Births In Japan Research Articles

Effects of ambient air pollution on the risk of small- and large-for-gestational-age births: an analysis using national birth data in Japan.

Small-for-gestational-age (SGA) and large-for-gestational-age (LGA) births are major adverse birth outcomes related to newborn health. In contrast, the association between ambient air pollution levels and SGA or LGA births has not been investigated in Japan; hence, the purpose of our study is to investigate this association. We used birth data from Vital Statistics in Japan from 2017 to 2021 and municipality-level data on air pollutants, including nitrogen dioxide (NO2), sulfur dioxide (SO2), photochemical oxidants, and particulate matter 2.5 (PM2.5). Ambient air pollution levels throughout the first, second, and third trimesters, as well as the whole pregnancy, were calculated for each birth. The association between SGA/LGA and ambient levels of the air pollutants was investigated using crude and adjusted log-binomial regression models. In addition, a regression model with spline functions was also used to detect the non-linear association. We analyzed data from 2,434,217 births. Adjusted regression analyses revealed statistically significant and positive associations between SGA birth and SO2 level, regardless of the exposure period. Specifically, the risk ratio for average SO2 values throughout the whole pregnancy was 1.014 (95% confidence interval [CI] 1.009, 1.019) per 1ppb increase. In addition, regression analysis with spline functions indicated that an increase in risk ratio for SGA birth depending on SO2 level was linear. Furthermore, statistically significant and negative associations were observed between LGA birth and SO2 except for the third trimester. It was suggested that ambient level of SO2 during the pregnancy term is a risk factor for SGA birth in Japan.

Strategy for Overcoming Population Growth Problems in Japan

<p><em>Japan is considered a developed country with an economy that is growing strongly from year to year. Even though Japan is currently a "developed" country, it does not mean that Japan is without problems. Currently, Japan's problem is the decline in the number of births in Japan. It's not new, but it's been around since 1975. The phenomenon of declining birth rates in Japan is known as shoushika. Shoushika phenomenon is a decline in the child population in Japan, this phenomenon is inseparable from the decline in birth rates and the rapid growth of the elderly population. Judging from the historical factors that after World War II, Japan built the country from adversity with the hard work of its people and made Japan a developed country. But the effect of its focus on development makes Japanese society individualistic. So it is not surprising that the Shoushika phenomenon emerged and turned Japan into a demographic crisis. Japan is experiencing a population decline due to a declining birth rate. In addition, the number of seniors (elderly) and older people over 65 is increasing. The phenomenon is predicted to continue in the future, the ratio of old to young is one in four.</em></p>

Holiday effect on childbirth: A population-based analysis of 21,869,652 birth records, 1979-2018.

Maternity and neonatal services always have to operate 24 hours a day and 7 days a week, and require well preparedness to guarantee safe deliveries for both mothers and babies. However, the evidence of holiday effect from large-scale data is still insufficient from the obstetrics perspective. We analyzed data of over 21 million births in Japan from January 1, 1979, to December 31, 2018. We revealed that the number of births is lower on holidays, and especially among high-risk births such as low birthweight and preterm births. The frequency of high-risk birth has been increasing over the study period, and the variation by the day of week and between holiday and non-holiday have become more prevalent in recent years.

The Population-Attributable Fractions of Small-for-Gestational-Age Births: Results from the Japan Birth Cohort Consortium.

A fetal growth restriction is related to adverse child outcomes. We investigated risk ratios and population-attributable fractions (PAF) of small-for-gestational-age (SGA) infants in the Japanese population. Among 28,838 infants from five ongoing prospective birth cohort studies under the Japan Birth Cohort Consortium, two-stage individual-participant data meta-analyses were conducted to calculate risk ratios and PAFs for SGA in advanced maternal age, pre-pregnancy underweight, and smoking and alcohol consumption during pregnancy. Risk ratio was calculated using modified Poisson analyses with robust variance and PAF was calculated in each cohort, following common analyses protocols. Then, results from each cohort study were combined by meta-analyses using random-effects models to obtain the overall estimate for the Japanese population. In this meta-analysis, an increased risk (risk ratio, [95% confidence interval of SGA]) was significantly associated with pre-pregnancy underweight (1.72 [1.42-2.09]), gestational weight gain (1.95 [1.61-2.38]), and continued smoking during pregnancy (1.59 [1.01-2.50]). PAF of underweight, inadequate gestational weight gain, and continued smoking during pregnancy was 10.0% [4.6-15.1%], 31.4% [22.1-39.6%], and 3.2% [-4.8-10.5%], respectively. In conclusion, maternal weight status was a major contributor to SGA births in Japan. Improving maternal weight status should be prioritized to prevent fetal growth restriction.

