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The article presents a case study of a female infant that was born at the 44rth week of gestation, having a birth weight of 3404 grams. She was noted of having a variable deceleration on the cardiotocogram. After delivery, the infant was transferred under an intensive care unit due to her respiratory distress secondary to pneumothorax. The infant was found to have a parasagittal injury (PSI), which was characterized by the infarction of the watershed zone, resulting to perinatal asphyxia.

Perinatal hypoxia--ischemia (HI) remains a critical issue. Cell transplantation therapy could be a potent treatment for many neurodegenerative diseases, but limited works on this kind of therapy have been reported for perinatal HI. In this study, the therapeutic effect of transplantation with neural stem/ progenitor cells (NSPCs) and chondrotinase ABC (ChABC) in a neonatal HI rat model is evaluated. Histological studies showed that the unaffected area of the brain in animals treated with NSPCs together with ChABC was significantly larger than that in the animals treated with vehicle or NSPCs alone. The wet weight of the brain that received the combined treatment was also significantly higher than those of the vehicle and their individual treatments. These results indicate that intracerebroventric-Mar injection of NSPCs with ChABC reduces brain injury in a rat neonatal HI model. [ABSTRACT FROM AUTHOR]

Abstract: Background: Using a new simple blood glucose measurement device (Free Style™), blood can thus be sampled from the forearm, which is less sensitive to pain than from the heel. Measuring the blood glucose levels in newborn infants using Free Style™ is therefore a potentially less painful testing modality than traditional blood sampling methods. Objective: To compare the pain intensity at the time of blood sampling from the forearm using the Free Style™ with the conventional method from the heel. Design: A prospective, randomized controlled clinical trial. Patients and methods: Sixty healthy neonates were randomized by the sealed envelope method into two groups—Group F, in which blood was sampled from the forearm using the Free Style™, and Group H, in which blood was conventionally sampled from the heel using a lancet. The pain intensity was assessed based on their crying, the Neonatal Facial Coding System (NFCS) and the Neonatal Infant Pain Scale (NIPS). Results: After skin puncture, 12 (40%) of the infants cried in Group F and 27 (90%) in Group H. The duration of crying was also significantly shorter in Group F than in Group H. Both of pain scores between the two groups differed significantly, these findings indicated less pain for Group F. Conclusion: The new blood sampling method from the forearm was found to be less painful than the conventional method, thus making it possible to clinically use this product as an innovative method for blood sampling in neonatal medicine. [Copyright &y& Elsevier]

Purpose: We compared the efficacy of thoracoscopic repair (TR) with that of open repair (OR) for neonatal congenital diaphragmatic hernia (CDH). Methods: The subjects of this multicenter retrospective cohort study were 524 infants with left-sided isolated CDH, diagnosed prenatally, and treated at one of 15 participating hospitals in Japan between 2006 and 2018. The outcomes of infants who underwent TR and those who underwent OR were compared, applying propensity score matching. Results: During the study period, 57 infants underwent TR and 467 underwent OR. Ten of the infants who underwent TR required conversion to OR for technical difficulties and these patients were excluded from the analysis. The survival rate at 180 days was similar in both groups (TR 98%; OR 93%). Recurrence developed after TR in 3 patients and after OR in 15 patients (TR 7%, OR 3%, p = 0.40). The propensity score was calculated using the following factors related to relevance of the surgical procedure: prematurity (p = 0.1), liver up (p < 0.01), stomach position (p < 0.01), and RL shunt (p = 0.045). After propensity score matching, the multivariate analysis adjusted for severity classification and age at surgical treatment revealed a significantly shorter hospital stay (odds ratio 0.50) and a lower incidence of chronic lung disease (odds ratio 0.39) in the TR group than in the OR group. Conclusions: TR can be performed safely for selected CDH neonates with potentially better outcomes than OR. [ABSTRACT FROM AUTHOR]

ABSTRACT. Objective. Preterm infants are at greater risk of symptomatic cytomegalovirus (CMV) infection than term infants. Breast milk is the main source of perinatal CMV infections. This study evaluated the kinetics of CMV load in breast milk and the rate of postnatal CMV transmission via breast milk from mothers to their preterm infants. Methods. This was a prospective study of 30 mothers and their 43 preterm infants. The infants either had a gestational age of <34 weeks or weighed <2000 g at birth. Breast milk, serum, and urine samples were collected every 2 weeks until discharge, and screened for CMV infection using a real-time PCR assay. Most of the breast milk had been preserved at 20 Celsius before feeding to the preterm infants. Results. Twenty-four mothers (24 of 30, 80%), who had 34 preterm infants, were CMV immunoglobulin G positive. Twenty-one (87.5%) of the 24 seropositive mothers, who had 30 preterm infants, had detectable CMV deoxyribonucleic acid (DNA) in breast milk during the study period. Most breast milk became positive for CMV DNA 2 weeks after delivery. Viral DNA copy numbers increased until they peaked at 4 to 6 weeks. Afterward, the CMV DNA copy numbers decreased. Of the 30 infants who were fed CMV DNA-positive breast milk, CMV infection was confirmed in 3 infants. However, they had no clinical symptoms of CMV infection. Conclusions. Despite the high rate of CMV DNA in breast milk, symptomatic infections in the preterm infants did not occur. These results might be associated with the method of breast milk preservation and the population we studied. CMV infections transmitted via breast milk feeding did not have much impact on preterm infants in our institutes. Pediatrics 2003;111:1333-1336; cytomegalovirus, breast milk, real-time PCR assay, preterm infants. [ABSTRACT FROM AUTHOR]

Perinatal hypoxic ischemic encephalopathy (HIE) results in serious neurological dysfunction and mortality. Clinical trials of multilineage-differentiating stress enduring cells (Muse cells) have commenced in stroke using intravenous delivery of donor-derived Muse cells. Here, we investigated the therapeutic effects of human Muse cells in an HIE model. Seven-day-old rats underwent ligation of the left carotid artery then were exposed to 8% oxygen for 60 min, and 72 hours later intravenously transplanted with 1 × 104 of human-Muse and -non-Muse cells, collected from bone marrow-mesenchymal stem cells as stage-specific embryonic antigen-3 (SSEA-3)+ and −, respectively, or saline (vehicle) without immunosuppression. Human-specific probe revealed Muse cells distributed mainly to the injured brain at 2 and 4 weeks, and expressed neuronal and glial markers until 6 months. In contrast, non-Muse cells lodged in the lung at 2 weeks, but undetectable by 4 weeks. Magnetic resonance spectroscopy and positron emission tomography demonstrated that Muse cells dampened excitotoxic brain glutamatergic metabolites and suppressed microglial activation. Muse cell-treated group exhibited significant improvements in motor and cognitive functions at 4 weeks and 5 months. Intravenously transplanted Muse cells afforded functional benefits in experimental HIE possibly via regulation of glutamate metabolism and reduction of microglial activation. [ABSTRACT FROM AUTHOR]

