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The Cochrane Database of Systematic... Apr 2023Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Several non-pharmacological, pharmacological, and surgical... (Review)
Review
BACKGROUND
Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Several non-pharmacological, pharmacological, and surgical approaches have been explored to prevent or treat a PDA.
OBJECTIVES
To summarise Cochrane Neonatal evidence on interventions (pharmacological or surgical) for the prevention of PDA and related complications, and interventions for the management of asymptomatic and symptomatic PDA in preterm infants.
METHODS
We searched the Cochrane Database of Systematic Reviews on 20 October 2022 for ongoing and published Cochrane Reviews on the prevention and treatment of PDA in preterm (< 37 weeks' gestation) or low birthweight (< 2500 g) infants. We included all published Cochrane Reviews assessing the following categories of interventions: pharmacological therapy using prostaglandin inhibitor drugs (indomethacin, ibuprofen, and acetaminophen), adjunctive pharmacological interventions, invasive PDA closure procedures, and non-pharmacological interventions. Two overview authors independently checked the eligibility of the reviews retrieved by the search, and extracted data from the included reviews using a predefined data extraction form. Any disagreements were resolved by discussion with a third overview author. Two overview authors independently assessed the methodological quality of the included reviews using the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews) tool. We reported the GRADE certainty of evidence as assessed by the respective review authors using summary of findings tables.
MAIN RESULTS
We included 16 Cochrane Reviews, corresponding to 138 randomised clinical trials (RCT) and 11,856 preterm infants, on the prevention and treatment of PDA in preterm infants. One of the 16 reviews had no included studies, and therefore, did not contribute to the results. Six reviews reported on prophylactic interventions for the prevention of PDA and included pharmacological prophylaxis with prostaglandin inhibitor drugs, prophylactic surgical PDA ligation, and non-pharmacologic interventions (chest shielding during phototherapy and restriction of fluid intake); one review reported on the use of indomethacin for the management of asymptomatic PDA; nine reviews reported on interventions for the management of symptomatic PDA, and included pharmacotherapy with prostaglandin inhibitor drugs in various routes and dosages, surgical PDA ligation, and adjunct therapies (use of furosemide and dopamine in conjunction with indomethacin). The quality of reviews varied. Two reviews were assessed to be high quality, seven reviews were of moderate quality, five of low quality, while two reviews were deemed to be of critically low quality. For prevention of PDA, prophylactic indomethacin reduces severe intraventricular haemorrhage (IVH; relative risk (RR) 0.66, 95% confidence interval (CI) 0.53 to 0.82; 14 RCTs, 2588 infants), and the need for invasive PDA closure (RR 0.51, 95% CI 0.37 to 0.71; 8 RCTs, 1791 infants), but it does not appear to affect the composite outcome of death or moderate/severe neurodevelopmental disability (RR 1.02, 95% CI 0.90 to 1.15; 3 RCTs, 1491 infants). Prophylactic ibuprofen probably marginally reduces severe IVH (RR 0.67, 95% CI 0.45 to 1.00; 7 RCTs, 925 infants; moderate-certainty evidence), and the need for invasive PDA closure (RR 0.46, 95% CI 0.22 to 0.96; 7 RCTs, 925 infants; moderate-certainty evidence). The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (RR 1.09, 95% CI 0.07 to 16.39; 1 RCT, 48 infants). Necrotising enterocolitis (NEC) was lower with both prophylactic surgical ligation (RR 0.25, 95% CI 0.08 to 0.83; 1 RCT, 84 