Cerebral venous thrombosis and deep medullary vein thrombosis: Padua experience over the last two decades.

BACKGROUND: Cerebral venous thrombosis (CVT) is a cerebrovascular disorder that accounts for 20% of perinatal strokes. CVT incidence ranges from 0.67 to 1.12 per 100,000 newborns, while the incidence of "deep medullary vein thrombosis" (DMVT), a subtype of CVT, cannot be accurately estimated. This study aims to analyze the case history of CVT in the neonatal period, with a specific focus on DMVT. MATERIALS AND METHODS: Newborns diagnosed with CVT, with or without DMVT, between January 2002 and April 2023, were collected using the Italian Registry of Infantile Thrombosis (RITI). Cerebral MRIs were reviewed by an expert neuroradiologist following a standardized protocol. RESULTS: Forty-two newborns with CVT were identified, of which 27/42 (64%) had CVT, and the remaining 15/42 (36%) had DMVT (isolated DMVT in 9/15). Symptom onset occurred in the first week of life (median 8 days, IQR 4-14) with a male prevalence of 59%. The most common risk factors for CVT were complicated delivery (38%), prematurity (40%), congenital heart diseases (48%), and infections (40%). Seizures were the predominant presenting symptom in 52% of all cases. Hemorrhagic infarction was higher in cases with isolated DMVT (77%) compared to patients with CVT without DMVT (p = 0.013). Antithrombotic treatment was initiated in 36% of patients. Neurological impairment was observed in 48% of cases at discharge, while 18 out of 31 infants (58%) presented one or more neurological deficits at long term follow up.     Conclusion: DMVT occurs in over a third of neonates with CVT. Multicentric studies are essential to establish standardized protocols for therapy, neuroimaging, and follow-up in these patients.

Prematurity and BPD: what general pediatricians should know.

More and more very low birth weight (VLBW) infants around the world survive nowadays, with consequently larger numbers of children developing prematurity-related morbidities, especially bronchopulmonary dysplasia (BPD). BPD is a multifactorial disease and its rising incidence in recent years means that general pediatricians are much more likely to encounter a child born extremely preterm, possibly with BPD, in their clinical practice. Short- and long-term sequelae in VLBW patients may affect not only pulmonary function (principally characterized by an obstructive pattern), but also other aspect including the neurological (neurodevelopmental and neuropsychiatric disorders), the sensorial (earing and visual impairment), the cardiological (systemic and pulmonary hypertension, reduced exercise tolerance and ischemic heart disease in adult age), nutritional (feeding difficulties and nutritional deficits), and auxological (extrauterine growth restriction). For the most premature infants at least, a multidisciplinary follow-up is warranted after discharge from the neonatal intensive care unit in order to optimize their respiratory and neurocognitive potential, and prevent respiratory infections, nutritional deficiencies or cardiovascular impairments.  Conclusion: The aim of this review is to summarize the main characteristics of preterm and BPD infants, providing the general pediatrician with practical information regarding these patients' multidisciplinary complex follow-up. We explore the current evidence on respiratory outcomes and their management that actually does not have a definitive available option. We also discuss the available investigations, treatments, and strategies for prevention and prophylaxis to improve the non-respiratory outcomes and the quality of life for these children and their families, a critical aspect not always considered. This comprehensive approach, added to the increased needs of a VLBW subjects, is obviously related to very high health-related costs that should be beared in mind. What is Known: • Every day, a general pediatrician is more likely to encounter a former very low birth weight infant. • Very low birth weight and prematurity are frequently related not only with worse respiratory outcomes, but also with neurological, sensorial, cardiovascular, renal, and nutritional issues. What is New: • This review provides to the general pediatrician a comprehensive approach for the follow-up of former premature very low birth weight children, with information to improve the quality of life of this special population.

Italian neonatologists and SARS-CoV-2: lessons learned to face coming new waves.

