paediatrics need to include periods of specific training in neonatology and PCCM. The Italian Society of Neonatology's Early Childhood Intensive Care Study Group is supporting certified training courses for its members involving both theory and practice. CONCLUSION: Scientific societies should promote awareness of the issues involved in the intensive management of infants and toddlers in NICUs and the training of all health workers involved. These societies include the Italian Society of Neonatology, the European Society of Paediatric and Neonatal Intensive Care, and the Union of European Neonatal and Perinatal Societies. They should also act in concert with the governmental institutional bodies to establish the standards for the "extended NICUs." WHAT IS KNOWN: • The mortality of critically ill infants and toddlers admitted to PICUs is lower than that for those admitted to adult ICUs. • In Italy, there are only a handful of PICUs, located mainly in the north. WHAT IS NEW: • Critically ill infants and small toddlers can be managed in "extended NICUs" in areas with a lack of paediatric intensive care beds. • "Extended NICUs" is our proposal for healthcare organization to compensate for the paucity of paediatric intensive care beds, but neonatologists must be trained to provide them with specific knowledge and technical skills in PCCM.

Evaluation of hemodynamics in healthy term neonates using ultrasonic cardiac output monitor.

BACKGROUND: Transition from intrauterine to extrauterine life is a critical phase during which several changes occur in cardiovascular system. In clinical practice, it is important to have a method that allows an easy, rapid and precise evaluation of hemodynamic status of a newborn for clinical management. We here propose a rapid, broadly applicable method to monitor cardiovascular function using ultrasonic cardiac output monitoring (USCOM). METHODS: We here present data obtained from a cohort of healthy term newborns (n = 43) born by programmed cesarean section at Fondazione MBBM, Ospedale San Gerardo. Measurements were performed during the first hour of life, then at 6 + 2, at 12-24, and 48 h of life. We performed a screening echocardiography to identify a patent duct at 24 h and, if patent, it was repeated at 48 h of life. RESULTS: We show that physiologically, during the first 48 h of life, blood pressure and systemic vascular resistance gradually increase, while there is a concomitant reduction in stroke volume, cardiac output, and cardiac index. The presence of patent ductus arteriosus significantly reduces cardiac output (p = 0.006) and stroke volume (p = 0.023). Furthermore, newborns born at 37 weeks of gestational age display significantly lower cardiac output (p < 0.001), cardiac index (p = 0.045) and stroke volume (p < 0.001) compared to newborns born at 38 and ≥ 39 weeks. Finally, birth-weight (whether adequate, small or large for gestational age) significantly affects blood pressure (p = 0.0349), stroke volume (p < 0.0001), cardiac output (p < 0.0001) and cardiac index (p = 0.0004). In particular, LGA infants display a transient increase in cardiac index, cardiac output and stroke volume up to 24 h of life; showing a different behavior from AGA and SGA infants. CONCLUSIONS: Compared to previous studies, we expanded measurements to longer time-points and we analyzed the impact of commonly used clinical variables on hemodynamics during transition phase thus making our data clinically applicable in daily routine. We calculate reference values for each population, which can be of clinical relevance for quick bedside evaluation in neonatal intensive care unit.

Early Neonatal SARS-CoV-2 Infection Manifesting With Hypoxemia Requiring Respiratory Support.

We describe a case of neonatal SARS-CoV-2 infection, in an infant diagnosed 3 days after birth, and manifesting with silent hypoxemia, requiring respiratory support.

Nationwide survey of neonatal transportation practices in Italy.

BACKGROUND: Despite regionalization of perinatal care provides for the "in utero" transfer of high-risk pregnancies, there will always be a number of neonates who undergo acute inter-facility transport. The presence of a well-organized Neonatal Emergency Transport Service (NETS) can prevent and reduce risks of transportation, especially for very preterm infants, and is therefore mandatory for any program of regionalization of perinatal care. Italian National Health System is highly decentralized and Regions are autonomous to structure, plan and delivery their regional health services. Consequently, organization models and resources available vary widely and significant regional differences in access and quality of health services have been reported in the past years. A national survey was conducted in 2015 by the neonatal transport study group of the Italian Society of Neonatology with the aim to describe neonatal transfer practices and to assess the Neonatal Emergency Transport Services (NETS) status in the 20 Italian regions. METHODS: A questionnaire regarding neonatal transfer practices and NETS activity for the previous year (2014) was sent to the 44 NETS operating in the 20 Italian regions. Demographic data were obtained from the Italian National Statistical Institute (ISTAT). RESULTS: The overall survey response rate was 100%. In 2014, only 12 (60%) of the 20 Italian regions were fully covered by NETS, 3 (15%) regions were partially covered, while neonatal transport was not available in 5 (25%) regions. Overall, in 2014, the 44 NETS operating in Italy transported a total of 6387 infants, including 522 (8.17%) having a gestational age < 28 weeks. CONCLUSIONS: The organization of NETS in Italy is devolved on a regional basis, resulting in a large heterogeneity of access and quality to services across the country. Where available, NETS are generally well-equipped and organized but limited volume of activities often cannot guarantee adequate levels of skills of personnel or an appropriate cost-efficiency ratio. The regions reported with lack of NETS have managed, or are trying, to fill the gap, but continuing efforts to reduce regional differences in the availability and quality of services are still needed.

Relationship between Mean Airways Pressure, Lung Mechanics, and Right Ventricular Output during High-Frequency Oscillatory Ventilation in Infants.

