The optimal drug treatment for preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA) is still controversial.The prophylactic intravenous injection of indomethacin can be considered for extremely preterm infants or extremely low birth weight infants with a high risk of severe intraventricular hemorrhage.The expectant management without drug intervention can be chosen in the following situations: asymptomatic; preterm infants with gestational age ≥28 weeks or birth weight ≥1 000 g are born within 7-14 days; and there are few risk factors affecting spontaneous closure of hsPDA.The drug intervention can be given if the expectant management fails.Oral administration of high-dose Ibuprofen, Acetaminophen and standard-dose Ibuprofen are recommended.

Objective:To study the efficacy and safety of oral acetaminophen or high-dose ibuprofen as rescue treatment after failure of conservative management in very preterm infants (VPIs) with haemodynamically significant patent ductus arteriosus (hsPDA).Methods:From May 2020 to November 2022, VPIs with hsPDA (gestational age<32 weeks and age 4~6 d) admitted to NICU of our hospital were prospectively enrolled. The rescue treatment was initiated if hsPDA still exist after 3~4 d of conservative management. The infants were randomly assigned into acetaminophen group (oral acetaminophen 15 mg/kg, once every 6 h for 3 d) and high-dose ibuprofen group (oral ibuprofen 20 mg/kg for the first dose, 10 mg/kg each dose after 24 h and 48 h). Before and after rescue treatment, the following were recorded: echocardiography, complete blood count, biochemistry, B-type natriuretic peptide (BNP), fecal occult blood test (FOBT) and transcranial Doppler ultrasound. Urine output and complications were also examined. SPSS 20.0 was used for statistical analysis.Results:A total of 36 cases were in the acetaminophen group and 37 in the high-dose ibuprofen group. The two groups showed similar efficacy as rescue treatment [80.6% (29/36) vs. 78.4% (29/37), P>0.05]. No significant differences existed in the incidences of upper gastrointestinal bleeding, positive FOBT, oliguria, stage Ⅱ-Ⅲ necrotizing enterocolitis and stage Ⅲ-Ⅳ intraventricular hemorrhage between the two groups ( P>0.05). After rescue treatment, the serum cystatin C in high-dose ibuprofen group was higher [(1.72±0.29) mg/L vs. (1.58±0.26) mg/L] and 24-hours urine output was lower [(3.1±1.0) ml/(kg·h) vs. (3.7±0.7) ml/(kg·h)] than the acetaminophen group (all P<0.05). No significant differences existed in serum creatinine, platelet count, BNP, alanine aminotransferase and total serum bilirubin between the two groups ( P>0.05). Conclusions:After failure of early conservative management in VPIs with hsPDA, when initiated within 7-10 d after birth, rescue treatment with oral acetaminophen or high-dose ibuprofen has a similar efficacy of 80%, and both drugs are safe. Oral high-dose ibuprofen may have a greater effect on renal function than acetaminophen.

Objective:To study the risk factors, diagnosis and treatment of transient hyperinsulinemic hypoglycemia (HH) in newborns.Methods:From January 2016 to December 2020, newborns with transient HH (HH group) admitted to our hospital were enrolled in this retrospective nested case-control study. Newborns with similar gestational age (GA) (differences of GA<2 w) without HH were matched with 1∶2 ratio as the non-HH group. Clinical characteristics of the two groups were compared and the risk factors and therapeutic results of HH in newborns were analyzed using SPSS 20.0 statistical software.Results:A total of 39 cases were included in the HH group and 75 cases were matched in the non-HH group. The proportion of small for gestational age (SGA) [51.3%(20/39) vs. 32.0%(24/75)], the amount of amino acids (AA) in intravenous infusion[1.0(0.0,1.0) g/(kg·d) vs. 0.0(0.0,1.0) g/(kg·d)], the incidence of hypoglycemia [(4.3±1.9) times vs. (3.6±1.3) times] and the maximum glucose infusion rate (GIR)[(8.3±2.5) mg/(kg·min) vs. (7.4±1.1) mg/(kg·min)] in the HH group were higher than the non-HH group (all P<0.05). The platelet count in the HH group were lower than the non-HH group [(186.9±60.9)×10 9/L vs. (215.3±61.7)×10 9/L, P<0.05]. SGA ( OR=2.535, 95% CI 1.077~5.971), the amount of intravenous AA ( OR=2.180, 95% CI 1.029~4.619) and the maximum GIR ( OR=1.405, 95% CI 1.088~1.815) were independent risk factors for transient HH. In the HH group, 28/39 cases were treated with Diazoxide or Octreotide and the therapeutic effects were good with few adverse drug reactions (ADR). 37/39 cases were recovered within 28 d of birth and the other 2 cases were recovered at 2.5 m and 3.5 m, respectively. Conclusions:SGA, the amount of intravenous AA and higher GIR are risk factors for transient HH in newborns. Diazoxide or Octreotide are effective with few ADR in the treatment of transient HH. Most patients will recover from transient HH in 2 w to 3 m.