Introduction: In extremely and very preterm infants, predicting individual risks for adverse outcomes antenatally is challenging but necessary for risk-stratified perinatal management and parents' participation in decision-making about treatment. Our aim was to develop and validate prediction models for short-term (neonatal period) and medium-term (3 years of age) outcomes based on antenatal maternal and fetal factors alone.Material and Methods: A population-based study was conducted on 31 157 neonates weighing ≤1500 g and born between 22 and 31 weeks of gestation registered in the Neonatal Research Network of Japan during 2006-2015. Short-term outcomes were assessed in 31 157 infants and medium-term outcomes were assessed in 13 751 infants among the 31 157 infants. The clinical data were randomly divided into training and validation data sets in a ratio of 2:1. The prediction models were developed by factors selected using stepwise logistic regression from 12 antenatal maternal and fetal factors with the training data set. The number of factors incorporated into the model varied from 3 to 10, on the basis of each outcome. To evaluate predictive performance, the area under the receiver operating characteristics curve (AUROC) was calculated for each outcome with the validation data set.Results: Among short-term outcomes, AUROCs for in-hospital death, chronic lung disease, intraventricular hemorrhage (grade III or IV) and periventricular leukomalacia were 0.85 (95% CI 0.83-0.86), 0.80 (95% CI 0.79-0.81), 0.78 (95% CI 0.75-0.80), and 0.58 (95% CI 0.55-0.61), respectively. Among medium-term outcomes, AUROCs for cerebral palsy and developmental quotient of <70 at 3 years of age were 0.66 (95% CI 0.63-0.69) and 0.72 (95% CI 0.70-0.74), respectively.Conclusions: Although the predictive performance of these models varied for each outcome, their discriminative ability for in-hospital death, chronic lung disease, and intraventricular hemorrhage (grade III or IV) was relatively good. We provided a bedside prediction tool for calculating the likelihood of various infant complications for clinical use. To develop these prediction models would be valuable in each country, and these risk assessment tools could facilitate risk-stratified perinatal management and parents' shared understanding of their infants' subsequent risks. [ABSTRACT FROM AUTHOR]

Purpose: To date, there is no compelling evidence of the optimal timing of surgery for congenital diaphragmatic hernia (CDH). This study aimed to establish the optimal timing of surgery in neonates with isolated left-sided CDH. Methods: This multicenter cohort study enrolled 276 patients with isolated left-sided CDH at 15 institutions. Based on the timing of surgery, the patients were classified into four groups [< 24 h (G1), 24–47 h (G2), 48–71 h (G3), and ≥ 72 h (G4)]. The clinical outcomes were compared among the groups using a logistic regression model, after adjusting for potential confounders, such as disease severity. Results: Multivariate analyses showed that G2 also had a lower mortality rate than the other groups. In mild and severe cases, there were no significant differences in mortality across the four groups. In moderate cases, G2 resulted in significantly increased survival rates, compared with G1. Conclusion: The study results suggest that surgery within 24 h of birth is not recommended for patients with moderate severity CDH, that there is no benefit in the delay of surgery for more than 72 h in mild severity CDH patients, and that there is no definite optimal time to perform surgery in severe cases of CDH. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm in which abdominal organs herniate through the defect into the thoracic cavity. The main pathophysiology is respiratory distress and persistent pulmonary hypertension because of pulmonary hypoplasia caused by compression of the elevated organs. Recent progress in prenatal diagnosis and postnatal care has led to an increase in the survival rate of patients with CDH. However, some survivors experience mid‐ and long‐term disabilities and complications requiring treatment and follow‐up. In recent years, the establishment of clinical practice guidelines has been promoted in various medical fields to offer optimal medical care, with the goal of improvement of the disease' outcomes, thereby reducing medical costs, etc. Thus, to provide adequate medical care through standardization of treatment and elimination of disparities in clinical management, and to improve the survival rate and mid‐ and long‐term prognosis of patients with CDH, we present here the clinical practice guidelines for postnatal management of CDH. These are based on the principles of evidence‐based medicine using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The recommendations are based on evidence and were determined after considering the balance among benefits and harm, patient and society preferences, and medical resources available for postnatal CDH treatment. [ABSTRACT FROM AUTHOR]

Purpose: Growth retardation is a severe morbidity in infants with congenital diaphragmatic hernia (CDH). This study aimed to determine when catch-up growth starts in infants with CDH and to determine the adequate amount of nutrition required during catch-up growth. Methods: This was a multicenter retrospective cohort study involving neonates with isolated CDH (born 2006–2010; n = 98). Weight gain velocity (WGV) was calculated using body weight Z-scores. The minimum required weight gain was defined as WGV ≥ 0. Patients were dichotomized into severe and non-severe cases according to diaphragmatic defects. Results: Average monthly WGV changed from < 0 to ≥ 0 at 2 months of age. Total caloric intake at 2 months of age was lower when the WGV between 1 and 3 months was < 0 in both severe cases [122 (95% confidence interval (CI) 116–128) vs. 97 (95% CI 84–110) kcal/kg/day, p = 0.02] and non-severe cases [115 (95% CI 110–120) vs. 99 (95% CI 87–111) kcal/kg/day, p < 0.001)]. Conclusion: Catch-up growth started at approximately 2 months of age. During this period, total caloric intake of > 122 kcal/kg/day was needed to avoid decreases in the body weight Z-score in severe cases. [ABSTRACT FROM AUTHOR]

To evaluate the impact of maternal hypertensive disorders of pregnancy (HDP) on mortality and neurological outcomes in extremely and very preterm infants using a nationwide neonatal database in Japan. This population-based retrospective study was based on an analysis of data collected by the Neonatal Research Network of Japan from 2003 to 2015 of neonates weighing 1,500 g or less at birth, between 22 and 31 weeks' gestation. A total of 21,659 infants were randomly divided into two groups, HDP (n = 4,584) and non-HDP (n = 4,584), at a ratio of 1:1 after stratification by four factors including maternal age, parity, weeks of gestation, and year of delivery. Short-term (neonatal period) and medium-term (3 years of age) mortality and neurological outcomes were compared between the two groups by logistic regression analyses. In univariate analysis, HDP was associated with an increased risk for in-hospital death (crude odds ratio [OR], 1.31; 95% confidence interval, 1.04–1.63) and a decreased risk for severe intraventricular haemorrhage (0.68; 0.53–0.87) and periventricular leukomalacia (0.60; 0.48–0.77). In multivariate analysis, HDP was significantly associated with a lower risk for in-hospital death (adjusted OR, 0.61; 0.47–0.80), severe intraventricular haemorrhage (0.47; 0.35–0.63), periventricular leukomalacia (0.59; 0.45–0.78), neonatal seizures (0.40; 0.28–0.57) and cerebral palsy (0.70; 0.52–0.95) at 3 years after adjustment for covariates including birth weight. These results were consistent with those of additional analyses, which excluded cases with histological chorioamnionitis and which divided the infants into two subgroups (22–27 gestational weeks and 28–31 gestational weeks). Maternal HDP was associated with an increased risk for in-hospital death without adjusting for covariates, but it was also associated with a lower risk for mortality and adverse neurological outcomes in extremely and very preterm infants if all covariates except HDP were identical. [ABSTRACT FROM AUTHOR]

Aim: To present the feasibility, safety and outcomes of fetoscopic endoluminal tracheal occlusion (FETO) for the treatment of severe congenital diaphragmatic hernia (CDH). Methods: This was a single‐arm clinical trial of FETO for isolated left‐sided CDH with liver herniation and Kitano Grade 3 stomach position (>50% stomach herniation into the right chest). FETO was performed at 27–29 weeks of gestation for cases with observed/expected lung to head ratio (o/e LHR) <25% and at 30–31 weeks for cases with o/e LHR ≥25%. Results: Eleven cases were enrolled between March 2014 and March 2016, and balloon insertion was successful in all cases. The median o/e LHR at entry was 27% (range, 20–33%). The median gestational age at FETO was 30.9 (range, 27.1–31.7) weeks. There were no severe maternal adverse events. One fetus died unexpectedly at 33 weeks of gestation due to cord strangulation by the detached amniotic membrane. There were 3 cases (27%) of preterm premature rupture of membranes. In all 10 cases, balloon removal at 34–35 weeks of gestation was successful. The median gestational age at delivery was 36.5 (range, 34.2–38.3) weeks. The median duration of occlusion and the median interval between balloon insertion and delivery were 26 days (range: 17–49 days) and 43 days (range, 21–66 days), respectively. Both the survival rate at 90 days of age and the rate of survival to discharge were 45% (5/11). Conclusion: The FETO is feasible without maternal morbidity in Japan and could be offered to women whose fetuses show severe isolated left‐sided CDH to accelerate fetal lung growth. [ABSTRACT FROM AUTHOR]

