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One-carbon metabolism (OCM) is a complex and interconnected network that undergoes drastic changes during pregnancy. In this study, we investigated the longitudinal distribution of OCM-related metabolites in maternal and cord blood and explored their relationships. Additionally, we conducted cross-sectional analyses to examine the interrelationships among these metabolites. This study included 146 healthy pregnant women who participated in the Chiba Study of Mother and Child Health. Maternal blood samples were collected during early pregnancy, late pregnancy, and delivery, along with cord blood samples. We analyzed 18 OCM-related metabolites in serum using stable isotope dilution liquid chromatography/tandem mass spectrometry. We found that serum S-adenosylmethionine (SAM) concentrations in maternal blood remained stable throughout pregnancy. Conversely, S-adenosylhomocysteine (SAH) concentrations increased, and the total homocysteine/total cysteine ratio significantly increased with advancing gestational age. The betaine/dimethylglycine ratio was negatively correlated with total homocysteine in maternal blood for all sampling periods, and this correlation strengthened with advances in gestational age. Most OCM-related metabolites measured in this study showed significant positive correlations between maternal blood at delivery and cord blood. These findings suggest that maternal OCM status may impact fetal development and indicate the need for comprehensive and longitudinal evaluations of OCM during pregnancy.

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.

Constipation is common in children and can significantly affect quality of life. Prebiotics are reportedly helpful for constipation in adults, but few studies have examined their use in young children. In this study, the effect of 1-kestose (kestose), which has excellent bifidobacterial growth properties, on constipation in kindergarten children (n = 11) was compared with that of maltose (n = 12) in a randomized, double-blind study. Three grams of kestose per day for 8 weeks did not affect stool properties, but significantly increased the number of defecations per week (Median; 3 → 4 times/week, p = 0.017, effect size = 0.53). A significant decrease in Intestinibacter, a trend toward increased bifidobacteria, and a trend toward decreased Clostridium sensu stricto were observed after kestose ingestion, while concentrations of short-chain fatty acids in stools were unchanged.

The increase in fetal requirements of long-chain polyunsaturated fatty acids (LCPUFAs) during pregnancy alters maternal fatty acid metabolism, and therefore, fatty acid desaturase (FADS) gene polymorphisms may change blood fatty acid composition or concentration differently during pregnancy. We investigated the relationship between a FADS1 single-nucleotide polymorphism (SNP) and maternal serum LCPUFA levels in Japanese pregnant women during the first and third trimesters and at delivery. Two hundred and fifty-three pregnant women were included, and fatty acid compositions of glycerophospholipids in serum (weight %) and the FADS1 SNP rs174547 (T/C) were analyzed. LCPUFAs, including arachidonic acid (ARA) and docosahexaenoic acid (DHA), significantly decreased from the first to the third trimester of pregnancy. Furthermore, DHA significantly decreased from the third trimester of pregnancy to delivery. At all gestational stages, linoleic acid (LA) and α-linolenic acid were significantly higher with the number of minor FADS1 SNP alleles, whereas γ-linolenic acid and ARA and the ARA/LA ratio were significantly lower. DHA was significantly lower with the number of minor FADS1 SNP alleles only in the third trimester and at delivery, suggesting that genotype effects become more obvious as pregnancy progresses.

Background: Discontinuing chemotherapy worsens cancer prognosis. This study aimed to investigate the relationship between nutritional status at the start of chemotherapy and chemotherapy discontinuation in patients with ovarian, fallopian tube, and primary peritoneal cancer. Methods: This was a retrospective cohort study. One hundred and forty-six patients to whom weekly paclitaxel and carboplatin were administered as postoperative chemotherapy were included. Six courses in 21-day cycles were defined as complete treatment. As nutritional indicators, body mass index, weight change rate, serum albumin, total lymphocyte count, prognostic nutritional index, and C-reactive protein-to-albumin ratio (CAR) were compared between complete and incomplete treatment groups. Patients were divided into two groups according to CAR. The number of chemotherapy cycles was compared between these two groups. A Cox proportional hazard model was used for covariate adjustment. Results: Several indicators differed between complete and incomplete treatment groups, and among the indicators, CAR had the highest discriminatory ability. The number of chemotherapy cycles was shorter in the high CAR group than in the low CAR group. A high CAR was associated with chemotherapy interruption even after adjusting for covariates. Conclusion: Based on CAR, nutritional status before chemotherapy is suggested to be associated with the risk of chemotherapy discontinuation.

