Objective:To study the clinical features and treatment strategy of neonatal ureaplasma meningitis.Methods:During 2021, the clinical data of 2 neonates with ureaplasma meningitis treated in Children's Hospital of Hunan Province were retrospectively analyzed. Literature on this subject were searched in the following databases: CNKI, Wanfang Database, Chinese Medical Journal Full-Text Database, CQVIP database, SinoMed, PubMed, Embase and Web of Science (up to March 2022). The key words included “infant”, “neonate”, “newborn”, “ureaplasma”, “mycoplasma urealytium”, “meningitis”, “central nervous system infection”, “brain”. The clinical data, treatment and prognosis of patients from the literature were summarized.Results:Case 1, female, gestational age(GA) 33 +3 weeks, intracranial hemorrhage (ICH) and ventricular dilatation were found on 2 d after birth. The cerebrospinal fluid (CSF) routine and biochemistry tests indicated meningitis, but the CSF culture was negative. No improvement after antibiotic treatment. CSF metagenomic next-generation sequencing (mNGS) and 23S rRNA showed Ureaplasma urealyticum on 30 d after birth. The patient was treated with doxycycline (DOX) for 21 d until mNGS turned negative and DOX was discontinued. However, the disease recurred 23 d later and erythromycin was added with DOX as combined therapy. The patient was followed up until 6 months without neurodevelopmental disabilities. Case 2, male, GA 26 weeks, ICH and ventricular dilatation were found on 10 d after birth. The CSF routine and biochemistry tests indicated meningitis, but the CSF culture was negative. No improvement after antibiotic treatment. CSF mNGS and 23S rRNA showed Ureaplasma parvum. The patient received erythromycin therapy for 32 d and had normal neurodevelopment at 5 months. According to the literature, 43 cases were reported including the 2 cases descirbed above, 17 cases were full-term infants and 26 cases were preterm infants. The median CSF leukocytes, glucose and proteins were 566 cells/mm 3, 0.2 mmol/L and 2.2 g/L. 27 cases were diagnosed based on CSF culture, 6 cases using mNGS, 4 cases with both CSF culture and PCR method and 6 cases with other methods. Macrolides alone were used in 14 cases, macrolides combined with another antibiotic were used in 8 cases, non-macrolide antibiotics were used in 9 cases and 12 cases didn't receive any anti-ureaplasma therapy. All 17 term infants survived, however, 8 cases with hydrocephalus. Among the 26 preterm infants, 8 patients died, 18 patients had periventricular-intraventricular hemorrhage and 15 patients had hydrocephalus. Conclusions:Neonatal ureaplasma meningitis has significantly lower CSF glucose level with hydrocephalus as the common complication. For intracranial infections of unknown etiology and no response to treatment, mNGS is helpful in determining the pathogen.Neonatal ureaplasma meningitis should be treated with macrolides alone or as add-on therapy.

Objective:To develop a self-made plasma quality control material for non-invasive prenatal testing (NIPT) and evaluate its performance.Methods:139 NIPT-negative maternal plasmas stored in the genetic department of Shaoxing maternal and child health hospital from January 1, 2019 to June 30, 2021 were divided into male groups (19 cases) and female groups (120 cases) according to the neonatal gender. 9360 cases from September 2020 to September 2021 were enrolled as clinical validation cases.First step, 200 μl plasma from a 47 years-old non-pregnant healthy women was used as a matrix. Different amounts (0.1, 0.2, 0.5, 2.5, and 5 μl) of positive DNA from fetal chromosome aneuploidy (T21, T18, T13) detection kit were added. The appropriate volume of positive DNA was 0.5 μl according to the test results. Second step,Plasma in male and female group was treated as matrix. 0.5 μl positive DNA was added per 205 μl. Plasma matrix from female group showed good repeatability and the sensitivity was 100%.Third step, evaluate the self-made plasma quality control material, including storage stability, matrix uniformity and repeatability, and the effect of different batch numbers of positive DNA, by calculating Z score and the CV of fetal DNA concentration (FF).Results:Plasma matrix from female group showed good repeatability and the sensitivity was 100%, while the sensitivity of male group was only 84%. The CV of FF in female matrix was 3.9% in the repetitive experiments. After adding 0.5 μl positive DNA, the mean FF of self-made positive plasma quality control was 5.63%±0.42%, Z values>6, and the CV was 7% after storage of three months. Considering the concentration variation of positive DNA in different lots, 1 μl of positive DNA should be added when the FF of positive DNA is lower than 10%.Used in 9360 clinical cases from September 2020 to September 2021, all positive plasma quality control materials showed positive results, and the positive predictive value of trisomy 21 was 100%.Conclusions:The NIPT self-made positive plasma quality control material has been successfully developed in this study. The preliminary experimental results show that it has good repeatability and stability, which is suitable for clinical application.

