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BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).
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Lactente Extremamente Prematuro , Doenças do Prematuro , Oximetria , Humanos , Lactente , Recém-Nascido , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/etiologia , Displasia Broncopulmonar/etiologia , Circulação Cerebrovascular , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/mortalidade , Doenças do Prematuro/terapia , Oximetria/métodos , Cérebro , Ultrassonografia , Retinopatia da Prematuridade/etiologia , Enterocolite Necrosante/etiologia , Sepse Neonatal/etiologiaRESUMO
BACKGROUND: The diagnosis of neonatal diabetes can be problematic in preterm infants with fetal growth restriction (FGR). Growth restricted fetuses may have impaired insulin production and secretion; low birthweight infants may have a reduced response to insulin. We report a novel missense ABCC8 variant associated with a clinical phenotype compatible with transient neonatal diabetes mellitus (TNDM) in a fetal growth restricted preterm infant. METHODS AND RESULTS: A preterm growth restricted infant experienced hyperglycemia from the first day of life, requiring insulin therapy on the 13th and 15th day of life and leading to the diagnosis of TNDM. Glycemic values normalized from the 35th day of life onwards. Genetic screening was performed by next generation sequencing, using a Clinical Exon panel of 4800 genes, filtered for those associated with the clinical presentation and by means of methylation-specific multiplex ligation-dependent probe amplification analysis to identify chromosomal aberrations at 6q24. Genetic tests excluded defects at 6q24 and were negative for KCNJ11, SLC2A2 (GLUT-2) and HNF1B, but revealed the presence of the heterozygous missense variant c.2959T > C (p.Ser987Pro) in ABCC8 gene. The presence of the variant was excluded in parents' DNA and the proband variant was then considered de novo. CONCLUSIONS: In our infant, the persistence of hyperglycemia beyond 3 weeks of life led us to the diagnosis of TNDM and to hypothesize a possible genetic cause. The genetic variant we found could be, most likely, the main cause of both FGR and TNDM.
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Diabetes Mellitus , Retardo do Crescimento Fetal , Mutação de Sentido Incorreto , Receptores de Sulfonilureias , Humanos , Retardo do Crescimento Fetal/genética , Mutação de Sentido Incorreto/genética , Receptores de Sulfonilureias/genética , Recém-Nascido , Diabetes Mellitus/genética , Feminino , Masculino , Recém-Nascido Prematuro , Insulina/metabolismo , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/diagnósticoRESUMO
Neonatal hypoglycemia is a major source of concern for pediatricians since it has commonly been related to poor neurodevelopmental outcomes. Diagnosis is challenging, considering the different operational thresholds provided by each guideline. Screening of infants at risk plays a crucial role, considering that most hypoglycemic infants show no clinical signs. New opportunities for prevention and treatment are provided by the use of oral dextrose gel. Continuous glucose monitoring systems could be a feasible tool in the next future. Furthermore, there is still limited evidence to underpin the current clinical practice of administering, in case of hypoglycemia, an intravenous "mini-bolus" of 10% dextrose before starting a continuous dextrose infusion. This brief review provides an overview of the latest advances in this field and neurodevelopmental outcomes according to different approaches. Conclusion: To adequately define if a more permissive approach is risk-free for neurodevelopmental outcomes, more research on continuous glucose monitoring and long-term follow-up is still needed. What is Known: ⢠Neonatal hypoglycemia (NH) is a well-known cause of brain injury that could be prevented to avoid neurodevelopmental impairment. ⢠Diagnosis is challenging, considering the different suggested operational thresholds for NH (<36, <40, <45, <47 or <50 mg/dl). What is New: ⢠A 36 mg/dl threshold seems to be not associated with a worse psychomotor development at 18 months of life when compared to the "traditional" threshold (47 mg/dl). ⢠Further studies on long-term neurodevelopmental outcomes are required before suggesting a more permissive management of NH.
