Incidence of Neonatal Seizures in China Based on Electroencephalogram Monitoring in Neonatal Neurocritical Care Units.

Importance: Neonatal seizures pose a significant challenge in critical care, and continuous video electroencephalography (cEEG) monitoring holds promise for early detection of seizures. However, large-scale data on the incidence of neonatal seizures and monitoring systems in China are lacking. Objectives: To determine the incidence of neonatal seizures in infants with high risk in China. Design, Setting, and Participants: A large, cross-sectional multicenter study was conducted from January 2017 to December 2018 in the neonatal intensive care units (NICUs) of 7 tertiary medical centers in China. Neonates with high risk were included, and cEEG monitoring was conducted. Data were collected between January 1, 2017, and January 31, 2020. The data were analyzed between January 2021 and January 2022. Main Outcomes and Measures: The incidence of neonatal seizures, categorized by etiology, and seizure burden. Results: A total of 20 310 neonates with high risk were included (10 495 [51.7%] male; mean [SD] postmenstrual age, 37.7 [3.7] weeks), and seizures were observed in 3423 infants (16.9%). The highest proportion of seizures was attributed to acute neonatal encephalopathy (1448 [42.3%]). The incidence of seizures decreased with postmenstrual age and birth weight, with the highest occurrence observed in neonates with postmenstrual age of less than 28 weeks (237 of 879 [27.0%]) or birth weight of less than 1.0 kg (269 of 914 [29.4%]). Preterm infants had a higher proportion of moderate and severe seizure burdens compared with full-term infants (moderate severity: 248 of 1199 [20.7%] vs 454 of 2224 [20.4%]), but no significant differences were observed in etiology. Seizure burden was highest with genetic syndromes (49 of 188 [26.1%]), central nervous system malformations (33 of 127 [26.0%]), and inborn errors of metabolism (27 of 113 [23.9%]). During hospitalization, 7.8% of neonates with seizures died (267 neonates), with 81.3% of these cases having a moderate or severe seizure burden (217 neonates). Mortality was generally higher in preterm vs full-term infants (98 of 1199 [8.2%] vs 169 of 2224 [7.6%]) and increased with the severity of seizure burden (217 of 267 neonates with moderate or severe burden [81.3%]). Conclusions and Relevance: This cross-sectional study of neonatal seizures underscores the substantial burden seizures pose to high-risk infants with brain injury in China, particularly those who are born prematurely or who have congenital conditions.

Changing trend of abdominal regional oxygen saturation in very/extremely low birth weight infants in the early postnatal stage: a prospective study. / 极/è¶ ä½Žå‡ºç”Ÿä½“é‡å„¿ç”ŸåŽæ—©æœŸè ¹éƒ¨å±€éƒ¨ç»„ç»‡æ°§é¥±å’Œåº¦å˜åŒ–è¶‹åŠ¿çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the changing trend of abdominal regional oxygen saturation (A-rSO2) in very/extremely low birth weight (VLBW/ELBW) infants after birth. METHODS: The VLBW/ELBW infants who were admitted to the neonatal intensive care unit from September 2019 to May 2021 were enrolled as subjects. Near-infrared spectroscopy was used to monitor A-rSO2 since day 1 after birth for 4 weeks. According to gestational age, the infants were divided into a low gestational age (<29 weeks) group and a high gestational age (≥29 weeks) group. The two groups were compared in terms of A-rSO2 within 4 weeks after birth. RESULTS: A total of 63 VLBW/ELBW infants were enrolled, with 30 infants in the <29 weeks group and 33 in the ≥29 weeks group. A-rSO2 fluctuated within the first 2 weeks after birth in the 63 infants and had the lowest level of 47.9% on day 1 after birth and then gradually increased, reaching the peak level of 67.4% on day 4; it gradually decreased on days 5-9, then gradually increased, and became relatively stable 2 weeks after birth. The ≥29 weeks group had significantly higher A-rSO2 than the <29 weeks group at weeks 1 and 2 after birth (P<0.05), while there was no significant difference in A-rSO2 between the two groups at weeks 3 and 4 after birth (P>0.05). CONCLUSIONS: In infants with VLBW/ELBW, A-rSO2 fluctuates within the first 2 weeks after birth and then gradually becomes stable. A-rSO2 is associated with gestational age within 2 weeks after birth.

