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Genetic risk assessment of thrombophilia in patients with adverse obstetric outcomes.

ABSTRACT: OBJECTIVES:To investigate the incidence of inherited thrombophilias in patients with adverse obstetric outcomes and to compare detection rates of thrombophilias between standard blood tests and a novel genetic test. METHODS:This is a case-control prospective study performed in Hospital Sant Joan de Déu in Barcelona, Spain. Cases had a history of intrauterine growth restriction requiring delivery before 34 weeks gestation, placental abruption before 34 weeks gestation, or severe preeclampsia. Controls had at least two normal, spontaneously conceived pregnancies at term, without complications or no underlying medical disease. At least 3 months after delivery, all case and control women underwent blood collection for standard blood tests for thrombophilias and saliva collection for the genetic test, which enables the diagnosis of 12 hereditary thrombophilias by analyzing genetic variants affecting different points of the blood coagulation cascade. RESULTS:The study included 33 cases and 41 controls. There were no statistically significant differences between cases and controls in the standard blood tests for thrombophilias in plasma or the TiC test for genetic variables. One clinical-genetic model was generated using variables with the lowest P values: ABO, body mass index, C_rs5985, C_rs6025, and protein S. This model exhibited good prediction capacity, with an area under the curve of almost 0.7 (P <0.05), sensitivity of almost 67%, and specificity of 70%. CONCLUSION:Although some association may exist between hypercoagulability and pregnancy outcomes, no significant direct correlation was observed between adverse obstetric outcomes and inherited thrombophilias when analyzed using either standard blood tests or the genetic test. Future studies with a larger sample size are required to create a clinical-genetic model that better discriminates women with a history of adverse pregnancy outcomes and an increased risk of poor outcomes in subsequent pregnancies.

SUBMITTER: Fernandez Arias M

PROVIDER: S-EPMC6392221 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Genetic risk assessment of thrombophilia in patients with adverse obstetric outcomes.

Fernández Arias M M Mazarico E E Gonzalez A A Muniesa M M Molinet C C Almeida L L Gómez Roig M D MD

PloS one 20190227 2

<h4>Objectives</h4>To investigate the incidence of inherited thrombophilias in patients with adverse obstetric outcomes and to compare detection rates of thrombophilias between standard blood tests and a novel genetic test.<h4>Methods</h4>This is a case-control prospective study performed in Hospital Sant Joan de Déu in Barcelona, Spain. Cases had a history of intrauterine growth restriction requiring delivery before 34 weeks gestation, placental abruption before 34 weeks gestation, or severe pr ...[more]

PMID: 30811416

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Project description:ImportanceTwin pregnancy is a common occurrence in pregnancies conceived with in vitro fertilization (IVF), but the absolute risk of adverse obstetric outcomes stratified by IVF, twin or singleton pregnancy, and maternal age are unknown.ObjectiveTo estimate the absolute risk of adverse obstetric outcomes at each maternal age among twin pregnancies conceived with IVF.Design, setting, and participantsThis retrospective cohort study included pregnant women with infants born from January 1, 2013, to December 31, 2018, based on the Hospital Quality Monitoring System in China. Data were analyzed from September 1, 2020, to June 30, 2021.ExposuresTwin pregnancy with IVF (IVF-T), singleton pregnancy with IVF (IVF-S), twin pregnancy with non-IVF (nIVF-T), and singleton pregnancy with non-IVF (nIVF-S).Main outcomes and measuresSixteen obstetric outcomes, including 10 maternal complications (gestational hypertension, eclampsia and preeclampsia, gestational diabetes, placenta previa, placental abruption, placenta accreta, preterm birth, dystocia, cesarean delivery, and postpartum hemorrhage) and 6 neonatal complications (fetal growth restriction, low birth weight, very low birth weight, macrosomia, malformation, and stillbirth).ResultsAmong 16 879 728 pregnant women aged 20 to 49 years (mean [SD] age, 29.2 [4.7] years), the twin-pregnancy rates were 32.1% in the IVF group and 1.5% in the non-IVF group (relative risk, 20.8; 95% CI, 20.6-20.9). The most common adverse obstetric outcomes after pregnancy conceived with IVF were cesarean delivery (88.8%), low birth weight (43.8%), preterm birth (39.6%), gestational diabetes (20.5%), gestational hypertension and preeclampsia and eclampsia (17.5%), dystocia (16.8%), and postpartum hemorrhage (11.9%). The absolute risk of most adverse obstetric outcomes in each subgroup presented in 2 dominant patterns: Pattern A indicated the absolute risk ranging from IVF-T to nIVF-T to IVF-S to nIVF-S, and pattern B indicated the absolute risk ranging from IVF-T to IVF-S to nIVF-T to nIVF-S. Both patterns showed an elevated obstetric risk with increasing maternal age in each subgroup.Conclusions and relevanceIn this cohort study, twin pregnancy, IVF, and advanced maternal age were independently associated with adverse obstetric outcomes. Given these findings, promotion of the elective single embryo transfer strategy is needed to reduce multiple pregnancies following IVF technologies. Unnecessary cesarean delivery shouldh be avoided in all pregnant women.