OBJECTIVE: To characterize changes in lung mechanics and right ventricular output (RVO) during incremental/decremental continuous distending pressure (CDP) maneuvers in newborn infants receiving high-frequency oscillatory ventilation, with the aim of evaluating when open lung maneuvers are needed and whether they are beneficial. STUDY DESIGN: Thirteen infants on high-frequency oscillatory ventilation were studied with a median (IQR) gestational age of 261 (253-291) weeks and median (IQR) body weight of 810 (600-1020) g. CDP was increased stepwise from 8 cmH2O to a maximum pressure and subsequently decreased until oxygenation deteriorated or a CDP of 8 cmH2O was reached. The lowest CDP that maintained good oxygenation was considered the clinically optimal CDP. At each CDP, the following variables were evaluated: oxygenation, respiratory system reactance (Xrs), and RVO by Doppler echocardiography. RESULTS: At maximal CDP reached during the trial, 19 [1] cmH2O (mean [SEM]), oxygenation markedly improved, and Xrs and RVO decreased. During deflation, oxygenation remained stable over a wide range of CDP settings, Xrs returned to the baseline values, and RVO increased but the baseline values were not readily restored in all patients. CONCLUSION: These results suggest that Xrs and RVO are more sensitive than oxygenation to overdistension and they may be useful in clinical practice to guide open lung maneuvers.

Risk factors for cerebral palsy in PPROM and preterm delivery with intact membranes (.).

OBJECTIVE: Gestational age (GA) at delivery and spontaneous prematurity are independent risk factors for cerebral palsy (CP). The aim of this study is to investigate perinatal risk factors for CP in spontaneous preterm delivery. METHODS: A retrospective cohort study of all single pregnancies complicated by spontaneous preterm labor (PTL) or PPROM with delivery at <34 weeks from January 2006 to December 2012 was performed. We compared demographic, obstetric, neonatal, and placental histology variables in cases of spontaneous preterm birth in reference to the development of CP. Statistical analysis included chi-square, one-way ANOVA and logistic regression analysis. p < 0.05 was considered significant. RESULTS: Two hundred sixty-one women were included for this study. Of 249 survivors, 5 babies died during the first year of life, 52 did not fulfill the inclusion criteria for neurologic follow-up, and 24 were lost to follow up. Thus 168 infants in the study cohort underwent neurologic follow-up. We observed 26 cases of CP. Factors related to CP were lower GA at PROM (p = 0.007) and longer latency from PPROM to delivery (p = 0.002) in the PPROM group, lower GA at delivery (p < 0.001) and presence of funisitis (p <0.001) in the PTL group. CONCLUSIONS: GA at membrane rupture in PPROM and GA at delivery in PTL are significantly associated with CP. A process leading to neurological damage may be initiated at the moment of membranes rupture in cases of PPROM and at the time of PTL in the group with intact membranes.

Perinatal complications in twin pregnancies after 34 weeks: effects of gestational age at delivery and chorionicity.

OBJECTIVE: To evaluate the perinatal outcome of twins approaching term in relation to chorionicity and gestational age at delivery. STUDY DESIGN: We accessed data pertaining to a cohort of 471 twin pregnancies with certain chorionicity delivered at > 34.0 weeks' gestation. Twin gestation per se, estimated fetal weight below the 10th percentile, or any intertwin discordance was not an indication for delivery before 40.0 weeks. Predictors of adverse perinatal outcome were identified using logistic regression analysis. RESULTS: There were no stillbirths. Adverse neonatal outcome occurred in 27% of monochorionic versus 16% of dichorionic gestations. At multivariate analysis, lower gestational age at delivery (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.57 to 0.87), monochorionicity (OR 2.06, 95% CI 1.16-3.63), and either twin being growth-restricted (OR 2.35, 95% CI 1.22 to 4.54) were independent predictors of adverse neonatal outcome. Analysis of adverse neonatal outcome stratified by gestational age and chorionicity identified 36 to 37 weeks as optimal timing for delivery of monochorionic twins, and dichorionic twin pregnancies should be allowed to continue until term. CONCLUSION: Among twin gestations delivered after 34 weeks with appropriate fetal growth, reassuring fetal status at weekly assessment, and absence of obstetric complications, delivery after 36 weeks for monochorionic twins and at term for dichorionic twins minimizes the risk of stillbirths and neonatal morbidity.

Two- or three-dimensional ultrasonography: which is the best predictor of pulmonary hypoplasia?

OBJECTIVE: The aim of our study is to compare the three-dimensional (3D) ultrasound fetal lung volume measurements with two-dimensional (2D) ultrasound biometric parameters in predicting pulmonary hypoplasia (PH). METHODS: From June 2006 to November 2008, we identified 35 fetuses at high risk for developing PH, including premature preterm rupture of membranes (17), fetal skeletal malformations (7), hydrothorax (7), and bilateral renal dysplasia (4). 3D lung volumes adjusted for gestational age (GA) or estimated fetal weight (EFW), thoracic circumference adjusted for GA or femur length, thoracic/abdominal circumference ratio, and thoracic/heart area ratio were measured. RESULTS: Three infants were excluded because no clinical or histological information regarding lung hypoplasia was available. Of the 32 remaining infants, 13 (41%) were diagnosed with PH at postmortem examination or by clinical and radiological examination. 3D lung volume measurements had a better diagnostic accuracy for predicting PH either when adjusted for GA [sensitivity, 12/13 (92%); specificity, 16/19 (84%); positive predictive value 12/15 (80%); negative predictive value, 16/17(94%)] or EFW [sensitivity, 11/13 (85%); specificity, 18/19 (94%); positive predictive value 11/12(92%); negative predictive value, 18/20(90%)] compared to the 2D biometric measurement. CONCLUSION: 3D lung volume measurements seem to be useful in the prenatal prediction of PH.