The level and clinical value of fecal calprotectin in very low birth weight infants / 中国小儿急救医学

Objective:To understand the change trend and influencing factors of fecal calprotectin(FC) in very low birth weight(VLBW) infants, and to explore the application value of FC detection in the diagnosis of necrotizing enterocolitis(NEC) in VLBW infants.Methods:VLBW infants hospitalized in the neonatal department at Quanzhou Children′s Hospital from June 2018 to May 2019 were selected as research object for a prospective study.Fecal samples from the 1st, 7th, 14th, 21st, 28th and 35th days after birth and fecal samples from the acute and recovery stages of NEC were collected continuously.The content of FC was determined quantitatively by immunofluorescence assay.Results:(1) The FC level of non NEC VLBW infants from 1 to 35 days after birth was 143.5(47.8, 391.2) μg/g.Univariate analysis showed that the level of FC fluctuated with the postnatal age, the level of FC was the highest at 21 days, and then decreased.The level of FC increased significantly in formula feeding, premature rupture of membranes, neonatal sepsis, feeding intolerance and pregnant mothers without glucocorticoid before delivery( P< 0.05). (2) Multivariate covariance analysis showed that prenatal application of glucocorticoid( F=10.550, P=0.001), premature rupture of membranes( F=13.311, P<0.001), neonatal sepsis( F=8.001, P=0.005), feeding intolerance( F=4.751, P=0.030) and NEC( F=54.566, P<0.001) had significant effects on FC level.After controlling the effects of prenatal corticosteroid, premature rupture of membranes, neonatal sepsis and feeding intolerance, the levels of FC in NEC group and non-NEC group were 3 162.3(1 412.5-7 244.4)μg/g and 141.3(125.9-162.2)μg/g, respectively.In NEC group, the levels of FC in acute stage and recovery stage were 3 166.9(1 745.1, 6 806.4)μg/g and 130.9(97.4, 273.9)μg/g, respectively, with significant difference( t=10.304, P<0.001). While the levels of FC were 2 347.9(1 404.4, 5 893.4)μg/g in the mild NEC and 4 114.7(2 764.5, 9 208.4)μg/g in the moderate or severe NEC, respectively, with no significant difference( t=1.131, P=0.280). Conclusion:The levels of FC fluctuate with postnatal age and it is affected by multiple factors.FC maybe a useful marker for the diagnosis and evaluation of efficacy of NEC in VLBW infants.

Relationship between intestinal fatty acid-binding protein expression and necrotizing enterocolitis in neonatal rat model / 中华围产医学杂志

Objective To analyze the role of intestinal fatty acid-binding protein (I-FABP) expression in a neonatal rat model of necrotizing enterocolitis (NEC).Methods A total of 24 newborn rats were randomly divided into two groups:control group (n=6) and NEC group (n=18).Rats in the NEC group were fed with formula and experienced hypoxia,reoxygenation,cold stress and sequentially Lipopolysaccharide (10 mg/kg) lavage for three consecutive days to establish NEC model,after which were respectively sacrificed on day 1,2 and 3 (six for each day).Those in the control group were all sacrificed on day 3.Ileocecal tissues were collected for morphological and histological analysis.I-FABP expression was detected using Western blot and immunohistochemistry (IHC).One-way analysis of variance,LSD-t test,Kruskal-Wallis H test,Mann-Whitney U test and Pearson's correlation analysis were used for statistical analysis.Results The NEC model (intestinal pathological score ≥ 2) was established successfully without causing death.Compared with the control group,the NEC group showed less body weight gain [M (P25-P75):1.00 (0.48-1.35) vs 1.74 (1.62-1.86),1.25 (0.75-1.40) vs 2.61 (2.53-2.99),1.35 (0.88-1.48) vs 3.60 (3.48-3.73);Z=-2.898,-2.903,-2.892;all P＜0.05] and higher intestinal pathological scores [(2 (2-3),3 (2-3),4 (3-4) vs 0 (0-1);all P＜0.05] on day 1,2 and 3.The intestinal pathological score on day 3 was significantly higher than that on day 2 and day 1 (both P＜0.05).Expression of I-FABP and the number of I-FABP positive enterocytes in the NEC model group were increased compared with those in the control group [Western blot:0.179 (0.179-0.186),0.231 (0.211-0.245),0.202 (0.192-0.225) vs 0.091 (0.086-0.093);IHC:59 (55-60),80 (83-86),80 (84-88) vs 44 (39-47);all P＜0.05].Moreover,the expression of I-FABP protein and the number of I-FABP positive enterocytes on day 2 and day 3 were significantly higher than those on day 1 (all P＜0.05).I-FABP expression was positively associated with intestinal pathological score (Western blot:r=0.932,95％CI:0.872-0.969;IHC:r=0.709,95％CI:0.484-0.872).Conclusions I-FABP is an efficient marker for NEC and correlates with the severity of intestinal injury.

