細野 茂春

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.

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.

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.

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.

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.

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 &lt;/=28 days of life were assessed. Death was associated with higher Thompson scores at admission (p &lt; 0.001); higher heart rates after 3-72 hours of cooling (p &lt; 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 &lt; 0.001); higher blood pH and base excess (both p &lt; 0.001); lower Thompson scores (at admission and after 24 hours of cooling; both p &lt; 0.001); lower heart rates at initiating cooling (p = 0.003) and after 24 hours of cooling (p &lt; 0.001) and lower avera

BackgroundWe measured changes in the blood level of high-mobility group box-1 (HMGB-1) at 24 h intervals in neonates treated with brain/body hypothermia (body hypothermia therapy: BHT) for hypoxic-ischemic encephalopathy (HIE), to evaluate the usefulness of HMGB-1 level for determining outcomes. MethodsWe studied 15 neonates with HIE who underwent BHT (BHT (+) group) and six neonates with HIE who did not (BHT (-) group). We recorded HMGB-1 changes at 24 h intervals, creatinine phosphokinase, and the resistance index of the anterior cerebral artery. Magnetic resonance imaging (MRI) was used to determine short-term outcome. ResultBaseline HMGB-1 was significantly higher in the BHT (+) group than in the BHT (-) group. Thereafter, HMGB-1 in the BHT (+) group significantly decreased at 24 h intervals, reaching the reference range by 2 days of age. In the BHT (+) group, when patients were classified into clinically significant neurological disorder due to HIE (+) and (-) according to MRI, the neurological disorder (+) group had higher mean HMGB-1. ConclusionsIn HIE, HMGB-1 differs according to the presence of BHT, suggesting that HMGB-1 measurement soon after birth might be useful for determining BHT necessity and short-term outcome.

BackgroundDuring neonatal resuscitation, careful oxygenation is needed. Pulse oximetry is recommended to evaluate the need for oxygenation, but it is not clear whether peripheral perfusion is adequate for the evaluation of arterial oxygen saturation (SpO(2)). Additionally, there has been no study on the changes in SpO(2) immediately after birth in Japan, despite the indispensable need for definitive oxygenation criteria. MethodsA prospective observational study was performed in neonates at gestational age 35-41weeks. An SpO(2) measurement probe was attached to the neonates immediately after birth at the right palm or wrist, and the perfusion index (PI), pulse rate, and SpO(2) were measured until 10min after birth. ResultsSixty neonates were examined. Stable PI was obtained soon after birth, preceding SpO(2) measurement. The median PI (%) was constant at approximately 1.3, and the median SpO(2) at 2-10min was 70%, 81%, 82%, 87%, 89%, 92%, 92%, 94%, and 95%, respectively. The current target value for SpO(2) in the Neonatal Cardiopulmonary Resuscitation (NCPR) guideline in Japan is approximately the 25th percentile. ConclusionPI is stable and sufficient in the early postnatal period, meaning that peripheral perfusion is adequate for the measurement of SpO(2). The current target SpO(2) used in the NCPR guidelines is at approximately the 25th percentile and is thought to be sufficient for meeting oxygenation criteria.

Sildenafil (SIL) is used as a rescue treatment for severe bronchopulmonary dysplasia and pulmonary arterial hypertension. SIL inhibits phosphodiesterase 6 (PDE6) as well as PDE5. Therefore, it is controversial as to whether SIL increases the risk of retinopathy of prematurity (ROP).

BackgroundGuidelines recommend avoiding excessive oxygen during neonatal resuscitation. Recent studies have suggested that oxygen titration can be achieved using a self-inflating bag, but data on the effectiveness of resuscitators used in neonatal ventilation are scarce, The aim of this study was therefore to determine the amount of oxygen delivered using several brands of neonatal self-inflating resuscitation bags without reservoirs under different conditions with regard to oxygen flow rate, ventilation rate (VR), peak inspiratory pressure (PIP) range, and test lung compliance. MethodsOxygen concentration was measured under a variety of conditions. Combinations of oxygen flow rate (10, 5.0, 3.0 and 1.0 L/min), VR (40, 60 inflations/min), PIP range (20-25 cmH(2)O, 35-40 cmH(2)O), and test lung compliance (0.6, 1.0, 3.0, and 5.0 mL/cmH(2)O) were examined using six kinds of self-inflating bag. ResultsDelivered oxygen concentration varied widely (30.1-96.7%) and had a significant positive correlation with gas flow rate in all of the bags. Delivered oxygen concentration was also negatively correlated with PIP in all of the bags and with VR in some of them. Test lung compliance did not affect delivered oxygen concentration. ConclusionThe use of neonatal resuscitation self-inflating bags without reservoirs resulted in different delivered oxygen concentrations depending on gas flow rate, VR, PIP, and manufacturer, but not on lung compliance. This suggests that targeted oxygen concentrations could be delivered, even in lungs with decreased compliance, during resuscitation.

