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bunya/kenkou/kenkou_eiyou_chousa.html [accessed July 28, 2021] (in Japanese)], the percentage of women in their 20s who were thin (BMI < 18.5 kg/m2) was 12-15% in the early 1980s, but later started rising, reaching to 29.0% in 2010. In recent years, the percentage has hovered around 20%. This trend is also observed in those in their 30s. The average age of the mother at the time of the birth of her first child was 29.2 years in 2006 and 30.7 years in 2016, an increase of 1.1-1.8 years in all prefectures. Takubo et al. reported in a nutritional survey of 135 normal pregnant women that the average daily energy intake throughout pregnancy was about 1600 kcal, which was 37% less than the recommended value by the Ministry of Health, Labour and Welfare in late pregnancy13). The epidemiological background of the increase in LBW infants in Japan has been assumed to be related to thinness in young women, followed by insufficient energy intake during pregnancy and increasing maternal age.The Relationship Between LBW and Non-communicable Disease1. EpigeneticsFetuses exposed to a low-nutrient environment in utero becomes FGR to become an LBW infant with restricted growth. At the same time, the fetuses try to adapt to the low-nutrient environ-ment after birth by adopting the situation that is favorable for survival, which is called PAR. This is supposed to be caused by acquired chemical modi-fications of genome, or epigenetic changes, that regulate the sites of gene expression9). Some animal studies suggest that diverse environmental factors during fetal life and development lead to epigenetic changes, such as DNA methylation and histone modifications, that are stored and maintained and involved in future health and disease risk14, 15). It is also supposed that FGR sacrifices the development of body size and organs in utero in order to survive in a poor nutritional environment. This abnormal response could become apparent after birth, and this response is called a trade-off16). The risk of lifestyle-related diseases in LBW infants is expected to arise on the basis of two responses: PAR and trade-off.5152. Insulin ResistanceMetabolic studies in LBW humans have demon-strated both glucose intolerance and hyperinsulin-emia17). Morrison et al. reported that extremely low birth weight (ELBW; defined as infants born weighing < 1,000 g) survivors (mean age 32 years) had a 4-fold increased risk of glucose intolerance compared with normal-onset adults18). Similarly, Hovi et al. reported that fasting serum insulin levels and the insulin resistance index were significantly higher in adults born as very low birth weight (VLBW; defined as infants born weighing < 1500 g) infants compared to full-term live birth adults4). In animal models, some studies reported that insu-lin-resistance could be associated with impaired pancreatic development, such as decreased pancre-atic β-cell mass19), β-cell secretory dysfunction20), and increased autophagy in β-cells21), but the underlying mechanism remains unclear.3. Nonalcoholic Fatty Liver DiseaseNon-alcoholic fatty liver disease (NAFLD) is a chronic liver disease in which fatty liver is present on imaging or histological diagnosis, and other liver diseases such as alcoholic liver disease have been excluded. A meta-analysis in adults estimated the prevalence of NAFLD to be 25.24% worldwide22). In Japan, the prevalence rate among adults is 41.0% and 17.7% in males and in females respectively, and 29.7% in total, with increasing trends23, 24). In addi-tion, the prevalence of pediatric NAFLD has been reported to be 7.6% in Western countries6). According to the data from Japan, the prevalence of NAFLD was 6.6% in boys, 2.0% in girls, and 4.4% overall by ultrasonography screening in elementary and junior high school students5). The prevalence of NAFLD among elementary and junior high school students in Japan is estimated to be approximately 4-5%5, 25).Newton et al. reported that children born LBW or high birth weight (HBW) had a significantly higher incidence of NAFLD than the general popu-lation of the same age at 13 years (9% vs 6% and 15% and 11%, respectively)11). Genetic predisposi-tion is also important in the development and progression of NAFLD. Genome-wide association analysis in 2008 showed that hepatic fat content of carriers of the I148M polymorphism of the patatin-like phospholipase domain containing 3 (PNPLA3) gene was more than twice that of