Tobacco Exposure During Pregnancy and Infections in Infants up to 1 Year of Age: The Japan Environment and Children's Study.

Tobacco exposure during pregnancy is associated with several adverse outcomes in infants. We investigated the association between tobacco exposure during pregnancy (both active and second-hand) and various infections in infants up to 1 year. This prospective cohort study used a fixed dataset (jecs-an-20180131) from the Japan Environment and Children's Study of registered births in Japan during 2011-2014 that included 104,065 fetal records from enrolled pregnant women. Based on the participants' responses to the questionnaire on smoking status, mothers were first divided into "Never smoked," "Quit smoking," and "Current smoker" groups and then into "No second-hand smoking (SHS)" and "SHS" groups. Infectious diseases included central nervous system infection, otitis media (OM), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), gastroenteritis (GI), and urinary tract infection. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression analysis and adjusted for maternal, socioeconomic, and postnatal confounding factors. Among the 73,205 newborns enrolled, multivariable analysis revealed that the aOR (95% CI) of LRTI and GI was 1.20 (1.07-1.33) and 1.18 (1.04-1.35), respectively, for the "Current smoker with/without SHS" group compared with the "Never smoked without SHS" group. "Quit smoking without SHS" was not associated with the risk of LRTI. SHS was associated with an increased risk of OM, URTI, LRTI, and GI, especially with LRTI and GI. Exposure to tobacco smoke during pregnancy was associated with an increased risk of OM, URTI, LRTI, and GI in infants during their first year of life.

Changes in preterm and extremely preterm birth rates in Japan after the introduction of obstetrical practice guidelines in 2008.

Obstetrical guidelines were established in Japan in 2008, and obstetrical diagnoses and treatments were subsequently standardized nationally. We examined changes in the preterm birth rate (PTBR) and extremely preterm birth rate (EPTBR) following the introduction of such guidelines. Information on 50 706 432 live births in Japan between 1979 and 2021, including Japanese reproductive medicine, the childbearing age of pregnant women, and the employment status of reproductive-age women between 2007 and 2020, were obtained from the Japanese government and academic societies. Regression analysis was used to compare chronological changes nationally and those of eight Japanese regions. Regional and national average PTBRs and EPTBRs from 2007 to 2020 were compared by using a repeated measures analysis of variance. From 1979 to 2007, PTBRs and EPTBRs in Japan increased significantly. However, from 2008, the national PTBR and EPTBR decreased until 2020 (p < 0.001) and 2019 (p = 0.02), respectively. From 2007 to 2020, overall PTBR and EPTBR were 5.68% and 0.255%, respectively. A significant difference in the PTBR and EPTBR existed between the eight Japanese regions. During this period, the number of pregnancies using assisted reproductive technology increased from 19 595 to 60 381, pregnant women became older, the employment rate of those of reproductive age increased, and nonregular employment was 54%, which was 2.5 times higher than for men. In Japan, after obstetrical guidelines were enacted in 2008, PTRBs decreased significantly even under the pressure of increasing preterm births. Countermeasures may be necessary for regions showing high PTBRs.

The Effect of Sexual Intercourse during Pregnancy on Preterm Birth: Prospective Single-Center Cohort Study in Japan.

Several studies in Europe and the United States have shown that sexual intercourse (SI) during pregnancy is not associated with preterm birth. However, it is unclear whether these findings apply to pregnant Japanese women. The aim of this prospective cohort study was to elucidate the influence of SI during pregnancy on preterm birth in Japan. A total of 182 women who underwent antenatal care and delivery were included in this study. The frequency of SI was assessed using a questionnaire, and its association with preterm birth was analyzed. The results showed that SI during pregnancy was associated with a significantly higher cumulative preterm birth rate (p = 0.018), which was more pronounced for SI more than once a week (p < 0.0001). Multivariate analysis showed that SI, bacterial vaginosis in the second trimester, previous preterm birth, and smoking during pregnancy were independent risk factors for preterm birth. The combination of SI and second trimester bacterial vaginosis was associated with a 60% preterm birth rate, whereas either factor alone was associated with a lower rate, suggesting a synergistic effect (p < 0.0001). Future studies are needed to investigate the effect of prohibiting SI in pregnant women with bacterial vaginosis on preterm birth.

