Variants of the promoter of MYH6 gene in congenital isolated and sporadic patent ductus arteriosus: case-control study and cellular functional analyses.

Patent ductus arteriosus (PDA) is a common form of congenital heart disease. The MYH6 gene has important effects on cardiovascular growth and development, but the effect of variants in the MYH6 gene promoter on ductus arteriosus is unknown. DNA was extracted from blood samples of 721 subjects (428 patients with isolated and sporadic PDA and 293 healthy controls) and analyzed by sequencing for MYH6 gene promoter region variants. Cellular function experiments with three cell lines (HEK-293, HL-1, and H9C2 cells) and bioinformatics analyses were performed to verify their effects on gene expression. In the MYH6 gene promoter, 11 variants were identified. Four variants were found only in patients with PDA and 2 of them (g.3434G>C and g.4524C>T) were novel. Electrophoretic mobility shift assay showed that the transcription factors bound by the promoter variants were significantly altered in comparison to the wild-type in all three cell lines. Dual luciferase reporter showed that all the 4 variants reduced the transcriptional activity of the MYH6 gene promoter (P < 0.05). Prediction of transcription factors bound by the variants indicated that these variants alter the transcription factor binding sites. These pathological alterations most likely affect the contraction of the smooth muscle of ductus arteriosus, leading to PDA. This study is the first to focus on variants at the promoter region of the MYH6 gene in PDA patients with cellular function tests. Therefore, this study provides new insights to understand the genetic basis and facilitates further studies on the mechanism of PDA formation.

Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network.

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28 weeks but not among infants born at 22-25 weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.

Assessment of Blood Prostaglandin E2 Metabolite Levels among Infants Born Preterm with Patent Ductus Arteriosus: A Prospective Study.

OBJECTIVE: To assess the role of prostaglandin E2 by measuring blood prostaglandin E2 metabolite (PGEM) concentrations in preterm infants with patent ductus arteriosus (PDA). STUDY DESIGN: A prospective observational study of preterm infants born before 32 weeks of gestational age (GA) was performed in a single tertiary hospital in Japan. Blood samples were collected to measure serum concentrations of PGEM, ibuprofen (IBU), and cytokines. Multiple regression analyses assessed associations between blood PGEM levels and perinatal factors, development of hemodynamically significant PDA (hsPDA), and IBU treatment response of hsPDA. RESULTS: Seventy-nine infants (median GA 28 weeks) were enrolled in this study. Forty-seven received IBU for hsPDA treatment 1 d after birth in median. PDA closure occurred in 25 infants after a single IBU treatment. Serum PGEM concentrations were associated with histologic chorioamnionitis (P < .01), but not with GA, respiratory distress syndrome, or serum IL-6 concentrations. Serum PGEM concentrations decreased after initial IBU treatment; however, they were not associated with hsPDA development (P = .39). IBU concentrations correlated with IBU treatment response (aOR 1.29, P < .01). However, pre-IBU serum PGEM levels and PGEM reduction ratio did not (P = .13, .15, respectively). CONCLUSIONS: Serum PGEM concentrations in preterm infants were associated with maternal histologic chorioamnionitis, but not hsPDA development. IBU treatment response was associated with higher blood IBU concentrations, but not PGEM concentrations.

Cardiorespiratory Instability after Percutaneous Patent Ductus Arteriosus Closure: A Multicenter Cohort Study.

OBJECTIVE: To evaluate postprocedural clinical characteristics of preterm infants undergoing transcatheter patent ductus arteriosus (PDA) closure, including oxygenation/ventilation failure and cardiovascular compromise. STUDY DESIGN: Multicenter retrospective cohort study of preterm infants who were ≤2 kg at the time of percutaneous PDA closure between August 2018 and July 2021. Indices of cardiorespiratory stability were collected pre-closure, immediately post-closure, and subsequently averaged every 4 hours for the first 24 hours post-procedure. The primary outcome was incidence of post-transcatheter cardiorespiratory syndrome: composite of hemodynamic instability (defined by systemic hypotension, systemic hypertension, or use of new inotropes/vasopressors in the first 24 hours after catheterization) and at least one of the following: (i) ventilation failure or (ii) oxygenation failure. RESULTS: A total of 197 patients were included with a median [IQR] age and weight at catheterization of 34 [25, 43] days and 1090 [900, 1367] grams, respectively. The primary composite outcome of post-transcatheter cardiorespiratory syndrome was reported in 46 (23.3%). CONCLUSION: Post-transcatheter cardiorespiratory syndrome is characterized primarily by systemic hypertension and oxygenation failure, with a very low incidence of hypotension and need for inotropes.

