Hideoki Fukuoka

Low birthweight and subsequent obesity in Japan

The Lancets World Report (Feb 10, p 451)1 rightly highlights the growing epidemic of obesity in Japan—a pattern that is also seen in other Asian countries and which might be of concern for future patterns of disease, given that susceptibility to the metabolic consequences of obesity seems to be higher in some Asian populations. There can be no doubt that this increasing prevalence of obesity is driven by changing patterns of nutrition and exercise, but there might also be other factors worthy of consideration. We have suggested that a mismatch between intrauterine constraint, arising from small maternal stature and suboptimum fetal nutrition, and a nutritionally rich postnatal environment might explain the high levels of metabolic compromise seen in some developing populations.2 Observations of social trends in Japan suggest that such a mismatch might also occur there. In Japan, birthweight has fallen rapidly (figure).3 and 4 This has been associated with a reduction in family size, increased maternal smoking, decreased maternal prepregnancy body-mass index resulting from dieting, and aggressive management of weight gain in pregnancy (mean weight gain in pregnancy has fallen by 2 kg in the past two decades, largely as a result of a zealous and unsupported obstetric belief that reduced weight gain is protective against pre-eclampsia5). The reduction in birthweight of more than 150 g represents a significant increase in maternal constraint and much reduced fetal nutrition. Thus if the developmental mismatch pathway has a role in the development of obesity in childhood and increases the risk of metabolic compromise,2 PD Gluckman and MA Hanson, Living with the past: evolution, development, and patterns of disease, Science 305(2004), pp. 1733–1736. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (282)2 then the developmental component is another factor in Japans obesity epidemic and a further point for intervention. Japans next 10-year public-health plans might have to include nutritional recommendations for pregnant women.

Risk factors for small for gestational age

Background: The purpose of the paper was to determine the risk factors for small‐for‐gestational‐age (SGA) infants at full term, in Japan.

Risk factors for term small for gestational age infants in women with low prepregnancy body mass index

Aim:  The purpose of our study was to investigate the association between low maternal prepregnancy body mass index (BMI) less than 18.5 kg/m2 and the incidence of small for gestational age (SGA) infants.

Maternal antenatal body mass index gains as predictors of large-for-gestational-age infants and cesarean deliveries in Japanese singleton pregnancies

Aim:  Greater antenatal weight or body mass index (BMI) gains may lead to larger fetuses and thus increase the risk for operative deliveries, such as cesarean deliveries. In order to examine the effect of weekly maternal weight and BMI changes on large‐for‐gestational‐age (LGA) infants and cesarean delivery, delivery records from overall healthy women were analyzed.

Metabolomics analysis of umbilical cord blood clarifies changes in saccharides associated with delivery method

BACKGROUND A metabolomic approach using umbilical cord blood from infants at birth has not been studied widely yet. AIM We examined changes in metabolite levels in umbilical cord blood at birth via gas chromatography/mass spectrometry (GC/MS)-based metabolomics, with the aim of achieving a detailed understanding of fetal stress during labor. STUDY DESIGN All procedures were reviewed and approved by the Institutional Review Board of Kobe University School of Medicine. This was a cohort study of pregnant women based in Palmore Hospital, which is located in an urban area of Japan, and was carried out between December 2010 and May 2011. SUBJECT Umbilical cord arterial blood samples were obtained from 41 infants immediately after delivery. OUTCOME MEASURES Metabolites in the blood samples were measured using GC/MS to investigate whether the delivery method (spontaneous onset of labor, induction of labor or elective cesarean section) affected the metabolite profile in umbilical cord blood. RESULTS Elective cesarean section without labor led to lower levels of isoleucine, fructose, mannose, glucose, allose, glucuronic acid, inositol and cysteine in comparison with vaginal delivery following spontaneous labor and without medication. CONCLUSION It is proposed that the stress associated with labor be involved in alterations in the levels of metabolites, particularly saccharides such as glucose, in umbilical cord blood.

Chiba study of Mother and Children's Health (C-MACH): cohort study with omics analyses

Purpose Recent epidemiological studies have shown that environmental factors during the fetal period to early childhood might affect the risk of non-communicable diseases in adulthood. This is referred to as the developmental origins of health and disease (DOHaD) concept. The Chiba study of Mother and Childrens Health (C-MACH) is a birth cohort study based on the DOHaD hypothesis and involves multiomics analysis. This study aims to explore the effects of genetic and environmental factors—particularly the fetal environment and postbirth living environment—on childrens health, and to identify potential biomarkers for these effects. Participants The C-MACH consists of three hospital-based cohorts. The study participants are pregnant women at <13 weeks gestation. Women who underwent an examination in one of the three hospitals received an explanation of the study. The participants consented to completing questionnaire surveys and the collection and storage of biological and house/environmental samples. Participants were provided unique study numbers. All of the data and biological specimens will be stored in the Chiba University Center for Preventive Medical Sciences and Chiba University Center for Preventive Medical Sciences BioBank, respectively. Findings to date Consent to participate was obtained from 433 women. Of these women, 376 women completed questionnaires in the early gestational period. The mean age was 32.5 (4.4) years. The mean body mass index (BMI) was 21.1 (3.0) kg/m2. Before pregnancy, 72.3% of the women had a BMI of 18.5–24.9 kg/m2. During early pregnancy, 5.0% of the participants smoked. Future plans Primary outcomes are allergy, obesity, endocrine and metabolic disorders, and developmental disorders. Genome-level, metabolome-level, umbilical cord DNA methylation (epigenome), gut microbiota and environmental chemical exposure variables will be evaluated. We will analyse the relationships between the outcomes and analytical variables.