Project description:BackgroundPolycystic ovary syndrome (PCOS) affects up to one in five women of childbearing age. Observational studies assessing the association between maternal PCOS and adverse obstetric outcomes have reported varying results, depending on patient population, diagnostic criteria for PCOS and covariates accounted for in their analyses. We aimed to assess the risk of obstetric outcomes among a population-based representative cohort of women with PCOS compared to an age-matched cohort of women without PCOS.MethodsA retrospective cohort study was conducted of pregnancies of women in England aged 15-49 years identified from the Clinical Practice Research Datalink (CPRD) GOLD pregnancy register and linked Hospital Episodes Statistic (HES) data between March 1997 and March 2020. Pregnancies from the register that had a linked HES delivery record were included. Linked CPRD primary care data was used to ascertain maternal PCOS exposure prior to pregnancy. To improve detection of PCOS, in addition to PCOS diagnostic codes, codes for (1) polycystic ovaries or (2) hyperandrogenism and anovulation together were also considered. Sensitivity analysis was limited to only pregnant women with a diagnostic code for PCOS. Primary outcomes ascertained from linked HES data were (1) preterm delivery (gestation < 37 weeks), (2) mode of delivery, (3) high (> 4000 g) or low birthweight (< 2500 g) and (4) stillbirth. Secondary outcomes were (1) very preterm delivery (< 32 weeks), (2) extremely preterm delivery (< 28 weeks), (3) small and (4) large for gestational age. Conditional logistic regression models were performed adjusting for age, ethnicity, deprivation, dysglycaemia, hypertension, thyroid disorders, number of babies born at index pregnancy, and pre-gravid BMI. Multiple imputation was performed for missing outcome data.Results27,586 deliveries with maternal PCOS were matched for age (± 1 year) to 110,344 deliveries without PCOS. In the fully adjusted models, maternal PCOS was associated with an increased risk of (1) preterm birth [aOR: 1.11 (95% CI 1.06-1.17)], and (2) emergency caesarean, elective caesarean and instrumental vaginal compared to spontaneous delivery [aOR: 1.10 (1.05-1.15), 1.07 (1.03-1.12) and 1.04 (1.00-1.09), respectively]. There was absence of association with low birthweight, high birthweight and stillbirth. In the sensitivity analysis, the association with preterm birth [aOR: 1.31 (95% CI 1.13-1.52)], emergency caesarean [aOR: 1.15 (95% CI 1.02-1.30)], and elective caesarean [aOR: 1.03 (95% CI 1.02-1.03)] remained. While there was no significant association with any of the secondary outcomes in the primary analysis, in the sensitivity analysis maternal PCOS was associated with increased risk of extremely preterm delivery [aOR: 1.86 (95% CI 1.31-2.65)], and lower risk of small for gestational age babies [aOR: 0.74 (95% CI 0.59-0.94)].ConclusionsMaternal PCOS was associated with increased risk of preterm and caesarean delivery. Association with low birthweight may be largely mediated by lower gestational age at birth.

Project description:ObjectiveThe objective of this study was to investigate whether moderately increased maternal age is associated with obstetric and neonatal outcome in a contemporary population, and to consider the possible role of co-morbidities in explaining any increased risk.Study designSecondary analysis of routinely collected data from a large maternity unit in London, UK. Data were available on 51,225 singleton deliveries (?22 weeks) occurring to women aged ?20 between 2004 and 2012. Modified Poisson regression was used to estimate risk ratios for the association between maternal age and obstetric and neonatal outcome (delivery type, postpartum haemorrhage, stillbirth, low birthweight, preterm birth, small for gestational age, neonatal unit admission), using the reference group 20-24 years. Population attributable fractions were calculated to quantify the population impact.ResultsWe found an association between increasing maternal age and major postpartum haemorrhage (?1000ml blood loss) (RR 1.36 95% CI 1.18-1.57 for age 25-29 rising to 2.41 95% CI 2.02-2.88 for age ?40). Similar trends were observed for caesarean delivery, most notably for elective caesareans (RR 1.64 95% CI 1.36-1.96 for age 25-29 rising to 4.94 95% CI 4.09-5.96 for age ?40). There was evidence that parity modified this association, with a higher prevalence of elective caesarean delivery in older nulliparous women. Women aged ?35 were at increased risk of low birthweight and preterm birth. We found no evidence that the risk of stillbirth, small for gestational age, or neonatal unit admission differed by maternal age.ConclusionsOur results suggest a gradual increase in the risk of caesarean delivery and postpartum haemorrhage from age 25, persisting after taking into account maternal BMI, hypertension and diabetes. The risk of low birthweight and preterm birth was elevated in women over 35. Further research is needed to understand the reasons behind the high prevalence of elective caesarean delivery in nulliparous older mothers.

Dataset Information

Genetic risk assessment of thrombophilia in patients with adverse obstetric outcomes.

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Genetic risk assessment of thrombophilia in patients with adverse obstetric outcomes.

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