Effect of Pre-Surgical Orthopedic Treatment on Hard and Soft Tissue Morphology in Infants with Cleft Lip and Palate

The frequency of cleft lip and palate births in Japan is approximately 0.146%. The study aimed to compare the effects of NAM on restoring nasal morphology and improving extraoral nasal morphology in children with cleft lip and palate in the first stage of treatment using 3D imaging and oral model analysis. The subjects were five infants (37.6 ± 14.4 days old) with unilateral cleft lip and palate. The images taken with the 3D analyzer and oral model used for constructing the NAM at the first examination (baseline) and at the completion of the pre-surgical orthodontic treatment (157.8 ± 37.8 days old) were analyzed. The cleft distance was measured at the upper, middle, and lower points on the 3D images. On the model, the cleft jaw width at the maximum protrusion of the healthy and affected sides of the alveolar bone was measured. After the pre-surgical orthopedic treatment, the measured value on the model decreased significantly by a mean of 8.3 mm from baseline, and the cleft lip width narrowed by an average of 2.8 ± 2.2, 4.3 ± 2.3, and 3.0 ± 2.8 mm at the upper, middle, and lower points of the cleft, respectively. Pre-surgical orthopedic treatment using NAM can help narrow the width of the cleft jaw and lip. The sample size is stated at the study limit in the paper.

Detecting geographical clusters of low birth weight and/or preterm birth in Japan

In Japan, mean birth weight has significantly decreased from 3152 g in 1979 to 3018 g in 2010 and the prevalence of preterm birth (PTB) has risen to 5.7% in the last thirty years. However, the presence and magnitude of geographical differences in low birthweight (LBW) and/or PTB in Japan is not well understood. We implemented spatial analysis to identify localized clusters and hot spots of LBW and/or PTB during 2012–2016. The Japan national birth database was used in this study. A total of 5,041,685 (male: 2,587,415, female: 2,454,270) births were used for spatial analysis using empirical Bayes estimates of the incidence rate of LBW and/or PTB and spatial scan tests to detect hot-spot areas with p values calculated from Monte Carlo iterations. The most and second likely clusters were located in two areas: (1) the small islands in south-west Japan (Amami and Okinawa, Relative risk = 1.09–1.67 with p < 0.001) and (2) the cities on the base of Mt. Fuji, stretching over three neighboring prefectures of Yamanashi, Shizuoka and Kanagawa (Relative risk = 1.10–1.55 with p < 0.001), respectively. We need to optimize the medical resource allocations based on the evidence in geographical clustering of LBW and/or PTB at specific locations in Japan.

Japan: Demographic Crisis

Japan has been adversely affected by the COVID-19pandemic which has had a negative impact on the demographics in the country in dramatic ways : the number of births in Japan has been on a downtrend since the government started compiling statistics on births in 1899 and this downtrend is expected to continue for years to come. On the one hand, the negative trend of declining fertility was laid down long before the pandemic by persistent features will continue including the gendered division of labor, rising rates of labor participation among women, breaking balance of work and life that ultimately has led to decrease of marriage rates and has caused women to delay plans to become pregnant due to economic reasons. On other hand, social distancing, changes brought upon by the prolonged coronavirus pandemic has continued to cause women to permanent stress which, in turn, also does not contribute to the solution of the fertility issue. For Japanese society, challenges which were caused by COVID-19pandemic may be an opportunity to re-imagine the larger role men play in their families (apart from work for family financial supporting) and this rethinking, with the adoption of certain decisions by the Japanese government, is likely to stop this negative trend in demography.

“A RARE CASE OF EARLY INFANTILE EPILEPTIC ENCEPHALOPATHY”

Early infantile epileptic encephalopathy (EIEE), also known as Ohtahara syndrome, is characterized by intractable tonic seizures in the setting of a severe encephalopathy and a burst-suppression background pattern on EEG. Incidence has been estimated at 1/100 000 births in Japan and 1/50,000 births in the U.K. Approximately 100 cases total have been reported but this may be an underestimate. Ohtahara syndrome is a rare clinico-EEG syndrome. Gold standard investigation is genetic panel for epilepsy in case of nil structural abnormalities. It is refractory to any mode of treatment including ketogenic diet and surgery and carries highest mortality rate, die in infancy.

The Long-Term Healthcare Utilization and Economic Burden of RSV Infection in Children ≤5 Years in Japan: Propensity Score Matched Cohort Study.

