A Retrospective Cohort Study on Mortality and Neurodevelopmental Outcomes of Preterm Very Low Birth Weight Infants Born to Mothers with Hypertensive Disorders of Pregnancy.

OBJECTIVE: We examined the effects of maternal hypertensive disorders of pregnancy (HDP) on the mortality and neurodevelopmental outcomes in preterm very low birth weight (VLBW) infants (BW ≤1,500 g) based on their intrauterine growth status and gestational age (GA). STUDY DESIGN: We included singleton VLBW infants born at <32 weeks' gestation registered in the Neonatal Research Network Japan database. The composite outcomes including death, cerebral palsy (CP), and developmental delay (DD) at 3 years of age were retrospectively compared among three groups: appropriate for GA (AGA) infants of mothers with and without HDP (H-AGA and N-AGA) and small for GA (SGA) infants of mothers with HDP (H-SGA). The adjusted odds ratios (AOR) and 95% confidence intervals (CI) stratified by the groups of every two gestational weeks were calculated after adjusting for the center, year of birth, sex, maternal age, maternal diabetes, antenatal steroid use, clinical chorioamnionitis, premature rupture of membranes, non-life-threatening congenital anomalies, and GA. RESULTS: Of 19,323 eligible infants, outcomes were evaluated in 10,192 infants: 683 were H-AGA, 1,719 were H-SGA, and 7,790 were N-AGA. Between H-AGA and N-AGA, no significant difference was observed in the risk for death, CP, or DD in any GA groups. H-AGA had a lower risk for death, CP, or DD than H-SGA in the 24 to 25 weeks group (AOR: 0.434, 95% CI: 0.202-0.930). The odds for death, CP, or DD of H-SGA against N-AGA were found to be higher in the 24 to 25 weeks (AOR: 2.558, 95% CI: 1.558-3.272) and 26 to 27 weeks (AOR: 1.898, 95% CI: 1.427-2.526) groups, but lower in the 30 to 31 weeks group (AOR: 0.518, 95% CI: 0.335-0.800). CONCLUSION: There was a lack of follow-up data; however, the outcomes of liveborn preterm VLBW infants of mothers with HDP depended on their intrauterine growth status and GA at birth. KEY POINTS: · The effects of HDP on preterm low birth weight infants need to be further examined.. · The outcomes were not different between AGA infants with and without maternal HDP.. · The outcomes of SGA infants with maternal HDP were dependent on their GA..

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.

How to avoid unnecessary surgical treatment for neonatal small left colon syndrome.

We report a case of neonatal small left colon syndrome (NSLCS) that underwent surgery. A female infant was born at 38 weeks of gestation. The mother had gestational diabetes requiring insulin therapy. The baby was admitted for respiratory distress. Abdominal distension was observed, and the gastric residue increased. Contrast enema revealed a small caliber of the left colon up to the splenic flexure. At 14 days, the full-thickness biopsy of the sigmoid and transverse colons was performed. Pathological diagnosis showed that the sigmoid colon had few ganglion cells, therefore the transverse colostomy was performed. At 6 months of age, a rectal biopsy was performed to confirm the diagnosis of Hirschsprung's disease; the intestinal plexus and ganglion cells were normal. The surgery was changed from a pull-through to a stoma closure. The postoperative diagnosis was NSLCS, and the course up to 3 years was good without defecation or growth problems.

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.

Family presence during resuscitation in paediatric and neonatal cardiac arrest: A systematic review.

CONTEXT: Parent/family presence at pediatric resuscitations has been slow to become consistent practice in hospital settings and has not been universally implemented. A systematic review of the literature on family presence during pediatric and neonatal resuscitation has not been previously conducted. OBJECTIVE: To conduct a systematic review of the published evidence related to family presence during pediatric and neonatal resuscitation. DATA SOURCES: Six major bibliographic databases was undertaken with defined search terms and including literature up to June 14, 2020. STUDY SELECTION: 3200 titles were retrieved in the initial search; 36 ultimately included for review. DATA EXTRACTION: Data was double extracted independently by two reviewers and confirmed with the review team. All eligible studies were either survey or interview-based and as such we turned to narrative systematic review methodology. RESULTS: The authors identified two key sets of findings: first, parents/family members want to be offered the option to be present for their child's resuscitation. Secondly, health care provider attitudes varied widely (ranging from 15% to >85%), however, support for family presence increased with previous experience and level of seniority. LIMITATIONS: English language only; lack of randomized control trials; quality of the publications. CONCLUSIONS: Parents wish to be offered the opportunity to be present but opinions and perspectives on the family presence vary greatly among health care providers. This topic urgently needs high quality, comparative research to measure the actual impact of family presence on patient, family and staff outcomes. PROSPERO REGISTRATION NUMBER: CRD42020140363.

