The use of low-dose aspirin during pregnancy decreases the risk of preeclampsia for women considered at increased risk. The effect is smaller for women without risk factors (strength of recommendation [SOR]: A, based on randomized controlled trials [RCTs] and systematic reviews [SRs] of RCTs)

Atlas, Michel C.

Gauer, Robert

University of Missouri: MOspace

CliniCal InquIrIes From the Family Physicians Inquiries Network54	 vol 57, no 1 / january 2008  The Journal of family PracTice		Does	low-dose	aspirin	reduce	preeclampsia	and	other		maternal-fetal	complications?Robert Gauer, MD Womack Army Medical Center Family Medicine Residency Program, Fort Bragg, NC Michel atlas, MliS Kornhauser Health Sciences Library, University of Louisville, Louisville, Kyyes. The use of low-dose aspirin during pregnancy decreases the risk of preeclampsia for women considered at increased risk. The effect is smaller for women without risk factors (strength of recommendation [sor]: a, based on randomized controlled trials [rCTs] and systematic reviews [srs] of rCTs).  rates of preterm delivery, perinatal death, and incidence of small-for-gestational age infants are decreased for women treated with low-dose aspirin (sor: a, based on srs and rCTs). a meta-analysis of rCTs has found no increased rates of harm from low-dose aspirin therapy, including placental abruption or other antepartum bleeding complications (sor: a, based on srs and rCTs). i prescribe 81 mg/day of aspirin for women with previous severe preeclampsia Confused about when to use aspirin in pregnancy? you’re not alone. over my 20 years of practice, I have reacted to disparate guidelines ranging from “never use aspirin in pregnancy” to “always use low-dose aspirin.” This review helps simplify my clinical practice. With the benefit of evidence from multiple rCTs over the past 7 years, I now personally use 81 mg of aspirin each day in 2 groups of women: those who had severe preeclampsia in a prior pregnancy, and those who develop signs of preeclampsia or strong risk factors for it before the third trimester in their current pregnancy.  John Hill, DODepartment of Family Medicine, university of Colorado, Denverz	Evidence	summarySystematic	reviews	show	aspirin	lowers	rates	of	preeclampsiaFour SRs published between 2001 and 20071–4 and a Cochrane Review up-dated in 20065 have demonstrated that low-dose aspirin helps to prevent pre-eclampsia, reduction in preterm delivery rates, and decreased perinatal mortality.The 2001 Sr by Duley1 included 39 trials and 30,563 patients. Patients were classified either as high-risk (previous se-vere preeclampsia, diabetes, chronic hy-pertension, renal disease, or autoimmune disease) or moderate-risk (remainder of subjects). Four individual studies (with a combined weight of 27%) did not sup-port aspirin therapy. The largest trial not supporting aspirin therapy included 6275 subjects and had a relative risk of 1.14 (95% CI, 0.94–1.38). Most studies in this review compared evidence-based answerclinical commentaryfast trackLow-dose aspirin helps prevent  preeclampsia  in higher-risk  patients  fast track vol 57, no 1 / january 2008 55www.jfponline.comaspirin alone with placebo (28,802 sub-jects). However, 4 studies either com-pared combination therapy with aspirin or other thromboprophylaxis therapy (dipyridamole, heparin, or ozagrel). Al-though there were differences in risk stratification, variable doses of aspirin, and varied gestational age at trial entry, all studies reported an overall 15% re-duction of preeclampsia (RR=0.85; 95% CI, 0.78–0.92).The 2003 Sr by coomarasamy2 in-cluded 14 trials and 12,416 patients. The study exclusively evaluated high-risk pregnancies:  women with history (or family history) of preeclampsia, chronic hypertension, gestational diabe-tes, or renal disease. The overall reduc-tion in preeclampsia was 14% (relative risk [RR]=0.86; 95% confidence interval [CI], 0.76–0.96). Results were consistent across RCTs, and only 2 of the 14 studies (with a combined weight of 7.1%) did not support aspirin therapy.ruano’s 2005 Sr3 included 22 tri-als with 33,598 subjects and specifically compared low-risk vs high-risk patients. The authors concluded that there was no significant reduction in preeclampsia with the use of low-dose aspirin in the low-risk arm (RR=0.95; 95% CI, 0.81–1.11), and a 13% reduction among high-risk sub-jects (RR=0.87; 95% CI, 0.79–0.96).3 a 2007 meta-analysis by askie4 in-cluded 31 trials with 32,217 women and their 32,819 infants. Main outcomes (re-gardless of initial maternal risks) were 1) onset of preeclampsia, 2) neonatal death, 3) preterm birth at <34 weeks gestation, 4) infant small for gestational age, and 5) pregnancy with serious adverse outcome. Results of these outcome measures con-sistently showed a relative risk reduction of 10% for subjects taking low-dose as-pirin, except for neonatal deaths, which had a 9% reduction. This study also suggested that multiparous women and women with a history of hypertensive disorder of pregnancy may derive a larg-er benefit from low-dose aspirin.a cochrane review5 updated in 2007 demonstrated that low-dose aspirin pro-Low-dose	aspirin	reduces	risk	of	preeclampsia,		but	how	does	it	affect	other	maternal	and	fetal	outcomes?STuDy  DeveloPmenT of PreTerm neonaTal SGa or low  riSk of abruPTion (year)  PreeclamPSia Delivery DeaTh  birTh weiGhT & bleeDinG Duley (2001)1 Moderate-risk patients:  8% reduction 14% reduction 8% reduction* not