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A clinical study on the effects of exchange transfusion and intensive phototherapy on neurodevelopment in neonates with severe hyperbilirubinemia

Min GE ; Jun TANG ; Dezhi MU ; Bin XIA

Chinese Journal of Neonatology.2019;34(1):8-13. doi:10.3760/cma.j.issn.2096-2932.2019.01.003

Objective To study the effects of exchange transfusion(ET) and intensive phototherapy (IPT) on neurodevelopment in neonates with severe hyperbilirubinemia reaching ET criteria.Method From January 2015 to March 2016,neonates with severe hyperbilirubinemia reaching ET criteria with gestational age ≥35 weeks,and hospitalized in the Department of Neonatology of our hospital were enrolled in the study.The parents were informed of the risks of acute bilirubin encephalopathy (ABE) and both the advantages and disadvantages of IPT and ET.Based on the different choices of their parents,the neonates were assigned into the ET group and the IPT group.General conditions,treatment effects,the incidences of ABE and the prognosis were recorded and analyzed.Result A total of 335 patients were included in this study,147 in the ET group and 188 in the IPT group.Before intervention,the peak of total serum bilirubin (TSB) in ET group (475.8± 100.6 μmol/L) was higher than IPT group (398.3±39.8 μmol/L) (the difference of TSB between two groups was 77.4 μmol/L,P＜0.001),and the incidences of high risk factors such as blood incompatibilities,sepsis,cranial hematoma and intracranial hemorrhage in ET group were higher than IPT group (P＜0.05).Compared with at admission,the incidence of ABE in the ET group increased from 32.0％ to 34.0％ at discharge,mainly due to moderate and severe ABE (the ratio of moderate ABE increased from 2.7％ to 10.2％,and severe ABE increase from 2.7％ to 4.8％).Statistically significant differences existed in the proportion of ABE with different severity at admission and discharge in ET group (P＜0.05),while that in IPT group wasn't statistically significant.241 patients were followed up (follow-up rate 71.9％),with the age ranging from 20 to 36 months.6 cases (5.7％,6/106) in the ET group showed hearing disorder while none (0％,0/135) in the IPT group (P＜0.05).The incidences of neuromotor dyskinesia,language development disorder and spasm in ET group were higher than IPT group(7.5％ vs.3.7％,3.8％ vs.1.5％,4.7％ vs.4.4％,respectively),but the differences weren't statistically significant(P＞ 0.05).No deaths were observed in both groups.Conclusion In neonates with severe hyperbilirubinemia whose TSB exceeding the upper limit of current ET criteria (and within upper limit+5 mg/dl),if the neonates have no risk factors nor clinical symptoms of moderate or severe ABE,only IPT and without ET does not increase the incidence of unfavourable prognosis of central nervous system.

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The influence of gestational age and postnatal age on neonatal cerebrospinal fluid parameters

Cui ZHAO ; Lan ZHANG ; Peng ZHANG ; Wenhao ZHOU ; Guoqiang CHENG ; Xunbin HUANG

Chinese Journal of Neonatology.2019;34(1):14-19. doi:10.3760/cma.j.issn.2096-2932.2019.01.004

Objective To study the influence of gestational age (GA) and postnatal age on neonatal cerebrospinal fluid parameters.Method From January 2013 to December 2015,the results of WBC counts,glucose and protein concentrations of cerebro-spinal fluid(CSF) were collected from neonates admitted to neonatal department of our hospitals.The neonates were assigned into different groups according to their GA and postnatal age.The CSF parameters were compared between different groups,and the changes of CSF parameters were analyzed.STATA 12.0 software was used for statistical analysis.Result A total of 1 410 infants were included.516 (36.6％) cases were preterm infants.1 208 cases (85.7％) received antibiotics before lumbar puncture.WBC counts in CSF between preterm and term infants showed no significant differences (upper reference limit,12.5 × 106/L).CSF glucose in term infants (lower reference limit,1.8 mmol/L) was higher than preterm infants (lower reference limit,1.6 mmol/L).CSF protein in preterm infants (upper reference limit,226.6 mg/ dl) was significantly higher than term infants (upper reference limit,140.3 mg/dl).CSF WBC counts decreased with the growth of postnatal age in preterm infants (regression coefficients-0.030,P=0.035).CSF protein also declined significantly with the increase of postnatal age in term infants (regression coefficients-1.254,P＜0.001).CSF glucose showed no significant decrease with the increase of postnatal age (regression coefficients-0.009,P=0.012).Conclusion GA and postnatal age did not produce an effect on WBC counts of CSF.The preterm infants had lower glucose level and higher protein level in CSF.CSF protein declined significantly with the increase of GA and postnatal age.

