Low serum carnitine level is associated with increased urinary carnitine excretion in late pregnancy.

BACKGROUND: Carnitine is essential for fatty acid metabolism. Free carnitine (FCA) is excreted in the urine in the glomerulus, but is partly reabsorbed by a carnitine transporter. The mechanism underlying the decrease in serum carnitine level during pregnancy is unclear. OBJECTIVE: To investigate whether low carnitine level is associated with increased renal excretion in pregnant women. METHODS: We recruited 43 healthy pregnant and 25 non-pregnant women. Total carnitine (TCA) and FCA levels were measured using the enzymatic cycling method, and the acylcarnitine (ACA) level was calculated. Fractional excretion (FE) was calculated as carnitine clearance divided by creatinine clearance. RESULTS: The mean TCA, FCA, and ACA levels were lower at 12 weeks of gestation in pregnant than non-pregnant women (P < .001); the levels decreased further at 36 weeks, reaching 39%, 36%, and 52% of those in non-pregnant women, respectively (P < .001). The FEs were 3-4-fold higher in pregnant women than non-pregnant women. Pregnant women had a lower serum FCA/TCA ratio than non-pregnant women (0.788 ± 0.098 vs 0.830 ± 0.074, respectively; P < .05), whereas the urine FCA/TCA ratio was similar between the groups. CONCLUSION: Low carnitine level is associated with increased renal excretion during late pregnancy.

Lipoprotein lipase concentration in umbilical cord blood reflects neonatal birth weight.

BACKGROUND: Insulin resistance (IR) is exacerbated during pregnancy via increases in insulin counterregulatory hormones. Maternal lipids are strong determinants of neonatal growth, although triglyceride-rich lipoproteins (TGRLs) cannot be transferred directly to the fetus through the placenta. The catabolism of TGRLs under physiological IR and the reduced synthesis of lipoprotein lipase (LPL) are poorly understood. We examined the association of maternal and umbilical cord blood (UCB)-LPL concentrations with maternal metabolic parameters and fetal development. METHODS: Changes in anthropometric measures and lipid-, glucose-, and insulin-related parameters, including maternal and UCB-LPL concentrations, were examined in 69 women during pregnancy. The relationship between those parameters and neonatal birth weight was assessed. RESULTS: Parameters reflecting glucose metabolism did not change during pregnancy, whereas those associated with lipid metabolism and IR changed markedly, particularly in the second and third trimesters. In the third trimester, the maternal LPL concentration gradually decreased, by 54%, whereas the UCB-LPL concentration was âˆ¼2-fold higher than the maternal LPL concentration. Univariate and multivariate analyses showed that the UCB-LPL concentration was a significant determinant of neonatal birth weight, together with placental birth weight. CONCLUSION: The LPL concentration in UCB reflects neonatal development under a decreased LPL concentration in maternal serum.

For making a declaration of countermeasures against the falling birth rate from the Japanese Society for Hygiene: summary of discussion in the working group on academic research strategy against an aging society with low birth rate.

In 1952, the Japanese Society for Hygiene had once passed a resolution at its 22nd symposium on population control, recommending the suppression of population growth based on the idea of cultivating a healthier population in the area of eugenics. Over half a century has now passed since this recommendation; Japan is witnessing an aging of the population (it is estimated that over 65-year-olds made up 27.7% of the population in 2017) and a decline in the birth rate (total fertility rate 1.43 births per woman in 2017) at a rate that is unparalleled in the world; Japan is faced with a "super-aging" society with low birth rate. In 2017, the Society passed a resolution to encourage all scientists to engage in academic researches to address the issue of the declining birth rate that Japan is currently facing. In this commentary, the Society hereby declares that the entire text of the 1952 proposal is revoked and the ideas relating to eugenics is rejected. Since the Society has set up a working group on the issue in 2016, there have been three symposiums, and working group committee members began publishing a series of articles in the Society's Japanese language journal. This commentary primarily provides an overview of the findings from the published articles, which will form the scientific basis for the Society's declaration. The areas we covered here included the following: (1) improving the social and work environment to balance between the personal and professional life; (2) proactive education on reproductive health; (3) children's health begins with nutritional management in women of reproductive age; (4) workplace environment and occupational health; (5) workplace measures to counter the declining birth rate; (6) research into the effect of environmental chemicals on sexual maturity, reproductive function, and the children of next generation; and (7) comprehensive research into the relationship among contemporary society, parental stress, and healthy child-rearing. Based on the seven topics, we will set out a declaration to address Japan's aging society with low birth rate.