Therapeutic hypothermia is recommended for moderate and severe neonatal encephalopathy, but is being applied to a wider range of neonates than originally envisaged. To examine the clinical use of therapeutic hypothermia, data collected during the first 3 years (2012-2014) of the Baby Cooling Registry of Japan were analysed. Of 485 cooled neonates, 96.5% were &gt;= 36 weeks gestation and 99.4% weighed &gt;= 1,800 g. Severe acidosis (pH &lt; 7 or base deficit &gt;= 16 mmol/L) was present in 68.9%, and 96.7% required resuscitation for &gt; 10 min. Stage II/III encephalopathy was evident in 88.3%; hypotonia, seizures and abnormal amplitude-integrated electroencephalogram were observed in the majority of the remainder. In-hospital mortality was 2.7%; 90.7% were discharged home. Apgar scores and severity of acidosis/encephalopathy did not change over time. The time to reach the target temperature was shorter in 2014 than in 2012. The proportion undergoing whole-body cooling rose from 45.4% to 81.6%, while selective head cooling fell over time. Mortality, duration of mechanical ventilation and requirement for tube feeding at discharge remained unchanged. Adherence to standard cooling protocols was high throughout, with a consistent trend towards cooling being achieved more promptly. The mortality rate of cooled neonates was considerably lower than that reported in previous studies.

Term neonates have high delta-6 desaturase (D6D) activity, which is important for regulating polyunsaturated fatty acid's (PUFA) nutritional status. The aim was to investigate D6D activity in preterm infants and its postnatal changes. Forty-three appropriate-for-gestational-age infants were included. PUFA in red blood cells was analyzed at birth and at one, six, and 12 months of age. D6D activity was estimated by 20:3n-6/18:2n-6 ratio. At birth, preterm infants had D6D activity as high as that of term infants; D6D activity declined to about one-third at one month, then further decreased to about one-sixth at six months and remained stable until 12 months. The postnatal change in arachidonic acid exhibited a similar pattern to that of D6D activity; however, docosahexaenoic acid showed a transient decrease at one month and recovered to the cord blood level at six months. D6D may regulate PUFA profile in preterm infants, especially during the early postnatal period.

AimThis study determined current international clinical practice and opinions regarding initial fractional inspired oxygen (FiO(2)) and pulse oximetry (SpO(2)) targets for delivery room resuscitation of preterm infants of less than 29 weeks of gestation. MethodsAn online survey was disseminated to neonatal clinicians via established professional clinical networks using a web-based survey programme between March 9 and June 30, 2015. ResultsOf the 630 responses from 25 countries, 60% were from neonatologists. The majority (77%) would target SpO(2) between the 10th to 50th percentiles values for full-term infants. The median starting FiO(2) was 0.3, with Japan using the highest (0.4) and the UK using the lowest (0.21). New Zealand targeted the highest SpO(2) percentiles (median 50%). Most respondents agreed or did not disagree that a trial was required that compared the higher FiO(2) of 0.6 (83%), targeting the 50th SpO(2) percentile (60%), and the lower FiO(2) of 0.21 (80%), targeting the 10th SpO(2) percentile (78%). Most (65%) would join this trial. Many considered that evidence was lacking and further research was needed. ConclusionClinicians currently favour lower SpO(2) targets for preterm resuscitation, despite acknowledging the lack of evidence for benefit or harm, and 65% would join a clinical trial.