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Clinical risk factors and cerebral magnetic resonance imaging characteristics of Tibetan newborns with hypoxic-ischemic encephalopathy in Lhasa, Tibet

Hong WU ; Rong ZHAO ; Minna SHAN ; Kanglu ZHAI

Chinese Journal of Neonatology.2019;34(1):20-23. doi:10.3760/cma.j.issn.2096-2932.2019.01.005

Objective To study the clinical risk factors and the characteristics of cerebral magnetic resonance imaging (MRI) of hypoxic-ischemia encephalopathy (HIE) in full-term infants in high-altitude area.Method From January 2014 to December,2016 full-term Tibetan infants with HIE and healthy full-term Tibetan infants admitted to our hospital were enrolled in the study.General conditions and perinatal status were retrospectively analyzed.Univariate analysis and multivariate analysis were used to determine the risk factors of the HIE.MRI characteristics,location of the brain injuries and the correlation between HIE clinical grading and MRI grading were analyzed.Result During the study period,5 172 full-term Tibetan neonates were born in our hospital,198 of them were diagnosed of HIE and the incidence was 3.8％.According to HIE clinical grading,31 were mild,110 were moderate and 57 were severe.MRI grading included 34 mild,131 moderate and 33 severe.The main manifestations of MRI included white matter injury,especially subcortical white matter injury of frontal,parietal and occipital lobes,gray matter injury and diffuse cerebral edema.Mild HIE had a certain correlation with MRI grading,however,severe HIE had poor correlation with MRI grading.Multivariate Logistic regression analysis showed that abnormal birth weight (＜2 500 g or＞4 000 g) and intrauterine distress were independent risk factors of HIE in full-term Tibetan neonates[OR (95％ CI):3.663 (1.961～6.843) and 5.419 (2.487～11.807)].Conclusion Macrosomia at birth,low birth weight and intrauterine distress are independent risk factors of HIE in Tibetan full-term neonates in Lhasa.White matter injury is the main MRI manifestation of HIE.Clinical grading of Mild HIE has good consistency with the MRI grading,but MRI grading is milder than the clinical grading for those with moderate and severe HIE.

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The clinical value of video-electroencephalogram on the diagnosis and prognosis of neonatal seizure

Xin CHEN ; Yadong LU ; Xiaoguang ZHOU ; Fei SHA ; Yu CHEN

Chinese Journal of Neonatology.2019;34(1):24-28. doi:10.3760/cma.j.issn.2096-2932.2019.01.006

Objective To study the clinical value of video-electroencephalogram (VEEG) on the diagnosis and prognosis of neonatal seizure.Method From January 2016 to December 2017,the medical records of 118 neonates who had seizure and received VEEG in our hospital were collected.The results of VEEG and medical records were analyzed using x2 test,Fisher's exact test or rank sum test.Result Among the 118 neonates,94 cases(79.6％) had abnormal VEEG results,including 59 mildly abnormal cases,21 moderately abnormal cases,and 14 severely abnormal cases.The characteristics of mildly abnormal VEEG was delayed mature,and moderately and severely abnormal VEEG were paroxysmal abnormal activities.All of the severely abnormal VEEGs showed abnormal background activities.The incidence of abnormal background activities of severely abnormal group was higher than mildly and moderately abnormal group,the difference was significant (P＜0.001).Neonates with abnormal background activities had higher rates of epileptic seizure and delayed maturation than those with normal background,and the differences were significant (P＜0.001).Among 32 neonates with paroxysmal events,17 cases had non-epileptic events including subtle seizures,myoclonus seizures,and symmnetrical tonic seizures;15 cases had epileptic electrographic seizures and electro-clinical seizures,12 cases had focal seizures.The degree of abnormal VEEG had positive correlations with the incidences of epileptic seizures and delayed maturation (P＜0.001).Conclusion Neonates with seizure has higher rate of abnormal VEEG.Non-epileptic events presents as subtle seizures and myoclonus seizures,and epileptic seizures as focal seizures.The background activities of neonatal VEEG has important predictive value for prognosis.The worse the VEEG is,the higher the possibility of epileptic seizure and delayed maturation.

