Long-term outcomes of very low birth weight infants with intraventricular hemorrhage: a nationwide population study from 2011 to 2019.

BACKGROUND: Advancements in neonatal care have increased preterm infant survival but paradoxically raised intraventricular hemorrhage (IVH) rates. This study explores IVH prevalence and long-term outcomes of very low birth weight (VLBW) infants in Korea over a decade. METHODS: Using Korean National Health Insurance data (NHIS, 2010-2019), we identified 3372 VLBW infants with IVH among 4,129,808 live births. Health-related claims data, encompassing diagnostic codes, diagnostic test costs, and administered procedures were sourced from the NHIS database. The results of the developmental assessments  are categorized into four groups based on standard deviation (SD) scores. Neonatal characteristics and complications were compared among the groups. Logistic regression models were employed to identify significant changes in the incidence of complications and to calculate odds ratios with corresponding 95% confidence intervals for each risk factor associated with mortality and morbidity in IVH. Long-term growth and development were compared between the two groups (years 2010-2013 and 2014-2017). RESULTS: IVH prevalence was 12% in VLBW and 16% in extremely low birth weight (ELBW) infants. Over the past decade, IVH rates increased significantly in ELBW infants (P = 0.0113), while mortality decreased (P = 0.0225). Major improvements in certain neurodevelopmental outcomes and reductions in early morbidities have been observed among VLBW infants with IVH. Ten percent of the population received surgical treatments such as external ventricular drainage (EVD) or a ventriculoperitoneal (VP) shunt, with the choice of treatment methods remaining consistent over time. The IVH with surgical intervention group exhibited higher incidences of delayed development, cerebral palsy, seizure disorder, and growth failure (height, weight, and head circumference) up to 72 months of age (P < 0.0001). Surgical treatments were also significantly associated with abnormal developmental screening test results. CONCLUSIONS: The neurodevelopmental outcomes of infants with IVH, especially those subjected to surgical treatments, continue to be a matter of concern. It is imperative to prioritize specialized care for patients receiving surgical treatments and closely monitor their growth and development after discharge to improve developmental prognosis. Supplementary file2 (MP4 77987 kb).

Temporal Trends in Severe Brain Injury and Associated Outcomes in Very Preterm Infants.

INTRODUCTION: Severe brain injury (SBI), including severe intraventricular haemorrhage (sIVH) and cystic periventricular leukomalacia, poses significant challenges for preterm infants, yet recent data and trends are limited. METHODS: Analyses were conducted using the Australian and New Zealand Neonatal Network data on preterm infants born <32 weeks' gestation admitted at Monash Children's Hospital, Australia, from January 2014 to April 2021. The occurrence and trends of SBI and sIVH among preterm infants, along with the rates and trends of death and neurodevelopmental impairment (NDI) in SBI infants were assessed. RESULTS: Of 1,609 preterm infants, 6.7% had SBI, and 5.6% exhibited sIVH. A total of 37.6% of infants with SBI did not survive to discharge, with 92% of these deaths occurring following redirection of clinical care. Cerebral palsy was diagnosed in 65.2% of SBI survivors, while 86.4% of SBI survivors experienced NDI. No statistically significant differences were observed in the temporal trends of SBI (adjusted OR [95% CI] 1.08 [0.97-1.20]; p = 0.13) or sIVH (adjusted OR [95% CI] 1.09 [0.97-1.21]; p = 0.11). Similarly, there was no statistically significant difference noted in the temporal trend of the composite outcome, which included death or NDI among infants with SBI (adjusted OR [95% CI] 0.90 [0.53-1.53]; p = 0.71). CONCLUSION: Neither the rates of SBI nor its associated composite outcome of death or NDI improved over time. A notable proportion of preterm infants with SBI faced redirection of care and subsequent mortality, while most survivors exhibited adverse neurodevelopmental challenges. The development of better therapeutic interventions is imperative to improve outcomes for these vulnerable infants.

Mode of delivery and adverse short- and long-term outcomes in vertex-presenting very preterm born infants: a European population-based prospective cohort study.