Objective:To study the clinical efficacy, safety and prognosis of systemic hypothermia therapy on neonatal hypoxic-ischemic encephalopathy (HIE)initiated at different times after birth.Method:From January 2013 to August 2018, term neonates (within 12 hours after birth) diagnosed with neonatal moderate to severe HIE and received systemic treatment in the neonatal intensive care unit of our hospital were retrospectively included. According to the starting time of hypothermia therapy, the neonates were assigned into three groups: within 6 h after birth (TH1 group), 6~12 h (TH2 group) and conventional treatment group (control group). Their clinical data during perinatal period, hospitalization period and follow-up at 6-month were reviewed. Their clinical and neurodevelopmental outcomes were compared using SPSS 25.0 statistical software.Result:A total of 147 neonates with moderate to severe HIE were enrolled. 111 received 72-hour hypothermia therapy, including 79 in the TH1 group, 32 in the TH2 group and 36 in the control group. The neurobehavioral test scores at 10-day of life in the TH1 group were significantly higher than the control group ( P<0.05). No significant differences existed among the TH2 group, the TH1 group and the control group ( P>0.05). The brain magnetic resonance imaging (MRI) showed injuries in the TH1 group and the TH2 group were significantly milder than the control group ( P<0.05). No significant differences of brain injuries existed between TH1 group and TH2 group ( P>0.05). 100 patients completed Bailey Infant Intelligence Development Scale at 6-month follow-up. 21 had abnormal scores. No statistically significant differences existed in the psychomotor development index (PDI) scores among the three groups ( P>0.05). TH1 and TH2 groups had significantly fewer cases with mental development index (MDI) <70 points than the control group ( P<0.05). No statistically significant differences existed of MDI scores between the TH1 group and the TH2 group ( P>0.05). No statistically significant differences existed of PDI scores among the 3 groups ( P>0.05). At 6-month, the mortality rate of the control group (32.1%, 9/28) was significantly higher than the TH1 group (6.6%, 4/61) ( P<0.05). No significant differences existed of mortality rate at 6-month among the TH2 group, the TH1 group and the control group ( P>0.05). Conclusion:Systemic hypothermia therapy for neonatal HIE is safe. Starting systemic hypothermia therapy at 6~12-hour after birth may also be effective in reducing mortality rate and improving neurodevelopmental outcome.

Due to low autoimmune function, imperfect development of various organs, coupled with a variety of invasive operations and other factors, premature infants are high-risk groups of invasive fungal infection.Invasive candida infection in premature infants accounts for more than 80% of invasive fungal infection. The main infection rate of invasive candida albicans was candida albicans. However, in recent years, the infection rate of non-candida albicans such as candida albicans, tropical candida, smooth candida and other non-candida albicans showed a gradual upward trend.In addition to blood culture, the latest diagnostic methods such as plasma (1-3)-β-D-glucan test and candida polymerase chain reaction are helpful for the diagnosis of invasive fungal infection. At the same time, attention should also be paid to prophylactic antifungal therapy and empirical antifungal therapy in premature infants.

High mobility group box 1 protein(HMGB1) is widely present in eukaryotic nuclei and named for its rapid migration during polyacrylamide gel electrophoresis. Studies have shown that HMGB1 playes an important role in the development of gene transcription,inflammation,cancer and other diseases. In this paper, the biological characteristics of HMGB1 and its research progress in pediatric diseases are reviewed.

