Transplacental SARS-CoV-2 protein ORF8 binds to complement C1q to trigger fetal inflammation.

Prenatal SARS-CoV-2 infection is associated with higher rates of pregnancy and birth complications, despite that vertical transmission rates are thought to be low. Here, multi-omics analyses of human placental tissues, cord tissues/plasma, and amniotic fluid from 23 COVID-19 mother-infant pairs revealed robust inflammatory responses in both maternal and fetal compartments. Pronounced expression of complement proteins (C1q, C3, C3b, C4, C5) and inflammatory cytokines (TNF, IL-1α, and IL-17A/E) was detected in the fetal compartment of COVID-19-affected pregnancies. While ~26% of fetal tissues were positive for SARS-CoV-2 RNA, more than 60% of fetal tissues contained SARS-CoV-2 ORF8 proteins, suggesting transplacental transfer of this viral accessory protein. ORF8-positive fetal compartments exhibited increased inflammation and complement activation compared to ORF8-negative COVID-19 pregnancies. In human placental trophoblasts in vitro, exogenous ORF8 exposure resulted in complement activation and inflammatory responses. Co-immunoprecipitation analysis demonstrated that ORF8 binds to C1q specifically by interacting with a 15-peptide region on ORF8 (C37-A51) and the globular domain of C1q subunit A. In conclusion, an ORF8-C1q-dependent complement activation pathway was identified in COVID-19-affected pregnancies, likely contributing to fetal inflammation independently of fetal virus exposure.

Placental abruption and the risk of necrotizing enterocolitis in neonates with birth weight ≥1500 grams; US national database study.

BACKGROUND: The pathogenesis of necrotizing enterocolitis (NEC) is multifactorial, placental abruption is associated with serious neonatal complications attributed to disruption of the maternal-fetal vascular interface. This study aimed to investigate the association between placental abruption and NEC. METHODS: We analyzed the United States (US) National Inpatient Sample (NIS) dataset for the years 2016-2018. Using the logistic regression model, the adjusted odds ratios (aOR) were calculated to assess the risk of NEC in infants born to mothers with placental abruption after controlling for significant confounders. Analyses were repeated after stratifying the population into two birth weight (BW) categories: <1500 g and ≥1500 g. RESULTS: The study included 11,597,756 newborns. Placental abruption occurred in 0.16% of the population. NEC was diagnosed in 0.18% of infants, with a higher incidence (2.5%) in those born to mothers with placental abruption (aOR = 1.2, 95% CI: 1.1-1.3, p < 0.001). Placental abruption was associated with NEC only in infants with BW ≥ 1500 g (aOR = 1.34, 95% CI: 1.11-1.62, p 0.003). CONCLUSION: Placental abruption is associated with an increased risk of NEC in neonates with BW ≥ 1500 g. Research is needed to explore the mechanisms behind this association and to develop targeted interventions to mitigate NEC risks in this population. IMPACT: Placental abruption is associated with an increased risk of developing necrotizing enterocolitis (NEC) in neonates with a birth weight ≥1500 grams. This effect could be via direct in utero bowel injury or due to indirect postnatal compromise that occurs in these infants. This is the first study to specifically address the association between placental abruption and NEC in neonates ≥1500 g. The study used a national dataset that included all neonates delivered in the US, thereby allowing for the generalization of the findings after adjustment for multiple confounding factors. This study lays the groundwork for subsequent studies aimed at modifying feeding strategies and other neonatal management for the prevention of NEC in infants delivered after placental abruption.

Acute kidney injury in infants with hypoxic-ischemic encephalopathy.

BACKGROUND: This study aimed to investigate the prevalence of acute kidney injury (AKI) in infants with varying degrees of hypoxic-ischemic encephalopathy (HIE) and its associated outcomes, including mortality and length of stay (LOS). METHODS: The study used the National Inpatient Sample (NIS) dataset from 2010 to 2018. Regression analysis was used to control confounding variables. RESULTS: Of 31,220,784 infants included in the study, 30,130 (0.1%) had HIE. The prevalence of AKI was significantly higher in infants with HIE (9.0%) compared to those without (0.04%), with an adjusted odds ratio (aOR) of 77.6 (CI:70.1-85.7, p < 0.001), with the highest prevalence of AKI in infants with severe HIE (19.7%), aOR:130 (CI: 107-159), p < 0.001). Infants with AKI had a higher mortality rate compared to those without AKI in those diagnosed with any degree of HIE (28.9% vs. 8.8%), aOR 3.5 (CI: 3.2-3.9, p < 0.001), particularly among those with severe HIE, aOR:1.4 (1.2-1.6, p < 0.001). CONCLUSIONS: HIE is associated with an increased prevalence of AKI. Infants with severe HIE had the highest prevalence of AKI and associated mortality. The study highlights the need for close monitoring and early detection of AKI in infants with HIE, particularly those with severe HIE, to ameliorate the associated adverse outcomes.