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Hipoglicemia , Doenças do Recém-Nascido , Recém-Nascido , Lactente , Humanos , Glicemia , Automonitorização da Glicemia , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Hipoglicemia/tratamento farmacológico , Doenças do Recém-Nascido/diagnóstico , Hipoglicemiantes/uso terapêutico , Géis/uso terapêutico , Glucose/uso terapêuticoRESUMO
BACKGROUND: During the last decade, there has been a growing number of cases of children born from pregnancy-associated cancer (PAC), however there are currently insufficient data on the follow up to be observed in this category of newborns. Objective of the study was to evaluate the neonatal outcomes of infants born to mother with PAC, the potential adverse effect of chemotherapy during pregnancy and the risk of metastasis to the fetus. METHODS: Maternal clinical data and neonatal outcomes of child born to mothers diagnosed with PAC were collected; infants were divided into those were and were not exposed to chemotherapy during fetal life and their outcomes were compered. RESULTS: A total of 37 newborn infants from 36 women with PAC were analyzed. Preterm delivery occurred in 83.8% of the cases. No significant differences in neonatal outcomes were found between infants who were and were not exposed to chemotherapy during pregnancy. The median follow-up period was 12 months. CONCLUSIONS: PAC treatment during the second or third trimester does not seem to be dangerous for the fetus, however infants born from PAC must be carefully evaluated for to rule out the consequences of chemotherapy and exclude the presence of metastasis. Long-term follow-up, especially in children exposed to chemotherapy, should be encouraged to obtain relevant data on long-term toxicity.
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Neoplasias , Nascimento Prematuro , Gravidez , Lactente , Criança , Recém-Nascido , Humanos , Feminino , Seguimentos , Nascimento Prematuro/epidemiologia , Cuidado Pré-Natal , Neoplasias/tratamento farmacológico , Estudos ProspectivosRESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is due to the homozygous absence of SMN1 in around 97% of patients, independent of the severity (classically ranked into types I-III). The high genetic homogeneity, coupled with the excellent results of presymptomatic treatments of patients with each of the three disease-modifying therapies available, makes SMA one of the golden candidates to genetic newborn screening (NBS) (SMA-NBS). The implementation of SMA in NBS national programmes occurring in some countries is an arising new issue that the scientific community has to address. We report here the results of the first Italian SMA-NBS project and provide some proposals for updating the current molecular diagnostic scenario. METHODS: The screening test was performed by an in-house-developed qPCR assay, amplifying SMN1 and SMN2. Molecular prognosis was assessed on fresh blood samples. RESULTS: We found 15 patients/90885 newborns (incidence 1:6059) having the following SMN2 genotypes: 1 (one patient), 2 (eight patients), 2+c.859G>C variant (one patient), 3 (three patients), 4 (one patient) or 6 copies (one patient). Six patients (40%) showed signs suggestive of SMA at birth. We also discuss some unusual cases we found. CONCLUSION: The molecular diagnosis of SMA needs to adapt to the new era of the disease with specific guidelines and standard operating procedures. In detail, SMA diagnosis should be felt as a true medical urgency due to therapeutic implications; SMN2 copy assessment needs to be standardised; commercially available tests need to be improved for higher SMN2 copies determination; and the SMN2 splicing-modifier variants should be routinely tested in SMA-NBS.
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Atrofia Muscular Espinal , Triagem Neonatal , Humanos , Recém-Nascido , Projetos Piloto , Triagem Neonatal/métodos , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Genótipo , ItáliaRESUMO
PURPOSE: Few guidelines exist for the perioperative management (PM) of neonates with surgical conditions (SC). This study examined the current neonatal PM in Italy. METHODS: We invited 51 neonatal intensive care units with pediatric surgery in their institution to participate in a web-based survey. The themes included (1) the involvement of the neonatologist during the PM; (2) the spread of bedside surgery (BS); (3) the critical issues concerning the neonatal PM in operating rooms (OR) and the actions aimed at improving the PM. RESULTS: Response rate was 82.4%. The neonatologist is involved during the intraoperative management in 42.9% of the responding centers (RC) and only when the surgery is performed at the patient's bedside in 50.0% of RCs. BS is reserved for extremely preterm (62.5%) or clinically unstable (57.5%) infants, and the main barrier to its implementation is the surgical-anesthesiology team's preference to perform surgery in a standard OR (77.5%). Care protocols for specific SC are available only in 42.9% of RCs. CONCLUSION: Some critical issues emerged from this survey: the neonatologist involvement in PM, the spread of BS, and the availability of specific care protocols need to be implemented to optimize the care of this fragile category of patients.
