The viability limit defined by the Japanese Eugenic Protection Act was amended from 24 to 22 completed weeks of gestation in 1991. To testify if the amendment is appropriate, we conducted a survey on the mortality and morbidity rates of infants less than 600 g born in Japan between 1984 to 1993.
Questionnaires were mailed to 205 hospitals with neonatal intensive care units (NICUs) and 165 (80%) responded. Of 1655 infants <600 g birth weight and admitted to the NICUs included in this survey, 457 (28%) survived to hospital discharge. The survival rates of infants born <24 weeks and ≧24 weeks of gestation were 17% (128/748) and 36% (329/903), respectively; and of infants <500 g and 500 to 599 g at birth were 16% (82/510) and 32% (375/1145), respectively. None of the infants ≦20 weeks of gestational age and ≦350 g at birth survived, but 4% (2/49), 12% (27/218), 21% (99/474), and 34% (131/381) born at 21, 22, 23, and 24 weeks of gestation survived, respectively. The majority (68%) died within 1 week after birth and only 10% died after the neonatal period. The main causes of death were: acute respiratory failure (33%), intraventricular hemorrhage (20%), infection (16%), and heart failure (10%). Of 457 survivors, 65% were free from handicaps. The incidence of mental retardation (DQ < 70), visual disturbance, and CP were 15%, 14%, and 11%, respectively.
Admission of micropremies to NICU increased markedly after the amendment of the Eugenic Protection Act, despite a marked decline in birth rate. The survival rate increased from 22% to 33% after generalized use of surfactant in 1988, but the handicap rate (35%) among survivors remained unchanged. The new viability limit of 22 complete weeks of gestation was feasible, since survival of less than 22 weeks was exceptional while survival of 22 to 23 weeks was 18%. neonate, morbidity, mortality, extremely low birth weight infants
Recent progress in neonatal medicine in Japan is striking. The infant and neonatal mortality rates in Japan from 1950 to 1993 declined sharply from 60.1 to 4.3 and 27.4 to 2.3 per 1000 live births, respectively.1 According to a recent nationwide survey,2 the survival rate of extremely low birth weight (ELBW) neonates with birth weights less than 1000 g reached 71.8%. The increased survival rate in ELBW infants was accomplished without an increase in handicap rate among survivors, which has remained unchanged at 10 to 15% for the past two decades.3 During 1986 to 1988, 60 infants born at 23 weeks’ gestation survived beyond the neonatal period, and one half of them were alive without major neurological sequelae at 1 year of age.4
Because of these rapid improvements in survival rate in ELBW neonates, the Eugenic Protection Act in Japan was amended in 1991, shortening the viability limit from 24 to 22 completed weeks of gestation. To testify if the amendment is appropriate, we conducted a survey on the mortality and morbidity rates of infants less than 600 g at birth for the past 10 years.
SUBJECT AND METHODS
A survey involving infants with birth weights <600 g born during 1984 to 1993 was conducted by sending questionnaires to hospitals having tertiary and secondary NICUs which are headed by members of the Japan Neonatologist Association. Out of 205 NICUs, 165 (80.5%) responded to our questionnaire and 1655 neonates <600 g at birth who were admitted to NICUs were enrolled into this survey.
Gestational age was determined by various obstetrical methods, including fetal size assessment by ultrasound, and confirmed by neonatal assessment after birth. Cause of death was determined by the given information on clinical course, ultrasound, and autopsy findings.
The outcome of survivors was also investigated, and CP, mental retardation (DQ < 70), hearing defect, visual defect, and epilepsy were regarded as major neurological sequelae. Surviving infants were followed from 1 to 10 years. At each clinical visit, complete physical and neurological examinations were performed mostly by the same neonatologist as the primary physician of the given patient with the assistance of neurologists. Developmental performance was assessed by the Enjoji Developmental Score, which was invented for the purpose of developmental evaluation for Japanese infants.5
Out of 1655 infants, 457 (27.6%) survived to hospital discharge. The number of neonates born <24 weeks and ≥24 weeks of gestation were 748 (45.2%) and 903 (54.6%), respectively, and the numbers of survivors were 128 (17.1%) and 329 (36.4%) respectively. Four infants with unidentified gestational age died. The survival rates of infants <500 g and 500 to 599 g at birth were 16.1% (82/510) and 32.8% (375/1145), respectively (Table 1).