Prevalence and Outcomes of Gastrointestinal Anomalies in Down Syndrome.

OBJECTIVES: Our objective was to investigate the prevalence of small intestinal atresia and Hirschsprung's disease (HD) in infants with Down syndrome (DS) and its impact on outcomes. STUDY DESIGN: We analyzed the National Inpatient Sample dataset. We included infants with DS, small intestinal atresia, HD, and the concomitant occurrence of both conditions. Regression analysis was used to control clinical and demographic variables. RESULTS: A total of 66,213,034 infants were included, of whom, 99,861 (0.15%) had DS. The concomitant occurrence of small intestinal atresia and HD was more frequent in infants with DS compared with the general population, adjusted odds ratio (aOR): 122, 95% confidence interval (CI): 96-154, (p < 0.001). Infants with DS and concomitant small intestinal atresia and HD had higher mortality compared with those without these conditions, aOR: 8.59, 95% CI: 1.95-37.8. CONCLUSION: Infants with DS are at increased risk of concomitant small intestinal atresia and HD, and this condition is associated with increased mortality. KEY POINTS: · Infants with Down syndrome are at increased risk of congenital GI anomalies.. · Infants with Down syndrome are at increased risk of necrotizing enterocolitis.. · Increased mortality in Down syndrome infants with concomitant small intestinal atresia and Hirschsprung's disease..

Outcomes of atrioventricular septal defects with and without down syndrome: analysis of the national inpatient database.

BACKGROUND: Controversial data exist about the impact of Down syndrome on outcomes after surgical repair of atrioventricular septal defect. AIMS: (A) assess trends and outcomes of atrioventricular septal defect with and without Down syndrome and (B) determine risk factors associated with adverse outcomes after atrioventricular septal defect repair. METHODS: We queried The National Inpatient Sample using International Classification of Disease codes for patients with atrioventricular septal defect < 1 year of age from 2000 to 2018. Patients' characteristics, co-morbidities, mortality, and healthcare utilisation were evaluated by comparing those with versus without Down syndrome. RESULTS: In total, 2,318,706 patients with CHD were examined; of them, 61,101 (2.6%) had atrioventricular septal defect. The incidence of hospitalisation in infants with atrioventricular septal defect ranged from 4.5 to 7.5% of all infants hospitalised with CHD per year. A total of 33,453 (54.7%) patients were associated with Down syndrome. Double outlet right ventricle, coarctation of the aorta, and tetralogy of Fallot were the most commonly associated with CHD in 6.9, 5.7, and 4.3% of patients, respectively. Overall atrioventricular septal defect mortality was 6.3%. Multivariate analysis revealed that prematurity, low birth weight, pulmonary hypertension, and heart block were associated with mortality. Down syndrome was associated with a higher incidence of pulmonary hypertension (4.3 versus 2.8%, p < 0.001), less arrhythmia (6.6 versus 11.2%, p < 0.001), shorter duration for mechanical ventilation, shorter hospital stay, and less perioperative mortality (2.4 versus 11.1%, p < 0.001). CONCLUSION: Trends in atrioventricular septal defect hospitalisation had been stable over time. Perioperative mortality in atrioventricular septal defect was associated with prematurity, low birth weight, pulmonary hypertension, heart block, acute kidney injury, and septicaemia. Down syndrome was present in more than half of atrioventricular septal defect patients and was associated with a higher incidence of pulmonary hypertension but less arrhythmia, lower mortality, shorter hospital stay, and less resource utilisation.

Continuous electroencephalography (cEEG) in infants with congenital heart disease (CHD).

