Ethnic differences in the prevalence of inherited thrombophilic polymorphisms in an asymptomatic Australian prenatal population

Differences in the prevalence of thrombophilias in different ethnic populations have been demonstrated. Because the Australian population includes many different ethnic groups, we sought to assess the effect of ethnicity in our Australian prenatal population on the prevalence of thrombophilic polymorphisms. Asymptomatic, nulliparous women (n = 1,129) recruited for a large prospective study were included in this analysis. These women had no personal or family history of venous thromboembolism and were not known to be carrying an inherited or acquired thrombophilia. Ethnicity was determined at recruitment, and women were categorized as being of Northern European, Southern European, Middle Eastern, Asian, or Other ethnicity. These women underwent genotyping for the following polymorphisms: factor V Leiden G1691A, prothrombin gene A20210G mutation, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and thrombomodulin C1418T. The factor V Leiden allele was seen significantly more frequently in patients of Middle Eastern background compared to those of Northern European and Asian ethnicity (p < 0.05). The prothrombin gene mutation was seen significantly more frequently in patients of Southern European ethnicity compared to those of Northern European or Asian ethnicity (p < 0.05). The MTHFR C677T allele (mutant) was significantly less common in those of Asian ethnicity compared to patients of Northern European and Southern European ethnicity (p < 0.0005). There were no significant differences seen with the MTHFR A1298C polymorphism. The mutant thrombomodulin allele was seen significantly more frequently in Asian women compared to Northern European, Southern European, or Middle Eastern women (p < 0.005). There are important ethnic differences in the prevalence of thrombophilic polymorphisms in the Australian prenatal population

Placental Vitamin D-Binding Protein Expression in Human Idiopathic Fetal Growth Restriction

Vitamin D-binding protein is a multifunctional serum protein with multiple actions related to normal health. Vitamin D-binding protein transports vitamin D and influences the metabolism of this key hormone but it also has additional immunomodulatory and actin-clearing properties. We investigated whether vitamin D-binding protein expression is altered in fetal growth restrictionassociated placental dysfunction. Protein was extracted from 35 placentae derived from 17 healthy control subjects and 18 gestationmatched subjects with fetal growth restriction (FGR). FGR subjects were further subdivided as idiopathic ( = 9) and nonidiopathic ( = 9). Vitamin D-binding protein and 25(OH) vitamin D were measured by ELISA and normalized to protein concentration. The results showed significantly reduced levels of placental vitamin D-binding protein (control versus FGR, &lt; 0.05, Student&apos;s -test) that were strongly associated with idiopathic fetal growth restriction ( &lt; 0.01, Kruskal-Wallis), whereas levels of vitamin D-binding protein were not associated with placental 25(OH) vitamin D stores ( = 0.295, Pearson&apos;s correlation). As such, vitamin D-binding protein may be a factor in unexplained placental dysfunction associated with idiopathic fetal growth restriction and may potentially serve as a biomarker of this disease

Genetic and Molecular Functional Characterization of Variants within TNFSF13B, a Positional Candidate Preeclampsia Susceptibility Gene on 13q

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Genome-Wide Association Scan Identifies a Risk Locus for Preeclampsia on 2q14, Near the Inhibin, Beta B Gene

Miira Klemetti ja Anna Inkeri Lokki FINNPEC Study Group'n jäseniä. Jäseniä yht. 16.Peer reviewe

Prostaglandin synthase inhibitory activity in the plasma of rhesus monkeys during late pregnancy: Effect of dexamethasone

Plasma from rhesus monkeys during late pregnancy contained a factor(s) that was inhibitory of prostaglandin synthase activity. There was no consistent trend in the inhibitory activity of plasma obtained between 120 days of gestation and term (approximately 167 days of gestation). Administration of dexamethasone (0.125 to 1.0 mg twice daily) consistently increased inhibitory activity in plasma after an initial treatment period of 5-10 days. Administration of dexamethasone for several weeks is associated with prolongation of gestation in rhesus monkeys. We suggest that the action of dexamethasone, to delay parturition is related, in part, to an enhancement of the activity of a circulating factor(s) that is inhibitory of prostaglandin synthase activity

