Long-Term Outcomes, Including Fetal and Neonatal Prognosis, of Renal Oligohydramnios: A Retrospective Study over 22 Years.

OBJECTIVE: To assess the long-term outcome of renal oligohydramnios and risk factors for fetal, neonatal, and postneonatal death. STUDY DESIGN: This retrospective cohort study included fetuses with prenatally detected renal oligohydramnios between 2002 and 2023. Patients who were lost to follow-up were excluded. Fetal, neonatal, and long-term outcomes were evaluated, and their risk factors were analyzed. RESULTS: Of 131 fetuses with renal oligohydramnios, 46 (35%) underwent a termination of pregnancy, 11 (8%) had an intrauterine fetal death, 26 (20%) had a neonatal death, nine (7%) had a postneonatal death, and 39 (30%) survived. Logistic regression analyses showed that an earlier gestational age at onset (OR 1.16, 95% CI 1.01-1.37) was significantly associated with intrauterine fetal death; anhydramnios (OR 12.7, 95% CI 1.52-106.7) was significantly associated with neonatal death as a prenatal factor. Although neonatal survival rates for bilateral renal agenesis, bilateral multicystic dysplastic kidney (MCDK), and unilateral MCDK with contralateral renal agenesis were lower than for other kidney diseases, 1 case of bilateral renal agenesis and two of bilateral MCDK survived with fetal intervention. Kaplan-Meier overall survival rates were 57%, 55%, and 51% for 1, 3, and 5 years, respectively. In the Cox proportional hazards model, birth weight <2000 g (hazard ratio 7.33, 95% CI 1.48-36.1) and gastrointestinal comorbidity (hazard ratio 4.37, 95% CI 1.03-18.5) were significant risk factors for postneonatal death. CONCLUSION: Long-term survival following renal oligohydramnios is a feasible goal and its appropriate risk assessment is important.

Inter-hospital variations in the respiratory outcomes of very and extremely pre-term infants: A cohort study in Japan.

BACKGROUND: Hospital-level and international variations exist in the management strategies of bronchopulmonary dysplasia (BPD). However, studies evaluating hospital-level variations in the respiratory outcomes of pre-term infants associated with differing management strategies of BPD are lacking. OBJECTIVE: Herein, we aimed to assess inter-hospital variations in the respiratory outcomes of BPD in very pre-term and extremely pre-term infants. METHODS: In this cohort study, the administrative claims and discharge summary data were extracted from 276 hospitals in Japan between April 2014 and March 2016. This study assessed neonates of a gestational age of 22-31 weeks old, who had been hospitalised for ≥7 days. The primary outcome was a BPD defined using any respiratory support, such as supplemental oxygen, high-flow nasal cannula, CPAP, or mechanical ventilation at 36 weeks PMA. The median odds ratio (MOR) was calculated using a multilevel logistic regression model, including baseline characteristics, comorbidities, and treatment as covariates, to evaluate the inter-hospital variation of the outcome. RESULTS: Of the 8143 neonates from across 132 hospitals, 53.7% were male, with a mean gestational age (standard deviation) of 28.0 (2.5)-weeks-old and birthweight of 1086 (386) g. Among these patients, BPD occurred in 2737 (33.6%). The MOR was 2.49, representing the median value of odds ratios when comparing two neonates with identical covariates from hospitals with high and low propensity for the outcomes to occur. CONCLUSIONS: Outcome variations in the BPD were observed among hospitals in Japan, even after adjusting for individual factors, including gestational age, birthweight, comorbidities, and treatments. Thus, in Japan, developing strategies is essential to decrease the BPD rates, while minimising inter-hospital heterogeneity, to improve the healthcare quality for pre-term neonates.

Furosemide for patent ductus arteriosus during cyclooxygenase inhibitor therapy: A systematic review.

