[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

[Analysis of survival and prognostic factors in extremely preterm infants].

OBJECTIVE: To investigate the survival rate, complications during hospitalization, and prognostic factors in extremely preterm infants (gestational age less than 28 weeks) in the neonatal intensive care unit (NICU). METHODS: A retrospective analysis was performed on 90 extremely preterm infants who were admitted to the NICU between January 2011 and March 2013 to investigate the perinatal data, delivery and resuscitation, ventilation/oxygen supply during hospitalization, mortality, and the incidence of severe (grade III/IV) intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), and septicemia. RESULTS: Among the 90 extremely preterm infants, the gestational age, birth weight, overall survival rate, mortality, and withdrawal rate were 26±1 weeks, 898±165 g, 57%, 9%, and 34%, respectively. The incidence rates of neonatal respiratory distress syndrome, BPD, PDA, ROP, and grade III/IV IVH were 88%, 85%, 69%, 68%, and 31%, respectively. The surviving infants had a mean length of hospital stay of 83±18 days and a mean weight at discharge of 2 419±300 g. The multivariate logistic regression analysis showed that grade III/IV IVH and pulmonary hemorrhage were high-risk factors for death or withdrawal, while antenatal corticosteroids were the protective factor for outcome (P<0.05). CONCLUSIONS: The survival rate of extremely preterm infants is still much lower than that in developed countries. grade III/IV IVH, and pulmonary hemorrhage are important prognostic factors.

[Advances in medical care for extremely low birth weight infants worldwide].

Dramatic advances in neonatal medicine over recent decades have resulted in decreased mortality and morbidity rates for extremely low birth weight infants. However, the survival of these infants is associated with short- and long-term morbidity, including severe intraventricular hemorrhage, periventricular leukomalacia, nosocomial infection and necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity and adverse long-term neurodevelopmental sequelae. This article reviewed the latest advances in the medical care for extremely low birth weight infants including survival rate, ethical issues and short- and long-term morbidity, domestically and abroad.

The differential associative relationship between early risk factors, neonatal morbidities and early neurodevelopmental outcome in preterm infants <29 weeks' gestation.

BACKGROUND: Very preterm infants of <29 weeks' gestation are at high risk for adverse neurodevelopment due to multiple risk factors in the early stages of life. There is little information regarding the associative effects of risk factors in early life, neonatal morbidities and subsequent neurodevelopmental outcomes. AIMS: Investigate the association of early neurodevelopmental outcomes, neonatal complications and the risk factors in the early hours of life in a cohort of preterm infants <29 weeks' gestational age. METHODS: We enrolled all surviving preterm neonates born at gestation <29 weeks between January 2015 and June 2021 in the University of Hong Kong-Shenzhen Hospital. Demographic and clinical characteristics were collected from a database of the neonatal intensive care unit. Neurodevelopmental outcomes of the survivors were evaluated using the Ages and Stages Questionnaire (ASQ-3) which were measured at the adjusted age of 12 to 18 months. The multivariate linear regression model was used to determine correlation presented as ß coefficient (ß) with 95 % confidence intervals (CI). RESULTS: In this cohort of 56 survivors <29 weeks' gestation, urine output within the first 12 h of life and Apgar score at 5 min were positively associated with different domains of ASQ-3 score, however male sex and highest fraction of inspired oxygen (FiO2) in the first 12 h of life were negatively related with at least one of neurocognitive domains of ASQ-3 at adjusted age of 12 to 18 months. During hospitalization, in addition to the frequency of packed red cell transfusions, the development of severe necrotizing enterocolitis was inversely associated with both neuromotor and neurocognitive skills (gross motor domain: ß = -16.93, CI: -32.04, -1.82; fine motor domain: ß = -16.42, CI: -28.82, -4.02; problem solving domain: ß = -13.14, CI: -24.45, -1.83; all P < 0.05), whereas severe intraventricular hemorrhage had adverse effects on gross motor only (ß = -13.04, CI: -24.42, -1.65; P = 0.03). Bronchopulmonary dysplasia and retinopathy of prematurity were not related with ASQ-3. CONCLUSIONS: In this small cohort study of very preterm neonates born at <29 weeks' gestation, risk factors in the early hours of life and neonatal morbidities during hospitalization had differential associative relationships with ASQ-3 at 12-18 months adjusted age. This information may be important for parental counseling and management including early diagnosis and intervention.

