Effect of neonatal neuronal intensive care unit on neonatal encephalopathy

Prophylaxis of brain injury in newborns has been a main concern since the first neonatal neuronal intensive care unit (NNICU) was established in the world in 2008. The aim of this study was to outline and evaluate the unit’s development by analyzing the demographics of the patients, the services delivered, the short-term outcomes before and after the establishment of NNICU. During the two investigation periods, 384 newborns were diagnosed or suspected as “neonatal encephalopathy”, among which 185 patients admitted to NNICU between 2011.03.01 and 2012.09.30 before the establishment of NNICU were enrolled in the pre-NNICU group, another 199 neonates hospitalized during 2018.03.01 to 2019.09.30 were included in the post-NNICU group. Patients in the post-NNICU group were more likely to have seizures (P = 0.001), incomplete or absent primitive reflexes (P = 0.002), therapeutic hypothermia (P<0.001) and liquid control (P<0.001) in acute phase. Meanwhile, amplitude-integrated electro encephalogram (aEEG) monitoring (P<0.001) and cranial ultrasound (P<0.001) were more often used in NNICU. Both of the follow-up rate in brain MRI and the assessment of neurodevelopment at 3 months were higher in the post-NNICU group (P<0.001). In conclusion, the NNICU focused on the neonatal neurocritical care for the babies susceptible to NE with the guidance of evidence-based medicine, the establishment of NNICU is gradually improving and standardizing the neuroprotective therapy and clinical follow-up to improve neurodevelopmental prognosis of the NE patients in CHCMU.

Lenticulostriate Vasculopathy in Very-Low-Birth-Weight Preterm Infants: A Longitudinal Cohort Study

Background: The pathogenesis and clinical significance of lenticulostriate vasculopathy (LSV) are unclear. Our study aimed to determine the prevalence, presentation, and evolution of LSV, and the perinatal risk factors associated with LSV among very-low-birth-weight (VLBW) preterm infants. Methods: One-hundred-and-thirty VLBW preterm infants were retrospectively enrolled in this study. Serial cranial ultrasound examinations were performed regularly from birth until a corrected age of 1 year. Infants with LSV were assigned to early-onset (≤10 postnatal days) and late-onset (>10 postnatal days) groups. Data describing the infants’ perinatal characteristics, placental histopathology, and neonatal morbidities were collected, and the groups were compared. Results: Of the VLBW infants, 39.2% had LSV before they were 1 year old. Linear-type LSV was the most common presentation, and >50% of the infants had bilateral involvement. LSV was first detected at 112 ± 83 postnatal days, and its detection timing correlated negatively with gestational age (GA) (R2 = 0.153, p = 0.005) and persisted for 6 months on average. The infants with and without LSV had similar perinatal characteristics, placental pathologies, cytomegalovirus infection rates, and clinical morbidities. The late-onset LSV group comprised 45 (88.2%) infants who had a significantly higher rate of being small for gestational age (SGA) and used oxygen for longer than the infants without LSV. After adjusting a multivariable regression model for GA and SGA, analysis showed that the duration of oxygen usage was an independent risk factor for late-onset LSV development in VLBW infants (odds ratio: 1.030, p = 0.032). Conclusion: LSV may be a nonspecific marker of perinatal insult to the developing brains of preterm infants. Prolonged postnatal oxygen usage may predispose VLBW preterm infants to late-onset LSV development. The long-term clinical impacts of LSV should be clarified.

Diagnostic challenges of an incidental finding: case report of definitely-congenital glioblastoma multiforme in a very preterm infant

Background Congenital brain tumors are extremely rare in the neonatal population, and often associated with a poor prognosis. The diagnostic suspicion is often aroused at antenatal scans or postnatally, if clinical signs and symptoms of increased intracranial pressure become evident. We present a case of definitely congenital glioblastoma multiforme incidentally diagnosed in a preterm infant, aiming to raise clinical awareness on this condition and to highlight the challenges of the related diagnostic work-up. Case presentation This female infant was born at 31 weeks’ gestation after an uneventful pregnancy. No abnormalities were detected at antenatal ultrasound scans and genetic tests. Head circumference at birth was on the 25th centile. A routine brain ultrasound scan performed on day 1 revealed a large, inhomogeneous lesion in the right cerebral hemisphere, with contralateral midline shift, which was confirmed by brain magnetic resonance imaging (MRI). Eye fundus and routine blood exams, including platelets count, coagulation screening and C-reactive protein, were normal. Given the high risk of complications, surgical biopsy of the lesion was temporarily hold and a daily sonographic follow-up was undertaken. Although head circumference growth was steady on the 25th centile, progressive changes of the lesion were detected by cranial ultrasound. The repeat MRI scans showed a significant enlargement of the mass, with contralateral midline shift and signs of intralesional and intraventricular bleeding. In view of this worsening, surgical resection was performed. The histological examination of the lesion biopsy documented a GFAP+ highly cellular neoplasm, with no mutation on SMARCB1 gene. At the molecular analysis, mutations on IDH and H3F3A genes were absent, whereas MGMT promoter was unmethylated. The diagnosis was grade IV glioblastoma IDH wild-type. Conclusions Congenital glioblastoma multiforme is an extremely rare but highly aggressive neoplasm. Since intralesional biopsy is not often feasible in affected neonates, knowledge of the associated clinical and neuroradiological features is particularly important, as they can also add useful information on the neoplasm behavior. Specimens from open surgical resection allow to perform a definite histological analysis and an extended molecular characterization, with relevant prognostic implications.

