Does Hydroxychloroquine Protect against Preeclampsia and Preterm Delivery in Systemic Lupus Erythematosus Pregnancies?
30 April 2019
02 December 2019
03 January 2020 (online)
Objective Systemic lupus erythematosus (SLE) increases the risk of complications in pregnancy. Hydroxychloroquine (HCQ) decreases flares and neonatal lupus syndrome. Limited evidence suggests that HCQ also reduces preeclampsia and preterm birth in SLE pregnancies. We studied whether HCQ was associated with lower odds of preeclampsia and preterm delivery in SLE pregnancies.
Study Design We conducted a retrospective cohort study of 129 deliveries of 110 patients with SLE delivered at a single institution (2000–2017). HCQ exposure and preeclampsia, along with other clinical data, were extracted from chart review. Crude and multivariable-adjusted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs).
Results A total of 41% were exposed to HCQ, of whom 13.5% were complicated by preeclampsia versus 26.3% unexposed to HCQ (adjusted OR = 0.5; 95% CI: 0.2–1.4). The difference was pronounced for first pregnancies (7 vs. 44%), but power was limited. The difference in preterm deliveries was less pronounced comparing HCQ-exposed pregnancies with HCQ-unexposed pregnancies (34 vs. 40.8%; OR = 0.3; 95% CI: 0.3–1.5).
Conclusion Pregnant SLE patients trended toward less preeclampsia and preterm delivery when treated with HCQ. Future larger studies are needed to increase the statistical power, account for additional potential confounders, and more fully account for parity.
- 1 Bundhun PK, Soogund MZS, Huang F. Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: a meta-analysis of studies published between years 2001-2016. J Autoimmun 2017; 79 (79) 17-27
- 2 Jakobsen IM, Helmig RB, Stengaard-Pedersen K. Maternal and foetal outcomes in pregnant systemic lupus erythematosus patients: an incident cohort from a stable referral population followed during 1990-2010. Scand J Rheumatol 2015; 44 (05) 377-384
- 3 Levy RA, Vilela VS, Cataldo MJ. , et al. Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus 2001; 10 (06) 401-404
- 4 Costedoat-Chalumeau N, Amoura Z, Duhaut P. , et al. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group. Arthritis Rheum 2003; 48 (11) 3207-3211
- 5 Lateef A, Petri M. Systemic lupus erythematosus and pregnancy. Rheum Dis Clin North Am 2017; 43 (02) 215-226
- 6 Bernas BL, Smith NA. Pregnancy in women with systemic lupus erythematosus. UpToDate. Available at: https://www.uptodate.com/contents/pregnancy-in-women-with-systemic-lupus-erythematosus . Accessed April 9, 2019
- 7 Götestam Skorpen C, Hoeltzenbein M, Tincani A. , et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016; 75 (05) 795-810
- 8 Clowse MEB, Magder L, Witter F, Petri M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 2006; 54 (11) 3640-3647
- 9 Izmirly PM, Costedoat-Chalumeau N, Pisoni CN. , et al. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation 2012; 126 (01) 76-82
- 10 Leroux M, Desveaux C, Parcevaux M. , et al. Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: a descriptive cohort study. Lupus 2015; 24 (13) 1384-1391
- 11 Seo MR, Chae J, Kim YM. , et al. Hydroxychloroquine treatment during pregnancy in lupus patients is associated with lower risk of preeclampsia. Lupus 2019; 28 (06) 722-730
- 12 Smyth A, Oliveira GHM, Lahr BD, Bailey KR, Norby SM, Garovic VD. A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis. Clin J Am Soc Nephrol 2010; 5 (11) 2060-2068
- 13 Chakravarty EF, Colón I, Langen ES. , et al. Factors that predict prematurity and preeclampsia in pregnancies that are complicated by systemic lupus erythematosus. Am J Obstet Gynecol 2005; 192 (06) 1897-1904
- 14 Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ 2013; 347: f6564
- 15 Kwok LW, Tam LS, Zhu T, Leung YY, Li E. Predictors of maternal and fetal outcomes in pregnancies of patients with systemic lupus erythematosus. Lupus 2011; 20 (08) 829-836
- 16 Bramham K, Hunt BJ, Bewley S. , et al. Pregnancy outcomes in systemic lupus erythematosus with and without previous nephritis. J Rheumatol 2011; 38 (09) 1906-1913
- 17 Eudy AM, Jayasundara M, Haroun T, Neil L, James AH, Clowse MEB. Reasons for cesarean and medically indicated deliveries in pregnancies in women with systemic lupus erythematosus. Lupus 2018; 27 (03) 351-356
- 18 Simard JF, Chaichian Y, Rossides M, Wikstrom AK, Shaw GM, Druzin ML. Preterm delivery phenotypes in systemic lupus erythematosus pregnancies. Am J Perinatol 2019; 36 (09) 964-968
- 19 Gómez-Guzmán M, Jiménez R, Romero M. , et al. Chronic hydroxychloroquine improves endothelial dysfunction and protects kidney in a mouse model of systemic lupus erythematosus. Hypertension 2014; 64 (02) 330-337
- 20 Abd Rahman R, DeKoninck P, Murthi P, Wallace EM. Treatment of preeclampsia with hydroxychloroquine: a review. J Matern Fetal Neonatal Med 2018; 31 (04) 525-529
- 21 Miyachi Y, Yoshioka A, Imamura S, Niwa Y. Antioxidant action of antimalarials. Ann Rheum Dis 1986; 45 (03) 244-248
- 22 Okoli GN, Sanders RD, Myles P. Demystifying propensity scores. Br J Anaesth 2014; 112 (01) 13-15
- 23 Simard JF, Arkema EV, Nguyen C. , et al. Early-onset preeclampsia in lupus pregnancy. Paediatr Perinat Epidemiol 2017; 31 (01) 29-36
- 24 Kroese SJ, de Hair MJH, Limper M. , et al. Hydroxychloroquine use in lupus patients during pregnancy is associated with longer pregnancy duration in preterm births. J Immunol Res 2017; 2017: 2810202
- 25 LeFevre ML. ; U.S. Preventive Services Task Force. Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2014; 161 (11) 819-826
- 26 Lu K, Kauff N, Powell CB, Cass I. ACOG Practice Bulletin No. 202: gestational hypertension and preeclampsia. Obstet Gynecol 2019; 133 (01) e1-e25
- 27 Henderson JT, Whitlock EP, Connor EO, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2014; 160 (10) 695-703
- 28 Parke A, West B. Hydroxychloroquine in pregnant patients with systemic lupus erythematosus. J Rheumatol 1996; 23 (10) 1715-1718
- 29 Hernández-Díaz S, Toh S, Cnattingius S. Risk of pre-eclampsia in first and subsequent pregnancies: prospective cohort study. BMJ 2009; 338: b2255