[Clinical characteristics and genetic analysis of two children with X-linked Centronuclear myopathy due to variants of MTM1 gene].

OBJECTIVE: To explore the clinical and genetic characteristics of two newborns with Central nuclear myopathy (CNM). METHODS: Two newborns with CNM diagnosed clinically at Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology in April 2019 and November 2021 were selected as the study subjects, and their clinical data was collected. Both newborns and their parents were subjected chromosomal karyotyping analysis and whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Pathogenicity of the candidate variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: Patient 1 was a male neonate and Patient 2 was a 20-day-old male infant. Both newborns had featured difficulty in breathing and swallowing. WES revealed that both had harbored hemizygous variants of the MTM1 gene, which were verified by Sanger sequencing. Patient 1 had harbored a c.1261A>G variant. Based on the ACMG guidelines, it was rated as pathogenic (PVS1+PM2_Supporting+PP3). Patient 2 harbored a c.342delT variant, which was also rated as pathogenic (PVS1+PM2_Supporting+PP3). CONCLUSION: The c.1261A>G and c.342delT variants of the MTM1 gene probably underlay the pathogenesis of CNM in the two patients.

[An infant with premature closure of cranial sutures due to variant of ERF gene and a literature review].

OBJECTIVE: To analyze the clinical and genetic characteristics of an infant with craniosynostosis. METHODS: An infant who was admitted to Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in April 2021 due to widening of the lateral ventricles for over a month was selected as the study subject. Clinical data of the patient was collected. Peripheral blood samples were collected from the infant and her parents for chromosomal karyotyping and whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was retrieved from the PubMed, Wanfang and CNKI databases (up to December 2021) by using key words including ERF gene, craniosynostosis, ERF mutation, craniosynostosis and ERF-related craniosynostosis. RESULTS: The infant, a 1-month-and-16-day-old female, was found to have sagittal synostosis by cranial X-ray radiography. Genetic testing revealed that she has harbored a heterozygous c.787C>T (p.Q263*) variant of the ERF gene, which was not found in either parent. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as pathogenic (PVS1+PS2+PM2_Supporting). In total 63 relevant cases were retrieved from the database, and a total of 64 individuals were analyzed by genetic testing. Most of the cases were sporadic and males. Multiple cranial sutures (including at least two of the sagittal suture, coronal suture, lambdoid suture, and frontal suture) were involved in 45.45% of the cases, and those with sagittal suture closure only have accounted for 20.00%. The main clinical manifestations have included hypertelorism, exophthalmos, development delay, malar dysplasia, etc. Chiari type 1 malformation may present in some patients. Variants of the ERF gene have mainly included splicing and deletional variants, and there was a strong genetic heterogeneity among the infants and their pedigrees. CONCLUSION: The c.787C>T (p.Q263*) variant of the ERF gene probably underlay the craniosynostosis of this infant. Above finding has enriched the phenotype ~ genotype spectrum of the ERF gene.

The safety and feasibility of the screening for retinopathy of prematurity assisted by telemedicine network during COVID-19 pandemic in Wuhan, China.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) epidemic, due to the traffic blockade and the shortage of medical resources, more and more premature infants could not receive timely and effective ROP screening, which delayed treatment and even caused children blindness. Therefore, how to carry out ROP screening safely and effectively during the epidemic was very important and urgent. This study aimed to evaluate the safety and feasibility of ROP screening assisted by telemedicine network during COVID-19 outbreak. METHODS: This retrospective study was conducted at Wuhan Children's hospital in Wuhan, China, from January to October, 2020. The measures which were performed to make the ROP screening more safe and effective were summarized and the comparison between ROP screening assisted by telemedicine network in 2020 and usual screening in 2019 were analyzed. RESULTS: A total of 267 outpatient infants completed ROP screening. The median gestational age was 32 weeks (30w to 34w) and the median birth weight was 1780 g (1460 g to 2100 g). Meanwhile, 149 (55.8%) out of 267 infants were males. During January to May in 2020, 86 screening appointments were received, among which 67 (77.9%) were from telemedicine platform online. The completing percentage of total online ROP appointments was higher than that of total face-to-face appointments (58.1% VS 22. 1%, P = 0.018). As for the number of infants screened between 2020 and 2019 from Februaryto October, 54 infants completed ROP screening in 2020, which was higher than that (51participants) in 2019 on September. Furthermore, compared with the usual screening in 2019, ROP screening assisted by telemedicine network in 2020 had smaller gestational age (32w VS 33w, p<0.001) and lower birth weight (1780 g VS 1900 g, p = 0.001). However, of the 267 infants screened, 18(6.7%) had ROP while the percentage of ROP screened in 2019 was the same (44[6.7%]). During follow-up, none of medical staffs was infected and no adverse reaction was reported. CONCLUSIONS: The screening for retinopathy of prematurity assisted by telemedicine network was safe and feasible during the COVID-19 pandemic. Preventive measures before and after screening were very necessary, which could effectively avoid cross infection.

