Μεταβολές των παραμέτρων της θρομβοελαστογραφίας στα νεογνά με περιγεννητική υποξία-ασφυξία και πιθανή χρήση της μεθόδου ως προγνωστικός και θεραπευτικός δείκτης στα νεογνά αυτά.

Εισαγωγή: Η περιγεννητική υποξία-ασφυξία προκαλεί άλλοτε άλλου βαθμού υποξαιμία, ισχαιμία και τελικά μεταβολική οξέωση. Η μειωμένη παροχή αίματος και οξυγόνου στους ιστούς διαταράσσει τη λειτουργία όλων των οργάνων του σώματος. Η επίδραση αυτών των παραγόντων στη λειτουργία του ήπατος και στο μυελό των οστών οδηγεί σε αυξημένη κατανάλωση αιμοπεταλίων και κάποιων παραγόντων πήξης, με αποτέλεσμα να επιβαρύνεται περαιτέρω το ήδη ανώριμο νεογνικό αιμοστατικό σύστημα. Έτσι η περιγεννητική υποξία συνδέεται με αυξημένο κίνδυνο διαταραχών της πήξης, η πρόληψη - ει δυνατόν - και έγκαιρη αντιμετώπιση των οποίων έχει μεγάλη σημασία. Η θρομβοελαστομετρία (ΤΕΜ), η οποία είναι μια ιξωδοελαστική μέθοδος που εκτιμά τη δυναμική της διαδικασίας της πήξης στο σύνολο της, θα μπορούσε να αποτελέσει ένα αξιόπιστο εργαλείο για τη μελέτη της κατάστασης της αιμόστασης στα νεογνά με περιγεννητική υποξία. Σκοπός της μελέτης αυτής ήταν η αξιολόγηση του αιμοστατικού προφίλ των νεογνών με περιγεννητική υποξία μέσω των μεταβολών των παραμέτρων της δοκιμασίας TEM-EXTEM καθώς επίσης και η αξιολόγηση της μεθόδου ως θεραπευτικού και προγνωστικού δείκτη για τα νεογνά αυτά. Μέθοδος και υλικό: Συνολικά μελετήθηκαν 164 νεογνά με περιγεννητική υποξία-ασφυξία, που νοσηλεύτηκαν στη ΜΕΝΝ του Γενικού Νοσοκομείου Νίκαιας. Τους μάρτυρες αποτέλεσαν 273 υγιή νεογνά που γεννήθηκαν στο Μαιευτήριο του ίδιου νοσοκομείου. Τα πάσχοντα νεογνά χωρίστηκαν σε δύο υποομάδες: 1) 16 νεογνά με περιγεννητική ασφυξία (σύμφωνα με τον ορισμό της AAP και του ACOG) και 2) 148 νεογνά με εμβρυϊκή δυσπραγία/stress. Σε όλα τα νεογνά της μελέτης καταγράφηκαν τα δημογραφικά τους στοιχεία, κλινικά χαρακτηριστικά και αποτελέσματα εργαστηριακών εξετάσεων. Υπολογίστηκε το SNAPPE score (Score for Neonatal Acute Physiology Perinatal Extension) τις πρώτες 12 ώρες νοσηλείας και πραγματοποιήθηκε η δοκιμασία TEM-EXTEM μέχρι το 3ο 24ωρο νοσηλείας. Αποτελέσματα: Σε όλα τα υποξικά νεογνά παρατηρήθηκε υποπηκτικό προφίλ, το οποίο εκφράστηκε με σημαντικά παρατεταμένα CT, CFT και μειωμένα τα A10, A20, A30, a angle και MCF σε σχέση με τα υγιή νεογνά. Οι παράμετροι EXTEM ανέδειξαν πιο έντονο υποπηκτικό προφίλ στα νεογνά με περιγεννητική ασφυξία σε σχέση με τα νεογνά με stress. Επίσης στα νεογνά με υποξία παρατηρήθηκε σημαντική συσχέτιση μεταξύ των παραμέτρων EXTEM και των δεικτών της ηπατικής και νεφρικής λειτουργίας (SGOT, LDH, ALBUMIN και Cr αντίστοιχα), των αιμοπεταλίων και των εμπύρηνων ερυθρών αιμοσφαιρίων. Τέλος όλες οι παράμετροι EXTEM παρουσίασαν συσχέτιση με το SNAPPE score και τη θνησιμότητα των νεογνών με υποξία. Συμπέρασμα: Το υποπηκτικό προφίλ το οποίο προέκυψε από τις μετρήσεις των παραμέτρων EXTEM στα υποξικά νεογνά, φαίνεται ότι μπορεί