OBJECTIVES: To compare mortality, morbidity and neurodevelopment by mode of delivery (MOD) for very preterm births with low prelabour risk of caesarean section (CS). METHODS: The study was a population-based prospective cohort study in 19 regions in 11 European countries. Multivariable mixed effects models and weighted propensity score models were used to estimate adjusted odds ratios (aOR) by observed MOD and the unit's policy regarding MOD. Population: Singleton vertex-presenting live births at 24 + 0 to 31 + 6 weeks of gestation without serious congenital anomalies, preeclampsia, HELLP or eclampsia, antenatal detection of growth restriction and prelabour CS for fetal or maternal indications. RESULTS: Main outcome measures: A composite of in-hospital mortality and intraventricular haemorrhage (grade III/IV) or periventricular leukomalacia. Secondary outcomes were components of the primary outcome, 5 min Apgar score <7 and moderate to severe neurodevelopmental impairment at two years of corrected age. The rate of CS was 29.6% but varied greatly between countries (8.0-52.6%). MOD was not associated with the primary outcome (aOR for CS 0.99; 95% confidence interval [CI] 0.65-1.50) when comparing units with a systematic policy of CS or no policy of MOD to units with a policy of vaginal delivery (aOR 0.88; 95% CI 0.59-1.32). No association was observed for two-year neurodevelopment impairment for CS (aOR 1.15; 95% CI 0.66-2.01) or unit policies (aOR 1.04; 95% CI 0.63-1.70). CONCLUSIONS: Among singleton vertex-presenting live births without medical complications requiring a CS at 24 + 0 to 31 + 6 weeks of gestation, CS was not associated with improved neonatal or long-term outcomes.

Neurodevelopmental outcomes of preterm infants conceived by assisted reproductive technology.

BACKGROUND: There have been concerns about the development of children conceived through assisted reproductive technology. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived through assisted reproductive technology and born preterm are limited. OBJECTIVE: This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at <29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally. STUDY DESIGN: This retrospective cohort study included inborn, nonanomalous infants, born at <29 weeks' gestation between January 1, 2010, and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of the 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of <85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived through assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment. RESULTS: Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes mellitus, receipt of antenatal corticosteroids, and cesarean delivery were higher in the assisted reproduction group than the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group (33% [181 of 546] vs 39% [1284 of 3318]; P=.01). Of the 4176 surviving infants, 3386 (81%) had a follow-up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes mellitus, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Conception through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score of <85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of <85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88). CONCLUSION: Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born at <29 weeks' gestation. Long-term follow-up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.

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.

Proactive neonatal treatment at 22 weeks of gestation: a systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to provide a systematic review and meta-analysis to quantify prognosis and identify factors associated with variations in reported mortality estimates among infants who were born at 22 weeks of gestation and provided proactive treatment (resuscitation and intensive care). DATA SOURCES: PubMed, Scopus, and Web of Science databases, with no language restrictions, were searched for articles published from January 2000 to February 2020. STUDY ELIGIBILITY CRITERIA: Reports on live-born infants who were delivered at 22 weeks of gestation and provided proactive care were included. The primary outcome was survival to hospital discharge; secondary outcomes included survival without major morbidity and survival without neurodevelopmental impairment. Because we expected differences across studies in the definitions for various morbidities, multiple definitions for composite outcomes of major morbidities were prespecified. Neurodevelopmental impairment was based on Bayley Scales of Infant Development II or III. Data extractions were performed independently, and outcomes agreed on a priori. STUDY APPRAISAL AND SYNTHESIS METHODS: Methodological quality was assessed using the Quality in Prognostic Studies tool. An adapted version of the Grading of Recommendations Assessment, Development and Evaluation approach for prognostic studies was used to evaluate confidence in overall estimates. Outcomes were assessed as prevalence and 95% confidence intervals. Variabilities across studies attributable to heterogeneity were estimated with the I2 statistic; publication bias was assessed with the Luis Furuya-Kanamori index. Data were pooled using the inverse variance heterogeneity model. RESULTS: Literature searches returned 21,952 articles, with 2034 considered in full; 31 studies of 2226 infants who were delivered at 22 weeks of gestation and provided proactive neonatal treatment were included. No articles were excluded for study design or risk of bias. The pooled prevalence of survival was 29.0% (95% confidence interval, 17.2-41.6; 31 studies, 2226 infants; I2=79.4%; Luis Furuya-Kanamori index=0.04). Survival among infants born to mothers receiving antenatal corticosteroids was twice the survival of infants born to mothers not receiving antenatal corticosteroids (39.0% vs 19.5%; P<.01). The overall prevalence of survival without major morbidity, using a definition that includes any bronchopulmonary dysplasia, was 11.0% (95% confidence interval, 8.0-14.3; 10 studies, 374 infants; I2=0%; Luis Furuya-Kanamori index=3.02). The overall rate of survival without moderate or severe impairment was 37.0% (95% confidence interval, 14.6-61.5; 5 studies, 39 infants; I2=45%; Luis Furuya-Kanamori index=-0.15). Based on the year of publication, survival rates increased between 2000 and 2020 (slope of the regression line=0.09; standard error=0.03; P<.01). Studies were highly diverse with regard to interventions and outcomes reported. CONCLUSION: The reported survival rates varied greatly among studies and were likely influenced by combining observational data from disparate sources, lack of individual patient-level data, and bias in the component studies from which the data were drawn. Therefore, pooled results should be interpreted with caution. To answer fundamental questions beyond the breadth of available data, multicenter, multidisciplinary collaborations, including alignment of important outcomes by stakeholders, are needed.