BACKGROUND: Neonates with congenital heart disease (CHD) undergoing cardiopulmonary bypass (CPB) surgery have increased risk of impaired neurodevelopmental outcomes secondary to brain injury. This study aims to characterize pre- and post-operative continuous EEG (cEEG) patterns to detect abnormal cerebral activity in infants with CHD and investigate whether an association exists between the degree of encephalopathy in pre- and post-operative cEEG. METHODS: This retrospective cohort study conducted between 2010 and 2018 at a tertiary hospital in Cleveland, OH included infants with CHD with cEEG monitoring, who underwent CPB surgery within first 6 months of life. RESULTS: Study included 77 patients, of which 61% were males who were operated at median age 6 days. Pre-operatively, 69% and 87% had normal cEEG and sleep-wake cycles, respectively. Post-operatively, 80% had abnormal cEEG. Longer circulatory arrest time and CPB were associated with lack of continuity (p 0.011), excessive discontinuity (p 0.007) and prolonged inter-burst interval (IBI) duration (p value < 0.001). A significant association existed between severity of encephalopathy in immediate and 24-h post-operative period (p value < 0.001). CONCLUSIONS: More than 80% of neonates with CHD have abnormal post-operative EEG. Longer circulatory arrest time and CPB were associated with lack of continuity, excessive discontinuity, and prolonged IBI duration on post-operative EEG. IMPACT: This study shows that majority of neonates with congenital heart disease (CHD) have normal pre-operative EEG with a continuous background and normal sleep-wake cycles. Also, 80% of neonates had abnormal post-operative EEG. Longer duration of arrest time and bypass time was associated with lack of continuity, excessive discontinuity, and prolonged IBI duration during post-operative EEG monitoring. These findings will help clinicians when counseling parents in the intensive care unit, risk stratification, and long-term neurodevelopmental monitoring in these high-risk patients.

Acute kidney injury in infants diagnosed with congenital diaphragmatic hernia.

BACKGROUND: To assess the association and outcomes of acute kidney injury (AKI) in infants diagnosed with congenital diaphragmatic hernia (CDH). METHODS: We analyzed the National Inpatient Sample dataset for the years 2010 through 2018. We evaluated the prevalence and outcomes associated with AKI in infants diagnosed with CDH. Outcomes were assessed using regression analysis while controlling for variables. RESULTS: A total of 32,042,481 term infants were identified, of them 10,804 had CDH. Prevalence of AKI in infants with CDH was 6.5% compared to 0.05% in those without CDH (aOR = 14.7, CI: 13.0-16.6). ECMO was utilized at 62% of CDH infants that had AKI compared to 17% in infants without AKI (aOR = 4.22, CI: 3.38-5.27). Mortality was greater in CDH infants who developed AKI when compared to those without AKI (57.3 vs. 16.7%, aOR = 3.65, CI: 2.99-4.46). The trend of mortality in CDH infants who developed AKI decreased overtime, p < 0.001, while the trends for mortality in the overall CDH infants and in CDH infants without AKI did not change during the study period, p = 0.12. CONCLUSION: AKI is not uncommon in infants diagnosed with CDH. ECMO utilization and mortality are substantially increased in CDH infants when they develop AKI. IMPACT: Mortality in infants diagnosed with congenital diaphragmatic hernia (CDH) is relatively high despite advances in neonatal care. Infants with CDH are potentially at increased risk of acute kidney injury (AKI). Within CDH population, infants diagnosed with AKI are at increased risk for ECMO use and mortality. This is the largest study to address the association and outcomes of AKI in term infants diagnosed with CDH.

Impact of postnatal steroids on peripheral avascular retina and severity of retinopathy of prematurity.

BACKGROUND: We investigated the role of postnatal steroids on the severity of retinopathy of prematurity (ROP) and its impact on peripheral avascular retina (PAR). METHODS: A retrospective cohort study of infants born at ≤32 weeks gestation and/or birth weight ≤1500 g. Demographics, the dose and duration of steroid treatment, and age when full retinal vascularization occurred were collected. The primary outcomes were the severity of ROP and time to full vascularization of the retina. RESULTS: A total of 1695 patients were enrolled, 67% of whom received steroid therapy. Their birth weight was 1142 ± 396 g and gestational age was 28.6 ± 2.7 weeks. The total hydrocortisone-equivalent dose prescribed was 28.5 ± 74.3 mg/kg. The total days of steroid treatment were 8.9 ± 35.1 days. After correction for major demographic differences, infants who received a higher cumulative dose of steroids for a longer duration had a significantly increased incidence of severe ROP and PAR (P < 0.001). For each day of steroid treatment, there was a 3.2% increase in the hazard of the severe form of ROP (95% CI: 1.022-1.043) along with 5.7% delay in achieving full retinal vascularization (95% CI: 1.04-1.08) (P < 0.001). CONCLUSION: Cumulative dose and duration of postnatal steroid use were independently associated with the severity of ROP and PAR. Thus, postnatal steroids should be used very prudently. IMPACT: We report ROP outcomes in a large cohort of infants from two major healthcare systems where we have studied the impact of postnatal steroids on the severity of ROP, growth, and development of retinal vessels. After correcting our data for three major outcome measures, we show that high-dose postnatal steroids used for a prolonged duration of time are independently associated with severe ROP and delay in retinal vascularization. Postnatal steroids impact the visual outcomes of VLBW infants significantly, so their clinical use needs to be moderated.