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Neonatologia , Recém-Nascido , Lactente , Criança , Humanos , Unidades de Terapia Intensiva Neonatal , Inquéritos e Questionários , ItáliaRESUMO
OBJECTIVE: To evaluate the role of cyanoacrylate glue in reducing dislodgement of umbilical venous catheters (UVCs). STUDY DESIGN: This was a single-center, randomized, controlled, nonblinded trial. All infants requiring an UVC according to our local policy were included in the study. Infants with a UVC with a centrally located tip as verified by real-time ultrasound examination were eligible for the study. Primary outcome was the safety and efficacy of securement by cyanoacrylate glue plus cord-anchored suture (SG group) vs securement by suture alone (S group), as measured by reduction in dislodgment of the external tract of the catheter. Secondary outcomes were tip migration, catheter-related bloodstream infection, and catheter-related thrombosis. RESULTS: In the first 48 hours after UVC insertion, dislodgement was significantly higher in the S group than in the SG group (23.1% vs 1.5%; P < .001). The overall dislodgement rate was 24.6% in the S group vs 7.7% in the SG group (P = .016). No differences were found in catheter-related bloodstream infection and catheter-related thrombosis. The incidence of tip migration was similar in both groups (S group 12.2% vs SG group 11.7%). CONCLUSIONS: In our single-center study, cyanoacrylate glue was safe and effective for securement of UVCs, and particularly effective in decreasing early catheter dislodgments. TRIAL REGISTRATION: UMIN-CTR Clinical Trial; Registration number: R000045844.
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Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Cateterismo Periférico , Sepse , Trombose , Doenças Vasculares , Lactente , Humanos , Cianoacrilatos/uso terapêutico , Catéteres , Veias , Veias UmbilicaisRESUMO
BACKGROUND: Pontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes. METHODS: We performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASK rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters. RESULTS: A genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which accounted for nearly half cases (45%) and was mutated in females and occasionally in males. The European founder mutation p.Ala307Ser in TSEN54 and pathogenic variants in EXOSC3 accounted for 18% and 9% of cases, respectively. VLDLR, TOE1 and RARS2 were mutated in single patients. We were able to confirm only few previously reported associations, including jitteriness and clonus with TSEN54 and lower motor neuron signs with EXOSC3. When considering multiple features simultaneously, a clear association with a phenotypic cluster only emerged for EXOSC3. CONCLUSION: CASK represents the major PCH causative gene in Italy. Phenotypic variability associated with the most common genetic causes of PCH is wider than previously thought, with marked overlap between CASK and TSEN54-associated disorders.
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Doenças Cerebelares , Atrofias Olivopontocerebelares , Doenças Cerebelares/genética , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Feminino , Humanos , Masculino , Mutação/genética , Proteínas Nucleares/genética , Atrofias Olivopontocerebelares/diagnóstico , Atrofias Olivopontocerebelares/genética , Atrofias Olivopontocerebelares/patologia , FenótipoRESUMO
OBJECTIVE: Recently, a novel approach to imaging Superior Vena Cava (SVC) flow has been presented, showing better repeatability and better agreement with MRI-derived SVC flow measures. The objective was to establish normal values of SVC flow with the novel approach in the first 48 h of life. STUDY DESIGN: This was a prospective, observational study. All infants with gestational age (GA) less than 31 weeks were eligible. Echocardiographic evaluation was performed at 5, 12, 24, 48 h of postnatal life. A subgroup of uncomplicated infants was studied to define a normal range for SVC flow. RESULTS: Forty-five infants were enrolled. We estimated normative values in a subgroup of 31 uncomplicated infants. The median SVC flow significantly increases from 83 ml/kg/min at 5 h of life to 153 ml/kg/min at 48 h (p < .001). CONCLUSION: Using the novel approach we derived normal values of SVC flow in a cohort of uncomplicated preterm population at high risk for developing IVH.