Silencing of Long Non-Coding RNA X Inactive Specific Transcript (Xist) Contributes to Suppression of Bronchopulmonary Dysplasia Induced by Hyperoxia in Newborn Mice via microRNA-101-3p and the transforming growth factor-beta 1 (TGF-ß1)/Smad3 Axis.

BACKGROUND Bronchopulmonary dysplasia (BPD) is a chronic lung disease mostly affecting premature infants. Long non-coding RNA (lncRNA) X inactive specific transcript (Xist) is actively involved in pulmonary disease development. The present study explored the potential mechanism of Xist in BPD development. MATERIAL AND METHODS First, newborn BPD mouse models were successfully established. lncRNAs and genes with differential expression were identified using microarray analysis. Various injuries and radial alveolar counts of lung tissues of BPD mice were detected by hematoxylin-eosin staining. Functional assays were utilized to detect alterations of superoxide dismutase (SOD), malondialdehyde (MDA), vascular endothelial growth factor, collagen I, alpha-smooth muscle Actin, TGF-ß1, and Smad3. Then, dual-luciferase reporter gene assay and RNA pull-down assay were performed to clarify the targeting relationship between Xist and miR-101-3p and between miR-101-3p and high-mobility group protein B3 (HMGB3). RESULTS In BPD mice, radial alveolar counts value and SOD activity declined while MDA level increased. Results of microarray analysis found that Xist and HMGB3 were highly expressed in BPD mice. Next, silenced Xist alleviated lung damage in BPD mice. Xist competitively bound to miR-101-3p to activate HMGB3, and overexpressed miR-101-3p mitigated lung damage in BPD mice. Additionally, silenced Xist downregulated the TGF-ß1/Smad3 axis. CONCLUSIONS Our study demonstrated that silencing of Xist suppressed BPD development by binding to miR-101-3p and downregulating HMGB3 and the TGF-b1/Smad3 axis. Our results may provide novel insights for BPD treatment.

[Effect of breastfeeding on insulin sensitivity in infants with intrauterine growth retardation: a follow-up study].

OBJECTIVE: To study insulin sensitivity and the serum level of adiponectin in infants with intrauterine growth retardation (IUGR) and the effect of breastfeeding on the insulin sensitivity through a follow-up study. METHODS: A total of 106 full-term IUGR infants who were hospitalized from October 2014 to October 2018 were enrolled as the IUGR group, and 90 full-term appropriate for gestational age (AGA) infants who were born during the same period of time were enrolled as the AGA group. Birth weight and body length were recorded. Serum levels of fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, and adiponectin were measured on day 7 after birth. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. According to the feeding pattern, the IUGR group was further divided into a breastfeeding group with 37 infants and a formula feeding group with 42 infants. The above serum indices and growth indices were also measured at the age of 3 and 6 months. RESULTS: Compared with the AGA group, the IUGR group had significantly increased levels in serum insulin and HOMA-IR and a significantly decreased level of adiponectin (P<0.05). There were no significant differences between the breastfeeding and formula feeding groups in growth indices and serum levels of FBG, TG, LDL, and HDL on day 7 after birth and at the ages of 3 and 6 months (P>0.05). In the breastfeeding group, serum insulin and HOMA-IR decreased and adiponectin level increased over the time of breastfeeding (P<0.05). CONCLUSIONS: Insulin sensitivity decreases in the early stage after birth in IUGR infants, and breastfeeding can improve insulin sensitivity.