infants), and fluid restriction (RR 0.43, 95% CI 0.21 to 0.87; 4 RCTs, 526 infants). For treatment of asymptomatic PDA, indomethacin appears to reduce the development of symptomatic PDA post-treatment (RR 0.36, 95% CI 0.19 to 0.68; 3 RCTs, 97 infants; quality of source review: critically low). For treatment of symptomatic PDA, all available prostaglandin inhibitor drugs appear to be more effective in closing a PDA than placebo or no treatment (indomethacin: RR 0.30, 95% CI 0.23 to 0.38; 10 RCTs, 654 infants; high-certainty evidence; ibuprofen: RR 0.62, 95% CI 0.44 to 0.86; 2 RCTs, 206 infants; moderate-certainty evidence; early administration of acetaminophen: RR 0.35, 95% CI 0.23 to 0.53; 2 RCTs, 127 infants; low-certainty evidence). Oral ibuprofen appears to be more effective in PDA closure than intravenous (IV) ibuprofen (RR 0.38, 95% CI 0.26 to 0.56; 5 RCTs, 406 infants; moderate-certainty evidence). High-dose ibuprofen appears to be more effective in PDA closure than standard-dose ibuprofen (RR 0.37, 95% CI 0.22 to 0.61; 3 RCTs, 190 infants; moderate-certainty evidence). With respect to adverse outcomes, compared to indomethacin administration, NEC appears to be lower with ibuprofen (any route; RR 0.68, 95% CI 0.49 to 0.94; 18 RCTs, 1292 infants; moderate-certainty evidence), oral ibuprofen (RR 0.41, 95% CI 0.23 to 0.73; 7 RCTs, 249 infants; low-certainty evidence), and with acetaminophen (RR 0.42, 95% CI 0.19 to 0.96; 4 RCTs, 384 infants; low-certainty evidence). However, NEC appears to be increased with a prolonged course of indomethacin versus a shorter course (RR 1.87, 95% CI 1.07 to 3.27; 4 RCTs, 310 infants).
AUTHORS' CONCLUSIONS
This overview summarised the evidence from 16 Cochrane Reviews of RCTs regarding the effects of interventions for the prevention and treatment of PDA in preterm infants. Prophylactic indomethacin reduces severe IVH, but does not appear to affect the composite outcome of death or moderate/severe neurodevelopmental disability. Prophylactic ibuprofen probably marginally reduces severe IVH (moderate-certainty evidence), while the evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH. All available prostaglandin inhibitor drugs appear to be effective in symptomatic PDA closure compared to no treatment (high-certainty evidence for indomethacin; moderate-certainty evidence for ibuprofen; low-certainty evidence for early administration of acetaminophen). Oral ibuprofen appears to be more effective in PDA closure than IV ibuprofen (moderate-certainty evidence). High dose ibuprofen appears to be more effective in PDA closure than standard-dose ibuprofen (moderate-certainty evidence). There are currently two ongoing reviews, one on fluid restriction for symptomatic PDA, and the other on invasive management of PDA in preterm infants.
Topics: Infant, Newborn; Humans; Ductus Arteriosus, Patent; Ibuprofen; Cyclooxygenase Inhibitors; Acetaminophen; Prostaglandin Antagonists; Systematic Reviews as Topic; Infant, Premature; Indomethacin
PubMed: 37039501
DOI: 10.1002/14651858.CD013588.pub2 -
The Cochrane Database of Systematic... Feb 2020Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin with fewer adverse effects.
OBJECTIVES
To determine the effectiveness and safety of ibuprofen compared with indomethacin, other cyclo-oxygenase inhibitor(s), placebo, or no intervention for closing a patent ductus arteriosus in preterm, low-birth-weight, or preterm and low-birth-weight infants.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 10), MEDLINE via PubMed (1966 to 30 November 2017), Embase (1980 to 30 November 2017), and CINAHL (1982 to 30 November 2017). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in preterm, low birth weight, or both preterm and low-birth-weight newborn infants.
DATA COLLECTION AND ANALYSIS
Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence.