Low cardiac output measured by bioreactance and adverse outcome in preterm infants with birth weight less than 1250 g.

BACKGROUND: Recently a new continuous non-invasive cardiac output measurement, bioreactance, has become available. Bioreactance measurement of cardiac output has been shown to correlate with left ventricular output detected by echocardiography in healthy term and preterm neonates. AIMS: Our aim was to correlate cardiac output measurements by bioreactance in the first 48 h of life with adverse outcomes attributable to hypoperfusion (peri/intraventricular haemorrhage (PIVH) and/or necrotising enterocolitis (NEC)) in the cohort of extremely preterm infants. STUDY DESIGN: A prospective observational cohort study. SUBJECTS: Preterm infants with birth weight less than 1250 g. OUTCOME MEASURES: Cardiac output was measured between six and 48 h of age by bioreactance. Our primary outcome was a difference in cardiac output between infants with an adverse outcome attributable to hypoperfusion (Group 1), and infants without the predefined adverse outcome (Group 2). RESULTS: There were 39 infants enrolled in the study. There were six infants in Group 1. These infants had a significantly lower minimal cardiac output measurement compared to Group 2 (mean 36.7 ml/kg/min vs 64.5 ml/kg/min, p = .0006). The mean cardiac output in Group 1 was significantly lower on day one of life, followed by a significant increase in cardiac output on day two of life compared to Group 2. CONCLUSIONS: Infants with birth weight less than 1250 g and PIVH and/or NEC had significantly lower cardiac output compared to infants without these complications on day one of life. This low cardiac output was then followed by a significant increase on day two of life.

Lumbar drain complications in patients undergoing fenestrated or branched endovascular aortic aneurysm repair: Development of an institutional protocol for lumbar drain management.

OBJECTIVE: Lumbar drain placement with cerebrospinal fluid (CSF) drainage is an effective adjunct for reducing the risk of spinal cord ischemia in patients undergoing complex aortic aneurysm repair. However, lumbar drain placement is a challenging procedure with potential for significant complications. We sought to characterize complications of lumbar drain placement in a large, single-center experience of patients who underwent fenestrated or branched endovascular aneurysm repair (F/BEVAR). METHODS: All patients who underwent F/BEVAR and attempted lumbar drain placement from 2010 to 2019 were retrospectively reviewed. All lumbar drains were placed by four cardiovascular anesthesiologists who compose the complex aortic anesthesia team. Lumbar drain placement was guided by a set protocol and used whenever the aortic stent graft coverage was planned to extend more proximal than 40 mm above the celiac artery. Details relating to lumbar drain placement, management, and frequency and type of associated complications were characterized. RESULTS: During the study period, 256 patients underwent F/BEVAR, of whom 100 (39%) were planned for lumbar drain placement. Successful placement occurred in 98 (98%) of the cases. All lumbar drains were placed before induction of general anesthesia, using fluoroscopy guidance in 28 cases (28%). The most common level of placement was L4-5 (n = 42 [42%]). The majority (n = 82 [82%]) were left in place ≤48 hours; 21% were removed during the first 24 hours, and 61% were removed between 24 and 48 hours. Nonfunctionality was the most common complication, occurring in 16 (16%) patients. Catheter dislodgment or fracture, CSF leak, and postdural puncture headache were observed in 4 (4%), 7 (7%), and 4 (4%) patients, respectively. The most common bleeding complication was the presence of asymptomatic blood in the CSF (n = 11 [11%]), whereas subarachnoid hemorrhage combined with intraventricular hemorrhage occurred in three patients (3%); none of these patients required surgical drainage or intervention. No infectious complications were observed. CONCLUSIONS: Lumbar drain placement for CSF drainage is a commonly employed adjunct to prevent spinal cord ischemia in F/BEVAR. Our experience demonstrates that lumbar drain placement can be performed successfully but is associated with a significant rate of nonfunctionality and a diverse range of complications that, fortunately, do not commonly have significant long-term sequelae.

Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Treatment Rates and Outcomes in Infants Born Extremely Preterm.

OBJECTIVES: To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes. STUDY DESIGN: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio. RESULTS: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis. CONCLUSIONS: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

BACKGROUND: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable gas exchange. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs. OBJECTIVES: To assess the benefits and harms of an initial sustained lung inflation (SLI) (> 1 second duration) versus standard inflations (≤ 1 second) in newborn infants receiving resuscitation with intermittent PPV. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 3), MEDLINE via PubMed (1966 to 1 April 2019), Embase (1980 to 1 April 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 1 April 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean standard deviation (SD), and weighted mean difference (WMD) for continuous data. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Ten trials enrolling 1467 infants met our inclusion criteria. Investigators in nine trials (1458 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review: mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40 (I² not applicable); typical RD 0.00, 95% CI -0.02 to 0.02; I² = 0%; 5 studies, 479 participants); and mortality during hospitalisation (typical RR 1.09, 95% CI 0.83 to 1.43; I² = 42%; typical RD 0.01, 95% CI -0.02 to 0.04; I² = 24%; 9 studies, 1458 participants). The quality of the evidence was low for death in the delivery room because of limitations in study design and imprecision of estimates (only one death was recorded across studies). For death before discharge the quality was moderate: with longer follow-up there were more deaths (n = 143) but limitations in study design remained. Among secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; I² = 95%; 5 studies, 524 participants; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study at high risk of bias: when this study was removed from the analysis, the size of the effect was reduced (MD -1.71 days, 95% CI -3.04 to -0.39; I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. risk of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.91, 95% CI 0.79 to 1.04; I² = 65%; 5 studies, 811 participants); risk of surfactant administration during hospital admission (typical RR 0.99, 95% CI 0.91 to 1.08; I² = 0%; 9 studies, 1458 participants); risk of chronic lung disease (typical RR 0.99, 95% CI 0.83 to 1.18; I² = 0%; 4 studies, 735 participants); pneumothorax (typical RR 0.89, 95% CI 0.57 to 1.40; I² = 34%; 8 studies, 1377 infants); or risk of patent ductus arteriosus requiring pharmacological treatment (typical RR 0.99, 95% CI 0.87 to 1.12; I² = 48%; 7 studies, 1127 infants). The quality of evidence for these secondary outcomes was moderate (limitations in study design ‒ GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates ‒ GRADE). We could not perform any meta-analysis in the comparison of the use of initial sustained inflation versus standard inflations in newborns receiving resuscitation with chest compressions because we identified only one trial for inclusion (a pilot study of nine preterm infants). AUTHORS' CONCLUSIONS: Our meta-analysis of nine studies shows that sustained lung inflation without chest compression was not better than intermittent ventilation for reducing mortality in the delivery room (low-quality evidence ‒ GRADE) or during hospitalisation (moderate-quality evidence ‒ GRADE), which were the primary outcomes of this review. However, the single largest study, which was well conducted and had the greatest number of enrolled infants, was stopped early for higher mortality rate in the sustained inflation group. When considering secondary outcomes, such as rate of intubation, rate or duration of respiratory support, or bronchopulmonary dysplasia, we found no benefit of sustained inflation over intermittent ventilation (moderate-quality evidence ‒ GRADE). Duration of mechanical ventilation was shortened in the SLI group (low-quality evidence ‒ GRADE); this result should be interpreted cautiously, however, as it might have been influenced by study characteristics other than the intervention. There is no evidence to support the use of sustained inflation based on evidence from our review.

