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Intraventricular Hemorrhage: Risk Factors and Association With Patent Ductus Arteriosus Treatment in Extremely Preterm Neonates.

ABSTRACT: Objectives: To assess maternal and neonatal risk factors for intraventricular hemorrhage (IVH). To examine the association of patent ductus arteriosus (PDA) and its treatment, with IVH and its severity. Study design: In this retrospective cohort study, we included preterm neonates born at <29 weeks, admitted to a tertiary level III Neonatal Intensive Care Unit in Calgary, Canada, between 2013 and 2016, who had a head ultrasound in the first 7 days of life. A subset analysis included neonates who also had cardiac ultrasound in the first 3 days of life. Results: Of the 495 neonates, 121 (24.4%) had IVH of any grade and 48 (9.7%) had severe IVH. Identified risk factors were small birth gestation and weight, lack of antenatal corticosteroids, maternal chorioamnionitis, Apgar score <5 at 5 min, umbilical cord pH < 7, respiratory distress syndrome, early onset sepsis, hypercapnia, pCO2 fluctuations, prolonged intubation, inhaled nitric oxide, inotropes or normal saline boluses, metabolic derangements, opioids infusions, and bicarbonate/THAM therapy. In a primary analysis of the total cohort, when the decision to treat a PDA was used as a surrogate marker of its clinical significance, a PDA requiring treatment was associated with a higher risk of IVH. There was no significant difference in the incidence of IVH between neonates with early treatment of a clinically significant PDA compared to late, however early indomethacin treatment was associated with reduced severity of IVH. In the subset analysis, the presence of a hemodynamically significant PDA (hs-PDA) was not associated with a higher probability of IVH. Of those with severe IVH, 18 (55%) had a hs-PDA; this is clinically but not statistically significant. Conclusions: Identified risk factors should be the target of IVH reduction bundles. Early indomethacin treatment for a clinically significant PDA may reduce IVH severity.

SUBMITTER: Khanafer-Larocque I

PROVIDER: S-EPMC6817605 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Intraventricular Hemorrhage: Risk Factors and Association With Patent Ductus Arteriosus Treatment in Extremely Preterm Neonates.

Khanafer-Larocque Ijab I Soraisham Amuchou A Stritzke Amelie A Al Awad Essa E Thomas Sumesh S Murthy Prashanth P Kamaluddeen Majeeda M Scott James N JN Mohammad Khorshid K

Frontiers in pediatrics 20191022

<b>Objectives:</b> To assess maternal and neonatal risk factors for intraventricular hemorrhage (IVH). To examine the association of patent ductus arteriosus (PDA) and its treatment, with IVH and its severity. <b>Study design:</b> In this retrospective cohort study, we included preterm neonates born at <29 weeks, admitted to a tertiary level III Neonatal Intensive Care Unit in Calgary, Canada, between 2013 and 2016, who had a head ultrasound in the first 7 days of life. A subset analysis include ...[more]

PMID: 31696098

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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: In extremely low birth weight (ELBW) infants, the patent ductus arteriosus (PDA) with left-to-right shunt and an increase in systemic artery resistance may cause increasing preload and afterload of the left ventricle. The immature myocardium in ELBW infants has a limited ability to respond to the change, which leads to hemorrhagic complications. In this study, we detected the hemodynamic change of cardiac performance and applied a clinical strategy to prevent PDA-associated hemorrhagic complications in ELBW infants. Methods: We enrolled ELBW infants at a single medical center in Taiwan. The customized circulatory management was performed by echocardiography after birth until the PDA closed. Inotropic agents were administrated according to the requirements of hemodynamic parameters or clinical conditions. The primary outcomes were hemorrhagic complications including pulmonary hemorrhage and intraventricular hemorrhage (IVH) greater than grade II. The secondary outcomes were the rate of surgical ligation of PDA, mortality, necrotizing enterocolitis, and bronchopulmonary dysplasia. Results: A total of 20 ELBW infants were evaluated by customized circulatory management from 2019 to 2020. We reviewed 35 ELBW infants born between 2017 and 2018 in our hospital, who served as the non-management group. The management group had a significantly lower incidence rate of IVH greater than grade 2 (p = 0.02). Other outcomes showed no significant differences. Dobutamine was prescribed in 8 cases in the management group, and end-systolic wall stress (ESWS) was significantly decreased after Dobutamine administration (p = 0.017). Conclusion: The incidence rate of IVH greater than grade II in ELBW infants decreased after use of customized circulatory management in our study. The strategy of customized circulatory management might be an effective "early target therapy" for hemodynamically significant PDA in high-risk ELBW infants. Inotropic therapy with Dobutamine could be a useful medical choice for improving cardiac function to prevent hemorrhagic complications.

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.

Dataset Information

Intraventricular Hemorrhage: Risk Factors and Association With Patent Ductus Arteriosus Treatment in Extremely Preterm Neonates.

Publications

Intraventricular Hemorrhage: Risk Factors and Association With Patent Ductus Arteriosus Treatment in Extremely Preterm Neonates.

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