細野 茂春

Background: The aim of the present paper was to investigate the effect of initial hemoglobin level on red blood cell transfusion and neonatal adaptation in extremely low-birthweight (ELBW) infants. Methods: Subjects consisted of 54 ELBW infants admitted to level III neonatal intensive care unit between 1995 and 2000, and divided into two groups based on hemoglobin level at birth. Hi h hemoglobin was defined as hemoglobin 9 >= 15.0 g/dL. Results: There were no significant differences in gestational age and birthweight between the high hemoglobin group (n = 28) and low hemoglobin group (n = 26). The high hemoglobin group had decreased probability of requiring red blood cell transfusion (P < 0.05) and number of red blood cell transfusions (P < 0.05). Mortality rate in the low hemoglobin group was significantly higher compared with the high hemoglobin group (P = 0.03). In the high hemoglobin group, blood pressures during the first 24 h were significantly higher (P < 0.05) and the risk of intraventricular hemorrhage was significantly lower (P = 0.04) compared with the low hemoglobin group. The predictive variables, initial hemoglobin level (odds ratio 1.93 [decrease by I g/dL]) and intraventricular hemorrhage >= III (odds ratio 21.76 [positive]) were found to be most predictive for death on logistic regression. Conclusion: High hemoglobin level at birth is associated with a significantly reduced requirement for red blood cell transfusion and might contribute to stabilization of blood pressure, and thus reduce mortality and the risk of severe intraventricular hemorrhage.

Objective: To investigate natural change of low-density lipoprotein (LDL) profile during the neonatal period and the impact of gestational age and birth weight on those changes. Study Design: We measured lipid composition in LDL fraction, LDL particle size and apolipoprotein B (apoB) concentration at birth, 5 days of age and 1 month of age in 63 healthy neonates that had 37 to 41-week gestational age. Result: Low-density lipoprotein cholesterol and apoB concentrations increased from birth to 5 days of age, and the concentration persisted at 1 month in breast-fed and mixed-fed infants. However, in formula-fed infants, the concentration decreased at 1 month. At 5 days of age, neonates had larger and more triglyceride (TG)-rich LDL particles than at birth. At 1 month of age, LDL particles were smaller and more cholesterol rich than at 5 days of age. Single regression analyses showed that gestational age had influenced the LDL profile at birth and 5 days of age, while at 1 month milk determined the profile. Conclusion: The number of LDL particles increased rapidly during the first 5 days of life, and the composition of LDL particles is modulated by TG content throughout the neonatal period. Gestational age and milk, rather than birth weight, determine postnatal changes in LDL profile.

Background: Several subclasses of HDL are demonstrated to have different roles in atherosclerosis based on adult studies, but the significance of HDL heterogeneity in the fetus and neonate has not been clarified. It has been described that the cholesterol supply from apoE-rich HDL is essential for central nerve system neuron growth. Methods: Sixty-five healthy, term, appropriate for gestational age neonates (38 males and 27 females) were included in the study. Serum lipoprotein analyses were performed by HPLC with gel permeation columns, which classified HDL into 5 subgroups (i.e., very large, large, medium, small, and very small) on the basis of particle size. Apolipoprotein A-I, B, and E were also determined by turbidimetric immunoassay. Results: Cord blood has higher very large and very small HDL-cholesterol levels. Cord blood apolipoprotein E was not uniformly distributed in the HDL subclasses, with a strong association with very large HDL-cholesterol levels (males, r=0.548, p<0.001; females, r=0.631, p<0.01). However, the association disappeared by I month of age in males; in females, the association remained during the neonatal period. Conclusions: These results suggest that HDL may play the role of a dominant cholesterol carrier in the human fetus, and very large HDL-cholesterol have some contribution to the neurodevelopment in the fetus and neonates because of the close relationship with apolipoprotein E levels. (C) 2007 Elsevier B.V. All rights reserved.