To examine the clinical characteristics of bilirubin encephalopathy in preterm infants (pBE) in Japan. We performed a two-step nationwide questionnaire survey. The initial survey determined the number of children with pBE. Using a structured questionnaire, the second survey clarified the clinical manifestations and characteristics of children with pBE, including the perinatal history, neonatal complications, neurological features, verbal communication, diet, and magnetic resonance imaging (MRI) and auditory brainstem response (ABR) findings. The initial survey included 190 pBE infants, indicating an incidence of approximately 10 per year. Clinical information was available for 142 of them. The median gestational age was 26 weeks and the median birthweight was 883 g. As to neonatal complications, 20% had none, 25% had one complication, 54% had two or more. Head control was observed in 45% and functional gait in 8%. Purposeful hand use was seen in 41% of patients and verbal communication in 40%. MRI showed T2 hyperintensities in the globi pallidi in 111 of 136 patients, especially between 7 and 18 months of corrected age. ABR abnormalities were present in 88 of 117 patients. pBE was infrequent but constantly observed during the study period, especially in very preterm infants, even in those with no severe neonatal complications. Severely impaired gross motor function and relatively preserved manual function and verbal communication were characteristic. MRI and ABR abnormalities will facilitate diagnosis. [ABSTRACT FROM AUTHOR]

Using a standard digital EEG system, we conducted simulations to determine the optimal locations and numbers of electrodes for seizure detection in neonates with reduced-channel EEG monitoring. The results showed that C3-C4 should be selected for a onechannel recording, but two-channel seizure monitoring is recommended for increased accuracy. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To determine whether the intrauterine environment affects lipid metabolism, we measured the fatty acid composition of the brain in rats with intrauterine growth retardation (IUGR) induced by synthetic thromboxane A2 (STA2). Additionally, we evaluated the effect of maternal docosahexaenoic acid (DHA)-enriched diet. Methods: Two experimental diets were provided: soy bean oil and DHA-enriched diets. Maternal rats were divided randomly into three groups, STA2−/Soy (Sham), STA2+/Soy (IUGR), and STA2+/DHA (DHA) groups. The Sham and IUGR groups were fed the soy diet, and the DHA group received the DHA-enriched diet from embryonic day 7 until delivery. On postnatal days 1 and 7, the pups were weighed and their brains were removed for lipid analysis. Results: The body weight of the IUGR and DHA groups was significantly less than that of the Sham group both on the postnatal days 1 and 7, whereas it was not significantly different between the IUGR and DHA groups either on postnatal day 1 or day 7. There was no significant difference in the percentage of DHA between the Sham and IUGR groups either on postnatal day 1 or 7. On the other hand, the percentage of DHA was higher in the DHA group than in the IUGR group both on the postnatal days 1 and 7. Conclusions: The fatty acid composition in the brain was not altered in the STA2-induced IUGR rat model. Increased DHA percentage was observed in the maternal DHA-enriched diet group, although no beneficial effect on body weight gain was observed. [Copyright &y& Elsevier]

Background: Magnetic resonance imaging (MRI) abnormalities in preterm infants with bilirubin encephalopathy (BE) become less clear as the infants age. We assessed MRI findings in children with preterm BE older than 36 months corrected age (CA).Methods: In a previous questionnaire survey, hospitals were asked to provide head MRI data of patients older than 36 months CA. MRI findings were reviewed by three pediatric neurology specialists and classified as no abnormalities, partial globus pallidus (GP) lesions, or diffuse GP lesions.Results: In total, 33 MRI scans were available from 28 patients. The median gestational age and birth weight were 26 weeks and 824 g, respectively. The prevalence of MRI abnormalities was 100% in patients at 37 to 48 months CA, 71% in those at 49 to 60 months CA, 50% in those at 61 to 72 months CA, 67% in those at 73 to 84 months CA, and 38% in those at 85 months CA or older. Partial GP lesions were more common than diffuse GP lesions at all ages. No significant differences in sex, gestational age, birth weight, or gross motor function impairment were observed among lesion groups.Conclusions: GP lesions were detected on MRI in most children with preterm BE when studied after 36 months CA, although MRI abnormalities became less apparent along with age. Partial GP lesions may be a characteristic of older children with preterm BE. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to elucidate the clinical characteristics of neonates with congenital diaphragmatic hernia (CDH) associated with pneumothorax and evaluate the risk factors for the development of pneumothorax.Methods: A retrospective cohort study was conducted in the 15 institutions participating in the Japanese CDH Study Group. A total of 495 neonates with isolated CDH who were born between 2011 and 2018 were analyzed in this study.Results: Among the 495 neonates with isolated CDH, 52 (10.5%) developed pneumothorax. Eighteen (34.6%) patients developed pneumothorax before surgery, while 34 (65.4%) developed pneumothorax after surgery. The log-rank test showed that the cumulative survival rate was significantly lower in patients with pneumothorax than in those without pneumothorax. Univariate analysis revealed significant differences between patients with pneumothorax and those without pneumothorax with regard to the best oxygenation index within 24 h after birth, mean airway pressure (MAP) higher than 16 cmH2O, diaphragmatic defect size, and need for patch closure. Multiple logistic regression analysis indicated that only the MAP was associated with an increased risk of pneumothorax.Conclusions: The cumulative survival rate was significantly lower in isolated CDH patients with pneumothorax than in those without pneumothorax. A higher MAP was a risk factor for pneumothorax in CDH patients. [ABSTRACT FROM AUTHOR]

Objective: To estimate whether improvement in outcomes from antenatal corticosteroid treatment in extremely and very preterm twins is similar to that observed in singletons, and to investigate whether antenatal corticosteroid treatment has different effects according to chorionicity or birth order.Methods: This population-based study was based on an analysis of data collected by the Neonatal Research Network of Japan from 2003 to 2015 of neonates weighing 1,500 g or less at birth, from gestational ages of 24 0/7 to 31 6/7 weeks of gestation. After propensity score matching, univariate logistic and interaction analyses were performed to compare short-term (neonatal period) and medium-term (3 years of age) outcomes of the children of mothers who received antenatal corticosteroids with those of children of mothers who did not receive antenatal corticosteroids. We focused on differences between singletons and twins, between monochorionic and dichorionic twins and between the first and second twin.Results: The study comprised 23,502 singletons and 6,546 twins. Antenatal corticosteroid treatment was associated with significant decreased short-term neurologic outcomes in both singletons and twins. However, antenatal corticosteroid treatment was associated with significantly decreased mortality (odds ratio [OR] 0.61; 95% CI 0.53-0.70), respiratory distress syndrome (OR 0.71, 95% CI 0.67-0.76), and cerebral palsy (OR 0.85, 95% CI 0.72-0.99) in singletons but not in twins (OR 0.89, 95% CI 0.68-1.17; OR 0.99, 95% CI 0.87-1.12; and OR 0.82, 95% CI 0.61-1.11, respectively). No association was found between chorionicity and the efficacy of antenatal corticosteroid treatment on outcomes. Further, no association was found between birth order and the efficacy of antenatal corticosteroid treatment on outcomes, except for periventricular leukomalacia and necrotizing enterocolitis (interaction: P=.02 and P=.04, respectively).Conclusion: Antenatal corticosteroid treatment in twins was associated with a beneficial effect on short-term neurologic outcomes only, without improvement in other short-term and medium-term outcomes. There was no difference related to chorionicity. [ABSTRACT FROM AUTHOR]

