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The Association of Factor V Leiden and Prothrombin Gene Mutation and Placenta-Mediated Pregnancy Complications: A Systematic Review and Meta-analysis of Prospective Cohort Studies


Background:
Factor V Leiden (FVL) and prothrombin gene mutation (PGM) are common inherited thrombophilias. Retrospective studies variably suggest a link between maternal FVL/PGM and placenta-mediated pregnancy complications including pregnancy loss, small for gestational age, pre-eclampsia and placental abruption. Prospective cohort studies provide a superior methodologic design but require larger sample sizes to detect important effects. We undertook a systematic review and a meta-analysis of prospective cohort studies to estimate the association of maternal FVL or PGM carrier status and placenta-mediated pregnancy complications.

Methods and Findings:
A comprehensive search strategy was run in Medline and Embase. Inclusion criteria were: (1) prospective cohort design; (2) clearly defined outcomes including one of the following: pregnancy loss, small for gestational age, pre-eclampsia or placental abruption; (3) maternal FVL or PGM carrier status; (4) sufficient data for calculation of odds ratios (ORs). We identified 322 titles, reviewed 30 articles for inclusion and exclusion criteria, and included ten studies in the meta-analysis. The odds of pregnancy loss in women with FVL (absolute risk 4.2%) was 52% higher (OR = 1.52, 95% confidence interval [CI] 1.06–2.19) as compared with women without FVL (absolute risk 3.2%). There was no significant association between FVL and pre-eclampsia (OR = 1.23, 95% CI 0.89–1.70) or between FVL and SGA (OR = 1.0, 95% CI 0.80–1.25). PGM was not associated with pre-eclampsia (OR = 1.25, 95% CI 0.79–1.99) or SGA (OR 1.25, 95% CI 0.92–1.70).

Conclusions:
Women with FVL appear to be at a small absolute increased risk of late pregnancy loss. Women with FVL and PGM appear not to be at increased risk of pre-eclampsia or birth of SGA infants.

: Please see later in the article for the Editors' Summary


Vyšlo v časopise: The Association of Factor V Leiden and Prothrombin Gene Mutation and Placenta-Mediated Pregnancy Complications: A Systematic Review and Meta-analysis of Prospective Cohort Studies. PLoS Med 7(6): e32767. doi:10.1371/journal.pmed.1000292
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1000292

Souhrn

Background:
Factor V Leiden (FVL) and prothrombin gene mutation (PGM) are common inherited thrombophilias. Retrospective studies variably suggest a link between maternal FVL/PGM and placenta-mediated pregnancy complications including pregnancy loss, small for gestational age, pre-eclampsia and placental abruption. Prospective cohort studies provide a superior methodologic design but require larger sample sizes to detect important effects. We undertook a systematic review and a meta-analysis of prospective cohort studies to estimate the association of maternal FVL or PGM carrier status and placenta-mediated pregnancy complications.

Methods and Findings:
A comprehensive search strategy was run in Medline and Embase. Inclusion criteria were: (1) prospective cohort design; (2) clearly defined outcomes including one of the following: pregnancy loss, small for gestational age, pre-eclampsia or placental abruption; (3) maternal FVL or PGM carrier status; (4) sufficient data for calculation of odds ratios (ORs). We identified 322 titles, reviewed 30 articles for inclusion and exclusion criteria, and included ten studies in the meta-analysis. The odds of pregnancy loss in women with FVL (absolute risk 4.2%) was 52% higher (OR = 1.52, 95% confidence interval [CI] 1.06–2.19) as compared with women without FVL (absolute risk 3.2%). There was no significant association between FVL and pre-eclampsia (OR = 1.23, 95% CI 0.89–1.70) or between FVL and SGA (OR = 1.0, 95% CI 0.80–1.25). PGM was not associated with pre-eclampsia (OR = 1.25, 95% CI 0.79–1.99) or SGA (OR 1.25, 95% CI 0.92–1.70).

Conclusions:
Women with FVL appear to be at a small absolute increased risk of late pregnancy loss. Women with FVL and PGM appear not to be at increased risk of pre-eclampsia or birth of SGA infants.