BACKGROUND: Fetal organs require much lipid for growth, but the cord blood had low TG concentrations, compared to adult serum. We investigated the association between the concentration of apolipoprotein A-V (apoA-V) and lipid profile in cord blood and neonatal serum. OBJECTIVE: ApoA-V was identified as an important determinant of plasma triglyceride concentrations. We sought to determine the association between serum apoA-V concentrations and lipoprotein profile in preterm infants and its early postnatal change. METHODS: Sixty-three neonates (35 males and 28 females; 15 term and 48 preterm) were included. Serum lipoprotein profile and apoA-V concentrations were determined at birth and 1 month. RESULTS: Cord blood apoA-V concentrations in appropriate-for-gestational age infants were extremely low (13.1 +/- 3.4 ng/mL in term infants, 4.4 +/- 0.9 ng/mL in preterm infants) compared with adult values, and those of small-for-gestational age infants were further low (6.4 +/- 4.2 ng/mL, 2.2 +/- 1.3 ng/mL, respectively). During the first month, serum apoA-V concentration markedly increased, and the concentration of preterm appropriate-for-gestational age infants caught up, whereas that of preterm small-for-gestational age infants did not. At birth, apoA-V concentration positively correlated with gestational age (r = 0.354, P = .0069) but not with birth weight Z-score. ApoA-V concentration had a positive association with very low density lipoprotein triglyceride concentrations (r = 0.646, P &lt; .0001), and the relationships still remained at 1 month (r = 0.283, P = .0348). CONCLUSIONS: ApoA-V in neonates was unique in its serum concentration and in the association with lipoprotein profile. (C) 2015 National Lipid Association. All rights reserved.

As part of quality assessment of a teleradiology program we evaluated the validity of patient information received, the quality of panoramic radiography imaging in Laos, and the ability of a Laotian radiologist to detect temporomandibular joint abnormalities. The amount of patient information gathered from 2,021 scans of panoramic radiographs was evaluated by triage before image diagnosis. Among the radiographs from 2,021 patients, primary triage indicated that there was insufficient information for 794 (39.3%) patients. Secondary triage to assess imaging failure included 1,227 radiographs, four of which were excluded from imaging diagnosis because of unacceptable image flaws. In total, 2,446 joints from 1,223 radiographs were evaluated for temporomandibular joint abnormalities in order to compare the image interpretation abilities of Laotian and Japanese radiologists. The kappa coefficient was 0.836 (P &lt; 0.01) for the agreement between the two observers in detecting temporomandibular joint abnormalities on radiographs. We conclude that additional efforts are needed in order to overcome the challenges of maintaining quality in imaging techniques and diagnoses in Laos.

BACKGROUND AND OBJECTIVES: Available data on survival rates and outcomes of extremely low gestational age (GA) infants (22-25 weeks' gestation) display wide variation by country. Whether similar variation is found in statements by national professional bodies is unknown. The objectives were to perform a systematic review of management from scientific and professional organizations for delivery room care of extremely low GA infants. METHODS: We searched Embase, PubMed, and Google Scholar for management guidelines on perinatal care. Countries were included if rated by the United Nations Development Programme's Human Development Index as "very highly developed." The primary outcome was rating of recommendations from "comfort care" to "active care." Secondary outcomes were specifying country-specific survival and considering potential for 3 biases: limitations of GA assessment; bias from different definitions of stillbirths and live births; and bias from the use of different denominators to calculate survival. RESULTS: Of 47 highly developed countries, 34 guidelines from 23 countries and 4 international groups were identified. Of these, 3 did not state management recommendations. Of the remaining 31 guidelines, 21 (68%) supported comfort care at 22 weeks' gestation, and 20 (65%) supported active care at 25 weeks' gestation. Between 23 and 24 weeks' gestation, much greater variation was seen. Seventeen guidelines cited national survival rates. Few guidelines discussed potential biases: limitations in GA (n = 17); definition bias (n = 3); and denominator bias (n = 7). CONCLUSIONS: Although there is a wide variation in recommendations (especially between 23 and 24 weeks' GA), there is general agreement for comfort care at 22 weeks' GA and active care at 25 weeks' GA.