Mobile bedside ductus arteriosus closure in severely premature neonates using only echocardiographic guidance.

BACKGROUND: Transcatheter closure of the patent ductus arteriosus (PDA) in premature infants is currently dependent on fluoroscopic guidance and transportation to the catheterization laboratory. AIM: We describe a new echocardiographically guided technique to allow our team to move to the bedside at the neonatal intensive care unit (NICU) of the referring center for percutaneous treatment of PDA in premature infants. METHODS: This is a single-center, retrospective, primarily descriptive analysis. Clinical details about the procedure, its outcomes, and complications were collected. RESULTS: Fifty-eight neonates with a median weight of 1110 g (range 730-2800) and postnatal age of 28 days (range 9-95) underwent percutaneous PDA closure. Five of them were treated in our center with ultrasound guidance only and the other 53 in 18 different neonatology units in 12 towns. The median duration of the procedure was 40 min (range 20-195 min). There were no procedural deaths. There was one residual shunt for 3 weeks, in all other patients the duct closed completely in the first few hours after the intervention. In one patient the procedure had to be interrupted because of a pericardial effusion which had to be drained, the PDA was closed successfully interventionally 5 days later. One device-related aortic coarctation had to be stented. One embolization and one late migration occurred and required treatment. CONCLUSIONS: Echocardiographically guided transcatheter closure of the PDA in prematures was repeatedly possible and allowed that the procedure is performed at the bedside at the NICU with an acceptable rate of complications.

Oral DHA supplementation and retinopathy of prematurity: the Joinville DHA Clinical Trial.

Retinopathy of prematurity (ROP) is a leading cause of blindness in premature infants. The condition is associated with DHA deficiency. This study aimed to investigate the effect of DHA supplementation on the occurrence of ROP in infants receiving oral oil drops. It is part of the Joinville DHA study, a non-parallel-group cohort study conducted from March 2020 to January 2023 at a public maternity hospital in Brazil. Infants born before 33 weeks of gestational age or with a birth weight ≤ 1500 g were recruited. Among 155 infants, 81 did not receive and 74 received DHA supplementation until complete vascularisation of the peripheral retina. There was a higher incidence of infants with ROP in the unsupplemented group (58·6 %) compared with the DHA group (41·4 %), but this difference was NS (P = 0·22). Unadjusted logistic regression analysis showed that patent ductus arteriosus and neonatal corticosteroids were significantly (P < 0·05) associated with ROP in both groups. In the DHA group, surfactant use was also associated with ROP (P = 0·003). After adjusting for important covariates, patent ductus arteriosus and neonatal corticosteroids continued to be significant for infants in the unsupplemented group (OR = 3·99; P = 0·022 and OR = 5·64; P = 0·019, respectively). In the DHA group, only surfactant use continued to be associated with ROP (OR = 4·84; P = 0·015). In summary, DHA supplementation was not associated with ROP. Further studies are necessary to better understand the relationship between DHA supplementation, ROP and associated comorbidities.

Whole-exome sequencing analysis of patent ductus arteriosus in a Japanese macaque (Macaca fuscata).

We performed whole-exome sequencing using a human exome capture kit to analyze the potential genetic factors related to patent ductus arteriosus in Japanese macaques. Compared with the reference sequences of other primates, we identified potential missense variants in five genes: ADAM15, AZGP1, CSPG4, TNFRSF13B, and EPOR.

Feasibility and Success of Muscular Ventricular Septal Defect Occluders and Mushroom-Shaped Occluders in Transcatheter Patent Ductus Arteriosus Closure in Low-Weight Children: A Propensity Score-Matched Retrospective Analysis from a Chinese National Regional Health Center.