BACKGROUND: Although furosemide is used during cyclooxygenase (COX) inhibitor therapy for patent ductus arteriosus (PDA), there are concerns regarding increased ductal closure failure and acute renal failure (ARF). This systematic review explores the effects of furosemide during COX inhibitor therapy. METHODS: We searched MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases for randomized clinical trials that assessed furosemide during COX inhibitor therapy for PDA in preterm infants. The primary outcome measure was PDA closure failure. Mortality and other complications were also assessed. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized control trials, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS: Overall, three trials involving 121 patients were included in the analysis. The overall incidence of PDA closure failure was 28%. Although the result of PDA closure failure, mortality, and ARF were obtained, other outcomes were not described in any of the studies. The risk of bias was high. The risk of PDA closure failure did not increase with furosemide administration. Furosemide was not associated with decreased mortality but was associated with an increased risk of ARF (risk ratio, 4.96 [95% confidence interval: 1.80-13.6]). The certainty of evidence for all outcomes was very low. CONCLUSION: Although furosemide is not associated with an increased risk of PDA closure failure or mortality, the risk of ARF increases after furosemide administration during COX inhibitor therapy.

Prophylactic sildenafil to prevent bronchopulmonary dysplasia: A systematic review and meta-analysis.

BACKGROUND: Bronchopulmonary dysplasia (BPD) persists as one of the foremost factors contributing to mortality and morbidity in extremely preterm infants. The effectiveness of administering sildenafil early on to prevent BPD remains uncertain. The aim of this study was to investigate the efficacy and safety of prophylactically administered sildenafil during the early life stages of preterm infants to prevent mortality and BPD. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and Ichushi were searched. Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated the certainty of evidence (CoE) following the Grading of Recommendations Assessment and Development and Evaluation approach. The random-effects model was used for a meta-analysis of RCTs. RESULTS: This review included three RCTs (162 infants). There were no significant differences between the prophylactic sildenafil and placebo groups in mortality (risk ratio [RR]: 1.32; 95% confidence interval [CI]: 0.16-10.75; very low CoE), BPD (RR: 1.20; 95% CI: 0.79-1.83; very low CoE), and all other outcome assessed (all with very low CoE). The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. CONCLUSIONS: The prophylactic use of sildenafil in individuals at risk of BPD did not indicate any advantageous effects in terms of mortality, BPD, and other outcomes, or increased side effects.

Pre-pregnancy body mass index and low birthweight: Secondary data analysis using health insurance claims data in Japan.

AIM: For women, being underweight increases their susceptibility to osteoporosis, anemia, and other conditions and affects the weight of their infants and the well-being of future generations. This study examined the association between low pre-pregnancy body mass index (BMI) and low birthweight using health insurance claims data and health checkup data, including weight measurements. METHODS: We used health insurance claims data and health checkup data (JMDC, Tokyo, Japan) of women and their newborns in Japan between 2006 and 2020. We used checkup data, which included more accurate weight measurements and blood test-based diagnoses of anemia and hyperlipidemia compared to self-reported data. Maternal pre-pregnancy BMI was compared across three groups: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), and overweight (BMI ≥25.0 kg/m2). The primary outcome was low birthweight (<2500 g), and secondary outcome was preterm childbirth. Logistic regression analyses were conducted to compare outcomes in the three groups by BMI. The underweight BMI group was considered as the reference group. A subgroup analysis was performed by maternal age. RESULTS: In total, 16 363 mothers (underweight, 3418 [21%], normal weight, 11 493 [70%], and overweight, 1452 [8.9%]) were included. The risk of primary outcome (low birthweight) was significantly lower in the normal weight group than in the underweight group (4.6% vs. 5.7%; adjusted odds ratio 0.78 [95% confidence interval: 0.65-0.96]). In the subgroup analyses, no significant differences were noted in the incidences of low birthweight and preterm childbirth between maternal age groups. CONCLUSIONS: Pre-pregnancy BMI was associated with an increased risk of delivering low-birthweight infant. Awareness about the importance of women's pre-pregnancy health and appropriate BMI may reduce the incidence of low birthweight.

Inhaled Nitric Oxide Therapy in the Post-Acute Phase in Extremely Preterm Infants: A Japanese Cohort Study.