The objective of this study was to estimate the long-term healthcare utilization and cost burden of RSV by chronological age of diagnosis (Year 1, Year 2 and Years 3-5 cohorts) as well as by gestational age at birth in Japan. The JMDC database was used to retrospectively identify RSV and control patients between February 1, 2011 and January 31, 2016 and follow them through December 31, 2017. Infants with RSV infection (n = 9028 in Year 1; n = 4929 in Year 2; n = 2004 in Years 3-5) were matched to controls (n = 17,886; n = 9351; n = 3655, respectively) based on gestational age and year and quarter of birth; controls were assigned the index date (ie, diagnosis) of their respective match. Covariate-balancing propensity score weights were employed adjusting for remaining imbalances between cohorts. The main outcomes were average cumulative rates for all-cause, asthma/wheezing, and respiratory-related hospitalizations, physician and urgent care/emergency visits and associated costs (reported as 2018 ¥JPY) over 36-months of follow-up since index. Healthcare utilization was significantly higher among RSV cases for most comparisons. All-cause average differential cost burden was higher for RSV, compared to controls, among the following cohorts: Year 1 full-term (¥277,727); Year 2 preterm (¥530,302), late preterm (¥270,797), full-term (¥238,832); Years 3-5 preterm (¥110,057), late preterm (¥486,670), full-term (¥289,986). While all-cause costs were similar for preterm and late preterm children in the Year 1 cohort, respiratory- and asthma/wheezing-related attributable costs were substantially higher for RSV. RSV infection had a significant long-term health and economic burden among children infected during their first year of life and later in life. Study findings have import for prevention strategies, currently directed at maternal immunization and monoclonal antibodies for preventing primary RSV infections in the first six months of life and beyond but also for older age not targeted currently.

An attempt of using public ambient temperature data in swine genetic evaluation for litter-size traits at birth in Japan

Context Large-scale genetic evaluation is promising for efficiently improving sow lifetime productivity, and therefore, a reasonable operational model should be pursued to analyse phenotypic data collected from around Japan, where unique seasonality exists. However, the information on establishing the model is currently insufficient. Aims To obtain the fundamental information on using ambient temperature information in developing the model for routine swine genetic evaluation in Japan, by analysing total number born, number born alive, and number stillborn collected at a Japanese farm, together with off-farm ambient temperature measured at the nearest Automated Meteorological Data Acquisition System station. Methods Five repeatability animal models were exploited, considering the effects of farrowing season (Model 1), farrowing month (Model 2), quadratic regressions of daily maximum ambient temperature of farrowing day (Model 3), season and temperature (Model 4), or month and temperature (Model 5). Key results Patterns of the effects of daily maximum temperature of farrowing day estimated using Model 3 were similar to those of farrowing season by Model 1 and those of farrowing month by Model 2. Adding the effect of daily maximum temperature of farrowing day (Models 4 and 5) could explain phenotypic variability better than only considering either of farrowing season or month (Models 1 and 2). Estimated heritability was stable among the models and the rank correlation of predicted breeding values among models was &gt;0.98 for all traits. Conclusions The results indicated the possibility that using public ambient temperature can capture a large part of the phenotypic variability in litter-size traits at birth caused by seasonality in Japan. Implications This study could support the availability of public meteorological data in the development of flexible operational models for future swine genetic evaluation in Japan.

Wisdom of Freezing All Valuable Embryos

Background: It is controversial whether that “Freeze-only” strategy is superior to Fresh embryo transfer in ART patients with normal ovarian response. There are two reasons supporting a “Freeze-only” strategy. One is that frozen-thawed embryos are transferred to a more physiologically receptive endometrium. While fresh embryos are transferred to a badly affected one because of controlled-ovarian stimulations, which cause the discordant development of the endometrium, when thawed-frozen embryos are transferred in a subsequent cycle the endometrium is not affected by high estrogen levels. The other reason is the big difference in cryopreservation and stimulation techniques. Methods: We investigated the annual ART reports in Japan from 1992 to 2018, and our clinical outcomes of frozen-thawed embryo transfers and fresh embryo transfers from 2015 to 2019. This enabled the assessment of the survival rate of frozen blastocyst by Cryotop safety kit after thawing in four different clinics. We compared the outcomes of frozen embryo transfer (FroET) to fresh embryo transfer. Results: The proportion of birth in Japan in the study interval found that FroET was responsible for 86.7% of births, compared to 13.3% of births resulting from fresh embryo transfers after IVF or intracytoplasmic sperm injection (ICSI). Clinical outcome of FroET in our clinic was significantly higher than that of fresh embryo transfer regardless of maternal age and number of collected oocytes. Average survival rate of frozen blastocyst by Cryotop safety kit after thawing in four clinics was over 95%. Conclusions: We believe that “Freeze-only high-quality blastocysts” is superior to fresh embryo transfer in terms of clinical outcome, at least when compared to historical results.