Objective To study the transport risk and factors that influence deaths of very low birth weight (VLBW) and extremely low birth weight (ELBW) infants.Method All infants transferred to our neonatal intensive care unit (NICU) by our hospital transport team or local hospital transport team from January 2014 to December 2015 were included in our study.Their clinical data were retrospectively studied.The risks of transport between hospitals were analyzed.The risk factors of deaths within and after 7 days of admission were further analyzed by multivariate Logistic regression analysis.The receiver operation characteristic (ROC) curve was used to assess the sensitivity and specificity of mortality index for neonatal transportation (MINT),transport related mortality score (TREMS),transport risk index of physiologic stability (TRIPS) for predicting mortality of preterm infants.Result (1) A total of 527 cases of ELBW/VLBW infants were included in our study.There were no deaths during transport.There were 10.2％ (54/527) died within and 8.9％ (42/473) died after 7 days of hospitalization.(2) Multivariate Logistic regression analysis showed that scleredema of newborn,secondary transport,gastrointestinal malformations,metabolic acidosis,high TREMS score,and high MINT score were risk factors of mortality within 7 days of admission for ELBW/VLBW infants;necrotizing enterocolitis,intraventricular hemorrhage ≥ three degree,high MINT score and low admission weight were risk factors of mortality after 7 days of admission.(3) The area under the ROC curve for MINT,TREMS,and TRIPS score were 0.672,0.655 and 0.665,respectively.The cut-off values for MINT score (cut-off 8,sensitivity 0.444,specificity 0.829),for TREMS score (cut-off 2,sensitivity 0.500,specificity 0.757,for TRIPS score (cut-off 20,sensitivity 0.444,specificity O.829) were selected to predict mortality within 7 days of admission.Conclusion (1) Secondary transport is the transport-related risk factor of mortality within 7 days of admission for ELBW/VLBW infants.(2) High MINT score is the risk factor of mortality within and after 7 days of admission.(3) If MINT ≥ 8,TREMS ≥2,or TRIPS ≥20,it might significantly increase the risk of mortality of ELBW/ VLBW infants within 7 days of admission after transport.

Objective To study the occurrence of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants and to determine the risk factors of severe BPD.Method From January 2007 to January 2017,ELBW infants admitted to neonatal intensive care unit (NICU) in Hunan Children's Hospital were retrospectively analyzed.They were assigned into severe and mild/moderate groups based on the severity of BPD.The general condition,maternal status,prenatal and delivery room treatment,transportation,clinical courses,therapy and outcome in NICU of the two groups were compared,and the risk factors of severe BPD were analyzed.Result A total of 367 cases were hospitalized during the 10 years.281 ELBW infants with complete medical records survived longer than 28 days were enrolled in this study.Among them,233 had BPD.Among BPD infants,116 cases were in the severe BPD group,47 cases (40.5％) died.117 cases were in the mild/moderate BPD group and 1 case (0.9％) died.The difference between the two groups was statistically significant (P ＜ 0.05).Multivariate Logistic regression analysis showed that the risk factors of severe BPD were duration of mechanical ventilation ≥ 7 days (OR =7.518,95 ％ CI 3.197 ～ 17.676),ventilator-associated pneumonia (OR =3.047,95 ％ CI 1.436 ～ 6.464),1 min Apgar score ≤7 (OR =2.341,95 ％ CI 1.142 ～ 4.796) and patent ductus arteriosus (OR =2.223,95 ％ CI 1.079 ～4.582).Conclusion The incidence and mortality of BPD,especially severe BPD,are high in ELBW infants.Avoiding asphyxia,shortening the time of mechanical ventilation,preventing infection and closing ductus arteriosus are important measures to reduce the severity of BPD.

