Background: The optimal timing of pharmacological treatment for patent ductus arteriosus (PDA) in extremely preterm infants is unknown. Objective: To investigate whether timing of pharmacological PDA treatment is associated with a risk of secondary PDA surgery or death before 3 months of age, or bronchopulmonary dysplasia (BPD) in extremely preterm infants. Methods: In this population-based cohort of infants born before 27 gestational weeks in Sweden in 2004-2007, 290/585 infants (50%) received pharmacological PDA treatment. Cox proportional hazards regression estimated the hazard ratio (HR, with 95% confidence interval, CI) of secondary PDA surgery or death as a composite outcome in relation to postnatal age at the start of pharmacological treatment: early (0-2 days); intermediate (3-6 days); late (≥7 days). Furthermore, the odds ratio (OR, with 95% CI) of BPD was estimated in relation to postnatal age at PDA treatment by conditional logistic regression. Results: The median postnatal age at the start of pharmacological PDA treatment was 4 days. 102 infants had secondary PDA surgery. Timing of PDA treatment was not associated with risk of PDA surgery or death; adjusted HRs were 0.89 (95% CI 0.57-1.39) after an intermediate start and 1.10 (95% CI 0.53-2.28) after a late start, compared to an early start of treatment. Compared to the early start of PDA treatment, the intermediate start was not associated with any risk of BPD, while late PDA treatment was associated with a lower BPD risk; adjusted ORs were 0.83 (95% CI 0.42-1.64) and 0.28 (95% CI 0.13-0.61), respectively. Conclusion: Timing of pharmacological PDA treatment after extremely preterm birth is not associated with the risk of secondary PDA surgery or death. Moreover, expectant PDA management is not associated with an increased risk of BPD. © 2014 S. Karger AG, Basel
Background: Spontaneous closure of patent ductus arteriosus (PDA) occurs frequently in very preterm infants and despite the lack of evidence for treatment benefits, treatment for PDA is common in neonatal medicine. Objectives: The aim of this work was to study regional variations in PDA treatment in very preterm infants (≤31 weeks of gestation), its relation to differences in perinatal characteristics, and associations with bronchopulmonary dysplasia (BPD) and survival without major neonatal morbidity. Methods: This was a population-based cohort study in 19 regions in 11 European countries conducted during 2011 and 2012. A total of 6,896 infants with data on PDA treatment were included. The differences in infant characteristics were studied across regions using a propensity score derived from perinatal risk factors for PDA treatment. The primary outcomes were a composite of BPD or death before 36 weeks postmenstrual age, or survival without major neonatal morbidity. Results: The proportion of PDA treatment varied from 10 to 39% between regions (p < 0.001), and this difference could not be explained by differences in perinatal characteristics. The regions were categorized according to a low (<15%, n = 6), medium (15-25%, n = 9), or high (>25%, n = 4) proportion of PDA treatment. Infants treated for PDA, compared to those not treated, were at higher risk of BPD or death in all regions, with an overall propensity score adjusted risk ratio of 1.33 (95% confidence interval 1.18-1.51). Survival without major neonatal morbidity was not related to PDA treatment. Conclusions: PDA treatment varies largely across Europe without associated variations in perinatal characteristics or neonatal outcomes. This finding calls for more uniform guidance for PDA diagnosis and treatment in very preterm infants.
Aim This study investigated patent ductus arteriosus (PDA) treatment and neurodevelopmental outcomes when extremely preterm born children reached 6.5 years. Method Our cohort was 435 children with neonatal PDA treatment data and neurodevelopmental follow‐up data, born in 2004‐2007, who participated in the Extremely Preterm Infants in Sweden Study. Pharmacological or surgical PDA treatment and the age at PDA treatment, were investigated in relation to the risks of moderate to severe neurodevelopmental impairment (NDI) and full‐scale intelligence quotient (FSIQ) at 6.5 years. Results The children who received PDA drug treatment, including those who also had surgery, had the same risk of moderate to severe NDI or lower FSIQ as untreated children. However, children who had primary PDA surgery faced increased risks of NDI, with an adjusted incidence rate ratio of 1.62 (95% confidence interval [CI] 1.28‐2.06) and a lower adjusted mean difference FSIQ of −7.1 (95% CI −11 to −3.2). Surgery at less than 10 days of life was associated with a significantly increased risk of moderate to severe NDI and lower FSIQ than surgery after 20 days. Conclusion Drug treatment followed by deferred surgery appeared to be a safer option for extremely preterm infants severely affected by PDA.
The aim was to investigate the association of gestational age (GA), echocardiographic markers and levels of plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) with the closure rate of a haemodynamically significant patent ductus arteriosus (hsPDA). Ninety-eight Swedish extremely preterm infants, mean GA 25.7 weeks (standard deviation 1.3), born in 2012–2014, were assessed with echocardiography and for levels of NTproBNP. Thirty-three (34%) infants had spontaneous ductal closure within three weeks of age. Infants having spontaneous closure at seven days or less had significantly lower NTproBNP levels on day three, median 1810 ng/L (IQR 1760–6000 ng/L) compared with: infants closing spontaneously later, 10,900 ng/L (6120–19,200 ng/L); infants treated either with ibuprofen only, 14,600 ng/L (7740–28,100 ng/L); or surgery, 32,300 ng/L (29,100–35,000 ng/L). Infants receiving PDA surgery later had significantly higher NTproBNP values on day three than other infants. Day three NTproBNP cut-off values of 15,001–18,000 ng/L, predicted later PDA surgery, with an area under the curve in ROC analysis of 0.69 (0.54–0.83). In conclusion, the spontaneous PDA closure rate is relatively high in extremely preterm infants. Early NTproBNP levels can be used with GA in the management decisions of hsPDA.
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