Maria Elena Cavicchiolo

Perinatal palliative care (PnPC) is critical for improving the quality of life of infants with extreme prematurity and life-limiting conditions. However, its implementation differs significantly worldwide. This systematic review will assess and compare PnPC models in neonatal intensive care units (NICUs) to identify best practices, challenges, and areas for improvement. Following PRISMA guidelines, a systematic search of PubMed, Embase, and CINAHL was conducted for studies published in the last decade describing PnPC delivery models. Data on study design, PnPC model characteristics, team composition, timing of involvement, and key outcomes were extracted and synthesized. Fourteen observational studies were included; no interventional trials were identified. The majority of studies originated from the USA (64%). Three primary PnPC delivery models were identified: consultative, integrative, and team-collaborative. Consultative models improved referral rates but were often associated with delays, whereas integrative and collaborative models provided more seamless, continuous care. Across all models, multidisciplinary teams were central to care delivery. Early integration of PnPC, particularly from the antenatal period, was associated with improved outcomes, including higher parental satisfaction, clearer goals of care, and reduced aggressive end-of-life interventions. Conclusion : Early, integrated PnPC delivered by a multidisciplinary team improves end-of-life care and family support in the NICU. However, significant heterogeneity in practice and a lack of high-level evidence persists. Future research should prioritize rigorous interventional designs, greater geographical diversity, and the use of standardized, family-centered outcome measures to establish evidence-based guidelines for neonatal palliative care. What is known:  • Perinatal Palliative Care is a vital part of neonatology, prioritizing the quality of life for extremely preterm infants and those with life-limiting conditions. What is New: • The review revealed variability in perinatal palliative care models, timing and team compositions, suggesting early integration can improve support for babies, families and healthcare teams. • Future research should focus on rigorous interventional designs, geographic diversity, and long-term family centered outcomes. • Integrating practical clinical experience with theoretical education strengthens healthcare professionals’ competencies and guidelines development.

Minimizing environmental stressors is crucial for neonatal health. The American Academy of Pediatrics and the World Health Organization have issued recommendations to limit noise levels for newborns, but no specific regulations currently address vibration exposure. This study’s objective is to quantitatively assess comfort and physiological stability in neonates and infants during a pram transport. Healthy neonates and infants (< 6 months old) were enrolled for a 15-min walk using a commercially available pram over different surfaces. Vibrations were recorded using accelerometers, while physiological parameters were monitored with a neonatal SpO₂ sensor. Comfort and physiological scores were assessed using the Transport Risk Index of Physiologic Stability score and Comfort Neo Scale. Eighteen subjects (median age: 93 days, IQR [59, 158]; median weight: 5.5 kg (IQR [5, 7.5]) were included. Median vibration total value ranged from 1.10 to 2.71 m/s², with the highest values recorded on gravel surfaces. Higher vibration total values correlated with greater agitation scores (r = .601, p = .001) and facial tension (r = 0.437, p = .011). Increased heart rate was associated with greater alertness (r = .559, p = .03) and body movement (r = .534, p = .039). Lower oxygen saturation correlated with increased agitation (r = − .239, p = .049) and facial tension (r = –.415, p > .001). Conclusions: Mechanical vibrations during pram transport were associated with behavioral changes in neonates and infants, with higher vibration exposure correlating with greater agitation scores. These findings highlight the need for further research to define safe vibration exposure thresholds, particularly for hospital neonatal transport. What is Known: • Neonatal and infant transport, both in and out of hospitals, causes significant stress due to mechanical vibrations. However, no specific regulations address vibration exposure, and its impact on overall physiological regulation remains poorly understood. What is New: • This study included healthy newborns and infants instead of manikins, allowing a direct assessment of vital parameters and comfort in response to vibration exposure. Our findings demonstrate that different vibration levels may impact both behavioral and physiological parameters in this population.

Appropriate nutrition is of paramount importance during infancy and childhood, and Parenteral Nutrition (PN), which is the intravenous infusion of nutrients in the elementary form, may be necessary as a supplement or a full replacement for enteral nutrition

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.

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.

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.

Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a systematic review of studies applying untargeted metabolomics and gut microbiota analysis to evaluate the differences between neonates affected by NEC (Bell’s stage II or III), and/or by spontaneous intestinal perforation (SIP) versus healthy controls. Five studies applying metabolomics (43 cases, 95 preterm controls) and 20 applying gut microbiota analysis (254 cases, 651 preterm controls, 22 term controls) were selected. Metabolomic studies utilized NMR spectroscopy or mass spectrometry. An early urinary alanine/histidine ratio >4 showed good sensitivity and predictive value for NEC in one study. Samples collected in proximity to NEC diagnosis demonstrated variable pathways potentially related to NEC. In studies applying untargeted gut microbiota analysis, the sequencing of the V3–V4 or V3 to V5 regions of the 16S rRNA was the most used technique. At phylum level, NEC specimens were characterized by increased relative abundance of Proteobacteria compared to controls. At genus level, pre-NEC samples were characterized by a lack or decreased abundance of Bifidobacterium. Finally, at the species level Bacteroides dorei, Clostridium perfringens and perfringens-like strains dominated early NEC specimens, whereas Clostridium butyricum, neonatale and Propionibacterium acnei those at disease diagnosis. Six studies found a lower Shannon diversity index in cases than controls. A clear separation of cases from controls emerged based on UniFrac metrics in five out of seven studies. Importantly, no studies compared NEC versus SIP. Untargeted metabolomics and gut microbiota analysis are interrelated strategies to investigate NEC pathophysiology and identify potential biomarkers. Expression of quantitative measurements, data sharing via biorepositories and validation studies are fundamental to guarantee consistent comparison of results.

Perinatal asphyxia (PA) still occurs in about three to five per 1,000 deliveries in developed countries; 20% of these infants show hypoxic-ischemic encephalopathy (HIE) on brain magnetic resonance imaging (MRI). The aim of our study was to apply metabolomic analysis to newborns undergoing therapeutic hypothermia (TH) after PA to identify a distinct metabotype associated with the development of HIE on brain MRI. We enrolled 53 infants born at >35 weeks of gestation with PA: 21 of them showed HIE on brain MRI (the “HIE” group), and 32 did not (the “no HIE” group). Urine samples were collected at 24, 48 and 72 hours of TH. Metabolomic data were acquired using high-resolution mass spectrometry and analyzed with univariate and multivariate methods. Considering the first urines collected during TH, untargeted analysis found 111 relevant predictors capable of discriminating between the two groups. Of 35 metabolites showing independent discriminatory power, four have been well characterized: L-alanine, Creatine, L-3-methylhistidine, and L-lysine. The first three relate to cellular energy metabolism; their involvement suggests a multimodal derangement of cellular energy metabolism during PA/HIE. In addition, seven other metabolites with a lower annotation level (proline betaine, L-prolyl-L-phenylalanine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E, 2,6 dimethylheptanoyl carnitine, Octanoylglucuronide, 19-hydroxyandrost-4-ene-3,17-dione) showed biological consistency with the clinical picture of PA. Moreover, 4 annotated metabolites (L-lysine, L-3-methylhistidine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E) retained a significant difference between the “HIE” and “no HIE” groups during all the TH treatment. Our analysis identified a distinct urinary metabotype associated with pathological findings on MRI, and discovered 2 putative markers (L-lysine, L-3-methylhistidine) which may be useful for identifying neonates at risk of developing HIE after PA.

Sucrose is effective in reducing pain during minor procedures in neonates. We evaluated whether a second dose of sucrose was more effective than a single dose during venipuncture. We performed a randomised, double-blind, controlled trial at the NICU of Padua Hospital (August 2016-October 2017). We randomised 72 preterm infants undergoing venipuncture for routine test to a control group, which received a single standard dose of sucrose 2′ before the procedure and a placebo 30″ after the venipuncture, and an experimental group in which they received two doses of 24% sucrose 2′ before and 30″ after the venipuncture. No difference in pain perception was found between the groups at 30″, 60″ and 120″. In conclusion, we do not recommend a second dose of sucrose during venipuncture in prematures.

Necrotizing enterocolitis (NEC) is the main gastrointestinal emergency of preterm infants for whom bowel rest and parenteral nutrition (PN) is essential. Despite the improvements in neonatal care, the incidence of NEC remains high (11% in preterm newborns with a birth weight <1500 g) and up to 20–50% of cases still require surgery. In this narrative review, we report how to optimize PN in severe NEC requiring surgery. PN should begin as soon as possible in the acute phase: close fluid monitoring is advocated to maintain volemia, however fluid overload and electrolytes abnormalities should be prevented. Macronutrients intake (protein, glucose, and lipids) should be adequately guaranteed and is essential in each phase of the disease. Composite lipid emulsion should be the first choice to reduce the risk of parenteral nutrition associated liver disease (PNALD). Vitamin and trace elements deficiency or overload are frequent in long-term PN, therefore careful monitoring should be planned starting from the recovery phase to adjust their parenteral intake. Neonatologists must be aware of the role of nutrition especially in patients requiring long-term PN to sustain growth, limiting possible adverse effects and long-term deficiencies.