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Retinopathy of prematurity (ROP) is a major cause of preventable blindness in preterm infants. The association between red blood cell (RBC) parameters and the development of ROP remains unclear. The objectives of the present study were to evaluate the association between RBC parameters and ROP treatment. This single-center, retrospective cohort study included preterm infants born at < 30 weeks of gestation. Data pertaining to RBC parameters and ROP treatment were obtained from the medical records. A receiver operating characteristic (ROC) analysis was performed to determine the cut-off values of the RBC parameters according to the need for ROP treatment. Multiple logistic regression analyses assessed the association between ROP treatment and RBC parameters at birth and on day of life (DOL) 28. We included 202 infants, and 44.1% were treated for ROP. After adjusting for confounders, we observed associations between ROP treatment and mean corpuscular volume (MCV) values > 117.3 fL at birth (adjusted odds ratio [aOR]:2.3; 95% confidence intervals CI 1.0–5.3). Additionally, on DOL 28, hemoglobin (Hb) values < 9.9 g/dL (aOR:3.0; 95% CI 1.4–6.7), hematocrit (Hct) values < 31.0% (aOR:2.7; 95% CI 1.3–5.6), and red cell distribution width (RDW) values > 18.5% (aOR:2.6; 95% CI 1.1–6.2) were associated with ROP treatment. In conclusion, our study indicated that infants born at < 30 weeks of gestation with an MCV > 117.3 fL at birth, along with Hb < 9.9 g/dL, Hct < 31.0%, and RDW > 18.5% on DOL 28, had an increased risk of requiring ROP, warranting treatment. [ABSTRACT FROM AUTHOR]

Background: Breast milk, nature's optimum source of nutrition for infants, can contain undesirable microorganisms that cause severe morbidity. After an outbreak of multidrug‐resistant Escherichia coli among neonates receiving breast milk donated by another mother in our neonatal intensive care unit (NICU), we were motivated to develop a high‐grade breast milk pasteurizer (BMP) designed to thaw and pasteurize breast milk at 63°C for 30 min in a sealed bag without having to open the bag or immerse it in water. Methods: Pre‐existing bacteria and spiked cytomegalovirus (CMV) were measured pre‐ and post‐pasteurization in frozen breast milk donated by mothers of children admitted to the NICU. Results: Among 48 breast milk samples (mean ± standard deviation [SD]), pre‐existing bacterial counts of 5.1±1.1 × 104 colony forming units (cfu)/mL decreased to less than 10 cfu/mL (below detection level) in 45 samples after pasteurization for 30 min. In three samples, 10–110 cfu/mL persisted. As no CMV was detected in any of the 48 samples, CMV at ≥5 × 104 pfu/mL was spiked into 11 breast milk samples. After just 10 min of pasteurization, infectious CMV was not detected (threshold <50 pfu/mL) in any sample. Conclusion: A new BMP was shown to pasteurize milk effectively with more than a 3‐log reduction of microorganisms. Compared to conventional pasteurizers, this device reduces the effort involved in pasteurizing breast milk, avoids various contamination risks, and may reduce the risk of infectious disease transmission via breast milk. [ABSTRACT FROM AUTHOR]

Caffeine consumption during pregnancy is reported to increase the risk of in utero growth restriction and spontaneous abortion. In the present study, we tested the hypothesis that modest maternal caffeine exposure affects in utero developing embryonic cardiovascular (CV) function and growth without altering maternal hemodynamics. Caffeine (10 mg.[kg.sup-1].[day.sup.-1] subcutaneous) was administered daily to pregnant CD-1 mice from embryonic days (EDs) 9.5 to 18.5 of a 21-day gestation. We assessed maternal and embryonic CV function at baseline and at peak maternal serum caffeine concentration using high-resolution echocardiography on EDs 9.5, 11.5, 13.5, and 18.5. Maternal caffeine exposure did not influence maternal body weight gain, maternal CV function, or embryo resorption. However, crown-rump length and body weight were reduced in maternal caffeine treated embryos by ED 18.5 (P < 0.05). At peak maternal serum caffeine concentration, embryonic carotid artery, dorsal aorta, and umbilical artery flows transiently decreased from baseline at ED 11.5 (P < 0.05). By ED 13.5, embryonic aortic and umbilical artery flows were insensitive to the peak maternal caffeine concentration; however, the carotid artery flow remained affected. By ED 18.5, baseline embryonic carotid artery flow increased and descending aortic flow decreased versus non-caffeine-exposed embryos. Maternal treatment with the adenosine [A.sub.2A] receptor inhibitor reproduced the embryonic hemodynamic effects of maternal caffeine exposure. Adenosine [A.sub.2A] receptor gene expression levels of ED 11.5 embryo and ED 18.5 uterus were decreased. Results suggest that modest maternal caffeine exposure has adverse effects on developing embryonic CV function and growth, possibly mediated via adenosine [A.sub.2A] receptor blockade. adenosine [A.sub.2A] receptor; cardiovascular development; carotid artery; pregnancy