[Historical Transition of Sexuality Education in Japan and Outline of Reproductive Health/Rights].

In this paper, we describe the historical transition of sexuality education in Japan and the direction of sexuality education taken by the Ministry of Education, Culture, Sports, Science and Technology (MEXT). Reproductive health/rights, a key concept in sex education, is also discussed. In Japanese society, discussion on sexuality has long been considered taboo. After the Second World War, sexuality education in Japan began as "purity education." From 1960 until the early 1970s, physical aspects such as genital organs, function, secondary sexual characteristics, and gender differences were emphasized. Comprehensive education as a human being, including physiological, psychological, and social aspects, began to be adopted in the late 1970s. In 2002, it was criticized that teaching genital terms at primary schools and teaching about sexual intercourse and contraceptive methods at junior high schools were "overdue guidance" and "extreme contents." Sexuality education in schools has become a problem and has stagnated for about 10 years. Currently, schools teach sexuality education that does not deviate from the MEXT course guidelines. The direction of MEXT regarding sexuality education should be examined from the basic position that sexual activity by children is inappropriate. Reproductive health/rights apply the concept of human rights to sexuality and reproduction. Reproductive health/rights are key concepts that support sex education and women's health.

[Trends in Research on Adolescent Sexuality Education, Fertility Awareness, and the Possibility of Life Planning Based on Reproductive Health Education].

In this paper, we describe the trends in research on adolescent sexuality education in Japan and other countries and on fertility awareness, as well as the possibility of life planning based on sex and reproductive health education. Mason-Jones AJ et al. reviewed the results of school-based intervention studies on the prevention of human immunodeficiency virus infection, sexually transmitted diseases, and pregnancy. There is little evidence supporting the idea that educational curriculum-based programs alone are effective in improving sex and reproductive health outcomes in adolescents. In another study, the effectiveness of school-based sexuality education for adolescents in Japan was evaluated. The Japan Medical Abstract Society was searched for articles published in the last 10 years. In many studies, the effects were compared before and after a single sexuality education lecture by professionals, such as doctors, midwives, and public health nurses. In Japan, effort has been directed toward sexuality education, but no systematic program based on behavior theory has been adopted. Therefore, sex education is insufficient. A third study clarified research on fertility awareness in adults and issues regarding improvements in related education and research. The Japan Medical Abstract Society and PubMed were searched for articles published in the last 10 years. The review suggested that awareness of female fertility is insufficient. Delaying childbearing based on inaccurate knowledge of the decline in female fertility could lead to unintended infertility. For males and females, sexual health education in schools and communities should include information on the age-related decline in female fertility. Although the determinants of the timing of childbearing are multifactorial, education on fertility issues is necessary to help adults make informed reproductive decisions based on accurate information. Finally, in this paper, we introduce examples of the pioneering efforts in sexual health education through collaboration between the governments of Oita and Okayama Prefectures and Oita and Okayama Universities.

[Effects of Trace Environmental Chemicals on Child Health-Lead as an Example].

The low birthrate and aging population of Japan are entering a serious phase. As measures against the declining birthrate, improvement of the environment is promoted to support childbirth and child-rearing, but even if the birthrate increases in the future, it will take time before the effect is observed as an increase in the population. As the number of children and young people is decreasing, in order to maintain a wealthy and sustainable society, we should create an environment wherein each child can grow healthily and demonstrate sufficient abilities in participating in society. The authors have been studying the influence of exposure to environmental chemical substances on the development of children. Lead is especially considered to impair neurological development even at low concentrations of exposure. In this paper, using lead as an example, we discuss risk assessment and countermeasures for the health effects of trace chemical substances on a society with a declining birthrate. Substances that show neurotoxicity increase social costs even at low concentrations of exposure. To preserve and promote social vitality in Japan despite the declining birthrate and aging population, it is essential that measures are taken on the basis of scientifically reasonable cost/benefit assessment. For this purpose, we think that it is necessary to analyze costs and benefits in addition to the risk assessment of low concentrations of chemical substances.