OBJECTIVE: To determine the trends in inhaled nitric oxide (iNO) utilization in the late phase of hospitalization in a large Japanese cohort of extremely preterm infants and evaluate its benefit on long-term outcomes. STUDY DESIGN: This was a retrospective multicenter cohort study of 15 977 extremely preterm infants born at <28 weeks of gestational age between 2003 and 2016, in the Neonatal Research Network, Japan. Demographic characteristics, morbidity, and mortality were compared between extremely preterm infants with and without post-acute iNO therapy. Multivariable logistic analysis was performed to determine factors associated with post-acute iNO and its impact on neurodevelopmental outcomes at 3 years of age. RESULTS: Post-acute iNO utilization rates increased from 0.3% in 2009 to 1.9% in 2016, even under strict insurance coverage rules starting in 2009. Gestational age (1-week increment; aOR 0.82, 95% CI 0.76-0.88), small for gestational age (1.47, 1.08-1.99), histologic chorioamnionitis (1.50, 1.21-1.86), 5-minute Apgar score <4 (1.51, 1.10-2.07), air leak (1.92, 1.30-2.83), and bubbly/cystic appearance on chest X-Ray (1.68, 1.37-2.06) were associated with post-acute iNO. Post-acute iNO was not associated with neurodevelopmental outcomes at 3 years of age. CONCLUSIONS: The increasing post-acute iNO utilization rate among extremely preterm infants has been concurrent with improved survival rates of extremely preterm infants in Japan. Infants treated with post-acute iNO had more severe disease and complications than the comparison group, but there were no differences in neurodevelopmental outcome at 3 years. This suggests post-acute iNO may benefit extremely preterm infants.

Predictive value of the Thompson score for short-term adverse outcomes in neonatal encephalopathy.

BACKGROUND: To explore the predictive value of the Thompson score during the first 4 days of life for estimating short-term adverse outcomes in neonatal encephalopathy. METHODS: This observational study evaluated infants with neonatal encephalopathy (≥36 weeks of gestation) registered in a multicenter cohort of cooled infants in Japan. The Thompson score was evaluated at 0-24, 24-48, 48-72, and 72-90 h of age. Adverse outcomes included death, survival with respiratory impairment (requiring tracheostomy), or survival with feeding impairment (requiring gavage feeding) at discharge. RESULTS: Of the 632 infants, 21 (3.3%) died, 59 (9.3%) survived with respiratory impairment, and 113 (17.9%) survived with feeding impairment. The Thompson score throughout the first 4 days accurately predicted death, respiratory impairment, or feeding impairment. The 72-90 h score showed the highest accuracy. A cutoff of ≥15 had a sensitivity of 0.85 and specificity of 0.92 for death or respiratory impairment, while a cutoff of ≥14 had a sensitivity of 0.71 and a specificity of 0.92 for death, respiratory or feeding impairment. CONCLUSION: A high Thompson score during the first 4 days of life, especially at 72-90 h could thus be useful for estimating the need for prolonged life support. IMPACT: The Thompson score on days 1-4 of age was useful in predicting death and respiratory or feeding impairments. The 72-90 h Thompson score showed the highest predictive capability. Owing to the rarity of withdrawal of life-sustaining treatment in Japan, 43% of infants with persistent severe encephalopathy with a Thompson score of ≥15 at 72-90 h of age could regain spontaneous breathing, be extubated, and survive without tracheostomy. Meanwhile, approximately 50% of infants who survived without tracheostomy required gavage feeding. Our results could provide useful information for clinical decision making regarding infants with persistent severe encephalopathy.

Early predictive factors for progression to kidney failure in infants with severe congenital anomalies of the kidney and urinary tract.

BACKGROUND: Severe congenital anomalies of the kidney and urinary tract (CAKUT) progress to infantile kidney failure with replacement therapy (KFRT). Although prompt and precise prediction of kidney outcomes is important, early predictive factors for its progression remain incompletely defined. METHODS: This retrospective cohort study included patients with CAKUT treated at 12 centers between 2009 and 2020. Patients with a maximum serum creatinine level ≤ 1.0 mg/dL during the first 3 days, patients who died of respiratory failure during the neonatal period, patients who progressed to KFRT within the first 3 days, and patients lacking sufficient data were excluded. RESULTS: Of 2187 patients with CAKUT, 92 were finally analyzed. Twenty-five patients (27%) progressed to KFRT and 24 (26%) had stage 3-5 chronic kidney disease without replacement therapy during the median observation period of 52.0 (interquartile range, 22.0-87.8) months. Among these, 22 (24%) progressed to infantile KFRT. The kidney survival rate during the infantile period was significantly lower in patients with a maximum serum creatinine level during the first 3 days (Cr-day3-max) ≥ 2.5 mg/dL (21.8%) compared with those with a Cr-day3-max < 2.5 mg/dL (95.2%) (log-rank, P < 0.001). Multivariate analysis demonstrated Cr-day3-max (P < 0.001) and oligohydramnios (P = 0.025) were associated with higher risk of infantile KFRT. Eighty-two patients (89%) were alive at the last follow-up. CONCLUSIONS: Neonatal kidney function, including Cr-day3-max, was associated with kidney outcomes in patients with severe CAKUT. Aggressive therapy for severe CAKUT may have good long-term life outcomes through infantile dialysis and kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prolonged requirements for mechanical ventilation and tube feeding support predicted 18-month outcomes for neonatal encephalopathy.