να αποτελέσει ένα χρήσιμο βιοδείκτη για την πρώιμη ανίχνευση των διαταραχών της αιμόστασης σε αυτά τα νεογνά, ενώ ταυτόχρονα ο βαθμός υποπηκτικότητας ίσως σχετίζεται με τη βαρύτητα της υποξίας.Introduction: Perinatal hypoxia/asphyxia results in varying degrees of hypoxemia, ischemia, and finally metabolic acidosis. Compromised blood and oxygen supply disrupt the function of all the organs. The impact of these disorders on liver and bone marrow function leads to increased consumption of platelets and several coagulation factors, and subsequently to further derangement of the already immature neonatal hemostatic system. Therefore, perinatal hypoxia is related to increased risk of coagulopathy, the prevention -if possible- and timely management of which is of great importance. Thromboelastometry (TEM), a viscoelastic method evaluating the whole coagulation process dynamics, could be a reliable tool for studying the hemostatic status of neonates with perinatal hypoxia. Aim: The aim of this study was to assess the hemostatic profile of neonates with perinatal hypoxia through alterations of the parameters of extrinsically activated TEM-EXTEM assay, as well as to evaluate this method as a prognostic and a therapeutic biomarker for hypoxic neonates. Methods and materials: A total of 164 neonates with perinatal hypoxia/asphyxia, hospitalized in the NICU of Nikaia General Hospital, were included. Healthy neonates (n=273) born at the maternity ward of the same hospital served as controls. Hypoxic neonates were divided in two subgroups: 1) 16 neonates with perinatal asphyxia (according to the AAP and ACOG definition), and 2) 148 neonates with fetal distress. Demographics, clinical characteristics, and laboratory results were recorded for all of the study neonates. SNAPPE score (Score for Neonatal Acute Physiology Perinatal Extension) was calculated within the first 12 hours of admission and TEM-EXTEM test was performed during the first 3 days. Results: All the hypoxic neonates demonstrated a hypocoagulable profile, presenting with significantly prolonged CT, CFT and reduced A10, A20, A30, a angle and MCF, when compared to healthy neonates. EXTEM variables showed a more intense hypocoagulable profile in neonates with perinatal asphyxia in comparison to the neonates with fetal distress. Moreover, in hypoxic neonates, significant correlation was noted between EXTEM parameters and hepatic and renal function biomarkers (SGOT, LDH, ALBUMIN and Cr), platelets, and nucleated red blood cells. Finally, for hypoxic neonates, all EXTEM variables were significantly correlated with SNAPPE score and mortality. Conclusion: In neonates with hypoxia, hypocoagulability deriving from EXTEM parameters’ results, seems to be a promising biomarker for early detection of coagulation disorders, while the degree of hypocoagulability may correlate with the severity of hypoxia

