Analysis of perinatal risk factors for massive pulmonary hemorrhage in very low birth weight infant: A nationwide large cohort database.

OBJECTIVE: To determine perinatal risk factors for Massive pulmonary hemorrhage (MPH) and MPH-caused mortality to guide clinicians in implementing preventive measures at the beginning of life for improving the survival of very low birth weight infant (VLBWIs). STUDY DESIGN: A total of 13,826 VLBWIs born between 2013 and 2020 in the Korean Neonatal Network database were included. RESULTS: MPH occurred in 870 (6.3 %) VLBWIs. Among infants with MPH, 162 (18.6 %) VLBWIs died due to MPH. In the multivariate logistic regression analysis, independent risk factors for MPH were identified as small for gestational age, multiple gestation, high CRIB-II score, use of surfactant, and symptomatic patent ductus arteriosus (sPDA) in VLBIWs. Independent risk factors for MPH-caused mortality were identified as multiple gestation in VLBWIs. Receiving a complete course of antenatal corticosteroids (ACS) was found to be a significant independent protective factor for MPH-caused mortality in VLBWIs. CONCLUSION: Proactive managements for reducing unnecessary use of pulmonary surfactant and for decreasing the risk of sPDA at the beginning of life could be recommended as preventive strategies to reduce the risk of MPH in extremely preterm infants. ACS therapy is highly recommended for women with a high likelihood of giving birth preterm to reduce the risk of mortality caused by MPH.

Particulate matter induces arrhythmia-like cardiotoxicity in zebrafish embryos by altering the expression levels of cardiac development- and ion channel-related genes.

Air pollution is a risk factor that increases cardiovascular morbidity and mortality. In this study, we investigated the cardiotoxicity of particulate matter (PM) exposure using a zebrafish embryo model. We found that PM exposure induced cardiotoxicity, such as arrhythmia, during cardiac development. PM exposure caused cardiotoxicity by altering the expression levels of cardiac development (T-box transcription factor 20, natriuretic peptide A, and GATA-binding protein 4)- and ion-channel (scn5lab, kcnq1, kcnh2a/b, and kcnh6a/b)-related genes. In conclusion, this study showed that PM induces the aberrant expression of cardiac development- and ion channel-related genes, leading to arrhythmia-like cardiotoxicity in zebrafish embryos. Our study provides a foundation for further research on the molecular and genetic mechanisms of cardiotoxicity induced by PM exposure.

The Effect of Maternal Exposure to Air Pollutants and Heavy Metals during Pregnancy on the Risk of Neurological Disorders Using the National Health Insurance Claims Data of South Korea.

The objective of this study was to evaluate the effects of high levels of maternal exposure to ambient air pollution and heavy metals on risks of autism spectrum disorder (ASD) and epilepsy using the National Health Insurance claims data of South Korea. The data of mothers and their newborns from 2016 to 2018 provided by the National Health Insurance Service were used (n = 843,134). Data on exposure to ambient air pollutants (PM2.5, CO, SO2, NO2, and O3) and heavy metals (Pb, Cd, Cr, Cu, Mn, Fe, Ni, and As) during pregnancy were matched based on the mother's National Health Insurance registration area. SO2 (OR: 2.723, 95% CI: 1.971-3.761) and Pb (OR: 1.063, 95% CI: 1.019-1.11) were more closely associated with the incidence of ASD when infants were exposed to them in the third trimester of pregnancy. Pb (OR: 1.109, 95% CI: 1.043-1.179) in the first trimester of pregnancy and Cd (OR: 2.193, 95% CI: 1.074-4.477) in the third trimester of pregnancy were associated with the incidence of epilepsy. Thus, exposure to SO2, NO2, and Pb during pregnancy could affect the development of a neurologic disorder based on the timing of exposure, suggesting a relationship with fetal development. However, further research is needed.

Association of delayed initiation of non-invasive respiratory support with pulmonary air leakage in outborn late-preterm and term neonates.

