A Meta-analysis Of The Efficacy And Safety Of Ibuprofen In The Treatment Of Patent Ductus Arteriosus In Very Preterm Infants

Background:Patent ductus arteriosus(PDA)is a common heart disease in premature infants,moreover is negatively correlated with gestational age and birth weight,which is to say those with lower gestational age and birth weight present higher prevalence rate.The persistent patency of the DA in preterm infants can lead to significant hemodynamic consequences.A ductal left-to-right shunt can cause a variety of serious complications,including intraventricular hemorrhage,necrotizing enterocolitis,pulmonary hypertension,and pulmonary edema,and it is one of the common causes affecting the survival of premature infants.Therefore,treating PDA to promote rapid ductal closure may be crucial.Owing to the risks associated with surgery,pharmacotherapy is the firstline treatment.Indomethacin and ibuprofen,prostaglandin inhibitors that are commonly used to achieve PDA closure,act on active cyclooxygenase(COX)receptors to promote ductal constriction by inhibiting prostaglandin synthesis.However indomethacin has been found to have high risks that can lead to complications such as renal insufficiency and intracranial hemorrhage Recently,ibuprofen has been recommended more frequently than indomethacin for PDA closure because although ibuprofen is equally effective,it has a lower risk of causing necrotizing enterocolitis(NEC)and transient renal injury.Objective:To systematically evaluate the efficacy and safety of ibuprofen in the treatment of patent ductus arteriosus(PDA)in very preterm infants,and to guide the treatment of patent ductus arteriosus in very preterm infants.Methods:(1)Computer was used to search Chinese and English databases,including:Chinese Journal Full-text Database(CNKI),Wanfang Data Knowledge Service Platform,Vipu Database(VIP)and the Chinese Journal of Biomedical Literature(CBM),PubMed,The Cochrane Library and EMBASE.We collected and meta-analyzed all the randomized controlled trials(RCTs)both at home and abroard about patients with symptomatic patent ductus arteriosus in very preterm infants.The retrieval duration is from January 2000 until December 2019.(2)Respectively by two noninterference people extract data alone,The risk of bias was assessed for the included studies.(3)The meta analysis was performed with Revman 5.3.Results:A total of 274 related articles were obtained through various searching.After screening the final 14 articles were included in the study,including 13 English literatures and 1 Chinese literatures,all of which were randomized controlled trials.The intervention measures for intravenous or oral standard doses of ibuprofen,control measures for the placebo,intravenous indomethacin,the different method of ibuprofen,different dosage of ibuprofen,and different drug doses of ibuprofen.Results of the meta-analysis showed that:(1)Three studies(303 very preterm infants)compared the ibuprofen treatment group with the placebo control group and found that the ibuprofen group could effectively close the catheterization(RR?1.63,95%CI=1.33-2.0,P<0.00001).(2)Five studies(674 very preterm infants)compared the ibuprofen treatment group with the indomethacin control group and found no significant difference in catheter closure rate(RR=0.98,95%CI=0.9-1.07,P=0.62).The incidence of oliguria was significantly reduced in the ibuprofen group after treatment(RR=0.39,95%CI=0.19-0.81,P=0.01),which was statistically significant.(3)There are too few studies comparing continuous ibuprofen infusion with intermittent ibuprofen infusion and high-dose ibuprofen with standard-dose ibuprofen to accurately evaluate any clinical results.