Intestinal fatty acid-binding protein expression in the intestinal tissue and clinical significance in neonatal rats with necrotizing enterocolitis / 中国新生儿科杂志

Objective To study the expression of intestinal intestinal fatty acid-binding protein (I-FABP) and its clinical significance in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. Method Twenty-four neonatal Sprague-Dawley (SD) rats were randomly assigned into 4 groups at 48 h after birth (6 rats in each group):group A (control group), group B (NEC group-1), group C (NEC group-2), and group D (NEC group-3). The neonatal rats were fed by the mother rats in the same cage within 48 h after birth. After 48 h, the NEC group received artificial feeding, hypoxia, cold stimulation and lipopolysaccharide (LPS) gavage (10 mg/kg). NEC group-1, 2 and 3 were sacrificed on an empty stomach at 1, 2 and 3 d after the modeling. The control group was sacrificed on an empty stomach 3 d after the modeling without special treatment. Intestinal tissue were obtained from each rats. The histological changes of ileal tissues were studied using hematoxylin-eosin (HE) staining. The expressions of intestinal I-FABP were detected using RT-PCR and ELISA methods. Result Compared with the control group, body weight of rats in NEC group-1, 2 and 3 were lower, and pathology scores in these three groups were higher (P<0.05). The levels of intestinal I-FABP mRNA in NEC group-1, NEC group-2 and NEC group-3 were 2.69±0.27, 2.12±0.09, 3.18± 0.22, respectively. The protein expression levels were 363.7 ± 11.4, 321.7 ± 45.8, 432.3 ± 50.3, respectively. The mRNA and protein levels were all significantly higher than the control group (mRNA: 1.00 ± 0.02, protein: 134.2 ± 24.0, P<0.05). Conclusion I-FABP was a useful marker for ischemic injury to the intestine. These findings may contribute to a better diagnosis of NEC in newborns.

Clinical effects of continuous blood purification in the treatment of newborns with severe sepsis and multiple organ dysfunction syndrome / 中国新生儿科杂志

Objective To study the clinical effects of continuous blood purification (CBP) in the treatment of newborns with severe sepsis and multiple organ dysfunction syndrome (MODS). Method From May 2013 to November 2018, the clinical data of infants with severe sepsis and MODS receiving CBP in the neonatal department of our hospital were retrospectively analysed. Changes of blood pressure, arterial partial pressure of oxygen/inhaled oxygen concentration (PaO2/FiO2), pH, serum potassium, sodium, urea nitrogen, creatinine, urine volume and maintenance dose of adrenaline at different time points before and after CBP were analysed. Result According to the inclusion and exclusion criteria, a total of 8 newborns with sepsis and MODS were enrolled in the study. One patient had the complication of perforated colon, and the other one had acute renal failure. The number of affected organs in these infants was 3～5. Six cases began CBP treatment within 1～5 days after admission, and the other two cases began CBP treatment on the 38th and 47th days after admission. The average treatment duration was (58.6±25.9) h. The effective rate of CBP in the treatment of severe sepsis with MODS was 75.0％(6/8). Blood pressure was increased at 6 h, 12 h, 24 h and 48 h after treatment and at the end of treatment. PaO2/FiO2 and blood pH were increased. The urine volume was increased at 24 h and 48 h after treatment and at the end of treatment (P<0.05). Serum potassium, urea nitrogen and creatinine were significantly decreased (P<0.05). The maintenance dose of adrenaline was also decreased significantly at 12 h after CBP (P<0.05), and withdrawn at 48 h after treatment. Only one case experienced membrane blockage during CBP. Dialysis was continued after the replacement of filtration membrane. No other complications existed. Conclusion CBP is effective in the treatment of neonatal severe sepsis with MODS. It can improve the circulation and renal function.

