| Part 1 Risk factors and clinical outcomes of preterm neonates with patent ductus arteriosus Objectives To investigate the incidence,risk factors and clinical outcomes of patent ductus arteriosus(PDA)in more than 1000 premature infants.Methods Retrospective analysis was performed on preterm infants with gestational age less than 34 weeks who were admitted from May 2016 to April 2019.Cases were divided into PDA group and non-PDA group according to echocardiography results.Clinical data of the two groups were collected.The incidence of PDA was summarized,the related factors of PDA were analyzed in a univariate manner,Logistic regression analysis was used to analyze the risk factors of PDA.Then the incidences of clinical outcomes were summarized.Results ?A total of 1040 premature infants were included during the study period,including 247 cases in the PDA group and 793 cases in the non-PDA group,the incidence of PDA was 23.9%.The incidence of PDA was higher in neonates with younger gestational age and lower birth weight.?Univariate analysis showed that the gestational age,birth weight,perinatal asphyxia,gestational hypertension,antenatal corticosteroids treatment,premature rupture of membranes>24 hours,platelet count,platelet distribution width,mean platelet volume and thrombocytocrit in the first week were related to PDA(P<0.05).Multivariate analysis showed that small gestational age(OR=0.700,95% CI 0.618?0.793),perinatal asphyxia(OR=0.585,95% CI 0.994?0.999)and low platelet count(OR=0.996,95% CI 0.994?0.999)were independent risk factors of PDA(P<0.05).Premature rupture of membranes>24 hours(OR=1.589,95% CI 1.125?2.246)and antenatal corticosteroids treatment(OR=1.892,95% CI 1.288?2.779)were independent protective factors for PDA(P<0.05).? The average length of stay was significantly longer in PDA group(P<0.05).The incidence of invasive and non-invasive ventilator application,pneumonia,pneumorrhagia,bronchopulmonary dysplasia(BPD),feeding intolerance,Bell stage ? and above with necrotizing enterocolitis(NEC),stage ? with intraventricular hemorrhage(IVH)and kidney injury were significantly higher in PDA group than that in non-PDA group(P<0.05).The incidence of retinopathy of prematurity(ROP)and periventricular leukomalacia(PVL)were not significantly different between the two groups(P>0.05).Conclusions The incidence of PDA was higher in preterm infants with younger gestational age and lower birth weight.Small gestational age,perinatal asphyxia and low platelet count were independent risk factors for PDA in premature infants,while antenatal corticosteroids treatment and premature rupture of membranes>24 hours were independent protective factors.Preterm PDA can increase the usage rate of invasive and non-invasive ventilation and incidences of pneumonia,pneumorrhagia,BPD,feeding intolerance,NEC,IVH and kidney injury.Part 2 Establishment and evaluation of predicting model for adverse outcomes of patent ductus arteriosus in very low birth weight infants Objectives To explore the establishment of predicting model for patent ductus arteriosus adverse outcomes(PDAao)in very low birth infants incorporating markers of echocardiography and N-terminal probrain natriuretic peptide(NT-proBNP),and to evaluate the predictive values of the model.Methods Prospective analysis was performed on very low birth weight infants who were admitted from May 2019 to September 2020.An echocardiogram and blood NT-proBNP test were carried out in the first 48 hours after birth,and the results showed that the arterial duct remained open in all cases.Cases were divided into adverse outcome group and normal outcome group whether occurring moderate to severe BPD,grade ? with IVH,Bell stage ? and above with NEC or death.Echocardiogram measurements including PDA diameter and maximum flow velocity,aortic(AO)diameter,left atrium(LA)diameter and LA/AO,left ventricular end-diastolic diameter and left ventricular end-systolic diameter,mitral valve inflow E wave,A wave,and E/A,left ventricular ejection fraction were recorded.Clinical data of all candidates were collected.Risk factors of PDAao were identified by univariate analysis and Logistic regression analysis.And the Logistic regression equation,namely PDAao index regression equation was established to construct the PDAao index prediction model.The difference of PDAao index between the two groups was compared and a receiver operating characteristics curve was constructed to assess the prediction value of PDAao index.The PDAao nomogram prediction model was established by R studio according to the results of Logistic regression analysis,C index and Calibration curves were used to evaluate and verify the differentiation and calibration of the PDAao nomogram model.Results ?A total of 82 premature infants were recruited during the study period,including each 41 cases in the adverse outcome group and the