Objective:To study the clinical value of bladder stimulation technique (BST) for clean-catch urine collection in late newborns.Methods:From November 2020 to March 2022, relatively stable late newborns hospitalized in the Department of Neonatology of our hospital were enrolled in the prospective randomized controlled trial. The newborns were assigned into BST group and control group. In BST group, urine was collected using BST (suprapubic tapping alternating with lumbosacral massage for 5 min) 20~30 min after feeding and specimen were collected using urine bag before and after BST. In the control group, urine was collected using urine bag method. The urine collection was considered successful if >1 ml of urine not contaminated by faeces were collected within 60 min. The t-test and χ 2 test were used for data analysis. Results:A total of 231 late newborns were included with 117 cases in BST group and 114 in control group. The rate of successful urine collection in BST group was higher than control group (65.8% vs. 39.4%).The time needed for successful urine collection [(30.2±8.5) min vs. (40.7±12.9) min], the incidences of faeces contamination (2.5% vs. 21.1%) and urine contamination (11.7% vs. 26.7%) in BST group were all significantly lower than control group(all P<0.05). Male and female newborns in BST group had similar success rates of urine collection (65.6% vs. 66.0%). Male newborns in BST group had similar urine contamination rate with control group (9.5% vs. 11.5%) and female newborns in BST group had significantly lower urine contamination rate than control group (14.3% vs. 47.4%, P<0.05). Urine was successfully collected in 71 newborns in BST group with median duration of BST for 81 (61,132) s. No adverse effects were observed except for transient consolable crying. Conclusions:Compared with urine bag collection method, BST improves successful urine collection rates and reduces the time needed for urine collection and urine contamination rates (especially for females).

OBJECTIVE: To compare the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old. METHODS: A prospective study was conducted. The febrile infants with less than 90 days old hospitalized in the department of pediatrics of Xuzhou Central Hospital from August 2019 to November 2021 were enrolled. The basic data of the infants were recorded. The infants with high risk or low risk of bacterial infection was evaluated by the step-by-step approach and the lab-score method, respectively. The step-by-step approach was based on clinical manifestations, age, blood neutrophil absolute value or C-reactive protein (CRP), urine white blood cells, blood venous blood procalcitonin (PCT) or interleukin-6 (IL-6) to gradually assess the high risk or low risk of bacterial infection in infants with fever. The lab-score method was based on the levels of laboratory indicators such as blood PCT, CRP and urine white blood cells, which were assigned different scores to evaluate the high risk or low risk of bacterial infection in febrile infants according to the total score. Using clinical bacterial culture results as the "gold standard", the negative predictive value (NPV), positive predictive value (PPV), negative likelihood ratio, positive likelihood ratio, sensitivity, specificity, and accuracy of the two methods were calculated. The consistency of the two evaluation methods was tested by Kappa. RESULTS: A total of 246 patients were enrolled in the analysis, and ultimately confirmed by bacterial culture as non-bacterial infections in 173 cases (70.3%), bacterial infection in 72 cases (29.3%), and unclear in 1 case (0.4%). There were 105 cases with low risk evaluated by the step-by-step approach, and 98 cases (93.3%) were ultimately confirmed as non-bacterial infection; 181 cases with low risk evaluated by the lab-score method, and 140 cases (77.4%) were ultimately confirmed as non-bacterial infection. The consistency of the two evaluation methods was poor (Kappa value = 0.253, P < 0.001). The ability of the step-by-step approach in early identification of non-bacterial infection in febrile infants with less than 90 days old was superior to the lab-score method (NPV: 0.933 vs. 0.773, negative likelihood ratio: 5.835 vs. 1.421), but the sensitivity of the former was lower than that of the latter (0.566 vs. 0.809). The ability of the step-by-step approach in early identification of bacterial infection in febrile infants with less than 90 days old was similar to the lab-score method (PPV: 0.464 vs. 0.484, positive likelihood ratio: 0.481 vs. 0.443), but the specificity of the former was higher than that of the latter (0.903 vs. 0.431). The overall accuracy of the step-by-step approach and the lab-score method was similar (66.5% vs. 69.8%). CONCLUSIONS The ability of the step-by-step approach in early identification of non-bacterial infections in febrile infants with less than 90 days old is superior to the lab-score method.
