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Background Low birth weight (LBW) and fetal growth restriction are associated with the development of cardio-metabolic diseases later in life. A recent Mendelian randomization study concluded that the susceptibility of LBW infants to develop hypertension during adulthood is due to the inheritance of hypertension genes from the mother and not to an unfavorable intrauterine environment. Therein, a negative linear association has been assumed between genetically estimated maternal blood pressure (BP) and birth weight, while the observed relationship between maternal BP and birth weight is substantially different from that assumption. As many hypertension genes are likely involved in vasculature development and function, we hypothesized that BP-increasing genetic variants could affect birth weight by reducing the growth of the placenta, a highly vascular organ, without overtly elevating the maternal BP. Methods Using a birth cohort in the Japanese population possessing time-series fetal growth velocity data as a target and a GWAS summary statistics of BioBank Japan as a base data, we performed polygenic score (PGS) analyses for systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure. A causal mediation analysis was performed to assess the meditation effect of placental weight on birth weight reduced by maternal BP-increasing PGS. Maternal genetic risk score constituted of only “vasculature-related” BP single nucleotide polymorphisms (SNPs) was constructed to examine the involvement of vascular genes in the mediation effect of placental weight. We identified gestational week in which maternal SBP-increasing PGS significantly decreased fetal growth velocity. Results We observed that maternal SBP-increasing PGS was negatively associated with offspring birth weight. A causal mediation analysis revealed that a large proportion of the total maternal PGS effect on birth weight was mediated by placental weight. The placental mediation effect was remarkable when genetic risk score was constituted of “vasculature-related” BP SNPs. The inverse association between maternal SBP PGS and fetal growth velocity only became apparent in late gestation. Conclusions Our study suggests that maternal hypertension genes are strongly associated with placental growth and that fetal growth inhibition is induced through the intrauterine environment established by the placenta.

The maternal diet can potentially influence the life-course health of the child. A poor-quality maternal diet creates nutrient deficiencies and affects immune–metabolic regulation during pregnancy. The nutrient-based overall dietary quality can be assessed using the Nutrient-Rich Food Index 9.3 (NRF9.3), which measures adherence to the national reference daily values of nutrient intake. Pro- and anti-inflammatory nutrient intake can be assessed using the energy-adjusted dietary inflammatory index (E-DII), a comprehensive index of diet-derived inflammatory capacity. Using these indices, we assessed the overall dietary quality and inflammatory potential of pregnant women during mid-gestation in an urban area of Japan (n = 108) and found that there was a strong inverse correlation between the NRF9.3 and E-DII scores. Comparison of the scores among the tertiles of NRF9.3 or E-DII indicated that dietary fiber, vitamin C, vitamin A, and magnesium mainly contributed to the variability of both indices. Intake of vegetables and fruits was positively associated with high NRF9.3 scores and negatively associated with high E-DII scores, after adjustment for maternal age, pre-pregnancy body mass index, and educational level. Consistent with the previous studies that used dietary pattern analysis, this study also demonstrated that vegetables and fruits were the food groups chiefly associated with high dietary quality and low inflammatory potential among pregnant Japanese women.

Low birth weight is associated with the development of cardio-metabolic diseases later in life1-4. A recent Mendelian Randomization Study concluded that the susceptibility of low-birth-weight infants to develop hypertension during adulthood is due to the inheritance of hypertension genes from the mother, and not to an unfavorable intrauterine environment5. Therein, it has been assumed that low birth weight is caused by maternal hypertension5,6, although there is no evidence to support such a linear relationship. In the present study, we have noted that most of blood pressure SNPs are related to vascular regulation7-9 and found that the relationship between maternal blood pressure-increasing polygenic score and reduction of offspring birth weight is mediated by a reduced growth of the placenta but not by the mother's high blood pressure. This suggests that the risk of hypertension of low-birth-weight infants may result from a poor placental environment.