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A study on the relationship between mean platelet volume and severe retinopathy of preterm infants

Huiqing SUN ; Mingchao LI ; Zengyuan YU ; Shan XING ; Mengmeng YUAN

Chinese Journal of Neonatology.2019;34(1):29-33. doi:10.3760/cma.j.issn.2096-2932.2019.01.007

Objective To study the relationship between mean platelet volume (MPV) and severe retinopathy of prematurity (ROP) in preterm infants.Method From January 2012 to June 2017,a retrospective case-control study was performed on preterm infants with gestational age (GA)＜32 weeks admitted to our hospital.The preterm infants with severe ROP were assigned into severe ROP group,and preterm infants with the same GA and birth weight but without ROP were assigned into the control group.The MPV were compared between the two groups,and Logistic regression method was used to analyze the risk factors for severe ROP.Result A total of 82 preterm infants with severe ROP were enrolled,including 51 males and 31 females with GA of 24～31 weeks.The control group also included 82 patients.The mechanical ventilation (MV) duration and continuous positive pressure ventilation duration of preterm infants in severe ROP group were significantly longer than the control group [7.2 (3.9,10.8) d vs.5.6 (3.5,8.9) d,7.8 (4.7,11.6) d vs.5.3 (2.3,9.2) d];the incidences of sepsis and intracranial hemorrhage were significantly higher than the control group [32.9％ (27/82) vs.17.1％ (14/82),31.7％(26/82) vs.17.1％ (14/82)],and the breast feeding rate was significantly lower than the control group[15.8％(13/82)vs.52.4％ (43/82)] (P＜0.05).The MPV of the preterm infants in the severe ROP group was significantly higher than the control group at 36-and 40-week of corrected GA [(10.6± 1.8) fl vs.(10.1± 1.4) fl,(10.8± 1.8) fl vs.(10.2± 1.5) fl] (P＜0.05).Multivariate Logistic regression analysis showed that high birth weight (OR=0.998,95％CI 0.996～ 0.999) protective factor for severe ROP,increased MPV (OR=1.084,95％CI 1.011 ～ 1.163) was risk factor for severe ROP.The ROC curve analysis indicated that threshold values of MPV at corrected GA of 32-week,36-week,and 40-week were 9.9 fl,10.9 fl,and 10.8 fl,respectively;and the sensitivities and specificities were 93.2％ and 68.0％,84.1％,and 92.3％,88.6％ and 89.5％,respectively.Conclusion MPV may be associated with the development of severe ROP in preterm infants.

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Effect of surfactant on respiratory distress syndrome: evaluation by bedside pulmonary ultrasonography

Fang YOU ; Xueyun REN ; Fenghai NIU ; Jing ZHAO ; Guangfeng QIANG ; Meiqin XIANG

Chinese Journal of Neonatology.2019;34(1):34-37. doi:10.3760/cma.j.issn.2096-2932.2019.01.008