Abstract Introduction Pulmonary interstitial emphysema is a serious complication of mechanical ventilation and can become life-threatening if progression occurs. Therapeutic lung puncture is a treatment option for severe pulmonary interstitial emphysema but has a limited use in babies with extremely low birth weight. We present a case of pulmonary interstitial emphysema in a Japanese baby (1-day-old) boy with extremely low birth weight. The emphysema was successfully decompressed by therapeutic lung puncture performed with a trocar catheter. Case presentation The baby was born with a weight of 420g, which, to the best of our knowledge, is the lowest reported birth weight among babies with pulmonary interstitial emphysema. A chest X-ray on postnatal day 2 revealed pulmonary interstitial emphysema, which gradually progressed to diffuse pseudocystic changes. His condition became life-threatening despite the use of high-frequency oscillatory ventilation and lateral decubitus positioning. We evacuated the pulmonary interstitial emphysema by lung puncture with a trocar catheter to avoid respiratory and cardiovascular collapse. This resulted in adequate evacuation of the emphysema and a dramatic improvement in his clinical condition. Conclusions Therapeutic lung puncture performed with a trocar catheter is beneficial in babies with extremely low birth weight and diffuse pulmonary interstitial emphysema. This treatment option may be broadly applicable, especially in an emergency situation.

Platelets parameters including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with various physiological and pathological functions in various disease. However, few studies have addressed whether perinatal factors may be associated with platelet parameters at birth in a large cohort of late preterm and term neonates. The aim of this study to investigate perinatal factors affecting platelet parameters in late preterm and term neonates. We retrospectively investigated platelet parameters including PLT, PCT, MPV, and PDW on the first day of life in 142 late preterm and 258 term neonates admitted to our NICU from 2006 through 2020. PLT, MPV, PCT, PDW on Day 0 did not significantly differ between the two groups. In term neonates, multivariate analysis revealed that PCT correlated with being small for gestational age (SGA) (β = -0.168, P = 0.006), pregnancy induced hypertension (PIH) (β = -0.135, P = 0.026) and male sex (β = -0.185, P = 0.002). PLT was associated with SGA (β = -0.186, P = 0.002), PIH (β = -0.137, P = 0.024) and male sex (β = -0.166, P = 0.006). In late preterm neonates, multivariate analysis revealed that PLT were associated with PIH, whereas no factors associated with PDW and MPV were found. In all patients studied, chorioamnionitis (CAM) was significantly associated with MPV (CAM = 10.3 fL vs. no CAM = 9.7 fL, P<0.001). Multivariate analysis showed that SGA, male sex and PIH were associated with PCT and PLT. This study demonstrates that different maternal and neonatal complications affect platelet parameters in late preterm and term neonates. [ABSTRACT FROM AUTHOR]

Background: During storage, the potassium level of red blood cell (RBC) components increases, especially after irradiation. Neonates are prone to hyperkalemia, for example, non‐oliguric hyperkalemia, so using potassium adsorption filters during transfusion may be helpful. To overcome dilution of RBC components caused by saline priming of existing potassium adsorption filters, a downsized potassium adsorption filter for neonates (PAF‐n, Kawasumi Laboratories Inc., Tokyo, Japan) was developed. Study Design and Methods: To assess the performance of PAF‐n, its adsorption efficiency and RBC recovery rate were evaluated by testing pre‐filtration and serial post‐filtration (0‐30 mL, 30‐60 mL, 60‐90 mL, and 90‐120 mL) samples from 8 RBC components. Results: The average potassium adsorption rate of the PAF‐n was 90.5% ± 0.78%, and never less than 89.0% in any of 8 RBC components. RBC recovery rates were 99.3% ± 1.12%. Conclusion: The PAF‐n showed an effective potassium ability with negligible RBC dilution. [ABSTRACT FROM AUTHOR]

