Incidence and predicting factors of hypozincemia in very-low-birth-weight infants at near-term postmenstrual age.

We prospectively investigated serum zinc (Zn) concentrations and clinical factors in 118 very-low-birth-weight infants with a gestational age of 29.5 +/- (SD) 2.5 weeks and a birth weight of 1,194 +/- 254 g at near-term postmenstrual age. The 25th percentile of the serum Zn concentration was 7.0 micromol/l. The infants whose serum Zn concentrations were less than 7.0 micromol/l (defined as hypozincemia) did not have apparent symptoms of Zn deficiency. Multivariate logistic regression analyses demonstrated that hypozincemia was associated with factors such as weight gain (1-g/kg/day increase of weight; OR 1.1762, 95% CI 1.0414-1.3286) and serum albumin concentration (1-g/dl increase of serum albumin; OR 0.0816, 95% CI 0.0152-0.4372). The types of milk feeding did not affect the serum Zn concentrations in the study subjects. This study suggests that hypozincemia in very-low-birth-weight infants at near-term postmenstrual age is associated with greater weight gain and lower serum albumin concentration. Nutritional supply of Zn by human milk fortifier and preterm formula does not appear to meet the demands of rapidly growing very-low-birth-weight infants.

End-tidal carbon monoxide is predictive for neonatal non-hemolytic hyperbilirubinemia.

BACKGROUND: The aim of the present study was to evaluate the value of an end-tidal carbon monoxide corrected for inhaled carbon monoxide concentration (ETCOc) at the early neonatal period. The value would be useful for predicting subsequent hyperbilirubinemia in non-hemolytic full-term infants. METHODS: The ETCOc levels were measured every 6 h during the first 72 h of life in healthy, full-term, non-hemolytic, newborn Japanese infants using a breath carbon monoxide analyzer. The ETCOc levels in hyperbilirubinemic infants were compared with those in non-hyperbilirubinemic infants. Hyperbilirubinemia was defined as the level of the peak total serum bilirubin concentration (TBC) greater than or equal to 257 micromol/L (15.0 mg/dL). The ETCOc measurement for predicting subsequent hyperbilirubinemia was evaluated with a receiver-operating characteristic (ROC) curve. RESULTS: Fifty-one infants were enrolled in the study. Seven of the 51 infants developed hyperbilirubinemia. The ETCOc levels in non-hyperbilirubinemic infants were decreased in the first 72 h after birth. However, those in the hyperbilirubinemic infants were not decreased significantly, and were higher than those in non-hyperbilirubinemic infants at 42, 48, 54 and 66 h of age. The ETCOc level at 42 h of age was the most predictive of subsequent hyperbilirubinemia by ROC analysis. At the cut-off level of 1.8 microL/L (p.p.m.), the sensitivity, the specificity, the positive predictive value and negative predictive value were 86, 80, 40 and 97%, respectively. CONCLUSION: Increased ETCOc level in the early neonatal period is associated with subsequent hyperbilirubinemia, even in infants without hemolytic disease. The ETCOc measurement may be useful as a screening test for predicting hyperbilirubinemia without hemolytic diseases.

Effect of dexamethasone therapy on pulmonary function in chronic lung disease: a comparison of disease types.

BACKGROUND: In the present study, we investigated the effect of dexamethasone (DEX) therapy on extubation and pulmonary function in patients with chronic lung disease (CLD) who required long-term mechanical ventilation. In addition, we compared the effects of DEX therapy among CLD types. METHODS: Twenty-two CLD patients who were ventilator dependent for 28 days or longer received DEX therapy for the purposes of extubation. A tapering dose of DEX, starting from 0.5 mg/kg per day, was administered for 7 days. Pulmonary function was measured at initiation of administration and 4 days after initiation. We evaluated static respiratory system compliance (Crs) and static respiratory system resistance (Rrs) adjusted by bodyweight. Chronic lung disease types were categorized according to the classification of the Ministry of Health and Welfare Research Project. We compared the effect of DEX therapy among CLD types. RESULTS: Dexamethasone therapy was started at a mean (+/-SD) 45 =/- 11 days after birth and 32.1 +/- 1.3 weeks of postconceptional age in infants with a mean bodyweight of 939 +/- 153 g. After DEX therapy, extubation was successful in all 22 patients. Following DEX administration, Crs was significantly increased from 0.69 +/- 0.13 to 1.17 +/- 0.21 mL/cm H2O per kg. In contrast, Rrs did not show any clear changes. Comparing CLD types, no difference was observed for Crs and Rrs in each disease type. CONCLUSIONS: Dexamethasone was administered to CLD patients requiring long-term mechanical ventilation for the purposes of extubation and extubation was successful in all patients. It was found that Crs was increased in all patients following DEX, regardless of CLD type. The increase in Crs following DEX administration may have been related to successful extubation.

