Actual electrolyte intake during the first week of life and morbidity in very-low-birthweight infants.

AIM: To describe sodium and potassium intake, their sources and plasma concentrations, and the association between intake and morbidity in very-low-birthweight (VLBW, <1500 g) infants during the first week of life. METHODS: This retrospective cohort study comprised 951 VLBW infants born at <32 weeks. Infants were divided into three groups according to gestational age: 23-26 (n = 275), 27-29 (n = 433) and 30-31 (n = 243) weeks. Data on fluid management and laboratory findings were acquired from an electronic patient information system. RESULTS: The median sodium intake was highest in the 23-26 week group, peaking at 6.4 mmol/kg/day. A significant proportion of sodium derived from intravascular flushes; it reached 27% on day 1 in the 23-26 week group. High cumulative sodium intake in the first postnatal week was associated with weight gain from birth to day 8 in the 23-26 week group. High intake of sodium associated with an increased risk of surgically ligated patent ductus arteriosus (PDA), bronchopulmonary dysplasia and intraventricular haemorrhage, whereas low intake of potassium associated with an increased risk of PDA. CONCLUSION: Sodium intake in the most premature infants exceeded recommendations during the first postnatal week. Saline flushes accounted for a significant proportion of the sodium load.

Risk factors for severe bronchopulmonary dysplasia in a Chinese cohort of very preterm infants.

OBJECTIVES: To examine the risk factors for severe bronchopulmonary dysplasia (BPD) in a cohort of very preterm infants (VPIs) in China, as BPD is common among VPIs and associated with a high mortality rate. METHODS: In this multicenter retrospective study, medical records from infants with BPD born at gestation age (GA) of <32 weeks with birth weight (BW) of <1,500 grams (g) in 7 regions of China were included. The cohort was stratified into different BPD severity groups based on their fraction of inspired oxygen requirement at a modified GA of 36 weeks or post discharge. Risk factors were identified using logistic regression analysis. RESULTS: A significant inverse correlation was revealed between BPD severity and both GA and BW (p<0.001). Independent risk factors for severe BPD (sBPD) were identified as invasive mechanical ventilation (≥7d), multiple blood transfusion (≥3), nosocomial infection (NI), hemodynamically significant patent ductus arteriosus (hsPDA), delayed initiation of enteral nutrition, and longer time to achieve total caloric intake of 110 kcal/kg. Conversely, administration of antenatal steroids was associated with reduced risk of sBPD. CONCLUSION: Our study not only reaffirmed the established risk factors of low GA and BW for sBPD in VPIs, but also identified additional, potentially modifiable risk factors. Further research is warranted to explore whether intervention in these modifiable factors might reduce the risk of sBPD.Clinical Trial Reg. No.: ChiCTR1900023418.

Active versus restrictive ligation strategy for patent ductus arteriosus - A retrospective two-center study of extremely preterm infants born between 22 + 0 and 25 + 6 weeks of gestational age.

BACKGROUND: Patent ductus arteriosus (PDA) in premature infants is associated with adverse clinical outcomes. Mode and timing of treatment are still controversial. Data are limited in the most extremely premature infants <26 weeks of gestational age (GA), where clinical problems are most significant and patients are most vulnerable. AIMS: To investigate whether different approaches to surgical closure of PDA in two large Swedish centers has an impact on clinical outcomes including mortality in extremely preterm infants born <26 weeks GA. STUDY DESIGN: Retrospective, two-center, cohort study. SUBJECTS: Infants born at 22+0-25+6 weeks GA between 2010 and 2016 at Uppsala University Children's Hospital (UUCH; n = 228) and Queen Silvia Children's Hospital Gothenburg (QSCHG; n = 220). MAIN OUTCOME MEASURES: Survival, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP). RESULTS: Surgical closure of PDA was more common and performed earlier at QSCHG (50 % vs 16 %; median age 11 vs 44 days; p < 0.01). Survival was similar in both centres. There was a higher incidence of severe BPD and longer duration of mechanical ventilation at UUCH (p < 0.01). There was a higher incidence of ROP, IVH and sepsis at QSCH (p < 0.05, p < 0.01 and p < 0.01). A sub-group analysis matching all surgically treated infants at QSCHG with infants at UUCH with the same GA showed similar results as the total cohort. CONCLUSION: Earlier and higher rate of surgical PDA closure in this cohort of extremely preterms born <26 weeks GA did not impact mortality but was associated with lower rates of severe BPD and higher rates of severe ROP.

