Cavallaro, G. (Giacomo)
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- Endothelial dysfunction in preterm infants: The hidden legacy of uteroplacental pathologies(Frontiers, 2022-11-04) Manzoni, F. (Francesca); Amodeo, I. (Ilaria); Gulden, S. (Silvia); Mosca, F. (Fabio); Provitera, L. (Livia); Tomaselli, A. (Andrea); Cavallaro, G. (Giacomo); Raffaeli, G. (Genny); Pravatà, V. (Valentina); Amelio, G.S. (Giacomo Simeone); Villamor, E. (Eduardo); Tripodi, M. (Matteo); Cortesi, V. (Valeria); Garrido-Martínez-de-Salazar, F. (Felipe); Cervellini, G. (Gaia)Millions of infants are born prematurely every year worldwide. Prematurity, particularly at lower gestational ages, is associated with high mortality and morbidity and is a significant global health burden. Pregnancy complications and preterm birth syndrome strongly impact neonatal clinical phenotypes and outcomes. The vascular endothelium is a pivotal regulator of fetal growth and development. In recent years, the key role of uteroplacental pathologies impairing endothelial homeostasis is emerging. Conditions leading to very and extremely preterm birth can be classified into two main pathophysiological patterns or endotypes: infection/inflammation and dysfunctional placentation. The first is frequently related to chorioamnionitis, whereas the second is commonly associated with hypertensive disorders of pregnancy and fetal growth restriction. The nature, timing, and extent of prenatal noxa may alter fetal and neonatal endothelial phenotype and functions. Changes in the luminal surface, oxidative stress, growth factors imbalance, and dysregulation of permeability and vascular tone are the leading causes of endothelial dysfunction in preterm infants. However, the available evidence regarding endothelial physiology and damage is limited in neonates compared to adults. Herein, we discuss the current knowledge on endothelial dysfunction in the infectious/inflammatory and dysfunctional placentation endotypes of prematurity, summarizing their molecular features, available biomarkers, and clinical impact. Furthermore, knowledge gaps, shadows, and future research perspectives are highlighted.
- Human bone marrow-derived mesenchymal stromal cells reduce the severity of experimental necrotizing enterocolitis in a concentration-dependent manner(MDPI, 2023) Manzoni, F. (Francesca); Amodeo, I. (Ilaria); Gulden, S. (Silvia); Lonati, C. (Caterina); Mosca, F. (Fabio); Provitera, L. (Livia); Maggioni, M. (Marco); Tomaselli, A. (Andrea); Cerasani, J. (Jacopo); Cavallaro, G. (Giacomo); Pesenti, N. (Nicola); Raffaeli, G. (Genny); Crippa, S. (Stefania); Bernardo, M.E. (Maria Ester); Arribas-Sánchez, C. (Cristina); Amelio, G.S. (Giacomo Simeone); Oldoni, S. (Samanta); Menis, C. (Camilla); Tripodi, M. (Matteo); Cortesi, V. (Valeria); Santi, L. (Ludovica); Algieri, F. (Francesca); Garrido-Martínez-de-Salazar, F. (Felipe); Cervellini, G. (Gaia): Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3–6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 106 or 1 × 106 ) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 106 ) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.