Background: The purpose of the present study was to evaluate the usefulness of serum S100B as a clinical marker of intracranial lesions in newborns. Methods: The study involved 22 normal and 40 diseased newborns. Serum S100B level was measured on days 1 and 6 in normal newborns. Diseased newborns were classified into four groups: birth asphyxia with hypoxic-ischemic encephalopathy (HIE); birth asphyxia without HIE; intracranial hemorrhage (mainly subarachnoid); and brain malformation. In each group the serum S100B level was measured on days 1, 2 and 6. Development was also assessed to investigate the relation between serum S100B level and prognosis at 18 months after birth. Results: In normal newborns, serum S100B level was significantly higher in those with liquor to meconium stain than in those without. In diseased newborns, serum S100B level on day 1 was significantly higher in the HIE group than in all other groups (P < 0.05). There was no significant difference in serum S100B level between control and intracranial hemorrhage, or brain malformation. In newborns with birth asphyxia, serum S100B level was significantly higher in severe birth asphyxia than in mild or moderate birth asphyxia; two newborns with serum S100B level >= 10 mu g/L on days 1 and 2 developed cerebral palsy, others with no increase of S100B were all developing normally. Conclusions: Serum S100B level is a useful marker of acute perinatal brain damage, and is particularly valuable for fetal distress. In newborns with birth asphyxia, serum S100B levels serve as a biochemical marker of HIE.

Objective: To investigate the effects of umbilical cord milking on the need for red blood cell (RBC) transfusion and morbidity in very preterm infants. Patients and Methods: 40 singleton infants born between 24 and 28 weeks' gestation were randomly assigned to receive umbilical cord clamped either immediately (control group, n = 20) or after umbilical cord milking (milked group, n = 20). Primary outcome measures were the probability of not needing transfusion, determined by Kaplan-Meier analysis, and the total number of RBC transfusions. Secondary outcome variables were haemoglobin value and blood pressure at admission. Results: There were no significant differences in gestational age and birth weight between the two groups. The milked group was more likely not to have needed red cell transfusion (p = 0.02) and had a decreased number (mean (SD)) of RBC transfusions (milked group 1.7 (3.0) vs controls 4.0 (4.2); p = 0.02). The initial mean (SD) haemoglobin value was higher in the milked group (165 (14) g/l) than in the controls (141 (16) g/l); p<0.01). Mean (SD) blood pressure at admission was significantly higher in the milked group (34 (9) mm Hg) than in the controls 28 (8) mm Hg; p = 0.03). There was no significant difference in mortality between the groups. The milked group had a shorter duration of ventilation or supplemental oxygen than the control group. Conclusion: Milking the umbilical cord is a safe procedure, reducing the need for RBC transfusions, and the need for circulatory and respiratory support in very preterm infants.

In term neonates, the adiponectin concentration is higher than it is in adults. To determine the relationship between adiponectin and early neonatal growth in a cohort study. Fifty-two neonates at term were studied. Serum adiponectin concentrations, body sizes, and skinfold thicknesses were measured at birth and at I mo of age. At birth, cord blood adiponectin concentration correlated positively with birth weight (r = 0.484, p = 0.0003), birth length (r = 0.524, p < 0.0001), and sum of the four skinfold thickness measurements (r = 0.378, p = 0.0057). In a stepwise regression, birth length was the only determinant of cord blood adiponectin concentration. However, at I mo of age, serum adiponectin concentration correlated with no anthropometric parameter at all. Between birth and I mo of age, the individual change in adiponectin concentration correlated negatively with birth weight. Thus, serum adiponectin concentrations in cord blood have a strong relationship to birth length rather than to body fatness, and this relationship is not demonstrated in 1-mo-old infants. These results imply that hormonal, substrate, or other mechanisms that regulate the relationship between body composition and growth in fetal life are different from those governing these relationships in early postnatal life.