Background: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare disorder of pulmonary vascular abnormality with persistent pulmonary hypertension of the newborn. The symptom usually presents within hours after birth, leading to an early demise. Heterozygous de novo point mutations and genomic deletions of the FOXF1 (forkhead box F1) gene or its upstream enhancer have been identified in most patients with ACD/MPV. Most cases of ACD/MPV are sporadic; however, familial cases are also reported in 10% of patients. Case presentation: We herein report a case of familial ACD/MPV that showed unusual glomeruloid proliferation of endothelial cells. In this family, three of the four siblings died within two to 3 days after birth because of persistent pulmonary hypertension and respiratory failure. Only the second child remains alive and healthy. An autopsy was performed for the third and fourth children, resulting in a diagnosis of ACD/MPV based on the characteristic features, including misalignment of smaller pulmonary veins and lymphangiectasis. In both of these children, glomeruloid endothelial proliferation of vessels was noted in the interlobular septa. The vessels were immunohistochemically positive for D2–40, CD31, Factor VIII, and ERG, suggestive of differentiation for both lymphatic and blood vessels. Conclusions: Unusual glomeruloid endothelial proliferation was observed in a familial ACD/MPV case. This histologic feature has not been described previously in ACD/MPV or any other pulmonary disease. Although the histogenesis of this histologic feature is unclear, this finding may suggest that ACD/MPV is a compound vascular and lymphovascular system disorder that exhibits various histologic features. [ABSTRACT FROM AUTHOR]

Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone. [ABSTRACT FROM AUTHOR]

Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. Preclinical studies show that the systemic administration of umbilical cord blood cells (UCBCs) is beneficial for neonatal HIE. We conducted a single-arm clinical study to examine the feasibility and safety of intravenous infusion of autologous UCBCs for newborns with HIE. When a neonate was born with severe asphyxia, the UCB was collected, volume-reduced, and divided into three doses. The processed UCB was infused at 12–24, 36–48, and 60–72 hours after the birth. The designed enrolment was six newborns. All six newborns received UCBC therapy strictly adhering to the study protocol together with therapeutic hypothermia. The physiological parameters and peripheral blood parameters did not change much between pre- and postinfusion. There were no serious adverse events that might be related to cell therapy. At 30 days of age, the six infants survived without circulatory or respiratory support. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants. This pilot study shows that autologous UCBC therapy is feasible and safe. [ABSTRACT FROM AUTHOR]

Recently, cell therapy has been developed as a novel treatment for perinatal hypoxic-ischemic encephalopathy (HIE), which is an important cause of neurological disorder and death, and stem cells from human exfoliated deciduous teeth (SHED) express early markers for mesenchymal and neuroectodermal stem cells. We investigated the treatment effect of SHED for HIE in neonatal rats. Seven-day-old rats underwent ligation of the left carotid artery and were exposed to 8% hypoxic treatment. SHED (1 × 105 cells) were injected via the right external jugular vein 24 h after the insult. The effect of intravenous administration of SHED cells was evaluated neurologically and pathophysiologically. In the evaluation of engraftment using quantum dots 655, only a few SHED were detected in the injured cortex. In the immunohistological evaluation 24 h after injection, the numbers of positive cells of active caspase-3 and anti-4 hydroxynonenal antiserum were lower in the SHED group than in the vehicle group. The number of Iba-1+ cells in the cortex was higher in the SHED group. However, the proportion of M1 microglia (Iba-1+/ED-1+) was significantly decreased, whereas M2 microglia (Iba-1+/CD206+) tended to increase in the SHED group. In the behavioral tests performed 5 months after hypoxic treatment, compared to the vehicle group, the SHED group showed significant elongation of the endurance time in the rotarod treadmill test, significantly ameliorated proportion of using the impaired hand in the cylinder test, significantly lower ratio of right/left front paw area in gait analysis, and significantly higher avoidance rate in the active avoidance test. In the in vitro experiment with cultured neurons exposed to oxygen-glucose deprivation, we confirmed the neuroprotective effect of the condition medium of SHED. These results suggested that intravenous administration of SHED exerted a treatment effect both histologically and functionally, possibly via a paracrine effect. [ABSTRACT FROM AUTHOR]

Hypophosphatasia (HPP) is a rare disorder caused by low serum tissue non-specific alkaline phosphatase (ALP) activity due to hypomorphic mutations in the ALPL gene. HPP is characterized by defective bone mineralization. It frequently accompanies pyridoxine-responsive seizures. Because alkaline phosphatase change pyridoxal 5′ phosphate (PLP) into pyridoxal (PL), which can cross the blood brain barrier and regulates inhibitory neurotransmitter gamma-aminobutyric acid. The female patient was born at a gestational age of 37 weeks 2 days. She presented severe respiratory disorder due to extreme thoracic hypoplasia. With the extremely low serum ALP value (14 IU/L), she was clinically diagnosed as HPP. The diagnosis was confirmed with genetic testing. On day1, the subclinical seizures were detected by aEEG. Together with enzyme replacement therapy by asfotase alfa, pyridoxine hydrochloride was administered, then the seizures were rapidly controlled. While confirming that there was no seizure by aEEG monitoring, pyridoxine hydrochloride was gradually discontinued after 1 month. Before administration of pyridoxine hydrochloride, PL was extremely low (4.7 nM) and PLP was increased (1083 nM). After the withdrawal, PL was increased to 84.9 nM only by enzyme replacement. Monitoring with aEEG enabled early intervention for pyridoxine responsive seizures. Confirming increased serum PL concentration is a prudent step in determining when to reduce or discontinue pyridoxine hydrochloride during enzyme replacement therapy. [ABSTRACT FROM AUTHOR]

Background: Many small for gestational age (SGA) infants have catch‐up growth during the first 2 years of life, but approximately 10% have no catch‐up growth, and short stature continues into adulthood. Identification of risk factors for absence of catch‐up growth at an early age may be useful for earlier diagnosis and earlier treatment. Methods: This was a retrospective multicenter study. The subjects were SGA infants with very low‐birthweight (VLBW), who were followed up until the age of 3 years. The risk factors for absence of catch‐up growth were identified on statistical analysis. Results: Of the 217 SGA infants in this study, 181 were in the catch‐up group and 36 were in the no catch‐up group. The catch‐up rate was 83%. On multivariate analysis adjusted for gestational age, birthweight, birth height, and birth head circumference, multipara, Z and ΔZ scores of length at 12 months of corrected age, and the Z score of height at 24 months of corrected age were risk factors for lack of catch‐up at 3 years. Conclusions: The length Z and ΔZ scores at 12 months of corrected age may be useful for an earlier diagnosis and earlier initiation of growth hormone treatment in VLBW infants. [ABSTRACT FROM AUTHOR]

Background: Bilateral congenital diaphragmatic hernia (CDH) is very rare. A few studies have reported the pathogenic role of 5p in CDH.Case Presentation: A 23-year-old primigravida Japanese woman was referred for the following abnormal findings at 33 weeks of gestation: polyhydramnios, macroglossia, talipes equinovarus, and levocardia. A marker chromosome was detected by amniocentesis. Fluorescence in situ hybridization with whole chromosome paint 5 and nucleolus organizer region probes confirmed its origin from chromosome 5 and an acrocentric chromosome. The karyotype of the fetus was diagnosed as 47, XY, +mar. ish +mar(WCP5+). At 39 + 5 weeks, a 2462 g male infant was delivered, with a specific facial configuration. Bilateral CDH, hypoplasia of the corpus callosum, atrial septal defect, and hypothyroidism were also detected in the baby. The karyotype of the peripheral blood was consistent with that of the amniocentesis.Conclusion: Genes coded on 5p might be associated with the pathogenesis of CDH; however, further investigation is required. [ABSTRACT FROM AUTHOR]