Objective To investigate the early growth and development of extremely low birth weight infants (ELBWI) and very low birth weight infants (VLBWI) through a follow-up study from hospital discharge until 18 months of corrected age.Methods ELBWI and VLBWI who were hospitalized and discharged alive from the Neonatal Intensive Care Unit of Hunan Children's Hospital from January 2013 to June 2014 were recruited.Follow-ups were performed at the corrected age of 40 weeks,as well as at one,three,six,12 and 18 months of corrected age.Several parameters indicating the growth and development of those infants were monitored and assessed.Extrauterine growth retardation (EUGR) was defined as head circumference (HC) or weight ≤ 10th percentile for gestational age at discharge.T-,rank-sum,or Chi-square (or Fisher's exact) test was performed for statistical analysis.Results (1) A total of 285 ELBWI and VLBWI were recruited.Among them,145 (50.9％) were alive at last follow-up,37 (13.0％) died,and 103 (36.1％) were lost.No significant differences in clinical data were observed between the infants who completed the follow-up and those who did not (all P＞0.05).(2) Based on HC and weight,the incidences of EUGR in the 145 infants reached the peak at the corrected age of three months [42.8％ (62/145) and 40.0％ (58/145)],and then declined with increasing age.At 18 months of corrected age,the incidences of EUGR dropped to 31.7％ (46/145) and 14.5％ (21/145),respectively.(3) There were no significant differences in gender,gestational age,birth weight,length of hospital stay,duration of oxygen therapy,and incidences of complications between the infants with and without EUGR (allP＞0.05).(4) The rate of pulmonary surfactant therapy in neonates with EUGR was lower than in those without [27.8％ (15/54) vs 53.8％ (49/91),x2=9.340,P＜0.05].There were no significant differences in mental development index and psycho-motor development index at 12 and 18 months of corrected age between the neonates with and without EUGR (all P＞0.05).Neither HC nor weight at the corrected age of 18 months showed significant differences between the two groups (both P＞0.05).(5) At 18 months of corrected age,31.7％ (46/145) of the infants had their HC ≤ 10th percentile,and 14.5％ (21/145) had their weight ≤ 10th percentile.Infants with HC ≤ 10th percentile were at higher risk of abnormal neurodevelopment than those with HC ＞10th percentile [67.4％ (31/45) vs 40.4％ (40/99),X=9.154].Infants with either HC or weight ≤ 10th percentile had higher risk of abnormal neurodevelopment that those with both HC and weight ＞10th percentile [65.5％ (36/55) vs 38.9％ (35/90),x2=9.641] (both P＞0.05).Conclusions ELBWI/VLBWI are at high risk of growth retardation.Incidence of growth restriction declines with age.

In order to understand the status of neonatal transport research at home and abroad,we summarized and analyzed the research progress of neonatal transport through the literature search.Thus we evaluated the current application of a variety of transport critical rating system.Intrauterine transport is considered the safest mode of transport,and promote intrauterine transport of high-risk mothers.It is suggested that the parents participate in the transshipment process and return the stable children to the local hospital for further treatment and promote the family-centered treatment mode.In transit,mobile ECMO,hypothermia and other advanced equipment in foreign countries have been applied.It is recommended to use the respiratory function monitor to monitor the respiration during transit.It can provide the parameters of respiratory wave,identify air leak,accidental release,spontaneous breathing.

Objective To evaluate the levels of plasma coupling factor 6(CF6) and cytochrome C(Cyt-c) in neonatal sepsis,and to explore the clinical significance in neonatal sepsis.Methods A total of 88 neonates admitted to Hunan Children's Hospital from January 2015 to April 2015 were collected.Neonates were divided into non-sepsis group(n=42) and sepsis group(n=46).According to the severity of infection,the non-sepsis group was further divided into non-infection group(n=20) and common infection group(n=22);the sepsis group was further divided into general sepsis group (31 cases,no organ failure) and severe sepsis group (15 cases,combined with multiple organ failure).Femoral venous blood was collected in all patients before the use of antibiotics after admission.The levels of Cyt-c and CF6 in plasma were measured by ELISA,and the levels of C-reactive protein(CRP),procalcitonin (PCT) were measured.The changes of CF6 and Cyt-c between these groups were compared,and the sensitivity and specificity with the traditional sepsis index (CRP,PCT) were analyzed.The correlation between the levels of CF6,Cyt-c and neonatal critical illness score was analyzed.Results (1)In sepsis group,the levels of CF6 and Cyt-c[(109.7±8.9)pg/ml and (44.5±4.9)ng/ml] were significantly higher than those in the non-sepsis group[(46.3±6.0)pg/ml,(31.8±6.7)ng/ml,P<0.01,respectively].(2) In the non-infection group,common infection group,general sepsis group and severe sepsis group,the levels of CF6 were (32.1±8.9)pg/ml,(59.3±7.2)pg/ml,(79.3±5.9)pg/ml,and (172.6±6.1)pg/ml,respectively;the levels of Cyt-c were (29.3±8.6)ng/ml,(35.4±4.1) ng/ml,(43.1±5.9) ng/ml,and (44.5±5.9)ng/ml,respectively.The differences between these groups were significant(P<0.01).(3)The receiver operating characteristic curve showed that the sensitivity and specificity of CF6 were 0.761,0.732,and the Cyt-c were 0.739,0.714.(4)Cyt-C and CF6 were negatively correlated with the neonatal critical illness score(r=-0.599,P<0.001;r=-0.337,P<0.01).Conclusion The levels of CF6 and Cyt-c increase in neonatal sepsis.The damage of mitochondria may be one of the pathological mechanisms in neonatal sepsis.The levels of CF6 and Cyt-c were closely related to the severity of neonatal sepsis.