Background: The purpose of the present paper was to detect the clinical factors most predictive of red blood cell (RBC) transfusion in extremely low-birthweight (ELBW) infants in the recombinant human erythropoietin era. Methods: Between 1995 and 2000, 66 ELBW infants were admitted to a level III neonatal intensive care unit. Fifty-four of 66 infants were eligible for enrollment in the present study. Infants were treated with erythropoietin 200 IU/kg per dose s.c. twice a week with 4-6 mg/kg per day iron supplement. Results: The mean gestational age and birthweight were 26.5 +/- 2.1 weeks and 776 +/- 134 g, respectively. Ten of 54 ELBW infants (18.5%) died during the first 21 days. Eight of 10 dead infants (80.0%) and 27 of 44 surviving infants (61.4%) received one or more RBC transfusions. The overall requirement for RBC transfusions in the surviving infants was 3.0 +/- 3.2 per infant/hospital course (range: 0-9) . There were significant differences in gestational weeks, birthweight, initial hemoglobin value, 5 min Apgar score, phlebotomy loss, phlebotomy loss/birthweight, duration of mechanical ventilation, duration of oxygen supplement, and incidence of both intraventricular hemorrhage and chronic lung disease between the transfused and non-transfused group. The predictive variables, initial hemoglobin level (odds ratio [OR] 2.61; 1 g/dL), birthweight (OR 3.00; 100 g), and gestational week (OR 1.89; 1 week), were found to be most predictive for transfusion on logistic regression analysis. Conclusions: ELBW infants are still the population at greatest risk for repeated blood transfusions after introduction of erythropoietin treatment. If labor develops, it is often impossible to extend the pregnancy period, therefore efforts should be made to increase hemoglobin level at birth.

Background: The purpose of the present paper was to evaluate the mortality and morbidity of infants born at 22-24 weeks gestation. Methods: A total of 78 infants born at 22-24 weeks gestation, who were admitted between January 1991 through December 2000, were retrospectively studied. Results: Seventy-one of 78 infants were enrolled in the present study. One year survival rates at 22, 23 and 24 weeks were 40.0% (2/5), 61.1% (11/18), and 50.0% (24/48), respectively. Failure of response to surfactant and air leak were associated with death in infants born at 23 weeks gestation. Low Apgar score, intraventricular hemorrhage (≥III), and sepsis were correlated with death in infants born at 24 weeks gestation. The handicap rates of survivors born at 22, 23, and 24 weeks gestation were 100, 36.4, and 26.1%, respectively. Conclusions: The present study indicates that infants born at 22 weeks gestation, in whom pulmonary structure is established, that is, a viable lung that can exchange gas with exogenous surfactant, have a chance to survive, but neurological outcome is still poor. Every possible effort should be made to extend gestation beyond 22 weeks.

Aim: To determine whether inhaled nitric oxide might reduce the need for excessive respiratory alkalosis to maintain systemic oxygenation in infants with persistent pulmonary hypertension of the newborn (PPHN). Materials and methods: A retrospective historical cohort study of 34 infants with PPHN with oxygenation index (OI) of 25 or more, including 19 infants without inhaled nitric oxide (i-NO) therapy (control group) and 15 infants with inhaled nitric oxide therapy (i-NO group) was performed. The initial dose of 10 ppm of i-NO was administered and no responders received the maximum dose of 25 ppm. We evaluated the mortality rate and the change of OI index and PaCO2 during the first 6 days. Results: There were no significant differences in characteristics between groups. Two of 15 in the i-NO group and 6 of 19 infants in the control group died during the first 48 h. Baseline OI, PaCO2 and arterial pH were similar in the two groups. OI in the i-NO group was significantly higher than in the control group between 12 and 96 h. PaCO2 in the i-NO group was higher than in the control group between 24 and 144 h. Conclusion: i-NO therapy for PPHN might improve systemic oxygenation without excessive hypocapnia. However there was no reduction in duration of ventilation support or oxygen supply.

We describe a case of cord blood harvest for autologous transfusion in a neonate weighing 3,992 g with a giant sacrococcygeal teratoma. The umbilical vein was pierced with an 18-gauge needle, and placental blood was withdrawn into two 50-ml syringes filled with 4 ml of citratephosphatedextrose solution. Resection of the sacrococcygeal teratoma was performed on day one. During the operation the infant lost 46 ml of whole blood, more than 15% of the estimated total blood volume, and thus underwent autologous transfusion with 27.8 ml of packed red cells obtained from autologous cord blood. Consequently, she could avoid homologous blood transfusion during the hospital stay. This case highlights the safety of this procedure, with no evidence of consumption coagulopathy, hemolysis or bacterial infection.

