Arterial Health Markers in Relation to Behavior and Cognitive Outcomes at School Age

BACKGROUND:Impaired arterial health is associated with a decline in cognitive function and psychopathology in adults. We hypothesized that these associations originate in early life. We examined the associations of blood pressure, common carotid artery intima media thickness, and carotid distensibility with behavior and cognitive outcomes during adolescence. METHODS AND RESULTS: This study was embedded in the Dutch Generation R Study, a population-based prospective cohort study from early fetal life onwards. Blood pressure, carotid intima media thickness, and carotid distensibility were measured at the age of 10 years. At the age of 13 years, total, internalizing and externalizing problems and attention-deficit hyperactivity disorder symptoms were measured using the parent-reported Child Behavior Checklist (CBCL/6-18), autistic traits were assessed by the Social Responsiveness Scale, and IQ was assessed using the Wechsler Intelligence Scale for Children-Fifth Edition. A 1-SD score higher mean arterial pressure was associated with lower odds of internalizing problems (odds ratio [OR], 0.92 [95% CI, 0.85-0.99]). However, this association was nonsignificant after correction for multiple testing. Carotid intima media thickness and carotid distensibility were not associated with behavior and cognitive outcomes at 13 years old. CONCLUSIONS: From our results, we cannot conclude that the associations of blood pressure, carotid intima media thickness, and carotid distensibility at age 10 years with behavior and cognitive outcomes are present in early adolescence. Further follow-up studies are needed to identify the critical ages for arterial health in relation to behavior and cognitive outcomes at older ages.</p

The association of maternal folic acid supplementation and prenatal folate and vitamin B12 concentrations with child dental development

OBJECTIVE: Low folic acid, folate and vitamin B12 might affect tooth formation and mineralization. The conversion of folic acid into folate is catalysed by the methylenetetrahydrofolate (MTHFR) enzyme which is encoded by the MTHFR gene. Among 3728 mothers and their 10‐year‐old children from the Generation R Study, we investigated associations of maternal folic acid supplementation and prenatal folate and vitamin B12 concentrations with child dental development. Secondly, we checked the modifying effect of MTHFR‐C677T polymorphism. METHODS: Information on folic acid supplementation was obtained by questionnaires. Concentrations of folate and vitamin B12 were measured from venous samples taken in early pregnancy. Developmental stages of teeth were defined by the Demirjian method at the age‐10 assessment. In addition, dental age of the children was calculated using the Dutch standard. GLM and multivariate linear regression models were built to study the associations. RESULTS: Folic acid supplementation started when pregnancy was known (β = −0.09; 95% CI: −0.17, −0.01) and folic acid supplementation started prior to known pregnancy (β = −0.12; 95% CI: −0.20, −0.04) were both associated with decelerated dental development by 1‐2 months lower dental age of 10‐year‐old children. Folate (β = −0.02, 95% CI: −0.05, 0.02) and vitamin B12 (β = 0.03, 95% CI: −0.00, 0.06) were not associated with dental age. MTHFR‐C677T did not modify the associations. CONCLUSIONS: Maternal folic acid supplementation delays dental development of children by 1‐2 months dental age, whereas maternal folate and vitamin B12 concentrations in early pregnancy do not affect the timing of child dental development

Maternal hypertensive disorders in pregnancy and early childhood cardiometabolic risk factors:The Generation R Study

