Polymorphisms of the angiotensin converting enzyme gene in relation to intrauterine growth restriction.

The aim of this case-control study was to explore the relation between maternal and infant angiotensin converting enzyme (ACE) activity and its genotypes in uncomplicated term pregnancies (> or =37 weeks) and pregnancies with growth-restricted infants (birthweight at or below the 5th centile). Venous cord bloods and maternal venous samples were obtained for serum ACE activity and ACE genotype. Growth-restricted infants (< or =5th centile) were more likely to be of the DD genotype compared to appropriately grown infants (42 vs. 13%, p = 0.003). There was no significant difference in the frequency of the maternal DD genotype between the two groups (33 vs. 22%, p = 0.43) and similarly no significant differences in the maternal or fetal ACE activities. Within the intrauterine growth restriction (IUGR) group, infants of the DD genotype had higher ACE activity compared to appropriately grown infants (p = 0.03). In conclusion, the DD genotype of the ACE gene appears to be associated with fetal growth and may be a factor in the increased risk of adult onset chronic diseases among growth-restricted infants.

Do LCPUFAs influence cardiovascular function in early childhood?

In recent years there have been reports linking breast milk intake in infancy to lower blood pressure during childhood. The mechanisms underlying the relationship remain uncertain however there has been recent interest in the role of long chain polyunsaturated fatty acids (LCPUFAs). Several studies involving human adults have reported a lowering of blood pressure with n-3 fatty acid supplementation. Data relating to children are limited: however, two published randomised controlled studies report that LCPUFA supplementation in infancy may be associated with lower blood pressure in early childhood.

The beneficial effects of breastfeeding on microvascular function in 11- to 14-year-old children.

Infant feeding practices have an impact on health in later life, although the evidence for its effects on cardiovascular health is not so clear. The aim of this study was to investigate the relationship between breastfeeding in infancy and vascular function in later childhood. Infant feeding data, together with demographic and clinical information, were obtained prospectively from a cohort of children from birth until 2 years of age. Vascular function was assessed in 159 children, now aged 11-14 years, by measuring their skin microvascular responses to iontophoretic administration of the endothelium-dependent vasodilator acetylcholine. Endothelial function was significantly better in children who had been breastfed than in those who had received infant milk formula (p = 0.001), after adjustment for potential confounding factors. Linear regression showed that acetylcholine responses were significantly related to the duration of breastfeeding (r = 0.30, p = 0.006). The risk of later cardiovascular disease may be reduced by exclusively breastfeeding during infancy. These findings have potential public health implications, and support policies aimed at promoting breastfeeding.

Correlation of angiotensin converting enzyme activity and the genotypes of the I/D polymorphism in the ACE gene with preterm birth and birth weight.

OBJECTIVE: Preterm birth remains one of the most challenging areas in obstetrics. The pathogenesis of preterm labor is multifactorial and research on preterm birth has focused principally on infection and inflammatory markers. Recently the focus has turned to potential genetic factors influencing preterm birth. Uteroplacental insufficiency and thrombotic vasculopathy are considered part of the pathogenesis of preterm labor. Investigating the gene expression in the maternal/fetal interface seems of importance to expand our knowledge of the pathophysiology of preterm birth. The renin-angiotensin system (RAS) appears to play an important role in fetal/placental development and uteroplacental circulation. Hence, the aim of this study was to investigate angiotensin converting enzyme (ACE) activity and I/D polymorphisms in the ACE gene in mothers and infants with appropriately grown infants in relation to preterm birth and infant birth weight. STUDY DESIGN: We conducted a cross-sectional study of 113 term pregnancies (> or =37 weeks) and 18 preterm pregnancies (<37 weeks). Umbilical cord bloods (venous and arterial) were obtained from the placenta immediately after delivery for serum ACE activity, ACE genotype analysis of the I/D polymorphism and the acid-base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype. RESULTS: The distribution of the maternal ACE genotypes was similar for preterm and term births as was maternal ACE activity. Preterm infants were more likely to be of the DD genotype than term infants (7/18 (39%) vs. 11/83 (13%), p=0.02) (adjusted p=0.04). There was no correlation between ACE activity and birth weight (r(2) 0.00, p=0.82). CONCLUSIONS: These findings suggest that the ACE genotype of the infant may influence the risk of preterm birth among appropriately grown fetuses.

