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APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women.

ABSTRACT: BACKGROUND: Activated Protein C Resistance (APCR), a poor anticoagulant response of APC in haemostasis, is the commonest heritable thrombophilia. Adverse outcomes during pregnancy have been linked to APCR. This study determined the frequency of APCR, factor V gene known and novel SNPs and adverse outcomes in a group of pregnant women. METHODS: Blood samples collected from 907 pregnant women were tested using the Coatest Classic and Modified functional haematological tests to establish the frequency of APCR. PCR-Restriction Enzyme Analysis (PCR-REA), PCR-DNA probe hybridisation analysis and DNA sequencing were used for molecular screening of known mutations in the factor V gene in subjects determined to have APCR based on the Coatest Classic and/or Modified functional haematological tests. Glycosylase Mediated Polymorphism Detection (GMPD), a SNP screening technique and DNA sequencing, were used to identify SNPs in the factor V gene of 5 APCR subjects. RESULTS: Sixteen percent of the study group had an APCR phenotype. Factor V Leiden (FVL), FV Cambridge, and haplotype (H) R2 alleles were identified in this group. Thirty-three SNPs; 9 silent SNPs and 24 missense SNPs, of which 20 SNPs were novel, were identified in the 5 APCR subjects. Adverse pregnancy outcomes were found at a frequency of 35% in the group with APCR based on Classic Coatest test only and at 45% in the group with APCR based on the Modified Coatest test. Forty-eight percent of subjects with FVL had adverse outcomes while in the group of subjects with no FVL, adverse outcomes occurred at a frequency of 37%. CONCLUSIONS: Known mutations and novel SNPs in the factor V gene were identified in the study cohort determined to have APCR in pregnancy. Further studies are required to investigate the contribution of these novel SNPs to the APCR phenotype. Adverse outcomes including early pregnancy loss (EPL), preeclampsia (PET) and intrauterine growth restriction (IGUR) were not significantly more frequent in subjects with APCR compared to normal pregnant women however Pregnancy induced hypertension (PIH) was found to be associated with FVL in our study group.

SUBMITTER: Sedano-Balbas S

PROVIDER: S-EPMC2853494 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women.

Sedano-Balbás Sara S Lyons Mark M Cleary Brendan B Murray Margaret M Gaffney Geraldine G Maher Majella M

BMC pregnancy and childbirth 20100310

<h4>Background</h4>Activated Protein C Resistance (APCR), a poor anticoagulant response of APC in haemostasis, is the commonest heritable thrombophilia. Adverse outcomes during pregnancy have been linked to APCR. This study determined the frequency of APCR, factor V gene known and novel SNPs and adverse outcomes in a group of pregnant women.<h4>Methods</h4>Blood samples collected from 907 pregnant women were tested using the Coatest Classic and Modified functional haematological tests to establi ...[more]

PMID: 20214832

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Project description:BACKGROUND:Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) associates with T2DM and CVD. The impact of maternal MetS on pregnancy outcomes, in nulliparous pregnant women, has not been investigated. METHODS AND FINDINGS:Low-risk, nulliparous women were recruited to the multi-centre, international prospective Screening for Pregnancy Endpoints (SCOPE) cohort between 11 November 2004 and 28 February 2011. Women were assessed for a range of demographic, lifestyle, and metabolic health variables at 15 ± 1 weeks' gestation. MetS was defined according to International Diabetes Federation (IDF) criteria for adults: waist circumference ?80 cm, along with any 2 of the following: raised trigycerides (?1.70 mmol/l [?150 mg/dl]), reduced high-density lipoprotein cholesterol (<1.29 mmol/l [<50 mg/dl]), raised blood pressure (BP) (i.e., systolic BP ?130 mm Hg or diastolic BP ?85 mm Hg), or raised plasma glucose (?5.6 mmol/l). Log-binomial regression analyses were used to examine the risk for each pregnancy outcome (GDM, PE, large for gestational age [LGA], small for gestational age [SGA], and spontaneous preterm birth [sPTB]) with each of the 5 individual components for MetS and as a composite measure (i.e., MetS, as defined by the IDF). The relative risks, adjusted for maternal BMI, age, study centre, ethnicity, socioeconomic index, physical activity, smoking status, depression status, and fetal sex, are reported. A total of 5,530 women were included, and 12.3% (n = 684) had MetS. Women with MetS were at an increased risk for PE by a factor of 1.63 (95% CI 1.23 to 2.15) and for GDM by 3.71 (95% CI 2.42 to 5.67). In absolute terms, for PE, women with MetS had an adjusted excess risk of 2.52% (95% CI 1.51% to 4.11%) and, for GDM, had an adjusted excess risk of 8.66% (95% CI 5.38% to 13.94%). Diagnosis of MetS was not associated with increased risk for LGA, SGA, or sPTB. Increasing BMI in combination with MetS increased the estimated probability for GDM and decreased the probability of an uncomplicated pregnancy. Limitations of this study are that there are several different definitions for MetS in the adult population, and as there are none for pregnancy, we cannot be sure that the IDF criteria are the most appropriate definition for pregnancy. Furthermore, MetS was assessed in the first trimester and may not reflect pre-pregnancy metabolic health status. CONCLUSIONS:We did not compare the impact of individual metabolic components with that of MetS as a composite, and therefore cannot conclude that MetS is better at identifying women at risk. However, more than half of the women who had MetS in early pregnancy developed a pregnancy complication compared with just over a third of women who did not have MetS. Furthermore, while increasing BMI increases the probability of GDM, the addition of MetS exacerbates this probability. Further studies are required to determine if individual MetS components act synergistically or independently.