The aim of this review was threefold: (a) to retrieve all SARS-CoV-2 evidences published by Italian neonatologists working in maternity centers and NICUs during the pandemic; (b) to summarize current evidence for the management of term and preterm infants with a SARS-CoV-2-related illness; and (c) to provide an update for dealing with the second wave of COVID-19 and discuss open questions. A review was conducted using MEDLINE/PubMed and the national COVID-19 registry of the Italian Society of Neonatology including citations from December 1, 2019 to October 28, 2020. Sixty-three articles were included. Collected data were divided into the following topics: (a) antenatal management, (b) management in delivery room, (c) postnatal management, (d) mother-baby dyad and breastfeeding management, (e) neonatal emergency transport system reorganization, (f) parents' management and perspective during SARS-CoV-2 pandemic, and (g) future perspective. Evidences have evolved over the pandemic period and the current review can be useful in the management of the mother-neonate dyad during SARS-CoV-2 future waves. Italian neonatologists have played an active role in producing official guidelines and reporting data that have contributed to improve the care of neonates. A joint European action plan is mandatory to face COVID-19 in neonates with more awareness. IMPACT: A joint European action plan is mandatory to face COVID-19 in neonates with more awareness. This review summarizes the available evidences from neonatal COVID-19 management in Italy analyzing all the published paper in this specific field of interest. The current review can be useful in the management of the mother-neonate dyad during the SARS-CoV-2 future waves.

The aftermath of SARS-CoV-2 in NICU: saving or checking accounts? Projected cost-effectiveness analysis.

In the aftermath of the SARS-CoV-2 pandemic, we revised the cost-effectiveness of the exploited interventions in neonatal intensive care unit, to redefine future strategies for hospital management. Costs were revised with respect to the lockdown R0 or under different R0 scenarios to estimate the cost-effectiveness of the screening program adopted. Weekly nasopharyngeal swabs for parents, neonates, and personnel were the major cost during the pandemic, although they effectively reduced the number of cases in our unit.Conclusion: Parents and healthcare personnel testing appears to be an effective strategy due to the high number of contact they have within the hospital environment and outside, able to minimize the cases within our unit. What is Known: • Costs of universal COVID-19 tests for parents, neonates, and NICU personnel have not been evaluated during the COVID-19 pandemic in neonatal intensive care unit in Europe. What is New: • Weekly nasopharyngeal swabs for parents, neonates, and personnel were the major cost during the COVID-19 pandemic in NICU. • Parents and healthcare personnel testing was effective to reduce costs related to COVID-19 due to the high number of contact they have within the hospital environment and outside.

Universal screening of high-risk neonates, parents, and staff at a neonatal intensive care unit during the SARS-CoV-2 pandemic.

Since February 21, 2020, SARS-CoV-2 has spread exponentially worldwide. Neonatal patients needing intensive care are considered a vulnerable population. To report the results of a policy based on multi-timepoint surveillance for SARS-CoV-2 of all neonates admitted to the neonatal intensive care unit (NICU), their parents, and all healthcare providers in a part of Italy with a high prevalence of the infection. Observational study conducted from 21 February to 21 April 2020. Intervention consisted of (a) parental triage on arrival at the neonatal ward; (b) universal testing with nasopharyngeal swabs and blood testing for SARS-CoV-2 IgM and IgG antibodies; (c) use of continuous personal protective equipment at the NICU by parents and staff. A total of 6726 triage procedures were performed on 114 parents, and 954 nasopharyngeal swabs were collected from 226 individuals. Five (2.2%) asymptomatic individuals (2 parents and 3 healthcare providers) tested positive on nasopharyngeal swabs and were kept isolated for 14 days. Of 75 admitted newborn, no one tested positive on nasopharyngeal swabs or antibody tests. Three parents presented with fever or flu-like symptoms at triage; they tested negative on swabs.Conclusion: With universal screening of neonates, parents, and staff, there were no cases of SARS-CoV-2 infection among the neonates admitted to a NICU in an area with a high incidence of SARS-CoV-2. Our experience could be usefully compared with other strategies with a view to developing future evidence-based guidelines for managing high-risk neonates in case of new epidemics. What is Known: • The novel coronavirus named SARS-CoV-2 has since spread worldwide at a remarkable rate, with more than 2.5 million confirmed cases. • Pediatric population may be less affected from COVID-19 than adult population but infants and newborn babies seem to be more vulnerable to SARS-CoV-2 infection. What is New: • Using an approach based on triage; testing with nasopharyngeal swabs and serology; and use of personal protective equipment, there were no cases of SARS-CoV-2 infection among neonates in a NICU in a high incidence of SARS-CoV-2 area. • Positive and asymptomatic individuals were identified and isolated early allowing the containment of infection's spread among healthcare providers and parents.

Repeating a dose of sucrose for heel prick procedure in preterms is not effective in reducing pain: a randomised controlled trial.