INTRODUCTION: Muscular ventricular septal defect occluders (MVSDOs) have been attempted as an option in low-weight patients with patent ductus arteriosus (PDA). However, few studies have assessed the safety of transcatheter patent ductus arteriosus closure (TCPC) using MVSDO. Therefore, we compared the outcomes in low-weight patients who used MVSDO and mushroom-shaped occluder (MSO). METHODS: Medical records of children under 10 kg (n = 417) who underwent TCPC from 2015 to 2021 at a Chinese health center were reviewed. They were divided into MSO (n = 372) and MVSDO (n = 45) groups. A 1:1 propensity score matching (PSM) was done considering gender, height, weight, body surface area (BSA), PDA diameter, and BSA-corrected PDA diameter. RESULTS: All 45 children in the MVSDO group (mean weight: 5.92 ± 1.32 kg) achieved successful immediate occlusion. One case in the MVSDO group experienced device migration within 24 h requiring unplanned surgery. MVSDO significantly ameliorated pulmonary artery hypertension. After PSM, each group comprised 41 children. The MVSDO group had a smaller effect on platelet counts (MVSDO vs. MSO = 259.85 ± 114.82 vs. 356.12 ± 134.37, p < 0.001), a reduced incidence of thrombocytopenia (MVSDO vs. MSO = 2/41 vs. 7/41, p = 0.001), and a higher rate of residual shunting (MVSDO vs. MSO = 16/41 vs. 5/41, p = 0.005), compared with the MSO group. Thrombocytopenia resolved during hospitalization and micro-shunts disappeared by 6 months. No pulmonary artery or descending aortic secondary stenosis was observed in 1-year follow-up. CONCLUSIONS: MVSDO used in low-weight children is feasible, with high success and satisfactory postoperative and short-term follow-up outcomes, including lower thrombocytopenia incidence, compared to MSO. Further long-term studies with larger samples are recommended.

The investigation of thrombocytopenia after transcatheter occlusion of patent ductus arteriosus.

OBJECTIVE: To investigate the risk factors for thrombocytopenia after transcatheter occlusion operation of patent ductus arteriosus (PDA). METHOD: Retrospective analyses were conducted using clinical data from 106 patients with PDA who underwent transcatheter closure operations at Henan Provincial Chest Hospital, Zhengzhou University, from January 2018 to June 2022. The study compared the changes in platelet counts before and after the operation, and investigated the risk factors for thrombocytopenia following PDA closure in different groups and layers. RESULTS: The platelet count of patients with PDA significantly decreased after undergoing transcatheter PDA occlusion. Logistic regression analysis revealed that factors such as PDA diameter, occluder diameter, pressure difference on the two sides of the occluder, and residual shunt were associated with an increased risk of thrombocytopenia following PDA occlusion. Specifically, the size of the occluder and the pressure difference between the two sides of the occluder were found to have a negative correlation with the postoperative platelet count. Further subgroup analysis demonstrated that the incidence of total thrombocytopenia was significantly higher in the large PDA group compared to the small-medium PDA groups. CONCLUSION: Our findings suggest that occluder diameter, the pressure difference between the two sides of the occluder, and the residual shunt are major risk factors correlated with the incidence of postoperative thrombocytopenia. However, a multicenter and long-term prospective study is required to further evaluate the prognosis of PDA patients with thrombocytopenia after transcatheter occlusion.

Is Takotsubo syndrome induced by patent ductus arteriosus occlusion?

Takotsubo syndrome (TTS), commonly referred to as "broken heart syndrome," is a distinctive form of acute and reversible heart failure that primarily affects young to middle-aged individuals, particularly women. While emotional or physical stressors often trigger TTS, rare cases have been linked to interventional procedures for congenital heart disease (CHD). Despite its recognition, the exact causes of TTS remain elusive. Research indicates that dysregulation in autonomic nerve function, involving sympathetic and parasympathetic activities, plays a pivotal role. Genetic factors, hormonal influences like estrogen, and inflammatory processes also contribute, unveiling potential gender-specific differences in its occurrence. Understanding these multifaceted aspects of TTS is crucial for refining clinical approaches and therapies. Continued research efforts will not only deepen our understanding of this syndrome but also pave the way for more targeted and effective diagnostic and treatment strategies. In this report, we conduct an in-depth analysis of a case involving a TTS patient, examining the illness progression and treatment procedures. The aim of this analysis is to enhance the understanding of TTS among primary care physicians. By delving into this case, we aspire to prevent misdiagnosis of typical TTS cases that patients may present, thereby ensuring a more accurate diagnosis and appropriate treatment.