Factors affecting length of stay according to bronchopulmonary dysplasia severity: a nationwide cohort study in Korea.

BACKGROUND: Longer hospitalizations for preterm infants with bronchopulmonary dysplasia (BPD) delay developmental outcomes, increase the risk for hospital-acquired complications, and exert a substantial socioeconomic burden. This study aimed to identify factors associated with an extended length of stay (LOS) at different levels of severity of BPD. METHODS: A cohort study was conducted using the Korean Neonatal Network registry of very low birth weight infants with BPD between 2013 and 2017 through retrospective analysis. RESULTS: A total of 4263 infants were diagnosed with BPD. For mild BPD, infants requiring surgical treatment for patent ductus arteriosus needed a longer LOS [eadjusted ß coefficients (adj ß) 1.041; 95% confidence interval (CI): 0.01-0.08] and hydrocephalus (eadj ß 1.094; 95% CI 0.01-0.17). In moderate BPD, infants administered steroids or with intraventricular hemorrhage required a longer LOS (eadj ß 1.041; 95% CI 0.00-0.07 and eadj ß 1.271; 95% CI 0.11-0.38, respectively). In severe BPD, infants with comorbidities required a longer LOS: pulmonary hypertension (eadj ß 1.174; 95% CI 0.09-0.23), administrated steroid for BPD (eadj ß 1.116; 95% CI 0.07-0.14), sepsis (eadj ß 1.062; 95% CI 0.01-0.11), patent ductus arteriosus requiring surgical ligation (eadj ß 1.041; 95% CI 0.00-0.08), and intraventricular hemorrhage (eadj ß 1.016; 95% CI 0.05-0.26). Additionally, the higher the clinical risk index score, the longer the LOS needed for infants in all groups. CONCLUSIONS: The factors affecting LOS differed according to the severity of BPD. Individualized approaches to reducing LOS may be devised using knowledge of the various risk factors affecting LOS by BPD severity.

Factors associated with the response to postnatal dexamethasone use in very low birthweight infants: a nationwide cohort study.

BACKGROUND: Dexamethasone is widely used as a systemic corticosteroid to treat and prevent bronchopulmonary dysplasia (BPD) in preterm infants. We evaluated the current epidemiology of dexamethasone use to prevent BPD and analyse the factors associated with the response to dexamethasone in very low birthweight infants using a nationwide database. METHODS: We included very low birthweight infants born between January 2013 and December 2020 with a gestational age of 23-31 weeks using data from the Korean Neonatal Network registry. Patients were grouped based on their dexamethasone use into 'Dex' or 'No Dex' groups. Clinical variables and data were collected, and the annual trends of dexamethasone use and the proportion of patients who received dexamethasone according to gestational age were analysed. Respiratory outcomes were compared between the groups. Univariate and multivariate analyses were performed to analyse factors associated with the response to dexamethasone in BPD. RESULTS: Of 11 261 eligible infants, 2313 (20.5%) received dexamethasone, and 1714 (74.1%) of them were diagnosed with moderate-to-severe BPD. The 8-year annual prevalence of dexamethasone use was 17.7-22.3%. The 'Dex' group had more moderate-to-severe BPD, more frequent invasive ventilation use at a postmenstrual age of 36 weeks and longer ventilator duration. Birth weight, 5-minute APGAR score, pulmonary hypertension within the first 28 days, surgical treatment of patent ductus arteriosus, medical treatment of patent ductus arteriosus, pathological chorioamnionitis, hydrocortisone or budesonide use, surgical management of necrotising enterocolitis and fungal sepsis were associated with BPD after dexamethasone use. CONCLUSIONS: Approximately 20.5% of preterm infants received dexamethasone, and the frequency increased as gestational age decreased. Poor response to dexamethasone was associated with antenatal and postnatal inflammation, low birth weight and early pulmonary hypertension.