Application of amplitude integrated electroencephalography in cerebral function monitoring in preterm infants younger than 30 weeks of gestation / 中国小儿急救医学

Objective To explore the value of amplitude integrated electroencephalography (aEEG) in cerebral function monitoring in preterm infants younger than 30 weeks of gestation. Methods A total of 165 cases of preterm infants younger than 30 weeks of gestation were prospectively enrolled in the study from September 2015 to February 2017,including 20 preterm infants with severe brain injury ( severe brain injury group) and 145 with non-severe brain injury ( non-severe brain injury group). Five aspects of each tracing, such as continuity(Co),sleep-wake cycling( Cy),amplitude of the lower border(LB),bandwidth( B) and total maturation scores,were evaluated and compared between two groups by applying a preterm infants aEEG scoring system. The neuromotor development of preterm infants survivors was assessed by using the 0 to 6 years old children′s neurological and psychological development scale of China Capital Institute of Pediatrics. Clinical data were collected and compared with the results of aEEG. Results The scores for Co,Cy,LB,B as well as total maturation scores of preterm infants with severe brain injury at different gestational age were lower than those of infants with non-severe brain injury at the same gestational age. The differences were sta-tistically significant (all P<0. 05). There were no statistical differences in Co,Cy,LB,B scores and total maturation scores between each gestational ages in severe brain injury group (all P>0. 05). Scores for Co, Cy,B and total maturation scores progressively increased with advancing gestational age in non-severe brain injury group( all P <0. 05),but there were no statistical differences between each gestational ages in LB scores(all P>0. 05). Follow-up results of 16 cases with severe brain injury:15 cases of DQ≤69,1 case of DQ 70－84,and no cases of DQ≥85; 130 cases of non-severe brain injury group:78 case of DQ≥85,42 cases of DQ 70－84,10 cases of DQ≤69. By chi-square analysis and Spearman rank correlation analysis,the results of aEEG total maturation scores were correlated with outcome of these preterm infants younger than 30 weeks of gestation ( r ＝0. 702,P <0. 05). Conclusion aEEG can provide important information of the status of cerebral function in preterm infants younger than 30 weeks of gestation and help to predict their outcome.

Transcutaneous CO2 and transcutaneous O2 monitoring in the evaluation of neonatal respiratory failure / 中国新生儿科杂志

Objective To study the clinical value of transcutaneous O2 (TcPO2) and transcutaneous CO2 (TcPCO2) monitoring among infants with respiratory failure.Method From August 2017 to February 2018,neonates with respiratory failure treated with nasal continuous positive airway pressure (NCPAP) or mechanical ventilation (MV) in the neonatal department were prospectively enrolled.At four time points of 30 min,6 h,24 h after respiratory support and before discharged,TcPO2 and TcPCO2 were compared with PaO2 and PaCO2 using the correlation and consistency analysis methods.Result A total of 368 paired samples from 92 infants were collected.The correlations of TcPCO2 and PaCO2 at 30 min,6 h,24 h and before discharged were strong (r =0.790,95 ％ CI 0.656 ～ 0.884;r =0.827,95 ％ CI 0.710 ～ 0.908;r =0.901,95 ％ CI 0.867 ～ 0.932;r =0.905,95 ％ CI0.830 ～ 0.954,P ＜ 0.05).The correlations of TcPO2 and PaO2 at 30 min,6 h,24 h were weak (r =0.629,95％ CI 0.461 ～ 0.767;r =0.638,95％ CI 0.465 ～ 0.793;r =0.739,95 ％ CI 0.619 ～ 0.831),but strong before discharged (r =0.886,95 ％ CI 0.818 ～ 0.934).Conclusion When tissue well perfused,TcPCO2 is an accurate,continuous and noninvasive marker to evaluate the PaCO2 of neonates with respiratory failure.But TcPO2 cannot reflect PaO2 accurately,and the combination of other index of oxygenation should be used.