Placenta-derived extracellular vesicles and their cargoes, especially microRNAs (EV-miRNAs), may contribute to fetal and placental development. During pregnancy, the levels of several maternal blood EV-miRNAs, including miRNAs of placental origin, vary among individuals and change throughout gestation. However, the effects of these miRNAs on fetal growth and trimester-specificity have not been fully elucidated. The purpose of this study is to test the hypothesis that the serum levels of two extracellular vesicles (EV)-miRNAs (miR-127-3p and miR-26b-5p), which may be involved in fetoplacental regulation, would be significantly associated with fetal growth in a trimester-specific manner. This is a single-center birth cohort of maternal serum samples obtained at both the second and third trimesters. To minimize the influence of confounding factors, the analysis was limited to singleton vaginal deliveries, resulting in 27 participants being included in this study. EV RNAs were isolated using a membrane affinity method, and the relative expression levels of miR-127-3p and miR-26b-5p were measured using the RT-qPCR method with miR-484 as control. The associations between the two EV-miRNAs and fetal and placental growth were evaluated using a linear regression model and compared between the two trimesters. EV-miR-127-3p levels tended to correlate inversely with the z-scores of birth weight for gestational age (BWGA) and placental weight for gestational age (PWGA) in the second trimester, but not in the third trimester. EV-miR-26b-5p levels were positively associated with birth weight in the second trimester, but this association was weakened in the third trimester. Our results suggest a trimester-specific association of circulating miRNA levels with fetal and placental growth. The precise roles of EV-miR-127-3p and EV-miR-26b-5p in fetal and placental development warrant further investigation.

Objective:To examine 44-year trends in height, weight and BMI, and the prevalence of overweight/obesity and underweight in the elderly Japanese population because Japan, the country with the longest life expectancy, has the highest ageing population.Design:Using the nationally representative cumulative data from the Japan National Health and Nutrition Survey 1973–2016, sex-specific and age-adjusted mean height, weight and BMI, and the prevalence of overweight/obesity and underweight were calculated for each year. Trend analyses were performed using the Joinpoint Regression Program. Next, changes in height, weight and BMI, and the prevalence of overweight/obesity and underweight were estimated for each age group (65–69, 70–79 and >80 years) according to the birth year groups.Setting:Japan.Participants:Individuals aged ≥65 years with complete data on height and body weight measurements (N 94 508).Results:Trends in average height and weight increased over the four decades in both men and women. The prevalence of overweight/obesity dramatically increased and nearly tripled in men, accompanied with significantly decreased underweight prevalence. Furthermore, the increasing trend in average BMI and overweight/obesity prevalence in women reached a peak in 2002 and showed a decreasing trend thereafter, while a downward trend in underweight prevalence showed a gradual increase in women since 2003.Conclusions:Trends in height, weight and BMI among the elderly population should continue to be closely monitored in parallel with the effects of dietary changes, energy intake and physical activity (step counts).

Consumption of dairy products in the usual diet may be important for improving the overall quality of dietary intake. This study aimed to assess the difference in nutrient intake adequacy according to the intake of dairy products based on a 1-day weighed dietary record of Japanese adults from the 2016 National Health and Nutrition Survey. Nutritional adequacy was determined based on the Dietary Reference Intakes for Japanese 2015, with 2 goals: Tentative dietary goals (DG) for preventing lifestyle-related diseases, and the estimated average requirement (EAR). According to the dairy products consumption, participants were categorized into three groups (milk, other dairy product, or non-dairy), and the total number of those not meeting DG and EAR was compared. Non-dairy consumers were less likely to meet both DG and EAR compared to dairy consumers. Dairy consumers were more likely to exceed the DG for saturated fat than non-dairy consumers. Japanese adult dairy consumers were more likely to have adequate nutritional intake than non-dairy consumers, especially for calcium. We also observed a higher saturated fat intake in dairy consumers, which might be due to a certain dietary pattern in this group. Further investigation is needed to determine dairy intake and its influence on dietary quality among the Japanese population.

Mid-to-late gestation is a unique period in which women experience dynamic changes in lipid metabolism. Although the recent intensive epigenome-wide association studies (EWAS) using peripheral leukocytes have revealed that lipid-related traits alter DNA methylation, the influence of pregnancy-induced metabolic changes on the methylation levels of these differentially methylated sites is not well known. In this study, we performed a prospective cohort study of pregnant women (n = 52) using the MassARRAY EpiTYPER assay and analyzed the methylation levels of variably methylated sites, including CPT1A intron 1 and SREBF1 intron 1 CpGs, which were previously verified to be robustly associated with adiposity traits. Although methylation of SREBF1 was associated with body mass index (BMI) and low-density lipoprotein cholesterol at mid-gestation, this association was attenuated at late gestation, which was consistent with the metabolic switch from an anabolic to a catabolic state. However, the BMI association with CPT1A intron 1 methylation appeared to strengthen at late gestation, this association was mediated by pre-pregnancy BMI-dependent change in the leukocyte proportion during mid-to-late gestation. Thus, the methylation of adiposity-related differentially methylated regions was sensitive to metabolic and immunological changes during mid-to-late gestation.