- Current pain management practices for preterm infants with necrotizing enterocolitis: a European survey(Nature Publishing Group, 2023) Simons, S.H.P. (Sinno H. P.); Meesters, N.J. (Naomi J.); Allegaert, K. (Karel); Vermeulen, M.J. (Marijn J.); Ten-Barge, J.A. (Judith A.); Cavallaro, G. (Giacomo); Raffaeli, G. (Genny); Bosch, G.E. (Gerbrich E.) van den; Arribas-Sánchez, C. (Cristina); Garrido-Martínez-de-Salazar, F. (Felipe)Background: Necrotizing enterocolitis (NEC) is a highly painful intestinal complication in preterm infants that requires adequate pain management to prevent short- and long-term effects of neonatal pain. There is a lack of international guidelines for pain management in NEC patients. Therefore, this study aims to describe current pain management for NEC patients in European neonatal intensive care units (NICUs). Methods: An online survey was designed and conducted to assess current practices in pain management for NEC patients in European NICUs. The survey was distributed via neonatal societies, digital platforms, and professional contacts. Results: Out of the 259 responding unique European NICUs from 36 countries, 61% had a standard protocol for analgesic therapy, 73% assessed pain during NEC, and 92% treated NEC patients with intravenous analgosedatives. There was strong heterogeneity in the used pain scales and initial analgesic therapy, which mainly included acetaminophen (70%), fentanyl (56%), and/or morphine (49%). A third of NICU representatives considered their pain assessment adequate, and half considered their analgesic therapy adequate for NEC patients. Conclusions: Various pain scales and analgesics are used to treat NEC patients in European NICUs. Our results provide the first step towards an international guideline to improve pain management for NEC patients. Impact: This study provides an overview of current pain management practices for infants with necrotizing enterocolitis (NEC) in European neonatal intensive care units. Choice of pain assessment tools, analgosedatives, and dosages vary considerably among NICUs and countries. A third of NICU representatives were satisfied with their current pain assessment practices and half of NICU representatives with their analgesic therapy practices in NEC patients in their NICU. The results of this survey may provide a first step towards developing a European pain management consensus guideline for patients with NEC.
- Description of the exposure of the most-followed spanish instamom's children to social medias(MDPI, 2022) García, P. (Pilar); Cavallaro, G. (Giacomo); González-Caballero, J.L. (Juan Luis); Raffaeli, G. (Genny); Merino, M. (María); Vacaroaia, A. (Alex); Sanmiguel, P. (Patricia); Arribas-Sánchez, C. (Cristina); Iriso, I. (Isabel); Couso, B. (Beatriz); Álvarez, A. (Alexandra); Garrido-Martínez-de-Salazar, F. (Felipe)There is evidence of the risk of overexposure of children on social networks by parents working as influencers. A cross-sectional study of the profiles of the sixteen most-followed Instamoms in Spain was carried out. An analysis of these profiles was performed over a full month (April 2022), three times a week, to describe the representation of influencers’ children in the posts shared by them, as well as their role in the Instamoms’ marketing. A total of 192 evaluations of the profiles were performed in the study period. The average number of children exposed by an Instamom was three, generally preschoolers and schoolchildren. The children appear in a context of the family home and accompanied by their mother. The type of advertising that accompanies the appearance of underage children is usually women or children’s clothing, but also food products, leisure, etc. Appearance of children in the posts had a statistically significant influence on followers measured by the number of likes. Results provided the identification of two Instamom clusters with differentiated behaviors in relation to appearance of children in posts. It is important to involve Social Pediatrics in the protection of the privacy and interests of children given the increase in sharenting. The authors believe that there are concerns about their explicit consent to public exposure from early childhood and about the medium and long-term effect that this may have on their future well-being.