[SARS-CoV-2 infection with gastrointestinal symptoms as the first manifestation in a neonate].

Since December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has occurred in Wuhan, Hubei Province, China. The infected cases were noted mostly in adults, but rarely reported in children, especially neonates. Most children with SARS-CoV-2 infection present mainly with respiratory symptoms, but less commonly with gastrointestinal symptoms, and tend to have mild clinical symptoms. A neonate with SARS-CoV-2 infection, who had vomiting and milk refusal as the first symptom, was recently admitted to Wuhan Children's Hospital. After two weeks of treatment, the patient recovered gradually and was discharged. Here, this case is reported to improve the understanding of SARS-CoV-2 infection in neonates.

[Effect of intrauterine growth retardation on insulin sensitivity and plasma adiponectin level in neonates].

OBJECTIVE: To explore the effect of intrauterine growth retardation (IUGR) on insulin sensitivity in neonates and the relationship between insulin sensitivity and plasma adiponectin level. METHODS: Eighty-two term neonates with IUGR and 90 term neonates born appropriate for gestational age (AGA) were enrolled. Weight, height, head circumference and abdomen circumference of the neonates were measured within 24 hours after birth. Fasting serum glucose (FG), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), plasma insulin and adiponectin were detected in two groups on the 7th day after birth. Homeostasis model assessment for insulin resistance (HOMA-IR) index and insulin sensitivity index (ISI) were calculated. RESULTS: There were no significant differences in the levels of FG, TG, HDL and LDL between the IUGR and AGA groups (P>0.05). The plasma insulin level in the IUGR group was higher than that in the AGA group, but the plasma adiponectin level was lower than that in the AGA group (P<0.05). HOMA-IR index in the IUGR group was higher than that in the AGA group, but ISI was lower than that in the AGA group (P<0.05). Both Pearson correlation analysis and multiple linear regression analysis showed HOMA-IR index was negatively correlated with plasma adiponectin level and birth weight (P<0.05). CONCLUSIONS: The neonates with IUGR display a higher plasma insulin level and decreased insulin sensitivity. The decreased plasma adiponectin level may be associated with the decreased insulin sensitivity.

[Value of arterial blood lactic acid in the evaluation of disease severity and prognosis in neonatal shock].

OBJECTIVE: To evaluate the value of blood lactic acid (BLA) as a predictor for the severity and prognosis of neonatal shock. METHODS: A total of 326 neonates with shock were enrolled and divided into three groups based on the severity, namely mild group (n=147), moderate group (n=105), and severe group (n=74). BLA level was measured during and early after (about 6 hours later) fluid resuscitation, and lactate clearance rate (LCR) was calculated. The receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of BLA in neonatal shock. RESULTS: BLA level was high in all subjects prior to treatment, and was highest in the severe group and lowest in the mild group (P<0.01). BLA level was significantly higher among patients with septic shock than among those with hypovolemic, cardiogenic, and asphyxiating shock (P<0.05). BLA level was significantly reduced in patients in recovery after treatment (P<0.05). Mortality was significantly lower in patients with BLA level ≤4 mmol/L or LCR ≥10% than in those with BLA level >4 mmol/L or LCR <10% (P<0.01). BLA at 11.15 mmol/L had 100% sensitivity and 96.8% specificity in predicting severe shock. BLA at 10.65 mmol/L had 88.9% sensitivity and 74.1% specificity in predicting the prognosis (survival or dead) of newborns with shock. CONCLUSIONS: In neonates with shock, arterial BLA level increases as the disease severity increases and is associated with prognosis, so it is a useful predictor of the severity and prognosis of neonatal shock.