Increased risk of intraventricular hemorrhage in low birth weight infants with aortic coarctation.

Objective: To determine if there is an association between aortic coarctation (CoA) and intraventricular hemorrhage (IVH) in low birth weight (LBW) infants that may justify earlier intervention. While there is an increasing number of reports of successful early CoA intervention in LBW infants, there are no data to justify this approach.Material and methods: Retrospective review of the University Health System Consortium Clinical Data Base/Resource Manager, a national hospital discharge database. LBW (≤2 kg) infants, with and without IVH and isolated CoA were identified; IVH was stratified into low (grade 1 or 2) and high (grade 3 or 4) severity. Odds ratios were calculated for any, low and high-grade IVH with CoA.Results: Forty-six thousand and twenty LBW infants were identified; 3716 (8.1%) had IVH, 3001 (81%) with low, and 724 (19%) with high severity. Sixty-four infants had CoA, 13 had associated IVH (10 with low and three with high severity). The odds ratio for any IVH with CoA was 2.91 (95% CI 1.58-5.35), low severity 2.77 (95% CI 1.41-5.46) and high severity 3.45 (95% CI 1.07-11.07).Conclusions: In conclusion, this large retrospective database review found that LBW infants with CoA may be at increased risk of IVH. Further study is needed to determine if earlier catheter- or surgical-based intervention for CoA could reduce the risk of IVH in this population.

Early versus delayed extubation in extremely preterm neonates: a retrospective cohort study.

OBJECTIVE: To evaluate clinical outcomes associated with extubation timing among extremely preterm neonates. DESIGN/METHODS: Neonates <26 weeks' GA admitted to four tertiary neonatal centers were included if they met predetermined extubation criteria within first postnatal week and classified into early extubation (≤24 h; exposure group) and delayed extubation (>24 h; control group) after meeting extubation criteria. Patients with known severe IVH and/or significant PDA prior to meeting extubation criteria were excluded. RESULTS: Of 197 included infants, 75 were in exposure group. Survival without BPD (aOR 1.26; 95% CI 0.62-2.56; P = 0.52) and survival without severe IVH (aOR 1.98; 95% CI 0.93-4.23; P = 0.08) were not different, adjusted for GA, SNAP, number of surfactant doses and center. CONCLUSIONS: Extubation within 24 h of meeting extubation criteria in neonates <26 weeks' GA was not associated with survival without BPD or survival without severe IVH. However, confounding by indication cannot be ruled out without a prospective trial.

Cumulative effect of evidence-based practices on outcomes of preterm infants born at <29 weeks' gestational age.

BACKGROUND: Extremely preterm infants born at <29 weeks' gestational age are at high risk of death or severe neurological injury. Several individual evidence-based practices have been associated with neuroprotection. OBJECTIVE: The objective of the study was to investigate the cumulative effect of 4 evidence-based practices and their association with death and/or severe neurological injury among infants born at <29 weeks' gestational age. STUDY DESIGN: Observational study of infants born at 230-286 weeks gestational age admitted to neonatal intensive care units participating in the Canadian Neonatal Network from 2015 through 2017. We evaluated 4 practices: antenatal corticosteroids, antenatal MgSO4 for neuroprotection, deferred cord clamping ≥30 seconds, and normothermia on admission. The effect of exposure to 1, 2, 3, and all 4 evidence-based practices compared with none on death and/or severe neurological injury was assessed using multivariable logistic regression models adjusted for patient characteristics. RESULTS: Rate of death and/or severe neurological injury was 20% (873 of 4297) and varied based on exposure to evidence-based practices: none, 34% (54 of 157); 1, 27% (171 of 626); 2, 20% (295 of 1448); 3, 18% (263 of 1448); and all 4, 14% (90 of 618). Significantly lower odds of death and/or severe neurological injury were observed with exposure to antenatal corticosteroids (adjusted odds ratio, 0.52, 95% confidence interval, 0.40-0.69) and deferred cord clamping (adjusted odds ratio, 0.81, 95% confidence interval, 0.68-0.96) but not MgSO4 (adjusted odds ratio, 0.88, 95% confidence interval, 0.72-1.08) or normothermia (adjusted odds ratio, 0.96, 95% confidence interval, 0.79-1.16). Infants exposed to ≥2 evidence-based practices had significantly lower odds of death and/or severe neurological injury than those exposed to no evidence-based practices (adjusted odds ratio, 0.61, 95% confidence interval, 0.43-0.88). CONCLUSION: Among infants born at <29 weeks' gestational age, exposure to at least 2 of the evidence-based practices assessed was associated with decreased odds of death and/or severe neurological injury.

