Limit of viability in Japan: ethical consideration.

Viability means "the quality or state of being able to live, grow and develop." Limit of viability has been changed along with the advancement of perinatal and neonatal medicine. The viability limit defined in the Japanese Motherhood Protection Act was amended from 24 to 22 completed weeks of gestation in 1991 based on the survival rate of extremely preterm infants. Survival rates of infants at 22 and 23 weeks' gestation born between 2002 and 2004 in Japan were 31% and 56%, respectively. Though medical data are the most important means to define viability, socio-economical and ethical factors should be also considered, especially when we discuss the group of marginally viable infants. We think there are two different categories of viability limits, one from biological survival limit and another from social agreement of providing active medical intervention. Currently in Japan, the former viability definition based on purely medical data is 22 completed weeks and the latter definition is the social consensus of about 24-28 weeks' gestation.

Clinical features of neonatal toxic shock syndrome-like exanthematous disease emerging in Japan.

OBJECTIVES: An epidemic of neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED) has emerged in Japan. NTED is caused by TSS toxin-1 produced predominantly by methicillin-resistant Staphylococcus aureus (MRSA). Using a large-scale investigation, the present study aimed to elucidate the overall clinical picture of NTED in Japan. METHODS: We performed nationwide surveys regarding NTED in Japanese neonatal intensive care units (NICUs) in 2000, 2002 and 2005, and summarized the clinical findings of 540 patients. We also performed a case-control study to identify the relationship between patients' clinical findings and NTED. RESULTS: The frequency of NTED in Japanese NICUs in 2000 was 52.2% and declined to 28.3% in 2005. The number of NTED patients in 2000 was 240 and decreased to 139 in 2005. In 2005, the isolation of methicillin-sensitive S. aureus (MSSA) increased to 20.0% in term patients. Although no term infants suffered shock or death, preterm patients sometimes developed severe symptoms. CONCLUSIONS: The number of NTED patients decreased over the 5-year period from 2000 to 2005, even though more than 100 patients contracted NTED in Japanese NICUs in 2005. MSSA as well as MRSA can cause NTED, and NTED is more severe in preterm infants than in term infants.

Comparison of serum cortisol concentrations in preterm infants with or without late-onset circulatory collapse due to adrenal insufficiency of prematurity.

A recent survey found that approximately 4% of very low birth weight infants in Japan were treated with glucocorticoids postnatally for circulatory collapse thought to be caused by late-onset adrenal insufficiency. We identified 11 preterm infants with clinical signs compatible with this diagnosis (hypotension, oliguria, hyponatremia, lung edema, and increased demand for oxygen treatment) and matched them for gestational age with 11 infants without such signs. Blood samples were obtained for cortisol and its precursors from the patient group before the administration of hydrocortisone, and from the control group during the same postnatal week. All samples were analyzed using a gas chromatography-mass spectrometry system. Cortisol concentrations did not differ between the two groups (6.6 +/- 4.5 vs 3.4 +/- 2.7 microg/dL); however, the total concentration of precursors in the pathway to cortisol production was significantly higher in the patient group (72.2 +/- 50.3 vs 25.0 +/- 28.5 microg/dL; p < 0.05). We conclude that the clinical picture of late-onset adrenal insufficiency in preterm infants is not a result of an absolute deficiency of cortisol production, but may be a result of a limited ability to synthesize sufficient cortisol for the degree of clinical stress.

Impact of being small-for-gestational age on survival and long-term outcome of extremely premature infants born at 23-27 weeks' gestation.

AIM: To evaluate factors affecting survival and long-term outcome of extremely premature infants and to determine whether small for gestational age (SGA) status is an additional risk factor. METHODS: Survival was analyzed in 193 infants born between 23 and 27 weeks of gestational age (GA) and compared between SGA (n=43) and appropriate for gestational age (AGA) infants. Long-term outcome was assessed in 123 infants at six years of chronological age by neurological evaluation and cognitive tests. RESULTS: The long-term survival rates were 72.1% for SGA and 84.0% for AGA infants. Significant independent factors affecting survival were GA (OR 1.79 for one week advance, 95% CI 1.36-2.34) and SGA (OR 0.42, 95% CI 0.18-0.997) in comparison with AGA. There were no significant differences in rates of cerebral palsy or mental retardation, 12.0% and 24.0% in SGA, 14.3% and 17.3% in AGA, respectively. Fifty-two percent of SGA and 70% of AGA infants had intact long-term outcome. The perinatal factor found to affect the intact long-term outcome was RDS with surfactant therapy (OR 0.17, 95% CI 0.07-0.45). CONCLUSION: SGA status as well as short gestation had significant effects on survival. Respiratory complications after birth had a larger detrimental effect on long-term outcome than whether the infant was SGA or AGA.

Morbidity and mortality of infants with very low birth weight in Japan: center variation.

OBJECTIVES: The objectives of this study were to describe the characteristics and morbidity of very low birth weight infants, to identify the medical intervention for these infants, and to evaluate the factors affecting the mortality of these infants among the participating hospitals. METHODS: A large multicenter neonatal research network that included level III NICUs from throughout Japan was established. A standardized mortality rate was formulated by giving a ratio of the observed deaths and the predicted deaths based on a 100-g birth weight interval mortality. A regression model was used to predict the factors that affect neonatal mortality. RESULTS: The network included 37 centers and 2145 infants weighing < or = 1500 g, born or admitted to the centers in 2003. Gestational age and birth weight of studied infants were 28.6 +/- 3.6 gestational weeks (mean +/- SD) and 1025 +/- 302 g, respectively. Overall, 11% of the infants died before being discharged from hospitals (range: 0%-21%). The standardized mortality rate varied among the facilities (range: 0%-30%). No association between the annual number of patients admitted and standardized mortality rate was found. Among all of the very low birth weight infants, 14% were outborn infants, 72% were delivered by cesarean sections, 27% had patent ductus arteriosus, 3% had gastrointestinal perforation, 8% had bacterial sepsis, and 13% had intraventricular hemorrhage. Medical interventions involved were: 41% antenatal corticosteroids, 54% surfactant therapy, 18% postnatal steroids for chronic lung disease, and 29% high-frequency oscillatory ventilation. We found variations in the medical interventions and the clinical outcomes among the centers. CONCLUSIONS: The overall survival rate for very low birth weight infants among neonatal centers in Japan was approximately 90%. However, differences in the morbidity and mortality were observed among these centers.

[Retinopathy of prematurity in extremely low birth weight infants: a Tokyo multicenter study].

OBJECTIVE: To investigate how the increase in survival rate in extremely low birth weight (a birth weight of 1,000 g or less) infants had affected the incidence of retinopathy of prematurity (ROP) and the frequency of laser treatment. METHODS: We retrospectively reviewed the medical records of 122 surviving premature infants with birthweights less than 1,000 g to determine the severity of ROP observed at 16 neonatal intensive care units in Tokyo between April and October 2002. RESULTS: The survival rate was 85.6%. The mean gestational age was 26.74 weeks and the mean birth weight was 782.25 g. One-hundred-and-five infants (86.1%) developed ROP, fifty (41.0%) received laser treatment, and six (4.9%) had retinal detachment. The median postmenstrual age (gestational age at birth plus chronological age in weeks, PMA) at the onset of ROP was 32.5 weeks, and the first laser treatment was performed at the median PMA of 35.7 weeks. CONCLUSIONS: In these extremely low birth weight infants, there was an increase in the survival rate and in the incidence of severe ROP that progressed to the stage that required treatment.