The number of admission of infants <600 g at birth showed a trend of increase, which became more marked after the amendment of the viability limit in the Japanese Eugenic Protection Act from 24 to 22 completed weeks of gestation in 1991 (Fig. 1). The survival rate was improved from 21.8% in 1988 to 32.9% in 1989, when surfactant replacement therapy became widely available in Japan.
The survival rates of these infants were further analyzed according to birth weight. None of the infants ≤350 g at birth survived, while 6 (10.3%) of 58 infants who were 350 to 399 g at birth survived. Even in these ultrasmall neonates, survival rates increased gradually with the increment of birth weight, and 247 of 655 neonates (37.7%) who were 550 to 599 g at birth survived (Fig. 2).
The survival rates by gestational age are shown in Fig.3. None of neonates at ≤20 weeks of gestation, and only 2 (4.1%) of 49 at 21 weeks of gestation survived, while nearly one half of neonates at 27 weeks of gestation survived. Survival rate of neonates born ≥27 weeks, decreased in spite of an improved maturity. In these cases, severe intrauterine growth retardation was probably an overwhelming factor.
Table 2 shows the main causes of death of 1198 micropremies <600 g at birth. Acute respiratory failure due to respiratory distress syndrome, air leak, and pulmonary hemorrhage were the major causes of death, followed by intraventricular hemorrhage and infection. It is noteworthy that necrotizing enterocolitis and bronchopulmonary dysplasia were not the main causes of death, even among these most vulnerable ultralow-weight infants.
Among 1191 fatal cases of infants <600 g at birth, the majority (807; 67.8%) died within 1 week after birth and only 119 (9.9%) died after the neonatal period. These will be important data to consider in discussions over the allocation of limited medical resources to these most high-risk infants.
Out of 457 survivors, 158 (34.6%) were regarded as handicapped. The incidence of mental retardation (DQ < 70), severe visual defect, and CP were 14.9% (68 infants), 14.3% (57), and 11.4% (52), respectively (Table 3). In spite of the extreme prematurity and smallness, over 65% of survivors were free from major neurological handicaps.
There are several excellent review articles on the mortality rate of ELBW infants,6 but reports on micropremies (<600 g at birth) are rare. The published mortality rates of ELBW infants <800 g at birth are summarized in Table 4.12Although mortality rates of infants <800 g at birth are still high except for the Japanese data, a surprisingly small infant of 280 g born at 27 weeks’ gestation was recently reported to have survived without apparent neurological sequelae.24
Nationwide surveys on neonatal mortality rates have been conducted every 5 years in Japan. They show clear improvements in survival rate in all birth weight categories which is more prominent in lower birth weight infants. The mortality rates of infants less than 1000 g at birth declined significantly in the past decade from 56.3% in 1980 to 26.9% in 1990.2
The Japan Pediatric Society conducted a survey on the outcome of infants <24 weeks’ gestation and/or <500 g at birth born between 1988 through 1990.23 The survival rates of infants born at 23, 22, and <22 weeks’ gestation were 43/118 (36%), 3/36 (8%), and 0/8 (0%), respectively. None of the infants at <400 g at birth survived, but 16 (12%) of 50 infants at 400 to 499 g at birth survived. Based on these results, the viability limit in the Japanese Eugenic Protection Act was amended from 24 to 22 completed weeks of gestation and came into force in January 1991.
