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Voice and Exercise Related Respiratory Symptoms in Extremely Preterm Born Children After Neonatal Patent Ductus Arteriosus.

ABSTRACT: Objective: To investigate voice characteristics and exercise related respiratory symptoms in extremely preterm born 11-year-old children, focusing particularly on associations with management of a patent ductus arteriosus (PDA). Study design: Prospective follow-up of all children born in Norway during 1999-2000 at gestational age <28 weeks or with birthweight <1,000 g. Neonatal data were obtained prospectively on custom-made registration forms completed by neonatologists. Voice characteristics and exercise related respiratory symptoms were obtained at 11 years by parental questionnaires. Result: Questionnaires were returned for 228/372 (61%) eligible children, of whom 137 had no history of PDA. PDA had been noted in 91 participants, of whom 36 had been treated conservatively, 21 with indomethacin, and 34 with surgery. Compared to the children treated with indomethacin or conservatively, the odds ratio (95% confidence interval) for the surgically treated children were 3.4 (1.3; 9.2) for having breathing problems during exercise, 16.9 (2.0; 143.0) for having a hoarse voice, 4.7 (1.3; 16.7) for a voice that breaks when shouting, 4.6 (1.1; 19.1) for a voice that disturbs singing, and 3.7 (1.1; 12.3) for problems shouting or speaking loudly. The significance of surgery per se was uncertain since the duration of mechanical ventilation was associated with the same outcomes. Conclusion: Extremely preterm born children with a neonatal history of PDA surgery had more problems with voice and breathing during exercise in mid-childhood than those whose PDA had been handled otherwise. The study underlines the causal heterogeneity of exercise related respiratory symptoms in preterm born children.

SUBMITTER: Engeseth MS

PROVIDER: S-EPMC7156623 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Voice and Exercise Related Respiratory Symptoms in Extremely Preterm Born Children After Neonatal Patent Ductus Arteriosus.

Engeseth Merete S MS Engan Mette M Clemm Hege H Vollsæter Maria M Nilsen Roy M RM Markestad Trond T Halvorsen Thomas T Røksund Ola D OD

Frontiers in pediatrics 20200408

<b>Objective:</b> To investigate voice characteristics and exercise related respiratory symptoms in extremely preterm born 11-year-old children, focusing particularly on associations with management of a patent ductus arteriosus (PDA). <b>Study design:</b> Prospective follow-up of all children born in Norway during 1999-2000 at gestational age <28 weeks or with birthweight <1,000 g. Neonatal data were obtained prospectively on custom-made registration forms completed by neonatologists. Voice cha ...[more]

PMID: 32322565

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Project description:Background: Left vocal cord paralysis (LVCP) is a known complication of patent ductus arteriosus (PDA) surgery in extremely preterm (EP) born neonates; however, consequences of LVCP beyond the first year of life are insufficiently described. Both voice problems and breathing difficulties during physical activity could be expected with an impaired laryngeal inlet. More knowledge may improve the follow-up of EP-born subjects who underwent PDA surgery and prevent confusion between LVCP and other diagnoses. Objectives: Examine the prevalence of LVCP in a nationwide cohort of adults born EP with a history of PDA surgery, and compare symptoms, lung function, and exercise capacity between groups with and without LVCP, and vs. controls born EP and at term. Methods: Adults born EP (<28 weeks' gestation or birth weight <1,000 g) in Norway during 1999-2000 who underwent neonatal PDA surgery and controls born EP and at term were invited to complete questionnaires mapping voice-and respiratory symptoms, and to perform spirometry and maximal treadmill exercise testing. In the PDA-surgery group, exercise tests were performed with a laryngoscope positioned to evaluate laryngeal function. Results: Thirty out of 48 (63%) eligible PDA-surgery subjects were examined at mean (standard deviation) age 19.4 (0.8) years, sixteen (53%) had LVCP. LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, not with lung function or peak oxygen consumption (VO2peak). In the PDA-surgery group, forced expiratory volume in 1 second z-score (z-FEV1) was reduced compared to EP-born controls (n = 30) and term-born controls (n = 36); mean (95% confidence interval) z-FEV1 was -1.8 (-2.3, -1.2), -0.7 (-1.1, -0.3) and -0.3 (-0.5, -0.0), respectively. For VO2peak, corresponding figures were 37.5 (34.9, 40.2), 38.1 (35.1, 41.1), and 43.6 (41.0, 46.5) ml/kg/min, respectively. Conclusions: LVCP was common in EP-born young adults who had undergone neonatal PDA surgery. Within the PDA-surgery group, LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, however we did not find an association with lung function or exercise capacity. Overall, the PDA-surgery group had reduced lung function compared to EP-born and term-born controls, whereas exercise capacity was similarly reduced for both the PDA-surgery and EP-born control groups when compared to term-born controls.

