Change over time in internal cerebral vein pulsation in premature infants at risk of intraventricular hemorrhage.

BACKGROUND: Prolonged continuation of augmented internal cerebral vein (ICV) pulsation may be related to the development of premature intraventricular hemorrhage (IVH). However, the characteristics of ICV flow patterns in premature infants are unclear. AIM: To investigate the changes over time in ICV pulsation in premature infants at risk of IVH. STUDY DESIGN: A 5-year retrospective observational study of a single-center trial. SUBJECTS: In total, 112 very-low-birth-weight infants with gestational age of ≤32 weeks. OUTCOME MEASURES: ICV flow was measured every 12 h until 96 h after birth and thereafter on days 7, 14, and 28. The ICV pulsation index (ICVPI), which is a ratio of the minimum/maximum speed of ICV flow, was calculated. We recorded longitudinal ICVPI change and compared ICVPI among three groups classified according to gestational age. RESULTS: ICVPI started declining after day 1 and reached the minimum median value in 49-60 h after birth (1.0 during 0-36 h, 0.9 during 37-72 h, and 1.0 after 73-84 h). ICVPI was significantly lower during 25-96 h than during 0-24 h and on days 7, 14, and 28. ICVPI in the 23-25-week group was significantly lower between 13-24 h and day 14 than that in the 29-32-week group, and the same was observed for the 26-28-week group between 13-24 h and 49-60 h. CONCLUSIONS: ICV pulsation was affected by time after birth and gestational age, and this ICVPI fluctuation may reflect a postnatal circulatory adaptation.

Prediction scores based on neonatal inflammatory markers for chorioamnionitis and funisitis in extremely low gestational age neonates.

AIM: The aim of the study was to examine the predictive value of inflammatory markers for chorioamnionitis and funisitis in extremely low gestational age neonates. METHODS: According to the Redline histopathological classification, extremely low gestational age neonates were classified into: (1) maternal inflammatory response ≤1 or ≥2, based on inflammatory findings of the placenta and (2) foetal inflammatory response ≤1 or ≥2, based on inflammatory findings of the umbilical cord. On admission and 12-36 h postnatally, procalcitonin and high-sensitivity C-reactive protein levels and white blood cell and neutrophil counts were compared. For both maternal and foetal inflammatory responses ≥2, the predictive value of each inflammatory marker was calculated. RESULTS: On admission, procalcitonin had the best predictive value for maternal and foetal inflammatory response ≥2. The maternal inflammatory response ≥2 prediction score includes procalcitonin level on admission, high-sensitivity C-reactive protein level and white blood cell count at 12-36 h postnatally. Foetal inflammatory response ≥2 prediction score includes procalcitonin level and white blood cell count on admission and 12-36 h postnatally. The sensitivities were 96.4% and 96.3%, respectively. CONCLUSION: Procalcitonin, high-sensitivity C-reactive protein levels and white blood cell count provide highly sensitive prediction scores for chorioamnionitis and funisitis in extremely low gestational age neonates.

Changes in Internal Cerebral Vein Pulsation and Intraventricular Hemorrhage in Extremely Preterm Infants.

OBJECTIVES: This study aimed to investigate the relationship between internal cerebral vein (ICV) pulsation and intraventricular hemorrhage (IVH) and to identify the cut-off values that predict IVH. We hypothesized that the severity of ICV flow pulsations was related to IVH severity. STUDY DESIGN: In this prospective observational study, ICV flow was measured in 61 extremely preterm infants using ultrasonography at every 12 hours until 96 hours after birth and on days 7, 14, and 28. The ICV pulsation index (ICVPI = minimum/maximum ICV speed) was calculated and compared among the groups determined by Papile's IVH classification. The ICVPI cut-off values for IVH were determined by receiver operating characteristic curve analysis. RESULTS: Compared with those in the no IVH (NIVH) group (n = 51), the ICVPI median values in the severe IVH (SIVH; grades 3 and 4) group (n = 5) were lower at 25 to 96 hours and on day 7, whereas those in the mild IVH (MIVH; grades 1 and 2) group (n = 5) were lower at 37 to 60 hours. All SIVH events were initially detected within 60 hours after birth. The ICVPI cut-off values for SIVH were 0.92 at 13 to 24 hours, 0.42 at 25 to 36 hours, 0.58 at 37 to 48 hours, and 0.55 at 49 to 60 hours. Infants whose ICVPI values were below the cut-off value ≥3 times between 13 and 60 hours had a significantly higher SIVH incidence than those whose ICVPI values were below the cut-off value ≤2 times (57.1 vs. 1.9%, p < 0.001). CONCLUSION: Our results indicate that SIVH had sustained pronounced internal cerebral vein pulsations and that the ICVPI values may help predict SIVH. Further research on strategies to decrease venous pressure for IVH prevention is needed. KEY POINTS: · IVH preterm infants had sustained ICV pulsations.. · ICV flow in SIVH pulsated stronger.. · ICVPI fluctuation implies postnatal adaptation.. · We newly defined ICVPI to predict SIVH..

