Urinary Acetaminophen Metabolites and Clinical Outcomes in Extremely Premature Infants.

Objective: Extremely premature infants are treated with acetaminophen (APAP) for pain and patent ductus arteriosus. High doses of APAP in adults are toxic, and a recent study found an association between APAP metabolite levels in mothers' breast milk and both bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) in their premature infants. In this study, we determined levels of APAP metabolites in urine of infants at high risk for BPD and ROP.

Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants <28 weeks' gestation.

Background: Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhage (grades 3, 4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Previous randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates.

Prophylactic indomethacin and the risk of serious pulmonary hemorrhages in preterm infants less than 28 weeks' gestation.

Objective: To determine if prophylactic indomethacin (PINDO) decreases serious pulmonary hemorrhages in infants <28 weeks.

Study Design: Intention-to-treat analysis of 615 consecutively admitted infants during four alternating protocol-driven epochs of PINDO or expectant patent ductus arteriosus (PDA) management.

Results: 41/615 (6.

Prophylactic indomethacin, antenatal betamethasone, and the risk of intestinal perforation in infants <28 weeks' gestation.

Objective: To determine if intestinal perforations before 14 days (either spontaneous (SIP) or necrotizing enterocolitis-induced) are increased when infants who received antenatal betamethasone shortly before birth are treated with prophylactic indomethacin (PINDO).

Study Design: Observational study of 475 infants <28 week's gestation assigned to either a PINDO-protocol (n = 231) or expectant management protocol (n = 244) during consecutive protocol epochs.

Results: Intestinal perforations before 14 days occurred in 33/475 (7%).

Patent ductus arteriosus (PDA) and pulmonary morbidity: can early targeted pharmacologic PDA treatment decrease the risk of bronchopulmonary dysplasia?

A persistent left-to-right shunt through a patent ductus arteriosus (PDA) increases the rate of pulmonary hydrostatic fluid filtration, impairs pulmonary mechanics, and prolongs the need for respiratory support. Infants with a moderate/large PDA shunt that persists for more than 7-14 days are at increased risk for developing bronchopulmonary dysplasia (BPD) if they also require invasive ventilation for more than 10 days. In contrast, infants who require invasive ventilation for less than 10 days have similar rates of BPD no matter how long they are exposed to a moderate/large PDA shunt.

Patent ductus arteriosus and the risk of bronchopulmonary dysplasia-associated pulmonary hypertension.

Background: The aim of the study was to determine whether prolonged exposure to a moderate/large patent ductus arteriosus left-to-right shunt (PDA) increases the risk of late (beyond 36 weeks) pulmonary hypertension (BPD-PH) and pulmonary vascular disease (BPD-PVD) during the neonatal hospitalization in preterm infants (<28 weeks' gestation) with bronchopulmonary dysplasia (BPD).

Methods: All infants requiring respiratory support ≥36 weeks had systematic echocardiographic evaluations for BPD-PH at planned intervals. Infants were classified as having either flow-associated BPD-PH (BPD-flow-PH) or BPD-PVD.

Effects of prophylactic indomethacin on morbidity and mortality in infants <25 weeks' gestation: a protocol driven intention to treat analysis.

Objective: To determine if prophylactic indomethacin (PINDO) decreases death or bronchopulmonary dysplasia-grades 2 and 3 (death/BPD) in newborns <25 weeks.

Study Design: Intention-to-treat, cohort-controlled study of 106 infants admitted during three alternating epochs of PINDO or Expectant patent ductus arteriosus (PDA) management.

Results: At 7-8 days 85% of Expectant Management epoch infants had a moderate/large PDA (median exposure was 23 days).

An Update on Patent Ductus Arteriosus and What is Coming Next.

Patent ductus arteriosus is the most common cardiovascular condition in preterm infants. There is a significant uncertainty about when and how to close ductus arteriosus in preterm infants due to a high spontaneous closure rate even in very immature preterm infants. Diagnosis and management of patent ductus arteriosus remain a challenge for both neonatologists and pediatric cardiologists.

Corrigendum: Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: An Updated Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fped.2020.

Interactions between PDA-associated polymorphisms and genetic ancestry alter ductus arteriosus gene expression.

Background: DNA polymorphisms in PTGIS and TFAP2B have been identified as risk factors for patent ductus arteriosus (PDA) in a population composed of preterm infants with European genetic ancestry but not in more genetically diverse populations.

Goal: To determine if the effects of TFAP2B and PTGIS polymorphisms on ductus arteriosus (DA) gene expression differ based on genetic ancestry.

Methods: DA from 273 human second trimester fetuses were genotyped for TFAP2B and PTGIS polymorphisms and for polymorphisms distributing along genetic ancestry lines.

Patent ductus arteriosus, tracheal ventilation, and the risk of bronchopulmonary dysplasia.