Patent Ductus Arteriosus and Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension: A Bayesian Meta-Analysis.

Importance: Bronchopulmonary dysplasia (BPD) is often associated with pulmonary vascular disease and secondary pulmonary hypertension (PH). The pathogenesis of BPD-associated PH (BPD-PH) is complex and involves prenatal and postnatal factors that disrupt pulmonary vascular development, and patent ductus arteriosus (PDA) is a factor potentially associated with risk of BPD-PH that has been identified in very recent studies. Objective: To explore the association of PDA with BPD-PH using a bayesian model-averaged (BMA) meta-analysis of studies. Data Sources: PubMed and Embase were searched up to April 2023. Key search terms included BPD and PH. Study Selection: Studies examining infants with gestational age 32 weeks or less and reporting data on PDA and risk of BPD-PH. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-Analysis of Observational Studies in Epidemiology reporting guidelines. Two independent reviewers extracted data, with a third reviewer checking for accuracy and completeness. Data pooling and effect size calculations were performed by BMA. Main Outcomes and Measures: The primary outcome was BPD-PH. BMA was used to calculate Bayes factors (BFs). The BF10 is the ratio of the probability of the data under the alternative hypothesis (H1, association of PDA with BPD-HP) over the probability of the data under the null hypothesis (H0). Results: A total of 32 studies (8513 infants) were included. BMA showed that the evidence in favor of H1 was weak for any PDA (BF10 = 2.90; 10 studies), moderate for hemodynamically significant PDA (BF10 = 3.77; 3 studies), and extreme for surgically ligated or catheter-occluded PDA (BF10 = 294.9; 16 studies). In contrast, the evidence in favor of H0 was weak for medically treated PDA (BF10 = 0.55; 6 studies). In addition, BMA found strong evidence in favor of H1 when prolonged exposure to PDA was analyzed as a dichotomous variable (BF10 = 11.80; 6 studies) and extreme evidence (BF10 = 113.60; 3 studies) when PDA exposure time was analyzed as a continuous variable. Conclusions and Relevance: In this bayesian meta-analysis, the data suggest that prolonged exposure to PDA might be associated with increased risk of pulmonary vascular disease in extremely preterm infants. This highlights the need to monitor for PH in high-risk preterm infants with prolonged exposure to PDA and to incorporate PH risk into clinical decisions regarding PDA management.

[Assessment of risk factors for bronchopulmonary dysplasia with pulmonary hypertension and construction of a prediction nomogram model].

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ2 test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.

Pediatric Cardiac Surgery in Ethiopia: A Single Center Experience in a Developing Country.

Background: In developing countries, the diagnosis of congenital heart diseases (CHD) is growing as the availability of echocardiography is increasing with most diagnoses made after birth. However, the access to pediatric surgery is still low and is mainly done by global surgical campaigns rather than local surgeons. Ethiopia has trained its local surgeons, and this is expected to improve the care of children with CHD. We aimed to evaluate the experience of local pediatric CHD surgery and its outcome in a single-center in Ethiopia. Methods: A hospital-based retrospective cohort study was done by including all patients with CHD and acquired heart disease in patients under the age of 18 operated at children's cardiac center in Addis Ababa Ethiopia. We set in-hospital mortality, 30-day mortality, and the prevalence of complications including major complications after cardiac surgery as the primary outcomes. Results: A total of 76 children were operated. The mean age at the time of diagnosis and surgery was 4 (±5) and 7 (±5) years, respectively. Forty-one (54%) were female. Ninety five percent of the 76 operated children were with the diagnoses of congenital heart diseases while the rest (5%) with acquired heart disease. Of those with congenital heart disease, Patent ductus arteriosus (PDA) accounted for (33.3%), Ventricular septal defect (VSD) for 29.5% and Atrial Septal Defect (ASD) for 10% and Tetralogy of Fallot (TOF) for 5%. According to the RACS-1 category, 26 (35.1%) were in category 1, 33 (44.6%) were in category 2, 15 (20.3%) were in category 3 and none of the children were in category 4 and 5. In-hospital mortality was 2.6% whereas there was no patient who died within 30 days after discharge. Operative mortality was 2.6%. Conclusions: Various types of lesions were treated in the hands of the local teams with VSD and PDA ligations as the commonest of all. The 30day mortality was within acceptable range and this outcome shows congenital and acquired heart diseases can be operated on in developing countries with good outcome despite the limited resources.