normal outcome group.?Gestational age was younger and birth weight was lower in the adverse outcome group(P<0.05),the systolic pressure and diastolic pressure on day 1 and day 2 were significantly lower in the adverse outcome group(P<0.05).NT-proBNP,PDA diameter and LA/AO were higher in the adverse outcome group(P<0.05),but PDA maximum flow velocity was lower in the adverse outcome group(P<0.05).? Logistic regression analysis indicated that PDA diameter,maximum flow velocity,LA/AO and NT-proBNP were independently risk factors of PDAao.? Those risk factors were substituted into the Logistic regression equation(namely PDAao index regression equation)to establish the PDAao index prediction model.The PDAao index of selected infants had a range from-7.3(low risk)to9.2(high risk).Infants in adverse outcome group had a higher score than that in normal outcome group(P<0.05).PDAao index had an area under the curve of 0.917(95% CI0.858?0.976,P<0.05)for the ability to predict adverse outcomes.A PDAao index cut-off of 0.3 has sensitivity and specificity of 75.6% and 92.7%.PDAao index had an area under the curve larger than NT-proBNP,PDA diameter,PDA maximum flow velocity,LA/AO,gestational age,birth weight,the systolic pressure and diastolic pressure on day 1and day 2respectively.?The PDAao nomogram prediction model was established by Logistic regression analysis results,the C index of the model was 0.917(95% CI 0.859?0.975),and the corrected C index was 0.894,indicating that the model has good prediction accuracy.Calibration curves showed that the predicted PDAao probability was consistent with the actual PDAao incidence.?The incidence of invasive ventilator application,pneumonia,feeding intolerance and IVH was significantly higher in adverse outcome group than that in normal outcome group.Conclusions PDAao prediction model can be established by NT-proBNP,PDA diameter,PDA maximum flow velocity and LA/AO on first 48 hours,which had good predictive value for the later occurrence of PDA adverse outcomes in very low birth weight infants.Part 3 Analysis of pre-symptomatic targeted medication for patent ductus arteriosus in very low birth weight infants Objectives To investigate the efficacy and clinical outcomes of pre-symptomatic targeted medication for patent ductus arteriosus in very low birth weight infants.Methods Retrospective analysis was performed on very low birth weight infants who were admitted from May 2019 to September 2020.An echocardiogram and was carried out in the first 48 hours after birth,and all the candidates were diagnosed with PDA.Cases were divided into pre-symptomatic targeted medication group and symptomatic medication group.Infants in pre-symptomatic targeted medication group were treated with oral ibuprofen immediately after diagnosis(10mg/kg?5mg/kg?5mg/kg,qd?3d),but in symptomatic medication group,no infant was treated with ibuprofen until at least 8postnatal days.Echocardiograms were reviewed on postnatal 8 days for both groups.If PDA was still present,and accompanied by clinical symptoms such as tachycardia or dyspnea aggravation,then ibuprofen was given for second course or first course in the two groups respectively(therapy was the same as above).Echocardiograms were performed at planned intervals until the PDA was closed or the patient discharged.A single stuff collected all data and analyze outcomes and complications.Results ?A total of 116 premature infants were included during the study period,including each 58 cases in pre-symptomatic targeted medication group and symptomatic medication group.There was no statistically significant difference in general data between the two groups.?After the first course of oral ibuprofen in pre-symptomatic targeted medication group,PDA was successfully closed in 44 cases(75.9%),and PDA was successfully closed in 9 cases(88.9%)after the second course of oral ibuprofen.While after the first course of oral ibuprofen in symptomatic medication group,PDA was successfully closed in 31 cases(53.4%),and PDA was closed in 6 cases(40.0%)after the second course of oral ibuprofen.The efficacy was significantly higher in pre-symptomatic targeted medication group than that in symptomatic medication group(P<0.05).?Infants in pre-symptomatic targeted medication group had significantly lower incidences of non-invasive ventilator application,pneumonia,BPD and IVH(P<0.05).There were no differences between the two groups in the length of stay,and incidences of pneumorrhagia,feeding intolerance,severe NEC,ROP,PVL or kidney injury(P>0.05).Conclusions Pre-symptomatic targeted medication with oral ibuprofen can significantly elevate PDA closure rate,decrease the incidence of non-invasive ventilator application,pneumonia,BPD and IVH,and the incidence of drug-related complications such as kidney injury was not affected. |
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