Objective To study the relationship between the lung ultrasonography and the chest X-ray and to study the value of lung ultrasonography score (LUS) in evaluating the effect of pulmonary surfactant (PS) on respiratory distress syndrome (RDS) of newborn.Method Preterm infants admitted to the neonatal intensive care unit of our Hospital from January 2016 to December 2017 and diagnosed with RDS were prospectively studied.LUS examinations were performed prior to,and within the first 6～12 hours after surfactant administration,chest X-rays were also performed at the same time so as to evaluate the effects of surfactant replacement therapy and the correlation between the lung ultrasonography and the chest X-rays.Lung ultrasonography findings at a total of six sites,with three sites in each lung were scored based on the presence of normal finding,the amount of B-lines and subpleural consolidations.Result A total of 45 preterm infants with RDS were enrolled.The cases of X-ray grades Ⅰ,Ⅱ,Ⅲ and Ⅳ before PS administration were 5 cases,21 cases,12 cases and 7 cases respectively.The scores of LUS 0～6,7～12,13～ 18 were 5 cases,37 cases and 3 cases respectively,and the median of LUS was 10 points.Chest X-ray grades Ⅰ,Ⅱ,Ⅲ and Ⅳ within 6～12 hours after PS administration were 18 cases,17 cases,8 cases and 2 cases respectively.LUS of 0～6,7～12,13～18 were 21 cases,20 cases and 4 cases respectively.The median of LUS after PS was 7 points.LUS after PS application was significantly lower than that before PS application (P＜0.001).The LUS was positively correlated with the grades of X-ray before and after surfactant administration (before surfactant administration r =0.688,P＜0.001,after surfactant administration r =0.777,P＜0.001).Conclusion LUS is positively correlated with the grade of chest X-ray and might enable an early detection of the surfactant replacement therapy effects in RDS.Further studies are necessary to define the role of LUS in this field.

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Early onset of group B streptococcal sepsis in newborn: clinical analysis of 27 cases

Limin ZHU ; Yanping ZHANG ; Xiangyong KONG ; Zhichun FENG ; Changshuan YANG ; Yunhui SONG

Chinese Journal of Neonatology.2019;34(1):38-41. doi:10.3760/cma.j.issn.2096-2932.2019.01.009

Objective To study the clinical features of early-onset Group B streptococcal(GBS) sepsis to improve the management of early-onset GBS sepsis.Method To review the clinical data of 27 cases of early-onset GBS sepsis in the Hospital over the past 5 years (January 2013 to November 2017),and analyze its clinical features,laboratory results,complications,prognosis and perinatal characteristics.Result A total of 27 cases of early-onset GBS sepsis were enrolled within 5 years,accounting for 0.85‰ (27/31 936) of total hospitalized patients over the same period.Among them,6 were premature infants and 21 full-term infants.The time of onset was within 24 hours.In all the cases,except for one full-term infant with fever as the initial symptom,the remainder had dyspnea as the initial symptom,accompanied by poor response and low poor muscle tone.Among them,17 patients required assisted ventilation.One of the full-term infant treated with ECMO within 48 hours after birth because of dyspnea,pulmonary hypertension and persistent hypoxemia,etc.,and improved and discharged;another 10 patients needed hood oxygen supply.5 cases (18.5％,5/27) diagnosed with purulent meningitis.In complete blood count,white blood cells ranged from (0.8～34.2)× 109/L,the minimum platelets counts was 16× 109/L,the maximum CRP was 249 mg/L,and maximum procalcitonin was＞ 100 ng/ml.All blood cultures were sensitive to penicillin.of the 27 patients,2 died despite of medical treatment,and 5 patients died as their parents worried about possible sequelae and discharged against medical advice.Therefore,tlhe total mortality rate was 25.9％ (7/27).All children were administered penicillin after the blood culture results were known,meropenem was subsequently added or replaced with vancomycin according to the clinical progress of the child.The remaining 20 patients recovered and discharged.Conclusion The clinical manifestation of early onset GBS septicemia is critically ill,with early onset,rapid progress,and high mortality.Special attention should be paid to high-risk cases during perinatal period,and early recognition with effective treatment would reduce morbidity and mortality.