OBJECTIVE: To compare two strategies to potentiate the effects of placental transfusion in infants born at &lt;29 weeks of gestation. STUDY DESIGN: Twenty infants who received one-time umbilical cord milking after umbilical cord cutting were compared with 20 infants from a previous study group who received multiple-time umbilical cord milking. The primary outcome measurements were the probability of not needing a red blood cell (RBC) transfusion during the hospital stay and the total number of RBC transfusions within 21 days after birth. RESULT: There was no significant difference in the probability of not needing a transfusion during the hospital stay (P = 0.75) and the mean number of RBC transfusions given within the first 21 days of life (1.1 +/- 1.8 for the one-time umbilical cord-milking group vs 0.7 +/- 1.2 for the multiple-time umbilical cord-milking group, P = 0.48). CONCLUSION: One-time umbilical cord milking after umbilical cord cutting had similar beneficial effects to multiple-time umbilical cord milking before umbilical cord cutting in very premature infants.

Clinical kernicterus in preterm infants has recently been reported in Japan, diagnosed on the basis of clinical findings during the neonatal and infancy periods. We investigated the incidence of clinical kernicterus in preterm infants &lt;30weeks gestational age (GA) based on a nationwide survey conducted in 233 certified educational facilities for neonatologists. The numbers of infants admitted and infants who died within 14days after birth during 2011, and the number of infants who subsequently developed clinical kernicterus, were recorded. A total of 2720 infants were analyzed, representing 59% (2720/4623) of all preterm live births &lt;30weeks GA in Japan in 2011. Of these, 159 (5.8%) died within 14days after birth, similar to the national rate. Five infants developed clinical kernicterus in infancy (5/2720, 0.18%). The current incidence of clinical kernicterus in Japan is therefore estimated at 1.8 per 1000 live births &lt;30weeks GA.

BackgroundThe aim of this study was to determine the current neonatal resuscitation practices for term infants in Japan, immediately before the 2010 publication of the international neonatal resuscitation consensus. MethodsIn January 2010, a 26-question survey was mailed to neonatal department directors. ResultsA total of 287 neonatal departments were identified. Four surveys were returned as undeliverable. A total of 191 surveys were returned completed, but four departments had no labor and delivery rooms (66.6% response rate, 65.2% survey available response rate). Flow-inflating bags were most commonly used (63.2%), followed by self-inflating bags (35.8%), and T-piece resuscitators (1.0%). Among the participants, 42.1% used oxygen blenders, 56.2% used pure oxygen for initial resuscitation, and 79.5% used a pulse oximeter to change the fraction of inspired oxygen. Among the participants, 45.3% used carbon dioxide detectors to confirm intubation, 42.5% routinely used the detectors, and 55.2% used them when confirming a difficult intubation. In addition, 42.5% of the participants used continuous positive airway pressure to treat breathing problems, most commonly with flow-inflating bags (93.2%). ConclusionsThe equipment and techniques used in Japanese perinatal center delivery room resuscitation practices are highly varied. Further research is required to determine which devices and techniques are appropriate for this important and common intervention.

BackgroundThe aim of this study was to investigate residual blood volume in the umbilical cord of extremely premature infants. MethodsTwenty extremely premature infants were held at or below the placenta while the umbilical cord was clamped and cut at approximately 2-3cm from the umbilicus within 30s after birth. The umbilical cord was then clamped near the placenta to obtain a length of approximately 30cm and cut. The residual blood volume in the segment of cord was drained and measured in milliliters. ResultsMean birthweight was 846 172g (range, 587-1180g). The average length of the clamped segment of umbilical cord was 29.8 +/- 1.5cm (range, 27-32cm). Total residual blood volume and residual blood volume per cm were 15.5 +/- 6.7mL (range, 6-25mL) and 0.5 +/- 0.2mL/cm (range, 0.2-0.8mL/cm), respectively. The residual cord blood volume per kilogram of infant weight per 30cm was 17.7 +/- 5.5mL/kg/30cm (range, 8.9-29.0mL/kg/30cm). ConclusionInfants could receive approximately 18mL/kg of whole blood by one-time milking of 30cm umbilical cord. With an average hematocrit of 40%, this volume is equivalent to approximately 13mL of packed red blood cells (hematocrit 55%).