AIM: We evaluated the predictive ability of prolonged requirements for mechanical ventilation or tube feeding support for 18-month composite outcomes in infants with hypoxic-ischaemic encephalopathy treated with hypothermia. METHODS: This retrospective, nationwide, observational study focused on newborn infants registered in Japan's Baby Cooling Registry between 1 January 2012 and 31 December 2016. The adverse outcomes were defined as death or survival with cerebral palsy, visual or auditory impairment or the requirement for mechanical ventilation or tube feeding at 18 months of age. RESULTS: Adverse outcomes occurred in 165 (28%) of the 591 children in the final cohort. These were predicted by prolonged dependence on mechanical ventilation or tube feeding for more than seven and more than 14 days. The respective values were positive predictive value 0.34 (95% CI 0.33-0.34) and 0.60 (95% CI 0.56-0.62), negative predictive value 0.97 (95% CI 0.91-0.99) and 0.93 (95% CI 0.90-0.95) and area under the curve 0.59 (95% CI 0.54-0.64) and 0.81 (95% CI 0.77-0.85). CONCLUSION: Prolonged dependence on mechanical ventilation or tube feeding for more than 14 days may be useful in predicting 18-month outcomes in newborn infants who have received therapeutic hypothermia.

Mortality and neurodevelopmental outcomes in very low birth weight infants with esophageal atresia.

PURPOSE: Very low birth weight infants (VLBWIs) have been thought as risk of bad outcomes in the patients with esophageal atresia (EA). However, detailed outcomes of EA within VLBWIs were not fully understood. We aimed to reveal short- and long-term outcomes in VLBWIs with EA. METHODS: Clinical data regarding VLBWIs with EA registered in Neonatal Research Network Japan, a multicenter research database in Japan, were collected. Patients with chromosomal abnormality were excluded. Short term outcome was survival discharge from NICU and long-term outcome was neurodevelopmental impairment (NDI) at 3 years. RESULTS: A total of 103 patients were analyzed. the overall survival discharge rate from NICU was 68.0% (70/103). The risk of death was increased as the birth weight got reduced. The presence of associated anomaly increased the risk of death. Three-year neurodevelopmental information was available in 32.9% (23/70) of patients. Of the 23 included patients for 3-year follow-up, 34.8% had NDI. The risk of NDI was increased as the birth weight reduced. CONCLUSIONS: In VLBWIs with EA, survival discharge from NICU was still not high. More immature patients and patients with an associated anomaly had worse outcomes. Among patients who survived, NDI was confirmed in a certain number of patients.

International Variation in the Management of Patent Ductus Arteriosus and Its Association with Infant Outcomes: A Survey and Linked Cohort Study.

OBJECTIVE: To assess whether treating patients with a presymptomatic patent ductus arteriosus (PDA), based on early routine echocardiography, performed regardless of clinical signs, improved outcomes. STUDY DESIGN: This multicenter, survey-linked retrospective cohort study used an institutional-level questionnaire and individual patient-level data and included infants of <29 weeks of gestation born in 2014-2016 and admitted to tertiary neonatal intensive care units (NICUs) of 9 population-based national or regional neonatal networks. Infants in NICUs receiving treatment of presymptomatic PDA identified by routine echocardiography and those not were compared for the primary composite outcome (early death [≤7 days after birth] or severe intraventricular hemorrhage) and secondary outcomes (any in-hospital mortality and major morbidities). RESULTS: The unit survey (response rates of 86%) revealed a wide variation among networks in the treatment of presymptomatic PDA (7%-86%). Among 246 NICUs with 17 936 infants (mean gestational age of 26 weeks), 126 NICUs (51%) with 7785 infants treated presymptomatic PDA. The primary outcome of early death or severe intraventricular hemorrhage was not significantly different between the NICUs treating presymptomatic PDA and those who did not (17% vs 21%; aOR 1.00, 95% CI 0.85-1.18). The NICUs treating presymptomatic PDA had greater odds of retinopathy of prematurity treatment (13% vs 7%; aOR 1.47, 95% CI 1.01-2.12); however, it was not significant in a sensitivity analysis excluding Japanese data. CONCLUSIONS: Treating presymptomatic PDA detected by routine echocardiography was commonplace but associated with no significant benefits. Well-designed trials are needed to assess the efficacy and safety of early targeted PDA treatment.