- Grading the level of evidence of neonatal pharmacotherapy: midazolam and phenobarbital as examples(Springer Nature, 2023-09-26) Simons, S.H.P. (Sinno H. P.); Beken, S. (Serdar); Kotidis, C. (Charalampos); Smits, A. (Anne); Mahoney, L. (Liam); Allegaert, K. (Karel); Cavallaro, G. (Giacomo); Bhatt, A. (Aomesh); Raffaeli, G. (Genny); Flint, R.B. (Robert B.); Dempsey, E.M. (Eugene M.); Ünal, S. (Sezin); Garrido-Martínez-de-Salazar, F. (Felipe)BACKGROUND: Many drugs are used off-label or unlicensed in neonates. This does not mean they are used without evidence or knowledge. We aimed to apply and evaluate the Grading and Assessment of Pharmacokinetic–Pharmacodynamic Studies (GAPPS) scoring system for the level of evidence of two commonly used anti-epileptic drugs. METHODS: Midazolam and phenobarbital as anti-epileptics were evaluated with a systematic literature search on neonatal pharmacokinetic (PK) and/or pharmacodynamic [PD, (amplitude-integrated) electroencephalography effect] studies. With the GAPPS system, two evaluators graded the current level of evidence. Inter-rater agreement was assessed for dosing evidence score (DES), quality of evidence (QoE), and strength of recommendation (REC). RESULTS: Seventy-two studies were included. DES scores 4 and 9 were most frequently used for PK, and scores 0 and 1 for PD. Inter-rater agreements on DES, QoE, and REC ranged from moderate to very good. A final REC was provided for all PK studies, but only for 25% (midazolam) and 33% (phenobarbital) of PD studies. CONCLUSIONS: There is a reasonable level of evidence concerning midazolam and phenobarbital PK in neonates, although using a predefined target without integrated PK/PD evaluation. Further research is needed on midazolam use in term neonates with therapeutic hypothermia, and phenobarbital treatment in preterms.
- Association between co‐sleeping in the first year of life and preschoolers ́ sleep patterns(Springer, 2024) Garrido, S. (Silvia); García, P. (Pilar); Cavallaro, G. (Giacomo); Garrido, F. (Felipe); González-Caballero, J.L. (Juan Luis); Raffaeli, G. (Genny); Atance, V. (Verónica); González, L. (Lucía); Gianni, M.L. (Maria Lorella)This study aimed to investigate the association between co-sleeping practiced during the first year of life and preschoolers' sleep patterns. A cross-sectional study including toddlers was designed to analyze their sleep patterns. The Brief Infant Sleep Questionnaire, validated in Spanish, was used to measure sleep quality. A latent class analysis was performed to identify qualitative subgroups in the sample and explore the effects of co-sleeping. The sleep patterns of 276 children were analyzed. A total of 181 (65%) parents reported having practiced co-sleeping with their children. The latent class analysis identified a two-class solution with two different sleep patterns. One of them showed a worse quality sleep pattern, which had a significant association with having practiced co-sleeping during the first year of life, and with the fact that they were still sleeping in the parents' room, among other characteristics related to co-sleeping and parental concerns. Breastfeeding also showed association with a worse quality sleep pattern. Conclusion: Based on the present findings, co-sleeping during the first year of life appears to be associated with poor sleep patterns in young preschoolers.
- Variations in antibiotic use and sepsis management in neonatal intensive care units: A European survey(2021) Paniagua, M. (Miren); Allegaert, K. (Karel); Cavallaro, G. (Giacomo); Raffaeli, G. (Genny); Arribas-Sánchez, C. (Cristina); Villamor, E. (Eduardo); Garrido-Martínez-de-Salazar, F. (Felipe)Management of neonatal sepsis and the use of antimicrobials have an important impact on morbidity and mortality. However, there is no recent background on which antibiotic regimens are used in different European neonatal intensive care units (NICUs). Our study aimed to describe the use of antibiotics and other aspects of early- and late-onset sepsis (EOS and LOS, respectively) management by European NICUs. We conducted an online survey among NICUs throughout Europe to collect information about antibiotic stewardship, antibiotic regimens, and general aspects of managing neonatal infections. NICUs from up to 38 European countries responded, with 271 valid responses. Most units had written clinical guidelines for EOS (92.2%) and LOS (81.1%) management. For EOS, ampicillin, penicillin, gentamicin, and amikacin were the most commonly used antibiotics. Analysis of the combinations of EOS regimens showed that the most frequently used was ampicillin plus gentamicin (54.6%). For LOS, the most frequently used antibiotics were vancomycin (52.4%), gentamicin (33.9%), cefotaxime (28%), and meropenem (15.5%). Other aspects of the general management of sepsis have also been analyzed. The management of neonatal sepsis in European NICUs is diverse. There was high self-reported adherence to the local clinical guidelines. There was homogeneity in the combination of antibiotics in EOS but less in LOS.