Association between gastrointestinal perforation and patent ductus arteriosus in extremely-low-birth-weight infants: a retrospective study of our decade-long experience.

PURPOSE: Management of persistently patent ductus arteriosus (PDA) in extremely low-birth-weight infants (ELBWIs) requires attention due to the risk of tissue hypoperfusion. We investigated the association between PDA and gastrointestinal perforation. METHODS: We performed a retrospective chart review from 2012 to 2021. Preterm (≤ 32 weeks) ELBWIs with PDA after birth who developed necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and idiopathic gastric perforation were included; ELBWIs with congenital heart disease were excluded. Data were analyzed using chi-squared tests with Yates; correction, and Student's t test. RESULTS: Five hundred thirty-five preterm ELBWIs were analyzed, including 20 with NEC, 22 with FIP, and 1 with gastric perforation. In NEC and FIP, the ductus arteriosus remained open in 40% (4/10) and 63.6% (14/22) of cases, respectively, and cyclo-oxygenase inhibitor treatment showed poor efficacy (p = 0.492 and 0.240). The incidence of perforation in NEC (4/9 vs. 6/11, p = 0.653), mortality in NEC (3/4 vs. 3/6, p = 0.895) and FIP (6/14 vs. 3/8, p = 0.838) did not differ according to whether the PDA persisted or resolved. CONCLUSION: The presentation of PDA did not affect the mortality or morbidity of ELBWIs. However, it is essential to consider the possibility of gastrointestinal perforation due to decreased organ blood flow caused by ductal steal.

The incidence of recurrent laryngeal nerve injury resulting in vocal cord paralysis following interventional congenital catheterisation procedures.

BACKGROUND: Recurrent laryngeal nerve injury leading to vocal cord paralysis is a known complication of cardiothoracic surgery. Its occurrence during interventional catheterisation procedures has been documented in case reports, but there have been no studies to determine an incidence. OBJECTIVE: To establish the incidence of left recurrent laryngeal nerve injury leading to vocal cord paralysis after left pulmonary artery stenting, patent ductus arteriosus device closure and the combination of the procedures either consecutively or simultaneously. METHODS: Members of the Congenital Cardiovascular Interventional Study Consortium were asked to perform a retrospective analysis to identify cases of recurrent laryngeal nerve injury after the aforementioned procedures. Twelve institutions participated in the analysis. They also contributed the total number of each procedure performed at their respective institutions for statistical purposes. RESULTS: Of the 1337 patients who underwent left pulmonary artery stent placement, six patients (0.45%) had confirmed vocal cord paralysis. 4001 patients underwent patent ductus arteriosus device closure, and two patients (0.05%) developed left vocal cord paralysis. Patients who underwent both left pulmonary artery stent placement and patent ductus arteriosus device closure had the highest incidence of vocal cord paralysis which occurred in 4 of the 26 patients (15.4%). Overall, 92% of affected patients in our study population had resolution of symptoms. CONCLUSION: Recurrent laryngeal nerve injury is a rare complication of left pulmonary artery stent placement or patent ductus arteriosus device closure. However, the incidence is highest in patients undergoing both procedures either consecutively or simultaneously. Additional research is necessary to determine contributing factors that might reduce the risk of recurrent laryngeal nerve injury.