: Please see later in the article for the Editors' Summary


Zdroje

1. BrennerB

2003 Antithrombotic prophylaxis for women with thrombophilia and pregnancy complications - Yes. J Thromb Haemost 1 2070

2. BrennerB

2006 Thrombophilia and adverse pregnancy outcome. Obstet Gynecol Clin North Am 33 443 456 ix

3. RodgerMA

PaidasM

McLintockC

MiddeldorpS

KahnS

2008 Inherited thrombophilia and pregnancy complications revisited. Obstet Gynecol 112 320

4. KujovichJL

2004 Thrombophilia and pregnancy complications. Am J Obstet Gynecol 191 412

5. BrownK

LuddingtonR

WilliamsonD

BakerP

BaglinT

1997 Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3′-untranslated region of the prothrombin gene. Br J Haematol 98 907

6. KosterT

BlannAD

BrietE

VandenbrouckeJP

RosendaalFR

1995 Role of clotting factor VIII in effect of von Willebrand factor on occurrence of DVT. Lancet 345 152

7. KraaijenhagenRA

AnkerPS

KoopmanMMW

ReitsmaPH

PrinsMH

2000 High plasma concentration of Factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 83 5

8. PoortSR

RosendaalFR

ReitsmaPH

BertinaRM

1996 A common genetic variation in the 3′ -untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88 3698

9. RodeghieroF

TosettoA

1997 The epidemiology of inherited thrombophilia: the VITA Project. Vicenza Thrombophilia and Atherosclerosis Project. Thromb Haemost 78 636

10. SoutoJC

CollI

LlobetD

del RioE

OliverA

1998 The prothrombin 20210A allele is the most prevalent genetic risk factor for venous thromboembolism in the Spanish population. Thromb Haemost 80 366

11. van der MeerFJ

KosterT

VandenbrouckeJP

BrietE

RosendaalFR

1997 The Leiden Thrombophilia Study (LETS). Thromb Haemost 78 631

12. IsermannB

SoodR

PawlinskiR

ZoggM

KallowayS

2003 The thrombomodulin-protein C system is essential for the maintenance of pregnancy. Nat Med 9 331

13. HowleyHE

WalkerM

RodgerMA

2005 A systematic review of the association between factor V Leiden or prothrombin gene variant and intrauterine growth restriction. Am J Obstet Gynecol 192 694

14. ReyE

KahnSR

DavidM

ShrierI

2003 Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 361 901

15. WuO

RobertsonL

TwaddleS

LoweGD

ClarkP

2006 Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study. Health Technol Assess 10 1

16. FunaiEF

2009 Inherited thrombophilia and preeclampsia: is the evidence beginning to congeal? [comment]. Am J Obstet Gynecol 200 121

17. SIGN. Scottish Intercollegiate Guidelines Network 2008 Search filters for study designs. Available: http://www.sign.ac.uk/methodology/filters.html. Accessed 12 April 2010

18. HelewaME

BurrowsRF

SmithJ

WilliamsK

BrainP

1997 Report of the Canadian Hypertension Society Consensus Conference: 1. Definitions, evaluation and classification of hypertensive disorders in pregnancy. CMAJ 157 715

19. SchroederBM

American College of Obstetricians and Gynecologists 2002 ACOG practice bulletin on diagnosing and managing preeclampsia and eclampsia. American College of Obstetricians and Gynecologists. American Family Physician 66 330 331

20. CoddingtomCC

JonesRO

2007 Pregnancy loss and spontaneous abortion. Manual of obstetrics.

EvansAT

Philadelphia Lippincott Williams & Wilkins

21. CunninghamFG

HaulthJC

LevenoKJ

BloomSL

WenstromKD

2005 Williams obstetrics New York McGraw-Hill

22. CorabianP

2005 Protocols for stillbirth investigation Calgary, Alberta Alberta Heritage Foundation for Medical Research 14

23. HelenK

2003 Placenta previa and abruption. Danforth's obstetrics & gynecology.

ScothhJR

GibbsRS

KarlanBY

HaneyAF

Philadelphia Lippicott Williams & Wilkins

24. AndersonMS

HayWW

2005 Intrauterine growth restriction and the small-for-gestational-age infant. Avery's neonatology.

MacDonaldMG

SeshiaMM

MulletMD

Philadelphia Lippicott Williams & Wilkins

25. GalanHL

HobbinsJC

2003 Intrauterine growth restriction. Danforth's obstetrics & gynecology.

ScothhJR

GibbsRS

KarlanBY

HaneyAF

Philadelphia Lippicott Williams & Wilkins

26. WellsGA

SheaB

O'ConnellD

PetersonJ

WelchV

2009 The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available: http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed 9 May 2010