The frequency of non-invasive respiratory support use has increased in neonates of all gestational ages with respiratory distress (RD). However, the impact of delayed initiation of non-invasive respiratory support in outborn neonates remains poorly understood. This study aimed to identify the impact of the delayed initiation of non-invasive respiratory support in outborn, late-preterm, and term neonates. Medical records of 277 infants (gestational age of ≥ 35 weeks) who received non-invasive respiratory support as primary respiratory therapy < 24 h of age between 2016 and 2020 were retrospectively reviewed. Factors associated with respiratory adverse outcomes were investigated in 190 outborn neonates. Infants with RD were divided into two groups: mild (fraction of inspired oxygen [FiO2] ≤ 0.3) and moderate-to-severe RD (FiO2 > 0.3), depending on their initial oxygen requirements from non-invasive respiratory support. The median time for the initiation of non-invasive respiratory support at a tertiary center was 3.5 (2.2-5.0) h. Male sex, a high oxygen requirement (FiO2 > 0.3), high CO2 level, and respiratory distress syndrome were significant factors associated with adverse outcomes. Subgroup analysis revealed that in the moderate-to-severe RD group, delayed commencement of non-invasive respiratory support (≥ 3 h) was significantly associated with pulmonary air leakage (p = 0.033). CONCLUSION: Our study shows that outborn neonates with moderate-to-severe RD, who were treated with delayed non-invasive respiratory support, were associated with an increased likelihood of pulmonary air leakage. Additional prospective studies are required to establish the optimal timing and methods of non-invasive respiratory support for outborn, late-preterm, and term infants. WHAT IS KNOWN: • Non-invasive respiratory support is widely used in neonates of all gestational ages. • Little is known on the impact of delayed initiation of non-invasive respiratory support in outborn, late preterm, and term neonates. WHAT IS NEW: • Male sex, high oxygen requirement (FiO2 >0.3), high initial CO2 level, and respiratory distress syndrome significantly correlated with adverse outcomes. • Outborn late-preterm and term neonates with high oxygen requirement who were treated with delayed non-invasive respiratory support indicated an increased likelihood of pulmonary air leakage.

The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study.

BACKGROUND: The genetic polymorphisms of the alpha-2A adrenergic receptor (ADRA2A), which plays a significant role in sedation, anxiety relief, and antinociception, particularly in dexmedetomidine, may differ in the degree of sedation. This study aimed to investigate the effect of the genetic polymorphisms of ADRA2A (rs11195418, rs1800544, rs2484516, rs1800545, rs553668, rs3750625) on the sedative effects of dexmedetomidine. METHODS: A total of 131 patients aged 50 years or more from May 2018 to August 2019 were included in this study. The ADRA2A gene variants were evaluated using the TaqMan Assay. Dexmedetomidine diluted in normal saline to a concentration of 4µg.mL-1 was infused at a dose of 2µg.kg-1 to achieve procedural sedation (modified Ramsay sedation scale 4 [mRSS 4]). RESULTS: A total of 131 patients were evaluated. The genetic polymorphisms (rs11195418) of the ADRA2A receptor gene demonstrated no variation in our participants. The ADRA2A receptor gene polymorphisms (rs1800544, rs2484516, rs1800545, rs553668, and rs3750625) exhibited no differences in total dexmedetomidine doses (p>0.217), bispectral index at mRSS 4 (p>0.620), and time to obtain mRSS 4 (p>0.349). CONCLUSION: This study suggested that the genetic polymorphisms of ADRA2A did not affect the sedative efficacy of dexmedetomidine.

Size of Patent Ductus Arteriosus and Echocardiographic Markers of Shunt Volume in Preterm Infants Based on Postnatal Age.