Patent ductus arteriosus and the association between lung ultrasound score and bronchopulmonary dysplasia: a secondary analysis of a prospective study.

Moderate-to-large patent ductus arteriosus (PDA) has been linked to increased risk of bronchopulmonary dysplasia (BPD), while lung ultrasound score (LUS) has been demonstrated to accurately predict BPD. We aimed to investigate the correlation of LUS as a marker of interstitial pulmonary edema and the severity of the ductal shunt in predicting future BPD development in very preterm infants. This secondary analysis of a prospective study recruited preterm infants with gestational age < 30 weeks. LUS on postnatal days 7 and 14, and echocardiographic data [PDA diameter and left atrium-to-aortic root ratio (LA/Ao)] near LUS acquisition were collected. Correlation coefficient, logistics regression analysis, and the area under the receiver operating characteristic (AUROC) procedure were used. A statistically significant and positive correlation existed between LUS and PDA diameter (ρ = 0.415, ρ = 0.581, and p < 0.001) and LA/Ao (ρ = 0.502, ρ = 0.743, and p < 0.001) at postnatal days 7 and 14, respectively, and the correlations of LUS and echocardiographic data were generally stronger in the non-BPD group. In the prediction of BPD, LUS incorporating echocardiographic data at postnatal days 7 obtained significantly higher predictive performance compared to LUS alone (AUROC 0.878 [95% CI 0.801-0.932] vs. AUROC 0.793 [95% CI 0.706-0.865]; Delong test, p = 0.013). CONCLUSIONS: There is a statistically significant correlation between LUS and echocardiographic data, suggesting their potential role as early predictors for respiratory outcomes in very preterm infants. WHAT IS KNOWN: • Lung ultrasound score (LUS) has shown good reliability in predicting bronchopulmonary dysplasia (BPD) development. • Some echocardiographic data that characterized ventricular function was reported to be used to predict severe BPD. WHAT IS NEW: • There is a positive and statistically significant correlation between LUS and echocardiographic data at postnatal days 7 and 14. • The integrated use of LUS and echocardiographic data may have potential value in predicting BPD.

Mortality and extrauterine growth restriction of necrotizing enterocolitis in very preterm infants with heart disease: a multi-center cohort study.

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6 weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC.     Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

Post-ligation cardiac syndrome after surgical versus transcatheter closure of patent ductus arteriosus in low body weight premature infants: a multicenter retrospective cohort study.

Transcatheter patent ductus arteriosus (PDA) closure is a safe and effective alternative to surgical ligation in low-body-weight infants. Post-ligation cardiac syndrome (PLCS) is defined as severe hemodynamic and respiratory collapse within 24 h of PDA closure, requiring initiation or an increase of an inotropic agent by > 20% of preligation dosing and an absolute increase of at least 20% in ventilation parameters compared with the preoperative value. Whilst PLCS is routinely observed after surgery, its incidence remains poorly described following transcatheter closure. This study aimed to compare the incidence of PLCS after surgical versus transcatheter closure of PDA in low-body-weight premature infants. Propensity scores were used to compare surgical (N = 78) and transcatheter (N = 76) groups of preterm infants who underwent PDA closure at a procedural weight less than 2000 g in two tertiary institutions between 2009 and 2021. The primary outcome was the incidence of PLCS. Secondary outcomes included overall mortality before discharge, risk factors for PLCS, and post-procedural complications. Procedural success was 100% in both groups. After matching, transcatheter group experienced no PLCS vs 15% in the surgical group (p = 0.012). Furthermore, overall mortality (2% vs 17%; p = 0.03) and major complications (2% vs 23%; p = 0.002) were higher in the surgical group. Surgery (100% vs 47%; p < 0.01), gestation age (25 ± 1 vs 26 ± 2 weeks, p < 0.05) and inotropic support before closure (90% vs 29%; p < 0.001) were associated with PLCS occurrence.          Conclusion: Transcatheter PDA closure may be equally effective but safer than surgical PDA closure in low-body-weight premature infants. What is Known: • Post-ligation cardiac syndrome is a serious and common complication of surgical closure of the ductus arteriosus in preterm infants. • Transcatheter closure of preterm ductus arteriosus is a safe and effective technique that is becoming more and more common worldwide. What is New: • Device closure is safer than surgical ligation for patent ductus arteriosus closure in preterm infants and may be the first-line non-pharmacological therapeutic option in this indication in experienced teams. • Our findings should encourage neonatologists and pediatric cardiologists to start and/or strengthen a durable interventional program for transcatheter PDA closure in premature infants.