The influence of mode of delivery and ACE genotype on serum angiotensin converting enzyme (ACE) activity in the mother and infant at term.

OBJECTIVE: Angiotensin converting enzyme (ACE) and its genotype have been shown to play a role in the pathophysiology of pregnancy complications such as pre-eclampsia and intrauterine growth restriction and possibly in adult onset chronic diseases. The physiological changes of ACE and the influence of its genotype during the intrapartum period are not well known. Hence the aim of this study was to assess serum ACE activity and its genotype in mothers and infants at term in relation to labour and mode of delivery. STUDY DESIGN: A cross sectional study of 99 women who laboured and 27 women who delivered by elective caesarean section after 36 completed weeks gestation with uncomplicated pregnancies. Venous cord bloods were obtained immediately after delivery of the placenta for serum ACE activity, ACE genotype and acid-base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype. Univariate analyses were performed using parametric tests for normally distributed data and nonparametric tests for the data that were not normally distributed. A multiple regression model was developed to adjust for potential confounding factors. RESULTS: The umbilical venous ACE activity was similar for infants delivered following labour compared to those delivered by elective caesarean section, 47.2 U/L (35-64) versus 40.1 U/L (31-60) (adjusted p=0.21). Maternal ACE activities were 28.9 U/L (22-35) and 32.1 U/L (22-40) respectively (adjusted p=0.17). The ACE activity in infants was higher than that of mothers 46 U/L versus 22 U/L, respectively (p= or <0.001). Neither the mode of delivery nor the presence of suspected fetal compromise influenced maternal or infant ACE activity. There was no influence of the infants' genotype on ACE activity in relation to mode of delivery. The DD genotype was associated with higher ACE activity in mothers (p=0.001) but not in infants (p=0.56). CONCLUSIONS: This study shows that intrapartum events do not affect ACE activity. These results will enhance our ability to investigate the role of ACE and its genotype in abnormal fetal growth and in subsequent adult onset chronic disease.

The Walker Project: a longitudinal study of 48,000 children born 1952-1966 (aged 36-50 years in 2002) and their families.

The Walker cohort is a database of over 48,000 birth records that has recently become available. It contains meticulously recorded details of pregnancy, labour, birth and care before discharge for babies born in hospital in Dundee, Scotland between 1952 and 1966. These babies accounted for 75% of all births in Dundee at this time. Over 34,000 (73%) of these subjects can be identified and this presents the opportunity to link this birth information with a large number of current health-outcome databases covering both primary and secondary care. Further, it allows linkage of records across siblings and over two and, in future, three generations. The number of birth records available and linkage to current databases make this a unique birth cohort with huge potential for the investigation of the fetal origins of adult disease.

Impaired microvascular function in normal children: effects of adiposity and poor glucose handling.

Clustering of cardiovascular risk factors is thought to occur early in life. The endothelium is an important regulator of microvascular function. We investigated the relationship between microvascular function and cardiovascular risk factors in 145 normal, healthy children aged 11-14 years. Skin microvascular responses, measured using laser Doppler imaging, to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), were negatively correlated with percentage body fat (r = -0.20, P < 0.05 and r = -0.18, P < 0.05, respectively). Subjects were stratified into quintiles based on 2-h, post-feeding glucose levels. Subjects in the upper glucose quintile (range 7.4-11.4 mmol l-1) showed significantly lower vasodilatation to both ACh (P < 0.005) and SNP (P < 0.02) than those in the lower quintile (range 3.9-4.9 mmol l-1). Waist-to-hip ratio and the fasting insulin resistance index were significantly greater in subjects in the upper quintile than those in the lower quintile (P < 0.001 and P < 0.05, respectively). Additionally, in subjects in the upper glucose quintile, fasting triglyceride correlated with fasting insulin (r = 0.59, P < 0.001) and with the fasting insulin resistance index (r = 0.49, P < 0.009), and plasma levels of cholesterol and 2-h glucose were also correlated (r = 0.40, P < 0.05). In a cross-section of normal children, microvascular function was negatively associated with adiposity. Additionally, in a subgroup of subjects, there was a clustering of high post-feeding glucose, impaired microvascular function, increased insulin resistance and higher central fat distribution. These findings suggest that risk factors for adult cardiovascular disease begin to cluster in normal children, which might have important consequences for development of atherosclerosis later in life.