A Family-Centered, Multidisciplinary Clinic for Early Diagnosis of Neurodevelopmental Impairment and Cerebral Palsy in China-A Pilot Observation.

Background: Comprehensive multidisciplinary assessment of neurodevelopmental outcomes of high-risk neonates may have significant challenges in low- and middle-income countries, in addition to socio-cultural barriers. We aimed to compare the time to diagnosis of neurodevelopmental impairment (NDI) and cerebral palsy (CP) in preterm neonates (<29 weeks) at a multidisciplinary assessment and care (MDAC) clinic with that of a conventional high-risk infant follow-up clinic in China. Methods: All eligible surviving very preterm neonates born at <29 weeks gestation at the University of Hong Kong-Shenzhen Hospital between January 2015 and December 2019 were followed up in conventional (2015-2017) and MDAC (2018-2020) clinics up to 2 years corrected age with clinical demographic information collected in a prospective database. The MDAC team used standardized developmental assessments. The rates and timing of diagnosing NDI and CP in two epochs were compared. Results: The rates of NDI and CP were not different in two epochs [NDI: 12 (50%) vs. 12 (41%); CP: 3 (12%) vs. 2 (7%) of 24 and 29 surviving infants assessed in conventional and MDAC clinics, respectively]. Infants in the MDAC clinic were diagnosed with NDI and CP earlier than those in the pre-MDAC epoch (6 vs. 14 months corrected age, respectively, P < 0.05). Conclusion: High-risk preterm neonates can be followed more effectively in a family-centered, child-friendly multidisciplinary clinic, leading to an earlier diagnosis of NDI and CP. Early counseling and interventions could be implemented accordingly.

Family-centered care management strategies for term and near-term neonates with brief hospitalization in a level III NICU in Shenzhen, China during the time of COVID-19 pandemic.

BACKGROUND: Adopting the family-centered care (FCC) approach in the neonatal care has been shown to improve breastfeeding rate and parental satisfaction. To minimize the transmission of COVID-19, family visit in neonatal intensive care unit (NICU) was suspended in China. In order to maintain the benefits of FCC, the Hong Kong University-Shenzhen Hospital NICU modified FCC strategies. We evaluated the effects of new strategies and aimed to share our results and experience with other NICUs during the COVID-19 pandemic. METHODS: Using prospectively collected hospital databases, we retrospectively compared the demographic and clinical data of neonates, rates of breastfeeding at discharge, nosocomial infection and parental satisfaction one month before (open group) and after (closed group) the implementation of alternative FCC management strategies when family visit was suspended during COVID-19 pandemic. RESULTS: During the COVID-19 pandemic, we organized a multidisciplinary task force and adopted strategies of triage and screening, management of suspected infants, and breastfeeding promotion with effective communication. The nosocomial infection rate and parental satisfaction for open and closed groups (144 and 108 term and near-term neonates with brief hospitalization, respectively) were not different (1% vs. 0%, p = 1.00; 98.6 vs. 98.8, p = .80; respectively). Breastfeeding rate at discharge decreased but the difference was not significant (74% vs. 80%, p = .29). CONCLUSIONS: In our experience, in term and near-term neonates with brief hospitalization, the alternative FCC strategies maintained high parental satisfaction without increased nosocomial infection rate, but strong support for breastfeeding was needed. Through multidisciplinary collaboration, the continuation of "modified" FCC in a level III NICU is feasible in the context of COVID-19 pandemic with reduced family visitation and participation in the care.

Hemidiaphragmatic paralysis related to extravasation of parenteral solution in very low birthweight neonates.