Reply to Ghirardello et al Letter to the Editor

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Alterations of thromboelastographic variables in neonates with perinatal hypoxia/asphyxia and potential use of this method as prognostic and therapeutic biomarker for these neonates

Introduction: Perinatal hypoxia/asphyxia results in varying degrees of hypoxemia, ischemia, and finally metabolic acidosis. Compromised blood and oxygen supply disrupt the function of all the organs. The impact of these disorders on liver and bone marrow function leads to increased consumption of platelets and several coagulation factors, and subsequently to further derangement of the already immature neonatal hemostatic system. Therefore, perinatal hypoxia is related to increased risk of coagulopathy, the prevention -if possible- and timely management of which is of great importance. Thromboelastometry (TEM), a viscoelastic method evaluating the whole coagulation process dynamics, could be a reliable tool for studying the hemostatic status of neonates with perinatal hypoxia. Aim: The aim of this study was to assess the hemostatic profile of neonates with perinatal hypoxia through alterations of the parameters of extrinsically activated TEM-EXTEM assay, as well as to evaluate this method as a prognostic and a therapeutic biomarker for hypoxic neonates. Methods and materials: A total of 164 neonates with perinatal hypoxia/asphyxia, hospitalized in the NICU of Nikaia General Hospital, were included. Healthy neonates (n=273) born at the maternity ward of the same hospital served as controls. Hypoxic neonates were divided in two subgroups: 1) 16 neonates with perinatal asphyxia (according to the AAP and ACOG definition), and 2) 148 neonates with fetal distress. Demographics, clinical characteristics, and laboratory results were recorded for all of the study neonates. SNAPPE score (Score for Neonatal Acute Physiology Perinatal Extension) was calculated within the first 12 hours of admission and TEM-EXTEM test was performed during the first 3 days. Results: All the hypoxic neonates demonstrated a hypocoagulable profile, presenting with significantly prolonged CT, CFT and reduced A10, A20, A30, a angle and MCF, when compared to healthy neonates. EXTEM variables showed a more intense hypocoagulable profile in neonates with perinatal asphyxia in comparison to the neonates with fetal distress. Moreover, in hypoxic neonates, significant correlation was noted between EXTEM parameters and hepatic and renal function biomarkers (SGOT, LDH, ALBUMIN and Cr), platelets, and nucleated red blood cells. Finally, for hypoxic neonates, all EXTEM variables were significantly correlated with SNAPPE score and mortality. Conclusion: In neonates with hypoxia, hypocoagulability deriving from EXTEM parameters’ results, seems to be a promising biomarker for early detection of coagulation disorders, while the degree of hypocoagulability may correlate with the severity of hypoxia.Εισαγωγή: Η περιγεννητική υποξία-ασφυξία προκαλεί άλλοτε άλλου βαθμού υποξαιμία, ισχαιμία και τελικά μεταβολική οξέωση. Η μειωμένη παροχή αίματος και οξυγόνου στους ιστούς διαταράσσει τη λειτουργία όλων των οργάνων του σώματος. Η επίδραση αυτών των παραγόντων στη λειτουργία του ήπατος και στο μυελό των οστών οδηγεί σε αυξημένη κατανάλωση αιμοπεταλίων και κάποιων παραγόντων πήξης, με αποτέλεσμα να επιβαρύνεται περαιτέρω το ήδη ανώριμο νεογνικό αιμοστατικό σύστημα. Έτσι η περιγεννητική υποξία συνδέεται με αυξημένο κίνδυνο διαταραχών της πήξης, η πρόληψη - ει δυνατόν - και έγκαιρη αντιμετώπιση των οποίων έχει μεγάλη σημασία. Η θρομβοελαστομετρία (ΤΕΜ), η οποία είναι μια ιξωδοελαστική μέθοδος που εκτιμά τη δυναμική της διαδικασίας της πήξης στο σύνολο της, θα μπορούσε να αποτελέσει ένα αξιόπιστο εργαλείο για τη μελέτη της κατάστασης της αιμόστασης στα νεογνά με περιγεννητική υποξία. Σκοπός της μελέτης αυτής ήταν η αξιολόγηση του αιμοστατικού προφίλ των νεογνών με περιγεννητική υποξία μέσω των μεταβολών των παραμέτρων της δοκιμασίας TEM-EXTEM καθώς επίσης και η αξιολόγηση της μεθόδου ως θεραπευτικού και προγνωστικού δείκτη για τα νεογνά αυτά. Μέθοδος και υλικό: Συνολικά μελετήθηκαν 164 νεογνά με περιγεννητική υποξία-ασφυξία, που νοσηλεύτηκαν στη ΜΕΝΝ του Γενικού Νοσοκομείου Νίκαιας. Τους μάρτυρες αποτέλεσαν 273 υγιή νεογνά που γεννήθηκαν στο Μαιευτήριο του ίδιου νοσοκομείου. Τα πάσχοντα νεογνά χωρίστηκαν σε δύο υποομάδες: 1) 16 νεογνά με περιγεννητική ασφυξία (σύμφωνα με τον ορισμό της AAP και του ACOG) και 2) 148 νεογνά με εμβρυϊκή δυσπραγία/stress. Σε όλα τα νεογνά της μελέτης καταγράφηκαν τα δημογραφικά τους στοιχεία, κλινικά χαρακτηριστικά και αποτελέσματα εργαστηριακών εξετάσεων. Υπολογίστηκε το SNAPPE score (Score for Neonatal Acute Physiology Perinatal Extension) τις πρώτες 12 ώρες νοσηλείας και πραγματοποιήθηκε η δοκιμασία TEM-EXTEM μέχρι το 3ο 24ωρο νοσηλείας. Αποτελέσματα: Σε όλα τα υποξικά νεογνά παρατηρήθηκε υποπηκτικό προφίλ, το οποίο εκφράστηκε με σημαντικά παρατεταμένα CT, CFT και μειωμένα τα A10, A20, A30, a angle και MCF σε σχέση με τα υγιή νεογνά. Οι παράμετροι EXTEM ανέδειξαν πιο έντονο υποπηκτικό προφίλ στα νεογνά με περιγεννητική ασφυξία σε σχέση με τα νεογνά με stress. Επίσης στα νεογνά με υποξία παρατηρήθηκε σημαντική συσχέτιση μεταξύ των παραμέτρων EXTEM και των δεικτών της ηπατικής και νεφρικής λειτουργίας (SGOT, LDH, ALBUMIN και Cr αντίστοιχα), των αιμοπεταλίων και των εμπύρηνων ερυθρών αιμοσφαιρίων. Τέλος όλες οι παράμετροι EXTEM παρουσίασαν συσχέτιση με το SNAPPE score και τη θνησιμότητα των νεογνών με υποξία. Συμπέρασμα: Το υποπηκτικό προφίλ το οποίο προέκυψε από τις μετρήσεις των παραμέτρων EXTEM στα υποξικά νεογνά, φαίνεται ότι μπορεί να αποτελέσει ένα χρήσιμο βιοδείκτη για την πρώιμη ανίχνευση των διαταραχών της αιμόστασης σε αυτά τα νεογνά, ενώ ταυτόχρονα ο βαθμός υποπηκτικότητας ίσως σχετίζεται με τη βαρύτητα της υποξίας