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A case report of neonatal-onset chronic granulomatosis disease with aspergillus infection and literature review

Ling WANG ; Xiaowen CHEN ; Shan OUYANG ; Li TAO ; Wei ZHOU ; Juan HE

Chinese Journal of Neonatology.2019;34(1):42-46. doi:10.3760/cma.j.issn.2096-2932.2019.01.010

Objective To study the clinical features,diagnosis,treatment and genetic characteristics of chronic granulomatosis disease (CGD) in neonates,and to improve the understanding of CGD.Method Clinical manifestations and treatments of one patient with CGD and aspergillus infection in our hospital were analyzed.Key words including "infant","newborn","chronic granulomatous disease","lung abscess",and "aspergillus infection"were searched in Chinese medical databases,PubMed and Embase until 2018 September.The clinical features and genetic mutations of CGD reported in literature were summarized.Result The patient in our hospital was a full-term male infant naturally delivered with birth weight of 3 400 g.The onset of the disease was on the 19th day after birth,and the initial clinical manifestations included fever,cough,and then pulmonary abscess,diarrhea,recurrent skin infection,and aspergillus infection.Anti-infection and symptom-alleviating treatments were not effective,and weight gain was poor.Laboratory examination indicated bacterial and fungal infection.The neutrophil respiratory burst test was positive and indicated CGD.Hetero-zygotic frameshift mutation [c.1599-1602delAGTTt (p.V534Sfs* 12)] of CYBB gene 13 exon was detected and the diagnosis of CGD was confirmed.The mother carried the heterozygous mutation and the father didn't.Antifungal therapy was continued after the children got better and discharged from hospital.The patient was followed up until 3-month-old and his condition was stable.Our literature review revealed 28 reports including 108 cases of CGD infants,including 79 male cases (73.1％) and 21 female cases (19.4％).Most of the CGD infants (79/108,73.1％) had the onset within 2 weeks of life.The main clinical features included pneumonia/pulmonary abscess/pleural effusion (87.0％),diarrhea (58.3％),perianal abscess (35.2％),skin infection (53.7％),aspergillus infection (41.7％),and tuberculosis infection (26.9％).75 cases had positive neutrophil respiratory burst test (69.4％),and 95 cases were diagnosed using genetic tests (88.0％).Over 300 loci of the CYBB gene mutation had been reported contributing to the disease.28 cases had abnormal family history (25.9％),19 cases received hematopoietic stem cell transplantation (17.6％),41 cases had clinical improvement (38.0％),and 35 cases died (32.4％).Conclusion CGD is rare in neonatal period.The main clinical manifestations included recurrent infection with pathogens like aspergillus,tuberculosis and others.CGD can be diagnosed based on recurrent multiple bacterial or fungal infections,neutrophil respiratory burst test and gene tests.CGD should be considered among children with recurrent infections at early life stage,especially those with poor maternal history or positive family history.

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Systematic review of preterm infants' body temperature at admission and its effects on the clinical outcome

Zhangbin YU ; Jia CHENG ; Yufang QIU ; Xiaohui CHEN ; Shuping HAN

Chinese Journal of Neonatology.2019;34(1):51-57. doi:10.3760/cma.j.issn.2096-2932.2019.01.012