Oral sucrose is included in almost all recommendations for treatment of pain in newborns, but evidence if multiple doses might be more effective than a single standard dose is lacking. We designed a single-centre, double-blind, randomised, controlled trial. We enrolled preterm infants needing the heel prick procedure. Each enrolled infant was randomised to receive a single standard dose of sucrose 2 min before or a double dose of sucrose 2 min before, and 30 s after heel prick. Primary outcome was the efficacy of the two interventions tested by the premature infant pain profile-PIPP scale obtained at 30 s, 60 s, and 120 s after heel prick. Secondary outcome was the evaluation of the concordance between the PIPP scale and other pain scores more feasible in clinical practice. Seventy-two infants were randomised. No difference in pain perception as measured by the PIPP scale was found between the groups: median PIPP values 4.0(IQR 3.0-4.0) vs 3.0(IQR 3.0-4.0) at baseline; 6.0(IQR 5.0-10.0) vs 6.0(IQR 4.0-8.5) at 30 s; 6.0(IQR 4.0-7.0) vs 5.0(IQR 4.0-8.5) at 60 s and 5.0(IQR 4.0-7.0) vs 5.0(IQR 4.0-7.5) at 2 min, in the experimental and standard treatment groups, respectively (p = 0.9020). There was no correlation between PIPP scores and other pain scales.Conclusion: We do not recommend doubling the dose during heel prick.What is Known:• Oral sucrose is included in almost all international position papers and recommendations for the treatment of mild to moderate pain in newborns, associated with non-nutritive sucking and facilitated tucking• Premature infant pain profile (PIPP) scale is the gold standard for evaluation of pain in preterms but it is difficult to use in clinical practiceWhat is New:• Repeating a dose of 24% sucrose is not effective in reducing pain during the recovery phase of a skin breaking procedure• Other pain scales, easier to use in clinical practice, are not comparable with PIPP for the evaluation of procedural pain in preterms.

Surfactant Components and Tracheal Aspirate Inflammatory Markers in Preterm Infants with Respiratory Distress Syndrome.

In 93 preterm infants ≤32 weeks of gestational age and 12 control infants, epithelial lining fluid disaturated-phosphatidylcholine, surfactant protein A and B, albumin, and myeloperoxidase activity were assessed after intubation and before exogenous surfactant administration. We found that disaturated-phosphatidylcholine, surfactant protein B, and myeloperoxidase were significantly higher in preterms with chorioamnionitis.

Neonatal tactile stimulation at birth in a low-resource setting.

BACKGROUND: Stimulation is the most common intervention during neonatal resuscitation at birth, but scarce information is available on the actual methods, timing and efficacy of this basic step. To evaluate the occurrence, patterns and response to tactile stimulation at birth in a low-resource setting. METHODS: We reviewed 150 video recordings of neonatal resuscitation at Beira Central Hospital (Beira, Mozambique). Timing, method, duration and response to tactile stimulation were evaluated. RESULTS: One hundred two out of 150 neonates (68.0%) received stimulation, while the remaining 48 (32.0%) received positive pressure ventilation and/or chest compressions directly. Overall, 546 stimulation episodes (median 4 episodes per subject, IQR 2-7) were performed. Median time to the first stimulation episode was 134 s (IQR 53-251); 29 neonates (28.4%) received stimulation within the first minute after birth. Multiple techniques of stimulation were administered in 66 neonates (64.7%), while recommended techniques (rubbing the back or flicking the soles of the feet) only in 9 (8.8%). Median duration of stimulation was 17 s (IQR 9-33). Only 9 neonates (8.8%) responded to stimulation. CONCLUSIONS: In a low-resource setting, stimulation of newly born infants at birth is underperformed. Adherence to international guidelines is low, resulting in delayed initiation, inadequate technique, prolonged duration and low response to stimulation. Back rubs may provide some benefits, but large prospective studies comparing different methods of stimulation are required.

Neonatal independent predictors of severe NEC.

PURPOSE: Necrotizing enterocolitis (NEC) is a severe neonatal disease. The present study aimed to identify factors predisposing the development of severe forms of NEC. METHODS: This retrospective study examined NEC patients in a single centre between 2002 and 2015. Data concerning clinical characteristics, therapeutic management as well as short-term outcomes were collected. We compared the patients receiving successful medical treatment and those requiring surgical intervention. Patients who underwent surgery were distinguished in three subcategories. Bivariate and multivariate analyses were used for the statistical analysis. RESULTS: We identified 155 patients in the study period. 102 were treated conservatively and 53 required surgery. 8 received a primary peritoneal drainage, 31 received a drainage and a subsequent laparotomy and 14 received a laparotomy. Multivariate regression analysis identified a lower risk for surgery with a later onset and higher serum pH values, whereas an increased risk with higher C reactive Protein (CRP) levels at the onset. Pneumatosis intestinalis was identified as a protective factor. Overall mortality was 6.4%, with higher percentage in surgical NEC. CONCLUSION: This study suggests that a later onset is a protective sign for the progression to surgery, whereas lower pH values and higher CRP levels are prognostic factors associated with the need for surgery. The line of treatment involving explorative laparotomy in case of perforation seems to be rewarded by low morbidity and mortality rate.