Outcomes of outborn extremely preterm neonates admitted to a NICU with respiratory distress.

OBJECTIVE: To compare the risk of mortality and morbidity between outborn and propensity score-matched inborn extremely preterm neonates. SETTING: Multiple neonatal intensive care units (NICU) across the USA. PATIENTS: Singleton neonates born at 22-29 weeks' gestation with no major anomalies who were admitted to a NICU and discharged between 2000 and 2014. Outborn neonates were restricted to those who transferred into a NICU on the day of birth. METHODS: The association between inborn-outborn status and the time-to-event outcomes of in-hospital mortality and necrotising enterocolitis (NEC) were assessed using Cox proportional hazards regression. Logistic regression was used to assess the remaining secondary outcomes: retinopathy of prematurity requiring treatment (tROP), chronic lung disease (CLD), periventricular leucomalacia (PVL) and severe intraventricular haemorrhage (IVH). Since outborn status was not random, we used 1:1 propensity score matching to reduce the imbalance in illness severity. RESULTS: There were 59 942 neonates (7991 outborn) included in the study. Outborn neonates had poorer survival than inborns and higher rates of NEC, severe IVH, tROP and PVL. Inborn-outborn disparities in mortality were reduced over the study period. When analysing the matched cohort (6524 matched pairs), outborns were less likely to die in-hospital compared with inborns (HR 0.84, 95% CI 0.77 to 0.91). However, outborns experienced higher rates of NEC (HR 1.14, 95% CI 1.04 to 1.25), severe IVH (OR 1.52, 95% CI 1.38 to 1.68), tROP (OR 1.45, 95% CI 1.25 to 1.69) and CLD (OR 1.12, 95% CI 1.01 to 1.24). CONCLUSION: Additional research is needed to understand the contributors to increased morbidity for outborn extremely preterm neonates and identify interventions that mitigate this risk.

Survival and early complications of preterm infants with birthweight less than 500 grams during a 10-year period in Hungary.

BACKGROUND: There are limited data available on the survival and early complications of preterm infants with less than 500 g birthweight. To estimate the outcomes for these infants, it is important for caregivers to be aware of perinatal factors that may affect survival. OBJECTIVES: We assessed the mortality and certain early complications of preterm infants born with less than 500 g in Hungary between 2006 and 2015. METHODS: We reviewed data of 486 infants from the database of the Hungarian Central Statistical Office and in parallel of 407 infants from the "NICU database." The study period was divided into two epochs: 2006-2010 and 2011-2015. RESULTS: The survival was 27.1% in the first epoch and 39.1% in the second epoch, and the incidence of early complications was slightly higher in the second epoch. In the surviving group (first and second epoch combined), gestational age (25.1 vs 23.7 weeks), birthweight (458 vs 447 g) antenatal steroid treatment (66.3% vs 52.3%), surfactant therapy (95.1% vs 84.3%), median Apgar scores (6 vs 3 and 8 vs 5 at 1 and 5 minutes, respectively) and proportion of caesarean delivery (89.3% versus 68.5%) were higher than in the non-surviving group (first and second epoch combined). The proportion of multiple births was lower in the surviving group (15.7% vs 33.4%). CONCLUSIONS: Survival of infants with less than 500 g improved between 2006-2010 and 2011-2015 in Hungary. The slightly higher occurrence of early complications might be associated with improving survival.

Prediction of ductus closure and development of adverse clinical outcome by functional echocardiography in very low birth weight newborn.