A prospective clinical study on inhaled nitric oxide therapy for neonates in Japan.

BACKGROUND: This is the first report about a prospective clinical investigation to study the efficacy and safety of nitric oxide (NO) inhalation in infants with persistent pulmonary hypertension of the newborn (PPHN) in Japan. METHODS: Patients in the present study had to meet the following entry criteria: (i) they had to be younger than 7 days of age; (ii) they had to have evidence of PPHN as defined by echocardiograph; (iii) they had to have severe systemic hypoxemia under mechanical ventilation at 100% oxygen supplementation; and (iv) they had to have a failure to respond to conventional therapies. Patients were excluded from this trial if they had any of the following: hypoplastic lung, structural cardiac lesions or severe multiple anomalies. RESULTS: Nitric oxide inhalation therapy was performed in 68 infants who had severe PPHN at 18 hospitals between May 1995 and May 1997. At birth, 21 of 68 infants (31%) weighed less than 1,500 g and 39 infants weighed more than 2,500 g. The diagnoses associated with PPHN were as follows: 27 infants had meconium aspiration syndrome, 15 infants had dry lung syndrome, nine infants had congenital diaphragmatic hernia, six infants had respiratory distress syndrome, three infants had pneumonia and eight infants had other diagnoses. The mean oxygenation index (OI) before NO inhalation therapy in 68 infants was 43.2; 55 infants (81%) had good responses. CONCLUSIONS: These results may be valuable for further randomized controlled and double-blind trials in Japan to evaluate whether NO inhalation therapy is more effective than conventional therapy in infants with severe PPHN.

[Incidence of cerebral palsy in Himeji City 1983-1992].

We investigated the incidence of cerebral palsy (CP) in Himeji City with a total population of about 470,000. In 1983-87 the total number of CP patients and the incidence of CP per 1,000 live births were 40 and 1.4, respectively. In 1988-92, the figures were 51 and 2.0. Periventricular leukomalacia was indicated in MRI in 11 out of 40 cases (27.5%) in 1983-87, and in 25 out of 51 (49.0%) in 1988-92. These results suggest that the increase in the incidence of CP mainly depends on changes of medical care for neonates.

Neonatal renal artery blood flow velocities using color Doppler ultrasonography.

BACKGROUND: It is essential to evaluate the renal function for the management of high risk neonates. Color Doppler ultrasound technique can provide a useful information to evaluate the neonatal renal artery blood flow velocities. This study was performed to obtain the normative data of renal blood flow velocities in preterm and fullterm neonates and to compare the renal blood flow velocities with the aortic blood flow velocities. The normal volumetric state of fluid balance and renal function are essential in the management of the sick neonates. METHODS: The renal peak systolic blood flow velocity (renal PSFV), the renal mean blood flow velocity (renal MFV), the renal end diastolic blood flow velocity (renal EDFV) and the renal resistance index (renal RI) and also the cardiac output, the aortic peak systolic blood flow velocity (aortic PSFV) and the aortic mean blood flow velocity (aortic MFV) were serially recorded from one to 7 days after birth in 16 preterm and one to 5 days in 23 normal fullterm neonates. RESULTS: The renal PSFV was significantly increased with the postnatal age, and the renal MFV was significantly increased between three and five days of age in the preterm neonates. In the fullterm neonates there was no significant change of the renal PSFV between one and five days of age, but the renal MFV was significantly increased between three and five days of age. There were no statistically significant differences of the renal PSFV, the renal MFV, the renal EDFV and the renal RI between the preterm and the fullterm neonates in the first five days after birth. The cardiac output in the preterm neonates was higher than that in the fullterm neonates: on day 3; 313 +/- 59 vs. 254 +/- 40 ml/kg/min. (p < 0.001) and on day 5; 357 +/- 95 vs. 280 +/- 35 ml/kg/min. (p < 0.01). The renal blood flow velocities were not significantly correlated with the aortic blood flow velocities in the normal fullterm neonates, whereas, in the preterm neonates the renal PSFV correlated with the cardiac output (r = 0.35, p < 0.01), the aortic PSFV (r = 0.45, p < 0.001) and the aortic MFV (r = 0.39, p < 0.01), and the renal MFV also correlated with the aortic PSFV (r = 0.30, p < 0.05) and the aortic MFV (r = 0.32, p < 0.05). CONCLUSIONS: The increased renal flow velocities with the postnatal age in the preterm infants might depend on the increased cardiac output.

