Factor V Leiden as a risk factor for preterm birth – a population‐based nested case–control study

Hiltunen, Leena; Laivuori, Hannele; Rautanen, Anna; Kaaja, Risto; Kere, Juha; Krusius, Tom; Rasi, Vesa; Paunio, Mikko

doi:10.1111/j.1538-7836.2010.04104.x

Cited by 22 publications

(16 citation statements)

References 31 publications

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“…A study of 100 000 consecutive pregnancies in Finland showed F5 G1691A, but not F2 polymorphism, to triple the risk for late preterm birth at or after 32 weeks of gestation (Hiltunen et al , ), A population‐based study of women delivering a singleton live birth found PE, fetal distress, SGA or PA in over half of all medically indicated preterm deliveries (less than 35 weeks; Ananth & Vintzileos, ). A nested case‐cohort study of pregnant women from the Danish National Birth Cohort showed that F5 G1691A increased the risk of severe PE (mean OR 1·6), severe FGR/SGA (defined bellow the 3rd percentile; mean OR 1·4) and clinically symptomatic PA (mean OR 1·7; Lykke et al , ).…”

Section: Thrombophilia and Placenta‐mediated Pregnancy Complicationsmentioning

confidence: 99%

Antithrombotic treatment for pregnancy complications: which path for the journey to precision medicine?

2014

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SummaryHaemostatic and vascular biology mechanisms appear to play an important role in the pathogenesis of placenta-mediated pregnancy complications. Although low-dose aspirin (LDA) has a modest effect in preventing preeclampsia, antithrombotic interventions, LDA and low molecular weight heparin (LMWH) have not definitively proven their effectiveness in women with placenta-mediated pregnancy complications selected by previous pregnancy outcome alone. Given the heterogeneous aetiology of placenta-mediated pregnancy complications, it is critical to stratify patients according to maternal and fetal characteristics and disease mechanisms rather than simply by pregnancy outcome, such as miscarriage. Such stratification could identify those who could benefit from antithrombotic interventions in pregnancy. We lack data on genome-wide association studies, biomarkers and trials of interventions applied to specific homogeneous populations. Future studies should focus on elaborating different disease mechanisms and examining antithrombotic interventions in specific and more homogeneous groups, such as thrombophilic women with well-characterized placenta-mediated pregnancy complications, stratified by disease severity and pathological findings. Because of fetal safety concerns with new anticoagulants, the intervention should focus on heparins alone or in combination with LDA. Thus, placentamediated pregnancy complications deserve precision medicine, defining disease by mechanism rather than outcome with interventions focused on a more personalized approach.

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Section: Thrombophilia and Placenta‐mediated Pregnancy Complicationsmentioning

confidence: 99%

Antithrombotic treatment for pregnancy complications: which path for the journey to precision medicine?

2014

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“…Researchers have identified a few potential maternal risk factors associated with preterm birth including maternal hypertension [5], Factor V Leiden [19], lower genital tract inflammatory milieu [20], prior preeclampsia [18], and Crohn’s disease [21]. Not only were these trials limited in statistical power, few studies explored potential risk factors for ePTB, which has a higher risk for poor health outcomes [13, 22].…”

Section: Introductionmentioning

confidence: 99%

Subgroup identification of early preterm birth (ePTB): informing a future prospective enrichment clinical trial design