Demographic and Clinical Features of Small-for-Gestational-Age Infants Born to Mothers With Gestational Diabetes Mellitus.

We studied the demographic and clinical characteristic, risk factors, outcomes of full-term small-for-gestational-age (SGA) infants born to mothers with gestational diabetes mellitus (GDM) in China. A retrospective case-control study that included 1981 SGA infants was conducted; the demographic and clinical data between SGA infants born to mothers with and without GDM were compared. Of 383 SGA infants born to mothers with GDM, 221 (57.7%) were female, and the incidence of these infants was 1 in 155 live births. The risk of SGA siblings (RR, 1.88; 95% CI, [1.23-2.86]), low 1- and 5-min Apgar scores (RR,2.04 and 4.21; 95%CI [1.05-4.00] and [1.05-16.89], respectively), early thrombocytopenia (RR, 3.39; 95%CI, [1.33-8.64]), hypoglycemia(RR, 2.49; 95%CI, [1.55-3.98]), and hypoxic-ischemic encephalopathy (RR,5.61; 95%CI, [1.25-25.18]) were increased in SGA infants born to mothers with GDM compared to SGA infants born to mothers without GDM. SGA girls born to mothers with GDM had a significantly higher ratio of catch-up growth (CUG) (RR, 1.73; 95%CI, [1.18-2.54]) in the first year of life. These results show that genetic factors may be one of the etiologies of SGA infants born to mothers with GDM; and these infants have more adverse perinatal outcomes compared to SGA infants born to mothers without GDM. SGA girls born to mothers with GDM had accelerated CUG in the first year of life.

Fully automated simultaneous peripheral arteriovenous exchange transfusion not seen to aggravate brain function and the disorder of the internal environment in neonates with severe hyperbilirubinemia.

BACKGROUND: The acute changes in brain function in newborn infants undergoing ET remain unclear. This study aimed to determine whether fully automated simultaneous peripheral arteriovenous ET would influence the brain function. METHODS: A retrospective analysis was conducted on the clinical data of 39 neonates with hyperbilirubinemia who received ET. Seventeen patients were in the encephalopathy group, and the other 22 patients were in the non-encephalopathy group. Changes in amplitude-integrated electroencephalogram (aEEG) during ETs were analyzed, including background activities, sleep-wake cycling (SWC), and seizures. Before and after the ET, routine blood test parameters, electrolytes, blood glucose, and blood gas parameters were measured. RESULTS: After ETs, there were no significant changes in the levels of pH, PaO2, PaCO2, lactate, and red blood cells, while the levels of total bilirubin, indirect bilirubin, blood potassium, blood sodium, serum calcium, while blood cells, and platelets were significantly lower and the level of blood glucose was significantly higher compared to those before therapy. There was no significant difference in the changes of electroencephalographic activities during ETs, including background activities, SWC, and seizures. However, there were significant differences in suppressions on background activities, while there were no significant statistical differences in SWC or seizures between the 2 groups. CONCLUSION: Fully automated simultaneous peripheral arteriovenous ET is safe and efficient without significant influence on the disorder of the internal environment and electroencephalographic activities after ET in neonates. However, background activities are more significantly depressed in infants of bilirubin encephalopathy than infants of non-encephalopathy during ET.

Application of Neurally Adjusted Ventilatory Assist in Premature Neonates Less Than 1,500 Grams With Established or Evolving Bronchopulmonary Dysplasia.