[The volume of white matter in cerebral palsy with MRI findings of periventricular leukomalacia].

The volume of the white matter in 5 cases of cerebral palsy (CP) of term delivery without hypoxic episodes with MRI findings of periventricular leukomalacia (PVL), was compared with that of 12 CP cases in preterm delivery manifesting typical MRI findings of PVL. It was significantly decreased in the latter. The volume for the full-term CP cases was the same as that for children born at term and developing normally. These findings suggest that the grade of perinatal brain damage is different between the full-term and pre-term CP cases, and that the intrauterine timing of fetal circulatory disturbance is different.

[Cognitive function and MRI findings in very low birth weight infants].

Twenty-two very low birth weight infants at preschool ages of 5-6 years were studied to clarify the correlation between cognitive function and MRI findings. Cognitive function was evaluated by the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Frostig developmental test of visual perception. Ventricular enlargement, assessed by the bioccipital index (B. I.) measured on MRI, was correlated to cognitive disorders. Children with periventricular high intensity areas (T2-weighted images) extending from the posterior periventricular region to the parietal lobe tend to highly suffer from cerebral palsy and visuo-perceptual impairment. These results indicate that the disorders of cognitive function in very low birth weight infants were caused by a damage of association fibers in periventricular areas which was detectable by MRI.

Acrania: report of the first surviving case.

The first known surviving case of acrania is presented. The patient was the first child of a 29-year-old Japanese woman. Fetal ventriculomegaly was documented in the 35th gestational week. Prenatal sonography and magnetic resonance imaging suggested hydrocephalus with a wide encephalomeningocele. The baby was born at 38 weeks of gestational age by vaginal delivery. The patient had no calvarium, but did have a complete skull base with a partial defect in the occipital scalp and an underlying dural defect. Subsequently, the patient underwent repair of the scalp defect. At 3 months of age, after hydrocephalus developed, a subduro-peritoneal shunt was placed because of cosmetic and nursing problems. His developmental quotient was 10 at 3 years.

Difficulties of families with handicapped children after the Hanshin-Awaji earthquake.

In order to clarify the difficulties which handicapped people experienced in the Hanshin-Awaji earthquake disaster, 678 families with handicapped children were studied 1.5 months after the earthquake. All the students who were enrolled in this study were going to some type of school or training classes for handicapped children in January 1995. The study was completed between 1 and 10 March. The questionnaires which were designed for this study consisted of three parts: the difficulties which the families were faced with, their requirements for social and medical services and the symptoms and reactions of their children after the earthquake. A total of 466 answers were obtained from their parents. The kinds of difficulties differed between the families of mentally retarded children and those of the physically handicapped. While many parents with physically handicapped children desired better medical information or materials, many parents with mentally retarded children wanted better care services for their children. Physical and psychological effects of the earthquake were only temporary in most cases. However, some of the handicapped children were still suffering from such reactions as of 10 March. From the results of our study it became evident that a systematic relief program for these handicapped people should be established. The relief program should include the distribution of information regarding medical and social services. Psychological reactions such as panic, excitement and suppression of mental activity were still observed in some handicapped children on 10 March. Further observation will therefore be necessary.

Utility of iodine-123-BMIPP in the diagnosis and follow-up of vasospastic angina.

UNLABELLED: Myocardial damage caused by vasospastic angina (VSA) may be detected by [123I]BMIPP, a beta-methyl-branched fatty acid. We investigated whether BMIPP could be used in the diagnosis and follow-up of patients with VSA. METHODS: Thirty-two patients with VSA were studied with resting BMIPP-SPECT in comparison to stress perfusion imaging with either 201Tl or 99mTc-MIBI. During coronary arteriography, spasm was induced by provocative testing with acetylcholine or ergonovine, and only total or subtotal occlusion was considered positive. Decreased BMIPP uptake was semiquantitatively evaluated segmentally aided by polar map display. RESULTS: Reduced BMIPP uptake was observed in 25 of 32 patients (78%), with complete or partial agreement between the BMIPP abnormality and coronary territory seen in 23 patients (72%). In contrast, a perfusion abnormality was seen in only 10 patients (31%). In the repeat BMIPP study (n = 23) during the follow-up period (average 206 days), 11 of 14 patients who showed BMIPP improvement also had improved angina attacks. Conversely, two of nine patients with nonimproved BMIPP showed improved symptoms (p < 0.05). CONCLUSION: BMIPP can detect myocardial injury associated with VSA and may be useful in monitoring response to treatment.

Acquired cytomegalovirus infection and blood transfusion in preterm infants.