To investigate the effects of milking of umbilical cord on red blood cell transfusion in extremely low birth weight (ELBW) infants. Forty infants born at 24 to 29 weeks' gestation were prospectively randomized to have the umbilical clamped either immediately or after milking of umbilical cord. Total of 31(15; milking group, 16; control group) ELBW infants were eligible in this study. The mean hemoglobin of 16.8+/-1.3g/dl at admission in the milking was higher compared with 13.8+/-1.4g/dl in the control group (p<0.01). Mortality rate was comparable in the both groups (p=0.53). Fifteen (87.5%) infants in the control group received red blood cell transfusion compared with 7 (46.7%) in the milking group (p=0.02). The milking of cord might be easy to perform in safety, and reduce the requirement for red blood cell transfusion.

Background : Several authors reported that there was a close relationship between unbound bilirubin concentrations and abnormal results of auditory brainstem responses. Full-term infants with high-unbound bilirubin concentrations who were treated with human albumin were followed to evaluate their hearing abilities by using auditory brainstem responses. Methods : Fifty-eight infants (gestational age, 39.4 +/- 1.4 weeks; birthweight, 3245 +/- 435 g) with high unbound bilirubin concentrations (greater than or equal to0.9 mug/dL) were treated with intensive phototherapy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given i.v. human albumin administration (1 g/kg bodyweight) during the first 2 h of phototherapy. The follow-up study of auditory brainstem responses was carried out at 6 and 12 months of age. Development quotient tests were carried out at 18 months of age. Results : Abnormalities of auditory brainstem response were detected in three infants in the albumin-treated group and six infants in the control group at 6 months. Two infants in the albumin-treated group and four infants in the control group had improved at 12 months. The results of the follow-up study at 18 months of age in the both groups were normal with development quotient >85. No patients with hearing disability and cerebral palsy were clinically detected at the age of 2 years. Conclusion : The results suggest that albumin priming might be effective for decreasing the rate of auditory brainstem response abnormalities at 6 months.

Purpose: To evaluate the hypothesis that bilirubin has a protective effect against the development of severe retinopathy of prematurity (ROP). Methods: An assessment of 76 infants born at 24 and 25 weeks' gestation and admitted to the level III neonatal intensive care unit at Saitama Children's Medical Center was made. Indirect ophthalmoscopy fundus examinations were performed on all infants to identify the degree and progression to threshold ROP. We analyzed the daily bilirubin levels and grouped the patients according to the severity of ROP based on the infant's worst ROP examination. The first group was comprised of infants with less than stage 3 ROP and infants with stage 3 ROP. The second group was infants with less than prethreshold ROP or prethreshold ROP, and infants with threshold ROP. Next, we divided the infants into 3 groups: less than prethreshold ROP, prethreshold ROP, and threshold ROP. The daily changes in serum bilirubin concentrations during the first 14 days of life were determined for each infant. Three groups (less than prethreshold ROP, prethreshold ROP, and threshold ROP) were comparable as to their basic data, clinical characteristics, and treatments. Results: ROP was found in 76 infants. There were no statistical differences in the clinical characteristics and treatments, excluding the duration of phototherapy, among the 3 groups. During the first 14 days of age, there were no significant differences in the daily mean bilirubin concentrations according to the groups separated by severity of ROP. Conclusion: These results indicate that there is no distinct protective effect of bilirubin on the development of severe ROP.

A fatality from a tracheoesophageal fistula (TEF) in two extremely low birth weight infants is presented. The sudden onset of intractable respiratory failure accompanied by the absence of chest movement and breathing sounds was observed. The typical clinical symptoms were concealed because the infants required mechanical ventilation and nasogastric feedings. When ventilated infants with these symptoms are suspected of the diagnosis of TEF, prompt reintubation under the guidance of a flexible bronchoscopy may be life saving because the endotracheal tube passes through the fistulas into the esophagus with ease.