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Recém-Nascido Prematuro , Veia Cava Superior , Recém-Nascido , Humanos , Lactente , Valores de Referência , Veia Cava Superior/diagnóstico por imagem , Estudos Prospectivos , Velocidade do Fluxo Sanguíneo , Ecocardiografia/métodosRESUMO
OBJECTIVE: Epicutaneo-caval catheters (ECCs) are essential for the care of sick infants who require long-term medical and nutritional management. The aim of this study was to investigate the use of real-time ultrasound as an alternative to X-rays to reduce the incidence of primary malpositions during catheter insertion. STUDY DESIGN: Data on ECCs were retrospectively collected in a tertiary neonatal intensive care unit. Catheter were analyzed considering the tip location technique (standard chest-abdominal radiograph vs real-time ultrasound) RESULTS: A total of 248 ECCs were analyzed. Of these, 118 catheters had primary malposition (47.6%). The tip of 165 catheters was assessed using standard chest-abdominal X-rays and 107 (64.8%) were found to be in an inappropriate location. In the group of 83 catheters that were placed using real-time ultrasound for tip location, only 11 catheters (13.2%) had primary malposition. The rate of malposition among the two groups showed a statistically significant difference (p < 0.001). Hypothetically, 300 chest X-rays could have been saved if real-time ultrasound had been used to locate the tip, reducing radiation exposure to infants. CONCLUSION: The use of a real-time ultrasound may be beneficial in reducing primary catheter malpositions compared with conventional radiography. In addition, secondary malpositions and catheter-related complications can be monitored over time. KEY POINTS: · Conventional radiology cannot be considered the "gold standard" for ECC tip location.. · Ultrasound is more accurate and reduces insertion time reducing the rate of primary malposition.. · Ultrasound can be performed in real time and it is the best technique for ECC tip location in infants..
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OBJECTIVE: In this study, we evaluated the safety of early discharge (ED) of newborns born to coronavirus disease 2019 (COVID-19)-positive mothers. STUDY DESIGN: All ED newborns from the postpartum wards of the Fondazione Policlinico Gemelli between January 1, 2022, and February 28, 2022, were retrospectively analyzed. Newborns from mothers with COVID-19 and those from uninfected mothers were considered. The primary outcome was to evaluate whether the rate of the composite outcome, which was the percentage of rehospitalization/access in emergency room (RH/ER) within the first week from discharge, differed between neonates born to mother with COVID-19 (COVID-19 group) and those born to uninfected mothers (no COVID-19 group). The secondary outcomes were to assess the quality of feeding and number of outpatient visits in the follow-up clinic between the two cohorts of patients. RESULTS: One hundred and thirty-four newborns in the no COVID-19 group and 26 in the COVID-19 group were analyzed. The rate of RH/ER in the no COVID-19 group was of 6 over 134 newborns (0.045, 95% confidence image [CI]: 0.017-0.095), while in COVID-19 group, it was of 2 over 26 newborns (0.077), which does not differ from the expected rate (1.17 over 26 newborns, 0.045, 95% CI: 0.017-0.095). CONCLUSION: ED for newborns from mothers with COVID-19 could be an actionable safe strategy. KEY POINTS: · We evaluated the feasibility of early discharge (ED) of mothers with COVID-19 and their newborns.. · Rate of rehospitalization between newborns from uninfected mothers and infected ones was comparable.. · ED could be an actionable practice for newborns from mothers with COVID-19..
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OBJECTIVE: During the early weeks of life optimization of nutrition in extremely preterm infants presents a critical opportunity to attenuate the adverse neurological consequences of prematurity and potentially improve neurodevelopmental outcome. We hypothesized that the use of multicomponent lipid emulsion (MLE) in parenteral nutrition (PN) would be related to larger volume of the cerebellum on brain magnetic resonance at term of equivalent age (TEA) in extremely low birth weight (ELBW) infants. STUDY DESIGN: We analyzed the brain magnetic resonance imaging (MRI) at TEA of a cohort of preterm infants with gestational age ≤28 weeks and/or birth weight <1,000 g randomly assigned in our previous trial to receive an MLE or soybean-based lipid emulsion (SLE). The primary outcome of the study was the cerebellar volume (CeV), valued on MRI acquired at TEA. Secondary outcomes included total brain volume (TBV), supratentorial volume, brainstem volume, and CeV corrected for TBV evaluated on MRI acquired at TEA. RESULTS: MRIs at TEA of 34 infants were then analyzed: 17 in the MLE group and 17 in the SLE group. The postmenstrual age (PMA) at which MRIs were performed were comparable between the two study groups. The CeV as well as the PMA-corrected CeV were significantly higher in the MLE group than in the SLE group. No difference was found among the other brain volumes considered. CONCLUSION: Our results suggest that the use of MLE in PN could promote CeV growth in ELBW infants, valued with MRI at TEA. KEY POINTS: · Optimization of nutrition in extremely low birthweight infants.. · Use of multicomponent lipid emulsions in parenteral nutrition.. · Larger cerebellar volume with use of multicomponent lipid emulsion..