Reduced neonatal mortality in a regional hospital in Mozambique linked to a Quality Improvement intervention.

BACKGROUND: Neonatal mortality remains a serious health issue especially in low resource countries, where 99% of neonatal deaths occur. Doctors with Africa CUAMM is an Italian non-governmental organization in the field of healthcare that has been working in Africa since 1955. In Mozambique, at the Central Beira Hospital (CBH), it has a project with the aim of supporting the neonatal intensive care unit (NICU) and the Obstetrical Department of the CBH through a multi-level intervention. Our aim was to evaluate the effectiveness of CUAMM continuous Quality Improvement intervention in terms of reduction of the overall neonatal mortality rate in the NICU of CBH. METHODS: A baseline analysis was performed in order to assess the actual standard of neonatal care. Subsequently, the intervention was focused on three main areas: infrastructure, equipment and clinical protocols improvement. A retrospective pre- (2013)/post- (2014) implementation analysis of clinical outcomes was performed. RESULTS: Total population included 4,276 newborns, 2,118 (50%) born in 2013 and 2158 (50%) born after implementation. Baseline characteristics of the two groups were similar apart from a higher incidence of outborn neonates (33% vs 30%, p = 0.02) and a lower incidence of Apgar score < 7 at 5 min (37% vs 43%, p < 0.01). The rates of admissions for asphyxia (22% vs 30%), sepsis (4% vs 7%) and prematurity (18% vs 28%) increased between the two study period. Mortality rate for each of these causes decreased from before to after the implementation: asphyxia (34% vs 19%, p < 0.01), sepsis (39% vs 28%, p = 0.06) and prematurity (43% vs 33%, p < 0.01). CONCLUSION: We found a reduction in mortality rate among newborns admitted to CBH's NICU after the first year of CUAMM intervention. Most of this reduction can be attributed to the decrease in deaths for asphyxia, sepsis and prematurity. A Quality Improvement intervention based on infrastructural, equipment and clinical objectives was associated with a reduction of neonatal mortality rate in a low-resource NICU.

Bitter lupine beans ingestion in a child: a disregarded cause of acute anticholinergic toxicity.

UNLABELLED: We describe the case of a 6-year-old girl brought to the emergency department for the sudden onset of anticholinergic syndrome after the ingestion of a few home-made partially debittered lupine beans. She complained of blurry vision, headache, photophobia and nausea. No specific treatment was needed, and the symptoms resolved about 12 h after the exposure. Lupine beans are a popular and worldwide-diffused food. The bitter variety is rich in alkaloids harbouring anticholinergic activity and thus requires a debittering process before lupines can be eaten. Only four cases of acute toxicity, due to the ingestion of incompletely detoxified bitter lupines, have been reported in children so far; notwithstanding the small amount of lupines ingested, three of these cases were lethal. CONCLUSION: Acute anticholinergic syndrome can arise after the consumption of a wide range of exogenous substances including partially debittered lupine beans. Paediatricians should be aware of bitter lupine toxicity, recognize possible cases of intoxication, ensure a prompt and appropriate supportive treatment and provide appropriate information about their danger.

Complementary feeding in infants born preterm: Aspects needing improvement.

Objective: The aim of our study was to collect data on complementary feeding (CF) in preterm infants (PIs). Methods: We enrolled PI ≤ 34 weeks of gestational age discharged from the neonatal intensive care unit (NICU) of the University Hospital of Padova. At 12 months of corrected age (CA), CF was investigated with questionnaires to the parents and a 24-h dietary recall. In a subgroup of newborns, we also evaluated bone status at a CA of 12 months using quantitative ultrasound. Results: We studied 167 ex PI at 1 year of CA. CF was introduced in 67.1% of them between 5 and 8 months of chronological age, with fruit as the first food (81%, n = 136). Sweet drinks were consumed by 17.4% of our sample, and salt was added in 33.5% of cases. PIs, at 1 year CA, introduced extra energy compared to the theoretical requirement (121 ± 31 kcal/kg/day) and higher protein intake than recommended (39 ± 11 g/day), while the intake of both total lipids and carbohydrates was slightly lower. Vitamins and minerals were adequate, except vitamin D. Regarding bone status, we found a correlation between vitamin D intakes from the diet and bone parameters (metacarpus-bone transmission time: r = 0.36, p = 0.01) at 1 year of CA. Conclusions: Our population of PIs started CF in agreement with current suggestions though with a notable heterogeneity and with some mistakes. Vitamin D intake was correlated with bone status at 1 year of CA.