Clinical analysis of 33 cases of neonatal group B streptococcal sepsis / 中国小儿急救医学

Objective To explore the clinical characteristics of neonatal group B streptococcal sepsis (GBS)sepsis in order to provide the guide for early diagnosis and appropriate treatment.Methods A retro-spective review was performed and a total of 33cases of neonatal GBS sepsis were identified in the NICU of Children′s Hospital of Quanzhou from March 2011to October 2014.The perinatal factors,clinical characteris-tics,laboratory finding,treatment and prognosis were analyzed.Results A total of 33cases of neonatal GBS sepsis were identified.The incidence of neonatal GBS sepsis was 2.0‰(33/16448)among all the NICU pa-tients admitted at the same period.All 21cases of early-onset GBS sepsis were term infants,which had 13ca-ses of respiratory distress,11cases of anhelation and 10cases of cyanosis as main initial clinical symptoms. Among 12late-onset cases,8occurred in term infants,10with ardent fever as the main initial clinical symp-toms,6combined with purulent meningitis.All the GBS strains were sensitive to vancomycin,then penicillin combined with meropenem therapy was effective.Of the 33patients,18cured,9discharged with improve-ment,2died,4patients died during hospitalization after being given up because of serious complication,total mortality was 18.2%.Conclusion The clinical manifestations of neonatal GBS sepsis are usually obviously and fatally,and with a high mortality.Antepartum prophylaxis,early diagnosis and timely sensitive antibiotics therapy are vital for reducing the incidence of complications and mortality of neonatal GBS sepsis.

Efficacy and safety of systemic mild hypothermia treatment for moderate or severe neonatal hypoxic-ischemic encephalopathy / 中华围产医学杂志

Objective To explore the efficacy and safety of systemic mild hypothermia in management of neonates with moderate or severe hypoxic-ischemic encephalopathy (HIE).Methods A retrospective case-control study was conducted on 75 neonates with moderate or severe HIE,who were admitted to the Neonatal Intensive Care Unit of Teaching Hospital of Fujian Medical University (Quanzhou Children's Hospital) from January 1,2011 to May 31,2015.The 75 neonates were divided into two groups,the conventional treatment group (33 cases,control group) and the mild hypothermia treatment group (42 cases,hypothermia group).Sequential management protocol for all subjects was followed,including amplitude-integrated electroencephalogram (aEEG) before treatment,aEEG and brain MRI at one week after birth,neonatal behavioral neurological assessment (NBNA) on the 14th day after birth,and determination of mental and psychomotor development index with Bayley Scales of Infant and Toddler Developmental at 18 months old.Adverse reactions,serious disability cases and deaths during the study were also recorded.Two sample-t test and Chi-square test were as statistical methods.Results There were six death cases in the control group,but on one died in the hypothermia group.In the survivals,The maximum voltage and minimum voltage in the hypothermia group were higher at 7-day old than that before treatment [maximum voltage:(31.3 ±2.4) vs (18.1± 2.2) μ V;minimum voltage:(13.5±2.1) vs (6.1 ±1.5) μ V,t=8.591 and 5.314,both P ＜ 0.05],and also higher than that of control group [(25.2±3.1) and (9.3±3.1) μV,respectively,both P ≤ 0.05].Compared with the control group,there were more babies with normal head MRI [43％(18/42) vs 18％(6/33),x2=4.814,P ≤ 0.05] in the hypothermia group at 7-day old and less cases of severe disability [21％(9/42) vs 45％(15/33),x2=4.902,P ≤ 0.05] and deaths [0％(0/42) vs 18％(6/33),x2=6.098,P ≤ 0.05].Higher NBNA score at 14 day and Bayley developmental index at 18 months were shown in the hypothermia group than in the control (39.4±2.6 vs 35.3 ±2.4,t=3.316;mental development index:96.3± 13.2 vs 84.3 ± 10.6,t=7.893;psychomotor development index:98.2 ±16.8 vs 85.4±13.2,t=8.753,all P ≤ 0.05).The adverse effects of hypothermia treatment included electrolyte imbalance (n=12),abnormal blood glucose level (n=8),hepatic and renal dysfunction (n=7),infections (n=6) and bradycardiac (n=4),and no cold injury syndrome case was reported.However,none of the above had significant difference compared with the control group (P ＞ 0.05).Conclusions Systemic mild hypothermia treatment is effective in reducing mortality rate and major disability rate in neonates with moderate or severe HIE and improves the neuromotor development when babies grow up to 18-month-old.