Elective cesarean delivery at term and its effects on respiratory distress at birth in Japan: The Japan Environment and Children's Study.

Background and AimsEarly‐term birth between 37 and 38 weeks of gestation increases the risk of mortality and morbidity. This study investigated the status and impact of early‐term birth among neonates born by cesarean section in Japan.MethodsAll singleton live births that had data of gestational age at birth available in the Japan Environment and Children's Study (JECS), a nationwide birth cohort study launched in 2011, were eligible for this study. Neonates born by cesarean delivery at term without indications for early delivery were included to examine the association between early‐term birth and respiratory distress at birth. The gestational age at birth was categorized as 37 weeks 0 day to 38 weeks 6 days (early‐term), 39 weeks 0 day to 40 weeks 6 day (full‐term), and 41 weeks 0 day to 41 weeks 6 days (late‐term). Respiratory distress at birth included respiratory distress syndrome, transient tachypnea, and difficulty in breathing after birth. Univariable and multivariable analyses were performed using logistic regression models with a two‐tailed significance level of 5%. All statistical analyses were performed using SAS, version 9.4, for Windows (SAS Institute, Cary, NC).ResultsIn total, 32 078 of 100 011 (32.1%) neonates had early‐term birth. At 37 gestational weeks, 49.7% of the deliveries were via cesarean section, and half of the cesarean deliveries were due to a previous cesarean section. Among the 10 051 neonates born by elective cesarean delivery at term, neonates with early‐term births were more likely to have respiratory distress at birth (adjusted odds ratio: 4.19; 95% confidence interval, 1.70, 10.34) than those born at full term.ConclusionsEarly‐term birth is associated with a high risk of respiratory distress in births involving cesarean delivery without indication for early delivery. There is a need for guidelines for early delivery considering adverse effects of early‐term births.

Current status of surviving patients with arginase 1 deficiency in Japan

Arginase 1 (ARG1) deficiency is a rare urea cycle disorder (UCD), with an estimated frequency of 1 per 2,200,000 births in Japan. Patients with ARG1 deficiency develop symptoms in late infancy or pre-school age with progressive neurological manifestations and sometimes present with severe hepatic disease. We previously investigated the status of UCDs in Japan; however, only one patient was identified as having ARG1 deficiency. Therefore, we aimed to investigate the current status of patients with ARG1 deficiency in 2018–2021 because almost 10 years have passed since the previous study. We present the disease history, clinical outcome, and treatment of five surviving patients with ARG1 deficiency and discuss the features of ARG1 deficiency in Japan. We found that clinicians often face difficulty in diagnosing ARG1 deficiency at the early stage of onset because of interpatient variability in onset time and clinical manifestations. Blood L-arginine and guanidino compounds were considered to be the major factors causing adverse neurodevelopmental outcomes. Therefore, early detection and intervention of ARG1 deficiency is essential for improved neurodevelopmental outcomes. Liver transplantation has been considered an effective treatment option that can dramatically improve the quality of life of patients, prior to the neurological manifestation of symptoms caused by ARG1 deficiency.

The inter-role conflicts among female workers playing a dual role in Japan

Since Shinzo Abe took the helm as prime minister in 2012, Japan’s female labour force participation has ticked up. Abe’s push for female empowerment was since the decline in births in Japan had been considered the fastest in the world. However, barriers are still common among female workers especially those having underage children, a condition in which inter-role conflicts occur. This research focuses on inter-role conflicts that arise on female workers playing a dual role and aims at looking into their way of playing the role in both public and domestic sectors. The research applies interviewing as the method in the qualitative approach. This research concludes that women in the workforce still face certain impediments including inflexible working hours and restrictions in family and household time.

The safety of ritodrine hydrochloride: Adverse effects on fetuses and newborns.