Background: The optimum enteral (EN) and parenteral nutrition (PN) regimens during acute management of congenital diaphragmatic hernia (CDH) remain unclear. We examined the effects of EN and PN on weight gain in CDH patients. Methods: A multicenter retrospective cohort study of neonates with CDH (born 2006–2010; n = 105) who survived to discharge was conducted. Patients were divided as receiving PN ≥ or <50 kcal/kg/day at 1 week of age, and EN ≥ or <60 kcal/kg/day at 2 weeks of age. Changes in bodyweight at 30, 60, and 90 days of age were compared. Results: The higher EN group (n = 39) had greater mean weight gain than the lower EN group (n = 66; 90 days: 2,501 g, 95% CI: 2,294–2,710 g vs 1,706 g, 95% CI: 1,553–1,861 g; P <0.001). When patients received lower EN, the higher PN group (n = 24) had greater mean weight gain than the lower PN group (n = 42; 90 days: 1,768 g, 95% CI: 1,574–1,961 g vs 1,411 g, 95% CI: 1,264–1,558 g; P = 0.004). Conclusion: The amount of EN in the acute phase of CDH management is essential for weight gain during infancy. When patients are intolerant to adequate EN, supportive PN is also essential. [ABSTRACT FROM AUTHOR]

Objective: The aim of this prospective multicenter randomized controlled trial was to compare the efficacy of silver nitrate cauterization against that of topical steroid ointment in the treatment of neonatal umbilical granuloma. Methods: An open-label, non-inferiority randomized controlled trial was conducted from January 2013 to January 2016. The primary endpoint for the silver nitrate cauterization and topical steroid ointment groups was the healing rate after 2 weeks of treatment, applying a non-inferiority margin of 10%. The healing rate was evaluated until completion of 3 weeks of treatment. Results: Participants comprised 207 neonates with newly diagnosed umbilical granuloma, randomized to receive silver nitrate cauterization (n = 104) or topical steroid ointment (n = 103). Healing rates after 2 weeks of treatment were 87.5% (91/104) in the silver nitrate cauterization and 82% (82/100) in the topical steroid ointment group group. The difference between groups was -5.5% (95% confidence interval, -19.1%, 8.4%), indicating that the non-inferiority criterion was not met. After 3 weeks of treatment, the healing rate with topical steroid ointment treatment was almost identical to that of silver nitrate cauterization (94/104 [90.4%] vs. 91/100 [91.0%]; 0.6% [-13.2 to 14.3]). No major complications occurred in either group. Conclusions: This study did not establish non-inferiority of topical steroid ointment treatment relative to silver nitrate cauterization, presumably due to lower healing rates than expected leading to an underpowered trial. However, considering that silver nitrate cauterization carries a distinct risk of chemical burns and that the overall efficacy of topical steroid ointment treatment is similar to that of silver nitrate cauterization, topical steroid ointment might be considered as a good alternative in the treatment of neonatal umbilical granuloma due to its safety and simplicity. To clarify non-inferiority, a larger study is needed. [ABSTRACT FROM AUTHOR]

Background Hydrops fetalis ( HF) has a low survival rate, particularly in the case of preterm birth. In addition, the severity index of HF has not been fully investigated yet. The aim of this study was to clarify the prognostic factors of HF with pleural effusion. Methods All live-born HF patients with pleural effusion, except for chromosomal abnormality or complex congenital heart disease, born from 2009 to 2013 in Aichi Prefecture in Japan were included. Prenatal, perinatal, and postnatal information was obtained from the medical records and was retrospectively analyzed. Results Forty-one HF patients with pleural effusion were included, and 28 patients (68%) survived. On multivariate logistic stepwise analysis, gestational birth week ( OR, 0.71; 95% CI: 0.52-0.96, P = 0.027) and standard deviation ( SD) score of the birthweight ( OR, 1.74; 95% CI: 1.01-2.99, P = 0.045) were significant factors for postnatal death. All patients with both ≥32 gestational weeks and <3.0 birthweight SD score survived. Conclusions Combined with the gestational weeks data, birthweight SD score may be useful to estimate the prognosis of HF with pleural effusion. [ABSTRACT FROM AUTHOR]

Background Preterm infants undergo stress owing to essential treatments and exposure to the extrauterine environment in neonatal intensive care units. Aims The aim of this study was to enable preterm infants to maintain adequate positioning with a newly developed swaddling clothing, in order to improve low muscle tone and sleep quality, and to confirm the safety of the clothing. Study design This prospective clinical trial included an intervention group (preterm infants wearing bag-shaped clothing, allowing only exposure of the head, n = 27), and a control group (preterm infants managed only with conventional swaddling, n = 12). Outcome measures We used the Dubowitz method to analyze behavior, recorded the frequency of vomiting and apnea in both groups, and assessed the sleep state in the intervention group. Results Muscle tone and total score for the Dubowitz method significantly improved in the intervention group, compared with those in the control group. We evaluated the sleep state before and after the introduction of the device in the intervention group, and State 1 increased from 53.5% to 69.2% after introduction. No significant difference was seen in the frequency of vomiting and apnea between the groups. Conclusions The new swaddling clothing with enhanced stretch capacity improved the muscle tone and increased sleep time by decreasing the state level of preterm infants. This is an effective tool to assist in infant development in neonatal intensive care units. [ABSTRACT FROM AUTHOR]

Background: Preterm infants undergo stress owing to essential treatments and exposure to the extrauterine environment in neonatal intensive care units.Aims: The aim of this study was to enable preterm infants to maintain adequate positioning with a newly developed swaddling clothing, in order to improve low muscle tone and sleep quality, and to confirm the safety of the clothing.Study Design: This prospective clinical trial included an intervention group (preterm infants wearing bag-shaped clothing, allowing only exposure of the head, n=27), and a control group (preterm infants managed only with conventional swaddling, n=12).Outcome Measures: We used the Dubowitz method to analyze behavior, recorded the frequency of vomiting and apnea in both groups, and assessed the sleep state in the intervention group.Results: Muscle tone and total score for the Dubowitz method significantly improved in the intervention group, compared with those in the control group. We evaluated the sleep state before and after the introduction of the device in the intervention group, and State 1 increased from 53.5% to 69.2% after introduction. No significant difference was seen in the frequency of vomiting and apnea between the groups.Conclusions: The new swaddling clothing with enhanced stretch capacity improved the muscle tone and increased sleep time by decreasing the state level of preterm infants. This is an effective tool to assist in infant development in neonatal intensive care units. [ABSTRACT FROM AUTHOR]

Background: 5p deletion syndrome is known as cri-du-chat syndrome, but there are no reports on congenital diaphragmatic hernia complications associated with it.Case Presentation: A 28-year-old primigravida Japanese woman was referred for 5 mm of nuchal translucency. Fetal growth restriction was found at 20 weeks, and a left-sided congenital diaphragmatic hernia was diagnosed at 24 weeks. The karyotype of the fetus was diagnosed as 46, XX, del(5)(p14) and referred to our hospital. At 36 + 6 weeks, a 1524 g female infant was delivered after premature membrane rupture, with Apgar scores of 4 and 6 at 1 and 5 minutes, respectively. The baby was intubated immediately with sedation and muscle relaxation, after birth for initial treatment for congenital diaphragmatic hernia. The peripheral blood karyotype was consistent with the prenatal result. The infant was discharged alive, without any respiratory support, after the defect of the diaphragm was repaired.Conclusion: The results of this study may be helpful for antenatal genetic counseling. [ABSTRACT FROM AUTHOR]

Objective This study used quantitative analysis to determine whether increased variability in fetal heart rate (FHR) is related to the risk of developing periventricular leukomalacia (PVL). Methods We analyzed 124 FHR traces of neonates delivered preterm at 27–33 weeks’ gestation to 105 mothers. FHR traces 1–3 h before delivery were translated into power-spectrum curves using a fast Fourier transformation. The total power (the area under the curve of 1–10 cycles per minute), segmental power of every cycle per minute, peak power, and frequency edges were calculated, and their relationship with the subsequent development of PVL was examined. Results Total power was significantly higher in the PVL group ( n = 9, median 1813, range 1064–2426) compared to the non-PVL group ( n = 114, median 1383, range 381–3324, p = 0.029). Infants in the PVL group had greater segmental power in segments with 1–2, 2–3, and 9–10 cycles per minute, than those in the non-PVL group. Total power of ⩾1550 was significantly correlated with the subsequent development of PVL and premature rupture of membranes. Furthermore, the frequency of pregnancy-induced hypertension was significantly reduced in the fetuses with a total power of ⩾1550. Conclusion Our study suggests that a fetus with increased FHR variability is at risk of developing PVL. This study provides additional evidence supporting the contribution of antenatal factors to the subsequent development of PVL. [ABSTRACT FROM AUTHOR]