Project description:ImportanceObservational studies have associated patent ductus arteriosus (PDA) ligation among preterm infants with adverse neonatal outcomes and neurodevelopmental impairment in early childhood, with a resultant secular trend away from surgical treatment. However, to our knowledge, studies have inadequately addressed sources of residual bias, including survival bias and major neonatal morbidities arising before exposure to ligation.ObjectiveEvaluate the association between PDA ligation vs medical management and neonatal and neurodevelopmental outcomes.Design, setting, and participantsThis retrospective cohort study of preterm infants younger than 28 weeks gestational age born between January 1, 2006, and December 31, 2012, with clinical and echocardiography diagnoses of hemodynamically significant PDA was conducted at 3 tertiary neonatal intensive care units and affiliated follow-up programs.ExposureSurgical ligation vs medical management.Main outcomes and measuresThe primary outcome was a composite of death or neurodevelopmental impairment (NDI) at 18 to 24 months corrected age. Secondary outcomes included death before discharge, NDI, moderate-severe chronic lung disease, and severe retinopathy of prematurity. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders.ResultsOf 754 infants with hemodynamically significant PDA (mean [standard deviation] gestational age 25.7 [1.2] weeks and birth weight 813 [183] grams), 184 (24%) underwent ligation. Infants who underwent ligation had a higher frequency of morbidities before PDA closure, including sepsis, necrotizing enterocolitis, and a dependence on mechanical ventilation. After adjusting for perinatal characteristics and preligation morbidities, there was no difference in the odds of death or NDI (adjusted odds ratio (aOR), 0.83; 95% CI, 0.52-1.32), NDI (aOR, 1.27; 95% CI, 0.78-2.06), chronic lung disease (aOR, 1.36; 95% CI, 0.78-2.39) or severe retinopathy of prematurity (aOR, 1.61; 95% CI, 0.85-3.06). Ligation was associated with lower odds of mortality (aOR, 0.09; 95% CI, 0.04-0.21).Conclusions and relevancePatent ductus arteriosus ligation among preterm neonates younger than 28 weeks gestational age was not associated with the composite outcome of death or NDI, and there were no differences in chronic lung disease, retinopathy of prematurity, or NDI among survivors. Mortality was lower among infants who underwent ligation, though residual survival bias could not be excluded. Previously reported associations of ligation with increased morbidity may be because of bias from confounding by indication.

Project description:Background: Amino acids are increasingly recognized as bioactive molecules in numerous physiological and pathophysiological pathways. The non-essential amino acid glutamate is vasoactive in the rat ductus arteriosus (DA) and a decrease in its levels within the 1st days of life has been associated with the presence of patent DA (PDA) in extremely preterm infants. However, these findings have not been confirmed in other studies. Objective: To investigate the possible association between amino acid concentrations in the 1st day of life and the presence of PDA in a cohort of 121 newborns with gestational age (GA) below 30 weeks and birth weight (BW) below 1,500 g. Methods: Plasma samples were collected 6-12 h after birth and amino acid concentrations were determined by tandem mass spectrometry. Besides PDA, we analyzed the potential association of amino acid concentrations with infant sex, small for GA (SGA, defined as BW < third percentile), antenatal corticosteroids, chorioamnionitis, and preeclampsia. Group differences were analyzed by ANOVA adjusted for GA and BW. A Bonferroni significance threshold of P < 0.0024 was used to correct for multiple testing. Results: PDA was found in 48 of the 121 infants examined. We observed higher mean levels of glutamate in infants with PDA (147.0 μmol/L, SD 84.0) as compared with those without (106.7 μmol/L, SD 49.1, P = 0.0006). None of the other amino acid concentrations in the PDA group reached the level of statistical significance that was pre-set to correct for multiple comparisons. Glutamate levels were not significantly affected by infant sex, being SGA, or by exposure to antenatal corticosteroids, clinical chorioamnionitis, or preeclampsia. Conclusion: Our study not only does not confirm the previous findings of low glutamate levels in preterm infants with PDA, but we have even found elevated glutamate concentrations associated with PDA. Nevertheless, despite the high statistical significance, the difference in glutamate levels may lack clinical significance or may be an epiphenomenon associated with the particular clinical condition of infants with PDA.

Project description:BackgroundSymptomatic 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.ObjectivesTo 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 methodsWe 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 criteriaWe included RCTs and quasi-RCTs that compared indomethacin (any dose, any route) versus placebo or no treatment in preterm infants.Data collection and analysisWe 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 resultsWe 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' conclusionsHigh-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.

Project description:BackgroundThe optimal treatment strategy for patent ductus arteriosus (PDA) in extremely preterm infants is currently highly controversial. This study aimed to evaluate the association between PDA treatment and short-term outcomes among extremely preterm infants.MethodsThis cohort study included all extremely preterm infants (≤27 and 6/7 weeks) who were admitted to hospitals participating in the Chinese Neonatal Network from January 2019 to December 2021, and were diagnosed to have PDA by echocardiogram. PDA treatment was defined as medical treatment and/or surgical ligation of PDA during hospitalization. Short-term outcomes included death, bronchopulmonary dysplasia (BPD), death/BPD, retinopathy of prematurity, necrotizing enterocolitis, and severe brain injury. Multivariate logistic regression was used to evaluate the association between PDA treatment and outcomes. Subgroup analysis were performed among infants with different respiratory support on 3 and 7 days of life.FindingsA total of 2494 extremely preterm infants with the diagnosis of PDA were enrolled, of which 1299 (52.1%) received PDA treatment. PDA treatment was significantly associated with lower risk of death (adjusted odds ratio, 0.48; 95% confidence interval, 0.38-0.60). The decreased risk of death was accompanied by increased risk of BPD and death/BPD. In subgroup analysis according to respiratory support, PDA treatment was associated with lower risk of death among infants who required invasive ventilation. However, the beneficial effect on death was not significant among infants who did not require invasive ventilation.InterpretationPDA treatment was associated with reduced mortality in extremely preterm infants, but this beneficial effect was mainly present among infants who required invasive ventilation.FundingThis study was funded by the Shanghai Science and Technology Commission's Scientific and Technological Innovation Action Plan (21Y21900800) and the Canadian Institutes of Health Research (CTP87518).

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Voice and Exercise Related Respiratory Symptoms in Extremely Preterm Born Children After Neonatal Patent Ductus Arteriosus.

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Voice and Exercise Related Respiratory Symptoms in Extremely Preterm Born Children After Neonatal Patent Ductus Arteriosus.

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