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.

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.

Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP): study protocol.

INTRODUCTION: Timing of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons. OBJECTIVES: (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA. METHODS AND ANALYSIS: Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks' gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored. ETHICS AND DISSEMINATION: Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases. REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12619001305112) and International Prospective Register of Systematic Reviews (PROSPERO, CRD42019136640).

Heart-rate evaluation using fetal ultrasonic Doppler during neonatal resuscitation.

BACKGROUND: The objective of the present study was to verify the speed and accuracy of fetal ultrasonic Doppler (fetal Doppler) in measuring heart rate of newborns at rest, including preterm, low-birthweight infants, and its efficacy during neonatal resuscitation, including cases of neonatal asphyxia. METHODS: A three-lead electrocardiogram and fetal Doppler were used to measure resting heart rates in 100 newborns, including 48 preterm, low-birthweight infants, at 0 to 72 h after birth. Times to display heart rate were compared between electrocardiogram and fetal Doppler by the Bland-Altman analysis and Wilcoxon signed-rank test. The time required for the fetal Doppler to measure heart rate during neonatal resuscitation was also assessed. RESULTS: In 100 newborns, the mean error of the resting heart rate in 1,293 measurement points was 0.07 beats/min. To display the heart rate, the fetal Doppler required a median time of 5 s, and electrocardiogram required a median time of 10 s (P < 0.001). During neonatal resuscitation, the heart rate was measured within 10 s in 18 of 21 cases (86%) and displayed with a median time of 5 s; this was measured in all neonatal asphyxia cases (9/9, 100%). CONCLUSIONS: Fetal Doppler can measure heart rate in newborns accurately and rapidly and is useful for evaluating heart rate not only at rest but also during neonatal resuscitation, especially in asphyxia.

Summary of Japanese Neonatal Cardiopulmonary Resuscitation Guidelines 2015.

The Japan Resuscitation Council joined the International Liaison Committee on Resuscitation (ILCOR) as a member of the Resuscitation Council of Asia in 2006. In 2007, the Japan Society of Perinatal and Neonatal Medicine (JSPNM), which is a member of an affiliated body, launched the Neonatal Cardiopulmonary Resuscitation (NCPR) program as an authorized project to ensure that all staff involved in perinatal and neonatal medicine can learn and practice neonatal cardiopulmonary resuscitation based on the Consensus on Science with Treatment Recommendations developed by ILCOR. The content of courses in the NCPR program is based on the NCPR guidelines. These guidelines are revised by the Japan Resuscitation Council according to the Consensus on Science with Treatment Recommendations, which is updated by ILCOR every 5 years. The latest updated edition in Japanese was published in 2016 and we translated these Japanese guidelines to English in 2018. Here, we introduce a summary of the NCPR guidelines 2015 in Japan. The NCPR 2015 algorithm has two flows, "lifesaving flow" and "stabilization of breathing flow" at the first branching point after the initial step of resuscitation.

Reference Value of Brain Tissue Oxygen Saturation in Newborns Immediately After Birth.

The Consensus on Resuscitation Science and Treatment Recommendations indicate the target SpO2 values during the first 10 min of life. There are a few studies of values of brain regional saturation of oxygen (rSO2) in newborns, conventional instruments are large and not suitable for measuring in the delivery room. The purpose of this study was to develop reference values for brain rSO2 up to 10 min after birth and to review the changes in cerebral oxygenation in late preterm and term newborn infants immediately after birth. METHOD: We evaluated both brain rSO2 and SpO2 at 1, 3, 5 and 10 min after birth in 100 neonates. rSO2, was measured at the forehead using a finger-mounted oximeter. This is 1/100 the size of conventional NIRS and can be carried. To measure SpO2, a Radical-7 was used. This study was approved by the institutional review board at our hospital. RESULTS: The gestational age and birth weight were 37.9 ± 1.2 weeks and 2825 ± 429 g, respectively. Eighty-seven infants and 13 infants were term and late preterm infants, respectively, and there were 21 vaginal deliveries and 79 cesarean sections. In all cases, rSO2 levels were measured at 1, 3, 5, and 10 min after birth. For the SpO2 measurements, nine cases at 1 min, 40 cases at 3 min, 81 cases at 5 min and 93 cases at 10 min were available. The median rSO2 level was 43% at 1 min after birth, 48% at 3 min, 52% at 5 min and 57% at 10 min. CONCLUSION: We used a finger-mounted oximeter to observe changes in brain rSO2 values of 100 normal transition infants. It was easier to detect rSO2 in comparison to the peripheral oxygen saturation monitored by our pulse oximeter. Brain rSO2 values might be useful to evaluate oxygenation immediately after birth.