Because of the amendment, the treatment policy for micropremies <600 g at birth became more active, which is one of the factors contributing to the increased number of admissions of infants <500 g and <24 weeks of gestational age which emphasizes the importance of a policy based on up-to-date medical achievements to the statistics. Survival rate of this weight group increased significantly after 1988, when the surfactant replacement therapy became popular in Japan. Although there is no analysis yet on this phenomenon, it could be postulated that introduction of this new mode of therapy was contributing to the improvement of the survival rate.
According to Webster’s dictionary, the term “viability” does not simply mean “the ability to be born alive” but denotes “the capability to grow and to develop normally in extrauterine environments.” Therefore, discussions on viability should include the ultimate outcome of these micropremies from the physical, neurological, and developmental viewpoints. As compared with the data on mortality rates, reliable morbidity data of ELBW infants (with a sufficient number of cases and with sufficient length of follow-up) have only recently become available. Most follow-up data of ELBW infants were based upon cases of apparent neurological abnormality which can be diagnosed at an early postnatal stage. A summary of the incidence of major neurological sequelae represented as CP, mental retardation (DQ < 70), and severe visual defect is summarized in Table5.17,23,25 A recent Canadian report comparing 3-year-old ELBW survivors born in 1977 through 1980 and in 1981 through 1984 indicated that the increased survival rate of ELBW infants was not necessarily associated with an increased incidence of major neurological sequelae.
In this study, 158 of 456 (35%) surviving infants were regarded as handicapped (Table 3). The high incidence of retinopathy of prematurity that defined the cases requiring coagulation therapy simply reflects extreme immaturity, but the number with blindness was very small. The incidence of CP is nearly the same as those <1000 g, because intraventricular hemorrhage which in the main cause of CP on such tiny infants may not allow them to survive. We could say that in spite of the extreme prematurity and smallness, over 65% of them were spared major handicaps. Interpretation of this figure as to whether it is acceptable or too high should vary from society to society.
As a result of the rapid progress in medical care for micropremies, the incidence of major neurological sequelae did not increase with decreases in birth weight and gestational age. By reviewing the data of micropremies weighing <600 g at birth, born between 1984 through 1993, 457 (27.6%) of 1655 such infants survived. But survival of infants <22 weeks of gestation was exceptional and only 2 out of 49 survived, while 126 (18%) of 692 infants at 22 and 23 weeks’ gestation survived. Therefore, it could be said that the recent amendment of the viability limit from 24 to 22 complete weeks of gestation is justified.
We thank members of the Committee of Newborn Infants, the Japan Neonatologist Association, and the doctors who participated in the survey for their support and cooperation.
- Received March 25, 1996.
- Accepted November 7, 1996.
Reprint requests to (M.O.) Maternal and Perinatal Center, Tokyo Women’s Medical College, Kawada-cho 8-1, Shinjyuku-ku, Tokyo, Japan, 162.
- ELBW =
- extremely low birth weight infant •
- NICU =
- neonatal intensive care unit •
- CP =
- cerebral palsy
- ↵Committee of Newborn Infant, Japan Society of Pediatrics. Neonatal white paper in Japan. J Jpn Pediatr Soc. 1986;90:2827–2855 (in Japanese)
- ↵Committee of Newborn Infant, Japan Society of Pediatrics. Report on the current status of NICU and neonatal mortality in Japan. J Jpn Pediatr Soc. 1991;95:2454–2461 (in Japanese)
- Nishida H
- ↵Ishizuka Y. Long-term survival and sequelae of premature infants weighing not greater than 500g at birth or born before 24 weeks’ gestation. J Jap Pediatr Soc. 1990;94:841 (in Japanese)
- ↵Enjoji M, Goya C. Method for analytical developmental examination in infants and children. Tokyo Keio Tsushin, 1977 (in Japanese)
- Ishizuka Y, Fujii T, Kouki K, et al. Mortality and morbidity rates of premature infants weighing less than 1,000 grams at birth: collaborated study of 110 hospitals in Japan. Shuusankiigaku.1980;10:433–443 (in Japanese)
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- Copyright © 1997 American Academy of Pediatrics