Central venous catheter (CVC) placement is common in the care of very low birthweight (VLBW) preterm neonates. Although it is generally considered to be safe, CVC placement is associated with complications, including extravasation that may lead to significant morbidity and mortality. We report the clinical course of an extremely preterm neonate born at 27 weeks gestation, and another 5 VLBW preterm neonates reported in the literature with hemidiaphragmatic paralysis related to extravasation of parenteral solution from CVC placement. In VLBW preterm neonates, spontaneous recovery of diaphragmatic paralysis related to extravasation of parenteral solution is possible.

Early Risk Factors for Retinopathy of Prematurity in Very and Extremely Preterm Chinese Neonates.

Objective: To investigate the incidence and risk factors of retinopathy of prematurity (ROP) in very and extremely preterm (28+0- <32+0, and <28+0 weeks gestation, respectively) neonates, and the predictive factors for ROP in the early hours after birth and during hospitalization. Methods: Using a prospective database supplemented with a retrospective chart review, we identified preterm neonates born at gestation <32 weeks at the University of Hong Kong-Shenzhen Hospital between January 2015 and August 2018. Demographic and clinical variables were studied including indicators of disease acuity in the first 24 h after birth. We also compared the difference in risk factors between survivors with ROP and survivors without ROP. Results: During the study period, there were 529 preterm neonates admitted to our neonatal intensive care unit with 120 (23%) born at <32 weeks' gestation. Thirteen (11%) neonates died. Among the 107 survivors, 23 (21%) had ROP, of whom five (22%) received laser and/or medical therapy for severe ROP. Compared with survivors without ROP, infants with ROP had lower mean blood pressure in the first 12 and 24 h after birth, respectively. Using multivariate regression, gestation age, mean blood pressure in the first 12 h after birth, hospital length of stay, and total days of blood gases pH <7.2 were independent risk factors for ROP. Conclusions: In this small cohort of Chinese neonates born <32+0 weeks' gestation, survivors with ROP had a lower blood pressure in the early hours after birth, younger gestation, longer hospital stay, and duration of acidosis when compared to those without ROP.

[Relation of insulin-like growth factor binding protein-2 with hyperoxia-induced lung injury in term and premature neonatal rats].

OBJECTIVE: To study the deleterious effect of prolonged hyperoxic exposure on term and premature neonatal rat lungs and investigate the relationship between insulin-like growth factor binding protein (IGFBP)-2 and hyperoxia-induced lung injury in neonatal rats. METHODS: At the 22nd postnatal day Sprague-Dawley (SD) term-newborn or preterm-newborn rats were randomly divided into 4 groups. group I: term-rats+air group; group II: term-rats+hyperoxia group; group III: preterm-rats+air group; group IV: preterm-rats+hyperoxia group. The rats in group II and IV were exposed to about 85% (in volume) O(2). The rats in group I and III were exposed to air in the same rooms. At 4, 7, 10, 14 and 21 days after birth, eight rats in each group were killed. The mortality of newborn rats was also recorded and lung radical alveolar counts (RAC) were examined. Lung histopathology with hematoxylin and eosin (HE) staining was examined; The protein and mRNA of IGFBP-2 in the lung tissue were determined by Western blotting and by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: After 7 days of 85% O(2) exposure, the survival rate in group II, IV were significant lower compared with group I, III (all P<0.01), but no difference was found between group IV and group II (P>0.05). No inflammatory change in lung tissue was found in group I and III. After 7-14 days of hyperoxia exposure, blood vessels in group II, IV were dilated. Red blood cells and inflammatory cells were seen infiltrating into the alveolar space, and interstitium was thickened. After 21 days of hyperoxic exposure, inflammatory changes in group II became more marked, and the alveolar walls or alveolar septa were markedly thickened. The formation of alveoli in group II, IV was retarded and RACs at all time points were significantly lower than those in group I, III (all P<0.01). After 4 days and 14 days, the expression of IGFBP-2 in the group II and IV were significantly higher than those in group I, III (all P<0.01). The expression of mRNA of IGFBP-2 showed the same tendency of the protein in all 4 groups. CONCLUSION: The prolonged exposure to hyperoxia may cause subacute lung injury and the retardation of lung development in term-neonatal or preterm-neonatal rats. The abnormal expressions of IGFBP-2 correlate with hyperoxia-induced lung injury in neonatal rats.