MAIN RESULTS
We included 39 studies enrolling 2843 infants. Ibuprofen (IV) versus placebo: IV Ibuprofen (3 doses) reduced the failure to close a PDA compared with placebo (typical relative risk (RR); 0.62 (95% CI 0.44 to 0.86); typical risk difference (RD); -0.18 (95% CI -0.30 to -0.06); NNTB 6 (95% CI 3 to 17); I = 65% for RR and I = 0% for RD; 2 studies, 206 infants; moderate-quality the evidence). One study reported decreased failure to close a PDA after single or three doses of oral ibuprofen compared with placebo (64 infants; RR 0.26, 95% CI 0.11 to 0.62; RD -0.44, 95% CI -0.65 to -0.23; NNTB 2, 95% CI 2 to 4; I test not applicable). Ibuprofen (IV or oral) compared with indomethacin (IV or oral): Twenty-four studies (1590 infants) comparing ibuprofen (IV or oral) with indomethacin (IV or oral) found no significant differences in failure rates for PDA closure (typical RR 1.07, 95% CI 0.92 to 1.24; typical RD 0.02, 95% CI -0.02 to 0.06; I = 0% for both RR and RD; moderate-quality evidence). A reduction in NEC (necrotising enterocolitis) was noted in the ibuprofen (IV or oral) group (18 studies, 1292 infants; typical RR 0.68, 95% CI 0.49 to 0.94; typical RD -0.04, 95% CI -0.07 to -0.01; NNTB 25, 95% CI 14 to 100; I = 0% for both RR and RD; moderate-quality evidence). There was a statistically significant reduction in the proportion of infants with oliguria in the ibuprofen group (6 studies, 576 infants; typical RR 0.28, 95% CI 0.14 to 0.54; typical RD -0.09, 95% CI -0.14 to -0.05; NNTB 11, 95% CI 7 to 20; I = 24% for RR and I = 69% for RD; moderate-quality evidence). The serum/plasma creatinine levels 72 hours after initiation of treatment were statistically significantly lower in the ibuprofen group (11 studies, 918 infants; MD -8.12 µmol/L, 95% CI -10.81 to -5.43). For this comparison, there was high between-study heterogeneity (I = 83%) and low-quality evidence. Ibuprofen (oral) compared with indomethacin (IV or oral): Eight studies (272 infants) reported on failure rates for PDA closure in a subgroup of the above studies comparing oral ibuprofen with indomethacin (IV or oral). There was no significant difference between the groups (typical RR 0.96, 95% CI 0.73 to 1.27; typical RD -0.01, 95% CI -0.12 to 0.09; I = 0% for both RR and RD). The risk of NEC was reduced with oral ibuprofen compared with indomethacin (IV or oral) (7 studies, 249 infants; typical RR 0.41, 95% CI 0.23 to 0.73; typical RD -0.13, 95% CI -0.22 to -0.05; NNTB 8, 95% CI 5 to 20; I = 0% for both RR and RD). There was low-quality evidence for these two outcomes. There was a decreased risk of failure to close a PDA with oral ibuprofen compared with IV ibuprofen (5 studies, 406 infants; typical RR 0.38, 95% CI 0.26 to 0.56; typical RD -0.22, 95% CI -0.31 to -0.14; NNTB 5, 95% CI 3 to 7; moderate-quality evidence). There was a decreased risk of failure to close a PDA with high-dose versus standard-dose of IV ibuprofen (3 studies 190 infants; typical RR 0.37, 95% CI 0.22 to 0.61; typical RD - 0.26, 95% CI -0.38 to -0.15; NNTB 4, 95% CI 3 to 7); I = 4% for RR and 0% for RD); moderate-quality evidence). Early versus expectant administration of IV ibuprofen, echocardiographically-guided IV ibuprofen treatment versus standard IV ibuprofen treatment, continuous infusion of ibuprofen versus intermittent boluses of ibuprofen, and rectal ibuprofen versus oral ibuprofen were studied in too few trials to allow for precise estimates of any clinical outcomes.
AUTHORS' CONCLUSIONS
Ibuprofen is as effective as indomethacin in closing a PDA. Ibuprofen reduces the risk of NEC and transient renal insufficiency. Therefore, of these two drugs, ibuprofen appears to be the drug of choice. The effectiveness of ibuprofen versus paracetamol is assessed in a separate review. Oro-gastric administration of ibuprofen appears as effective as IV administration. To make further recommendations, studies are needed to assess the effectiveness of high-dose versus standard-dose ibuprofen, early versus expectant administration of ibuprofen, echocardiographically-guided versus standard IV ibuprofen, and continuous infusion versus intermittent boluses of ibuprofen. Studies are lacking evaluating the effect of ibuprofen on longer-term outcomes in infants with PDA.