Humans ; Infant ; Child ; Prospective Studies ; Bacterial Infections ; C-Reactive Protein ; Hospitals ; Interleukin-6 ; Procalcitonin

Objective:To investigate the efficacy and safety of initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen in preterm infants with haemodynamically significant patent ductus arteriosus (hsPDA).Methods:The preterm infants (gestational age ≤ 32 weeks) with hsPDA who were admitted to neonatal intensive care unit (NICU) of Xuzhou Central Hospital from October 2016 to November 2019 were enrolled in the study. A total of 110 eligible cases were included and randomly divided into three groups for initial treatment: 38 cases received oral ibuprofen 10 mg/kg, and 5 mg/kg after 24 h and 48 h (ibuprofen group), 37 cases received oral paracetamol 15 mg/kg, q.8.h for 3 d (paracetamol group) and 35 cases received oral injection water 1 ml/kg, and 0.5 ml/kg after 24 h and 48 h (conservative management group). The preterm infants who failed in the initial treatment were given high-dose ibuprofen for rescue treatment (oral ibuprofen 20mg/kg, and 10 mg/kg after 24 h and 48 h). Serum creatinine, cystatin C, glutamic-pyruvic transaminase (GPT), total bilirubin, fecal occult blood and urinary prostaglandin E 2 were measured; echocardiography and brain color Doppler ultrasonography examinations were performed before and after treatment. Urine output and complications were recorded. The data were analyzed by ANOVA, t-test, non-parametric test, chi-square test and Pearson correlation coefficient with SPSS 20.0 statistical software. Results:During initial treatment, the success rates of ibuprofen group and paracetamol group were higher than that of conservative management group [71.1% (27/38) and 70.3%(26/37) vs. 40.0% (14/35), P=0.008 and 0.010]. Thirty one patients, who failed in initial treatment, received rescue treatment (8, 7, 16 cases from ibuprofen, paracetamol and conservative groups, respectively). The success rate of rescue treatment with high-dose ibuprofen was 58.1% (18/31). During initial treatment, there were no significant differences in the incidence of oliguria, upper gastrointestinal bleeding, positive fecal occult blood tests, Ⅲ-Ⅳ grade intraventricular hemorrhage, and ≥Ⅱ stage necrotizing enterocolitis among the three groups (all P>0.05). There were no significant differences in the incidence of above complications between rescue treatment and initial treatment [6.5% (2/31) vs. 6.4%(7/110), 3.2%(1/31) vs. 4.5%(5/110), 12.9%(4/31) vs. 6.4%(7/110), 0 vs. 4.5%(5/110), 3.2%(1/31) vs. 1.8%(2/110), all P>0.05]. The changes of serum creatinine and GPT before and after treatment were not significant in all groups ( P>0.05). Serum cystatin C were increased in both ibuprofen group[(0.44±0.17)μmol/L] and paracetamol group [(0.18±0.09)μmol/L] after treatment ( t=-15.70, -14.64; P<0.001), and the increase in ibuprofen group was greater than that in paracetamol group ( P<0.001). Urinary prostaglandin E 2 were decreased in both ibuprofen group [(-11.63±3.70)ng/L] and paracetamol group[(-4.89±1.91)ng/L] after treatment ( t=15.57, 7.03; P<0.001), and the decrease in ibuprofen group was greater than that in paracetamol group ( P<0.001). Serum cystatin C was not significantly increased after high dose ibuprofen rescue treatment [(1.67±0.17)mg/L vs.(1.71±0.21)mg/L; t=-1.12, P=0.273]. Conclusion:Both initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen can effectively promote hsPDA closure in preterm infants without increase of complications. However, renal function indexes such as urine output and serum cystatin C should be monitored. The high-dose ibuprofen is relatively safe, and can be used as one of rescue treatment.