Prematurely born infants face unique risks, and the treatment of imminent preterm birth is thus an important part of perinatal care. Ritodrine hydrochloride (Rito) is widely used as a therapeutic agent to treat imminent preterm birth in Japan. Following assessment of the risks and benefits of short-acting β-agonists, including Rito, in Europe, however, the use of Rito has begun to be questioned. Thus, in this study we investigated the safety of Rito in the treatment of imminent preterm birth, with a particular focus on the adverse effects (AEs) on fetuses and newborn infants. Using the Pharmaceuticals and Medical Devices Agency of Japan's Japanese Adverse Drug Event Report (JADER) database, the AEs on fetuses and newborns caused by oral and injected Rito were extracted and analyzed. The reported odds ratios for oral Rito were significantly higher for fetal tachycardia, fetal bradycardia, neonatal hypoglycemia, and neonatal heart failure than for other drugs. The reported odds ratios for Rito injection were significantly higher for fetal tachycardia and neonatal hypoglycemia than for other drugs. Oral drugs had more adverse effect reports than injectable drugs.

Reduction in live births in Japan nine months after the Fukushima nuclear accident: An observational study.

BackgroundAfter the Chernobyl accident on 26 April 1986, a drop in birth-rate was found in several European countries in the first quarter of 1987. The objective of the present study was to investigate whether a similar drop in live births occurred in Japan after the Fukushima nuclear accident.Data and methodsA study region was defined consisting of Fukushima prefecture plus 10 nearby prefectures. The observed monthly numbers of live births (LB) in October 2011 through December 2012 were compared with the predicted numbers determined from the trend of live births in the remaining months from January 2006 through December 2018. The study region was divided into Fukushima plus three adjacent prefectures (Area A, assumed effective mean dose in the first year 1 mSv) and seven surrounding prefectures (Area B, 0.5 mSv). The rest of Japan (Area C) served as the comparison (control) region (0.1 mSv). A combined regression of live births (LB) in areas A, B, C was conducted with individual trend parameters but common parameters for monthly variations.ResultsIn the study region as a whole (areas A and B combined) a highly significant 9.1% (95% CI: -12.2%, -6.0%) drop in LB was found in December 2011. Reduced numbers of live births were also observed in October-November 2011 (-3.3%, p = 0.006), i.e. in births exposed early in pregnancy. In the second quarter of 2012, i.e. in live births conceived more than 3 months after the Fukushima accident, the decrease was greater (-4.3%, p < 0.001) than in the first quarter (-1.6%, p = 0.11). i.e. in those conceived within the first three months after the accident while no significant decrease was detected in the third (-0.7%, p = 0.44) and fourth (-0.5%, p = 0.62) quarters. The effect in Dec 2011 was greater in Area A with -14.0 (-17.6, -10.3) % than in Area B with -7.8 (-11.1, -4.5) % and non-significant in Area C with -1.3 (-4.2, +1.6) %, p = 0.38. The combined regression of the data in areas A, B, and C found a highly significant association of the effect in December 2011 with radiation dose. Conclusion: It is suggested that the observed drop in LB in December 2011 may reflect early deaths of the conceptus from high radiation exposure following the triple meltdown at the Fukushima Daiichi nuclear power plant on March 12–15, 2011.

Nationwide survey of late-onset hemolysis in very low birthweight infants.

BackgroundIn Japan, some cases of late‐onset acute hemolysis in very low birthweight (VLBW) infants have been reported. These cases had common features but the cause of hemolysis was unknown. The incidence and prognosis of this disease are also unknown. However, there are only few reports of such hemolytic episodes in countries other than Japan. Thus, this study aimed to examine the incidence and clinical course of late‐onset acute hemolysis and to establish it as a new disease concept.MethodsA nationwide prospective survey was conducted from 2011 to 2015 as a rare disease surveillance project of the Japan Society for Neonatal Health and Development.ResultsTwenty‐four cases were confirmed. The median (range) gestational age, birthweight, and onset of hemolytic episodes were 26 weeks and 2 days (23 weeks and 4 days–31 weeks and 2 days), 898 g (627–1,416 g), and 19 days after birth (9–33 days), respectively. Phototherapy, blood transfusion, and exchange transfusion were required in 22 (96%), 24 (100%), and 7 (29%) cases, respectively. During the observation period, no recurrence of the hemolytic episode occurred. All patients survived; however, one case developed kernicterus and suffered severe neurological sequelae.ConclusionsIn this study, at least 1 out of 1,259 VLBW infants developed hemolysis at 9–33 days after birth in Japan. Owing to the risk of kernicterus, this disease should be recognized as among the important pathological conditions of VLBW infants, suggesting the need to manage jaundice and anemia until 5 weeks after birth.