Kidney replacement therapy in neonates: utilization trends and outcomes.

BACKGROUND: We aimed to assess prevalence and clinical characteristics of newborns receiving kidney replacement therapy (KRT). METHODS: We used the National Inpatient Sample (NIS) dataset for the years 2000-2017. Newborns treated with peritoneal dialysis (PD), hemodialysis (HD), and continuous KRT (CKRT) were included. Trend analysis using the Cochran-Armitage test was used to assess prevalence over the years. RESULTS: A total of 64,532,552 hospitalized newborns were included. Among the 4281 infants treated with KRT, 2501 (58.4%) were treated with PD, 997 (23.3%) had HD, and 783 (18.3%) used CKRT. Associated diagnoses included congenital kidney anomalies (37.4% vs. 15% vs. 9.5%), urinary tract anomalies (35% vs. 12.5% vs. 6.3%), and congenital heart disease (68% vs. 25.7% vs. 72.3%). Median length of stay was longest in PD patients (39 days vs. 18 days vs. 26 days), respectively. However, cost of hospitalization was greatest in CKRT patients (US $490,916 vs. US $218,514 vs. US $621,554), respectively. In the entire cohort, 54,424 newborns had acute kidney injury (AKI); of them 16,999 (31%) died. KRT was used in 2,688 (4.9%) of infants with AKI. Over the study period, trends for utilization of PD (from 0.042 to 0.06%) and CKRT (from 0.03 to 0.21%) increased whereas the hemodialysis trend decreased (from 0.021 to 0.013%). CONCLUSIONS: Congenital heart disease (CHD) and congenital anomalies of the kidneys and urinary tract (CAKUT) are the major diagnoses in newborns receiving KRT. Utilization of PD was greater than HD and CKRT. Trends of PD and CKRT utilization increased over time. Less than 5% of infants diagnosed with AKI received KRT.

Artificial intelligence in early detection and prediction of pediatric/neonatal acute kidney injury: current status and future directions.

Acute kidney injury (AKI) has a significant impact on the short-term and long-term clinical outcomes of pediatric and neonatal patients, and it is imperative in these populations to mitigate the pathways leading to AKI and be prepared for early diagnosis and treatment intervention of established AKI. Recently, artificial intelligence (AI) has provided more advent predictive models for early detection/prediction of AKI utilizing machine learning (ML). By providing strong detail and evidence from risk scores and electronic alerts, this review outlines a comprehensive and holistic insight into the current state of AI in AKI in pediatric/neonatal patients. In the pediatric population, AI models including XGBoost, logistic regression, support vector machines, decision trees, naïve Bayes, and risk stratification scores (Renal Angina Index (RAI), Nephrotoxic Injury Negated by Just-in-time Action (NINJA)) have shown success in predicting AKI using variables like serum creatinine, urine output, and electronic health record (EHR) alerts. Similarly, in the neonatal population, using the "Baby NINJA" model showed a decrease in nephrotoxic medication exposure by 42%, the rate of AKI by 78%, and the number of days with AKI by 68%. Furthermore, the "STARZ" risk stratification AI model showed a predictive ability of AKI within 7 days of NICU admission of AUC 0.93 and AUC of 0.96 in the validation and derivation cohorts, respectively. Many studies have reported the superiority of using biomarkers to predict AKI in pediatric patients and neonates as well. Future directions include the application of AI along with biomarkers (NGAL, CysC, OPN, IL-18, B2M, etc.) in a Labelbox configuration to create a more robust and accurate model for predicting and detecting pediatric/neonatal AKI.

Trends of neonatal hypoxic-ischemic encephalopathy prevalence and associated risk factors in the United States, 2010 to 2018.