Project description:ImportanceWomen with disabilities have a higher risk of preterm birth, gestational diabetes, preeclampsia, and cesarean delivery; however, their risk of other obstetric interventions, adverse maternal outcomes, and clinical indications for increased cesarean delivery is unclear.ObjectiveTo evaluate risk of a range of obstetric interventions and adverse maternal outcomes, including severe maternal morbidities (SMM) and mortality, among women with and without disabilities.Design, setting, and participantsThe Consortium on Safe Labor was a retrospective cohort that included comprehensive medical chart review for deliveries between January 2002 and January 2008. Data were collected from 12 clinical sites, which included 19 hospitals across the United States. This secondary analysis was conducted in February to July 2021.ExposuresUsing International Classification of Diseases, Ninth Revision, codes and a validated algorithm to define disability, participants were classified as having physical, intellectual, sensory, or any disability, and compared with women with no documented disability.Main outcomes and measuresThe relative risk (RR) of 23 obstetric interventions and adverse maternal outcomes, including SMM and mortality, was evaluated.ResultsOf the 223 385 women in the study, 9206 (4.1%) were Asian or Pacific Islander, 50 235 (22.5%) were Black, 39 039 (17.5%) were Hispanic, and 110 443 (49.4%) were White, with a mean (SD) age of 27.6 (6.2) years. There were 2074 (0.9%) women with disability and 221 311 (99.1%) without. Among women with disabilities, 1733 (83.5%) were physical, 91 (4.4%) were intellectual, and 250 (12.1%) were sensory. Compared with women with no disability, women with disabilities had higher risk of gestational diabetes, placenta previa, premature rupture of membranes, preterm premature rupture of membranes, and postpartum fever as well as maternal death (adjusted relative risk [aRR], 11.19; 95% CI, 2.40-52.19) and individual SMMs: severe preeclampsia/eclampsia (aRR, 2.15; 95% CI, 1.80-2.56), hemorrhage (aRR, 1.27; 95% CI, 1.09-1.49), and fever (aRR, 1.32; 95% CI, 1.03-1.67), with the highest risk observed for thromboembolism (aRR, 6.08; 95% CI, 4.03-9.16), cardiovascular events (aRR, 4.02; 95% CI, 2.87-5.63), and infection (aRR, 2.69; 95% CI, 1.97-3.67). Women with any disability also had higher risk of interventions, including oxytocin augmentation, operative vaginal delivery, and cesarean delivery (aRR, 1.33; 95% CI, 1.25-1.42), with the cesarean indication less likely to be medically indicated (aRR, 0.79; 95% CI, 0.70-0.89). Risk of adverse outcomes and interventions remained consistent across disability categories.Conclusions and relevanceIn this study, women with physical, intellectual, and sensory disability during pregnancy were at higher risk of adverse outcomes, including a broad range of SMM and maternal mortality.

Project description:Background:It is well documented that overt hypothyroidism is associated with adverse pregnancy outcomes, but studies of subclinical hypothyroidism have demonstrated conflicting results. Objective:Thyroid hormones are known to regulate mitochondrial function, and the aim of this study was to examine the possible relationship of subclinical hypothyroidism and mitochondrial dysfunction to adverse pregnancy outcomes in pregnant women. Methods:Women in their third trimester of pregnancy (n = 113) who did not receive thyroid medication were included in this cross-sectional study. All participants were interviewed, and their thyroid status was determined. All participants had concentrations of thyroid hormones (fT4 and tT3) within the reference range. In addition to thyroid status, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were measured by flow cytometry. To establish a reference range of MMP and ROS, a group of euthyroid, nonpregnant women were used as euthyroid controls. Adverse pregnancy outcome was defined as preterm delivery, preeclampsia, placental abruption, Apgar score <7 points 1 minute after birth, or postpartum hemorrhage. Results:The prevalence of subclinical hypothyroidism among pregnant women was 17% (n = 19), and the number of overall adverse pregnancy outcomes was increased (p = 0.02) compared with that in euthyroid pregnant women. Preeclampsia, poor Apgar score, and postpartum hemorrhage were more frequent in the subclinical hypothyroidism group than in the euthyroid group (p = 0.04, p = 0.001 and p = 0.03, respectively), and more women showed prolonged gestation and gave birth later than 41 weeks of gestation than in the euthyroid group (p = 0.04). Compared with euthyroid, nonpregnant controls, a physiological upregulation of mitochondrial function was observed in euthyroid pregnant women. This was impaired in pregnant women with subclinical hypothyroidism. Compared with euthyroid, nonpregnant controls, pregnant women had increased ROS regardless of their thyroid status. Conclusion:We speculate that the unfavorable effects on mitochondrial function in women with subclinical hypothyroidism may be associated with higher prevalence of adverse pregnancy outcomes.

Dataset Information

APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women.

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APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women.

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