Congenital chloride diarrhea (CCD) beginning in utero is a rare autosomal recessive inherited disorder characterized by impairment of Cl-/HCO3- exchange in an otherwise normal distal ileum and colon. Life-long secretory diarrhea is caused by mutations in solute carrier family 26, member 3, (SLC26A3), which disrupt epithelial Cl-/HCO3- transport in the ileum and colon. Although 55 mutations in SLC26A3 have been identified throughout the world, few Japanese cases have been confirmed on genetic analysis. We report the successful treatment of a Japanese neonate with CCD caused by SLC26A3 mutation.

The concept of the developmental origins of health and disease is based on studies by Barker et al. They proposed a hypothesis that undernutrition in utero permanently changes the body's structure, function, and metabolism in ways that lead to atherosclerosis and insulin resistance in later life. In addition, profound effects on the extent of body fatness and insulin sensitivity are demonstrated, if there is a "mismatch" between prenatal and postnatal environments. In previous studies, undernutrition in utero has been evaluated simply by birth weight itself or birth weight for gestational age, and the degree of mismatch has been estimated by postnatal rapid weight gain. Recently, we investigated subcutaneous fat accumulation in small-for-gestational-age infants and found that a rapid catch-up in skinfold thickness developed prior to the body weight catch-up. Furthermore, insulin-like growth factor-I and lipoprotein lipase mass concentrations also demonstrate rapid increase during the neonatal period with fat accumulation. Investigating the precise mechanisms of developmental origins of health and disease including mediating metabolic and hormonal factors may provide a new approach to prevent atherosclerosis and insulin resistance. Better management of undernutrition during gestation and neonatal growth during the early postnatal period is an important theme for future health.

BackgroundRisks and benefits of increasing placental transfusion in extremely preterm infants (extremely low birthweight [ELBW], &lt;1000g) are ill defined. We performed a meta-analysis to compare long- and short-term outcomes of ELBW infants in trials of enhanced placental transfusion regimens. Study Design and MethodsWe conducted a meta-analysis of randomized controlled trials (RCTs) of delayed umbilical cord clamping or umbilical cord milking in compliance with PRISMA and Cochrane Collaborative guidelines for systematic reviews. We searched multiple databases for medical literature up to December 2012. Inclusion criteria were preterm infants less than 30 weeks and less than 1000g birthweight, randomly assigned to enhanced placental transfusion (either delayed cord clamping or cord milking) versus immediate cord clamping. The primary outcome was standardized neurodevelopmental outcome at 18 to 24 months corrected age using a standardized scale. Several short-term outcomes were also evaluated as secondary variables. ResultsWe found 19 studies of which 10 studies could be included (n=199). Three reported neurodevelopmental outcomes, none of which showed significant rates of disability. Two reported these at 18 to 24 months (n=42) but used different scales preventing pooling. Short-term benefits of enhanced placental strategies included better blood pressure and hemoglobin on admission, along with reduced blood transfusions, a trend to reduced intraventricular hemorrhage, and episodes of late-onset sepsis. ConclusionsStrategies to enhance placental transfusion may improve short-term outcomes of ELBW infants. However, paucity of data on neurodevelopmental outcomes and safety concerns tempers enthusiasm for these interventions. Appropriately designed RCTs to assess short-term and long-term outcomes are needed in ELBW infants.

BackgroundHypoxic-ischemic encephalopathy (HIE) is one of the most critical pathologic conditions in neonatal medicine due to the potential for neurological deficits in later life. We investigated the incidence of term infants with moderate or severe HIE in Japan and identified prognostic risk factors for poor outcome in HIE. MethodsData on 227 infants diagnosed with moderate or severe HIE and born between January and December 2008 were collected via nationwide surveys from 263 responding hospitals. Using logistic regression, we examined the relationship between maternal, antepartum, intrapartum, and neonatal risk factors and clinical outcome at 18 months following birth. ResultsIn Japan, the incidence of moderate or severe HIE was 0.37 per 1000 term live births. Outborn births, low Apgar score at 5min, use of epinephrine, and low cord blood pH were intrapartum factors significantly associated with neurodevelopmental delay and death at 18 months. Serum lactate, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase (all, P &lt; 0.001) and creatine kinase (P = 0.002) were significantly higher in infants with poor outcome compared to those with favorable outcomes. Abnormal brain magnetic resonance imaging (MRI), an important prognostic factor, was significantly associated with poor outcome (odds ratio, 11.57; 95% confidence interval: 5.66-23.64; P &lt; 0.001). ConclusionsRisk factors predicting poor outcome in HIE include outborn birth, low Apgar score at 5min, use of epinephrine, laboratory abnormalities, and abnormal MRI findings.

Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14 female) born at &lt 37-week gestational age, including 10 small for gestational age (SGA) infants (&lt 10th percentile). IGF-1 levels and serum lipids were measured in cord blood, and high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1 ± 5.3 ng/ml), total cholesterol (TC) (55.0 ± 14.8), LDLC (21.6 ± 8.3) and HDLC (26.3 ± 11.3) levels, and higher VLDLTG levels (19.0 ± 12.7 mg/dl) than in appropriate for gestational age (AGA) infants (53.6 ± 25.6, 83.4 ± 18.9, 36.6 ± 11.1, 38.5 ± 11.6, 8.1 ± 7.0, respectively). In simple regression analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P &lt 0.001), TC (r = 0.636, P &lt 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels (r = 0.648, P &lt 0.001), and negatively with log TG (r = -0.484, P = 0.002) and log VLDL-TG (r = -0.393, P = 0.018). Multiple regression analyses demonstrated that IGF-1 was an independent predictor of TC, HDLC and TG levels after the gestational age and birth weight were taken into account. In preterm SGA infants, cord blood lipids profile altered with the concomitant decrease in IGF-1 level. © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013.

Gray matter develops rapidly during the third trimester of pregnancy, which is a critical period for lipid deposition. We measured brain volume in term and late-preterm infants to determine if it is related to disabilities in late-preterm infants. In addition, we measured serum lipid concentrations to investigate the relationship between brain volume and lipid nutrition. Magnetic resonance imaging scans were obtained in 16 late-preterm and 13 term infants. We measured cerebrum, gray matter, and white matter volumes. We performed serum cholesterol, triglyceride (TG), and lipoprotein analyses in cord blood by high-performance liquid chromatography using gel permeation columns to assess lipid nutritional levels. The gray matter volume and percent cerebrum volume of gray matter were significantly smaller in late-preterm infants (p &lt; 0.001). Head circumference and cerebrum and white matter volume did not differ between the two groups. Gray matter volume correlated positively with gestational age (r = 0.647, p &lt; 0.001), head circumference (r = 0.688, p &lt; 0.001), and high-density lipoprotein (HDL)-TG levels (r = 0.496, p = 0.006). Late-preterm infants had a normal head circumference and a lower gray matter volume than term infants. Gestational age and head circumference were significantly associated with gray matter volume. Only HDL-TG levels were significantly associated with gray matter volume. HDL-TG might contribute to the transport of fatty acids and gray matter development during the postnatal period. Thus, delayed gray matter development may partly contribute to neurodevelopmental disabilities in late-preterm infants. (C) 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Background/Objectives: Subcutaneous adipose tissue grows rapidly during the first months of life. Lipoprotein lipase (LPL) has a quantitatively important function in adipose tissue fat accumulation and insulin-like growth factor-I (IGF-I) is a determinant of neonatal growth. Recent studies showed that LPL mass in non-heparinized serum (LPLm) was an index of LPL-mediated lipolysis of plasma triacylglycerol (TG). The objective was to know the influence of serum LPL and IGF-I on neonatal subcutaneous fat growth, especially on catch-up growth in low birth weight infants. Subjects/Methods: We included 47 healthy neonates (30 males, 17 females), including 7 small for gestational age. We measured serum LPLm and IGF-I concentrations at birth and 1 month, and analyzed those associations with subcutaneous fat accumulation. Results: Serum LPLm and IGF-I concentrations increased markedly during the first month, and positively correlated with the sum of skinfold thicknesses both at birth (r = 0.573, P = 0.0001; r = 0.457, P = 0.0035) and at 1 month (r = 0.614, P&lt;0.0001; r = 0.787, P&lt;0.0001, respectively). In addition, serum LPLm concentrations correlated inversely to very low-density lipoprotein (VLDL)-TG levels (r = -0.692, P&lt;0.0001 at birth; r = -0.429, P = 0.0052 at 1 month). Moreover, the birth weight Z-score had an inverse association with the postnatal changes in individual serum LPLm concentrations (r = -0.639, P&lt;0.0001). Conclusions: Both serum LPLm and IGF-I concentrations were the determinants of subcutaneous fat accumulation during the fetal and neonatal periods. During this time, LPL-mediated lipolysis of VLDL-TG may be one of the major mechanisms of rapid growth in subcutaneous fat tissue. Moreover, LPL, as well as IGF-I, may contribute to catch-up growth in smaller neonates. European Journal of Clinical Nutrition (2010) 64, 447-453; doi:10.1038/ejcn.2010.25; published online 3 March 2010