Breastfeeding in the era of COVID-19. A narrative review

Human milk is the best possible nutrition for infants, as it supplies them with nutrients, bioactive molecules as well as antibodies, which contribute to immune maturation, organ development, and healthy microbial colonisation. Few situations are considered definitive contraindications for breastfeeding. The disastrous Coronavirus Disease-2019 (COVID-19) pandemic raised many health issues, including the safety of breastfeeding for infants born to affected mothers. To date relevant data are limited. This review will make an account of the published data so far, regarding the transmission risk of SARS-CoV-2 via human milk; it will also present the current feeding recommendations, issued by several international boards, though not always in agreement, for infants born to mothers suspected or positive for SARS-CoV-2. In most studies existing so far on women with COVID-19, the virus was not detected in breastmilk. Based on currently available data, it seems that breastfeeding and human milk are not contraindicated for infants born to mothers suspected or confirmed with COVID-19

Breastfeeding in the era of COVID-19. A narrative review

Human milk is the best possible nutrition for infants, as it supplies them with nutrients, bioactive molecules as well as antibodies, which contribute to immune maturation, organ development, and healthy microbial colonisation. Few situations are considered definitive contraindications for breastfeeding. The disastrous Coronavirus Disease-2019 (COVID-19) pandemic raised many health issues, including the safety of breastfeeding for infants born to affected mothers. To date relevant data are limited. This review will make an account of the published data so far, regarding the transmission risk of SARS-CoV-2 via human milk; it will also present the current feeding recommendations, issued by several international boards, though not always in agreement, for infants born to mothers suspected or positive for SARS-CoV-2. In most studies existing so far on women with COVID-19, the virus was not detected in breastmilk. Based on currently available data, it seems that breastfeeding and human milk are not contraindicated for infants born to mothers suspected or confirmed with COVID-19

Congenital diaphragmatic hernia and double-outlet right ventricle: elements of trisomy 18?

We present a case of a term male neonate born with congenital diaphragmatic hernia (CDH), double-outlet right ventricle (DORV) and a “picture of genetic syndrome”, antenatally diagnosed, without any confirmation of a particular syndrome as no amnioparacentesis was performed. The postnatal chromosomal analysis revealed trisomy 18

Umbilical Venous Catheters and Peripherally Inserted Central Catheters: Are They Equally Safe in VLBW Infants? A Non-Randomized Single Center Study

Background and Objective: Peripherally inserted central catheters (PICC) and umbilical venous catheters (UVC) are frequently used for vascular access in neonatal intensive care units (NICUs). While there is a significant need for these devices for critically ill neonates, there are many complications associated with their use. We aimed at investigating the incidence of UVC and PICC complications in very low birth weight (VLBW) infants. Materials and Methods: This is an observational study performed with neonates of the tertiary General Hospital of Piraeus, Greece, during an 18 month-period. Seventy-one neonates were recruited and divided into two groups: 34 neonates with PICC and 37 neonates with UVC. We recorded: Catheter dwell time, the causes of catheter removal, other complications, infections, and catheter tip colonization rates. Results: No significant statistical differences were noticed between the 2 study groups with regards to demographic characteristics, causes for catheter removal, catheter indwelling time or the incidence of nosocomial infection. Eleven UVC tips and no PICC tips were proved colonized (p = 0.001) following catheter removal. Conclusions: The incidence of complications associated with the use of UVCs and PICCs in VLBW infants did not significantly differ in our study. Their use seems to be equally safe. Further studies, with larger samples, are necessary to confirm our results