Impact of antenatal corticosteroids-to-delivery interval on very preterm neonatal outcomes: a retrospective study in two tertiary centers in Japan.

BACKGROUND: Antenatal corticosteroids (ACS) are administered to prevent neonatal complications and death in women at risk of imminent preterm birth. Internationally, the optimal interval from ACS to delivery (ACS-to-delivery interval) is within seven days; however, evidence in Asian populations specifically is limited. This study aimed to investigate the association between ACS-to-delivery interval and the incidence of neonatal complications in Japan. METHODS: This retrospective observational study enrolled singleton neonates born preterm at < 32 weeks of gestational age between 2012 and 2020 at two tertiary centers. A total of 625 neonates were divided into the following four groups according to the timing of ACS (measured in days): no ACS (n = 145), partial ACS (n = 85), ACS 1-7 (n = 307), and ACS ≥ 8 (n = 88). The following outcomes were compared between the groups: treated respiratory distress syndrome (RDS), severe intraventricular hemorrhage (IVH), treated patent ductus arteriosus (PDA), necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (ROP), periventricular leukomalacia, and death discharge. RESULTS: The ACS 1-7 group had significantly decreased adjusted odds ratios (ORs) for treated RDS (0.37 [95% confidence interval: 0.23, 0.57]), severe IVH (0.21 [0.07, 0.63]), treated PDA (0.47 [0.29, 0.75]), and treated ROP (0.50 [0.25, 0.99]) compared with the no ACS group. The ACS ≥ 8 group also showed significantly reduced adjusted ORs for RDS (0.37 [0.20, 0.66]) and treated PDA (0.48 [0.25, 0.91]) compared with the no ACS group. However, the adjusted ORs for BPD significantly increased in both the ACS 1-7 (1.86 [1.06, 3.28]) and ACS ≥ 8 groups (2.94 [1.43, 6.05]) compared to the no ACS group. CONCLUSIONS: An ACS-to-delivery interval of 1-7 days achieved the lowest incidence of several complications in preterm neonates born at < 32 weeks of gestational age. Some of the favorable effects of ACS seem to continue even beyond ≥ 8 days from administration. In contrast, ACS might be associated with an increased incidence of BPD, which was most likely to be prominent in neonates delivered ≥ 8 days after receiving ACS. Based on these findings, the duration of the effect of ACS on neonatal complications should be studied further.

Patent Ductus Arteriosus and Development of Bronchopulmonary Dysplasia-associated Pulmonary Hypertension.

Rationale: Extremely preterm infants with evolving bronchopulmonary dysplasia (BPD) are at risk for development of BPD-associated pulmonary hypertension (BPD-PH). A patent ductus arteriosus (PDA) shunt may be a modifiable risk factor for BPD-PH development. Objective: To determine whether the presence and duration of ductus arteriosus patency differs between extremely preterm infants with and without BPD-PH. Methods: We conducted a retrospective case-control study among preterm infants of gestational age 22 weeks, 0 days, to 28 weeks, 6 days, who remained on respiratory support on postnatal day 28 at the University of Alabama at Birmingham from 2017 to 2020. Infants who were diagnosed with PH (cases) by echocardiography were compared with infants without PH (control subjects). Data from echocardiograms performed during the hospitalization after postnatal day 28 were included. Logistic regression adjusted for covariates that differed significantly between groups. A probit analysis related the duration of ductal patency to the development of BPD-PH. Measurements and Main Results: A total of 138 infants developed BPD alone, and 82 infants developed BPD-PH. After adjustment for differing covariates between groups, both PDA (adjusted odds ratio, 4.29; 95% confidence interval, 1.89-9.77) and moderate to large PDA (adjusted odds ratio, 4.15; 95% confidence interval, 1.78-9.64) remained significantly related to BPD-PH at discharge. By probit analysis, each additional month of PDA and hemodynamically significant PDA exposure was associated with an increased probability for the composite outcome of BPD-PH at discharge or death with coefficients of 0.40 (P < 0.001) and 0.45 (P < 0.001), respectively. Conclusions: In extremely preterm infants on respiratory support on postnatal day 28, both the presence of and a longer duration of ductus arteriosus patency were associated with the development of BPD-PH.