A prospective evaluation of the efficacy of the laryngeal mask airway during neonatal resuscitation.

OBJECTIVE: To study the feasibility, efficacy and safety of using the laryngeal mask airway (LMA) in neonatal resuscitation. METHODS: In total, 369 neonates (gestational age ≥ 34 weeks, expected birth weight ≥2.0 kg) requiring positive pressure ventilation at birth were quasi-randomised to resuscitation by LMA (205 neonates) or bag-mask ventilation (164 neonates). RESULTS: (1) Successful resuscitation rate was higher with the LMA compared with bag-mask ventilation (P<0.001) and the total ventilation time was shorter with the LMA than with bag-mask ventilation (P<0.001). Seven of nine neonates with an Apgar score of 2 or 3 at 1 min after birth were successfully resuscitated in the LMA group, while in the BMV group all six neonates with an Apgar score of 2 or 3 at 1 min required tracheal intubation and ventilation. In neonates with an Apgar score of 4 or 5 at 1 min after birth, successful resuscitation rate with the LMA was higher than with bag-mask ventilation (P<0.01). (2) Successful insertion rate of the LMA at the first attempt was 98.5% and the insertion time was 7.8 s ± 2.2 s. There were few adverse events (vomiting and aspiration) in the LMA group. CONCLUSION: The LMA is safe, effective and easy to implement for the resuscitation of neonates with a gestational age of 34 or, more weeks.

[Retinoic acid diminished the expression of lung tissue matrix metalloproteinase-2 and matrix metalloproteinase-9 in hyperoxia-exposed premature rats through regulating mitogen-activated protein kinases].

OBJECTIVE: To further investigate the protective effect of retinoic acid (RA) on hyperoxia induced lung injury and the role of RA as a modulator on mitogen-activated protein kinases (MAPKs). METHODS: Establishment of hyperoxia (85%) induced lung injury model of premature Sprague-Dawley (SD) rats: 21 d gestational age SD rat's fetuses (term = 22 d) were delivered by hysterectomy. Within 12 - 24 h after birth, the premature rat pups were randomly divided into 4 groups: Group I, air-exposed control group; Group II, hyperoxia-exposed group; Group III, air plus RA-exposed group, Group IV, hyperoxia plus RA-exposed group. Group I and III were remained in room air, and group II and IV were placed in 85% oxygen. The pups in Group III and IV were injected with RA (500 microg/kg, every day) intraperitoneally. The entire lung tissues of premature rat pups were collected at 4 d, 7 d and 14 d. The mRNA levels of MMP-2 and MMP-9 were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). MMP-2 and MMP-9 activities were measured by zymography. Western blot was used to detect phosphorylated and total nonphosphorylated form of ERKs, JNKs and p38. RESULTS: Exposure to oxygen for 4 d, 7 d, and 14 d resulted in increased mRNA levels of MMP-2 and MMP-9 compared with air-exposed control group (P < 0.01 for all). The mean protein levels of active MMP-2 and pro/active MMP-9 after exposure to O2 were higher than air control groups on each experimental day (P < 0.01 or < 0.05). The phosphorylated ERK1/2, JNK1/2 and p38 proteins in hyperoxia-exposed group increased markedly compared with air-exposed control group (P < 0.01 for all). The pups treated with RA in the hyperoxic environment expressed significantly lower mRNA levels of MMP-2 and MMP-9 than the hyperoxic control pups on each experimental day (P < 0.05 for all). The levels of active MMP-2 and pro/active MMP-9 decreased to a different degree after RA treatment in hyperoxia exposure rat pups. In addition, RA treatment led to a decrease of p-JNK1/2 and p-38 (P < 0.01 for all) protein levels and a further elevation of p-ERK1/2 compared with hyperoxia-exposed group. CONCLUSION: Hyperoxia exposure elevated the expression of MMP-2 and MMP-9 markedly, which played a role in oxygen-induced lung injury. RA could have a protective effect on hyperoxia induced lung injury by decreasing active levels of JNK and p38, which subsequently reduce the expression and activation of MMP-2 and MMP-9.