A novel splice variant in intron 10 of PEX6 is associated with Zellweger Syndrome in a Chinese neonate.

BACKGROUND: Zellweger Syndrome (ZS), or cerebrohepatorenal syndrome, is a rare disorder due to PEX gene mutations affecting peroxisome function. While PEX6 coding mutations are known to cause ZS, the impact of noncoding mutations is less clear. METHODS: A Chinese neonate and his family were subjected to whole exome sequencing (WES) and bioinformatics to assess variant pathogenicity. A minigene assay was also performed for detailed splicing variant analysis. RESULTS: WES identified compound heterozygous PEX6 variants: c.315G>A (p. Trp105Ter) and c.2095-3 T>G. Minigene assays indicated that the latter variant led to abnormal mRNA splicing and the loss of exon 11 in PEX6 expression, potentially causing nonsense-mediated mRNA decay (NMD) or truncated protein structure. CONCLUSION: The study suggests that PEX6: c.2095-3 T>G might be a genetic contributor to the patient's condition, broadening the known mutation spectrum of PEX6. These insights lay groundwork for potential gene therapy for such variants.

Spontaneous intestinal perforation among very preterm infants in China: a multicenter cohort study.

Background: Spontaneous intestinal perforation (SIP) is one of the most serious surgical bowel conditions affecting preterm infants. There are limited data on the mortality and morbidities of very preterm infants [VPIs, <32 weeks' gestational age (GA)] with SIP in China. The study aimed to describe the prevalence, treatment, and outcomes of SIP among VPIs in China. Methods: This retrospective cohort study included all infants born at 24+0-31+6 weeks GA from January 1, 2019, to December 31, 2020, and admitted within seven days after birth to the neonatal intensive care units in the Chinese Neonatal Network. The primary outcome was survival without major morbidities. The association between SIP and neonatal outcomes was evaluated using multivariate logistic regression controlling for possible confounders. Results: Out of the 15,814 enrolled infants, 150 (1.0%) developed SIP with a median onset age of four (IQR 2-6) days. Infants with GA 24+0-25+6 weeks had the highest incidence of SIP (13/532, 2.4%), followed by those with GA 26+0-27+6 weeks (22/2,005, 1.1%), 28+0-29+6 weeks (44/5,269, 0.8%) and 30+0-31+6 weeks (71/8,008, 0.9%). Ten SIP cases were lost to follow-up with unknown survival status and 41 (29.3%) of the remaining 140 infants with SIP died during hospitalization. Only 29.3% of infants with SIP survived without major morbidities, significantly lower than those without SIP (59.2%; P<0.01). Multivariate analysis revealed SIP was associated with a higher risk of overall death (adjusted OR 3.36; 95% CI: 1.85 to 6.08), late-onset sepsis (adjusted OR 2.10; 95% CI: 1.02 to 4.31), and bronchopulmonary dysplasia (adjusted OR 2.49; 95% CI: 1.44 to 4.30). Among all infants with SIP, 28 (18.7%) did not receive any surgical intervention. Laparotomy was provided to 113 (92.6%) of the remaining 122 infants, solely (84/122, 68.9%) or following peritoneal drainage (29/122, 23.8%), while nine (7.4%) infants underwent peritoneal drainage only. Conclusions: Around 1% of VPIs in China developed SIP, associated with increased risk of mortality and morbidities. Over 90% of VPIs with SIP underwent laparotomy as initial or subsequent surgical treatment. Effective and evidence-based strategies are needed for the prevention and management of SIP.

Pulmonary fungal infection in a neonate with methylmalonic acidemia: A case report.

BACKGROUND: Methylmalonic acidemia (MMA) is characterized by non-specific symptoms such as vomiting, and feeding difficulties, along with delayed mental and physical development. However, no case of MMA combined with pulmonary fungal infection has been reported yet. CASE SUMMARY: We report the case of a neonate who presented pulmonary fungal infection along with the non-specific features of MMA. Exome sequencing revealed a c.331C>T variant in exon 3 of MMACHC from the father, and a c.658-c.660delAAG variant in exon 4 from the mother, which confirmed the diagnosis of cblC type MMA combined with hyperhomocysteinemia. CONCLUSION: Invasive fungal infection might occur in some infants with MMA. Therefore, early diagnosis is recommended for unexplained pulmonary infection.