Comparison of neurally adjusted ventilatory assist and synchronized intermittent mandatory ventilation in preterm infants after patent ductus arteriosus ligation: a retrospective study.

OBJECTIVE: This study aimed to compare the efficacy of neurally adjusted ventilatory assist (NAVA) to synchronized intermittent mandatory ventilation (SIMV) in preterm infants requiring mechanical ventilation after patent ductus arteriosus (PDA) ligation. METHODS: A retrospective analysis was conducted on intubated preterm infants who underwent PDA ligation at our hospital from July 2021 to January 2023. Infants were divided into NAVA or SIMV groups based on the ventilation mode after surgery. RESULTS: Fifty preterm infants were included. During treatment, peak inspiratory pressure (PIP) and mean airway pressure (MAP) were lower with NAVA compared to SIMV (PIP: 19.1 ± 2.9 vs. 22.4 ± 3.6 cmH2O, P < 0.001; MAP: 9.1 ± 1.8 vs. 10.9 ± 2.7 cmH2O, P = 0.002). PaO2 and PaO2/FiO2 were higher with NAVA (PaO2: 94.0 ± 11.7 vs. 84.8 ± 15.8 mmHg, P = 0.031; PaO2/FiO2: 267 [220-322] vs. 232 [186-290] mmHg, P = 0.025). Less sedation was required with NAVA (midazolam: 1.5 ± 0.5 vs. 1.1 ± 0.3 µg/kg/min, P < 0.001). CONCLUSION: Compared to SIMV, early use of NAVA post PDA ligation in preterm infants was associated with decreased PIP and MAP. Early NAVA was also associated with reduced sedation needs and improved oxygenation. However, further studies are warranted to quantify the benefits of NAVA ventilation.

Risk factors for PDA ligation and neurodevelopmental outcomes at corrected 18-24 months in very low birth weight infants.

BACKGROUND: Patent ductus arteriosus (PDA) is commonly encountered morbidity which often occurs as up to 60% of extremely preterm infants born at < 29 weeks gestational age (GA). PURPOSE: This study aims to assess the clinical risk factors associated with PDA ligation among very low birth weight infants (VLBWI) and evaluate the neurodevelopmental outcomes of those who underwent PDA ligation. METHODS: A total of 540 VLBWI were initially diagnosed with PDA in our 50-bed level IV NICU at Seoul St. Mary's Hospital, The Catholic University of Korea, between January 2015 and June 2023. Among these 540 VLBWI with PDA, only 221 had consistent hemodynamically significant (hs) PDA which required intervention including fluid restriction, medical treatment, or surgical ligation. In this study, only those 221 VLBWI with hsPDA who underwent neurodevelopmental assessment at corrected 18-24 months of age were included in this study analysis. RESULTS: Out of 221 VLBWI diagnosed with hemodynamically significant (hs) PDA, 133 (60.2%) underwent PDA ligation, while the remaining 88 (39.8%) had their hs PDAs closed either medically or with fluid restriction. The mean gestational age and birth weight were significantly lower in PDA ligation group compared to no PDA ligation group (27.02 ± 2.17 vs. 27.98 ± 2.36, 907.31 ± 258.36 vs. 1006.07 ± 283.65, p = 0.001, 0.008). Resuscitation including intubation at delivery and intraventricular hemorrhage (IVH) (grade ≥ 3) were significantly higher in PDA ligation group. The clinical outcomes in the PDA ligation group revealed significantly worse oucomes compared to the no PDA ligation group. Both resuscitation, including intubation at delivery, and IVH (grade ≥ 3), consistently exhibited an increased risk for PDA ligation in a multivariable logistic regression analysis. Concerning neurodevelopmental outcomes, infants who underwent PDA ligation demonstrated significantly lower cognitive scores. However, only IVH (grade ≥ 3) and PVL were consistently associated with an increased risk of abnormal neurodevelopment at the corrected age of 18-24 months. CONCLUSION: In our study, despite the consistent association between cognitive developmental delays in VLBWI who underwent PDA ligation, we observed that sicker and more vulnerable VLBWIs, specifically those experincing severe IVH, consistently exhibited an increased risk for both PDA ligation and abnormal neurodevelopment at the corrected age of 18-24 months.