The urinary excretion of cytomegalovirus (CMV) DNA, amplified by polymerase chain reaction using two pairs of primers for late antigen (LA) and major immediate-early antigen (MIE), and serum CMV IgM were examined in 85 pre-term infants (birth-weight less than 2000 g) on admission and monthly until 6 months after birth. Of these 85 infants, 27 had blood exchange transfusions (BET) and 28 had bolus blood transfusions two to nine times. Fifteen of 27 infants underwent BET with blood that had been filtered through Pall RC100 leukocyte removal filter; the other 12 with unfiltered blood. Neither urinary CMV DNA nor serum CMV-specific IgM was detected at birth in any of the 85 pre-term infants; during the first 6 months after birth urinary CMV DNA, for both MIE and LA, appeared in 22 of the 85 infants (25.9%) and CMV IgM was positive in 14 of the 85 (16.5%). Nine of the 12 (75%) infants who received BET of unfiltered blood showed a significantly higher prevalence of urinary CMV DNA compared to the infants in the other three groups (i.e., those who received no blood transfusion, those who had bolus blood transfusions, or those who received BET of filtered blood; P < 0.01 in each instance). In a logistic regression model, CMV DNA urinary excretion was significantly associated with the mode of blood transfusion (unfiltered BET), and the Odds ratio was 38.9 (95% confidence interval, 9.4-160). There was no significant association with other independent variables such as gender, mother's seropositivity, gestational age, birth-weight or delivery mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Preventive effects of dexamethasone on hypoxic-ischemic brain damage in the neonatal rat.

To clarify the preventive effects of glucocorticoid on perinatal hypoxic-ischemic (HI) brain damage, an experiment was carried out on 4-day-old rats pretreated for 4 consecutive days with 3 different regimens; namely, a low dose dexamethasone (Dex) (0.1 mg/kg/day), a high dose Dex (0.5mg/kg/day), and a saline administration. On the 7th postnatal day, after ligation of the left common carotid artery, the rats were exposed to 8% oxygen and decapitated on the 10th, 14th, 21st and 28th postnatal days. Ligated side brain damage was observed in 75, 7 and 3% of the rats in the saline, low and high dose Dex groups, respectively. However, a high mortality rate (42%) was noted in the high dose Dex group. The cumulative number of animals with poor outcome (death or brain damage) was 49 (80%), 13 (33%) and 24 (44%) in the saline, low and high dose Dex groups, respectively. On the 10th and 14th postnatal days, the rats in both the Dex groups showed delayed neuronal maturation and myelination in the non-ligated side motor cortex, however, these maturational differences disappeared on the 21st postnatal days. Otherwise, the number of cortical cells in both the Dex groups were significantly lower than that in the saline group on the 28th postnatal days (P < 0.05 in each). These findings suggest that the pretreatment with Dex protects the developing brain from HI injury through the suppression of the neuronal maturation. However, a decreased number of cortical cells may give rise to psychomotor retardation later.

Effects of maternal administration of dexamethasone and thyrotropin-releasing hormone on fetal rat pulmonary surfactant synthesis.

To determine the effects of maternal administration of dexamethasone (DEX) and thyrotropin-releasing hormone (TRH) on fetal lung maturation, 16 pregnant rats were divided into the following four groups: 20 micrograms/kg TRH twice a day was given intraperitoneally to the TRH group rats, 0.5 mg/kg/day DEX to the DEX group and both DEX and TRH to the DEX + TRH group for 3 consecutive days from gestational day 17. The control rats were given an equivalent volume of saline. The pregnant rats were sacrificed on gestational day 20 and the fetal lungs were removed. The relative amounts of surfactant protein A (SP-A), B (SP-B) and C (SP-C) mRNAs were analyzed by Northern blotting and the total lung disaturated phosphatidylcholine (DSPC) contents were determined using an enzymatic method. The SP-B and -C mRNA and DSPC contents in the DEX and DEX + TRH groups were significantly higher than those in the control group, whereas the SP-A mRNA levels did not differ significantly among the four groups. The SP-B and -C mRNA and DSPC contents in the DEX and DEX + TRH groups did not differ significantly. These findings suggest that TRH has no effects on the regulation of surfactant protein mRNAs or DSPC contents in the fetal rat lung and has no additive effects when combined with DEX.

[A study on the causes of the physical and mental disabilities in children].

The causes and time of onset of physical and mental disabilities in children were investigated. Among 72 subjects, the causes of the disabilities were clearly verified in 43 cases, that is, 21 cases of hypoxic ischemic encephalopathy (29%), 12 cases of cerebral malformations (17%), 7 cases of other congenital malformations (10%), and 3 cases of intrauterine infections (4%). In 10 cases from the remaining 29 subjects, the disorders during perinatal period were strongly suggested from the findings of CT and MRI.