Objective:To compare left and right ventricular Tei indexes and to determine the reference range in newborns of different gestational age (GA) and birth weight (BW).Methods:From February 2019 to June 2021, newborns admitted to the Neonatal Intensive Care Unit of our hospital were enrolled. Tei indexes were measured and calculated during 24 h~7 d after birth and reexamined 1~2 weeks later in some of the newborns. The newborns were assigned into <32 w group, 32~36 w group and ≥ 37 w group according to their GA, < 1 500 g group, 1 500~2 499 g group and ≥2 500 g group according to their BW, and early newborn group (1~7 d) and late newborn group (>7 d) according to their age of evaluation. The data were analyzed using t test, one-way analysis of variance (ANOVA) and correlation analysis with SPSS 20.0 statistical software. Results:A total of 128 cases were included. 42 cases in <32 w group, 43 in 32~36 w group and 43 in ≥37 w group. 42 cases in <1 500 g group, 42 in 1 500 ~ 2 499 g group and 44 in ≥2 500 g group. Tei indexes were reexamined after 7 d of age in 63 preterm infants and in 31 full-term infants. The left and right ventricular Tei indexes of the ≥37 w group were less than the 32~36 w group and the <32 w group in early newborns (left ventricular: 0.382±0.069 vs. 0.431±0.069 and 0.439±0.060, right ventricular: 0.373±0.038 vs. 0.431±0.035 and 0.452±0.064); the right ventricular Tei index of the 32~36 w group was significantly less than the <32 w group ( P<0.05). No significant differences existed in the left ventricular Tei index between the 32 ~ 36 w group and the < 32 w group ( P>0.05). The left and right ventricular Tei indexes of the ≥2 500 g group were significantly less than the 1 500~2 499 g group and the <1 500 g group (left ventricular: 0.385±0.069 vs. 0.434±0.067 and 0.434±0.064, right ventricular: 0.376±0.039 vs. 0.431±0.043 and 0.450±0.061) ( P<0.05).No significant differences existed between the 1 500~2 499 g group and the <1 500 g group ( P>0.05). No significant differences existed in the left and right ventricular Tei indexes between the late newborn group and early newborn group ( P>0.05). For early newborns (1~7 d of age), the reference range of Tei index gradually decreased along with the increase of GA and BW. Conclusions:The left and right ventricular Tei indexes of full-term infants and infants with BW ≥2 500 g are less than preterm and low birth weight infants. The reference range of Tei index in early newborns shows negative correlation with GA and BW.

Objective:To investigate the effects of non-invasive positive pressure ventilation (NPPV) on plasma B-type natriuretic peptide (BNP) level and Tei index of right ventricle in preterm infants.Methods:Premature infants of gestational age<34 weeks with respiratory distress syndrome who were admitted in Neonatal Intensive Care Unit of Xuzhou Central Hospital and requiring for NPPV from December 2018 to October 2020, were enrolled in the study. Patients were randomly divided into two groups 46 patients received nasal continuous positive airway pressure ventilation (NCPAP group) and 49 patients received bi-level positive airway pressure ventilation (BiPAP group); 42 preterm infants of gestational age<34 weeks and without NPPV were selected as the control group. The plasma BNP, Tei index of right ventricle, mean airway pressure and oxygen index at 0-12 h and 48-60 h after NPPV were monitored in NCPAP group and BiPAP group. The plasma BNP and Tei index of right ventricle at 0-12 h and 48-60 h after admission were monitored in the control group. SPSS 20.0 statistical software was used for data analysis.Results:(1)The plasma BNP and Tei index of right ventricle at 48-60 h after NPPV were significantly higher than those at 0-12 h after NPPV in NCPAP group and BiPAP group [NCPAP group: (287.5±155.5) vs. (179.9±102.3) ng/L, (0.43±0.08) vs. (0.38±0.06); BiPAP group: (303.1±135.4) vs. (186.5±95.6) ng/L, (0.45±0.08) vs. (0.39±0.06); t=6.00, 3.34, 7.47, 4.48; all P<0.05]. There were no significant differences in the plasma BNP and Tei index of right ventricle at 48-60 h and 0-12 h after admission in the control group [(181.9±86.8) vs. (169.5±78.9) ng/L, (0.34±0.05) vs. (0.36±0.05); t=0.83, -1.59; all P>0.05].