Hyperoxia Induced Bronchopulmonary Dysplasia-Like Inflammation via miR34a-TNIP2-IL-1ß Pathway.

Lung injury induced by oxygen is a key contributor to the pathogenesis of preterm infant bronchopulmonary dysplasia (BPD). To date, there are comprehensive therapeutic strategy for this disease, but the underlying mechanism is still in progress. By using lentivirus, we constructed microRNA34a (miR34a)-overexpressing or knockdown A549 cell lines, and exposure to hyperoxia to mimic oxygen induce lung injury. In this study, we investigated 4 proinflammatory cytokines, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), angiopoietin-1 (Ang-1), and Cyclooxygenase-2 (COX-2) in the secreted sputum of infants who received mechanical ventilation, and found that IL-1ß was substantially elevated in the first week after oxygen therapy and with no significant decrease until the fourth week, while TNF-α, Ang-1, and COX-2 were increased in the first week but decreased quickly in the following weeks. In addition, in vitro assay revealed that hyperoxia significantly increased the expression of miR-34a, which positively regulated the proinflammatory cytokine IL-1ß in a time- and concentration-dependent manner in A549 cells. Overexpressing or knockdown miR34 would exacerbate or inhibit production of IL-1ß and its upstream NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathway. Mechanically, it's found that TNFAIP3 interacting protein 2 (TNIP2), an inhibitor of nuclear factor κB (NF-κB), is a direct target of miR34a, negatively regulated activation of NLRP3 inflammasome and the production of IL-1ß. Overexpressing TNIP2 ameliorated hyperoxia-induced production of IL-1ß and cell apoptosis. Our findings suggest that TNIP2 may be a potential clinical marker in the diagnosis of BPD.

Effects of hyperoxia on cytoplasmic thioredoxin system in alveolar type epithelial cells of premature rats.

This study investigated the effects of hyperoxia on dynamic changes of thioredoxin-1 (Trx1) and thioredoxin reductase-1 (TrxR1) in alveolar type II epithelial cells (AECII) of premature rats. Pregnant Sprague-Dawley rats were sacrificed on day 19 of gestation. AECII were isolated and purified from the lungs of premature rats. When cultured to 80% confluence, in vitro cells were randomly divided into air group and hyperoxia group. Cells in the hyperoxia group were continuously exposed to 95% O(2)/5% CO(2) and those in the air group to 95% air/5% CO(2). After 12, 24 and 48 h, cells in the two groups were harvested to detect their reactive oxygen species (ROS), apoptosis, TrxR1 activity and the expressions of Trx1 and TrxR1 by corresponding protocols, respectively. The results showed that AEC II exposed to hyperoxia generated excessive ROS and the apoptosis percentage in the hyperoxia group was increased significantly at each time points as compared with that in the air group (P<0.001). Moreover, TrxR1 activity was found to be markedly depressed in the hyperoxia group in comparison to that in the air group (P<0.001). RT-PCR showed the expressions of both Trx1 and TrxR1 mRNA were significantly increased in AECII exposed to hyperoxia for 12 and 24 h (P<0.01), respectively. At 48 h, the level of Trx1 mRNA as well as that of TrxR1 mRNA in the hyperoxia group was reduced and showed no significant difference from that in the air group (P>0.05). Western blotting showed the changes of Trx1 protein expressions in the hyperoxia group paralleled those of Trx1 mRNA expressions revealed by RT-PCR. It was concluded that hyperoxia can up-regulate the protective Trx1/TrxR1 expressed by AECII in a certain period, however, also cause dysfunction of the cytoplasmic thioredoxin system by decreasing TrxR1 activity, which may contribute to the progression of oxidative stress and cell apoptosis and finally result in lung injury.

Quantitative assessment of COVID-19 pneumonia in neonates using lung ultrasound score.