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OBJECTIVES: Coronavirus disease (COVID-19) can present with various symptoms and can involve multiple organs. Women infected during pregnancy have a higher incidence of obstetrical complications and infants born to "positive" mothers may get the infection with different manifestations. Presepsin seems to be a promising sepsis biomarker in adults and neonates. The aim of this study was to assess if presepsin levels in neonatal cord blood could be influenced by maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A total of 119 neonates born from women with a confirmed diagnosis of SARS-CoV-2 infection were enrolled and presepsin levels of cord blood samples were collected. All neonates were tested for SARS-CoV-2 infection at birth and after 48-72 h. RESULTS: The median presepsin value in umbilical cord blood samples collected after birth was 455 pg/mL. Presepsin levels were not influenced by maternal symptoms of COVID-19, weight for gestational age, or delivery mode, and did not significantly differ between infants with and without adverse neonatal outcomes. Infants hospitalized for more than 5 days had a significantly higher presepsin level at birth rather than those discharged up to 4 days of life. Three infants with positive nasopharyngeal swab at birth had higher Presepsin levels than two infants tested positive at 48 h. CONCLUSIONS: This is the first study reporting cord presepsin levels in term and preterm infants born to mothers with COVID-19, that appeared to be not influenced by maternal clinical presentation. However, further studies are needed to explain the mechanisms of P-SEP increase in neonates exposed to perinatal maternal SARS-CoV-2 infection or with an indeterminate/possible SARS-CoV-2 infection in the same neonates.
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COVID-19 , Adulto , COVID-19/diagnóstico , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Transmissão Vertical de Doenças Infecciosas , Receptores de Lipopolissacarídeos , Fragmentos de Peptídeos , Gravidez , SARS-CoV-2RESUMO
AIM: To describe the profile of global and single items of the Hammersmith Infant Neurological Examination (HINE) in a population of low-risk infants born very preterm during the first year of life. METHOD: The HINE was performed at 3, 6, 9, and 12 months' corrected age in a population of low-risk infants born preterm with a gestational age of fewer than 32 weeks and with normal or minimal changes on neuroimaging. RESULTS: A total of 174 infants born preterm (96 males, 78 females; mean gestational age = 27 weeks [SD = 1.8], range 23-31 weeks) fulfilled the inclusion criteria. The 10th centile cut-off score with median and range was reported for the HINE global and subsection scores. A progressive increase in global HINE scores was observed. Most of the single items, especially those related to tone, posture, and reflexes, showed progressive maturation. INTERPRETATION: Our results, which provide longitudinal data for single-item and global scores in a population of low-risk infants born very preterm, can be used as a reference in both clinical and research settings to monitor early neurological signs in these infants. These data could be used as normative data when examining low-risk infants born preterm.
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Lactente Extremamente Prematuro , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Exame Neurológico/métodos , Estudos ProspectivosRESUMO
AIM: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify cognitive performance delay at 2 years in a large cohort of infants born at term. METHOD: We conducted a retrospective study of infants born at term at risk of neurodevelopmental impairments assessed using the HINE between 3 and 12 months post-term age and compared them with a cohort of typically developing infants born at term. All infants performed a neurodevelopmental assessment at 2 years of age using the Mental Development Index (MDI) of the Bayley Scales of Infant Development, Second Edition; the presence of cerebral palsy (CP) was also reported. The infants were classified as being cognitively normal/mildly delayed or significantly delayed (MDI < 70). The predictive validity of HINE scores for significantly delayed cognitive performance, in infants with and without CP, was calculated using specific cut-off scores according to age at assessment. RESULTS: A total of 446 at-risk and 235 typically developing infants (345 males, 336 females; mean [SD] gestational age 38.7 weeks [1.4], range 37-43 weeks) were included. Of the at-risk infants, 408 did not have CP at 2 years; 243 had a normal/mild delayed MDI and 165 had an MDI less than 70. Of the at-risk infants, 38 developed CP. HINE scores showed a good sensitivity and specificity, mainly after 3 months, for identifying significantly delayed cognitive performance in infants without CP. In those with CP, the score was associated with their cognitive performance. The comparison group had the highest HINE scores. INTERPRETATION: The HINE provides evidence about the risk of delayed cognitive performance at age 2 years in infants born at term with and without CP.
