Endothelial nitric oxide synthase gene polymorphism (Glu298Asp) and development of pre-eclampsia: a case-control study and a meta-analysis

BACKGROUND: Pre-eclampsia is thought to have an important genetic component. Recently, pre-eclampsia has been associated in some studies with carriage of a common eNOS gene Glu298Asp polymorphism, a variant that leads to the replacement of glutamic acid by aspartic acid at codon 298. METHOD: Healthy women with singleton pregnancies were recruited from 7 district general hospitals in London, UK. Women at high risk of pre-eclampsia were screened by uterine artery Doppler velocimetry at 22–24 weeks of gestation and maternal blood was obtained to genotype the eNOS Glu298Asp polymorphism. Odds ratios (OR) and 95%CI, using logistic regression methods, were obtained to evaluate the association between the Glu298Asp polymorphism and pre-eclampsia. A meta-analysis was then undertaken of all published studies up to November 2005 examining the association of eNOS Glu298Asp genotype and pre-eclampsia. RESULTS: 89 women with pre-eclampsia and 349 controls were included in the new study. The Glu298Asp polymorphism in a recessive model was not significantly associated with pre-eclampsia (adjusted-OR: 0.83 [95%CI: 0.30–2.25]; p = 0.7). In the meta-analysis, under a recessive genetic model (1129 cases & 2384 controls) women homozygous for the Asp298 allele were not at significantly increased risk of pre-eclampsia (OR: 1.28 [95%CI: 0.76–2.16]; p = 0.34). A dominant model (1334 cases & 2894 controls) was associated with no increase of risk of pre-eclampsia for women carriers of the Asp298 allele (OR: 1.12 [95%CI: 0.84–1.49]; p = 0.42). CONCLUSION: From the data currently available, the eNOS Glu298Asp polymorphism is not associated with a significant increased risk of pre-eclampsia. However, published studies have been underpowered, much larger studies are needed to confirm or refute a realistic genotypic risk of disease, but which might contribute to many cases of pre-eclampsia in the population

Maternal Arterial Stiffness in Women Who Subsequently Develop Pre-Eclampsia

BACKGROUND/OBJECTIVES: Pre-eclampsia (PE) is associated with profound changes in the maternal cardiovascular system. The aim of the present study was to assess whether alterations in the maternal arterial stiffness precede the onset of PE in at risk women. METHODOLOGY/PRINCIPAL FINDINGS: This was a cross sectional study involving 70 pregnant women with normal and 70 women with abnormal uterine artery Doppler examination at 22-24 weeks of gestation. All women had their arterial stiffness (augmentation index and pulse wave velocity of the carotid-femoral and carotid-radial parts of the arterial tree) assessed by applanation tonometry in the second trimester of pregnancy, at the time of the uterine artery Doppler imaging. Among the 140 women participating in the study 29 developed PE (PE group) and 111 did not (non-PE group). Compared to the non-PE group, women that developed PE had higher central systolic (94.9 ± 8.6 mmHg vs 104.3 ± 11.1 mmHg; p  =  < 0.01) and diastolic (64.0 ± 6.0 vs 72.4 ± 9.1; p < 0.01) blood pressures. All the arterial stiffness indices were adjusted for possible confounders and expressed as multiples of the median (MoM) of the non-PE group. The adjusted median augmentation index was similar between the two groups (p  =  0.84). The adjusted median pulse wave velocities were higher in the PE group compared to the non-PE group (carotid-femoral: 1.10 ± 0.14 MoMs vs 0.99 ± 0.11 MoMs; p < 0.01 and carotid-radial: 1.08 ± 0.12 MoMs vs 1.0 ± 0.11 MoMs; p < 0.01). CONCLUSIONS/SIGNIFICANCE: Increased maternal arterial stiffness, as assessed by pulse wave velocity, predates the development of PE in at risk women

First-trimester maternal serum vitamin D and mode of delivery

Low maternal vitamin D levels have been associated with adverse pregnancy outcome. A recent study has suggested that low maternal vitamin D levels at the time of delivery are also associated with an almost fourfold increase in caesarean section risk. The aim of the present study was to investigate whether there is a difference in maternal serum 25-hydroxyvitamin D (25(OH)D) levels at 11-13 weeks' gestation according to the mode of delivery. Maternal serum 25(OH)D levels were measured at 11-13 weeks' gestation in 995 singleton pregnancies resulting in the birth of phenotypically normal neonates at term. The measured 25(OH)D levels were adjusted for maternal age, BMI, racial origin, smoking, method of conception and season of blood testing, and the adjusted levels (multiple of the median; MoM) were compared between those who subsequently delivered vaginally and those that delivered by caesarean section. Delivery was vaginal in 79.6% of cases, by emergency caesarean section in 11.6% and by elective caesarean section in 8.8%. The median 25(OH)D level in our population was 46.82 (interquartile range (IQR) 27.75-70.13) nmol/l. The adjusted maternal median 25(OH)D levels in the emergency and elective caesarean section groups (0.99, IQR 0.71-1.46 MoM and 0.96, IQR 0.73-1.27 MoM, respectively) were not significantly different from the vaginal delivery group (0.99, IQR 0.71-1.33 MoM; P = 0.53 and P = 0.81, respectively). First-trimester maternal serum 25(OH)D levels are similar between women who subsequently have a vaginal delivery and those who deliver by elective or emergency caesarean section.</p

Circulating levels of adiponectin and leptin at 23-25 weeks of pregnancy in women with impaired placentation and in those with established fetal growth restriction

International audienceAdiponectin and leptin, two adipose tissue-derived proteins, have been reported to be elevated in women with established pre-eclampsia (PE). The aim of the current study was to investigate whether alterations of adiponection and leptin levels predate the development of PE and fetal growth restriction (FGR) in women at increased risk of these complications, as assessed by Doppler examination of the uterine arteries during the second trimester of pregnancy. We also sought to investigate the circulating levels of adiponection and leptin in women with established severe, early onset FGR. The study included three groups of pregnant women at 23-25 weeks: Group A (n=44) with normal uterine artery Doppler waveforms, Group B (n=49) with abnormal Doppler waveforms and normal fetal growth at the time of the examination and Group C (n=15) with established, severe FGR and abnormal Doppler. All women had plasma adiponectin and leptin measured by sensitive immunoassays. In Group B, 19 women had normal outcome, 17 delivered FGR infants and 13 developed PE. The women who developed PE delivered smaller babies earlier compared to women with normal outcome (p<0.001). There were no significant differences in adiponectin levels between any of the groups (overall p=0.3). Leptin concentrations, expressed as multiples of the median (MoM) of Group A, were higher in women of Group C i.e established severe FGR at 2.5 (1.2-2.7) MoM's (overall p<0.001) compared to all the other groups and subgroups. In summary, we found that in pregnancies complicated by severe, early onset FGR maternal plasma concentration of leptin is twice as high as in normal pregnancies. However, the second trimester levels of maternal plasma adiponectin and leptin in pregnancies that subsequently develop PE and/or FGR are not significantly different from normal and consequently it is unlikely that these markers will be useful as predictors of these pregnancy complications