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

Abstract

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.

Ethnic Differences in the Association of Thrombophilic Polymorphisms with Obstetric Complications in Slovak and Roma (Gypsy) Populations

“…MTHFR 677T was associated with placental infarcts and subsequent fetal growth restriction (Hefler et al, 2004;Lin and August, 2005). In the study from Lykke et al (2012), MTHFR C677T was significantly associated only with severe preeclampsia (OR = 1.3). Nair et al (2012) reported strong association of this polymorphism with recurrent pregnancy loss in the population from northern India.…”

“…However, Subrt et al (2008) did not confirm the association of factor V Leiden with recurrent pregnancy loss in Czech patients. An extensive association study (Lykke et al, 2012) found out that factor V Leiden increased the risk of severe preeclampsia (OR = 1.6), fetal growth restriction (OR = 1.4), and placental abruption (OR = 1.7). Several studies dealing with pregnancy loss and thrombophilia were summarized in meta-analyses (Rey et al, 2003;Dudding and Attia, 2004), which describe the increased level of risk with OR ‡ 2 for carriers of factor V Leiden.…”

Thrombosis during pregnancy: Risks, prevention, and treatment for mother and fetus—harvesting the power of omic technology, biomarkers and in vitro or in vivo models to facilitate the treatment of thrombosis

“…Preterm delivery (<37 weeks of gestation) accounts for 6 to 12% of deliveries in the developed world (Beck et al, ). The hazard ratios for CVD associated with total preterm delivery are on the order of 1.3 to 2.6 when compared with term births (Irgens et al, ; Smith et al, ; Pell et al, ; Wikstrom et al, ; Nardi et al, ; Catov et al, ; Lykke et al, ,b, ,b,c; Bonamy et al, ; Rich‐Edwards et al, ).…”

Differences in Thrombotic Risk Factors in Black and White Women with Adverse Pregnancy Outcome

“…Thrombotic risk factors have been associated with pregnancy complications [4–8]. Many previous studies have found an association between inherited thrombophilia and adverse pregnancy outcomes, however there has been wide variability in the strength of the association and some studies have not found a relationship [4,6–12].…”