Outcomes related to 10-min Apgar scores of zero in Japan.

OBJECTIVE: Apgar scores of zero at 10 min strongly predict mortality and morbidity in infants. However, recent data reported improved outcomes among infants with Apgar scores of zero at 10 min. We aimed to review the mortality rate and neurodevelopmental outcomes of infants with Apgar scores of zero at 10 min in Japan. DESIGN: Observational study. PATIENTS: Twenty-eight of 768 infants registered in the Baby Cooling Registry of Japan between 2012 and 2016, at >34 weeks' gestation, with Apgar scores of zero at 10 min who were treated with therapeutic hypothermia. INTERVENTIONS: We investigated the time of first heartbeat detection in infants with favourable outcomes and who had neurodevelopmental impairments or died. MAIN OUTCOME MEASURES: Clinical characteristics, mortality rate and neurodevelopmental outcomes at 18-22 months of age were evaluated. RESULTS: Nine (32%) of the 28 infants died before 18 months of age; 16 (57%) survived, but with severe disabilities and 3 (11%) survived without moderate-to-severe disabilities. At 20 min after birth, 14 of 27 infants (52%) did not have a first heartbeat, 13 of them died or had severe disabilities and one infant, who had the first heartbeat at 20 min, survived without disability. CONCLUSION: Our study adds to the recent evidence that neurodevelopmental outcomes among infants with Apgar scores of zero at 10 min may not be uniformly poor. However, in our study, all infants with their first heartbeat after 20 min of age died or had severe disabilities.

An Asian multicenter retrospective study on persistent pulmonary hypertension of the newborn: incidence, etiology, diagnosis, treatment and outcome.

Objectives: To explore the incidence, etiologies, diagnostic methods, treatment options and outcomes in neonates with persistent pulmonary hypertension of the newborn (PPHN) and to identify mortality risk factors in a study from six Asian countries.Methods: A retrospective chart review of patients with documented PPHN from seven centers in six Asian countries (Japan, Kuwait, India, Pakistan, Singapore, and Thailand) between 1 January, 2014 and 31 December, 2016, was performed.Results: A total of 369 PPHN infants were identified. The incidence of PPHN ranged from 1.2 to 4.6 per 1000 live births. The all-cause mortality rate was 20.6% (76 of 369). Meconium aspiration syndrome was the primary cause of PPHN (24.1%). In most cases (84.8%) echocardiography was used to establish the diagnosis of PPHN. Sildenafil was the most commonly used pulmonary vasodilator (51.2%). Multivariate multiple regression analysis indicated gestational age <34 weeks (adjusted odds ratio (OR) = 3.27; 95% CI 1.56-6.74), congenital diaphragmatic hernia (CDH)/lung hypoplasia (LH) (adjusted OR = 6.13 (95% CI 2.28-16.42)), treatment with high frequency oscillation ventilation (HFOV) with or without inhaled nitric oxide (iNO) (adjusted OR = 3.11 (95% CI 1.52-6.34)), and inotropic agents (adjusted OR = 9.43 (95% CI 2.71-32.83)) were independently associated with increased risk of death.Conclusions: The incidence of PPHN in the current study was higher than in western settings. Birth weight, gestational age, CDH/LH, HFOV/iNO, and inotropic agents were significant mortality risk factors.

Neonatal cardiopulmonary resuscitation project in Japan.