[Protective effects of amygdalin on hyperoxia-exposed type II alveolar epithelial cells isolated from premature rat lungs in vitro].

OBJECTIVE: To analyze the effect of hyperoxia on the proliferation and surfactant associated protein messenger RNA levels of type II alveolar epithelial cells (AECIIs) of premature rat, and to investigate the effect of amygdalin on the change resulted from hyperoxia in AECIIs isolated from premature rat lung in vitro. METHODS: The lung tissue of 20-day fetal rat was digested by trypsin and collagenase. AECIIs and lung fibroblasts (LFs) were isolated and purified at different centrifugal force and different adherence, then cultured. The nature of the cultures was identified by cytokeratin staining, vimentin staining and transmission electron micrography. For establishing hyperoxia-exposed cell model, purified AECIIs were cultured for 24 hours after culture flasks were filled with 95% oxygen-5% CO2 at 3 L/min for 10 min, and then sealed. Oxygen concentrations were tested in CYS-1 digital oxygen monitor after 24 hours of exposure. A sample was discarded if its oxygen concentration was < 90%. Cell proliferating vitality was examined by MTT assay after treatment with amygdalin at various concentrations. DNA content, protein expression of proliferating cell nuclear antigen (PCNA) and mRNA levels of SPs of AECIIs were analyzed with flow cytometric assay, Western blot and reverse transcription polymerase chain reaction (RT-PCR) respectively after 24 hours of air or hyperoxia exposure in the presence or absence of 200 micromol/L amygdalin. RESULTS: Excellent yields of highly purified, culturable AECIIs could be obtained from 20-day fetal lungs. The expression of cytokeratin in AECIIs was positive and that of vimentin negative by immunocytochemistry. Those, however, in LFs were just opposite. Lamellar bodies in purified AECIIs were revealed by transmission electron micrography. The established hyperoxia-exposed cell model assured the oxygen concentrations of culture flasks more than 90%. Amygdalin at the concentration range from 50 micromol/L to 200 micromol/L stimulated the proliferation of AECIIs in a dose-dependent manner; however, at the concentration of 400 micromol/L inhibited the proliferation of AECII. Flow cytometric analysis showed that the apoptosis rate and G0/G1 phase percentage increased significantly (P < 0.01), S phase and G2/M phase percentage decreased significantly (P < 0.01), in hyperoxia group compared with that of air group. The apoptosis rate of air plus 200 micromol/L amygdalin group, compared with air group, was not significantly different (P > 0.05); however, G0/G1 phase percentage decreased markedly, S phase percentage increased significantly, G2/M phase percentage did not significantly change (P > 0.05). The apoptosis rate of hyperoxia plus 200 micromol/L amygdalin group was not significantly different (P > 0.05) from that of hyperoxia group, S phase and G2/M phase percentage increased significantly (P < 0.01), G0/G1 phase percentage decreased significantly (P < 0.01). Western blot analysis showed that the protein expression levels of PCNA in all group was significantly different, in turn, hyperoxia group < hyperoxia plus 200 micromol/L amygdalin < air group < air puls 200 micromol/L amygdalin (P < 0.01). SPs mRNA levels were significantly decreased in hyperoxia group, as compared with air group (P < 0.01). After amygdalin was added, SPs mRNA levels were elevated in air plus amygdalin group and hyperoxia plus amygdalin group, as compared with hyperoxia group (P < 0.01, P < 0.05, respectively), but compared with air group, SP mRNA levels were not significantly elevated (P > 0.05). CONCLUSION: AECIIs of premature rats were isolated, purified and cultured successfully. Hyperoxia-exposed cell model was established in AECIIs of premature rat in this experiment. Amygdalin promotes the proliferation of premature rat AECII exposed to air or hyperoxia, the concentration of amygdalin with the best effect was 200 micromol/L. Hyperoxia inhibited the proliferation and decreased SPs mRNAs levels in AECIIs in vitro, which may contribute to hyperoxia-induced lung injury in premature rats. Amygdalin could inhibit the changes of SPs mRNAs levels and cell proliferation of AECIIs resulted from hyperoxia and may play partial protective role in hyperoxia-induced premature lung injury.