Topics: Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Enzyme Inhibitors; Humans; Ibuprofen; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic
PubMed: 32045960
DOI: 10.1002/14651858.CD003481.pub8 -
Paediatrics & Child Health Aug 2023Acetaminophen has gained interest in the neonatal community for its use in the management of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm...
OBJECTIVES
Acetaminophen has gained interest in the neonatal community for its use in the management of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. We conducted a systematic review of randomized controlled trials (RCTs) comparing the efficacy and safety of acetaminophen with indomethacin for the management of HsPDA in preterm infants.
METHODS
We searched PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library (CDSR and Central), EBSCO CINAHL, and SCOPUS from inception to June 15, 2021. Bibliographies of identified studies were searched for additional references. Data were analyzed with Review Manager (RevMan) Version 5.3.
RESULTS
Four RCTs were identified, enrolling a total of 380 subjects. There was no difference between the interventions for the outcome of PDA closure after one course (RR 1.04 [95% CIs: 0.84, 1.29], -value 0.70) or after two courses of treatment (RR 1.01 [95% CIs: 0.92, 1.12], -value 0.77); and for the outcome of PDA ligation (RR 1.56 [95% CIs: 0.48, 5.12], -value 0.46). However, patients who received acetaminophen had lower rates of necrotizing enterocolitis (RR 0.37 [95% CIs: 0.14, 0.95], -value 0.04). There were no significant differences noted in the other clinical outcomes, that is, intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, and death. Two studies noted significant post-treatment elevation of serum creatinine and blood urea with indomethacin, as compared to none with acetaminophen use.
CONCLUSIONS
Acetaminophen has comparable efficacy to indomethacin for the outcome of HsPDA closure, with a better safety profile, that is, lesser rates of necrotizing enterocolitis and post-treatment azotemia noted with its use.
PubMed: 37484043
DOI: 10.1093/pch/pxac130 -
Frontiers in Pediatrics 2020Patent ductus arteriosus (PDA) is a dramatically harmful disease in the neonatal period, in particular common in preterm infants, and our study was to determine related...
Patent ductus arteriosus (PDA) is a dramatically harmful disease in the neonatal period, in particular common in preterm infants, and our study was to determine related factors of PDA in preterm infants. A comprehensive literature review was conducted in PubMed, EMBASE, and Web of Science. The pooled odds ratio and standard mean difference were calculated to compare dichotomous and continuous variables, respectively. In addition, we also assessed the heterogeneity and publication bias and carried out sensitivity analysis for each related factor. We included 45 studies with 87,419 individuals. After the primary analysis and a series of adjustments, results showed chorioamnionitis, lower gestational age, lower birth weight, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, respiratory distress syndrome, sepsis, surfactant treatment, ventilation, and lower platelet count had a positive correlation with PDA, while small for gestational age decreased the incidence of PDA in preterm infants. Besides, premature rupture of membranes, preeclampsia, antenatal steroids, male gender, mean platelet volume, and platelet distribution width were found to have no statistically significant relationship with PDA. Preterm infants with more immature characteristics generally have a higher likelihood to develop PDA. The prevention, diagnosis, and management of PDA may depend on these results, and effective measures can be taken accordingly.
PubMed: 33469523
DOI: 10.3389/fped.2020.605879 -
Frontiers in Pediatrics 2020A meta-analysis published in 2015 showed a significant association between low platelet counts in the first day(s) of life and risk of patent ductus arteriosus (PDA)....