Introduction: Little information exists about the physical growth of patients with congenital diaphragmatic hernia (CDH). This study aimed to assess the growth of patients with CDH during long follow-up periods, and to identify growth retardation (GR) risk factors.Patients and Methods: A multicenter retrospective observational study was conducted in 2013. Of the 228 patients with CDH born between 2006 and 2010, 182 (79.8%) survived to discharge, and 174 cases were included in the study. Body weights and heights were measured at 1.5, 3, and 6 years of age. GR was defined as a Z-score relating to the weight or height of < - 2.0. Cases with GR at 1.5, 3, or 6 years of age comprised the GR group. The clinical variables of the GR and non-GR groups were compared using univariate analysis. Multiple logistic regression analyses were conducted successively on the factors that were significant at p < 0.01 in the univariate analysis and had low correlations with other factors (r < 0.7). The numerical data were divided into two groups based on a cutoff value that was calculated from a receiver operating characteristic curve.Results: The GR group comprised 35 cases (22.7%). The rates of GR at 1.5, 3, and 6 years of age were 19.5 (26/133), 14.4 (16/111), and 13.5% (5/37), respectively. The body weight Z-scores improved in cases with GR between the ages of 1.5 and 3 years (p = 0.036). As the patients aged, the wasting type of GR decreased in frequency (31, 0, and 0% at 1.5, 3, and 6 years of age, respectively) and the stunting type of GR increased in frequency (27, 31, and 100% at 1.5, 3, and 6 years of age, respectively). The univariate analysis showed that birth weight and height, liver-up, large defect size of the diaphragm, use of nitric oxide, patch repair, long hospital stay, home oxygen treatment (HOT), and vasodilator administration at discharge were significant risk factors of GR. The multivariate analysis determined that a birth weight of < 2,698 g (odds ratio [OR] = 5.5, 95% confidence interval [CI] = 2.1-16.8, p < 0.001) and HOT (OR = 5.8, 95%CI = 1.6-23.8, p = 0.007) were significant risk factors for GR.Conclusion: GR was observed in 22.7% of the CDH survivors. Body weight improved between 1.5 and 3 years of age in the GR cases, but some patients developed chronic malnutrition via acute malnutrition. Low birth weight and the need for HOT were GR risk factors. Aggressive management of acute malnutrition may improve the growth of patients with CDH. [ABSTRACT FROM AUTHOR]

Purpose: To report the results of scleral buckling (SB) with or without photocoagulation (PC) and intravitreal bevacizumab (IVB) for stage 4 retinopathy of prematurity (ROP) eyes. Methods: Forty-two eyes of 28 patients with SB and/or PC or IVB were studied. Twenty-nine eyes had stage 4A and 13 eyes had stage 4B ROP. Seventeen eyes underwent SB combined with additional intraoperative or postoperative treatments (combined group). Twenty-five eyes underwent SB without additional therapy (non-combined group). The concentrations of vascular endothelial growth factor (VEGF) in the aqueous humor determined by enzyme-linked immunosorbent assay were compared between the two groups. The initial and final reattachment rates were also compared. Results: The gestational age and birth weight were 25.0 ± 2.0 weeks and 786 ± 222 g in the combined group, and 25.5 ± 2.1 weeks and 899 ± 315 g in the non-combined group. The postmenstrual age at the time of initial surgery was 38.0 ± 1.9 in the combined and 44.1 ± 4.0 weeks in the non-combined group ( P < 0.001). The initial reattachment rate was 92 % in stage 4A and 75 % in stage 4B of ROP eyes in the combined group, and the rate was 93 % in stage 4A and 33 % in stage 4B of ROP eyes in the non-combined group. The mean VEGF concentration in aqueous humor was 1923 ± 779 pg/ml in the combined group and 985 ± 303 pg/ml in the non-combined group ( P < 0.05). Conclusion: Our results show that the retinal reattachment rate after combined therapy was comparable to that in the non-combined group. We conclude that combined therapy may be effective even in ROP eyes with high activity. [ABSTRACT FROM AUTHOR]

Purpose: The optimal surgical approach for neonatal congenital diaphragmatic hernia (CDH) remains unclear. We conducted a systematic review and meta-analysis of the effectiveness of endoscopic surgery (ES) for neonatal CDH.Methods: A systematic literature search was conducted using MEDLINE and the Cochrane Library. Studies that compared surgical approaches for neonatal CDH were selected. Mortality and recurrence of herniation were analyzed as primary endpoints. Each study was evaluated following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.Results: Eight observational studies comparing ES and open surgery (OS) met the criteria. As compared with the OS group, the ES group showed both a significantly lower mortality rate [risk ratio (RR) 0.18, 95 % confidence interval (CI) 0.09-0.38, p < 0.0001] and a significantly higher recurrence rate (RR 3.10, 95 % CI 1.95-4.88, p < 0.00001). However, serious selection bias was seen in seven of the eight studies-because the indication of ES had been determined intentionally, the ES groups may have included less severe cases.Conclusion: Although the evidence was insufficient, ES was clearly associated with more recurrence than was OS. Therefore, ES should not be the routine treatment for every neonate. It is crucially important to select suitable cases for ES. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to clarify how extracorporeal membrane oxygenation ( ECMO) is used to treat congenital diaphragmatic hernia ( CDH) in Japan. Methods We completed a nationwide survey of CDH involving 614 infants. The subjects included 43 patients who underwent ECMO. We compared the clinical data of the patients who did and did not survive ≥90 days, and analyzed the 24 h blood gas data in isolated CDH cases in both groups. Results Of the 43 CDH patients, non-isolated CDH associated with other life-threatening or chromosomal anomalies was diagnosed in six patients. Only one of these six patients was able to discontinue ECMO and survived, and the other five died shortly after birth. The other 37 patients all had isolated CDH. The reason for initiating ECMO in 31 of these patients was persistent pulmonary hypertension of the newborn ( PPHN). In the 37 patients with isolated CDH, ECMO was initiated within 24 h after birth. Sixteen patients (37%) survived ≥90 days, and intact discharge was possible in eight cases. Among the isolated CDH patients, on ROC analysis of the lowest oxygenation index ( OI) to predict 90 day survival, the cut-off was 15. Conclusions ECMO is used to treat PPHN starting from an early period after birth, but the mortality and morbidity are not favorable. For lowest OI, the index used to predict survival following ECMO, the cut-off was 15. [ABSTRACT FROM AUTHOR]