Aim: Effects of nicotine on fetal hemodynamics are not well known, especially in the first trimester fetus. We investigated the acute and chronic effects of nicotine on hemodynamics in pregnant mice and their fetuses using ultrasound. Postnatal health status including growth and hemodynamics was also examined. Methods: To investigate the acute effects of nicotine on fetal hemodynamics, we injected nicotine 0.2 mg/kg subcutaneously into pregnant mice on gestational days (GD) 9.5, 11.5 and 13.5 and compared with saline‐injected group. To determine the chronic effects of nicotine on fetal hemodynamics, we administered nicotine in drinking water (0.1 mg/mL) to pregnant mice from GD 6.5 until they gave birth and compared hemodynamics with water‐administered mice. Results: Regarding the acute effects of nicotine, we found no intergroup difference in maternal hemodynamics; however, fetal blood flow through the dorsal aorta, carotid artery and umbilical artery tended to decrease, particularly on GD 11.5. Regarding the chronic effects of nicotine, we observed no intergroup difference in maternal body weight changes and hemodynamics; however, blood flow to all fetal organs tended to be lower in the nicotine water group than in the water group with significant difference on GD 13.5. The offspring of the nicotine water group had significantly low birth weights and continued to have low body weight until 9 weeks of age. In addition, these offspring developed postnatal cardiac hypertrophy. Conclusion: Nicotine adversely affects fetal hemodynamics acutely and chronically in early pregnancy, potentially leading to fetal tissue hypoxia, intrauterine growth restriction and adverse postnatal health effects. [ABSTRACT FROM AUTHOR]

To date, few studies have investigated whether perinatal factors affect coagulation parameters at birth in preterm and term neonates. We retrospectively investigated coagulation factors on day 1 in 609 consecutive neonates admitted to our neonatal intensive care unit between January 2010 and December 2017. We measured coagulation factors on day 1 using peripheral blood samples. Multivariate analysis revealed that prothrombin time–international normalized ratio correlated with intraventricular hemorrhage ( p  = 0.000; β  = 0.180) and placental abruption (PA; p  = 0.000; β  = 0.142). Activated partial thromboplastin time (aPTT) correlated with birth weight (BW; p  = 0.000; β  =  − 0.217), gestational age (GA; p  = 0.000; β  =  − 0.282), and PA ( p  = 0.000; β  = 0.181). Fibrinogen concentration was associated with respiratory distress syndrome ( p  = 0.007; β  =  − 0.114), pregnancy-induced hypertension ( p  = 0.000; β  =  − 0.141), and Apgar score at 1 minute ( p  = 0.043; β  = 0.147). Furthermore, the level of d-dimer inversely correlated with Apgar score at 5 minutes ( p  = 0.049). Finally, antithrombin III levels positively correlated with GA ( p  = 0.000) and BW ( p  = 0.000). Thus, maternal and neonatal complications affect coagulation parameters in preterm and term neonates. [ABSTRACT FROM AUTHOR]

We investigated the relationship of neonatal and maternal serum creatinine (nSCr and mSCr, respectively) with various maternal/infant characteristics at different gestational ages (GA). We reviewed medical records of neonates admitted to NICU. We collected data on birth weight, GA, Apgar scores, medications, etc. Spearman’s test was used to analyze the correlation between serum creatinine and continuous variables, and the Mann-Whitney U and Kruskal-Wallis tests for continuous variables between groups. The changes in nSCr, mSCr, and nSCr/mSCr ratio because of gestational age and the points in gestational changes in trends were estimated using joinpoint trend analysis. From 614 neonate and mother pairs, we found that nSCr was significantly correlated with GA. However, mSCr at >28 wks decreased with GA. The nSCr/mSCr ratio was correlated with GA. In infants born <29 weeks, pregnancy-induced hypertension (PIH) (p = 0.000, β = 0.20) and mSCr (p = 0.000, β = 0.73) were significantly associated with nSCr. In term infants, maternal magnesium administration (p = 0.000, β = 0.25), respiratory distress syndrome (p = 0.013, β = 0.16), PIH (p = 0.005, β = 0.19), and mSCr (p = 0.000, β = 0.33) were significantly associated with nSCr. nSCr reflected mSCr at all gestational ages. The correlation between nSCr and mSCr in preterm infants (p = 0.000, β = 0.74) was stronger than in term infants (p = 0.000, β = 0.34). [ABSTRACT FROM AUTHOR]