A meta-analysis published in 2015 showed a significant association between low platelet counts in the first day(s) of life and risk of patent ductus arteriosus (PDA). The meta-analysis pooled data from 11 studies cohorts (3,479 preterm infants). To update the meta-analysis by adding new studies on the topic and including other platelet parameters different from platelet counts. PubMed/Medline and Embase databases were searched. Random-effects risk ratios (RR) and differences in means (DM) and 95% confidence intervals (CI) were calculated. We included 31 studies (7,638 infants). Meta-analysis showed that the risk of developing any PDA was significantly associated with platelet counts<150 × 10/L (11 studies, RR 1.58, 95% CI 1.28 to 1.95), and <100 x 10/L (7 studies, RR 1.61, 95% CI 1.14 to 2.28), but not <50 x 10/L (4 studies, RR 1.34, 95% CI 0.77 to 2.32). Risk of developing hemodynamically significant PDA (hsPDA) was significantly associated with platelet counts<150 x 10/L (12 studies, RR 1.33, 95% CI 1.09 to 1.63), and <100 x 10/L (7 studies, RR 1.39, 95% CI 1.06 to 1.82), but not <50 x 10/L (6 studies, RR 1.24, 95% CI 0.86 to 1.79). Infants with hsPDA had significantly lower mean platelet counts (19 studies, DM 22.0 x 10, 95% CI 14.9 to 29.1) and platelet mass (11 studies, DM 214.4, 95% CI 131.2 to 297.5) and significantly higher platelet distribution width (PDW, 9 studies, DM -0.53, 95% CI -1.01 to -0.05) than infants without hsPDA. Meta-analysis could not demonstrate significant differences in mean platelet volume (MPV). Compared to the previous analysis, this updated meta-analysis included 21 additional studies that provide stronger evidence of the association between low platelet counts and PDA/hsPDA. Other platelet parameters such as platelet mass and PDW are also associated with hsPDA risk. However, the low number of platelets may be an epiphenomenon associated with the maturity and clinical stability of preterm infants rather than a contributing factor in the pathogenesis of PDA.
PubMed: 33553072
DOI: 10.3389/fped.2020.613766 -
The Cochrane Database of Systematic... Jan 2021Symptomatic patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. In these infants, prophylactic use of indomethacin, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Symptomatic patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. In these infants, prophylactic use of indomethacin, a non-selective cyclooxygenase inhibitor, has demonstrated short-term clinical benefits. The effect of indomethacin in preterm infants with a symptomatic PDA remains unexplored.
OBJECTIVES
To determine the effectiveness and safety of indomethacin (given by any route) compared to placebo or no treatment in reducing mortality and morbidity in preterm infants with a symptomatic PDA.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 7), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 31 July 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs.
SELECTION CRITERIA
We included RCTs and quasi-RCTs that compared indomethacin (any dose, any route) versus placebo or no treatment in preterm infants.
DATA COLLECTION AND ANALYSIS
We used the standard methods of Cochrane Neonatal, with separate evaluation of trial quality and data extraction by at least two review authors. We used the GRADE approach to assess the certainty of evidence for the following outcomes: failure of PDA closure within one week of administration of the first dose of indomethacin; bronchopulmonary dysplasia (BPD) at 28 days' postnatal age and at 36 weeks' postmenstrual age; proportion of infants requiring surgical ligation or transcatheter occlusion; all-cause neonatal mortality; necrotizing enterocolitis (NEC) (≥ Bell stage 2); and mucocutaneous or gastrointestinal bleeding.
MAIN RESULTS
We included 14 RCTs (880 preterm infants). Four out of the 14 included studies were judged to have high risk of bias in one or more domains. Indomethacin administration was associated with a large reduction in failure of PDA closure within one week of administration of the first dose (risk ratio (RR) 0.30, 95% confidence interval (CI) 0.23 to 0.38; risk difference (RD) -0.52, 95% CI -0.58 to -0.45; 10 studies, 654 infants; high-certainty evidence). There may be little to no difference in the incidence of BPD (BPD defined as supplemental oxygen need at 28 days' postnatal age: RR 1.45, 95% CI 0.60 to 3.51; 1 study, 55 infants; low-certainty evidence; BPD defined as supplemental oxygen need at 36 weeks' postmenstrual age: RR 0.80, 95% CI 0.41 to 1.55; 1 study, 92 infants; low-certainty evidence) and probably little to no difference in mortality (RR 0.78, 95% CI 0.46 to 1.33; 8 studies, 314 infants; moderate-certainty evidence) with use of indomethacin for symptomatic PDA. No differences were demonstrated in the need for surgical PDA ligation (RR 0.66, 95% CI 0.33 to 1.29; 7 studies, 275 infants; moderate-certainty evidence), in NEC (RR 1.27, 95% CI 0.36 to 4.55; 2 studies, 147 infants; low-certainty evidence), or in mucocutaneous or gastrointestinal bleeding (RR 0.33, 95% CI 0.01 to 7.58; 2 studies, 119 infants; low-certainty evidence) with use of indomethacin compared to placebo or no treatment. Certainty of evidence for BPD, surgical PDA ligation, NEC, and mucocutaneous or gastrointestinal bleeding was downgraded for very serious or serious imprecision.