Procalcitonin is associated with postnatal respiratory condition severity in preterm neonate.

INTRODUCTION: Postnatal respiratory failure is common in preterm neonates and is difficult to distinguish from early-onset neonatal bacterial infection by clinical symptoms. Similar to C-reactive protein (CRP), procalcitonin (PCT) is used as a marker of bacterial infection. Recently, it has been reported that the serum PCT levels increase because of respiratory failure immediately after birth. However, there is insufficient information concerning the relationship between biological inflammation markers, such as PCT and CRP, and postnatal respiratory condition severity. METHODS: Preterm neonates were classified according to the received respiratory management as follows: nonrespiratory support (NRS), respiratory support (RS), surfactant administration therapy (STA), and STA with nitric oxide inhalation therapy (NO). The median serum PCT and CRP levels at 12-36 h postnatally were compared among the four groups. Additionally, the median serum PCT and CRP levels in the STA group were compared by STA timing and STA number. RESULTS: The PCT levels for the NRS, RS, STA, and NO groups were 1.04, 6.46, 12.93, and 86.79 µg/L, respectively; the CRP levels were 0.40, 0.80, 1.10, and 16.40 mg/L, respectively. The PCT levels were significantly lower among neonates receiving STA in the birth subgroup (4.82 µg/L) than among those receiving STA in the admission subgroup (14.71 µg/L). The PCT levels were significantly higher among the STA multiple-dose subgroup (24.87 µg/L) than among the STA single-dose subgroup (12.47 µg/L). No significant differences in the CRP levels were observed. CONCLUSION: The serum PCT levels in preterm neonates were associated with postnatal respiratory condition severity.

A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome.

Astrocytes exert adverse effects on the brains of individuals with Down syndrome (DS). Although a neurogenic-to-gliogenic shift in the fate-specification step has been reported, the mechanisms and key regulators underlying the accelerated proliferation of astrocyte precursor cells (APCs) in DS remain elusive. Here, we established a human isogenic cell line panel based on DS-specific induced pluripotent stem cells, the XIST-mediated transcriptional silencing system in trisomic chromosome 21, and genome/chromosome-editing technologies to eliminate phenotypic fluctuations caused by genetic variation. The transcriptional responses of genes observed upon XIST induction and/or downregulation are not uniform, and only a small subset of genes show a characteristic expression pattern, which is consistent with the proliferative phenotypes of DS APCs. Comparative analysis and experimental verification using gene modification reveal dose-dependent proliferation-promoting activity of DYRK1A and PIGP on DS APCs. Our collection of human isogenic cell lines provides a comprehensive set of cellular models for further DS investigations.

The Predictive Value of Procalcitonin and High-Sensitivity C-Reactive Protein for Early Bacterial Infections in Preterm Neonates.