BACKGROUND: Lung ultrasound (LUS) and lung ultrasound score (LUSS) have been successfully used to diagnose neonatal pneumonia, assess the lesion distribution, and quantify the aeration loss. The present study design determines the diagnostic value of LUSS in the semi-quantitative assessment of pneumonia in coronavirus disease 2019 (COVID-19) neonates. METHODS: Eleven COVID-19 neonates born to mothers with COVID-19 infection and 11 age- and gender-matched controls were retrospectively studied. LUSS was acquired by assessing the lesions and aeration loss in 12 lung regions per subject. RESULTS: Most of the COVID-19 newborns presented with mild and atypical symptoms, mainly involving respiratory and digestive systems. In the COVID-19 group, a total of 132 regions of the lung were examined, 83 regions (62.8%) of which were detected abnormalities by LUS. Compared with controls, COVID-19 neonates showed sparse or confluent B-lines (83 regions), disappearing A-lines (83 regions), abnormal pleural lines (29 regions), and subpleural consolidations (2 regions). The LUSS was significantly higher in the COVID-19 group. In total, 49 regions (37%) were normal, 73 regions (55%) scored 1, and 10 regions (8%) scored 2 by LUSS. All the lesions were bilateral, with multiple regions involved. The majority of the lesions were located in the bilateral inferior and posterior regions. LUS detected abnormalities in three COVID-19 neonates with normal radiological performance. The intra-observer and inter-observer reproducibility of LUSS was excellent. CONCLUSIONS: LUS is a noninvasive, convenient, and sensitive method to assess neonatal COVID-19 pneumonia, and can be used as an alternative to the use of diagnostic radiography. LUSS provides valuable semi-quantitative information on the lesion distribution and severity.

Effects of SARS-CoV-2 infection on neuroimaging and neurobehavior in neonates.

BACKGROUND: We collected neonatal neurological, clinical, and imaging data to study the neurological manifestations and imaging characteristics of neonates with coronavirus disease 2019 (COVID-19). METHODS: This case-control study included newborns diagnosed with COVID-19 in Wuhan, China from January 2020 to July 2020. All included newborns had complete neurological evaluations and head magnetic resonance imaging. We normalized the extracted T2-weighted imaging data to a standard neonate template space, and segmented them into gray matter, white matter, and cerebrospinal fluid. The comparison of gray matter volume was conducted between the two groups. RESULTS: A total of five neonates with COVID-19 were included in this study. The median reflex scores were 2 points lower in the infected group than in the control group (P = 0.0094), and the median orientation and behavior scores were 2.5 points lower in the infected group than in the control group (P = 0.0008). There were also significant differences between the two groups in the total scale score (P = 0.0426). The caudate nucleus, parahippocampal gyrus, and thalamus had the strongest correlations with the Hammersmith neonatal neurologic examination (HNNE) score, and the absolute correlation coefficients between the gray matter volumes and each part of the HNNE score were all almost greater than 0.5. CONCLUSIONS: We first compared the neurological performance of neonates with and without COVID-19 by quantitative neuroimaging and neurological examination methods. Considering the limited numbers of patients, more studies focusing on the structural or functional aspects of the virus in the central nervous system in different age groups will be carried out in the future.