Objective: This study was conducted in order to compare the strength of correlation between echocardiographic markers of shunt volume and patent ductus arteriosus (PDA) diameter based on postnatal age. Methods: This retrospective study focused on preterm infants (aged <32 weeks of gestation) admitted to the Neonatal Intensive Care Unit of Korea University Ansan Hospital, between April 2014 and December 2017, who studied serial targeted neonatal echocardiography (TNE) for PDA during hospitalization. The association between echocardiographic characteristics and duct size was divided into the following days: within 3 days (very early, VE), 4-7 days after birth (early, E), and after 8 days of birth (late, L). Results: We found 113 assessments conducted on 57 infants in the VE period, 92 assessments on 40 infants in the E period, and 342 assessments on 37 infants in the L period. Median gestational age and birth weight were 28+2 weeks of gestation and 1,115 g, respectively. In the univariate regression analysis, we found a statistically significant correlation between PDA diameter and all TNE markers in the E and L days, but not in the VE period. Only ductal velocity [coefficient of determination (R 2) = 0.224], antegrade left pulmonary artery diastolic flow velocity (R 2 = 0.165), left ventricular output (LVO)/superior vena cava (SVC) flow ratio (R 2 = 0.048), and E/A wave ratio (R 2 = 0.092) showed weak correlations with PDA diameter in the VE period. The slopes of the regressions showed significant changes based on postnatal age in the maximum ductal velocity, left atrium/aorta ratio, LVO/SVC flow ratio, and LVO. Conclusions: It is difficult to predict the echocardiographic markers of shunt volume based on the PDA diameter in preterm infants younger than 4 days. A better understanding of the changes in the hemodynamic consequences of PDA based on postnatal age is needed when considering treatment.

Perinatal Outcomes Associated with Latency in Late Preterm Premature Rupture of Membranes.

This study aims to evaluate the perinatal outcomes of preterm premature rupture of membrane (PPROM) with latency periods at 33 + 0-36 + 6 weeks of gestation. This retrospective case-control study included women with singleton pregnancies who delivered at 33 + 0-36 + 6 weeks at Korea University Ansan Hospital in South Korea between 2006-2019. The maternal and neonatal characteristics were compared between different latency periods (expectant delivery ≥72 h vs. immediate delivery <72 h). Data were compared among 345 women (expectant, n = 39; immediate delivery, n = 306). There was no significant difference in maternal and neonatal morbidities between the groups, despite the younger gestational age in the expectant delivery group. Stratified by gestational weeks, the 34-week infants showed a statistically significant lower exposure to antenatal steroids (73.4% vs. 20.0%, p < 0.001), while the incidence of respiratory distress syndrome (12.8%) and the use of any respiratory support (36.8%) was higher than those in the 33-week infants, without significance. Our study shows that a prolonged latency period (≥72 h) did not increase maternal and neonatal morbidities, and a considerable number of preterm infants immediately delivered at 34 weeks experienced respiratory complications. Expectant management and antenatal corticosteroids should be considered in late preterm infants with PPROM.

Liver Transplant Patients with High Levels of Preoperative Serum Ammonia Are at Increased Risk for Postoperative Acute Kidney Injury: A Retrospective Study.

Acute kidney injury (AKI) is one of the most frequent postoperative complications after liver transplantation (LT). Increased serum ammonia levels due to the liver disease itself may affect postoperative renal function. This study aimed to compare the incidence of postoperative AKI according to preoperative serum ammonia levels in patients after LT. Medical records from 436 patients who underwent LT from January 2010 to February 2020 in a single university hospital were retrospectively reviewed. The patients were then categorized according to changes in plasma creatinine concentrations within 48 h of LT using the Acute Kidney Injury Network criteria. A preoperative serum ammonia level above 45 mg/dL was associated with postoperative AKI (p < 0.0001). Even in patients with a normal preoperative creatinine level, when the ammonia level was greater than 45 µg/dL, the incidence of postoperative AKI was significantly higher (p < 0.0001); the AKI stage was also higher in this group than in the group with preoperative ammonia levels less than or equal to 45 µg/dL (p < 0.0001). Based on the results of our research, an elevation in preoperative serum ammonia levels above 45 µg/dL is related to postoperative AKI after LT.

Liver Transplant Patients with High Preoperative Serum Bilirubin Levels Are at Increased Risk of Postoperative Delirium: A Retrospective Study.