BACKGROUND: Despite recent advances in perinatal care, neonatal hypoxic-ischemic encephalopathy remains one of the most common causes of neonatal morbidity and mortality. The trends for prevalence and mortality of neonatal hypoxic-ischemic encephalopathy have not been examined in the era of therapeutic hypothermia in the United States. OBJECTIVE: This study aimed to determine (1) the overall and gestational age-specific (35-36, ≥37, and >42 weeks) trends of hypoxic-ischemic encephalopathy prevalence and use of therapeutic hypothermia, (2) the trends of mortality in association with hypoxic-ischemic encephalopathy, (3) the confounding variables associated with hypoxic-ischemic encephalopathy, and (4) the clinical outcomes of neonates with hypoxic-ischemic encephalopathy. STUDY DESIGN: This study used National Inpatient Sample datasets from 2010 to 2018. Moreover, the study included infants with a gestational age of ≥35 weeks with a documented hypoxic-ischemic encephalopathy diagnosis (mild, moderate, severe, or unspecified). We calculated trends in hypoxic-ischemic encephalopathy prevalence and the use of therapeutic hypothermia using chi-squared testing. Furthermore, this study used logistic regression models to control for confounders. RESULTS: A total of 32,180,617 infants were included, of which 31,249,100 were term (gestational age of ≥37 weeks) and 931,517 were late preterm (gestational age of 35-36 weeks). Hypoxic-ischemic encephalopathy prevalence slightly increased from 0.093% in 2010-2012 to 0.097% in 2016-2018 (P=.01) in term infants and did not significantly change in late preterm infants (P=.20). There were 6235 term infants (20.8%) and 449 late preterm infants (21.1%) with hypoxic-ischemic encephalopathy who were managed with therapeutic hypothermia. The use of therapeutic hypothermia in both term and late preterm infants has increased over the years (P<.01). The mortality rate with hypoxic-ischemic encephalopathy decreased over time from 11.5% to 12.3% between 2010 to 2012, and from 8.3% to 10.6% betweenn 2016 to 2018 (P<.01). The factors with the strongest association with hypoxic-ischemic encephalopathy were placental infarction or insufficiency (odds ratio, 144; 95% confidence interval, 134-157), placental abruption (odds ratio, 101; 95% confidence interval, 91-112), cord prolapse (odds ratio, 74; 95% confidence interval, 65-84), and maternal anemia (odds ratio, 26; 95% confidence interval, 20-37). CONCLUSION: Hypoxic-ischemic encephalopathy prevalence in neonates essentially remained the same at 1 per 1000 live births. The use of therapeutic hypothermia increased, and the mortality rate decreased in infants with hypoxic-ischemic encephalopathy. The identification of hypoxic-ischemic encephalopathy-associated factors should promote increased vigilance to optimize newborn outcomes.

Neonatal hyperbilirubinemia and bilirubin neurotoxicity in hospitalized neonates: analysis of the US Database.

OBJECTIVE: The objective of this study was to assess the prevalence and trends for neonatal hyperbilirubinemia, and the development of bilirubin neurotoxicity in the USA. STUDY DESIGN: We used a de-identified national dataset for the years 2002-2017. The study included all newborn inpatients with postnatal age ≤28 days. Cochran-Armitage trend test was used for trend analyses. Regression analyses were performed and adjusted odds ratios (aOR) were reported. RESULTS: The study included 57,989,476 infants; of them 53,259,758 (91.8%) were term infants and 4,725,178 (8.2%) were preterm infants. Bilirubin neurotoxicity decreased over the years in term infants (Z = 0.36, p = 0.03) without change in preterm infants (Z = 42.5, p = 0.12). Black neonates were less likely to be diagnosed with hyperbilirubinemia than White neonates (aOR = 0.77, 95% confidence interval (CI): 0.77-0.78, p < 0.001) and more likely to develop bilirubin neurotoxicity than White neonates (aOR = 3.0.5, 95% CI: 2.13-4.36, p < 0.001). Bilirubin neurotoxicity rate in the overall population was 2.4 per 100,000 live births. CONCLUSIONS: Bilirubin neurotoxicity has significantly decreased in term infants and did not change in preterm infants. Despite the less diagnosis of hyperbilirubinemia in Black newborns, they are disproportionately at increased risk of developing bilirubin neurotoxicity when compared to White newborns. IMPACT: In this article, we analyzed the National Inpatient Database. This is the largest study of its kind using data on 57,989,476 neonates. The article has multiple novel findings: (1) it demonstrated that utilization of phototherapy has increased significantly over the years, (2) the rate of kernicterus for neonates decreased in term infants and did not change in preterm babies, (3) kernicterus was mostly encountered in infants without isoimmunization jaundice, and (4) there is a clear racial disparity in neonatal jaundice; although Black newborns have less neonatal jaundice, they are at increased risk of developing kernicterus.

Stroke in pediatric ECMO patients: analysis of the National Inpatient Sample (NIS) database.