The objective of this study was to determine the associations between hypertensive disorders of pregnancy and early childhood cardiometabolic risk factors in the offspring. Therefore, 7794 women from the Generation Rotterdam Study were included, an ongoing population-based prospective birth cohort. Women with a hypertensive disorder of pregnancy were classified as such when they were affected by pregnancy induced hypertension, pre-eclampsia or the haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome during pregnancy. Early childhood cardiometabolic risk factors were defined as the body mass index at the age of 2, 6, 12, 36 months and 6 years. Additionally, it included systolic blood pressure, diastolic blood pressure, total fat mass, cholesterol, triglycerides, insulin and clustering of cardiometabolic risk factors at 6 years of age. Sex-specific differences in the associations between hypertensive disorders and early childhood cardiometabolic risk factors were investigated. Maternal hypertensive disorders of pregnancy were inversely associated with childhood body mass index at 12 months (confounder model: -0.15 SD, 95% CI -0.27; -0.03) and childhood triglyceride at 6 years of age (confounder model: -0.28 SD, 95% CI -0.45; -0.10). For the association with triglycerides, this was only present in girls. Maternal hypertensive disorders of pregnancy were not associated with childhood body mass index at 2, 6 and 36 months. No associations were observed between maternal hypertensive disorders of pregnancy and systolic blood pressure, diastolic blood pressure, body mass index, fat mass index and cholesterol levels at 6 years of age. Our findings do not support an independent and consistent association between maternal hypertensive disorders of pregnancy and early childhood cardiometabolic risk factors in their offspring. However, this does not rule out possible longer term effects of maternal hypertensive disorders of pregnancy on offspring cardiometabolic health

Innovative approach for first-trimester fetal organ volume measurements using a Virtual Reality system:The Generation R <i>Next</i> Study

INTRODUCTION: To investigate the reproducibility of first‐trimester fetal organ volume measurements using three‐dimensional (3D) ultrasound and a Virtual Reality system. METHODS: Within a population‐based prospective cohort study, 3D ultrasound datasets of 25 first‐trimester fetuses were collected by three sonographers. We used the V‐scope application to perform Virtual Reality volume assessments of the fetal heart, lungs, and kidneys. All measurements were performed by two independent researchers. RESULTS: Intraobserver analyses for volume measurements of the fetal heart, lungs, and kidneys showed intraclass correlation coefficients ≥0.86, mean differences ≤8.3%, and coefficients of variation ≤22.8%. Interobserver analyses showed sufficient agreement for right lung volume measurements, but consistent measurement differences between observers for left lung, heart, and kidney volume measurements (p‐values <0.05). CONCLUSION: We observed sufficient intraobserver reproducibility, but overall suboptimal interobserver reproducibility for first‐trimester fetal heart, lung, and kidney volume measurements using an innovative Virtual Reality approach. In the current stage, these measurements might be promising for the use in research settings. The reproducibility of the measurements might be further improved by novel post‐processing algorithms

Breast-Feeding Modifies the Association of PPARγ2 Polymorphism Pro12Ala With Growth in Early Life: The Generation R Study

OBJECTIVE-We examined whether the PPARyγ2 Ala12 allele influences growth in early life and whether this association is modified by breast-feeding. RESEARCH DESIGN AND METHODS-This study was embedded in the Generation R Study, a prospective cohort study from early fetal life onward. PPARy2 was genotyped in DNA obtained from cord blood samples in 3,432 children. Information about breast-feeding was available from questionnaires. Weight, head circumference, and femur length were repeatedly measured in second and third trimesters of pregnancy, at birth, and at the ages of 1.5, 6, 11, 14, and 18 months. RESULTS-Genotype frequency distribution was 77.6% (Pro12Pro), 20.7% (Pro12Ala), and 1.7% (Ala12Ala). Growth rates in weight from second trimester of pregnancy to 18 months were higher for Pro12Ala and Ala12Ala than for Pro12Pro carriers (differences 1.11 g/week [95% CI 0.47-1.74] and 2.65 g/week [0.45-4.87], respectively). We found an interaction between genotype and breast-feeding duration (P value for interaction nths, PPARy2 Pro12Ala was not associated with growth rate. When breast-feeding duration was <2 months or 2-4 months, growth rate was higher in Ala12Ala than Pro12Pro carriers (differences 9.80 g/week [3.97-15.63] and 6.32 g/week [-1.04 to 13.68], respectively). CONCLUSIONS-The PPAR7gamma;2 Ala12 allele is associated with an increased growth rate in early life. This effect may be influenced by breast-feeding duration. Further studies should replicate these findings, identify the underlying mechanisms, and assess whether these effects persist into later life

原子炉圧力容器の設計規格への弾塑性有限要素解析の導入に関する研究

博士（工学）神戸大