Management of obesity in pregnancy

Maternal pregravid obesity is associated with adverse outcomes in pregnancy. There are many complications by maternal obesity during pregnancy, such as spontaneous abortion, congenital malformations, gestational hypertention, preeclampsia, gestational diabetes mellitus, fetal macrosomia, and so on. Also, at parturition, the prevalence of cesarean section and associated complications such as deep vein thrombosis, wound disruption, and infection increase. Further- more, offspring of obese women increases the risk of adolescent components of the metabolic syndrome. To improve short- and long-term adverse outcome associated with obese pregnant women, we need to encourage obese women to lose body weight before pregnancy. During pregnancy, weight gain should be limited to Institute of Medicine guidelines.

DOHaD (developmental origins of health and disease) and birth cohort research

Epidemiological and animal experimental studies are disclosing that the malnutrition or overnutrition in utero would induce epigenetic changes of fetus, what is the origin of lifestyle-related disease in adult. Representative birth cohorts studies in DOHaD are explained.

The methylation levels of the H19 differentially methylated region in human umbilical cords reflect newborn parameters and changes by maternal environmental factors during early pregnancy

Abstract H19 is a tumor‐suppressor gene, and changes in the methylation of the H19‐differential methylation region (H19‐DMR) are related to human health. However, little is known about the factors that regulate the methylation levels of H19‐DMR. Several recent studies have shown that maternal environmental factors during pregnancy, such as smoking, drinking, chemical exposure, and nutrient intake, can alter the methylation levels of several genes in fetal tissues. In this study, we examined the effects of maternal factors on changes in the methylation levels of H19‐DMR in the human umbilical cord (UC), an extra‐embryonic tissue. Participants from the Chiba study of Mother and Childrens Health (C‐MACH) were enrolled in this study. Genomic DNA was extracted from UC samples, and the methylation level of H19‐DMR was evaluated by methylation‐sensitive high resolution melting analysis. Individual maternal and paternal factors and clinical information for newborns at birth were examined using questionnaires prepared in the C‐MACH study, a brief‐type self‐administered diet history questionnaire (BDHQ) during early pregnancy (gestational age of 12 weeks), and medical records. Univariate and multivariate logistic regression analyses indicated that reduced H19‐DMR methylation (<50% methylation) in UC tissues was positively related to decreased head circumference in newborns [odds ratio (OR) =2.82; 95% confidence intervals (CI): 1.21–6.87; p=0.0183 and OR =2.51; 95% CI: 1.02–6.46; p=0.0499, respectively]. Moreover, multiple comparison test showed that H19‐DMR methylation in UC tissues was significantly reduced in the low calorie group (intake of less than 1,000 kcal/day; methylation level: 40.98%; 95% CI: 33.86–48.11) compared with that in the middle (1,000–1,999 kcal/day; methylation level: 51.28%; 95% CI: 48.28–54.27) and high (≥2,000 kcal/day; methylation level: 52.16%; 95% CI: 44.81–59.51) calorie groups (p=0.0054 and 0.047, respectively). In the subpopulations with low to moderate calorie intake (<2,000 kcal/day), reduced H19‐DMR methylation in UC tissues was significantly related to serum homocysteine concentration (OR =0.520; 95% CI: 0.285–0.875; p=0.019), maternal age (OR =1.22; 95% CI: 1.01–1.52; p=0.049), and serum folate levels (OR =0.917; 95% CI: 0.838–0.990; p=0.040). These data indicated that H19‐DMR methylation levels in human UC tissues could be modulated by maternal factors during early pregnancy and may affect fetal and newborn growth. HighlightsWe examined the effect of maternal factors on H19‐DMR methylation in umbilical cords (UC).Reduced H19‐DMR methylation in UCs was related to decreased head circumference.H19‐DMR methylation in UCs was reduced in the low calorie group.Decreased serum folate levels were associated with lower H19‐DMR methylation in UCs.H19‐DMR methylation in UCs could be modulated by maternal factors during pregnancy.

Folate Status and Depressive Symptoms in Reproductive-Age Women

Folate is a water-soluble B-vitamin necessary for the proper biosynthesis of the monoamine neurotransmitters serotonin, epinephrine, and dopamine. Epidemiological and biological evidence suggests that low folate appears to be most closely linked to depressive disorders among individuals with epilepsy, people suffering from neurological and psychiatric problems, as well as the elderly. Folic acid influences the rate of synthesis of the neurotransmitters dopamine, norepinephrine, and serotonin and acts as a cofactor in the hydroxylation of phenylalanine and tryptophan. A disturbance of biogenic amine metabolism may lead to various psychiatric disorders. Folic acid deficiency may contribute to pathogenesis of neuropsychiatric disorders such as mental confusion, memory changes, cognitive slowing, and mood disorder. However, since almost all published studies have been conducted with the elderly or with persons with dementia disease, the effects of folate on the mental health of people of reproductive age are not yet known. Findings from this review suggest that low folate status can be a key factor in the expression of depressive symptoms. However, it is difficult to evaluate whether folate deficiency is a substantial contributor to depressive symptoms in reproductive-age women in scan data compared to the numerous data for older women. A critical goal is for women to make behavior changes for good nutritional status before, during, and beyond pregnancy, as this may lead to improved mental and physical health in later life for both themselves and their family members.