Existing evidence on the correlation between maternal vitamin D concentrations and birth outcomes is conflicting. Investigation of these associations requires accurate assessment of vitamin D status, especially in individuals with low 25-hydroxyvitamin D (25(OH)D) concentrations. This study examined the correlations between birth outcomes and the maternal vitamin D metabolite ratio (VMR) 1 (defined as the ratio of 24,25(OH)2D3 to 25(OH)D) and VMR2 (defined as the ratio of 3-epi-25(OH)D3 to 25(OH)D) using data from the Japan Environment and Children’s Study at Chiba Regional Center. A total of 297 mother–neonate pairs were analyzed. Using liquid chromatography–tandem mass spectrometry, we measured 25(OH)D2, 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 concentrations in maternal serum samples. These data were analyzed in relation to birth anthropometric data using multivariable linear regression. Of the study participants, 85.2% showed insufficient vitamin D concentrations. VMR1 was strongly correlated with 25(OH)D concentrations, whereas VMR2 showed a weak correlation. Only VMR2 was associated with all anthropometric data. VMR2 in pregnant women with low vitamin D blood concentrations is a useful marker for neonatal anthropometric data and is independent of 25(OH)D. Accurate measurement of vitamin D metabolites could help better understand the effects of vitamin D on birth outcomes.

Inadequate maternal iodine intake affects thyroid function and may impair fetal brain development. This study investigated the association between maternal iodine intake during pregnancy and neurodevelopmental delay in offspring at 1 and 3 years of age using a nationwide birth cohort: the Japan Environment and Children’s Study. We assessed dietary iodine intake during pregnancy using a food frequency questionnaire and child neurodevelopment using the Japanese translation of the Ages and Stages Questionnaire, Third Edition. The risk of delay (score below the cut-off value) for fine motor domain at 1 year of age was increased in the lowest quintile iodine intake group compared with the fourth quintile iodine intake group. The risk of delay for problem-solving at 1 year of age was increased in the lowest and second quintile iodine intake group and decreased in the highest quintile iodine intake group. The risk of delay for communication, fine motor, problem-solving, and personal–social domains at 3 years of age was increased in the lowest and second quintile iodine intake group compared with the fourth quintile iodine intake group, while the risk of delay for fine motor and problem-solving domains was decreased in the highest quintile iodine intake group. Low iodine intake levels in pregnancy may affect child neurodevelopment.

Chemokine (C-C motif) ligand 17 (CCL17) is a pro-allergic factor: high CCL17 levels in cord blood (CB) precede later allergic predisposition. Short-chain fatty acid (SCFA) treatment during pregnancy has been shown to protect mouse pups against allergic diseases. The maternal microbial metabolome during pregnancy may affect fetal allergic immune responses. We therefore examined the associations between CB CCL17 and gut SCFA levels in healthy pregnant Japanese women. CB CCL17 serum levels at birth, and maternal non-specific IgE levels in maternal sera at 32 weeks of gestation were measured. Maternal stool samples were collected at 12 (n = 59) and 32 (n = 58) weeks of gestation for gut microbiota analysis, based on barcoded 16S rRNA sequencing and metabolite levels. The CB CCL17 levels correlated negatively with butyrate concentrations and positively with isobutyrate at 12 weeks; CB CCL17 correlated positively with valerate and lactate at 32 weeks. Similarly, butyrate levels correlated negatively with maternal non-specific IgE levels, whereas the lactate concentration correlated positively with IgE levels. At 32 weeks, the Shannon diversity index (SDI) of Firmicutes and Proteobacteria correlated negatively with CB CCL17 levels, while those of the total microbiota correlated positively with the CB CCL17 levels. These metabolites may alter fetal immune responses. This study provides the first link between maternal metabolites during pregnancy and the risk of allergic diseases in human offspring.

“Total” folate in blood has usually been measured to evaluate the folate status of pregnant women. However, folate is composed of many metabolites. The main substrate is 5-methyltetrahydrofolate (5-MTHF), with folic acid (FA) representing a very small component as an unmetabolized species in blood. We longitudinally evaluated 5-MTHF, FA and total homocysteine in maternal and cord blood from Japanese pregnant women. Subjects were 146 pregnant women who participated in the Chiba study of Mother and Child Health (C-MACH) prospective cohort study. Sera were obtained in early and late pregnancy, at delivery, and from cord blood. Species levels were measured by isotope-dilution mass spectrometry. Both 5-MTHF and FA levels were lower than reported levels from pregnant women in populations from countries with mandatory FA fortification. As gestational age progressed, serum 5-MTHF levels decreased, whereas serum FA levels were slightly reduced only at delivery compared to early pregnancy. A significant negative association between serum 5-MTHF and total homocysteine was shown at all examined times, but no associations with FA were evident. At delivery, cord 5-MTHF was significantly higher than maternal levels, while FA again showed no significant correlation. These results suggest that 5-MTHF is actively transported to the fetus through placental transporters and may reflect folate status during pregnancy as a physiologically important species.