Background: Although glucocorticoid hormones play important roles in fetal development, the expression of their receptors in the whole blood of preterm infants remains unknown. Objectives: The aim of this study was to investigate the levels of glucocorticoid receptor (GR) α and β in the whole blood of preterm and term infants. Study design: The study group consisted of 131 infants, of which 54 (41%) were preterm. Whole blood from preterm and term infants was analyzed by real-time PCR to monitor the levels of each receptor mRNA. Results: GRβ mRNA were detected in 96.6% and GRα mRNA in 100% of participants. The GRα and GRβ isoforms were detected at a ratio of 1:0.0002. GRβ mRNA/GAPDH expression in preterm infants was significantly higher than that in term infants (p=0.002). There was significant correlation between GRα/GRβ ratio and birth weight in preterm infants (rs=0.317, p=0.019), as well as between GRβ/GAPDH expression and birth weight (rs=-0.296, p=0.030). Furthermore, in preterm infants, GRβ/GAPDH expression was higher in those with SGA than in those without SGA (p=0.022). Conclusion: Importantly, in preterm infants, both the expression of GRβ and the GRα/GRβ ratio were associated with birth weight. Further studies with larger populations are necessary to determine the relation between the expression of GR and the clinical relevance of preterm infants. [ABSTRACT FROM AUTHOR]

Unlabelled: Introduction: Pulmonary interstitial emphysema is a serious complication of mechanical ventilation and can become life-threatening if progression occurs. Therapeutic lung puncture is a treatment option for severe pulmonary interstitial emphysema but has a limited use in babies with extremely low birth weight. We present a case of pulmonary interstitial emphysema in a Japanese baby (1-day-old) boy with extremely low birth weight. The emphysema was successfully decompressed by therapeutic lung puncture performed with a trocar catheter.Case Presentation: The baby was born with a weight of 420g, which, to the best of our knowledge, is the lowest reported birth weight among babies with pulmonary interstitial emphysema. A chest X-ray on postnatal day 2 revealed pulmonary interstitial emphysema, which gradually progressed to diffuse pseudocystic changes. His condition became life-threatening despite the use of high-frequency oscillatory ventilation and lateral decubitus positioning. We evacuated the pulmonary interstitial emphysema by lung puncture with a trocar catheter to avoid respiratory and cardiovascular collapse. This resulted in adequate evacuation of the emphysema and a dramatic improvement in his clinical condition.Conclusions: Therapeutic lung puncture performed with a trocar catheter is beneficial in babies with extremely low birth weight and diffuse pulmonary interstitial emphysema. This treatment option may be broadly applicable, especially in an emergency situation. [ABSTRACT FROM AUTHOR]

Objective. To examine the expression levels of glucocorticoid receptor (GR) isoforms in peripheral blood mononuclear cells (PBMCs) and serum cortisol levels in cord blood from term infants. Methods. The study population consisted of 172 term infants who were delivered from healthy pregnant women. GRalpha and GRbeta expression levels, and serum cortisol level in cord blood were determined by real-time PCR and ELISA, respectively. Results. Detection rates of GRalpha, GRbeta, and GAPDH were 100%%, 63.4%%, and 100%%, respectively. The expression level of GRalpha was about 200 times that of GRbeta. There were no associations between GR expression level and clinical variables. There were significant associations of low UmApH, maternal gravidity or parity, and vaginal delivery with a high cortisol level; however, there were no correlations between GR expression levels and cortisol level. Conclusions. It is considered that glucocorticoid effects could be expected from the fetal period to the neonatal period, because GRalpha expression level was not related to perinatal factors, GRbeta expression level, and cortisol level in term infants. Further studies of larger populations including very preterm and small for gestational age infants are necessary to determine the balance of expression between GRalpha and GRbeta, and cortisol level. [ABSTRACT FROM AUTHOR]