Aim To determine the early changes and evolutions of brain diffusion-weighted imaging (DWI), and analyze prognostic factors of the early changes among patients with neonatal herpes simplex encephalitis (NHSE). Method We selected patients who developed encephalitis by 28 d after birth; had herpes simplex infection; and who underwent magnetic resonance imaging, including DWI, ⩽7 d of symptom onset. Thirty-two DWI scans between 0 and 28 d after onset in 13 patients and the clinical data were recruited. The distribution, evolution of the lesions, and neurological outcome were analyzed. Results DWI frequently showed multiple cortical lesions in both hemispheres in the early period and both hemispheres on DWI (8/9 scans at ⩽48 h, 7/7 patients). As time from onset increased, the cortical lesions tended to coincide with subcortical white matter lesions beneath the initial cortical lesions ( p < 0.01). Lesions from the cortex extended to the subcortical white matter in 7 patients. Deep cerebral lesions, involving basal ganglia, internal capsules, thalamus, were also found in 9 patients ⩽7 d of onset. The distributions of deep cerebral lesions (none/unilateral/bilateral) ⩽7 d of onset showed significant correlations with neurological prognoses (gross motor functions: p < 0.01; developmental or intellectual quotient scores: p < 0.01). Interpretation Cortical lesions were main findings of DWI in NHSE in the early period. Bilateral deep cerebral lesions ⩽7 d were highly indicative of poor motor and cognitive outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Gastroesophageal reflux disease (GERD) is one of the concomitant problems in infants with congenital diaphragmatic hernia (CDH). We assessed risk factors of GERD in CDH patients. Methods: The retrospective observational study for CDH infants was conducted. Cases of CDH who were born between January 2006 and December 2010, were operated in the 9 participating institutions, and survived to discharge were included. Completion of medical therapy for GERD and incidence of surgery were primary outcomes. Kaplan-Meier survival analysis and Cox proportional hazards regression were used. Results: In 182 cases of CDH, the medical therapies for GERD were performed in 23.8 % (40/168), and were completed in 60.0 % (24/40). Prenatal detection of CDH (HR 5.87, CI 1.6-18.8, p = 0.012) and tube feeding at discharge (HR 5.04, 95 % CI 1.3-33.1, p = 0.016) were significantly correlated with unsuccessful weaning from medical therapy. Surgery for GERD was performed in 10.7 % (18/169). Gestational age (HR 4.78, 95 % CI 1.5-21.1, p = 0.006) and diaphragmatic defect of more than 75 % (HR 4.3, 95 % CI 1.6-12.9, p = 0.005) were significantly correlated with need for antireflux surgery. Conclusion: Diaphragmatic defect of more than 75 % was risk factor of future need for antireflux surgery. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to characterize the surgical complications, especially gastroesophageal reflux disease (GERD), intestinal adhesion obstruction (IAO), and diaphragmatic hernia recurrence, in patients with congenital diaphragmatic hernia (CDH). Methods: Between January 1995 and December 2013, we determined the incidence of surgical complications and their predictors in CDH patients. We also examined whether the CDH repair and patch closure were associated with the incidence of IAO and the severity of adhesion. Results: Seventy-four CDH survivors were evaluated. GERD occurred in 28 patients (37.8 %) and recurred in 8 patients (10.8 %). Stomach herniation was a risk factor for GERD, and occurred in 25 patients. IAO occurred in 13 patients (17.6 %). In 240 neonatal laparotomies in the same period, the incidence of IAO was significantly higher in patients who underwent CDH repair than in patients who underwent other neonatal laparotomy ( p = 0.023). Surgical time and intraoperative bleeding were significantly greater following CDH repair with an artificial patch compared with CDH repair with direct closure. Conclusion: Surgical complications are major sequelae in survivors of CDH repair. CDH repair and artificial patch closure were significantly associated with the incidence of IAO and the severity of adhesion. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To clarify the differences between infants with periventricular hemorrhagic infarction (PVHI) and those with periventricular leukomalacia (PVL). Methods: We retrospectively evaluated the clinical features, ultrasonography, and electroencephalogram (EEG) findings in 22 preterm infants with PVHI and 49 with PVL. EEG and cranial ultrasonography were serially performed in all participants starting immediately after birth. Acute and chronic stage EEG abnormalities were evaluated separately. Results: Gestational age and birth weight were significantly lower in infants with PVHI than those with PVL. EEGs were normal in the majority of infants with PVHI on days 1–2. However, EEG abnormalities appeared after ultrasonography abnormalities. The majority of infants with PVL showed acute-stage EEG abnormalities on days 1–2. The rate of infants with acute-stage EEG abnormalities decreased with age, whereas the rate of infants with chronic-stage EEG abnormalities increased with age. Normal EEG before ultrasonography abnormalities was more common in infants with PVHI than in those with PVL. However, deterioration of acute-stage EEG abnormalities was more frequent in infants with PVHI than in those with PVL. Conclusions: PVHI was presumed to cause mostly postnatal injury, whereas PVL was presumed to cause mostly pre-or perinatal injury. [Copyright &y& Elsevier]

Background The aim of this study was to clarify the outcome of patients with cardiovascular malformation ( CVM) among those with congenital diaphragmatic hernia ( CDH) who are indicated for the Fontan procedure. Methods The subjects included 76 CDH patients with CVM recruited from a national survey of 614 CDH patients. The outcomes were evaluated between two groups divided according to indication for the Fontan procedure. Patients with functional univentricular disease were considered to be candidates for the Fontan procedure. Results Sixteen (21.1%) of the 76 patients were candidates for the Fontan procedure, accounting for 2.6% of all 614 patients with CDH. None of these patients, however, underwent the Fontan procedure. Among the 16 patients, the absence of obstruction of the left ventricular outflow tract ( LVOTO) was significantly associated with better 90 day survival (71.4%, 5/7, for those without LVOTO vs 0.0%, 0/9, for those with LVOTO, P = 0.0007). After excluding 22 patients with chromosomal and/or genetic abnormalities or syndromes, the 90 day survival rate was significantly better in neonates without than with indication for the Fontan procedure (62.5%, 25/40 vs 28.6%, 4/14, P = 0.0271). Conclusions Patients with indications for the Fontan procedure are rare, and the outcome of patients with LVOTO among those with CDH is especially poor. [ABSTRACT FROM AUTHOR]

Abstract: Background: Pregnancies with placenta previa are significantly associated with preterm delivery and cesarean section. Therefore particular attention should be paid to the incidence of neonatal respiratory disorders in pregnancies with placenta previa. Aims: The purpose of this study is to examine the relationship between placenta previa and neonatal respiratory disorders, including respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), and to evaluate the impact of placenta previa on the amniotic lamellar body count (LBC) values. Methods: We analyzed the data from 186 registered elective cesarean cases without fetal or maternal complications at 36–38weeks of gestation. Amniotic fluid samples were analyzed immediately without centrifugation, and the LBC was measured using a platelet channel on the Sysmex XE-2100. Results: RDS was present in four neonates (2.2%) and TTN in 12 neonates (6.5%). The rate of TTN was significantly higher and the LBC values were significantly lower in the placenta previa group than in the control group (P=0.002 and P=0.024). The adjusted odds ratio for neonatal TTN was 7.20 (95% confidence interval: 6.58–7.88) among females with placenta previa. In placenta previa, warning bleeding was a significant factor protecting against neonatal respiratory disorders (P=0.046). Conclusions: Placenta previa in itself is a risk factor for neonatal TTN. When an elective cesarean section is performed in cases with uncomplicated placenta previa, special care should be taken to monitor for neonatal TTN even at 36–38weeks of gestation. [Copyright &y& Elsevier]

Background Congenital cytomegalovirus ( CMV) infection and neonatal herpes are major mother-to-child infections, and analyses of the important clinical issues, including risk factors for prognosis, are essential. Methods A secondary survey of congenital CMV infection and neonatal herpes was performed using questionnaires for cases reported in the primary survey between 2006 and 2008. Results Univariate analysis of 71 cases of congenital CMV infection showed that intrauterine growth restriction ( IUGR) or other specific findings on fetal ultrasonography ( US), microcephaly, intracranial calcification, disseminated intravascular coagulation, abnormal findings on computed tomography, and the use of i.v. gammaglobulin were all significantly correlated with poor outcome (death or severe sequelae). Multivariate analysis showed that only IUGR was significantly associated with poor outcome. Hearing impairment is one of the major abnormalities associated with congenital CMV infection. Automatic auditory brainstem response (automatic ABR) appeared to be useful for detection of hearing impairment in comparison with conventional ABR. Moreover, univariate analysis showed that specific fetal US or abnormal magnetic resonance imaging findings were correlated with sensorineural hearing loss. In 24 cases of neonatal herpes, fever and seizure were correlated with poor outcome on univariate analysis. All patients received acyclovir treatment, although substantial numbers of patients in severe clinical categories (disseminated or central nervous system diseases) received a low dose of acyclovir (<60 mg/kg per day). Conclusions This secondary survey has identified the risk factors associated with outcome and important issues in diagnosis and treatment of two mother-to-child infections: congenital CMV and neonatal herpes, in Japan. [ABSTRACT FROM AUTHOR]