Background: An increased risk for bronchopulmonary dysplasia (BPD) exists when moderate-to-large patent ductus arteriosus shunts (hsPDA) persist beyond 14 days.

Goal: To examine the interaction between prolonged exposures to tracheal ventilation (≥10 days) and hsPDA on the incidence of BPD in infants <28 weeks gestation.

Study Design: Predefined definitions of prolonged ventilation (≥10 days), hsPDA (≥14 days), and BPD (room air challenge test at 36 weeks) were used to analyze deidentified data from the multicenter TRIOCAPI RCT in a secondary analysis of the trial.

Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: An Updated Systematic Review and Meta-Analysis.

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.

Effect of Early Targeted Treatment of Ductus Arteriosus with Ibuprofen on Survival Without Cerebral Palsy at 2 Years in Infants with Extreme Prematurity: A Randomized Clinical Trial.

Objective: To examine the effects of early echocardiography-targeted ibuprofen treatment of large patent ductus arteriosus (PDA) on survival without cerebral palsy at 24 months of corrected age.

Study Design: We enrolled infants born at <28 weeks of gestation with a large PDA on echocardiography at 6-12 hours after birth to ibuprofen or placebo by 12 hours of age in a multicenter, double blind, randomized-controlled trial. Open-label ibuprofen was allowed for prespecified criteria of a hemodynamically significant PDA.

Prolonged Tracheal Intubation and the Association Between Patent Ductus Arteriosus and Bronchopulmonary Dysplasia: A Secondary Analysis of the PDA-TOLERATE trial.

In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required <10 days of intubation. However, in infants requiring intubation for ≥10 days, prolonged PDA exposure (≥11 days) was associated with an increased risk of moderate/severe BPD.

The effect of prolonged tracheal intubation on the association between patent ductus arteriosus and bronchopulmonary dysplasia (grades 2 and 3).

Objective: To determine if the need for mechanical ventilation alters the association between prolonged patent ductus arteriosus (PDA) exposure and bronchopulmonary dysplasia (grades 2 and 3) (BPD).

Study Design: Observational study of 407 infants (<28 weeks' gestation) with echocardiograms performed at planned intervals.

Results: Twelve percent (48/407) of study infants had BPD (grades 2 and 3).

A role for neonatal bacteremia in deaths due to intestinal perforation: spontaneous intestinal perforation compared with perforated necrotizing enterocolitis.

Objective: To examine the relationship between intestinal perforations (caused by either spontaneous perforation (SIP) or necrotizing enterocolitis (NEC)) and the outcome "death due to intestinal perforation".

Methods: Multivariable logistic regression analyses were used to compare infants <28 weeks' gestation with SIP (n = 32) and perforated-NEC (n = 45) for the outcome perforation-related death.

Results: In univariate analyses the incidence of death due to perforation was higher among infants with perforated-NEC (36%) than infants with SIP (13%).

Relationship between Duration of Infant Exposure to a Moderate-to-Large Patent Ductus Arteriosus Shunt and the Risk of Developing Bronchopulmonary Dysplasia or Death Before 36 Weeks.

Objective: This study was aimed to examine the relationship between duration of infant exposure to a moderate-to-large patent ductus arteriosus (PDA) shunt and the risk of developing bronchopulmonary dysplasia (BPD) or death before 36 weeks (BPD/death).

Study Design: Infants <28 weeks' gestation who survived ≥7 days ( = 423) had echocardiograms performed on day 7 and at planned intervals.

Results: In multivariable regression models, BPD/death did not appear to be increased until infants had been exposed to a moderate-to-large PDA for at least 7-13 days: OR (95%CI) (referent = closed or small PDA): moderate-to-large PDA exposure for <7 days: 0.

is associated with indomethacin treatment failure for patent ductus arteriosus.

To identify clinical andgenetic factors associated with indomethacin treatment failure in preterm neonates with patent ductus arteriosus (PDA). This is a multicenter cohort study of 144 preterm infants (22-32 weeks gestational age) at three centers who received at least one treatment course of indomethacin for PDA. Indomethacin failure was defined as requiring subsequent surgical intervention.

Lack of Equipoise in the PDA-TOLERATE Trial: A Comparison of Eligible Infants Enrolled in the Trial and Those Treated Outside the Trial.

The PDA: TO LEave it alone or Respond And Treat Early trial compared the effects of 2 strategies for treatment of patent ductus arteriosus (PDA) in infants <28 weeks of gestation; however 137 potentially eligible infants were not recruited and received treatment of their PDA outside the PDA-TOLERATE trial due to "lack-of-physician-equipoise" (LPE). Despite being less mature and needing more respiratory support, infants with LPE had lower rates of mortality than enrolled infants. Infants with LPE treated before day 6 had lower rates of late respiratory morbidity than infants with LPE treated ≥day 6.