Outcomes among preterm infants with patent ductus arteriosus: Relationship with treatment, gestational age, hemodynamic status and timing of treatment.

BACKGROUND: There remains controversy regarding the outcomes resulting from treatment versus conservative management of patent ductus arteriosus (PDA) among preterm infants. The effects of extreme prematurity, hemodynamic status of the PDA, and age at treatment remain poorly defined. STUDY DESIGN: This retrospective case-control study including infants < 1250 gm who were categorized into 3 groups: Group 1: without PDA, Group 2: with untreated PDA, and Group 3: treated PDA. Diagnosis and treatment of PDA extracted from the medical records. Demographics, clinical characteristics, and outcomes compared using chi-square and analysis of variance. Logistic regression used to estimate adjusted odds ratios. RESULTS: The study included 734 infants, with 141(19%) in Group 1, 329 (45%) in 2, and 264 (36%) in 3. Group 3 had higher incidence of bronchopulmonary dysplasia (BPD) (aOR, 2.9; 95%CI 1.7-4.8). Infant treated for hemodynamically significant PDA (HSPDA) had higher incidence of BPD (aOR, 1.9; 95%CI 1.0-3.8) and retinopathy of prematurity (ROP) (aOR, 3.4; 95%CI 1.6-6.9). There were no differences in outcome associated with treatment among≤26 weeks gestation and the age when treated. CONCLUSION: Infants with PDA who were treated had higher incidence of BPD. Among those who were treated, those with HSPDA had a higher incidence of BPD and ROP.

Trends in patent ductus arteriosus ligation in neonates and changes in outcomes: A 10-year multicenter experience.

RATIONALE: The management of neonates with patent ductus arteriosus (PDA) has changed over time. METHODS: We conducted a single-city, retrospective review of neonates who underwent PDA ligation over a 10-year time period and compared infants from the first 5 years to the second 5 years to evaluate how clinical characteristics changed over this time. RESULTS: Infants from the second 5-year epoch were older at time of ligation (38 vs. 30 days), had a higher ligation weight (1432 vs. 1121 g) and a lower incidence of postligation cardiac syndrome (1.9% vs. 11.5%). No differences in mortality, length of hospital-stay or major morbidities were seen. Compared to neonates who underwent PDA ligation at ≤28 days of life, those with a ligation age >28 days had a higher ligation weight (1421 vs. 1039 g), a higher proportion of COX inhibitor use (92.5% vs. 83.8%), and a higher incidence of moderate-severe bronchopulmonary dysplasia (BPD) (60.4% vs. 44.4%). Only 10.7% (25/233) patients were evaluated by laryngoscopy, in which the incidence of vocal cord paralysis (VCP) was 36.0%; 2 patients were clinically diagnosed with VCP for a total 4.7% incidence of VCP (11/233). CONCLUSIONS: Over the 10 years examined, neonates underwent PDA ligation at an older age in the second 5-year time period; this change was not associated with a change in the incidence of major morbidities. Ligation age >28 days was associated with an increase incidence of moderate-severe BPD. The overall incidence of documented VCP post-PDA ligation was relatively low but was seen in over 1/3 who were evaluated by laryngoscopy.

Surgical management of patent ductus arteriosus in pre-term infants - a british paediatric surveillance study.

BACKGROUND: This study aimed to provide UK data describing the incidence of patent ductus arteriosus (PDA) surgery in the neonatal population, including: pre-ligation management, and outcomes until discharge. We used British Paediatric Surveillance Unit (BPSU) methodology; collecting data via questionnaires for preterm neonates undergoing PDA ligation (PDAL) between 1st Sept 2012 - 30th Sept 2013. Infants born less than 37 weeks gestation, who underwent PDAL prior to discharge home, with no other structural cardiac abnormality, were included. Information collected included: patient demographics, pre and post-operative clinical characteristics, pre-operative medical management, post-operative complications and outcome. RESULTS: Over the study, 263 infants underwent PDAL an incidence of 3.07 per 10,000 live births. 88% were born extremely preterm (< 28 weeks) and 60% were male. The commonest reasons for ligation were inability to wean respiratory support (83.7%) and haemodynamically significant PDA (87.8%). Pre-operatively 65.7% received medical therapy. Surgery was performed at a median age of 33 days (range 9-260, IQR 24-48); the corrected age was less than 31 + 6 week in 50.6% babies at PDAL. Most, (90%), of procedures were open ligation; only 9 (3.4%) were catheter occlusions (PDACO). 20.5% of patients had post-operative complications. The 30-day mortality was 3%, with 93.5% surviving to hospital discharge. CONCLUSION: This study showed there was little consensus over medical and surgical management of the PDA or timing of surgery.