Background Congenital diaphragmatic hernia is associated with cardiovascular malformation. Many prognostic factors have been identified for isolated congenital diaphragmatic hernia; however, reports of concurrent congenital diaphragmatic hernia and cardiovascular malformation in infants are limited. This study evaluated congenital diaphragmatic hernia associated with cardiovascular malformation in infants. Factors associated with prognosis for patients were also identified. Methods This retrospective cohort study was based on a Japanese survey of congenital diaphragmatic hernia patients between 2006 and 2010. Frequency and outcome of cardiovascular malformation among infants with congenital diaphragmatic hernia were examined. Severity of congenital diaphragmatic hernia and cardiovascular malformation were compared as predictors of mortality and morbidity. Results Cardiovascular malformation was identified in 76 (12.3%) of 614 infants with congenital diaphragmatic hernia. Mild cardiovascular malformation was detected in 19 (33.9%) and severe cardiovascular malformation in 37 (66.1%). Their overall survival rate at discharge was 46.4%, and the survival rate without morbidity was 23.2%. Mortality and morbidity at discharge were more strongly associated with severity of cardiovascular malformation (adjusted OR 7.69, 95% CI 1.96-30.27; adjusted OR 7.93, 95% CI 1.76−35.79, respectively) than with severity of congenital diaphragmatic hernia. Conclusions The prognosis for infants with both congenital diaphragmatic hernia and cardiovascular malformation remains poor. Severity of cardiovascular malformation is a more important predictive factor for mortality and morbidity than severity of congenital diaphragmatic hernia. [ABSTRACT FROM AUTHOR]

Background: Infants born to mothers with hypertensive disorders of pregnancy (HDP) have adverse neurodevelopmental consequences in later life. Magnetic resonance spectroscopy (MRS) is used to predict subsequent neurodevelopment in the field of perinatology.Aim: We aimed to determine whether exposure to HDP in utero leads to alterations in brain metabolites in preterm infants using multi-voxel proton MRS at term-equivalent age.Study Design: Retrospective cohort study.Subjects: A total of 103 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible. Twenty-seven infants were born to mothers with HDP (HDP group), and 76 were born to mothers without HDP (non-HDP group).Outcome Measures: The peak area ratios of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr), and Cho/Cr were evaluated at 10 designated regions of interest (bilateral frontal lobes, basal ganglia, thalami, temporal lobes, and occipital lobes).Results: The peak area ratios of NAA/Cho and NAA/Cr in the bilateral thalami were significantly higher in the HDP group than in the non-HDP group after adjustment for covariates (postmenstrual age at MRS assessment and infant sex). No significant differences were observed in other regions. Preeclampsia, abnormal umbilical artery blood flow, and fetal growth restrictions were significantly associated with increased NAA/Cho and NAA/Cr ratios in the thalami.Conclusions: Based on the evidence that NAA/Cho and NAA/Cr ratios constantly increase with postmenstrual age in normal brain development, exposure to maternal HDP in utero may accelerate brain maturation and increase neuronal activity in preterm infants. [ABSTRACT FROM AUTHOR]

Aim To explore a less invasive way of assessing preload in neonates than fitting catheters to measure central venous pressure ( CVP). This study evaluated the relationship between inferior vena cava ( IVC) measurements and gestational age ( GA) or body weight ( BW) in term and premature infants and the correlation between those measurements and CVP in sick infants under mechanical ventilation. Methods We studied 57 clinically stable infants, together with14 sick infants fitted with central venous catheters to measure CVP. Subcostal transverse views were recorded at the level of the left branch of portal vein, and the minimum ( DS) and maximum ( DL) diameters of the IVC were measured. We evaluated the values of DS and DL and the S/L ratio ( DS divided by DL) in the clinically stable infants and the correlation between S/L and CVP in the sick infants with central catheters. Results DS and DL correlated positively and strongly with both GA and BW, whereas S/L was almost independent of both GA and BW and correlated strongly with CVP. Conclusion At the subcostal transverse views, S/L is much less affected by either GA or BW than DS or DL and correlates strongly with CVP in mechanically ventilated infants. [ABSTRACT FROM AUTHOR]

Abstract: Dexamethasone (DEX), a synthetic glucocorticoid, has been widely used to prevent the development of a variety of poor health conditions in premature infants including chronic lung disease, inflammation, circulatory failure, and shock. Although there are some reports of neurologic complications related to DEX exposure, its full effects on the premature brain have not been examined in detail. To investigate the effects of DEX on neural development, we first administered low doses (0.2mg/kg bodyweight or less) of the glucocorticoid to neonatal rats on a daily basis during the first postnatal week and examined subsequent behavioral alterations at the juvenile stage. DEX-treated rats exhibited not only a significant reduction in both somatic and brain weights but also learning disabilities as revealed in the shuttle avoidance test. The hippocampi of DEX-treated rats displayed a high apoptotic and a low mitotic cell density compared to control rats on day 7 after birth. In a subsequent experiment, neural stem/progenitor cells were cultured in the presence of DEX for 6days. The glucocorticoid inhibited cell growth without an increase in cell death. These results suggest that administration of DEX to premature infants induces neurological dysfunction via inhibition of the proliferation of neural stem/progenitor cells. [Copyright &y& Elsevier]

Aims: The purpose of this study is to predict the occurrence of transient tachypnea of the newborn (TTN) using amniotic lamellar body count (LBC) and compare the LBCs in neonates with TTN with the LBCs in neonates with respiratory distress syndrome (RDS) and controls. Methods: Three hundred and eighty-one amniotic fluid samples were obtained at cesarean section from 27 to 40 weeks of gestation. Samples were analyzed immediately without centrifugation and the number of lamellar bodies was counted. Results: The LBC in amniotic fluid ranged from 1,000 to 577,000/μL. An LBC cut-off value of 48,500/μL resulted in 84.7% sensitivity, 76.2% specificity, and 98.1% negative predictive value for predicting TTN. The LBC in neonates with TTN was significantly lower than that in controls (50,000 vs. 122,000; P<0.001) and significantly higher than that in neonates with RDS (50,000 vs. 21,000; P=0.042). Conclusions: We established a cut-off value of LBC for predicting the occurrence of TTN. The LBC in neonates with TTN was significantly lower than that in controls. Amniotic LBC can be a useful marker to predict if neonatal respiratory management is required. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study is to predict the occurrence of transient tachypnea of the newborn (TTN) using amniotic lamellar body count (LBC) and compare the LBCs in neonates with TTN with the LBCs in neonates with respiratory distress syndrome (RDS) and controls. Methods: Three hundred and eighty-one amniotic fluid samples were obtained at cesarean section from 27 to 40 weeks of gestation. Samples were analyzed immediately without centrifugation and the number of lamellar bodies was counted. Results: The LBC in amniotic fluid ranged from 1,000 to 577,000/μL. An LBC cut-off value of 48,500/μL resulted in 84.7% sensitivity, 76.2% specificity, and 98.1% negative predictive value for predicting TTN. The LBC in neonates with TTN was significantly lower than that in controls (50,000 vs. 122,000; P<0.001) and significantly higher than that in neonates with RDS (50,000 vs. 21,000; P=0.042). Conclusions: We established a cut-off value of LBC for predicting the occurrence of TTN. The LBC in neonates with TTN was significantly lower than that in controls. Amniotic LBC can be a useful marker to predict if neonatal respiratory management is required. [ABSTRACT FROM AUTHOR]