Body temperature, heart rate and long-term outcome of cooled infants: an observational study.

BACKGROUND: Therapeutic hypothermia is a standard of care for neonatal encephalopathy; however, approximately one in two newborn infants fails to respond to this treatment. Recent studies have suggested potential relationships between body temperature, heart rate and the outcome of cooled infants. METHODS: The clinical data of 756 infants registered to the Baby Cooling Registry of Japan between January 2012 and December 2016 were analysed to assess the relationship between body temperature, heart rate and adverse outcomes (death or severe impairment at 18 months corrected age). RESULTS: A lower body temperature at admission was associated with adverse outcomes in the univariate analysis (P < 0.001), the significance of which was lost when adjusted for the severity of encephalopathy and other covariates. A higher body temperature during cooling and higher heart rate before and during cooling were associated with adverse outcomes in both univariate (all P < 0.001) and multivariate (P = 0.012, P < 0.001 and P < 0.001, respectively) analyses. CONCLUSIONS: Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling, whereas causal relationships between slightly higher temperatures during cooling and adverse outcomes need to be elucidated in future studies. IMPACT: In a large cohort of encephalopathic newborn infants, dual roles of body temperature to the outcome were shown; adverse outcomes were associated with a lower body temperature at admission and higher body temperature during cooling. A higher heart rate before and during cooling were associated with adverse outcomes. Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling. The exact mechanism underlying the relationship between slightly higher body temperature during cooling and adverse outcomes remains unknown, which needs to be elucidated in future studies.

The status of chronic lung disease diagnosis in Japan: Secondary publication.

BACKGROUND: In Japan, the definition and classification of neonatal chronic lung disease (CLD) used for its diagnosis are a combination of those used in Japan and abroad. METHODS: To clarify the current state of CLD diagnosis, a questionnaire survey was conducted. RESULTS: Half of the patients of the medical centers included in the study were diagnosed with CLD in real time, while the other half were diagnosed after discharge. In addition, in approximately 70% of the facilities, diagnosis was made after discussions various among medical teams. In approximately 80% of the centers, the chest radiography used for CLD diagnosis were evaluated by multiple doctors. Furthermore, some centers used chest X-rays that were taken at approximately 28 days of age for CLD diagnosis, whereas at other facilities, diagnosis was made regardless of time at which the chest radiography were obtained. Only a small number of centers have established criteria for determining the necessity of oxygen at the corrected age of 36 weeks, and the target saturation of peripheral oxygen levels also tend to vary for each facility. Whether the conditions wherein the patient receives respiratory support for apnea or respiratory tract diseases should be considered as CLD also differed among the facilities. CONCLUSIONS: It is necessary to reassess the definition and classification of CLD in Japan to accurately evaluate and improve the quality of respiratory management based on the long-term prognosis.

Mechanical versus bioprosthetic valves in chronic dialysis: a systematic review and meta-analysis.