Objective: To investigate the effects of umbilical cord milking on cardiopulmonary adaptation in very low birth weight infants. Patients and methods: This study was the secondary analysis of a randomised control study of the effect of umbilical cord milking in premature infants. Forty singleton infants born between 24 and 28 weeks&apos; gestation were randomly assigned to groups in which the umbilical cord was clamped either immediately after birth (control group, n = 20) or after umbilical cord milking (milked group, n = 20). Blood pressure, heart rate, urine output, fluid intake, and ventilatory index values in both groups were measured during the first 120 h after birth. Results: There were no significant differences in gestational age or birth weight between the two groups. The initial haemoglobin value was higher in the milked group (mean (SD) 16.5 (1.4) g/dl in the milked vs 14.1 (1.6) g/dl in the control; p&lt;0.01). During the first 12 h, blood pressure was significantly higher in the milked group. Urine output in the milked group was higher than that in the control group during the first 72 h. There were no significant differences in heart rate, water intake, or ventilatory index values between the groups. Conclusion: Umbilical cord milking may facilitate early stabilisation of both blood pressure and urine output in very low birth weight infants.

Human fetuses have markedly low levels of serum lipids and a unique lipoprotein profile with respect to quality, with low-density lipoprotein (LDL)-like particle as the dominant cholesterol carrier. However, little is known about triglyceride (TG) distribution. In addition, lipid metabolism is important in lung development, with indications that TG from very low-density lipoprotein (VLDL) is essential for surfactant synthesis. We investigated TG distribution in preterm neonate cord blood and the relationship of VLDL-TG levels with respiratory distress syndrome (RDS). The study included 103 appropriate-for-gestational-age neonates (61 males). We performed serum lipoprotein analyses in cord blood by high-performance liquid chromatography with gel permeation columns. Term neonates had low cord blood TG, an, concentrations distributed equally to the LDL and VLDL fractions. However, preterm neonates had even lower TG concentrations, with VLDL as the dominant carrier. The LDL-TG and high-density lipoprotein-TG concentrations in cord blood increased gradually with gestational age, but cord blood VLDL-TG concentrations increased dramatically from 32 to 34 weeks of gestational age. Neonates with RDS exhibited no RDS-specific lipoprotein profiled however, most were born before the timing of the dramatic VLDL-TG increase. Our results suggest that 34 weeks of gestation is a critical period for TG metabolism, indicating the need for evaluation of the lipid nutritional state in preterm neonates. (C) 2009 Elsevier Inc. All rights reserved.

The aim of the present study was to assess 3 year auditory and neurodevelopmental outcomes of persistent pulmonary hypertension of the newborn (PPHN) before and after introducing inhaled nitric oxide (i-NO) therapy, and to detect the clinical factors affecting poor outcome. A retrospective historical cohort study of 26 survivors with PPHN with oxygenation index (OI) &gt;= 25 (13 infants without i-NO therapy, control group; 13 with i-NO therapy, i-NO group) was performed. Auditory brainstem response (ABR) at 6 and 12 months and neurodevelopmental outcomes at 3 years of age were evaluated. ABR abnormalities at 6 months were observed in one infant in the i-NO group and six in the control group (P = 0.04). At 1 year, one infant in the i-NO group and two of six infants in the control group still had ABR abnormality. In the i-NO group, two children had abnormal neurodevelopmental outcomes, as compared with five children in the control group at 3 year follow up. Two children in the control group and no children in the i-NO group had hearing loss at 3 years of age. Hypocapnea (P = 0.04) and elevated creatine phosphokinase (P = 0.04) were found to be most predictive for neurodevelopmental abnormality. Avoidance of excessive hypocapnea via introduction of i-NO therapy might reduce both ABR and neurodevelopmental abnormalities.

