Primary prophylaxis to prevent obstetric complications in asymptomatic women with antiphospholipid antibodies: a systematic review

Abstract

Objective

Obstetric complications are common in patients with antiphospholipid syndrome. However, the impact of antiphosholipid antibodies (aPL) in the pregnancy outcomes of asymptomatic aPL carriers is uncertain. The aim of this systematic review is to assess whether primary prophylaxis is beneficial to prevent obstetric complications during pregnancy in asymptomatic women positive for aPL who have no history of recurrent pregnancy loss or intrauterine fetal death.

Methods

Studies evaluating the effect of prophylactic treatment versus no treatment in asymptomatic pregnant aPL carriers were identified in an electronic database search. Design, population and outcome homogeneity of studies was assessed and meta-analysis was performed. The pooled Mantel–Haenszel relative risk of specific pregnancy outcomes was obtained using random effects models. Heterogeneity was measured with the I² statistic. All analyses were conducted using Review Manager 5.3.

Results

Data from five studies involving 154 pregnancies were included and three studies were meta-analysed. The risk ratio and 95% confidence interval (CI) of live birth rates, preterm birth, low birth weight and overall pregnancy complications in treated and untreated pregnancies were 1.14 (0.18–7.31); 1.71 (0.32–8.98); 0.98 (0.07–13.54) and 2.15 (0.63–7.33),respectively. Results from the meta-analysis revealed that prophylactic treatment with aspirin is not superior to placebo to prevent pregnancy complications in asymptomatic aPL carriers.

Conclusion

This systematic review did not find evidence of the superiority of prophylactic treatment with aspirin compared to placebo or usual care to prevent unfavourable obstetric outcomes in otherwise healthy women with aPL during the first pregnancy.

Keywords

Pregnancy morbidity obstetric outcome aspirin lupus anticoagulant anticardiolipin antibodies

Get full access to this article

View all access options for this article.

References

Miyakis

Lockshin

Atsumi

. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295–306.

Mehrani

Petri

Epidemiology of the antiphospholipid syndrome. In: Cervera

Reverter

Kamashta

(eds). Handbook of Systemic Autoimmune Diseases 2009; Vol. 10. Oxford, UK: Elsevier, pp. 13–34. .

Tektonidou

Laskari

Panagiotakos

Moutsopoulos

. Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies. Arthritis Rheum 2009; 61: 29–36.

Sene

Piette

Cacoub

. Antiphospholipid antibodies, antiphospholipid syndrome and infections. Autoimmun Rev 2008; 7: 272–277.

Caporali

Pallavicini

Filippini

. Treatment of rheumatoid arthritis with anti-TNF-alpha agents: a reappraisal. Autoimmun Rev 2009; 8: 274–280.

Cervera

Piette

Font

. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46: 1019–1027.

Cervera

. Lessons from the “Euro-Phospholipid” project. Autoimmun Rev 2008; 7: 174–178.

Le Thi Thuong

Tieulie

Costedoat

. The HELLP syndrome in the antiphospholipid syndrome: retrospective study of 16 cases in 15 women. Ann Rheum Dis 2005; 64: 273–278.

Mak

Cheung

Cheak

. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology 2010; 49: 281–288.

10.

Nodler

Moolamalla

Ledger

Nuwayhid

Mulla

. Elevated antiphospholipid antibody titers and adverse pregnancy outcomes: analysis of a population-based hospital dataset. BMC Pregnancy Childbirth 2009; 9: 11.

11.

Rai

Clifford

Cohen

Regan

. High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies. Hum Reprod 1995; 10: 3301–3304.

12.

Wells GA, Shea B, O'Connell D, et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality of non-randomised studies in meta-analyses. 2010. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

13.

Higgins J, Green S Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.12011 [updated March 2011].

14.

Kaaja

Julkunen

Viinikka

Ylikorkala

. Production of prostacyclin and thromboxane in lupus pregnancies: effect of small dose of aspirin. Obstet Gynecol 1993; 81: 327–331.

15.

Julkunen

Jouhikainen

Kaaja

. Fetal outcome in lupus pregnancy: the prognostic significance of an untreated and treated lupus anticoagulant. J Rheumatol 1994; 21: 970–971.

16.

Cowchock

Reece

. Do low-risk pregnant women with antiphospholipid antibodies need to be treated? Organizing Group of the Antiphospholipid Antibody Treatment Trial. Am J Obstet Gynecol 1997; 176: 1099–1100.

17.

Kahwa

Sargeant

McCaw-Binns

. Anticardiolipin antibodies in Jamaican primiparae. J Obstet Gynaecol 2006; 26: 122–126.

18.

Del Ross

Ruffatti

Visentin

. Treatment of 139 pregnancies in antiphospholipid-positive women not fulfilling criteria for antiphospholipid syndrome: a retrospective study. J Rheumatol 2013; 40: 425–429.

19.

Metjian

Lim

. ASH evidence-based guidelines: should asymptomatic patients with antiphospholipid antibodies receive primary prophylaxis to prevent thrombosis? Hematology Am Soc Hematol Educ 2009, pp. 247–249.

20.

Cowchock

Reece

Balaban

Branch

Plouffe

. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol 1992; 166: 1318–1323.

21.

Golding

. A randomised trial of low dose aspirin for primiparae in pregnancy. The Jamaica Low Dose Aspirin Study Group. Br J Obstet Gynaecol 1998; 105: 293–299.