Objective To study the distribution of preterm infants' body temperature at admission and its effects on the clinical outcome.Method The distribution of preterm infants' body temperature at admission and its effects on their clinical outcome were searched in the Cochrane library,PubMed,Embase,Wanfang,CNKI,VIP from the initial establishment of these databases to June 2018.The quality of the included studies were assessed.STATA 12.0 software was used for statistical analysis.The odds ratio (OR) and 95％ confidence interval(CI) were used for continuous variables.Result A total of 16 studies (including 15 clinical trials) with 47 113 cases were included.The incidences of different admission temperatures were as follows:＜35℃:10.3％ (7.6％～13.1％),＜36℃:45.3％ (35.0％～55.5％),＜36.5℃:63.5％ (51.8％～75.2％),36.5～37.4℃:35.1％ (25.6％～44.7％),≥37.5℃:4.2％ (2.6％～5.7％).Compared with normothermia (36.5～37.4℃),hypothermia (＜35℃,35～35.9℃,36～36.4℃) increased the mortality,with the OR and 95％CI as follows:6.10(4.88～7.62),1.96(1.45～2.66),1.31(1.16～1.48);hyperthermia (≥37.5℃) was not associated with higher mortality (OR =0.98,95％CI 0.73～1.32,P=0.91).Compared with normothermia (36.5～37.4℃),hypothermia (＜36℃) increased the risks of severe retinopathy of prematurity (ROP),necrotizing enterocolitis (NEC),sepsis,periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH),with the OR and 95％CI as follows:ROP:1.70(1.45～2.00),NEC:1.27(1.08～1.49),sepsis:1.44(1.28～ 1.61),PVL/IVH:1.26(1.07～1.48),but not the risk of bronchopulmonary dysplasia (BPD,OR =1.03,95％CI 0.76～1.38,P=-0.87).Compared with normothermia (36.5～37.4℃),the temperature between 36～36.4℃ did not increase the risk of severe ROP,NEC,BPD,sepsis,PVL/IVH,with the OR and 95％CI as follows:1.19(0.92～ 1.54),1.01(0.86～1.18),0.91(0.68～1.22),1.02(0.91～1.14),0.98(0.85～1.14).Conclusion Admission temperature of ＜35℃,35～35.9℃,and 36～36.4℃ increased the mortality risk compared with 36.5～37.4℃,and the lower admission temperature,the higher mortality risk.Admission hypothermia (＜36℃) increased the risk of severe ROP,NEC,sepsis,PVL/IVH compared with normothermia (36.5～37.4℃).

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The regulatory effects of microRNA-200b on hypoxia-inducible factor-1α in neonatal immature rats with hypoxic-ischemic brain damage

Xiaoni GAO ; Lijun YANG ; Nan ZHANG ; Hong CUI

Chinese Journal of Neonatology.2019;34(1):58-62. doi:10.3760/cma.j.issn.2096-2932.2019.01.013

Objective To study the regulatory effects of microRNA-200b (miR-200b) on hypoxia-inducible factors-1α (HIF-1α） in neonatal immature rats with hypoxic-ischemic brain damage (HIBD).Method A total of 240 three-day-old neonatal Sprague-Dawley (SD) rats were randomly assigned into six groups with 40 rats in each group:the hypoxic-ischemic group (HI group),intraventricular injection of miR-200b agomir,intraventricular injection of miR-200b antagomir,intraventricular injection of agomir negative control group,intraventricular injection of antagomir negative control group and the normal control group.The HIBD models of immature neonatal rats were established except for the normal control group.The relative expressions of HIF-1 α in brain tissues of each group were detected using quantitative real-time-PCR at 12 h,1 d,3 d and 7 d after ventricular injection,and the changes of HIF-1α expression in each group were compared.Result (1) Compared with the control group,the expression of HIF-1oα of the HI group began to increase 12 h after the injection of normal saline into the lateral ventricle (P＜0.05),and reached the peak at 1d,with statistically significant difference (P＜0.05),and then gradually decreased to the normal control group level at 7 d.(2) No significant differences of HIF-1α existed among the HI group and the HI+ agomir negative control group and the HI + antagomir negative control group (P＞0.05),and the miR-200b carrier had no significant effects on the expression of HIF-1α.(3)HIF-1α continued to be highly expressed after the injection of antagomir into the lateral ventricle of HI,and was significantly higher than the HI group at 12 h (P＜0.05).No significant differences existed between the HI+antagomir group and the H1 group at 1 d,3 d and 7 d after antagomir injection (P＞0.05).The expression of HIF-1α was constantly lower than the HI group after the injection of agomir,and significantly lower than the HI group at 1d after injection (P＜0.05).Conclusion MiR-200b overexpression inhibits the expression of HIF-1α,and the low expression of miR-200b can increase the level of HIF-1oα in a limited time window.Therefore,miR-200b may participate in the regulation of brain injury in neonatal rats after HIBD by regulating the expression of HIF-1α.

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