Hydroxychloroquine (HCQ) is regarded as a mainstay in the treatment of systemic lupus erythematosus (SLE) because of its efficacy in preventing flares, achieving remission, and reducing overall mortality. However, the impact of HCQ on pregnancy outcomes remains controversial.
Objective
We aimed to investigate the effect of HCQ on pregnancy outcomes in patients with SLE.
Methods
We performed a retrospective cohort study of 151 pregnancies in 122 patients with SLE (80 pregnancies in the HCQ treatment group and 71 pregnancies in the HCQ nontreatment group). We reviewed baseline characteristics including maternal comorbidities such as antiphospholipid syndrome, lupus nephritis, and autoimmune hepatitis. Pregnancy outcomes (preeclampsia, preterm delivery, and fetal growth restriction) and neonatal outcomes (gestational age at delivery and birth weight) were compared between HCQ treatment and nontreatment groups.
Results
Preeclampsia was significantly less complicated (7.5% vs 19.7%, p = 0.032) and neonatal birth weight was significantly greater (2757.0 ± 583.5 g vs 2542.3 ± 908.3 g, p = 0.001) in the HCQ treatment group than in the HCQ nontreatment group. Multiple logistic analysis adjusting for body mass index (BMI), lupus nephritis, serum uric acid, and estimated glomerular filtration rate revealed HCQ treatment was associated with exceedingly lower risk of preeclampsia in SLE pregnancy (odds ratio (OR) 0.106 (confidence interval (CI) 0.017–0.671)). Other independent risk factors for preeclampsia were a high prepregnancy BMI (OR 1.575 (CI 1.114–2.227)) and low eGFR level (OR 0.931 (CI 0.886–0.979)) before pregnancy.
Conclusion
Our data showed pregnancy outcomes in SLE patients can be improved in the HCQ treatment group with about 90% reduction of preeclampsia.
LimJSLimSWAhnJHSongBSShimKSHwangIT. New Korean reference for birth weight by gestational age and sex: Data from the Korean Statistical Information Service (2008–2012). Ann Pediatr Endocrinol Metab2014; 19: 146–153.
2.
LockshinMDSammaritanoLRMedical disorders during pregnancy. In: BarronWMLindheimerMD (eds). Rheumatic disease, 3rd ed. St. Louis: Mosby, 2000.
3.
SinghAGChowdharyVR. Pregnancy-related issues in women with systemic lupus erythematosus. Int J Rheum Dis2015; 18: 172–181.
4.
ClowseMEJamisonMMyersEJamesAH. A national study of the complications of lupus in pregnancy. Am J Obstet Gynecol 2008; 199127: e121–e126.
5.
YasmeenSWilkinsEEFieldNTSheikhRAGilbertWM. Pregnancy outcomes in women with systemic lupus erythematosus. J Matern Fetal Med2001; 10: 91–96.
6.
ClarkCASpitzerKALaskinCA. Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period. J Rheumatol2005; 32: 1709–1712.
7.
RahmanRMurthiPSinghHet al.The effects of hydroxychloroquine on endothelial dysfunction. Pregnancy Hypertens2016; 6: 259–262.
8.
TandonAIbañezDGladmanDDUrowitzMB. The effect of pregnancy on lupus nephritis. Arthritis Rheum2004; 50: 3941–3946.
9.
LateefAPetriM. Management of pregnancy in systemic lupus erythematosus. Nat Rev Rheumatol2012; 8: 710–718.
10.
ClowseMEMagderLSWitterFPetriM. The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum2005; 52: 514–521.
11.
Götestam SkorpenCHoeltzenbeinMTincaniAet al.The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis2016; 75: 795–810.
12.
Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum1999; 42: 1785–1796.
13.
HaładyjESikoraMFelis-GiemzaAOlesińskaM. Antimalarials—Are they effective and safe in rheumatic diseases?. Reumatologia2018; 56: 164–173.
14.
Gómez-GuzmánMJiménezRRomeroMet al.Chronic hydroxychloroquine improves endothelial dysfunction and protects kidney in a mouse model of systemic lupus erythematosus. Hypertension2014; 64: 330–337.
15.
RyanMJMcLemoreGR Jr. Hypertension and impaired vascular function in a female mouse model of systemic lupus erythematosus. Am J Physiol Regul Integr Comp Physiol2007; 292: R736–R742.
16.
SelzerFSutton-TyrrellKFitzgeraldSTracyRKullerLManziS. Vascular stiffness in women with systemic lupus erythematosus. Hypertension2001; 37: 1075–1082.
17.