Background: To evaluate the effects of an increase in glucose infusion rate of 2 mg/kg per min from the basal infusion rate on the prevention of hypoglycemia in very low-birthweight (VLBW) infants, following indomethacin therapy for patent ductus arteriosus (PDA). Methods: Forty VLBW infants with PDA were given indomethacin 0.2 mg/kg intravenously up to three doses. In 15 of the 40 infants (supplemented group: between April 1995 and March 1996) the glucose infusion rate was increased in 2 mg/kg per min increments from the basal rate just before the initial indomethacin administration, compared with 25 historical control infants who received a fixed glucose infusion rate during the first 12 h after the initial dose. We evaluated the changes in blood glucose levels and glucose infusion rates in both groups. Results: In the control group 11 of 25 (44%) infants had a blood glucose value below 40 mg/dL between 12 and 60 h (mean 32.7 h). In contrast only two out of 15 infants in the supplemented group reached the glucose level below 40 mg/dL between 72 and 96 h but both two were light-for-dates infants (defined as birthweight below the 10th percentile for gestational age on the standard intrauterine growth curve). Blood glucose values in the supplemented group were significantly higher than those in the control group between 12 and 96 h. However, glucose infusion rates were similar before and between 72 and 96 h. Conclusions: This retrospective study shows that an increase in glucose infusion rate of 2 mg/kg per min, in addition to the pre-existing stable maintenance glucose intake, might prevent against the occurrence of unexpected hypoglycemia in VLBW infants following indomethacin therapy.

Background: The purpose of the present study was to evaluate the effect of intravenous albumin administration on the serum total and unbound bilirubin values in term non-hemolytic hyperbilirubinemic neonates during intensive phototherapy. Methods: Fifty-eight infants (gestational age 39.4+/-1.4 weeks; birth weight 3245+/-435 g) were given phototherapy with similar light energy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given human albumin at 1 g/kg bodyweight, i.v., during the first 2 h of phototherapy. Results: When comparing changes in total and unbound bilirubin values 0, 2, 6 and 24 h after entering the study between the albumin-treated group and the control group, there was a significant reduction in the serum unbound bilirubin values at the end of albumin treatment and at 6 and 24 h. However, there was no significant reduction in total serum bilirubin values during the study period. In the albumin-treated group, the mean serum unbound bilirubin reduction from the baseline level at the end of albumin treatment and at 6 and 24 h was 0.40+/-0.19, 0.41+/-0.20 and 0.43+/-0.20 mug/dL, respectively. Conclusions: The results suggest that albumin priming may be effective for an immediate reduction in serum unbound bilirubin values, the fraction that is potentially neurotoxic.

Background: To determine the effects of vibration exposure caused by high-frequency oscillatory ventilation (HFOV) on the auditory organ systems in low-birth weight (LBW) infants. Methods: Between 1989 and 1990, 30 LBW infants who received assisted ventilation with HFOV (n=14) or conventional mechanical ventilation (CMV; n=16) in the level III neonatal intensive care unit at Tokyo Metropolitan Ohtsuka Hospital were enrolled in this study. The effects of vibration exposure on the auditory system structures were investigated with auditory brainstem responses (ABR) at 37-41 weeks of post-conceptional age and at 6, 12, 18 and 24 months of age until they passed and follow-up studies were performed at least until 5 years of age. Results: All infants enrolled in the study survived at discharge and one (7.1%) infant in the HFOV group and two (12.5%) in the CMV group failed the initial ABR test, but there were no significant differences between the two groups. Auditory brainstem response abnormalities were still observed in one infant in the HFOV group at 6 months of age, but this child died at 9 months of age because of meningitis. In contrast, in the CMV group, one patient passed the ABR test at 6 months of age, but another remained abnormal at 5 years of age. One of three infants with ABR abnormalities at 6 months of age had neurologic sequelae at 5 years of age and one of 28 infants who passed the initial ABR test was detected with cerebral palsy. No patients with hearing loss were clinically detected at 5 years of age. Conclusions: The results of the serial ABR examinations and the 5 year follow-up studies suggest that vibration exposure caused by HFOV may not increase the adverse effects on the auditory system in LBW infants.