Protective factors against preterm infants to develop significant patent ductus arteriosus.

BACKGROUND: Identifying preterm infants with a higher likelihood of spontaneous patent ductus arteriosus (PDA) closure would be desirable. This study aimed to examine daily PDA status during the first week of life for very low birthweight (VLBW, <1500 g) preterm infants and to develop a scoring system to predict spontaneous PDA closure. METHODS: We enrolled VLBW infants admitted between January 2016 and January 2017 and performed daily echocardiographic screening for PDA existence. Oxygen index (OI, mean airway pressure × fraction of inspired oxygen/partial pressure of arterial oxygen) was applied to represent the respiratory condition. RESULTS: A total of 215 VLBW infants were enrolled, and the accumulative incidence of spontaneous PDA closure by age 1 week was 80%, 70%, and 34% for infants born of gestational age (GA) ≥30, 28-29, and ≤27 weeks, respectively. Of these 215 infants, 184 infants entered the second phase to establish the scoring system. Infants with spontaneous PDA closure were more mature (GA 29.2 ± 2.3 vs. 26.9 ± 2.3 weeks, p < 0.001), had lower OI (2.8 ± 2.2 vs. 5.6 ± 5.3, p < 0.001) and were less likely to need endotracheal intubation (23% vs. 68%, p < 0.001). Using the receiver operating characteristics curve, OI <2.5 was determined favoring higher PDA closure incidence. The score was calculated based on the odds ratio generated in multiple regression: 4, 3 and 1 points for GA ≥30, 28-29 and ≤27 weeks, 2 and 1 points for OI <2.5 and ≥2.5, and 3 and 1 points for without and with endotracheal intubation. Using score ≥6 to predict PDA closure, the sensitivity and specificity were 0.77 and 0.72. CONCLUSION: A score made up of GA, OI and need for intubation was proposed to predict spontaneous PDA closure by age 1 week, which could be helpful to clinicians in the management of PDA in preterm infants.

Patent ductus arteriosus treatment trends and associated morbidities in neonates.

To evaluate national epidemiologic data on infants treated for patent ductus arteriosus (PDA) in Korea and analyze outcomes associated with different PDA treatments. We retrospectively evaluated data on 12,336 patients diagnosed with PDA (International Classification of Diseases-10 code: Q250) between 2015 and 2018 from the Health Insurance Review and Assessment database. Among them, 1623 patients underwent surgical ligation (code: O1671). We used birth certificate data from Statistics Korea to estimate the prevalence, diagnosis, and treatment of PDA. The prevalence of infants with PDA was 81 infants per 10,000 live births and 45.2% in very low birth weight (VLBW) infants, which increased from 2015 to 2018. PDA ligation was performed in 2571 infants and 22% VLBW infants. Medical treatment was administered to 4202 infants, which decreased significantly, especially in VLBW infants (62% to 53%). The proportion of treatment was as follows: conservative treatment (53.1%), intravenous ibuprofen (24.4%), surgery (20.4%), and oral ibuprofen (10.7%); that among 4854 VLBW infants was as follows: intravenous ibuprofen (46.3%), conservative treatment (33.2%), surgery (22.2%), and oral ibuprofen (14.2%). Surgical treatment had a significantly higher risk (odds ratio 1.36) of mortality than conservative treatment. Surgical and/or medical treatments were associated with a higher risk of morbidity. Recently, increased use of conservative management of PDA has contributed to improved neonatal outcomes in VLBW infants. Select patients may still benefit from surgical ligation following careful consideration.