Short-term developmental outcomes in neonates born to mothers with COVID-19 from Wuhan, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease. The consequences of SARS-CoV-2 exposure in infants remain unknown. Therefore, this study aims to investigate whether neonates born to mothers with COVID-19 have adverse brain development. METHODS: This multicenter observational study was conducted at two designated maternal and children's hospitals in Hubei Province, mainland China from February 1, 2020 to May 15, 2020. Neonates born to mothers with COVID-19 were enrolled. Brain magnetic resonance imaging (MRI) findings, and volumes of grey and white matters, and physical growth parameters were observed at 44 weeks corrected gestational age. RESULTS: Of 72 neonates born to mothers with COVID-19, 8 (11%) were diagnosed with COVID-19, 8 (11%) were critically ill, and no deaths were reported. Among the eight neonates that underwent brain MRI at corrected gestational age of 44 weeks, five neonates were diagnosed with COVID-19. Among these five neonates, three presented abnormal MRI findings including abnormal signal in white matter and delayed myelination in newborn 2, delayed myelination and brain dysplasia in newborn 3, and abnormal signal in the bilateral periventricular in newborn 5. The other three neonates without COVID-19 presented no significantly changes of brain MRI findings and the volumes of grey matter and white matter compared to those of healthy newborns at the equivalent age (P > 0.05). Physical growth parameters for weight, length, and head circumference at gestational age of 44 weeks were all above the 3rd percentile for all neonates. CONCLUSIONS: Some of the neonates born to mothers with COVID-19 had abnormal brain MRI findings but these neonates did not appear to have poor physical growth. These findings may provide the information on the follow-up schedule on the neonates exposed to SARS-CoV-2, but further study is required to evaluate the association between the abnormal MRI findings and the exposure to SARS-CoV-2.

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study.

BACKGROUND: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. METHODS: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. FINDINGS: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). INTERPRETATION: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. FUNDING: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.

A newborn with normal IgM and elevated IgG antibodies born to an asymptomatic infection mother with COVID-19.

Pregnant women are susceptible population of COVID-19 which are more likely to have complications and even progress to severe illness. Pregnancy with COVID-19 and neonates are rarely reported. We report a newborn with normal IgM and elevated IgG antibodies born to an asymptomatic infection mother with COVID-19. We assessed whether there was intrauterine vertical transmission potential of COVID-19.

Infants Born to Mothers With a New Coronavirus (COVID-19).

A novel viral respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for an epidemic of the coronavirus disease 2019 (COVID-19) in cases in China and worldwide. Four full-term, singleton infants were born to pregnant women who tested positive for COVID-19 in the city of Wuhan, the capital of Hubei province, China, where the disease was first identified. Of the three infants, for who consent to be diagnostically tested was provided, none tested positive for the virus. None of the infants developed serious clinical symptoms such as fever, cough, diarrhea, or abnormal radiologic or hematologic evidence, and all four infants were alive at the time of hospital discharge. Two infants had rashes of unknown etiology at birth, and one had facial ulcerations. One infant had tachypnea and was supported by non-invasive mechanical ventilation for 3 days. One had rashes at birth but was discharged without parental consent for a diagnostic test. This case report describes the clinical course of four live born infants, born to pregnant women with the COVID-19 infection.

LncRNA MEG3 ameliorates respiratory syncytial virus infection by suppressing TLR4 signaling.

Maternally expressed gene 3 (MEG3), a long noncoding RNA (lncRNA) has been dysregulated in various tumors. However, the expression level and functional role of MEG3 in the progression of respiratory syncytial virus (RSV) infection remains to be elucidated. The present study quantified the expression level of MEG3 in the nasopharyngeal (NPA) samples of RSV­infected patients and in BEAS­2B cells infected with RSV. The findings of the present study demonstrated that the expression level of lncRNA MEG3 was reduced in the NPA samples of RSV­infected patients and in BEAS­2B cells infected with RSV. In vitro transfection revealed increased mRNA expression levels of toll­like receptor 4 (TLR4), tumor necrosis factor­α (TNFα) and interleukin (IL)­8 following RSV infection in BEAS­2B cells. Additionally, ectopic expression of MEG3 reduced the expression level of TLR4, subsequently suppressing the mRNA expression levels of TNFα and IL­8, indicating the protective role of MEG3 in the process of RSV infection. It is of note, that RSV infection­induced p38 mitogen activated protein kinase (MAPK) and nuclear factor­κB (NF­κB) activation was partly abolished by overexpression of MEG3. In conclusion, to the best of our knowledge, the present study provided the first evidence that lncRNA MEG3 expression level was reduced in the NPA samples of patients with RSV infection and RSV­infected cells. Additionally, it was demonstrated that MEG3 protected human airway epithelial cells from RSV infection, primarily by suppressing TLR4­dependent p38 MAPK and NF­κB signaling.