Prenatal mercury exposure and birth weight.

Adverse effects of prenatal mercury exposure on pregnancy outcomes remain a public health concern. We assessed the relationship between prenatal mercury exposure and newborn anthropometric characteristics in 334 mother-child pairs from the early stages of pregnancy to delivery in Tokyo, Japan, between December 2010 and October 2012. We found a negative correlation between blood mercury levels during the first and second trimesters of gestation and birth weight (r = -0.134 and -0.119, respectively; p < 0.05). Multiple linear regression analysis confirmed the relationship between first-trimester maternal blood mercury levels and birth weight when adjusted for independent variables (ß = -0.170, t = -2.762; p = 0.006). Mean mercury levels in umbilical cord blood were twice as high as maternal blood levels (10.15 ±â€¯7.74 and 4.97 ±â€¯3.25 µg/L, respectively; r = 0.974, p < 0.001). Our findings suggest that pregnant women and women of reproductive age should avoid mercury exposure, even at low levels, because of its potentially adverse effects on fetal development.

Increased prenatal blood manganese may induce gestational blood pressure.

OBJECTIVE: Pregnancy hypertension is the most common gestational complication and poses a critical risk for mother and fetus. Whether environmental factors may play an important role in disease occurrence is not fully determined. METHODS: To investigate the effects of prenatal manganese (Mn) exposure on gestational blood pressure, 386 women were examined. RESULTS: Early pregnancy blood Mn was significantly (p < 0.05) correlated with blood pressure through gestation. A significant association between odds of pre-hypertension with blood Mn was shown (OR:1.150, 95% CI:1.052-1.258). CONCLUSION: The current study results might suggest the blood Mn level during early stage of pregnancy as a potential risk factor for increasing the risk of gestational blood pressure.

Relationship between maternal thyroid-stimulating hormone (TSH) elevation during pregnancy and low birth weight: a longitudinal study of apparently healthy urban Japanese women at very low risk.

OBJECTIVE: Thyroid hormones cross the placenta and promote fetal development and growth. The present study investigated whether an increase in maternal thyroid-stimulating hormone (TSH) concentration between the first and third trimesters is a determinant of birth weight during normal pregnancy. METHODS: Maternal thyroid hormones and TSH were longitudinally measured at 12, 25, and 36weeks of pregnancy in 163 healthy pregnant women. Low birth weight (LBW) was defined as less than 2500g. ∆TSH12-36W was calculated as the difference in TSH concentrations between 12 and 36weeks of pregnancy. RESULTS: Of the 163 neonates, 10 (6.1%) were LBW neonates. Free triiodothyronine and free thyroxine levels were similar at all gestational ages in the normal birth weight (Normal) and LBW groups. However, the median ∆TSH12-36W value was higher in the LBW than the Normal group (1.67 vs. 0.54mIU/L, P=0.008). Multivariate linear regression analysis showed that ∆TSH12-36 was inversely correlated with birth weight (ß=-0.179, P=0.008). CONCLUSION: An increase in maternal TSH concentration between the first and third trimesters is an independent determinant of birth weight in normal pregnancy.

Evidence that birth weight is decreased by maternal lead levels below 5µg/dl in male newborns.

To assess the association between birth weight and maternal blood lead (BPb) levels, 386 pregnant women and their newborn offspring were surveyed. Mean±SD (range) maternal BPb concentrations were 0.98±0.55 (0.10-3.99), 0.92±0.63 [<0.09 (limit of quantification)-3.96], and 0.99±0.66 (<0.09-3.96)µg/dl at 12, 25 and 36 weeks' gestation, respectively. Mean±SD (range) gestational age at delivery was 38.9±1.3 (35-41) weeks. In male newborns, a significant correlation between birth weight and logBPb at 12 weeks' gestation was observed (Spearman's rank correlation coefficient=-0.145, p<0.05). Multiple regression analysis indicated that birth weight was significantly inversely associated with logBPb at 12 weeks' gestation, controlling for possible confounding variables. These results suggest that low-level exposure to lead in early gestation could be a risk factor for reduced birth weight in male offspring.