Ethnic Differences in the Prevalence of Inherited Thrombophilic Polymorphisms in an Asymptomatic Australian Prenatal Population

Differences in the prevalence of thrombophilias in different ethnic populations have been demonstrated. Because the Australian population includes many different ethnic groups, we sought to assess the effect of ethnicity in our Australian prenatal population on the prevalence of thrombophilic polymorphisms. Asymptomatic, nulliparous women (n = 1,129) recruited for a large prospective study were included in this analysis. These women had no personal or family history of venous thromboembolism and were not known to be carrying an inherited or acquired thrombophilia. Ethnicity was determined at recruitment, and women were categorized as being of Northern European, Southern European, Middle Eastern, Asian, or Other ethnicity. These women underwent genotyping for the following polymorphisms: factor V Leiden G1691A, prothrombin gene A20210G mutation, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and thrombomodulin C1418T. The factor V Leiden allele was seen significantly more frequently in patients of Middle Eastern background compared to those of Northern European and Asian ethnicity ( p \u3c 0.05). The prothrombin gene mutation was seen significantly more frequently in patients of Southern European ethnicity compared to those of Northern European or Asian ethnicity ( p \u3c 0.05). The MTHFR C677T allele (mutant) was significantly less common in those of Asian ethnicity compared to patients of Northern European and Southern European ethnicity ( p \u3c 0.0005). There were no significant differences seen with the MTHFR A1298C polymorphism. The mutant thrombomodulin allele was seen significantly more frequently in Asian women compared to Northern European, Southern European, or Middle Eastern women ( p \u3c 0.005). There are important ethnic differences in the prevalence of thrombophilic polymorphisms in the Australian prenatal population

5β-Dihydroprogesterone and steroid 5β-reductase decrease in association with human parturition at term

The role of progesterone withdrawal in human parturition continues to provoke controversy. One possible mechanism by which functional progesterone withdrawal may be achieved is by a decrease in the circulating concentration of its bioactive metabolites. The progesterone metabolite 5 beta-dihydroprogesterone (5 beta DHP) has been shown to be a potent tocolytic in vitro. We quantified plasma concentrations of 5 beta DHP in association with the onset of spontaneous labour in women at term and steroid 5 beta-reductase mRNA expression in placenta, myometrium, chorion and amnion in relation to parturition, using real time RT-PCR. Serial blood samples were obtained from patients late in pregnancy, before term labour, during term labour and within the first 24 h postpartum. Following organic solvent extraction, steroids including 5 beta DHP were separated by high-performance liquid chromatography ( HPLC) and then quantified by radioimmunoassay (RIA). 5 beta DHP concentration decreased two-fold ( P = 0.00001, n = 25) from 0.317 +/- 0.039 nmol/ml to 0.178 +/- 0.017nmol/ml in association with active labour. Tissue 5 beta-reductase mRNA-relative abundance was determined in placenta, myometrium, chorion and amnion obtained from labouring and non-labouring women. In placenta and myometrium, relative expression decreased significantly in association with labour, by about two-fold and 10-fold, respectively. These data are consistent with a possible role for 5 beta DHP in the onset of spontaneous human labour. Further studies exploring this hitherto unrecognized endocrinological pathway are indicated

First-Trimester Uterine Artery Doppler Analysis in the Prediction of Later Pregnancy Complications

Uterine artery Doppler waveform analysis has been extensively studied in the second trimester of pregnancy as a predictive marker for the later development of preeclampsia and fetal growth restriction. The use of Doppler interrogation of this vessel in the first trimester has gained momentum in recent years. Various measurement techniques and impedance indices have been used to evaluate the relationship between uterine artery Doppler velocimetry and adverse pregnancy outcomes. Overall, first-trimester Doppler interrogation of the uterine artery performs better in the prediction of early-onset than late-onset preeclampsia. As an isolated marker of future disease, its sensitivity in predicting preeclampsia and fetal growth restriction in low risk pregnant women is moderate, at 40–70%. Multiparametric predictive models, combining first-trimester uterine artery pulsatility index with maternal characteristics and biochemical markers, can achieve a detection rate for early-onset preeclampsia of over 90%. The ideal combination of these tests and validation of them in various patient populations will be the focus of future research