Perioperative changes in superoxide production in neonates and infants.

We conducted a prospective study to investigate perioperative changes in the production of superoxide anion (O2-) by neutrophils isolated from ten neonates between the ages of five and 16 days (N group) and ten infants ranging in age from one to ten months (I group). They underwent abdominal surgery under general anaesthesia with halothane and nitrous oxide in oxygen. The O2- production (speed and amount) was measured perioperatively using the cytochrome c reduction method. Both groups showed a decrease in the speed and amount of O2- production during and after surgery. The decrease in O2- production reached its lowest level three hours postoperatively or at the end of surgery in both groups. The O2- production in the I group returned to the basal value 48 hr postoperatively. In contrast, the O2- production in the N group was still lower 48 hr after surgery than before anaesthesia. Although the total amount of O2- production by neutrophils in one mL of peripheral blood remained unchanged in the I group, the total amount of O2- production in the N group decreased at the end of surgery and thereafter. These data indicate that even relatively minor abdominal surgery with halothane anaesthesia may be associated with perioperative neutrophil impairment in both neonates and infants. This impairment of neutrophil function in infants but not in neonates may be compensated by an increase in neutrophil numbers. It is possible that perioperative susceptibility of neonates to bacterial infections is attributable, at least in part, to the inhibition of O2- production in neutrophils by surgery and general anaesthesia.

[Severely handicapped children and its relationship with perinatal medical care].

We studied the etiology for sixty-eight severely handicapped children aged between 3 and 6 years, who were born in the Himeji city and the environs (9,900 live births/year). The prevalence was around 1.7/1,000 live births. The factors of their handicaps were as follows: congenital 25%; perinatal 40%; neonatal period 21%; and unknown onset 15%. Thirty-six patients out of 54 (67%) were admitted to neonatal intensive care unit (NICU) and visited the Center for neurological follow up immediately after their discharge. The high frequency of patients from NICU, compared with previous reports, might be due to a cooperative network between NICUs and the Center with medical support for handicapped children in this area.

[Cerebral palsy in children and its relationship with perinatal medical care].

We studied the etiology of 76 children with cerebral palsy (CP) aged 3 to 6 years, who visited the Himeji City Center for the Handicapped for neurological follow up. The patients for this study composed of 30 cases with severe handicap. 8 cases of CP with mental retardation and 10 cases of CP without mental retardation. Nine cases of CP had congenital anomalies of central nervous system, of which 8 cases showed severe handicap. Main perinatal factors were asphyxia, dyspneic condition needed for mechanical ventilation, prolonged apneic spells, and hyperbilirubinemia. All full-term birth children were accompanied with asphyxia, in which 43% had intracranial hemorrhage. A cooperative network between neonatal intensive care unit and an institute for the handicapped is essential for the care of infants with cerebral palsy.

Determination of serum unbound bilirubin for prediction of kernicterus in low birthweight infants.

Serum unbound bilirubin concentrations (UBC) and serum total bilirubin concentrations (TBC) were measured serially in 138 low birthweight (LBW) infants treated with phototherapy for non-hemolytic hyperbilirubinemia. We attempted to assign the suitable critical UBC levels for predicting bilirubin encephalopathy into two different birthweight groups: a very low birthweight (VLBW) group (birthweight < 1,500 g) and an LBW group (birthweight between 1,500 g and 2,499 g). Twelve infants were diagnosed as 'at risk' for kernicterus, of whom 11 had signs of acute bilirubin encephalopathy and received exchange transfusion. One VLBW infant had neurological sequelae at a 3 year follow-up, although exchange transfusion was not carried out because of low TBC. Sensitivity and specificity for predicting kernicterus were calculated at different UBC levels between 0.6 microgram/dl and 1.5 micrograms/dl and TBC levels between 8 mg/dl and 26 mg/dl. The receiver-operating characteristic (ROC) curves plotted for UBC as a predictor of kernicterus were clearly shifted up and to the left compared with the curves for TBC in the VLBW and LBW groups. Thus, the UBC measurement may well provide a more rational basis for evaluating the risk of kernicterus in LBW infants. The optimal cut-off points were derived from these curves. In the VLBW group, the sensitivity was 100% and the specificity was 96% for a UBC of 0.8 microgram/dl, and 80% and 64% for a TBC of 11 mg/dl. In the LBW group, the sensitivity was 100% and the specificity was 98% for a UBC of 1.0 microgram/dl and 71% and 78% for a TBC of 16 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)