OBJECTIVE: To evaluate the role of functional echocardiography for prediction of patent ductus arteriosus (PDA) closure and development of adverse outcome in very low birth weight newborn. METHODS AND STUDY DESIGN: Functional echocardiography was done in 143 neonates with birth weight less than 1250 g on day 3. Nine echocardiographic parameters were analyzed for babies with PDA for prediction of spontaneous closure and development of one or more adverse outcomes (bronchopulmonary dysplasia, necrotizing enterocolitis≥stage 2 and intraventricular hemorrhage > grade 2) during hospital stay. RESULT: The mean (±SD) birthweight and gestational age of the cohort were 1017 (±17) g and 30.8 (±2.7) weeks. PDA was found in 60 (41.9%) babies on day 3 among the recruited babies. Binary logistic regression model showed strong prediction ability of early (day 3) functional echocardiography markers in predicting future spontaneous closure of PDA and development of one or more adverse clinical outcome. In multivariate analysis, abnormal flow pattern (growing or pulsatile) was found to have increased risk for persistence of PDA (adjusted OR 22.9, CI 1.97-269) in comparison to PDA with closing/bidirectional pattern. CONCLUSION: Early functional echocardiography, especially the flow pattern, is useful for prediction of PDA closure. Adverse clinical outcome prediction is possible with functional echocardiography markers when combined with gestational age and PDA closure status.

Short-term outcomes of extremely preterm infants at discharge: a multicenter study from Guangdong province during 2008-2017.

BACKGROUND: An increasing number of extremely preterm (EP) infants have survived worldwide. However, few data have been reported from China. This study was designed to investigate the short-term outcomes of EP infants at discharge in Guangdong province. METHODS: A total of 2051 EP infants discharged from 26 neonatal intensive care units during 2008-2017 were enrolled. The data from 2008 to 2012 were collected retrospectively, and from 2013 to 2017 were collected prospectively. Their hospitalization records were reviewed. RESULTS: During 2008-2017, the mean gestational age (GA) was 26.68 ± 1.00 weeks and the mean birth weight (BW) was 935 ± 179 g. The overall survival rate at discharge was 52.5%. There were 321 infants (15.7%) died despite active treatment, and 654 infants (31.9%) died after medical care withdrawal. The survival rates increased with advancing GA and BW (p < 0.001). The annual survival rate improved from 36.2% in 2008 to 59.3% in 2017 (p < 0.001). EP infants discharged from hospitals in Guangzhou and Shenzhen cities had a higher survival rate than in others (p < 0.001). The survival rate of EP infants discharged from general hospitals was lower than in specialist hospitals (p < 0.001). The major complications were neonatal respiratory distress syndrome, 88.0% (1804 of 2051), bronchopulmonary dysplasia, 32.3% (374 of 1158), retinopathy of prematurity (any grade), 45.1% (504 of 1117), necrotizing enterocolitis (any stage), 10.1% (160 of 1588), intraventricular hemorrhages (any grade), 37.4% (535 of 1431), and blood culture-positive nosocomial sepsis, 15.7% (250 of 1588). The multivariate logistic regression analysis indicated that improved survival of EP infants was associated with discharged from specialist hospitals, hospitals located in high-level economic development region, increasing gestational age, increasing birth weight, antenatal steroids use and a history of premature rupture of membranes. However, twins or multiple births, Apgar ≤7 at 5 min, cervical incompetence, and decision to withdraw care were associated with decreased survival. CONCLUSIONS: Our study revealed the short-term outcomes of EP infants at discharge in China. The overall survival rate was lower than the developed countries, and medical care withdrawal was a serious problem. Nonetheless, improvements in care and outcomes have been made annually.

[Early and late complications of hyperglycemic extremely low birth-weight infants]. / Az extrém alacsony születési súlyú koraszülöttek hyperglykaemiájának korai és késoi szövodményei.