Background: Very low birth weight premature (VLBW) infants with bronchopulmonary dysplasia (BPD) often need prolonged respiratory support, which is associated with worse outcomes. The application of neurally adjusted ventilatory assist ventilation (NAVA) in infants with BPD has rarely been reported. This study investigated whether NAVA is safe and can reduce the duration respiratory support in VLBW premature infants with established or evolving BPD. Methods: This retrospective matched-cohort study included patients admitted to our NICU between April 2017 to April 2019 who were born at <32 weeks' gestation with birthweight of <1,500 g. The study groups (NAVA group) were infants who received NAVA ventilation as a sequel mode of ventilation after at least 2 weeks of traditional respiratory support after birth. The control group were preterm infants who required traditional respiratory support beyond first 2 weeks of life and were closely matched to the NAVA patients by gestational age and birthweight. The primary outcome was to compare the total duration of respiratory support between the NAVA group and the control group. The secondary outcomes were comparisons of duration of invasive and non-invasive support, oxygen therapy, length of stay, severity of BPD, weight gain and sedation need between the groups. Results: There were no significant differences between NAVA group and control group in the primary and most of the secondary outcomes (all P > 0.05). However, NAVA was well tolerated and there was a decrease in the need of sedation (p = 0.012) after switching to NAVA. Conclusion: NAVA, when used as a sequel mode of ventilation, in premature neonates <1,500 g with evolving or established BPD showed a similar effect compared to conventional ventilation in respiratory outcomes. NAVA can be safely used in this patient population and potentially can decrease the need of sedation.

Effects of different surfactant administrations on cerebral autoregulation in preterm infants with respiratory distress syndrome.

To treat respiratory distress syndrome, surfactant is currently delivered via less invasive surfactant administration (LISA) or INtubation SURfactant Extubation (INSURE). The aim of this study was to compare the effect of the two delivery methods of surfactant on cerebral autoregulation. Near infrared spectroscopy monitoring was carried out to detect cerebral oxygen saturation (ScO2), and the mean arterial blood pressure (MABP) was simultaneously recorded. Of 44 preterm infants included, the surfactant was administrated to 22 via LISA and 22 via INSURE. The clinical characteristics, treatments and outcomes of the infants showed no significant differences between the two groups. The correlation coefficient of ScO2 and MABP (r ScO2-MABP) 5 min before administration was similar in the two groups. During surfactant administration, r ScO2-MABP increased in both groups (0.44±0.10 to 0.54±0.12 in LISA, 0.45±0.11 to 0.69±0.09 in INSURE). In the first and second 5 min after instillation, r ScO2-MABP was not significantly different from baseline in the LISA group, but increased in the first 5 min after instillation (0.59±0.13, P=0.000 compared with the baseline in the same group) and recovered in the second 5 min after instillation (0.48±0.10, P=0.321) in the INSURE group. There were significant differences in the change rates of r ScO2-MABP between the two groups during and after surfactant administration. Our results suggest that cerebral autoregulation may be affected transiently by surfactant administration. The effect duration of LISA is shorter than that of INSURE (<5 min in LISA vs. 5-10 min in INSURE).

De novo GLI3 mutation in esophageal atresia: reproducing the phenotypic spectrum of Gli3 defects in murine models.

Esophageal atresia is a common and life-threatening birth defect with a poorly understood etiology. In this study, we analyzed the sequence variants of coding regions for a set of esophageal atresia-related genes including MYCN, SOX2, CHD7, GLI3, FGFR2 and PTEN for mutations using PCR-based target enrichment and next-generation sequencing in 27 patients with esophageal atresia. Genomic copy number variation analysis was performed using Affymetrix SNP 6.0. We found a de novo heterozygous mutation in the N-terminal region of the GLI3 gene (c.332T>C, p.M111T) in a patient with esophageal atresia and hemivertebrae. The N-terminal region (amino acids 1-397) of GLI3 contains the repressor domain, which interacts with SKI family proteins. Using the co-immunoprecipitation assay, we found that interaction of GLI3 with the SKI family protein SKIL was significantly compromised by the p.M111T mutation of GLI3. Thus far, all the identified mutations mapped within the repressor domain of GLI3 were nonsense and frame-shift mutations. In this study, a missense mutation was initially detected in this region. Our finding is the first to link this GLI3 gene mutation with esophageal atresia in humans, which was previously suggested in an animal model.