AUTHORS' CONCLUSIONS
High-certainty evidence shows that indomethacin is effective in closing a symptomatic PDA compared to placebo or no treatment in preterm infants. Evidence is insufficient regarding effects of indomethacin on other clinically relevant outcomes and medication-related adverse effects.
Topics: Bias; Bronchopulmonary Dysplasia; Cause of Death; Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Enterocolitis, Necrotizing; Gastrointestinal Hemorrhage; Humans; Incidence; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Ligation; Oxygen Inhalation Therapy; Placebos; Randomized Controlled Trials as Topic
PubMed: 33448032
DOI: 10.1002/14651858.CD013133.pub2 -
Frontiers in Pediatrics 2020The optimal management strategy for patent ductus arteriosus in preterm infants remains a topic of debate. Available evidence for a treatment strategy might be biased by...
The optimal management strategy for patent ductus arteriosus in preterm infants remains a topic of debate. Available evidence for a treatment strategy might be biased by the delayed spontaneous closure of the ductus arteriosus in preterm infants, which appears to depend on patient characteristics. We performed a systematic review of all literature on PDA studies to collect patient characteristics and reported numbers of patients with a ductus arteriosus and spontaneous closure. Spontaneous closure rates showed a high variability but were lowest in studies that only included preterm infants with gestational ages below 28 weeks or birth weights below 1,000 g (34% on day 4; 41% on day 7) compared to studies that also included infants with higher gestational ages or higher birth weights (up to 55% on day 3 and 78% on day 7). The probability of spontaneous closure of the ductus arteriosus keeps increasing until at least 1 week after birth which favors delayed treatment of only those infants that do not show spontaneous closure. Better prediction of the spontaneous closure of the ductus arteriosus in the individual newborn is a key factor to find the optimal management strategy for PDA in preterm infants.
PubMed: 33014935
DOI: 10.3389/fped.2020.00541 -
Journal of Personalized Medicine Jul 2022A widely accepted concept in perinatal medicine is that boys are more susceptible than girls to complications of prematurity. However, whether this 'male disadvantage of... (Review)
Review
Sex Differences in Patent Ductus Arteriosus Incidence and Response to Pharmacological Treatment in Preterm Infants: A Systematic Review, Meta-Analysis and Meta-Regression.
A widely accepted concept in perinatal medicine is that boys are more susceptible than girls to complications of prematurity. However, whether this 'male disadvantage of prematurity' also involves persistent patent ductus arteriosus (PDA) has been scarcely investigated. Our aim was to conduct a systematic review and meta-analysis on studies addressing sex differences in the risk of developing PDA among preterm infants. We also investigated whether the response to pharmacological treatment of PDA differs between boys and girls. PubMed/Medline and Embase databases were searched. The random-effects male/female risk ratio (RR) and 95% confidence interval (CI) were calculated. We included 146 studies (357,781 infants). Meta-analysis could not demonstrate sex differences in risk of developing any PDA (37 studies, RR 1.03, 95% CI 0.97 to 1.08), hemodynamically significant PDA (81 studies, RR 1.00, 95% CI 0.97 to 1.02), or in the rate of response to pharmacological treatment (45 studies, RR 1.01, 95% CI 0.98 to 1.04). Subgroup analysis and meta-regression showed that the absence of sex differences was maintained over the years and in different geographic settings. In conclusion, both the incidence of PDA in preterm infants and the response rate to pharmacological treatment of PDA are not different between preterm boys and girls.