Introduction: During recent decades, the perinatal mortality of extremely low-birth weight infants has decreased. An important task is to recognize complications of prematurity. Aim: We made an attempt to explore the relationship between complications of prematurity and neonatal hyperglycemia. Method: From 1 January 2014 to 31 December 2017, 188 infants with birth weight below 1000 g were admitted. For each infant, the frequencies of hyperglycemia (blood glucose >8.5 mmol/l), retinopathy of prematurity, intraventricular hemorrhage, and bronchopulmonary dysplasia were determined. Animal studies were performed in Sprague Dawley rats. Hyperglycemia was achieved by intraperitoneal injection of streptozotocin (100 mg/kg). On the 7th day of life, aorta sections were prepared and stained with hematoxylin eosin. Wall thickness was measured using QCapture Pro 7 image analysis software. Results: The mean ± SD gestational age and birth weight were 27.1 ± 2.2 weeks and 814.9 ± 151.9 g; 33 infants (17.5%) died. Hyperglycemia was confirmed in 62 cases (32.9%), and insulin treatment was given to 43 infants (22.8%). The gestational age and birth weight of the hyperglycemic infants were significantly lower (p<0.001), the incidence of severe retinopathy (p = 0.012) and the mortality of insulin-treated patients were higher (p = 0.02) than in normoglycemic infants. Among survivors (n = 155), we found by logistic regression analysis that hyperglycemia was a risk factor for severe retinopathy (p<0.001). In the rat model, neonatal hyperglycemia caused significant thickening of the aortic wall. Conclusion: Our studies indicate that hyperglycemia is common in extremely low birth-weight infants. Monitoring of these infants for retinopathy of prematurity, kidney dysfunction, and hypertension is recommended. Orv Hetil. 2019; 160(32): 1270-1278.

Pulmonary hemorrhage in neonatal respiratory distress syndrome: Radiographic evolution, course, complications and long-term clinical outcomes.

BACKGROUND: Pulmonary hemorrhage (PH) is occasionally seen in premature infants after surfactant treatment for respiratory distress syndrome (RDS). These infants receive frequent chest radiographs (CXR) during and after hospitalization enabling long-term radiographic-clinical correlation. OBJECTIVE: To chart the natural evolution of CXR findings of PH in RDS and correlate radiographic patterns to supplemental oxygen requirement. MATERIALS AND METHODS: Retrospective review of clinical notes for gestational age (GA), birth weight (BW), intraventricular hemorrhage (IVH) and oxygen requirement were performed. CXRs were reviewed at 4 time-points; during PH, 28 days postnatal age, 36 weeks and at farthest available clinical follow-up. RESULTS: 18 infants born (2003-2016), GA (24-30 weeks); BW (482-1590 grams) were included. Mean onset of PH was 1.94 (0-5) days. 9/18 (50%) had IVH. 3 died during PH; all had IVH. During PH, CXR showed whiteout 9/18 (50%); patchy opacities 5/18 (27%); diffuse haziness 1/18 (6%) and no change 3/18 (17%). At 28 days postnatal age, CXR showed fine-interstitial (FI) markings 14/15 (93%) and whiteout 1/15 (7%). At 36 weeks,12/14 (85%) had FI and 2/14 (15%) developed cystic-interstitial changes. At farthest follow-up, FI 3/13 (23%); coarse-interstitial 4/13 (30%); peri-bronchial cuffing 5/13 (38%); normal 1/13 (9%) and the majority had hyperinflation 9/13 (69%). At discharge, 9/14 (64%) required home-oxygen and 5/14 (36%) were on room-air. At farthest follow-up, 6/14 (42%) required home-oxygen and 8/14 (58%) were on room-air. CONCLUSION: Premature infants that survive PH may later develop chronic lung disease of prematurity with an evolving interstitial pattern on CXR that clears overtime as they outgrow the need for supplemental oxygen.

Hypertensive disorders during pregnancy are associated with reduced severe intraventricular hemorrhage in very-low-birth-weight infants.

OBJECTIVE: To determine differences in severe intraventricular hemorrhage (IVH) between very-low-birth-weight (≤1500 g, VLBW) infants born to mothers with and without hypertensive disorders (HD). DESIGN/METHODS: Retrospective analysis from the Optum Neonatal Database. The primary outcome of interest was severe IVH (grade 3 or 4). Secondary outcomes included other neonatal morbidities, mortality, and length of hospitalization. Outcomes were compared between VLBW infants born to mothers with and without HD. RESULTS: A total of 5456 infants met inclusion criteria. After multivariable regression analysis, risks of severe IVH and bronchopulmonary dysplasia (BPD) were lower ([OR 0.42, 95% CI 0.33-0.89, p = 0.01] and [OR 0.75, 95% CI 0.58-0.97, p = 0.03], respectively) and median length of hospitalization was decreased in the HD group (49 versus 61 days, p < 0.001). CONCLUSIONS: VLBW infants born to mothers with HD have a decreased risk of severe IVH, BPD, and a shorter duration of hospitalization.