[Effects of glycomacropeptide on damage to intestinal tissue and apoptosis of intestinal epithelial cells in neonatal rats with necrotizing enterocolitis].

OBJECTIVE: To establish an appropriate neonatal rat model of necrotizing enterocolitis (NEC) and to investigate the protective effects of glycomacropeptide (GMP) on the gut from injury in neonatal rats with NEC. METHOD: A total of 36 neonatal SD rats were randomly divided into 3 groups: NEC model group (Group M), NEC + GMP group (Group G) and normal control group (Group N), each group had 12 rats. All the neonatal rats were fed with breast milk in the first 3 days after birth. During the second 3 days after birth, the rats of Group N were still maternal breast-fed, but the rats of Group M and Group G were separated from their mothers and lived in incubator and began to be formula fed, and were subjected to cold exposure shortly after hypoxic-reoxygenation treatment. After being fed in such means for 6 days, all the neonatal rats were placed into the incubator and fasted for 24 hours. Then all the rats were sacrificed by cervical dislocation. Intestinal tissue located at the boundary of ileum and cecum was obtained for: (1) histological examination after HE staining, (2) TUNEL detection, (3) electron microscopic observation; and the tissue homogenate was obtained for checking TNF-α and IL-1ß levels by ELISA and platelet activating factor (PAF) mRNA expression by quantitative fluorescence (QF)-PCR. RESULT: (1) The pathological scores of the 3 groups were 2.17 ± 0.83 (Group M), 0.92 ± 0.79 (Group G) and 0.17 ± 0.39 (Group N) separately. There was significant difference between Group M and Group G (H = 8.819, P = 0.003). (2) TNF-α levels of 3 groups were (41.94 ± 13.51) pg/ml (Group M), (31.69 ± 11.68) pg/ml (Group G) and (17.42 ± 7.18) pg/ml (Group N) separately, and TNF-α level in Group G was significantly lower than that of Group M (F = 3.959, P = 0.030). (3) IL-1ß levels of 3 groups were (150.33 ± 36.41) pg/ml (Group M), (118.36 ± 33.00) pg/ml (Group G) and (28.44 ± 15.04) pg/ml (Group N) separately, and IL-1ß level in Group G was lower than that of Group M (F = 5.080, P = 0.013). (4) Expression levels of intestinal PAF mRNA (2(-ΔΔCt) value): 3.01 ± 0.96 (Group M), 1.56 ± 0.29 (Group G), 1.01 ± 0.13 (Group N), the level of Group G was significantly lower than that of Group M (F = 25.251, P = 0.000). (5)Electron microscopy: Group N showed that its cell volume was mostly occupied by the nucleus, the structure was clear, nuclear membrane existed, suggesting the normal phase of cell; Group M showed that apoptotic body existed, suggesting that the advanced stage phase of apoptosis; Group G showed that condensed chromatin marginated around the nuclear envelope, nuclear pores expanded, suggesting the early phase of apoptosis. (6) The apoptosis rate of intestinal epithelial cells by TUNEL detection: 38.79 ± 9.79 (Group M), 29.54 ± 7.30 (Group G), 6.37 ± 1.96 (Group N); the apoptosis rate of intestinal epithelial cells of Group G was significantly lower than that of Group M (F = 6.888, P = 0.003). CONCLUSION: GMP has protective effects on guts of neonatal rats with NEC, which may probably work by reducing TNF-α, IL-1ß and PAF expression, inhibiting the apoptosis of intestinal epithelial cells and reducing intestinal tissue injury.