Mind the gap-missing device on the shelf? Retrospective experience with 5/7 Occlutech duct Occluder.

AIM: To describe our initial experience with the indications and results of the 5/7 Occlutech® duct Occluder (ODO, Occlutech International AB, Helsingborg, Sweden). A small incremental increase in occluder sizes is of utmost importance for successful outcomes, especially in smaller patients in whom protrusion of the distal disk towards the aorta should be minimised. METHODS: Retrospective study of all patients undergoing PDA closure with the 5/7 ODO in three institutions since 2018. RESULTS: The 5/7 ODO was used in 18 patients with median age and weight at the time of the procedure of 17.5 months (interquartile range 25th to 75th percentile 8 months- 4.4 years) and 13.6 kg (interquartile range 25th to 75th percentile 6.4-22.5 kg) respectively. All cases were successful. There were no cases of device embolisation, haemolysis, or flow disturbance of the LPA or the aorta. CONCLUSIONS: This small retrospective study demonstrated an excellent outcome of transcatheter PDA closure with the 5/7 ODO. The device is a beneficial complement to the existing sizes of PDA devices, filling the gap between the 4/6 and 6/8 ODO and avoiding protrusion of a larger disk in the aortic isthmus.

The Bronchopulmonary Dysplasia score: A predictive model for bronchopulmonary dysplasia or death in high-risk preterm infants.

AIM: Progressive respiratory deterioration in infants at high risk of bronchopulmonary dysplasia (BPD) is associated with patent ductus arteriosus (PDA) exposure. This study aimed to design an early predictive model for BPD or death in preterm infants using early echocardiographic markers and clinical data. METHODS: Infants born with gestational age (GA) ≤ 29 weeks and/or birth weight (BW) < 1500 g at Cork University Maternity Hospital, Ireland were retrospectively evaluated. Those with echocardiography performed between 36 h and 7 days of life were eligible for inclusion. Exclusion criteria were pulmonary hypertension and major congenital anomalies. The primary outcome was a composite of BPD and death before discharge. RESULTS: The study included 99 infants. A predictive model for the primary outcome was developed, which included three variables (BW, Respiratory Severity Score and flow pattern across the PDA), and yielding an area under the curve of 0.98 (95% CI 0.96-1.00, p < 0.001). Higher scores were predictive of the primary outcome. A cut-off of -1.0 had positive and negative predictive values of 89% and 98%, and sensitivity and specificity of 98% and 88%, respectively. CONCLUSION: Our prediction model is an accessible bedside tool that predicts BPD or death in premature infants.

Renal function after ductus arteriosus transcatheter closure with or without angiography in very preterm infants.

AIM: Transcatheter closure of the patent ductus arteriosus (TCPDA) is increasingly used in preterm infants as an alternative to surgical ligation. However, clinically ill preterm infants are at risk of contrast nephropathy due to the angiography contrast agents used during the procedure. METHODS: We performed a single-centre before-and-after comparative study in VLBW infants to compare the kinetics of serum creatinine during the first 4 days after TCPDA with or without angiography. RESULTS: 69 patients were included and divided into two groups: TCPDA with (contrast+; n = 37) and without (contrast-, n = 32) use of contrast agent. The median dose [range] of contrast agent was 1.0 mL/kg [0.6-2.4 mL/kg]. The change in serum creatinine level between day 2 to 4 after TCPCA and baseline decreased in the contrast- group (-17% [-46%; 18%]), while it increased in the contrast+ group (7% [-24%; 202%] p = 0.002). Comparison of blood urea levels between groups showed similar significant differences. The change in serum creatinine between day 2 to 4 and baseline was significantly correlated with the dose of contrast agent (r2 = 0.682; p < 0.001). CONCLUSION: The use of contrast agents during TCPDA can potentially harm the renal function of very preterm infants. Therefore, we advise minimising or avoiding the use of contrast agents.