Diencephalic syndrome as sign of tumor progression in a child with neurofibromatosis type 1 and optic pathway glioma: a case report.

ILLUSTRATIVE CASE: We describe the case of a 3-year-old child, diagnosed with familial neurofibromatosis type 1 (NF1) and asymptomatic optic pathway tumor at the age of two, who developed diencephalic syndrome (DS) due to tumor progression 1 year after diagnosis. Magnetic resonance imaging disclosed an enlarging hypothalamic contrast-enhanced mass. Because of the tumor progression, in terms of tumor volume and DS, chemotherapy (CT) treatment was started according to the international protocol for progressive low-grade glioma, with rapid clinical improvement in terms of gain weight and DS resolution. Interestingly, tumor volume was unchanged after CT. CONCLUSIONS: This case report highlights the following facts: (1) optic pathway glioma (OPG) in young children with NF1 may have definitive growth potentials and thus, they are worth an accurate clinical follow-up; (2) also, OPG occurring in NF1 patients can be responsible for DS in case of hypothalamus involvement; (3) consequently, the child's growth pattern must be included among the clinical parameters, which must be specifically evaluated during the follow-up of children, with or without NF1, bearing an OPG; and, finally, (4) that DS can improve after CT, even in face of a stable tumor volume.

Efficacy and safety of ketamine for neonatal refractory status epilepticus: case report and systematic review.

Background: Evidence-based data on treatment of neonatal status epilepticus (SE) are scarce. We aimed to collect data on the efficacy and safety of ketamine for the treatment of neonatal SE and to assess its possible role in the treatment of neonatal SE. Methods: We described a novel case and conducted a systematic literature review on neonatal SE treated with ketamine. The search was carried out in Pubmed, Cochrane, Clinical Trial Gov, Scopus and Web of Science. Results: Seven published cases of neonatal SE treated with ketamine were identified and analyzed together with our novel case. Seizures typically presented during the first 24 h of life (6/8). Seizures were resistant to a mean of five antiseizure medications. Ketamine, a NMDA receptor antagonist, appeared to be safe and effective in all neonates treated. Neurologic sequelae including hypotonia and spasticity were reported for 4/5 of the surviving children (5/8). 3/5 of them were seizure free at 1-17 months of life. Discussion: Neonatal brain is more susceptible to seizures due to a shift towards increased excitation because of a paradoxical excitatory effect of GABA, a greater density of NMDA receptors and higher extracellular concentrations of glutamate. Status epilepticus and neonatal encephalopathy could further enhance these mechanisms, providing a rationale for the use of ketamine in this setting. Conclusions: Ketamine in the treatment of neonatal SE showed a promising efficacy and safety profile. However, further in-depth studies and clinical trials on larger populations are needed.

Bone Status and Early Nutrition in Preterm Newborns with and without Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR) together with preterm birth could be harmful to bone health. The aim of the study was to examine bone status in IUGR versus non-IUGR preterms and to analyze the nutritional management best correlated with its improvement. Newborns < 34 weeks of gestational age (wGA), 75 IUGR and 75 non-IUGR, admitted to the Neonatal Intensive Care Unit of the University Hospital of Padova were enrolled and monitored from birth until 36 wGA through anthropometry (weight, length, head circumference, lower limb length (LLL)), biochemistry, bone quantitative ultrasound assessment of bone status (metacarpus bone transmission time, mc-BTT, us) and nutritional intakes monitoring during parenteral nutrition. IUGR compared to non-IUGR showed lower mean mc-BTT (0.45 vs. 0.51, p = 0.0005) and plasmatic phosphate (1.45 vs. 1.79, p < 0.001) at birth. Mc-BTT at 36 wGA, though equal between groups, correlated in IUGR newborns with basal phosphate, mean total energy of the first week and month (positively) and days to reach full enteral feeding (negatively). Lower i.v. vitamin D intake, LLL and prolonged total parenteral nutrition predicted worse mc-BTT at 36 wGA in the enrolled infants. These results suggest that preterms and in particular IUGR newborns need special nutritional care to promote bone development.