In July 2007, the Neonatal Cardiopulmonary Resuscitation (NCPR) program in Japan was launched to ensure that all staff involved in perinatal and neonatal medicine can learn and practice NCPR based on the Consensus on Science with Treatment Recommendations developed by the International Liaison Committee on Resuscitation. In 1978 in North America, a working group on pediatric resuscitation was formed by the American Heart Association Emergency Cardiac Care Committee and concluded that the resuscitation of newborns required a different strategy than the resuscitation of adults. The original first edition of the Neonatal Resuscitation Program textbook was published in 1987. The NCPR program consists of three courses for health-care providers and two courses for instructors. A course and B course are for newly certified health-care providers and course S is for health-care providers who are renewing their certification. As of 31 March 2019, 3,227 advanced instructors (I instructor) and 1,877 basic instructors (J instructor) were trained to teach A, B, and S courses to health-care providers on the basis of their license. In total 7,075 A courses and 4,012 B courses were held; 131 651 people attended A course or B course of the NCPR program, and 77 367 were certified. A total of 1,865 S courses, which were developed in 2015, were held and 12 875 people attended this course. Here, we introduce the background, purpose, history, and content of the development of the NCPR program in Japan.

Body Temperature, Heart Rate, and Short-Term Outcome of Cooled Infants.

Therapeutic hypothermia following neonatal encephalopathy is neuroprotective. However, approximately one in two cooled infants still die or develop permanent neurological impairments. Further understanding of variables associated with the effectiveness of cooling is important to improve the therapeutic regimen. To identify clinical factors associated with short-term outcomes of cooled infants, clinical data of 509 cooled infants registered to the Baby Cooling Registry of Japan between 2012 and 2014 were evaluated. Independent variables of death during the initial hospitalization and survival discharge from the cooling hospital at ≤28 days of life were assessed. Death was associated with higher Thompson scores at admission (p < 0.001); higher heart rates after 3-72 hours of cooling (p < 0.001); and higher body temperature after 24 hours of cooling (p = 0.002). Survival discharge was associated with higher 10 minutes Apgar scores (p < 0.001); higher blood pH and base excess (both p < 0.001); lower Thompson scores (at admission and after 24 hours of cooling; both p < 0.001); lower heart rates at initiating cooling (p = 0.003) and after 24 hours of cooling (p < 0.001) and lower average values after 3-72 hours of cooling (p < 0.001); higher body temperature at admission (p < 0.001); and lower body temperature after 24 hours and lower mean values after 3-72 hours of cooling (both p < 0.001). Survival discharge was best explained by higher blood pH (p < 0.05), higher body temperature at admission (p < 0.01), and lower body temperature and heart rate after 24 hours of cooling (p < 0.01 and <0.001, respectively). Lower heart rate, higher body temperature at admission, and lower body temperature during cooling were associated with favorable short-term outcomes.

Characterization of chylomicron in preterm infants.

BACKGROUND: The aim of this study was to investigate cholesterol and triglyceride levels in the chylomicron fraction of preterm infants at birth and during the early postnatal period. METHODS: The subjects consisted of 133 infants (81 boys and 52 girls): 74 were term infants born at 37-41 weeks of gestation and 59 were preterm infants born at 29-36 weeks of gestation. Cholesterol and triglyceride in the chylomicron fraction were measured using high-performance liquid chromatography. RESULTS: Compared with term infants, preterm infants had higher cholesterol and lower triglyceride in the chylomicron fraction, both in cord blood and at 1 month after birth. Thus, the chylomicron triglyceride/cholesterol ratio was significantly lower in preterm infants than in term infants in cord blood and at 1 month of age. On single regression analysis the chylomicron triglyceride/cholesterol ratio correlated positively with gestational age at birth (r = 0.331, P = 0.0003) and at 1 month (r = 0.221, P = 0.0119). CONCLUSIONS: Preterm infants have a less-lipidated chylomicron composition at birth and at 1 month of age. Some prenatal factors may persist to influence chylomicron lipidation during the early postnatal period.

A new wrinkle: Umbilical cord management (how, when, who).

In the past five years, umbilical cord management in both term and preterm infants has come full circle, going from the vast majority of infants receiving immediate cord clamping to virtually all governing organizations promoting placental transfusion, mainly in the form of delayed cord clamping (DCC). Placental transfusion refers to the transfer of more blood components to the infant during the first few minutes after birth. The different strategies for ensuring placental transfusion to the baby include delayed (deferred) cord clamping, milking of the attached cord before clamping, and milking of the cut cord. In this review, we address the current evidence to date for providing placental transfusion in different circumstances and the methods for implementation. We also highlight the gaps in knowledge and areas for future research.