Ezetimibe decreases serum oxidized cholesterol without impairing bile acid synthesis in Japanese hypercholesterolemic patients.

OBJECTIVE: Cholesterol and diet-derived oxidized cholesterol are absorbed in the small intestine and eliminated by bile acids. We determined whether ezetimibe, a selective cholesterol absorption inhibitor, changes serum oxidized cholesterol levels. METHODS: We measured levels of plant sterols, cholesterol precursors, and oxysterols by gas chromatography-mass spectrometry in 47 hypercholesterolemics and 32 controls. Twenty-four hypercholesterolemics received 10 mg ezetimibe/day for 4 weeks. RESULTS: Plant sterols were 30-42% higher in hypercholesterolemics than in controls and positively correlated with low-density lipoprotein-cholesterol (LDL-C). Ezetimibe decreased plant sterols by 21-53%, but did not change bile acid synthesis markers. 7ß-hydroxycholesterol, a marker for non-enzymatic oxidation of cholesterol, was 66% higher in hypercholesterolemics than controls. Ezetimibe decreased 7ß-hydroxycholesterol levels by 15% regardless of LDL-C reduction. CONCLUSIONS: Ezetimibe decreases serum oxidized cholesterol generated by non-enzymatic reactions without impairing bile acid synthesis. Ezetimibe may maintain cholesterol excretion into bile and alleviate the diet-derived oxidative burden.

Albumin concentration determined by the modified bromocresol purple method is superior to that by the bromocresol green method for assessing nutritional status in malnourished patients with inflammation.

BACKGROUND: The controlling nutritional status (CONUT) score (CS), a simple score for assessing nutritional status, is calculated using laboratory data, including serum albumin concentration. Although dye-binding assays such as the bromocresol green (BCG) and modified bromocresol purple (mBCP) methods are widely used for albumin measurement, acute-phase proteins interfere with the BCG method. OBJECTIVE: We aimed to determine whether the choice of albumin assay affects assessment of nutritional status using CONUT scores (CSs). DESIGN: We measured serum albumin concentrations by the BCG (ALBBCG) and mBCP (ALBmBCP) methods in 44 malnourished inpatients, 27 of whom underwent nutritional intervention, and compared them to 30 age-matched healthy volunteers. In treated patients, CSs were calculated by ALBBCG (CS-BCG) and ALBmBCP (CS-mBCP). RESULTS: C-reactive protein (CRP) concentrations were positively correlated with the difference between ALBBCG and ALBmBCP in malnourished inpatients (r = 0.59, p < 0.001). CS-BCG was always lower than CS-mBCP (lower CS indicates superior nutritional status) in treated patients with persistently high CRP levels. However, in patients whose CRP decreased gradually, this difference diminished over the clinical course. CS-BCG and CS-mBCP were similar throughout their courses in patients with normal CRP concentrations. Adding haptoglobin to the human albumin solutions increased ALBBCG in a dose-dependent manner. CONCLUSIONS: The choice of albumin assay affected the assessment of nutritional status using CSs in patients with inflammation. We recommend that the modified BCP assay be used to assess nutritional status, particularly in patients with inflammation.

A prospective study of the relationship between breastfeeding and postpartum depressive symptoms appearing at 1-5 months after delivery.

Despite the fact that more than 90% of mothers in Japan prefer breastfeeding, the breastfeeding rate at 6 months postpartum is as low as approximately 35%. Postpartum depression and bonding disorder are recognized as factors associated with discontinuation of breastfeeding. However, these factors remain controversial. The purpose of the present study was to clarify the effect of postpartum depressive symptoms and bonding on the feeding pattern from 1- to 5-month postpartum. A longitudinal study was conducted at 1- and at 5-month postpartum, in 405 mothers who attended health check at three hospitals in the Tokyo metropolitan area at 1-month postpartum, and completed longitudinal questionnaires. A high proportion of breastfeeding mothers at 1 month postpartum had Edinburgh Postpartum Depression Scale (EPDS) score of ≥ 9 at 5 months postpartum (p=0.01), and these mothers changed to formula milk-based feeding at 5-month postpartum, when compared with those of the breastfeeding-based group at both 1- and 5-month postpartum,. The appearance of depressive symptoms seems to promote discontinuation of breastfeeding at 5-month postpartum.