BACKGROUND: Many patients with end-stage kidney disease (ESKD) have valvular heart disease requiring surgery. The optimal prosthetic valve is not established in this population. We performed a systematic review and meta-analysis to assess outcomes of patients with dialysis-dependent ESKD who received mechanical or bioprosthetic valves. METHODS: We searched Cochrane Central, Medline and Embase from inception to January 2020. We performed screening, full-text assessment, risk of bias and data collection, independently and in duplicate. Data were pooled using a random-effects model. RESULTS: We identified 28 observational studies (n = 9857 patients, including 6680 with mechanical valves and 3717 with bioprosthetic valves) with a median follow-up of 3.45 years. Twenty-two studies were at high risk of bias and 1 was at critical risk of bias from confounding. Certainty in evidence was very low for all outcomes except bleeding. Mechanical valves were associated with reduced mortality at 30 days (relative risk [RR] 0.79, 95% confidence interval [CI] 0.65-0.97, I 2 = 0, absolute effect 27 fewer deaths per 1000) and at 6 or more years (mean 9.7 yr, RR 0.83, 95% CI 0.72-0.96, I 2 = 79%, absolute effect 145 fewer deaths per 1000), but increased bleeding (incidence rate ratio [IRR] 2.46, 95% CI 1.41-4.27, I 2 = 59%, absolute effect 91 more events per 1000) and stroke (IRR 1.63, 95% CI 1.21-2.20, I 2 = 0%, absolute effect 25 more events per 1000). CONCLUSION: Mechanical valves were associated with reduced mortality, but increased rate of bleeding and stroke. Given very low certainty for evidence of mortality and stroke outcomes, patients and clinicians may choose prosthetic valves based on factors such as bleeding risk and valve longevity. STUDY REGISTRATION: PROSPERO no. CRD42017081863.

Neonatal Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for neonatal life support includes evidence from 7 systematic reviews, 3 scoping reviews, and 12 evidence updates. The Neonatal Life Support Task Force generally determined by consensus the type of evidence evaluation to perform; the topics for the evidence updates followed consultation with International Liaison Committee on Resuscitation member resuscitation councils. The 2020 CoSTRs for neonatal life support are published either as new statements or, if appropriate, reiterations of existing statements when the task force found they remained valid. Evidence review topics of particular interest include the use of suction in the presence of both clear and meconium-stained amniotic fluid, sustained inflations for initiation of positive-pressure ventilation, initial oxygen concentrations for initiation of resuscitation in both preterm and term infants, use of epinephrine (adrenaline) when ventilation and compressions fail to stabilize the newborn infant, appropriate routes of drug delivery during resuscitation, and consideration of when it is appropriate to redirect resuscitation efforts after significant efforts have failed. All sections of the Neonatal Resuscitation Algorithm are addressed, from preparation through to postresuscitation care. This document now forms the basis for ongoing evidence evaluation and reevaluation, which will be triggered as further evidence is published. Over 140 million babies are born annually worldwide (https://ourworldindata.org/grapher/births-and-deaths-projected-to-2100). If up to 5% receive positive-pressure ventilation, this evidence evaluation is relevant to more than 7 million newborn infants every year. However, in terms of early care of the newborn infant, some of the topics addressed are relevant to every single baby born.

Variations in Neonatal Length of Stay of Babies Born Extremely Preterm: An International Comparison Between iNeo Networks.

OBJECTIVE: To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. RESULTS: Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (-4.8 days less than reference, 95% CI -7.3 to -2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI -12.3 to -11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. CONCLUSIONS: We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Neonatal systemic juvenile Xanthogranuloma with Hydrops diagnosed by Purpura skin biopsy: a case report and literature review.

BACKGROUND: Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of congenital neonatal systemic juvenile xanthogranuloma with atypical skin appearance that made the diagnosis difficult. CASE PRESENTATION: A preterm Japanese female neonate with prenatally diagnosed fetal hydrops in-utero was born with purpuric lesions involving the trunk and face. Since birth, she had hypoxemic respiratory failure, splenomegaly, anemia, thrombocytopenia, coagulopathy, and was transfusion dependent for red blood cells, fresh frozen plasma, and platelets. Multiple cystic lesions in her liver, part of them with vascular, were detected by ultrasound. A liver biopsy was inconclusive. A skin lesion on her face similar to purpura gradually changed to a firm and solid enlarged non-yellow nodule. Technically, the typical finding on skin biopsy would have been histiocytic infiltration (without Touton Giant cells) and immunohistochemistry results which then would be consistent with a diagnosis of systemic juvenile xanthogranuloma, and chemotherapy improved her general condition. CONCLUSIONS: This case report shows that skin biopsies are necessary to detect neonatal systemic juvenile xanthogranuloma when there are organ symptoms and skin eruption, even if the skin lesion does not have a typical appearance of yellow papules or nodules.

Learning From Strengths: Improving Care by Comparing Perinatal Approaches Between Japan and Canada and Identifying Future Research Priorities.