27. HigginsJP

ThompsonSG

DeeksJJ

AltmanDG

2003 Measuring inconsistency in meta-analyses. BMJ 327 557

28. HigginsJP

ThompsonSG

2002 Quantifying heterogeneity in a meta-analysis. Stat Med 21 1539

29. BradburnMJ

DeeksJJ

BerlinJA

RussellLA

2007 Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med 26 53

30. MullanRJ

FlynnDN

CarlbergB

TleyjehIM

KamathCC

2009 Systematic reviewers commonly contact study authors but do so with limited rigor. J Clin Epidemiol 62 138

31. SalomonO

SeligsohnU

SteinbergDM

ZalelY

LernerA

2004 The common prothrombotic factors in nulliparous women do not compromise blood flow in the feto-maternal circulation and are not associated with preeclampsia or intrauterine growth restriction. Am J Obstet Gynecol 191 2002

32. RodgerM

2007 Abstract: Factor V Leiden (FVL) and prothrombin gene variant (PGV) may be only weakly associated with placenta mediated pregnancy complications: a large prospective cohort study. J Thromb Haemost 5 0S 054

33. ClarkP

WalkerID

GovanL

WuO

GreerIA

2008 The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes. Br J Haematol 140 236

34. Dizon-TownsonD

MillerC

SibaiB

SpongCY

ThomE

2005 The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstet Gynecol 106 517

35. DuddingT

HeronJ

ThakkinstianA

NurkE

GoldingJ

2008 Factor V Leiden is associated with pre-eclampsia but not with fetal growth restriction: a genetic association study and meta-analysis. J Thromb Haemost 6 1869

36. KarakantzaM

AndroutsopoulosG

MougiouA

SakellaropoulosG

KourounisG

2008 Inheritance and perinatal consequences of inherited thrombophilia in Greece. Int J Gynaecol Obstet 100 124

37. LindqvistPG

SvenssonP

DahlbackB

2006 Activated protein C resistance in the absence of factor V Leiden and pregnancy. J Thromb Haemost 42 361

38. MurphyRP

DonoghueC

NallenRJ

D'MelloM

ReganC

2000 Prospective evaluation of the risk conferred by factor V Leiden and thermolabile methylenetetrahydrofolate reductase polymorphisms in pregnancy. Arterioscler Thromb Vasc Biol 20 266

39. SaidJM

HigginsJR

MosesEK

WalkerSP

BorgAJ

2010 Inherited thrombophilia polymorphisms and pregnancy outcomes in nulliparous women. Obstet Gynecol 115 5

40. SilverRM

ZhaoY

SpongCY

SibaiB

WendelG

2010 Prothrombin gene G20210A mutation and obstetric complications. Obstet Gynecol 115 14

41. KupfermincMJ

EldorA

SteinmanN

ManyA

Bar-AmA

1999 Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 340 9

42. GrisJ-C

2009 Thrombophilia and pregnancy loss: cause or association. Thromb Res 123 S105

43. StraussRS

2000 Adult functional outcome of those born small for gestational age: twenty-six-year follow-up of the 1970 British Birth Cohort. JAMA 283 625

44. FaccoF

YouW

GrobmanW

2009 Genetic thrombophilias and intrauterine growth restriction: a meta-analysis. Obstet Gynecol 113 1206

45. KistWJ

JanssenNJ

KalkJJ

HagueWM

DekkerGA

2008 Thrombophilias and adverse pregnancy outcome - A confounded problem! Thromb Haemost 99 77

46. BrennerB

2003 Inherited thrombophilia and pregnancy loss. Best Pract Res Clin Haematol 16 311

47. NorrieG

FarquharsonRG

GreavesM

2009 Screening and treatment for heritable thrombophilia in pregnancy failure: inconsistencies among UK early pregnancy units. Br J Haematol 144 241 244

48. ClarkP

WalkerID

LanghorneP

CrichtonL

ThomsonA

2010 SPIN: the Scottish Pregnancy Intervention Study: a multicentre randomised controlled trial of low molecular weight heparin and low dose aspirin in women with recurrent miscarriage. Blood In press

49. KaandorpSP

GoddijnM

van der PostJA

HuttenBA

VerhoeveHR

2010 Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med 362 1586 1596

Štítky
Interné lekárstvo

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PLOS Medicine


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