The role of aspirin in prevention of preeclampsia in twin pregnancies: does the dose matter?
Erkan Kalafat, Amani Shirazi, B. Thilaganathan, Asma Khalil
Abstract
The use of aspirin in twin pregnancies for the prevention of preeclampsia is a controversial topic, and evidence on the required dose of aspirin is scarce. We aimed to assess the efficacy of 75 mg/day vs 150 mg/day aspirin for the prevention of preeclampsia in twin pregnancies. This is a retrospective cohort study of twin pregnancies managed at St George’s University Hospital between 2012 and 2019. The National Institute for Health and Care Excellence guideline published in 2010 has recommended low-dose aspirin to women at high risk of preeclampsia.1National Institute for Health and Care ExcellenceHypertension in pregnancy: diagnosis and management (NICE guideline [NG133]).https://www.nice.org.uk/guidance/ng133Date: 2019Google Scholar Monochorionic and dichorionic twin pregnancies were included in the cohort. Pregnancies between 2010 and 2012 were excluded to ensure thorough implementation of the national guideline. High-order multifetal gestations and pregnancies complicated by fetal anomalies also were excluded. Twin pregnancies with any of these risk factors (hypertension in a previous pregnancy, chronic hypertension, renal disease, autoimmune disorder, diabetes, nulliparity, maternal age >40 years, pregnancy interval >10 years, body mass index >35 kg/m2, or family history of preeclampsia) as per the National Institute for Health and Care Excellence guideline were started on aspirin.1National Institute for Health and Care ExcellenceHypertension in pregnancy: diagnosis and management (NICE guideline [NG133]).https://www.nice.org.uk/guidance/ng133Date: 2019Google Scholar The aspirin dose was changed from 75 mg/day to 150 mg/day after 2017, following reports of effective prevention of preeclampsia using aspirin 150 mg/day.2Rolnik D.L. Wright D. Poon L.C. et al.Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia.N Engl J Med. 2017; 377: 613-622Crossref PubMed Scopus (1115) Google Scholar, 3Poon L.C. Wright D. Rolnik D.L. et al.Aspirin for evidence-based preeclampsia prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history.Am J Obstet Gynecol. 2017; 217: 585.e581-585.e585Abstract Full Text Full Text PDF Scopus (117) Google Scholar, 4Roberge S. Nicolaides K. Demers S. Hyett J. Chaillet N. Bujold E. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis.Am J Obstet Gynecol. 2017; 216: 110-120.e116Abstract Full Text Full Text PDF PubMed Scopus (362) Google Scholar The main outcome was preeclampsia diagnosed according to International Society for the Study of Hypertension in Pregnancy guideline.5Tranquilli A.L. Dekker G. Magee L. et al.The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP.Pregnancy Hypertens. 2014; 4: 97-104Crossref PubMed Scopus (988) Google Scholar Hypertensive disorders of pregnancy (HDP) included preeclampsia or gestational hypertension. There were 630 pregnancies in the cohort; 404 received aspirin (108 received 150 mg/day and 296 received 75 mg/day), whereas 226 did not. There were 28 (4.4%) cases of preeclampsia and 47 (7.5%) cases of HDP in the cohort. No significant differences in maternal age (P=.510), nulliparity (P=.945), and chorionicity (P=.700) were observed between the 75 mg/day and 150 mg/day aspirin groups. The incidence of preeclampsia was similar between the aspirin 150 mg/day and no aspirin groups (1.8% vs 3.1%, P=.510). However, there was a trend toward a significant decrease in preeclampsia in those receiving aspirin 150 mg/day compared with 75 mg/day (1.8% vs 6.4%, P=.067). There were no statistically significant differences between aspirin 150 mg/day and the no aspirin groups regarding the incidence of HDP (1.8% vs 5.3%, P=.140), but the incidence of HDP was significantly lower in aspirin 150 mg/day group compared with the 75 mg/day group (1.8% vs 11.1%, P=.003) (Figure 1). The incidence of HDP was significantly greater in the aspirin 75 mg/day group compared with no aspirin (11.1% vs 5.3%, P=.018). We investigated the association of aspirin dose with HDP in a multivariable logistic regression model after adjusting for maternal age in years, chorionicity, and smoking during pregnancy. The reference group was the low-risk twin pregnancies who did not receive aspirin. The direction of the association changed from a significant increase in HDP (odds ratio, 2.01; 95% confidence interval, 1.03–4.18; P=.048) to a nonsignificant decrease (odds ratio, 0.31; 95% confidence interval, 0.05–1.16; P=.127) when the aspirin dose was increased from 75 mg/day to 150 mg/day. The incidence of hypertensive disorders in twin pregnancies with additional risk factors for preeclampsia was significantly lower in those receiving aspirin 150 mg/day compared with 75 mg/day.