Postoperative delirium is a common complication after liver transplantation (LT). A high model for end-stage liver disease (MELD) score is an independent risk factor for postoperative delirium, but it is unclear which of the components of this score are risk indicators. The aim of this study was to analyze the incidence of postoperative delirium according to the preoperative serum bilirubin level, a component of the MELD score, in patients who underwent LT. The medical records of 325 patients who underwent LT from January 2010 to February 2019 at a single university hospital were retrospectively reviewed. The patients were divided into two groups: those who experienced postoperative delirium (Delirium group, n = 69) and those who did not (Control group, n = 256). Data on the patients' demographic characteristics, perioperative management, and postoperative complications were collected. Mean preoperative bilirubin level was higher in the Delirium group than in the Control group (p < 0.0001). In the Delirium group, 54 (78.26%) patients had preoperative bilirubin levels above 3.5 mg/dL. In the multivariate analysis, preoperative bilirubin above 3.5 mg/dL was associated with postoperative delirium (p = 0.002). Therefore, preoperative hyperbilirubinemia is an independent risk factor for postoperative delirium.

Effectiveness of nCPAP for moderate preterm infants compared to BiPAP: A Randomized, Controlled Non-Inferiority Trial.

BACKGROUND: Bilevel positive airway pressure (BiPAP) has recently been used in preterm infants with respiratory distress as an alternative to nasal continuous positive airway pressure (nCPAP) because, theoretically, BiPAP is thought to be more effective than nCPAP. However, the results of some studies comparing nCPAP with BiPAP as the initial respiratory support were controversial. The aim of this study is to compare the clinical effectiveness and safety of nCPAP with BiPAP at gestational ages of 30+0 to 34+6  weeks. METHODS: A total of 93 infants with gestational ages of 30+0 to 34+6  weeks, who presented with respiratory distress within 24 h after birth, were randomized to the nCPAP group or the BiPAP group. The primary outcome was the incidence of treatment failure with these two non-invasive respiratory support devices. Criteria for treatment failure included any of the following: respiratory acidosis (PaCO2 >65 mmHg with pH <7.2), hypoxia (FiO2 >0.4), or apnea (>2-3 episodes of apnea/h). RESULTS: There was no statistically significant difference in treatment failure between the two groups (P = 0.576). The risk difference comparing treatment failure rate between nCPAP and BiPAP groups was -4.7% (95% CI: -21.5-11.9). CONCLUSIONS: Nasal continuous positive airway pressure is not inferior to BiPAP as an initial management of respiratory distress in these premature infants. We therefore conclude that nCPAP can be used as an initial management for preterm infants at gestational age of between 30 and 35 weeks as a substitute for BiPAP.

Analysis of the association between necrotizing enterocolitis and transfusion of red blood cell in very low birth weight preterm infants.

PURPOSE: To investigate the association between necrotizing enterocolitis (NEC) and red blood cell transfusions in very low birth weight (VLBW) preterm infants. METHODS: We studied were 180 VLBW preterm infants who were admitted to the neonatal intensive care unit of CHA Gangnam Hospital from January of 2006 to December of 2009. The subjects were divided into 2 groups: an NEC group (greater than stage II on the modified Bell's criteria) and a control group (less than stage II on the modified Bell's critieria). We defined red blood cell transfusion before NEC diagnosis as the frequency of transfusion until NEC diagnosis (mean day at NEC diagnosis, day 18) in the NEC group and the frequency of transfusion until 18 days after birth in the control group. RESULTS: Of the 180 subjects, 18 (10%) belonged to the NEC group, and 14 (78%) of these 18 patients had a history of transfusion before NEC diagnosis. The NEC group received 3.1±2.9 transfusions, and the control group received 1.0±1.1 transfusions before the NEC diagnosis (P=0.005). In a multivariate logistic regression corrected for gestational age, Apgar score at 1 minute, the presence of respiratory distress syndrome, patent ductus arteriosus, premature rupture of membrane, disseminated intravascular coagulopathy and death were confounding factors. The risk of NEC increased 1.63 times (95% confidence interval, 1.145 to 2.305; P=0.007) with transfusion before the NEC diagnosis. CONCLUSION: The risk for NEC increased significantly with increased transfusion frequency before the NEC diagnosis.

Can early B-type natriuretic peptide assays predict symptomatic patent ductus arteriosus in extremely low birth weight infants?