OBJECTIVE: Preterm birth (PTB) is the leading cause of infant morbidity and mortality worldwide. Canada and Japan each have strengths that can inform clinical decision-making, research, and health care policy regarding the prevention of PTB and its sequelae. Our objectives were to: 1) compare PTB rates, risk factors, management, and outcomes between Japan and Canada; 2) establish research priorities while fostering future collaborative opportunities; and 3) undertake knowledge translation of these findings. METHODS: We conducted a literature review to identify publications that examined PTB rates, risk factors, prevention and management techniques, and outcomes in Japan and Canada. We conducted site visits at 4 Japanese tertiary centres and held a collaborative stakeholder meeting of parents, neonatologists, maternal-fetal medicine specialists, and researchers. RESULTS: Japan reports lower rates of PTB, neonatal mortality, and several PTB risk factors than Canada. However, Canadian PTB data is population-based, whereas, in Japan, the rate of PTB is population-based, but outcomes are not. Rates of severe neurologic injury and necrotizing enterocolitis were lower in Japan, while Canada's rates of bronchopulmonary dysplasia and retinopathy of prematurity were lower. PTB prevention approaches differed, with less progesterone use in Japan and more long-term tocolysis. In Japan, there were lower rates of neonatal transfers and non-faculty overnight care, but also less use of antenatal corticosteroids and deferred cord clamping. Research priorities identified through the stakeholder meeting included early skin-to-skin contact, parental well-being after PTB, and transitions in care for the child. CONCLUSION: We identified key differences between Japan and Canada in the factors affecting PTB management and patient outcomes, which can inform future research efforts.

Low vancomycin trough concentration in neonates and young infants.

BACKGROUND: Vancomycin (VCM) is useful for treating methicillin-resistant Staphylococcus aureus. In infants, calibrating the initial VCM dose is difficult, and many regimens have been proposed. For instance, our center uses the VCM regimen recommended for infants in the 2012-13 Nelson's Pediatric Antimicrobial Therapy. Nonetheless, our experience has shown that the initial VCM trough concentrations were frequently off target. We therefore analyzed the data on the initial VCM trough concentration in infant patients at our center. METHODS: The study subjects were inborn infants born between July 2014 and June 2019 who were given VCM at earlier than day 60 in the neonatal intensive care unit. The primary outcome was the initial VCM trough concentration. The patients were divided into three groups by VCM trough concentration: <10, 10-15, and >15 mg/L. We also estimated VCM trough concentration by one method using Monte Carlo simulation, based on Nelson regimen dosage. RESULTS: Thirty-three patients were analyzed. The number of patients with <10, 10-15, and >15 mg/L was 24, 4, and 5, respectively. There was no significant difference in clinical characteristics between <10 versus 10-15 and 10-15 versus >15 mg/L. The numbers of patients with <10, 10-15, and >15 mg/L in the simulation were 26, 6, and 1, respectively. CONCLUSIONS: Most initial VCM trough concentrations were below the target. We could not find any significant clinical characteristics, which affected VCM trough concentration. Increasing the VCM dosage of the Nelson regimen with simulation should therefore be considered.

Management of infants born to mothers with suspected or confirmed SARS-CoV-2 infection in the delivery room: A tentative proposal 2020.

Coronavirus disease 2019 (COVID-19) has spread worldwide within a short period, and there is still no sign of an end to the pandemic. Management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pregnant women at the time of delivery presents a unique challenge. To fulfill the goal of providing adequate management of such women and their infants, and to decrease the risk of exposure of the healthcare providers, tentative guidelines are needed until more evidence is collected. Practical preventative action is required that takes into account the following infection routes: (i) aerosol transmission from mothers to healthcare providers, (ii) horizontal transmission to healthcare providers from infants infected by their mothers, and (iii) horizontal transmission from mothers to infants. To develop standard operating procedures, briefings/training simulations should be carried out, taking into account the latest information. Briefings should be carefully conducted to clarify the role and procedures. Healthcare providers should wear personal protective equipment. If it is physically possible, neonatal resuscitation should be performed in a separate area next to the delivery room. If a separate area is not available, the infant warmer should be placed at least 2 m away from the delivery table, or partitioned off in the same room. A minimum number of skilled personnel should participate in resuscitation using the latest neonatal resuscitation algorithms.