Aim: To investigate whether end-tidal CO2 monitoring is useful for more rapid recognition of tracheal vs. esophageal intubation as compared to standard clinical evaluation in very low birth weight infants during neonatal resuscitation at birth. Patients and methods: Forty infants were prospectively identified. Tracheal tube placement was evaluated either using an end-tidal CO2 monitor by an investigator not involved in the resuscitation, or by evaluation of clinical parameters by a resuscitation team unaware of the end-tidal CO2 data. The time taken to detect accurate placement of the tube using capnometory vs. clinical determination of tracheal or esophageal tube placement was compared. Results: A total of 54 intubations was analyzed from 40 neonates. End-tidal CO2 monitoring correctly identified all 40 tracheal and all 11 esophageal intubations with 100% accuracy. On the other hand, clinical evaluation demonstrated discrepancies in three cases. The mean time in seconds for capnographic determination was significantly faster than clinical determination for both tracheal (7.5 +/- 1.3 vs. 17.0 +/- 3.4, P &lt; 0.01) and esophageal intubation (6.5 +/- 0.7 vs. 19.9 +/- 1.8, P &lt; 0.01). Conclusion: Exhaled CO2 detection is a sensitive and accurate technique to confirm tracheal tube placement in very low birth weight infants during neonatal resuscitation.

Background: The purpose of the present paper was to identify the predictive factors for survival for out-born infants born between 23 and 24 weeks of gestation. Methods: Ninety-two infants born between 23 and 24 weeks&apos; gestation who were admitted to a level III neonatal intensive care unit from 1987 to 2000, were retrospectively studied. Survival was defined as discharge from the neonatal intensive care unit. Logistic regression was done to determine which clinical factors were most predictive of survival. The independent variables that were entered into the models were determined by preliminary univariate analysis. Results: Ninety-two infants were enrolled in the present study, 49 of whom survived in the surfactant era. The four variables that were found to be most predictive for survival on logistic regression were systolic blood pressure at 6 h (odds ratio [OR], 1.3; 95% confidence interval [CI]: 1.11-1.44 1 mmHg), ventilatory index &lt; 0.047 (OR, 4.8; 95%CI: 1.07-21.65), initial hemoglobin value (OR, 1.6; 95%CI: 1.09-2.34/1 g/dL), and base excess at 6 h (OR, 2.1; 95%CI: 1.08-1.84/5 mEq/L). Conclusions: A total of 53.2% of infants delivered between 23 and 24 weeks of gestation survived at discharge after introduction of surfactant replacement therapy. Early cardiopulmonary adaptation and initial hemoglobin value are key factors for survival in infants born at 23-24 weeks of gestation.

Background: The purpose of the present paper was to identify the predictive factors for survival for out-born infants born between 23 and 24 weeks of gestation. Methods: Ninety-two infants born between 23 and 24 weeks&apos; gestation who were admitted to a level III neonatal intensive care unit from 1987 to 2000, were retrospectively studied. Survival was defined as discharge from the neonatal intensive care unit. Logistic regression was done to determine which clinical factors were most predictive of survival. The independent variables that were entered into the models were determined by preliminary univariate analysis. Results: Ninety-two infants were enrolled in the present study, 49 of whom survived in the surfactant era. The four variables that were found to be most predictive for survival on logistic regression were systolic blood pressure at 6 h (odds ratio [OR], 1.3; 95% confidence interval [CI]: 1.11-1.44 1 mmHg), ventilatory index &lt; 0.047 (OR, 4.8; 95%CI: 1.07-21.65), initial hemoglobin value (OR, 1.6; 95%CI: 1.09-2.34/1 g/dL), and base excess at 6 h (OR, 2.1; 95%CI: 1.08-1.84/5 mEq/L). Conclusions: A total of 53.2% of infants delivered between 23 and 24 weeks of gestation survived at discharge after introduction of surfactant replacement therapy. Early cardiopulmonary adaptation and initial hemoglobin value are key factors for survival in infants born at 23-24 weeks of gestation.