(2) There were no significant differences in the plasma BNP and Tei index of right ventricle at 48-60 h after NPPV between NCPAP group-and BiPAP group (all P>0.05), but they were significantly higher than those in control group at 48-60 h after admission(all P<0.05). (3)The mean airway pressure and oxygen index at 48-60 h after NPPV in NCPAP group and BiPAP group showed a decrease trend compared to those at 0-12 h after NPPV, but the differences were not significant [NCPAP group: (6.8±1.2) vs. (7.0±1.3) cmH 2O(1 cmH 2O=0.098 kPa), (5.7±2.1) vs. (6.1±2.3); BiPAP group: (7.0±1.3) vs. (7.2±1.2) cmH 2O, (5.5±2.0) vs. (5.8±2.1); t=-1.05, -0.80, -1.88, -0.67; all P>0.05]; while there were no significant differences between the two groups (all P>0.05). (4)There was a positive correlation between the plasma BNP and mean airway pressure ( r=0.48, P<0.001), but no correlation between Tei index of right ventricle and mean airway pressure ( r=0.17, P=0.119) at 48-60 h after NPPV. Conclusion:The cardiac function indexes such as plasma BNP and Tei index of right ventricle in preterm infants are increased at 48-60 h after NPPV. When mean airway pressure is the same, the effects of NCPAP and BiPAP on plasma BNP and Tei index of right ventricle in preterm infants are similar.

Objective:To assess the effects of noninvasive positive pressure ventilation on premature infants' cardiac function using Tei index combined with corrected QT dispersion (QTcd) and B- type natriuretic peptide (BNP).Methods:This prospective study involved premature infants from 28 to 32 weeks of gestational age diagnosed with respiratory distress syndrome (RDS) and treated with noninvasive positive pressure ventilation in the Neonatal Intensive Care Unit of Xuzhou Central Hospital from December 2017 to December 2020. According to the mean airway pressure (MAP) during noninvasive positive pressure ventilation, the patients were divided into the low-pressure group (≤6 cmH 2O, 1 cmH 2O=0.098 kPa), medium-pressure group (>6-<9 cmH 2O), and high-pressure group (≥9 cmH 2O). The right ventricular Tei index, QTcd, and blood BNP were monitored during the first 2 h of noninvasive positive pressure ventilation and 12 h after continuous ventilation with stable MAP. Chi-square test, one-way analysis of variance, paired t-test, and Pearson product-moment correlation coefficient were adopted for statistical analysis. Results:Totally 178 premature infants were enrolled, including 75 in the low-pressure, 62 in the medium-pressure, and 41 in the high-pressure group. After continuous ventilation with stable MAP for 12 h, the right ventricle Tei index and QTcd in the high-pressure group were higher than those in the medium- and low-pressure group [Tei index: (0.38±0.05) vs (0.33±0.04) and (0.33±0.04), F=29.18; QTcd: (27.6±4.2) vs (22.8±4.4) and (22.2±4.2) ms, F=23.26, all P<0.001], and the comparison between the medium- and the low-pressure group did not differ significantly. No significant difference was observed in blood BNP levels among the three groups ( F=1.33, P=0.267). The right ventricle Tei index and QTcd increased in the high-pressure group after continuous ventilation with stable MAP for 12 h as compared with those within the first 2 h of noninvasive positive pressure ventilation [Tei index: (0.38±0.05) vs (0.34±0.04), t=－6.61; QTcd: (27.6±4.2) vs (23.4±4.4) ms, t=－5.06, all P<0.001]. However, the figures did not change significantly in the medium- or the low-pressure group (all P>0.05). There were no significant changes in blood BNP in the three groups (all P>0.05). The right ventricle Tei index and QTcd were moderately positively correlated with MAP ( r=0.56 and 0.50, both P<0.001). Conclusions:For the premature infants with RDS, noninvasive positive pressure ventilation has no significant effect on the cardiac function when MAP is less than 9 cmH 2O, but would have a certain effect on the right ventricular function when used at higher pressure (MAP≥9 cmH 2O) and for longer time (>12 h).