ShenFWeiJSnowiseSet al.Trophoblast debris extruded from preeclamptic placentae activates endothelial cells: A mechanism by which the placenta communicates with the maternal endothelium. Placenta2014; 35: 839–847.
18.
MandangSManuelpillaiUWallaceEM. Oxidative stress increases placental and endothelial cell activin A secretion. J Endocrinol2007; 192: 485–493.
19.
GuYLewisDFWangY. Placental productions and expressions of soluble endoglin, soluble fms-like tyrosine kinase receptor-1, and placental growth factor in normal and preeclamptic pregnancies. J Clin Endocrinol Metab2008; 93: 260–266.
20.
HungTHBurtonGJ. Hypoxia and reoxygenation: A possible mechanism for placental oxidative stress in preeclampsia. Taiwan J Obstet Gynecol2006; 45: 189–200.
21.
MurphySRLaMarcaBBCockrellKGrangerJP. Role of endothelin in mediating soluble fms-like tyrosine kinase 1-induced hypertension in pregnant rats. Hypertension2010; 55: 394–398.
22.
LaMarcaBBCockrellKSullivanEBennettWGrangerJP. Role of endothelin in mediating tumor necrosis factor-induced hypertension in pregnant rats. Hypertension2005; 46: 82–86.
23.
RobertsLLaMarcaBBFournierLBainJCockrellKGrangerJP. Enhanced endothelin synthesis by endothelial cells exposed to sera from pregnant rats with decreased uterine perfusion. Hypertension2006; 47: 615–618.
24.
ClowseMEMagderLWitterFPetriM. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum2006; 54: 3640–3647.
25.
LevyRAVilelaVSCataldoMJet al.Hydroxychloroquine (HCQ) in lupus pregnancy: Double-blind and placebo-controlled study. Lupus2001; 10: 401–404.
26.
HochbergMC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1997; 40: 1725.
27.
ParkEJJungHHwangJet al.Pregnancy outcomes in patients with systemic lupus erythematosus: A retrospective review of 62 pregnancies at a single tertiary center in South Korea. Int J Rheum Dis2014; 17: 887–897.
28.
Committee on Practice Bulletins—Obstetrics, American College of Obstetricians and Gynecologists. Practice bulletin no. 132: Antiphospholipid syndrome. Obstet Gynecol2012; 120: 1514–1521.
29.
American College of Obstetricians, Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol2013; 122: 1122–1131.
30.
TettSECutlerDJDayROBrownKF. Bioavailability of hydroxychloroquine tablets in healthy volunteers. Br J Clin Pharmacol1989; 27: 771–779.
31.
ChakravartyEFColónILangenESet al.Factors that predict prematurity and preeclampsia in pregnancies that are complicated by systemic lupus erythematosus. Am J Obstet Gynecol2005; 192: 1897–1904.
32.
BramhamKHuntBJBewleySet al.Pregnancy outcomes in systemic lupus erythematosus with and without previous nephritis. J Rheumatol2011; 38: 1906–1913.
33.
KohJHKoHSKwokSKJuJHParkSH. Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus. Lupus2015; 24: 210–217.
34.
ZhangHParkYWuJet al.Role of TNF-alpha in vascular dysfunction. Clin Sci (Lond)2009; 116: 219–230.
35.
CaiHHarrisonDG. Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circ Res2000; 87: 840–844.
36.
YuWGaoWRongDWuZKhalilRA. Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia. Microcirculation2018, pp. e12508.
37.
ClarkCASpitzerKANadlerJNLaskinCA. Preterm deliveries in women with systemic lupus erythematosus. J Rheumatol2003; 30: 2127–2132.
38.
LerouxMDesveauxCParcevauxMet al.Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: A descriptive cohort study. Lupus2015; 24: 1384–1391.
39.
SperberKHomCChaoCPShapiroDAshJ. Systematic review of hydroxychloroquine use in pregnant patients with autoimmune diseases. Pediatr Rheumatol Online J2009; 7: 9.
40.
GarsensteinMPollakVEKarkRM. Systemic lupus erythematosus and pregnancy. N Engl J Med1962; 267: 165–169.
41.
PetriMHowardDRepkeJGoldmanDW. The Hopkins Lupus Pregnancy Center: 1987–1991 update. Am J Reprod Immunol1992; 28: 188–191.
42.
Martínez-RuedaJOArce-SalinasCAKrausAAlcocer-VarelaJAlarcón-SegoviaD. Factors associated with fetal losses in severe systemic lupus erythematosus. Lupus1996; 5: 113–119.
43.
van VollenhovenRFMoscaMBertsiasGet al.Treat-to-target in systemic lupus erythematosus: Recommendations from an international task force. Ann Rheum Dis2014; 73: 958–967.