Zhang

Garrard

Keighley

et al. 2017

BMC Pregnancy Childbirth

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BackgroundDespite the widely recognized association between the severity of early preterm birth (ePTB) and its related severe diseases, little is known about the potential risk factors of ePTB and the sub-population with high risk of ePTB. Moreover, motivated by a future confirmatory clinical trial to identify whether supplementing pregnant women with docosahexaenoic acid (DHA) has a different effect on the risk subgroup population or not in terms of ePTB prevalence, this study aims to identify potential risk subgroups and risk factors for ePTB, defined as babies born less than 34 weeks of gestation.MethodsThe analysis data (N = 3,994,872) were obtained from CDC and NCHS’ 2014 Natality public data file. The sample was split into independent training and validation cohorts for model generation and model assessment, respectively. Logistic regression and CART models were used to examine potential ePTB risk predictors and their interactions, including mothers’ age, nativity, race, Hispanic origin, marital status, education, pre-pregnancy smoking status, pre-pregnancy BMI, pre-pregnancy diabetes status, pre-pregnancy hypertension status, previous preterm birth status, infertility treatment usage status, fertility enhancing drug usage status, and delivery payment source.ResultsBoth logistic regression models with either 14 or 10 ePTB risk factors produced the same C-index (0.646) based on the training cohort. The C-index of the logistic regression model based on 10 predictors was 0.645 for the validation cohort. Both C-indexes indicated a good discrimination and acceptable model fit. The CART model identified preterm birth history and race as the most important risk factors, and revealed that the subgroup with a preterm birth history and a race designation as Black had the highest risk for ePTB. The c-index and misclassification rate were 0.579 and 0.034 for the training cohort, and 0.578 and 0.034 for the validation cohort, respectively.ConclusionsThis study revealed 14 maternal characteristic variables that reliably identified risk for ePTB through either logistic regression model and/or a CART model. Moreover, both models efficiently identify risk subgroups for further enrichment clinical trial design.

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“…In contrast, Hiltunen et al. [29] in a Finish case–control study found FV Leiden to be associated with late preterm delivery (gestational age [GA] 32–36 weeks), but not with very preterm delivery (GA < 32 weeks); PTM was not associated with preterm delivery. We did not find evidence of any association with very preterm delivery.…”

Section: Discussionmentioning

confidence: 94%

Thrombophilias and adverse pregnancy outcomes: results from the Danish National Birth Cohort

Lykke

Bare²,

Olsen

et al. 2012

Journal of Thrombosis and Haemostasis

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Summary. Background: Inherited thrombophilias have inconsistently been linked to adverse pregnancy outcomes. Differences in study design, size and population could explain this heterogeneity. Objective: The aim of the present study was to evaluate if factor (F)V Leiden G1691A, prothrombin mutation G20210A (PTM) and methylenetetrahydrofolate reductase C677T (MTHFR) increased the risk of severe preeclampsia, fetal growth restriction, very preterm delivery, placental abruption and a composite of these outcomes also including stillbirth. Patients and methods: In a nested case–cohort study of pregnant women in Denmark, we genotyped 2032 cases and 1851 random controls. Each of the medical records of the cases was validated. We calculated both genomic and allelic models, and present both models. We also performed sensitivity analyses adjusting for parity, age, smoking, body mass index and socioeconomic status. Results: In the allelic models, FV Leiden increased the risk of the composite outcome (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1–1.8), severe preeclampsia (OR 1.6, 95% CI 1.1–2.4), fetal growth restriction (OR 1.4, 95% CI 1.1–1.8) and placental abruption (OR=1.7 (95% CI 1.2–2.4). In the sensitivity analyses, adjustment diminished these estimates slightly. PTM was not significantly associated with any of the outcomes, and MTHFR was only significantly associated with severe preeclampsia (OR 1.3, 95% CI 1.1–1.6). Conclusion: FV Leiden predisposes to adverse pregnancy outcomes in a setting of Scandinavian women.

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Factor V Leiden as a risk factor for preterm birth – a population‐based nested case–control study

Cited by 22 publications

References 31 publications

Antithrombotic treatment for pregnancy complications: which path for the journey to precision medicine?

Antithrombotic treatment for pregnancy complications: which path for the journey to precision medicine?

Subgroup identification of early preterm birth (ePTB): informing a future prospective enrichment clinical trial design

Thrombophilias and adverse pregnancy outcomes: results from the Danish National Birth Cohort

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