Classical citrullinemia generally involves hyperammonemic coma in the first few days of life and leads to neurological sequelae in survivors. We report a case of an elder sister who fell into a hyperammonemic coma on the fifth day after birth. She was successfully treated with intravenous benzoate and hemodialysis, and was subsequently diagnosed with citrullinemia on the basis of biochemical analysis. Two years later, a younger sister was born without prenatal diagnosis. We monitored plasma ammonia and citrulline levels after birth, and again diagnosed her with CTLN1 on the basis of biochemical and DNA analyses. There have been few reports of the prospective treatment of citrullinemia; however, our experience indicates the need for the prospective management and the rapid reduction of ammonia levels to avoid neonatal hyperammonemic coma and subsequent sequelae. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the therapeutic potential of human skeletal muscle-derived myoendothelial cells for myocardial infarct repair. Background: We have recently identified and purified a novel population of myoendothelial cells from human skeletal muscle. These cells coexpress myogenic and endothelial cell markers and produce robust muscle regeneration when injected into cardiotoxin-injured skeletal muscle. Methods: Myoendothelial cells were isolated from biopsies of human skeletal muscle using a fluorescence-activated cell sorter along with populations of regular myoblasts and endothelial cells. Acute myocardial infarction was induced in male immune-deficient mice, and cells were directly injected into the ischemic area. Cardiac function was assessed by echocardiography, and donor cell engraftment, angiogenesis, scar tissue, endogenous cardiomyocyte proliferation, and apoptosis were all evaluated by immunohistochemistry. Results: A greater improvement in left ventricular function was observed after intramyocardial injection of myoendothelial cells when compared with that seen in hearts injected with myoblast or endothelial cells. Transplanted myoendothelial cells generated robust engraftments within the infarcted myocardium, and also stimulated angiogenesis, attenuation of scar tissue, and proliferation and survival of endogenous cardiomyocytes more effectively than transplanted myoblasts or endothelial cells. Conclusions: Our findings suggest that myoendothelial cells represent a novel cell population from human skeletal muscle that may hold promise for cardiac repair. [Copyright &y& Elsevier]

Objectives: We investigated whether vascular endothelial growth factor (VEGF) was associated with the angiogenic and therapeutic effects induced after transplantation of skeletal muscle-derived stem cells (MDSCs) into a myocardial infarction (MI). Background: Because very few MDSCs were found to differentiate into new blood vessels when injected into the heart, the mechanism underlying the occurrence of angiogenesis after MDSC transplantation is currently unknown. In the present study, we used a gain- or loss-of-VEGF function approach with skeletal MDSCs engineered to express VEGF or soluble Flt1, a VEGF-specific antagonist, to identify the involvement of VEGF in MDSC transplantation-induced neoangiogenesis. Methods: Vascular endothelial growth factor- and soluble Flt1-engineered MDSCs were injected into an acute MI. Angiogenesis and cardiac function were evaluated by immunohistochemistry and echocardiography. Results: Both control and VEGF-overexpressing MDSCs induced angiogenesis, prevented adverse cardiac remodeling, and improved function compared with saline-injected hearts. However, these therapeutic effects were diminished in hearts transplanted with MDSCs expressing soluble Flt1 despite successful cell engraftment. In vitro experiments demonstrated that MDSCs increased secretion of VEGF in response to hypoxia and cyclic stretch (likely conditions in ischemic hearts), suggesting that transplanted MDSCs release VEGF in vivo. Conclusions: Our findings suggest that VEGF is essential for the induction of angiogenesis and functional improvements observed after MDSC transplantation for infarct repair. [Copyright &y& Elsevier]

Objectives: Our objective in this study was to apply an elastic, biodegradable polyester urethane urea (PEUU) cardiac patch onto subacute infarcts and to examine the resulting cardiac ventricular remodeling and performance. Background: Myocardial infarction induces loss of contractile mass and scar formation resulting in adverse left ventricular (LV) remodeling and subsequent severe dysfunction. Methods: Lewis rats underwent proximal left coronary ligation. Two weeks after coronary ligation, a 6-mm diameter microporous PEUU patch was implanted directly on the infarcted LV wall surface (PEUU patch group, n = 14). Sham surgery was performed as an infarction control (n = 12). The LV contractile function, regional myocardial wall compliance, and tissue histology were assessed 8 weeks after patch implantation. Results: The end-diastolic LV cavity area (EDA) did not change, and the fractional area change (FAC) increased in the PEUU patch group (p < 0.05 vs. week 0), while EDA increased and FAC decreased in the infarction control group (p < 0.05). The PEUU patch was largely resorbed 8 weeks after implantation and the LV wall was thicker than infarction control (p < 0.05 vs. control group). Abundant smooth muscle bundles with mature contractile phenotype were found in the infarcted myocardium of the PEUU group. The myocardial compliance of the PEUU group was distributed between normal myocardium and infarction control (p < 0.001). Conclusions: Implantation of a novel biodegradable PEUU patch onto a subacute myocardial infarction promoted contractile phenotype smooth muscle tissue formation and improved cardiac remodeling and contractile function at the chronic stage. Our findings suggest a new therapeutic option against post-infarct cardiac failure. [Copyright &y& Elsevier]