INTRODUCTION: Evidence on the reliability of using procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) as diagnostic markers for early-onset neonatal bacterial infections is still insufficient because of their physiological elevation during the early neonatal period. This study aimed to assess the respiratory influence of serum PCT and hs-CRP levels and evaluate their predictive value for bacterial infections during the first 72 h of life in preterm neonates. METHODS: The preterm neonates enrolled in this single-center retrospective cohort study were categorized into 3 groups: reference, infection-unlikely respiratory failure, and probable bacterial infection; their serum PCT and hs-CRP levels were assessed. Subsequently, age-specific 95th percentile curves were plotted and the median and cutoff PCT and hs-CRP levels for predicting bacterial infections at birth and 7-18, 19-36, and 37-72 h after birth were determined. Moreover, the analysis of PCT and hs-CRP with a neonatal sequential organ failure assessment (nSOFA) score was performed in very low birth weight neonates. RESULTS: Serum PCT levels were influenced by respiratory failure. A significant difference was found in the median PCT and hs-CRP levels among the 3 groups at each time point. PCT sensitivities for predicting bacterial infection were slightly higher than those of hs-CRP in each time frame during the first 72 h of life. In both PCT and hs-CRP, there was no significant difference between infants with nSOFA scores of >4 and those with nSOFA scores of ≤4. DISCUSSION/CONCLUSION: Age-specific evaluation showed that PCT has better predictive value than hs-CRP for early-onset bacterial infections in preterm neonates.

4-Phenylbutyrate ameliorates apoptotic neural cell death in Down syndrome by reducing protein aggregates.

Individuals with Down syndrome (DS) commonly show unique pathological phenotypes throughout their life span. Besides the specific effects of dosage-sensitive genes on chromosome 21, recent studies have demonstrated that the gain of a chromosome exerts an adverse impact on cell physiology, regardless of the karyotype. Although dysregulated transcription and perturbed protein homeostasis are observed in common in human fibroblasts with trisomy 21, 18, and 13, whether and how this aneuploidy-associated stress acts on other cell lineages and affects the pathophysiology are unknown. Here, we investigated cellular stress responses in human trisomy 21 and 13 neurons differentiated from patient-derived induced pluripotent stem cells. Neurons of both trisomies showed increased vulnerability to apoptotic cell death, accompanied by dysregulated protein homeostasis and upregulation of the endoplasmic reticulum stress pathway. In addition, misfolded protein aggregates, comprising various types of neurodegenerative disease-related proteins, were abnormally accumulated in trisomic neurons. Intriguingly, treatment with sodium 4-phenylbutyrate, a chemical chaperone, successfully decreased the formation of protein aggregates and prevented the progression of cell apoptosis in trisomic neurons. These results suggest that aneuploidy-associated stress might be a therapeutic target for the neurodegenerative phenotypes in DS.

New reference ranges of procalcitonin excluding respiratory failure in neonates.

BACKGROUND: Existing reference data on serum procalcitonin (PCT) in neonates include the effects of respiratory disorders commonly occurring during birth. We aimed to determine new 95% reference intervals in neonates after excluding the influence of respiratory failure at birth, and to investigate the effects of gestational age (GA) and respiratory condition at birth on postnatal transient serum PCT elevation. METHODS: Samples were obtained from term and preterm neonates during the first 3 days of life. Neonates were classified into reference, respiratory failure, and bacterial infection groups. In the reference group, the correlation between PCT level and GA was investigated. RESULTS: The median PCT level within the 95% range 12-36 h after birth was 1.05 ng/mL (0.14-4.39) in term neonates (143 samples) and 1.01 ng/mL (0.15-4.44) in preterm neonates (95 samples). There was no correlation between GA and serum PCT level during 1-48 h after birth. There was a significant difference in median serum PCT level during 12-36 h after birth between the respiratory failure (9.56 ng/mL) and bacterial infection (49.82 ng/mL) groups in preterm neonates but no difference between term neonates (respiratory failure 6.83 ng/mL, and bacterial infection 7.43 ng/mL). CONCLUSIONS: Respiratory failure is the main effector for the transient elevation in serum PCT levels at 3 days of life. After excluding the influence of respiratory failure, the chronological pattern and range were very similar between term and preterm neonates. Procalcitonin can be useful for clinicians in distinguishing bacterial infection from respiratory failure, aiding decisions on appropriate antibiotic use.

Sac-Type Congenital Diaphragmatic Hernia: A Case Report of Two Siblings.

Congenital diaphragmatic hernia (CDH), a herniation of the abdominal contents through a defect or hypoplasia of the diaphragm, is a relatively common, severe congenital anomaly. Here we present the first case of two siblings with possibly isolated sac-type CDH and with a suspected genetic etiology. Although sibling recurrence of isolated CDH is rare, the incidence is higher than in the general population. Additionally, the second child had a more severe respiratory disorder than the first child. It is to be noted that siblings of children having isolated CDH are at risk for CDH, and prenatal evaluation should be considered individually.