BACKGROUND: Earlier and more accurate identification of a high-risk group of preterm infants that are likely to develop a hemodynamically significant patent ductus arteriosus (hsPDA) would allow specific targeting of early treatment and thus possibly minimize the morbidity and mortality associated with a PDA in extremely low birth weight (ELBW) infants. OBJECTIVE: To investigate the predictability of B-type natriuretic peptide (BNP) for early targeted treatment of hsPDA in ELBW infants. METHODS: 73 ELBW infants that underwent echocardiographic evaluation and plasma BNP measurement after birth were enrolled. 31 infants developed hsPDA (HsPDA group) and 42 infants did not develop hsPDA (nPDA group). RESULTS: BNP levels of the HsPDA group were significantly higher than those of the nPDA group at 24 h of age (921 [318-2,133] vs. 152 [91-450] pg/ml) but not different at 12 h of age. BNP levels at 24 h of age were significantly correlated with the magnitudes of the ductal shunt but not at 12 h of age. The area under the receiver operator characteristic curve of BNP levels for prediction of hsPDA at 24 h of age was 0.830. At the cutoff BNP levels of 200 and 900 pg/ml at 24 h of age, sensitivity was 83.9 and 54.8% and specificity was 61.9 and 95.2%, respectively. CONCLUSIONS: BNP levels at 24 h of age can be used as a guide for early targeted treatment of hsPDA and avoid the unnecessary use of cyclooxygenase inhibitors in ELBW infants.

Early neurodevelopment in very low birth weight infants with mild intraventricular hemorrhage or those without intraventricular hemorrhage.

PURPOSE: This study aimed to assess early development in very low birth weight (VLBW) infants with mild intraventricular hemorrhage (IVH) or those without IVH and to identify the perinatal morbidities affecting early neurodevelopmental outcome. METHODS: Bayley Scales of Infant Development-II was used for assessing neurological development in 49 infants with a birth weight <1,500 g and with low grade IVH (≤grade II) or those without IVH at a corrected age of 12 months. RESULTS: Among the 49 infants, 19 infants (38.8%) showed normal development and 14 (28.6%) showed abnormal mental and psychomotor development. Infants with abnormal mental development (n=14) were mostly male and had a longer hospitalization, a higher prevalence of patent ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD), and were under more frequent postnatal systemic steroid treatment compared with infants with normal mental development (n=35, P<0.05). Infants with abnormal psychomotor development (n=29) had a longer hospitalization and more associated PDA compared to infants with normal psychomotor development (n=20, P<0.05). Infants with abnormal mental and psychomotor development were mostly male and had a longer hospitalization and a higher prevalence of PDA and BPD compared to infants with normal mental and psychomotor development (n=19, P<0.05). Using multiple logistic regression analysis, a longer duration of hospitalization and male gender were found to be significant risk factors. CONCLUSION: Approximately 62% of VLBW infants with low grade IVH or those without IVH had impaired early development.

Prognostic factors for treatment outcomes in transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn (TTN) is a clinical syndrome associated with respiratory distress usually seen shortly after delivery in infants. This study aims to determine the risk factors predicting treatment outcomes in infants with TTN. METHODS: Data from 236 infants diagnosed with TTN during the study period were evaluated retrospectively. Logistic regression analyses were performed to select significant risk factor for prognosis (prolonged oxygen therapy, application of mechanical ventilator, and prolonged hospital stay) of TTN among components of clinical variables. RESULTS: Of the 236 TTN infants, 111 (47.0%) infants were delivered via cesarean section (CS) without labor, 29 (12.3%) infants were delivered via CS with labor, and 96 (40.7%) were delivered via vaginal birth. Lower Apgar score at 1 min (OR: 3.03; 95%CI: 1.25-7.36) and lower umbilical artery pH (OR: 4.00; 95%CI 1.55-10.49) were associated with a significantly increased risk for mechanical ventilator care. Also, late-preterm delivery (OR: 4.70; 95%CI: 2.11-10.49) was independently associated with risk of prolonged duration of hospital stay. CONCLUSIONS: Late-preterm delivery, lower initial umbilical artery pH (<7.25), and lower Apgar score at 1 min were independently associated with poor prognostic treatment outcomes in infants with TTN.