Purpose: To evaluate the effects of indomethacin on blood glucose Values in premature infants with patent ductus arteriosus (PDA). Methods: Twenty-five very low birthweight infants with PDA were given 0.2 mg/kg, i.v., indomethacin for up to three doses. We examined the relationship between blood glucose values and glucose infusion rate before and after indomethacin therapy. Results: There was a significant reduction in blood glucose values between 12 and 96 h following i.v. indomethacin therapy. Eleven of 25 infants (44%) had blood glucose values below 40 mg/dL between 12 and 60 h (mean 32.7 h) after the initial dose. Although the glucose infusion rate during the first 12 h was constant (3.56 +/- 0.98 mg/kg per min), the blood glucose values decreased from 96 +/- 32 mg/dL at the starting point to 75 +/- 29 mg/dL at 12 h (P < 0.05). The maximum blood glucose reduction was 51.6 +/- 34.7 mg/dL and the maximum blood glucose reduction rate was 50.4 +/- 20.2%. Conclusions: The results suggest that blood glucose values should be measured at least every 6 h for 72 h until they stabilize in order to prevent unexpected hypoglycemia.

We describe the case of a patient with a neonatal giant cutaneous hemangioma with high-output cardiac failure and Kasabach-Merritt syndrome and successfully treated with transcutaneous arterial embolization aimed at controlling severe congestive heart failure and consumption coagulopathy. A patient was admitted to the neonatal care unit on the first day of age because of a large hemangioma on his right lateral chest wall and respiratory distress, associated with cardiac failure resulting from arteriovenous shunting. On the secund day of age the platelet count decreased to 5.7 x 10(4)/mu l and fibrinogen level was 85 mg/dl. The values of prothrombin time and activated partial thromboplastin time were prolonged. Intravenous predonisone therapy was started immediately, but bleeding tendency was getting worse and the evidence of congestive heart failure persisted. On the third day the patient then underwent embolization of feeding arteries with microcoils. The cardiac failure and thrombocytopenic coagulopathy had improved significantly without complications. We conclude that transcutaneous arterial embolization is an effective and safe treatment in this neonate and should be considered for the treatment of control high-output cardiac failure and coagulopathy in infants with hemangioma and Kasabach-Merritt syndrome.

Background: The His Majesty's Government/Japan International Cooperation Agency Primary Health Care Project began in April 1993 in collaboration with the Saitama Prefectural Government, for the purpose of improving the health status of the people in model districts of the Kingdom of Nepal. Growth monitoring is one of the basic methods that defines the health and nutritional status of children. Methods: Anthropometric indices were measured in 759 children in the Bhaktapur district. We used the World Health Organization prototype growth chart and national,growth standard for Japanese children (1990) to analyze the growth data. Results: We found that the average bodyweight growth curve of children up to 4 months of age followed the 50th percentile reference curve. For children of 5-12 months of age, there was a delay in bodyweight gain and the growth curve reached the 3rd percentile curve. For children more than 1 year old, the growth curve moved below the third percentile curve. Catch-up growth did not occur before the children reached 5 years of age. The main causes of catch-up growth being hampered were chronic undernutrition and inadequate nutritional balance. Conclusions: As this was the first opportunity to evaluate infant growth in this district, the first important consequence of the results was to analyze the causes of growth faltering and failure-to-thrive in Nepalese children. Even more important, was the need to give appropriate counseling on improving feeding and other health-related practices, and the most important consequence of all was to instruct Nepalese health workers that utilizing the growth charts is an integral part of health care.

To establish mineral and trace element requirements for very low birth it is important to prevent bone mineral disorder. Those infants fed mother's milk only are thought to be at higher risk of this disorder. Both calcium and phosphorus supplementation were thought to be needed to prevent it. Copper and zinc are important as cofactors of major enzymes involved in the synthesis of collagen. These trace elements especially zinc may not be enough for very low birth weight infants fed mother's milk. At present however the realtionship between these trace elements and minerals, and bone metabolic disease in preterm infants is not completely clear.