reported  15% reduction  nnT=72 nnT= 250 High-risk patients: 15% reduction   nnT=100 coomarasamy  14% reduction 14% reduction 21% reduction 215-g weight gain  no significant clinical  (2003)2    in aspirin group difference in risk       (rr=0.98)ruano (2005)3 Low-risk patients:     not reported  no significant reduction High-risk patients: 13% reduction    askie (2007)4 10% reduction 10% reduction 9% reduction 10% reduction no significant clinical       difference in risk      (rr=0.90–1.15)cochrane  19% reduction 7% reduction 16% reduction 8% reduction* no significant clinical (2007)5 nnT=69 (overall), 118 (moderate  nnT=83 nnT=227  difference in risk   risk), 18 (high-risk)    (rr=1.06)* Borderline for statistical significance (rr=0.92). sGa, small for gestational age; nnT, number needed to treat; rr, relative risk.tableLow-dose aspirin  does not appear to increase the risk of labor induction  or neonatal  bleeding fast trackCliniCal InquIrIes56	 vol 57, no 1 / january 2008  The Journal of family PracTicevided a moderate (19%) reduction in the overall risk of developing preeclampsia. New stratified analysis of the data in-dicates that in moderate-risk women, antiplatelet therapy is associated with a 15% reduction, and that high-risk women have a 27% reduction in the risk of developing preeclampsia. The ef-fect on small-for-gestational-age infants revealed no overall clinically significant differences.Aspirin	dosing:	One	study		recommends	>75	mg/dayStudies varied in the aspirin dosage they used and duration of treatment. In all RCTs, the dose of aspirin ranged from 50 mg/day to 150 mg/day. Earlier trials used lower doses of aspirin (50–75 mg/day), while recent trials used 100 mg or more per day. Early RCTs revealed no correlation between the dose of aspirin and the pre-vention of preeclampsia. However, Vil-lar et al6 showed a greater effect among women treated with doses greater than 75 mg/day of aspirin (RR=0.49; 95% CI, 0.38–0.63).6No	evidence	of	harm		from	aspirinThere is no evidence of harm from low-dose aspirin therapy—including placen-tal abruption, antenatal admissions, fetal intraventricular hemorrhage and other neonatal bleeding complications, admis-sion to neonatal care unit, induction of labor, or caesarean delivery—regardless of initial risk stratification.7 Recommendations	from	othersThe 2002 American College of Obstetri-cians and Gynecologists Practice Bulletin states that low-dose aspirin in women at low risk has not been shown to prevent preeclampsia and therefore is not recom-mended. They make no specific statement regarding the use of low-dose aspirin in moderate- to high-risk pregnancies.8 The Australasian Society for the Study of Hypertension in Pregnancy conclude that low-dose aspirin for pre-vention of preeclampsia is reasonable for the following conditions: 1) prior fetal loss after first trimester due to placental insufficiency or severe fetal growth retar-dation, and 2) women with severe early onset preeclampsia in previous pregnan-cy necessitating delivery ≤32 weeks ges-tation. Despite difficulties in predicting who will deliver preterm, consider wom-en who have had severe early-onset pre-eclampsia in a previous pregnancy for low-dose aspirin therapy.9 The Canadian Hypertension Soci-ety Consensus Panel concludes low-dose aspirin therapy is effective in decreasing the incidence of preterm delivery and early-onset preeclampsia among women at risk of developing the syndrome.10  nreferences  1.  Duley l, Henderson-smart Dj, Knight M, King jF. antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review. BMJ 2001; 322:329–333.  2.  Coomarasamy a, Papaioannou s, Gee H, Khan Ks. aspirin for prevention of pre-eclampsia in women with historical risk factors: a systematic review. Ob-stet Gynecol 2003; 101:1319–1332.  3.  ruano r, Fontes rs, Zugaib M. Prevention of pre-eclampsia with low-dose aspirin—a systematic review and meta-analysis of the main randomized controlled trials. Clinics 2005; 60:407–414.  4.  askie lM, Duley l, Henderson-stewart Dj, et al. antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet 2007; 369:1791–1798.  5.  Duley l, Henderson-smart Dj, Knight M, King jF. antiplatelet agents for preventing pre-eclampsia and its complication (review). Cochrane Database Syst Rev 2003; (4):CD004659.  6.  villar j, abalos e, nardin jM, et al. strategies to prevent and treat pre-eclampsia: evidence from randomized controlled trials. Semin Nephrol 2004; 24:607–615.  7.  Coomarasamy a, Braunholtz D, song, F, et al. Indi-vidualizing use of aspirin to prevent pre-eclampsia: a framework for clinical decision making. BJOG 2003; 110:882–888.  8.  aCoG Committee on obstetric Practice. Diagnosis and management of pre-eclampsia and eclampsia. aCoG Practice Bulletin, no 33. Int J Gynaecol Ob-stet 2002; 77:67–75.  9.  Brown Ma, Brennecke sP, Crowther Ca, et al. as-pirin and prevention of pre-eclampsia. Aust NZ J Obstet Gynaecol 1995; 35:38–41. 10.  Moutquin jM, Garner Pr, Burrows rF, rey e, et al. report of the Canadian Hypertension society Consensus Conference: 2. nonpharmacologic management and prevention of hypertensive dis-orders in pregnancy. Can Med Assoc J 1997; 57: 907–919.Multiparous  women and women  with a history  of hypertensive  disorder of  pregnancy may derive a larger  benefit from  low-dose aspirin

Does low-dose aspirin reduce preeclampsia and other maternal-fetal complications?

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