BACKGROUND: The rates, outcomes, and long-term trends of stroke complicating the use of extracorporeal membrane oxygenation (ECMO) have been inconsistently reported. We compared the outcomes of pediatric ECMO patients with and without stroke and described the frequency trends between 2000 and 2017. METHODS: Using the National Inpatient Sample (NIS) database, pediatric patients (age ≤18 years) who received ECMO were identified using ICD-9&10 codes. Binary, regression, and trend analyses were performed to compare patients with and without stroke. RESULTS: A total of 114,477,997 records were reviewed. Overall, 28,695 (0.025%) ECMO patients were identified of which 2982 (10.4%) had stroke, which were further classified as hemorrhagic (n = 1464), ischemic (n = 1280), or combined (n = 238). Mortality was higher in the hemorrhagic and combined groups compared to patients with ischemic stroke and patients without stroke. Length of stay (LOS) was significantly longer in stroke vs. no-stroke patients. Hypertension and septicemia were more encountered in the hemorrhagic group, whereas the combined group demonstrated higher frequency of cardiac arrest and seizures. CONCLUSIONS: Over the years, there is an apparent increase in the diagnosis of stroke. All types of stroke in ECMO patients are associated with increased LOS, although mortality is increased in hemorrhagic and combined stroke only. IMPACT: Stroke is a commonly seen complication in pediatric patients supported by ECMO. Understanding the trends will help in identifying modifiable risk factors that predict poor outcomes in this patient population.

Trends in Procedures in the Neonatal Intensive Care Unit.

OBJECTIVE: The aim of the study is to identify the rates and trends of various procedures performed on newborns. STUDY DESIGN: The Healthcare Cost and Utilization Project (HCUP) database for the years 2002 to 2015 was queried for the number of livebirths, and various procedures using International Classification of Diseases, Ninth Revision (ICD-9) codes. These were adjusted to the rate of livebirths in each particular year. A hypothetical high-volume hospital based on data from the last 5 years was used to estimate the frequency of each procedure. RESULTS: Over the study period, there was a decline in the rates of exchange transfusions and placement of arterial catheters. There was an increase in the rates of thoracentesis, abdominal paracentesis, placement of umbilical venous catheter (UVC) lines, and central lines with ultrasound or fluoroscopic guidance. No change was observed in the rates of unguided central lines, pericardiocentesis, bladder aspiration, intubations, and LP. Intubations were the most performed procedures. Placement of UVC, central venous lines (including PICCs), arterial catheters, and LP were relatively common, whereas others were rare such as pericardiocentesis and paracentesis. CONCLUSION: Some potentially lifesaving procedures are extremely rare or decreasing in incidence. There has also been an increase in utilization of fluoroscopic/ultrasound guidance for the placement of central venous catheters. KEY POINTS: · Advances in neonatal care have impacted the number of procedures performed in the NICU.. · It is unclear whether invasive procedures occur at rates sufficient for adequate training and maintenance of skills.. · Understanding the NICU procedural trends is important in designing simulation and competency-based medical education programs..

The U.S. National Trend for Retinopathy of Prematurity.

OBJECTIVE: The use of supplemental oxygen in premature infants is essential for survival. However, its use has been associated with unintended complications. The restricted use of oxygen is associated with increased mortality and necrotizing enterocolitis (NEC), whereas its liberal use is associated with increased risk for retinopathy of prematurity (ROP). Although there is no clear consensus on the acceptable oxygen saturation range, clinicians have recently become more liberal with the use of oxygen. We aim to assess (1) the national trends for ROP in very low birth weight preterm infants, and (2) the associated trends in mortality, NEC, intraventricular hemorrhage (IVH), and length of hospital stay (LOS). STUDY DESIGN: We analyzed deidentified patient data from the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) from 2002 to 2017. All infants with gestational age ≤32 weeks and birth weight <1,500 g were included. Trends in ROP, severe ROP, mortality, NEC, IVH, severe IVH, and LOS were analyzed using Jonckheere-Terpstra test. RESULTS: A total of 818,945 neonates were included in the study. The overall mortality was 16.2% and the prevalence of ROP was 17.5%. There was a significant trend for increased ROP over the years (p < 0.001). Severe ROP was also significantly increased (p < 0.001). This was associated with a significant trend for increased median LOS in survived infants (p < 0.001). Mortality was significantly decreased (p < 0.001), whereas NEC and severe NEC did not change over time (p = 0.222 and p = 0.412, respectively). CONCLUSION: There is a national trend for increased ROP and severe ROP over the 16 years of the study period. This trend was associated with a significant increase in the LOS in survived infants without change in NEC. KEY POINTS: · Prevalence of ROP and severe ROP has increased in VLBW infants over the 16-year study period.. · The prevalence of NEC did not change over the same time period.. · Increased ROP and severe ROP were consistent in all three GA and BW subgroups..

A Randomized Controlled Trial of a 30- versus a 120-Second Delay in Cord Clamping after Term Birth.