Changes in Patent Ductus Arteriosus Treatment Strategy and Respiratory Outcomes in Premature Infants.

OBJECTIVE: To evaluate whether change in patent ductus arteriosus (PDA) management strategies over time had an impact on respiratory outcomes in premature infants. STUDY DESIGN: Prospectively collected data were included from all preterm infants born at 23-30 weeks gestational age with PDA admitted to the Children's Hospital of the University of Miami/Jackson Memorial Medical Center from January 1, 2005 to December 31, 2007 (epoch 1) and January 1, 2011 to December 31, 2015 (epoch 2). The 2 epochs were compared for approach with PDA diagnosis and subsequent management strategies and respiratory outcomes. RESULTS: Significantly fewer infants were treated for PDA in epoch 2 (54%) compared with epoch 1 (90%). Multivariable logistic regression analysis demonstrated that infants in epoch 2, with later PDA diagnosis and less frequent PDA treatment, had greater odds of bronchopulmonary dysplasia (BPD), composite of BPD or death, and more treatment with postnatal steroids than in epoch 1. CONCLUSIONS: The change in approach to diagnosis and management of PDA, from a more proactive and aggressive approach during the earlier epoch 1 to a more expectant approach during the subsequent epoch 2, was associated with worse respiratory outcomes, including increase in BPD and in BPD or death.

[Predictive value of platelet aggregation rate in hemodynamically significant patent ductus arteriosus in preterm infants].

Objective: To explore the predictive value of platelet aggregation rate in patent ductus arteriosus in preterm infants. Methods: This prospective nested case-control study enrolled 72 preterm infants with gestational age<32 weeks, who were admitted to Neonatal Intensive Care Unit of Xuzhou Central Hospital from August 2017 to October 2019. The echocardiography was performed on the 4th to 5th day after birth, and the preterm infants who met the diagnostic criteria of hemodynamically significant patent ductus arteriosus (hsPDA) were included into hsPDA group, and the control group was comprised of matched preterm infants with non-hsPDA according to the proportion of 1∶2. The basic characteristics of the preterm infants were recorded, and their complete blood counts and platelet aggregation function were examined. Clinical data were compared by student's t test and chi-square test between the two groups. The risk factors and their predictive values were analyzed by binary logistic regression analysis and receiver operating characteristic curve. Results: There were 24 preterm infants (16 boys) in the hsPDA group, and 48 (30 boys) in the control group. The incidence of neonatal respiratory distress syndrome (NRDS) grade II-IV in the hsPDA group was higher than that in the control group (67% (16/24) vs. 27% (13/48), χ²=10.422, P=0.001). The thrombocytocrit and adenosine diphosphate-induced platelet aggregation rate in the hsPDA group were lower than those in the control group (0.002 1±0.000 9 vs. 0.002 8±0.000 9, 0.21±0.10 vs. 0.32±0.07, t=-3.043 and -5.093, P=0.004 and <0.01, respectively); while the platelet volume in the hsPDA group was greater than that in the control group ((10.3±2.4) vs. (9.2±2.0) fl, t = 2.713, P = 0.033). The other platelet parameters (platelet count, platelet distribution width, and large platelet ratio) and platelet aggregation rate induced by other inducers (collagen, epinephrine and arachidonic acid) were not significantly different between the two groups (all P>0.05). The low platelet aggregation rate induced by adenosine diphosphate and low thrombocytocrit were independent risk factors for hsPDA in preterm infants (OR=4.525 and 3.994, 95%CI: 1.305-15.689 and 1.143-13.958, respectively). And the adenosine diphosphate-induced platelet aggregation rate had moderate predictive value for hsPDA in preterm infants, as the area under the receiver operating characteristic curve was 0.809, and the cutoff value was 0.245 with 0.67 sensitivity and 0.86 specificity. Conclusions: Poor platelet aggregation function and low thrombocytocrit are independent risk factors for hsPDA in preterm infants with gestational age<32 weeks. Low platelet aggregation rate induced by adenosine diphosphate has moderate predictive value for hsPDA patency.