Brain GRowth Evaluation Assessed with Transfontanellar (B-GREAT) ultrasound. Old and new bedside markers to estimate cerebral growth in preterm infants: a pilot study

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, 7 of life and then weekly until discharge and at term) in preterm infants born with a gestational age less than 32 weeks. We evaluated Corpus Callosum (CC) length, Corpus Callosum-Fastigium (CCF) length, Anterior Horn Width (AHW), Frontal White Matter (FWM) height, Total brain Surface (TBS), Deep Grey Matter (DGM) height, Hemisphere Height (HH), Transverse Cerebellar Diameter in the axial view (TCDax) and coronal view (TCDcor). 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 was performed in 80 neonates (median birth gestational age: 28+5 weeks, interquartile range: 27+3 to 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.

Inflammatory cytokines, placental pathology, and neurological outcomes in infants born to preterm preeclamptic mothers

Preeclampsia is both a vascular and inflammatory disorder. Since the placenta is a conduit for fetal development, preeclampsia should be a presumed cause of adverse infant outcomes. Yet, the relationship of placental pathology, inflammation and neurological outcomes after preeclampsia are understudied. We prospectively examined a cohort of maternal-infant dyads with preeclampsia for maternal inflammatory cytokines at time of preeclampsia diagnosis and delivery, and fetal cord blood cytokines (IL-1β, IL-6, IL-8, and TNF-α). Placentas were analyzed for inflammatory and vascular pathologies. Neurodevelopmental assessment of infants utilizing the Pediatric Stroke Outcome Measure (PSOM) was conducted at 6-month corrected gestational age. Eighty-one maternal-newborn dyads were examined. Worse neurological outcomes were not associated with elevated maternal / fetal cytokines. Early preterm birth (gestational age ≤ 32 weeks) was associated with worse neurological outcomes at 6-months regardless of maternal/ fetal cytokine levels, placental pathology, or cranial ultrasound findings (OR 1.70, [1.16–2.48], p = 0.006). When correcting for gestational age, elevated IL-6 approached significance as a predictor for worse developmental outcome (OR 1.025 [0.985–1.066], p = 0.221). Pathological evidence of maternal malperfusion and worse outcomes were noted in early preterm, although our sample size was small. Our study did not demonstrate an obvious association of inflammation and placental pathology in preeclampsia and adverse neurodevelopmental outcome at 6-month corrected age but does suggest maternal malperfusion at earlier gestational age may be a risk factor for worse outcome.

Impact of a “Brain Protection Bundle” in Reducing Severe Intraventricular Hemorrhage in Preterm Infants <30 Weeks GA: A Retrospective Single Centre Study

Background: despite advances in perinatal care, periventricular/intraventricular hemorrhage (IVH) continues to remain high in neonatal intensive care units (NICUs) worldwide. Studies have demonstrated the benefits of implementing interventions during the antenatal period, stabilization after birth (golden hour management) and postnatally in the first 72 h to reduce the incidence of IVH. Objective: to compare the incidence of severe intraventricular hemorrhage (IVH ≥ Grade III) before and after implementation of a “brain protection bundle” in preterm infants <30 weeks GA. Study design: a pre- and post-implementation retrospective cohort study to compare the incidence of severe IVH following execution of a “brain protection bundle for the first 72 h from 2015 to 2018. Demographics, management practices at birth and in the NICU, cranial ultrasound results and short-term morbidities were compared. Results: a total of 189 and 215 infants were included in the pre- and post-implementation phase, respectively. No difference in the incidence of severe IVH (6.9% vs. 9.8%, p = 0.37) was observed on the first cranial scan performed after 72 h of age. Conclusion: the implementation of a “brain protection bundle” was not effective in reducing the incidence of severe IVH within the first 72 h of life in our centre.

Decreased Cerebral Oxygenation in Premature Infants with Progressive Posthemorrhagic Ventricular Dilatation May Help with Timing of Intervention

Objective The objective of this study was to determine the degree of progressive posthemorrhagic ventricular dilatation (PHVD) that is associated with a significant decrease in regional cerebral oxygen saturation (rScO2) in premature infants at risk for periventricular–intraventricular hemorrhage (PIVH). Study Design Cranial ultrasound (US) and near-infrared spectroscopy (NIRS) measurements of rScO2 were performed on inborn infants with birth weights less than 1,250 g on admission and at 1, 4, and 8 weeks of age. Infants with severe PIVH were studied weekly. A 1-hour average of rScO2 was compared with the frontal–occipital horn ratio (FOHR) measured the same day. Generalized linear models were used to analyze the relationship between FOHR and rScO2, by severity of PIVH, and adjusted for gestational age. Cut-off points of 0.55 for FOHR and 45% for rScO2 were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Results The study cohort included 63 infants with normal US, 15 with grade-1 or -2 PIVH (mild group), and 21 with grade-3 or -4 PIVH (severe group). Increases in FOHR in the severe group were associated with decreases in rScO2 at 1 week (p = 0.036), 4 weeks (p = 0.013), and 8 weeks of life (p = 0.001) compared with the normal and mild groups. Infants with FOHR greater than 0.55 were 92% more likely to have rScO2 less than 45% when compared with infants with FOHR less than 0.55 (OR = 0.08, 95% CI: [0.04, 0.13], p < 0.001). Conclusion Progressive PHVD (FOHR > 0.55) is a strong predictor of compromised cerebral oxygenation. A combination of rScO2 and FOHR measurements may aid in identifying infants with PHVD that would benefit from early intervention. Key Points