OBJECTIVE: Delayed cord clamping (DCC) has been recently adopted in neonatal resuscitation. The immediate cardiac hemodynamic effects related to DCC more than 30 seconds was not studied. We aimed to study the effect of DCC at 120 seconds compared with 30 seconds on multiple hemodynamic variables in full-term infants using an electrical cardiometry (EC) device. STUDY DESIGN: Present study is a randomized clinical trial. The study was conducted with full-term infants who were delivered at the Obstetrics and Gynecology Department in Cairo University Hospital. Sixty-eight full term infants were successfully enrolled in this trial. Cardiac output (CO) and other hemodynamic parameters were evaluated in this study by EC device. Hemoglobin, glucose, and bilirubin concentrations were measured at 24 hours. Newborn infants were assigned randomly into group 1: DCC at 30 seconds, and group 2: DCC at 120 seconds, based on the time of cord clamping. RESULTS: Stroke volume (SV) (mL) and CO (L/min) were significantly higher in group 2 compared with group 1 at 5 minutes (6.71 vs. 5.35 and 1.09 vs. 0.75), 10 minutes (6.43 vs. 5.59 and 0.88 vs. 0.77), 15 minutes (6.45 vs. 5.60 and 0.89 vs. 0.76), and 24 hours (6.67 vs. 5.75 and 0.91vs. 0.81), respectively. Index of contractility (ICON; units) was significantly increased in group 2 at 5 minutes compared with group1 (114.2 vs. 83.8). Hematocrit (%) and total bilirubin concentrations (mg/dL) at 24 hours were significantly increased in group 2 compared with group 1 (51.5 vs. 40.5 and 3.8 vs. 2.9, respectively). CONCLUSION: Stroke volume and cardiac output are significantly higher in neonates with DCC at 120 seconds compared with 30 seconds that continues for the first 24 hours. KEY POINTS: · CO is significantly increased with DCC at 120 seconds.. · SV is significantly increased with DCC at 120 seconds.. · Such effects continued during the entire 24 hours of life in full-term infants..

Superior Mesenteric Artery Blood Flow in Parenterally Fed Versus Enterally Fed Preterm Infants.

OBJECTIVES: The aim of the study was to compare superior mesenteric artery (SMA) flow in premature infants with parenteral and enteral nutrition. METHODS: A prospective study was conducted on 2 groups of preterm infants with gestational age of 280/7 to 366/7 weeks: group 1 did not qualify for early enteral feeds and received parenteral nutrition (PN), and group 2 received early enteral feeding. SMA peak systolic velocity (PSV), end diastolic velocity (EDV), and pulsatility index (PI) were measured using Doppler ultrasound before starting feeds at day 1 and at day 5. RESULTS: The study recruited 40 infants; 20 in each group. At baseline, PSV, EDV, and PI did not differ between groups. At day 5, enteral nutrition was associated with significant increases in PSV (91.53 ±â€Š29.15 vs 65.49 ±â€Š19.18, P = 0.003) and EDV (15.91 ±â€Š7.01 vs 11.65 ±â€Š5.58, P = 0.026) and a decrease in PI (1.28 ±â€Š0.40 vs 2.48 ±â€Š0.83, P < 0.001). Regression analysis to control for confounders showed enterally fed infants to have increased PSV (adjusted odds ratio [aOR] = 25.45; 95% confidence interval [CI]: 8.53-42.38, P = 0.004) and EDV (aOR 8.630; 95% CI: 2.987-14.273, P = 004) and decreased PI (aOR = -1.133; 95% CI: -1.603 to -0.664, P < 0.001). Infants in the PN group later developed more frequent feeding intolerance when compared with the enterally fed group (65% vs 15%, respectively, P < 0.001). CONCLUSIONS: In preterm neonates, early EF is associated with increased SMA blood flow, decreased vascular intestinal resistance, and less frequent incidence of feeding intolerance.

Trends and racial disparities for acute kidney injury in premature infants: the US national database.