Morbidity associated with patent ductus arteriosus in preterm newborns: a retrospective case-control study.

INTRODUCTION: Association between persistency of a patent ductus arteriosus (PDA) and morbidity in preterm newborns is still controversial. We aimed to investigate the relation between PDA and morbidity in a large retrospective study. METHODS: A case-control study including neonates consecutively admitted to the Neonatal Intensive Care Unit (NICU), with gestational age (GA) < 32 weeks or body birth weight (BW) < 1500 g, over a 5-year period. Newborns were divided into Cases and Controls, according with the presence or absence of a hemodynamically significant PDA (hs-PDA). RESULTS: We enrolled 85 Cases and 193 Controls. Subjects with hs-PDA had significantly (p < 0.001) lower GA (26.7 w, 95%CI 27.1-28.0 vs. 30.1 w, 95%CI 29.7-30.4), BW (1024 g, 95% CI 952-1097 vs. 1310 g 95%CI 1263-1358) and an increased morbidity (60.0% vs. 18.7%). In a sub-group of extremely preterm newborns (GA ≤ 28 weeks and BW ≤ 1000 g), the rate of bronchopulmonary dysplasia (BPD) was significantly increased in Cases (31.7%) compared with Controls (5.9%, p = 0.033). Multivariate analysis showed that morbidity significantly depended on hs-PDA, GA and BW, and that, in extremely preterms, the hs-PDA represented an independent risk factor for BPD. CONCLUSIONS: Occurrence of the main morbidities of prematurity depended by hs-PDA, in association with GA, BW, and use of prenatal steroids. In extremely premature babies, hs-PDA is a risk factor for BPD, one of the most important morbidity of prematurity, independently by other confounding variables.

Spontaneous twin anemia polycythemia sequence: diagnosis, management, and outcome in an international cohort of 249 cases.

BACKGROUND: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. OBJECTIVE: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. STUDY DESIGN: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. RESULTS: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7-28.8; range, 15.1-35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P=.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4-27.8; P=.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1-45.5; P=.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0-146.4; P=.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7-0.9; P=.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4-43.3; P=.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5-2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins.

High Dose Indomethacin for Patent Ductus Arteriosus Closure Increases Neonatal Morbidity.

OBJECTIVE: Symptomatic patent ductus arteriosus (sPDA) is the most common heart abnormality in preterm infants. Optimal duration and dose of medical treatment is still unclear. We assessed undesired effects and closure rate of high-dose indomethacin (HDI) for pharmacological closure of sPDA. STUDY DESIGN: Retrospective single center analysis of 248 preterm infants born between January 2006 and December 2015 with a birth weight <2,000 g and sPDA which was treated with indomethacin. Patients were treated with either standard dose indomethacin (SDI; n = 196) or HDI (n = 52). Undesired effects and PDA closure were compared between patients treated with SDI and HDI. RESULTS: In univariate analysis, patients receiving HDI had a significant increase in gastrointestinal hemorrhage (32.7 vs.11.7%, p = 0.001), bronchopulmonary dysplasia (BPD) (77.8 vs. 55.1%, p = 0.003), and retinopathy of prematurity (13.5 vs. 2.6%, p = 0.004). Moreover, HDI patients needed longer mechanical ventilation (2.5 vs. 1.0 days, p = 0.01). Multivariate analyses indicated that necrotizing enterocolitis (17 vs. 7%, p = 0.01) and BPD (79 vs. 55%, p = 0.02) were more frequent in HDI patients. PDA closure rate was 79.0% with HDI versus 65.3% with SDI. CONCLUSION: HDI used for PDA closure is associated with an increase in necrotizing enterocolitis and BPD. Risks of HDI should be balanced against other treatment options.