Efficacy of caffeine citrate for treating primary apnea in premature infants / 中国小儿急救医学

Objective To investigate the clinical efficacy and safety of caffeine citrate in the treat-ment of primary apnea in premature infants. Methods A non-randomized controlled trial had been designed in which 96 premature infants would be enrolled form Oct 2013 to Sep 2014 in our hospital. According to the therapeutic strategy,the patients were divided into treatment group(n=51) and control group(n=45). The treatment group was treated with caffeine citrate,and the control group was treated with placebo. The overall response rates and the complication rates in the two groups were compared. Results The effective rate of the treatment group was 80. 4%(41/51),while the control group was 51. 1%(23/45). There was a significant difference between the two groups(χ2 =9. 224,P =0. 002). The incidence of bronchopulmonary dysplasia (7 cases vs. 14 cases),patent ductus arteriosus(7 cases vs. 15 cases),retinopathy of prematurity(4 cases vs. 10 cases),intraventricular hemorrhage(9 cases vs. 20 cases),showed significant differences between the two groups( P<0. 05 ) . Conclusion Caffeine citrate is significantly more effective than placebo in reducing apnea episodes and reduces the rate of bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity and intraventricular hemorrhage in premature infants.

Efficacy of inhaled nitric oxide combined with oral sildenafil on persistent pulmonary hypertension in the newborn infants / 中国小儿急救医学

Objective To evaluate the effects of inhaled nitric oxide(iNO)combined with oral sil-denafil therapy in the newborn infants with persistent pulmonary hypertension(PPHN).Methods Forty-six neonates with PPHN were devided into group A(n ﹦23)and group B(n ﹦23).The combined treatment of iNO and oral sildenafil was used in group A,and iNO was used in group B.During the therapy,the following factors were monitored:blood gas analysis,systolic blood pressure(SBP),systolic pulmonary artery pressure (SPAP),inspired oxygen fraction (FiO2 ),iNO concentration,iNO duration,ventilation time and hospital stay.The effective rate,mortality and the risk of pneumothorax,intraventricular hemorrhage,pulmonary hem-orrhage,bronchopulmonary dysplasia were compared between the two groups.All patients were treated in the same neonatal unit and received the same standard therapy throughout the study period.Results The effec-tive rates of group A and group B were 87.0%(20 /23)and 78.3%(18 /23)respectively.There was no sig-nificant difference between the two groups(χ2 ﹦0.15,P 〉0.05).The levels of SPAP/SBP decreased signifi-cantly,and the levels of PaO2 /FiO2 rised significantly at baseline 30 min,6 h and after the treatment.But there were no significant differences between the two groups(P 〉0.05).In group A,the iNO concentration stared at ≥15 ×10 -6 for 14 infants,〉15 ×10 -6 for 6 infants,which were lower than those in the group B (χ2 ﹦6.71 ,P 〈0.05).The iNO would be stopped when the concentration reached 40 ×10 -6 without any sign of improvement.Compared to group B,the duration of iNO[(57.3 ±27.8)h vs.(87.7 ±47.0)h],the ven-tilation time[(94.44 ±31 .88)h vs.(123.20 ±47.43)h],and the time of hospital stay[(14.55 ±3.19)d vs.(18.78 ±4.60)d]in group A were shorter(P 〈0.05),whereas the mortality and the incidence of pneu-mothorax,intraventricular hemorrhage,pulmonary hemorrhage and bronchopulmonary dysplasia had not sig-nificantly differences between the two groups.Conclusion The effects of iNO combined with oral sildenafil in the newborn infants with PPHN was same compared to iNO.But it can effectively reduced the iNO concen-tration and shorten the duration of iNO,the ventilation time and the hospital stay without augmentation of risk of mortality,pneumothorax,intraventricular hemorrhage,pulmonary hemorrhage,bronchopulmonary dysplasia in neonatal patients.