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.

Polymorphisms of the angiotensin converting enzyme gene in early-onset and late-onset pre-eclampsia.

OBJECTIVE: The aim of this study was to investigate differences in maternal and infant ACE genotypes in early-onset and later-onset pre-eclampsia/toxemia (PET). METHODS: We conducted a case-control study of 22 cases of early-onset pre-eclampsia (before 34 weeks gestation), 38 cases of later-onset pre-eclampsia (after 34 weeks gestation), and 108 healthy controls delivered at term (38-40 weeks gestation) within a stable Caucasian population. Maternal venous blood and cord bloods were obtained for serum angiotensin converting enzyme (ACE) activity, ACE genotype, and acid-base status. RESULTS: Mothers who developed early-onset PET were more likely to be homozygous for the deletion allele of the ACE genotype (DD) than mothers with late-onset PET or uncomplicated pregnancies (12/22 (55%) vs. 7/38 (18%) vs. 22/105 (21%), respectively; OR 2.96 [95% confidence intervals (CI) 1.37-6.31]. Infants of mothers with early-onset PET were more likely to be homozygous for the DD genotype than infants of mothers with late-onset PET or controls (7/19 (37%) vs. 9/36 (25%) vs. 11/78 (14%); OR 2.51 (95% CI 1.12-5.61). There were no differences in maternal or infant ACE activities in relation to onset of pre-eclampsia. CONCLUSIONS: Our findings suggest an association between the DD genotype of the ACE gene and early-onset but not later-onset pre-eclampsia which may give a partial explanation for the higher recurrence risk with early-onset pre-eclampsia.

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.

Obstetric management of a woman's first delivery and the implications for pelvic floor surgery in later life.

OBJECTIVE: To determine the influence of intrapartum care during a first delivery on the risk of pelvic floor surgery in later life. DESIGN: Nested case-control study with record linkage of a historical cohort and a current morbidity database. SETTING: Hospital births in Dundee 1952-1966. POPULATION: The 7556 primiparous women from the Walker cohort. METHODS: The cases (n= 352) were women who delivered a first singleton baby at term (> or =37 weeks) and subsequently had pelvic floor surgery. Controls (n= 1403) were women who delivered their first baby during the same time period and did not undergo surgery. Univariate and multivariate logistic regression analyses were performed taking account of demographic, anthropometric and obstetric factors. MAIN OUTCOME MEASURE: Pelvic floor surgery. RESULTS: Caesarean section was associated with a reduced risk of pelvic floor surgery compared with spontaneous vaginal delivery (odds ratio 0.16, 95% CI 0.05-0.55). Forceps delivery and infant birthweight >4.0 kg were not identified as significant risk factors (OR 0.94, 95% CI 0.71, 1.25, and OR 0.94, 95% CI 0.50, 1.75, respectively). Episiotomy and prolonged labour (>12 hours) may be associated risk factors but were of borderline significance (OR 1.46, 95% CI 0.99, 2.10, and OR 1.51, 95% CI 1.00, 2.27). CONCLUSION: Caesarean section in a first pregnancy appears to protect against pelvic floor surgery in later life.