PubMed: 35887640
DOI: 10.3390/jpm12071143 -
PeerJ 2024This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse... (Meta-Analysis)
Meta-Analysis
The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis.
BACKGROUND
This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse events when administering medications to premature infants with patent ductus arteriosus (PDA).
METHOD
The protocol for this review has been registered with PROSPERO (CRD 42022324598). We searched relevant studies in PubMed, Embase, Cochrane, and the Web of Science databases from March 26, 1996, to January 31, 2022.
RESULTS
A total of six randomized controlled trials (RCTs) and five observational studies were included for analysis, involving 630 premature neonates in total. Among these infants, 480 were in the ibuprofen group (oral intravenous routes), 78 in the paracetamol group (oral intravenous routes), and 72 in the ibuprofen group (rectal oral routes). Our meta-analysis revealed a significant difference in the rate of PDA closure between the the initial course of oral ibuprofen and intravenous ibuprofen groups (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.13-1.44]; < 0.0001, = 0%). In contrast, the meta-analysis of paracetamol administration via oral versus intravenous routes showed no significant difference in PDA closure rates (RR = 0.86, 95% CI [0.38-1.91]; = 0.71, = 76%). However, there was no statistically significant difference in the risk of adverse events or the need for surgical intervention among various drug administration methods after the complete course of drug therapy.
CONCLUSION
This meta-analysis evaluated the safety and effectiveness of different medication routes for treating PDA in premature infants. Our analysis results revealed that compared with intravenous administration, oral ibuprofen may offer certain advantages in closing PDA without increasing the risk of adverse events. Conversely, the use of paracetamol demonstrated no significant difference in PDA closure and the risk of adverse events between oral and intravenous administration.
Topics: Infant, Newborn; Humans; Ductus Arteriosus, Patent; Ibuprofen; Indomethacin; Cyclooxygenase Inhibitors; Infant, Low Birth Weight; Acetaminophen; Infant, Premature
PubMed: 38304184
DOI: 10.7717/peerj.16591 -
British Journal of Clinical Pharmacology Jul 2022Ibuprofen and indomethacin are the preferred drug treatment for patent ductus arteriosus (PDA) in preterm neonates. The comparative safety and efficacy of paracetamol as... (Meta-Analysis)
Meta-Analysis Review
Comparative safety and efficacy of paracetamol versus non-steroidal anti-inflammatory agents in neonates with patent ductus arteriosus: A systematic review and meta-analysis of randomized controlled trials.
AIM
Ibuprofen and indomethacin are the preferred drug treatment for patent ductus arteriosus (PDA) in preterm neonates. The comparative safety and efficacy of paracetamol as an alternative has not yet been well established. The aim of our study was to define the comparative efficacy and safety of paracetamol versus ibuprofen and indomethacin for PDA.
METHODS
We performed a systematic literature search in PubMed, Scopus and Cochrane databases on randomized controlled trials comparing the efficacy and/or the safety of paracetamol versus ibuprofen and/or indomethacin and meta-analysed the available data.
RESULTS
There were 1718 neonates from 20 eligible studies. Paracetamol did not differ from ibuprofen or indomethacin regarding the primary (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.69-1.26, P-value: 0.650, when compared to ibuprofen, and OR: 0.78; 95% CI: 0.20-3.02, P-value: 0.716, when compared to indomethacin) and overall (OR: 1.17; 95% CI: 0.82-1.66, P-value: 0.394, when compared to ibuprofen, and OR: 1.12; 95% CI: 0.58-2.15, P-value: 0.733, when compared to indomethacin) PDA closure rates. Paracetamol resulted in significantly reduced risk of oliguria and a tendency towards less gastrointestinal bleeding.
CONCLUSION
There was no significant difference between paracetamol and ibuprofen or indomethacin in the PDA closure rates. However, paracetamol caused fewer adverse effects.
Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Ductus Arteriosus, Patent; Humans; Ibuprofen; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic
PubMed: 35203104
DOI: 10.1111/bcp.15291