EXAMEN NEUROLÓGICO INFANTIL DE HAMMERSMITH EN BEBÉS NACIDOS A TÉRMINO: SU USO PARA PREDECIR OTRAS CONDICIONES ADEMÁS DE LA PARÁLISIS CEREBRAL: OBJETIVO: Valoramos la capacidad del examen neurológico infantil de Hammersmith (HINE) para identificar el retraso en el rendimiento cognitivo a los 2 años en una cohorte grande de bebés nacidos a término. MÉTODO: Realizamos un estudio retrospectivo de bebés nacidos a término con riesgo de trastornos del desarrollo neurológico evaluados mediante el HINE entre los 3 y los 12 meses de edad postérmino y los comparamos con una cohorte de bebés nacidos a término con un desarrollo típico. Todos los bebés realizaron una evaluación del desarrollo neurológico a los 2 años de edad utilizando el Índice de Desarrollo Mental (MDI) de las Escalas de Desarrollo Infantil de Bayley, Segunda Edición; también se informó la presencia de parálisis cerebral (PC). Los bebés se clasificaron como cognitivamente normales/levemente con retreaso o significativamente con retraso (MDI < 70). La validez predictiva de las puntuaciones HINE para el rendimiento cognitivo con retraso significativo, en bebés con y sin parálisis cerebral, se calculó utilizando puntuaciones de corte específicas según la edad en la evaluación. RESULTADOS: Se incluyeron un total de 446 lactantes en riesgo y 235 con desarrollo normal (345 varones, 336 mujeres; edad gestacional media [DE] 38,7 semanas [1,4], rango de 37 a 43 semanas). De los lactantes en riesgo, 408 no tenían parálisis cerebral a los 2 años; 243 tenían un MDI con retraso normal/leve y 165 tenían un MDI inferior a 70. De los bebés en riesgo, 38 desarrollaron PC. Las puntuaciones HINE mostraron una buena sensibilidad y especificidad, principalmente después de 3 meses, para identificar un rendimiento cognitivo severo en lactantes sin PC. En aquellos con PC, la puntuación se asoció con su rendimiento cognitivo. El grupo de comparación tuvo las puntuaciones HINE más altas. INTERPRETACIÓN: El HINE proporciona evidencia sobre el riesgo de retraso en el rendimiento cognitivo a los 2 años de edad en bebés nacidos a término con y sin parálisis cerebral.
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Paralisia Cerebral , Paralisia Cerebral/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Lactente , Masculino , Exame Neurológico , Estudos RetrospectivosRESUMO
Our aim was to develop a new module for assessing the floppy infant, to describe the application of the module in a cohort of low-risk newborns and piloting the module in a cohort of floppy infants. The module was applied to a cohort of 143 low-risk newborns and piloted in in a cohort of 24 floppy infants. The new add-on module includes a neurological section and provides a section for recording information obtained by physical examination and antenatal history. For each item, column 1 reports abnormal findings, column 3 normal findings, and column 2 intermediate signs to be followed. Consistent with previous studies, in low-risk infants, none had definitely abnormal or mildly abnormal signs, with the exception of tendon reflexes that were not easily elicitable in 17.14% of term-born infants. CONCLUSION: Our study suggest that the module can be easily used in a clinical setting as an add-on to the regular neonatal neurological examination in newborns identified as hypotonic on routine examination. Larger cohorts are needed to establish the accuracy of the prognostic value of the module in the differential diagnosis of floppy infant. WHAT IS KNOWN: ⢠Hypotonia is one of the key signs in newborns with neuromuscular disorders and can be associated with a wide range of other conditions (central nervous system involvement, genetic and metabolic diseases). ⢠Weakness or/and contractures can identify infants with a neuromuscular disorder and help in the differential diagnosis of floppy infants. WHAT IS NEW: ⢠To date, this is the first attempt to develop and apply a specific neurological module for the assessment of the floppy infant. ⢠The module can be used in a routine clinical setting as an add-on to the regular neurological examination and has potential to differentiate the floppy infants from the low-risk infants.