Breastfeeding in Neonates Admitted to an NICU: 18-Month Follow-Up

Introduction: The admission of neonates to Neonatal Intensive Care Units (NICUs) has been identified as a primary inhibiting factor in the establishment of breastfeeding. The aims of this study were to (1) estimate the prevalence and duration of breastfeeding in infants/toddlers who had been admitted to an NICU in Greece and (2) to investigate factors, associated with the NICU stay, which affected the establishment and maintenance of breastfeeding in infants/toddlers previously admitted to the NICU. Materials and methods: Data for this cohort study were retrieved from interviews with mothers of infants/toddlers who had been admitted to our NICU as neonates during the period of 2017–2019. Interviews were conducted based on a questionnaire regarding the child’s nutrition from birth to the day of the interview, including previous maternal experience with breastfeeding. Information related to the prenatal period, gestation age, delivery mode, duration of NICU stay, and neonatal feeding strategies during their hospital stay were recorded. Results: The response rate to the telephone interviews was 57%, resulting in 279 mother–infant pairs being included in this study. The results showed that 78.1% of children received maternal milk during their first days of life. Of all infants, 58.1% were exclusively breastfed during their first month, with a gradual decrease to 36.9% and 19.4% by the end of the third and sixth months of life, respectively. The prevalence of breastfed children reached 14.7% and 7.5% at the ages of twelve and eighteen months, respectively. In the multivariate analysis, prematurity emerged as an independent prognostic factor for the duration of exclusive and any breastfeeding (aHR 1.64, 95% CI: 1.03–2.62; and 1.69, 95% CI: 1.05–2.72, respectively; p < 0.05). Additionally, the nationality of the mother, NICU breastfeeding experience, the administration of maternal milk during neonatal hospital stay, and previous breastfeeding experience of the mother were independent prognostic factors for the duration of breastfeeding. Conclusions: Although breastfeeding is a top priority in our NICU, the exclusive-breastfeeding rates at 6 months were quite low for the hospitalized neonates, not reaching World Health Organization (WHO) recommendations. Mothers/families of hospitalized neonates should receive integrated psychological and practical breastfeeding support and guidance

The Non-Activated Thromboelastometry (NATEM) Assay’s Application among Adults and Neonatal/Pediatric Population: A Systematic Review

The non-activated thromboelastometry (NATEM) assay is a point-of-care assay that can provide a comprehensive insight into the actual hemostatic mechanism. However, there are very limited data about its use in clinical practice. The aim of this study was to systematically review the literature for any data regarding the use of NATEM in several clinical settings. A systematic review of PubMed and Scopus databases was conducted through 20 January 2022 for studies evaluating the use of the NATEM assay in different clinical settings. The literature search yielded a total of 47 publications, 30 of which met the eligibility criteria for this review. Evaluation of NATEM’s detecting ability for hemostasis disorders is limited in the literature. The results of the included studies indicate that NATEM seems to be a sensitive method for the detection of hyperfibrinolysis and may have an advantage in the diagnosis of hemostatic disorders. It could be more informative than the other ROTEM assays for detecting changes in coagulation parameters in patients who receive anticoagulants. However, the reported outcomes are highly varying among the included studies. NATEM has a high sensitivity to detect hypo- or hypercoagulability and provides a detailed insight into the whole hemostatic process from clot formation to clot breakdown. It could be a useful technique in variable fields of medicine, not only in adults, but also in pediatric and neonatal populations, to guide different hemostatic treatments and predict coagulation disorders or mortality/morbidity; this issue remains to be further investigated

Congenital Diaphragmatic Eventration in the Neonatal Period: Systematic Review of the Literature and Report of a Rare Case Presenting with Gastrointestinal Disorders

Background: The term congenital diaphragmatic eventration (CDE) refers to an anatomical abnormality of the diaphragm. It is a very rare condition; however, early and prompt diagnosis is of very great importance due to possible life-threatening complications. Most severely affected patients are neonates, usually presented with respiratory distress symptoms. The aim of this study was to systematically review the existing literature and to consolidate data on CDE in neonates as well as to report a case of a neonate with congenital diaphragmatic eventration of the left hemidiaphragm and clinical signs and symptoms of the gastrointestinal tract. Methods: An electronic search of the PubMed and Scopus databases was performed regarding studies evaluating the clinical presentation, diagnosis methods, treatments, and outcomes of CDE in the neonatal population. Results: Data from 93 studies were integrated into our review, reporting 204 CDE cases, and according to them, the male/female ratio was 1/1 with a predominance of right-sided eventration. The diagnosis was primarily established by chest X-ray; surgical intervention was the most frequent treatment. The recurrence rate was 8.3% (9/109 cases). Conclusions: Early and accurate diagnosis of CDE and repair of the diaphragm can prevent complications, reduce morbidity, and improve the quality of patient’s life