BACKGROUND: To assess prevalence and outcomes of acute kidney injury (AKI) in very-low-birth-weight infants. METHODS: This cross-sectional study utilized the National Inpatient Sample (NIS) dataset for years 2000-2017. All premature infants with birth weight (BW) <1500g and/or gestational age (GA) ≤32 weeks were included. Analyses were conducted for overall population and two BW categories: <1000g and 1000-1499g. Adjusted odds ratios were calculated after controlling for confounding variables in logistic regression analysis. Cochrane-Armitage test was used to assess for statistically significant trends in AKI frequency over the years. RESULTS: In total, 1,311,681 hospitalized premature infants were included; 19,603 (1.5%) were diagnosed with AKI. The majority (74.3%) were BW <1000g and 63.9% ≤28 weeks gestation. Prevalence of AKI differed by ethnicity; White had significantly less AKI than Black (OR=0.79, p<0.001) and Hispanic (OR=0.83, p<0.001). AKI was significantly associated with higher mortality compared to controls (35.1 vs. 3.0%, p<0.001). AKI was associated with comorbidities such as necrotizing enterocolitis, patent ductus arteriosus, bronchopulmonary dysplasia, intraventricular hemorrhage, and septicemia. In a regression model, AKI was associated with higher mortality after controlling confounding factors (aOR=7.79, p<0.001). AKI was associated with significant increase in length of stay (p<0.001) and cost of hospitalization in survivors (p<0.001). There is a significant trend for increased AKI frequency over the years (Z score=4.33, p<0.001). CONCLUSION: AKI is associated with increased mortality and comorbidities in preterm infants, especially in infants with BW <1000g. Further studies are needed to understand precipitating factors and assess preventative measures for this serious complication.

Esophageal perforation in very low birth weight infants.

We aimed to assess the prevalence and outcomes of esophageal perforation in very low birth weight infants. This retrospective cohort study utilized the US National Inpatient Sample dataset for the years 2000 to 2017. A total of 1,755,418 very low birth weight infants were included; of them, 861 (0.05%) were diagnosed with esophageal perforation. The majority (77.9%) of infants were in the birth weight category < 1000 g and 77.7% in infants ≤ 28 weeks of gestation. The majority (73%) of infants were tracheally intubated and received mechanical ventilation; of them, 24 infants (2.8%) had tracheostomy. Mortality associated with esophageal perforation was 25.8%. Regression analysis did not show an association between esophageal perforation and increased mortality in preterm infants (aOR = 1.0, CI: 0.83-1.20, p = 0.991). Procedures encountered in these infants include thoracentesis (10.8%), laparotomy (4.1%), percutaneous abdominal drainage (4.1%), and gastrostomy tube insertion (6.2%), whereas the rest of the infants were managed conservatively. There was a significant trend for increasing prevalence of esophageal perforation over the years.Conclusion: Esophageal perforation does not independently increase the risk for mortality in very low birth weight infants. The increasing prevalence is possibly related to increased care offered to infants at limits of viability in recent years. What is Known: • Knowledge about esophageal perforation is derived from anecdotal single-center case reports. • Esophageal perforation in neonates is mostly iatrogenic. • It is considered a critical complication that is associated with high mortality. What is New: • This is the first and largest national study on prevalence of esophageal perforation in preterm infants. • Esophageal perforation does not independently increase the risk for mortality. • Septicemia and pneumothorax are frequent complications to esophageal perforation.

Construct validity and response to therapy of the U9 ultrasonographic scale for assessment of disease activity in rheumatoid arthritis.

OBJECTIVES: To test the construct validity of the U9 ultrasonographic scale, to determine the cut-off points for different degrees of rheumatoid arthritis (RA) activity, and to determine whether or not US assessment with the U9 score is useful for monitoring the response to treatment of RA. MATERIAL AND METHODS: A prospective, multicenter study was conducted in 4 different centers in Egypt. All RA patients who were recruited were subject to evaluation of clinical disease activity by the Clinical Disease Activity Index (CDAI) and Disease Activity Score of 28 joints based on erythrocyte sedimentation rate (DAS28-ESR). Assessment of the Functional Status by the Health Assessment Questionnaire (HAQ) and U9 ultrasound score was performed. All the targeted joints were assessed by EULAR recommendations and the combined score of EULAR/OMERACT (0-3). Targeted tendons scored 0-3. After three months of treatment, CDAI and DAS28-ESR, HAQ, and U9 were repeated to detect the response. RESULTS: One hundred and forty patients with mean age 39.26 ±11.30 were recruited from 4 centers. With regard to convergent validity, the U9 ultrasonographic scale was significantly associated with clinical parameters (CDAI and DAS28-ESR) as well as functional state (HAQ) at both visits. Likewise, concerning discriminative validity, the U9 scale showed the ability to distinguish different grades of RA activity, presenting well-defined cut-off points of different grades (severe, moderate, and mild), with very good specificity and sensitivity (11.5, 5.5, and 3.5, respectively). A significant parallel decrease was detected in clinical and sonographic scales at the follow-up assessment. CONCLUSIONS: The U9 ultrasound scale showed good construct (convergent and discriminative) validity and can be used to monitor the disease and therapeutic response to treatment in RA.