Objective:To investigate the role of platelets aggregation in the developing process of ductus arteriosus closure of newborn pups, and the effect of platelet membrane glycoprotein Ⅱb-Ⅲa (GPⅡb-Ⅲa) receptor antagonist (tirofiban).Methods:Four 24-month-old Beagle bitches were selected and numbered 1, 2, 3, and 4 respectively, and their pups were removed by cesarean section in two batches 1-2 days before the expected date of delivery. Bitches 1 and 2 were the first batch. Eighteen newborn pups were removed after cesarean section as the control group. They were divided into three subgroups: 1-hour subgroup, 4-hour subgroup, and 12-hour subgroup according to postnatal time point, with 6 pups in each subgroup. The newborn pups were injected with normal saline 10 mL/kg via jugular vein immediately after birth. Bitches 3 and 4 were the second batch. Nineteen newborn pups were removed by cesarean section as tirofiban group. They were also divided into three subgroups: 1-hour subgroup ( n = 6), 4-hour subgroup ( n = 6), and 12-hour subgroup ( n = 7) according to the postnatal time point. The newborn pups were injected with tirofiban hydrochloride injection 10 mL/kg (10 mL injection including 2.5 mg of tirofiban) via jugular vein immediately after birth. The diameter of ductus arteriosus was measured by echocardiography. Ductus arteriosus was removed by surgical dissection and divided into two parts. Western blotting and immunohistochemistry were used to detect the expression of platelet membrane GPⅡb-Ⅲa, respectively. Results:In the control group, 1 newborn pup died at 0.5 hour after birth in the 1-hour subgroup. The experiment was completed by 19 in the tirofiban group. Ductus arteriosus of all pups were not closed in 1-hour subgroups of the two groups, and there was no significant difference in the diameter of ductus arteriosus between the control group and the tirofiban group (mm: 1.72±0.08 vs. 1.70±0.11, P > 0.05). Ductus arteriosus of 1 newborn pup in 4-hour subgroup of the control group was closed, but the ductus arteriosus of all the newborn pups in 4-hour subgroup of the tirofiban group were not closed. The diameter of ductus arteriosus of the tirofiban group was significantly larger than that of the control group (mm: 1.52±0.15 vs. 0.95±0.48, P < 0.05). Ductus arteriosus of all pups were closed in 12-hour subgroup of the control group, but the ductus arteriosus of 2 pups of the tirofiban group were still not closed, with the diameter of ductus arteriosus of 1.0 mm and 1.1 mm, respectively. Western blotting showed that at 1-hour, 4-hour and 12-hour after birth, the expression of platelet membrane GPⅡb-Ⅲa was gradually increased in ductus arteriosus of newborn pups of the two groups. The expression of GPⅡb-Ⅲa in 1-hour subgroup of the tirofiban group was significantly lower than that in the control group (GPⅡb-Ⅲa/β-actin: 0.67±0.07 vs. 0.84±0.16, P < 0.05). The expression of GPⅡb-Ⅲa in 4-hour and 12-hour subgroups of the tirofiban group were slightly lower than those in the control group (GPⅡb-Ⅲa/β-action: 0.85±0.12 vs. 0.95±0.11 in 4-hour subgroup, 1.04±0.16 vs. 1.09±0.17 in 12-hour subgroup, both P > 0.05). Immunohistochemistry showed that the change trend of platelet membrane GPⅡb-Ⅲa in ductus arteriosus of newborn pups in both groups was similar to the results of Western blotting. Conclusions:The ductus arteriosus of newborn pups begin to close 1-4 hours after birth, and all closed at 12 hours after birth. The expression of platelet membrane GPⅡb-Ⅲa in ductus arteriosus increase gradually after birth, and the platelet aggregation may participate in and promote ductus arteriosus closure to some extent. Tirofiban, a platelet membrane GPⅡb-Ⅲa receptor antagonist, may delay ductus arteriosus closure of newborn pups to some extent by inhibiting platelet aggregation.