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Doenças do Recém-Nascido , Doenças Musculares , Doenças Neuromusculares , Feminino , Humanos , Lactente , Recém-Nascido , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/genética , Exame Neurológico , Doenças Neuromusculares/diagnóstico , GravidezRESUMO
The possibility to identify patients with spinal muscular atrophy through neonatal screenings has highlighted the need for clinical assessments that may systematically evaluate the possible presence of early neurological signs. The aim of this study was to use the Hammersmith Neonatal Neurological Examination (HNNE) and a module specifically designed for floppy infants to assess the possible variability of neurological findings in infants identified through neonatal screening. The infants included in this study were identified as part of a pilot study exploring neonatal screening in two Italian regions. A neurological examination was performed using the HNNE and an additional module developed for the assessment of floppy infants. Seventeen infants were identified through the screening. One patient had 1 SMN2 copy, 9 had 2 copies, 3 had 3, and 4 had more than 3 copies. Nine of the 17 infants (53%) had completely normal results on both scales, 3 had minimal signs, and the other 5 had more obvious clinical signs. The number of SMN2 copies was related to the presence of abnormal neurological signs (p = 0.036) but two SMN2 copies were associated with variable clinical signs as they were found in some infants with respectively normal examination or obvious severe early signs. CONCLUSIONS: Our results suggest that the combination of both scales increases the possibility to detect neonatal neurological signs and to define different early patterns of involvement also identifying paucisymptomatic patients. WHAT IS KNOWN: ⢠The use of new therapeutic options in presymptomatic SMA patients leads to a dramatic reduction of the onset and severity of the diesease. ⢠The already existing tools commonly used in Type I SMA (HINE and CHOP-intend) may not be suitable to identify minor neurological signs in the neonatal period. WHAT IS NEW: ⢠Combining the HNNE and the floppy infant module, we were able to identify early neurological signs in SMA infants identified through newborn screening and may help to predict the individual therapeutic outcome of these patients. ⢠Iinfants with 2 SMN2 copies identified through the screening had a more variable neonatal examination compared to those with three or more copies, in agreement with similar findings in older infants.
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Atrofia Muscular Espinal , Triagem Neonatal , Idoso , Humanos , Lactente , Recém-Nascido , Atrofia Muscular Espinal/diagnóstico , Triagem Neonatal/métodos , Exame Neurológico , Projetos PilotoRESUMO
The long-term outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are still unknown. We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery. Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48-72 h of life, auxological growth and neurological development, serologic testing, and audiological and ophthalmological assessments. One-hundred ninety-eight mothers and 199 newborns were enrolled. Of the 199 newborns, 171 underwent nasopharyngeal swab, four (2.3%) and two (1.15%) children tested positive at birth and 48-72 h of life, respectively. None had SARS-CoV-2 related symptoms. Auxologic and neurologic development were normal in all children during follow-up. Nine out of 59 infants had SARS-CoV-2 IgG at 3 months of life, which was associated with a positive nasopharyngeal swab at birth (P = 0.04). Twenty seven out of 143 (18.8%) newborns had pathologic transitory evoked otoacoustic emissions at birth, although 14/27 repeated after 1 month were normal. Audiological evaluation was completed with Auditory Brainstem Response between the third and sixth month of life in 34 children, showing in all normal hearing threshold. The ophthalmological evaluation found retinal vascular anomalies in 3/20 (15%) children, immature visual acuity in 5/20 (25%) children, and reduced distance attention in 6/20 cases (30%). CONCLUSIONS: Our study showed that the neonatal and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are mostly positive, with the exception of ophthalmologic findings which, in a preliminary cohort, were abnormal in about 15% of cases. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of children exposed to SARS-CoV-2 in utero and in the early postnatal life. WHAT IS KNOWN: ⢠In utero mother-to-child transmission of SARS-CoV-2 has been documented by several independent studies. ⢠Neonatal COVID-19 is a systemic disease that can be severe, although rarely. WHAT IS NEW: ⢠Newborns exposed in utero to SARS-CoV-2 have mostly a normal auxological, audiological, and neurological development during the first months of life. ⢠Fundus fluorescein angiography revealed that up to 5% of newborns exposed in utero to SARS-CoV2 can show retinal and choroidal abnormalities, including peripheral hypofluorescence of the choroid and increased vascular tortuosity.
Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , COVID-19/diagnóstico , COVID-19/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , RNA Viral , SARS-CoV-2RESUMO
OBJECTIVE: We aimed to investigate the feasibility of evaluating overall preterm brain growth using a gathered set of measurements of brain structures in standard cranial ultrasound planes. We called this method of assessment Brain Growth Evaluation Assessed with Transfontanellar ultrasound (B-GREAT). STUDY DESIGN: In this prospective observational cohort study, cranial ultrasound was regularly performed (on day 1, 2, 3, and 7 of life, and then weekly until discharge, and at term) in preterm infants born with gestational age (GA) less than 32 weeks. We evaluated corpus callosum length, corpus callosum-fastigium length, anterior horn width, frontal white matter height, total brain surface, deep grey matter height, hemisphere height, transverse cerebellar diameter in the axial view, and transverse cerebellar diameter coronal view. Measurements obtained were used to develop growth charts for B-GREAT markers as a function of postmenstrual age. Reproducibility of B-GREAT markers was studied. RESULTS: A total of 528 cranial ultrasounds were performed in 80 neonates (median birth GA: 28+5 weeks and interquartile range: 27+3-30+5). The intraclass correlation coefficients for intra-observer and inter-observer analyses showed substantial agreement for all B-GREAT markers. Growth curves for B-GREAT markers were developed. CONCLUSION: B-GREAT is a feasible and reproducible method for bedside monitoring of the growth of the main brain structures in preterm neonates. KEY POINTS: · Overall neonatal brain growth is not routinely monitored using ultrasound.. · Old and new markers were used to build a standardized and non-invasive tool to monitor brain growth.. · All B-GREAT measurements had a good intra-observer and inter-observer agreement..
RESUMO
OBJECTIVE: The extent of vertical transmission (VT) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from mothers their fetuses or neonates is still uncertain. We aimed to determine the incidence of VT. STUDY DESIGN: In this prospective cohort study. All mother diagnosed with SARS-CoV-2 infection at the time of delivery or up to 1 week prior and their neonates, managed in a tertiary referral hospital for pregnancy complicated by coronavirus disease 2019 (COVID-19) in Rome, from April 2 to December 22, 2020, were included. Maternal infection was defined as nasopharyngeal swab test results positive for SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR). Biological samples were collected before, at, and after delivery to test positivity for SARS-CoV-2 RT-PCR and anti-SARS-CoV-2-specific antibodies. RESULTS: The cohort included 95 women and 96 neonates with documented SARS-CoV-2 test results. Four neonates (4.2%) tested positive. The incidence of VT, according to the guidance criteria for diagnosing perinatal SARS-CoV-2 infection, was 5.2%. Neonatal symptoms were due to prematurity or fetal distress: symptomatic infants had lower median (min-max) gestational age, 38.1 (29.3-40.6) versus 39.3 (33.9-41.9) weeks (p = 0.036), and 1-minute and 5-minute Apgar scores, 9 (3-9) versus 9 (7-10) (p = 0.036) and 10 (6-10) versus 10 (8-10) (p = 0.012), respectively, than asymptomatic infants and needed more frequent assistance in the delivery room (22.2 vs 2.5%; p = 0.008). Only six (7.1%) neonates had anti-SARS-CoV-2-specific antibodies, despite the ongoing maternal infection. CONCLUSION: The incidence of VT is low as is the detection of specific anti-SARS-CoV-2 antibodies in cord blood when infection is contracted late in pregnancy. This would suggest poor protection of infants against horizontal transmission of the virus. KEY POINTS: · VT of SARS-CoV-2 from pregnant mothers to fetuses or neonates can be possible.. · In this prospective cohort study, the incidence of VT is found to be 5.2%.. · VT is low but exists..