Sjögren Syndrome and Pregnancy: A Literature Review


Suruchi Gupta, MS, MBBS; Nikhil Gupta, MD, MBBS

Perm J 2017;21:16-047 [Full Citation]
E-pub: 11/09/2016


Objectives: Autoimmune diseases do not impair fertility, and women with autoimmune diseases who become pregnant are likely to experience more complicated pregnancies than are women without the disease. Pregnancies complicated by these disorders have a high clinical impact on both the pregnancy and the disease. The effect of autoimmune disease on pregnancy differs according to the type of maternal disease, disease activity, severity of organ damage, antibody profile, and drug treatment. Sjögren syndrome is an autoimmune disease with a high prevalence of anti-SS-A (anti-Ro) and anti-SS-B (anti-La) antibodies. Anti-SS-A antibodies are associated with congenital heart block. Data on pregnancy outcomes in primary Sjögren syndrome are scarce.
Methods: We performed a review of the literature regarding pregnancy outcomes in women with Sjögren syndrome.
Results: Women with Sjögren syndrome are likely to experience more complications during pregnancy than women without an autoimmune disease. Studies show a high incidence of poor fetal outcomes for these patients.
Conclusion: Women with Sjögren syndrome require prenatal counseling explaining the risks involved and the need to control the disease well before conception. High-risk pregnancies can be optimally managed by a multidisciplinary team.


Sjögren syndrome is an autoimmune disease that can present either alone, as in primary Sjögren syndrome (pSS), or in association with an underlying connective tissue disease, most commonly rheumatoid arthritis or systemic lupus erythematosus (secondary Sjögren syndrome).1 The spectrum of clinical presentation of Sjögren syndrome extends from dryness of the main mucosal surfaces to systemic involvement (extraglandular manifestations). Dryness of mucosal surfaces occurs because of immune-mediated inflammation causing secretory gland dysfunction.2 Sicca features primarily affect the quality of life, whereas the disease prognosis is marked by systemic involvement.3 Sjögren syndrome is known to occur predominantly in women. Affected women are likely to experience more complicated pregnancies than are women without the disease.4,5

The effect of autoimmune disease on pregnancy differs according to the maternal disease, disease activity, severity of organ damage, antibody profile, and drug treatment.6 Data on pregnancy outcomes in pSS are scarce, and results have been conflicting. Only a few studies have evaluated the pregnancy and fetal outcomes in patients with Sjögren syndrome. This prompted us to perform a review of the literature on the effect of Sjögren syndrome on pregnancy and fetal outcomes compared with those in the general obstetric population.



Sjögren syndrome is one of the most common autoimmune diseases, with a reported prevalence between 0.1% and 4.8% in various populations when defined strictly according to the American-European Consensus Criteria.7 It may occur at any age but affects mainly women at the fourth decade of life; the female-male ratio is estimated at 9:1.8 The increasing frequency rate of pregnancies in women with pSS and hence the increased impact of the disease on pregnancies complicated by it can be explained by these epidemiologic data and the prevailing recent social trend toward late marriages and advanced maternal age at the time of first pregnancy or increased interval between marriage and conception.


The histologic hallmark of the disease is the focal lymphocytic infiltration of the exocrine glands. Laboratory diagnosis of Sjögren syndrome is usually made by the following markers: antinuclear antibodies (most frequently detected), anti SS-A (also called anti-Ro; most specific), anti-SS-B (also called anti-La), and cryoglobulins and hypocomplementemia (main prognostic markers).9 These markers mediate the tissue damage and are thus responsible for complications in pregnancies of women with Sjögren syndrome. These antibodies cross the placenta beginning at approximately 12 weeks of gestation and may exert the following effects on the fetal tissues: 1) inducing myocarditis; 2) binding apoptotic cells, blocking presumed physiologic clearance, and diverting clearance to macrophages; and 3) producing arrhythmia.10,11

Clinical Manifestations

Effect of Pregnancy on Sjögren Syndrome

Sjögren syndrome is likely to worsen during pregnancy and more so in the postpartum period. This is because the disease is sometimes complicated by pulmonary hypertension, which frequently worsens during pregnancy and in the postpartum period.

Effect of Sjögren Syndrome on Pregnancy

Women with Sjögren syndrome are likely to experience more complications during pregnancy compared with those without the disease. Pregnancy outcomes in women with Sjögren syndrome have not been extensively studied. Several studies have reported an increased rate of spontaneous abortion and fetal loss associated with Sjögren syndrome (Table 1).4,12-14 This may be explained by, first, the usually older age of the patients at the time of conception and, second, a possible immunologic factor involved in the mechanisms of miscarriage.14

Various studies have demonstrated an extremely variable rate of induced abortions, depending on the counseling given about the fetal-maternal risks and the socioeconomic status of the patient (Table 1).5,14-17 A significant increase in the rate of preterm deliveries was found in pregnant women with pSS in most of the studies.16,17 The mean neonatal birth weight was significantly lower in the offspring of women with pSS. This may be related to a pathologic intrauterine growth restriction and is not influenced by the timing of the delivery.13 An increased frequency of cesarean delivery was observed in patients with Sjögren syndrome.17 This might be caused by an increased risk of severe fetal outcomes in pregnancies in the Sjögren syndrome population resulting from an increased risk of fetal growth restriction.

Well-known fetal outcomes in Sjögren syndrome-complicated pregnancies are neonatal lupus and congenital heart block (CHB).18 CHB is the most severe fetal complication and supposedly occurs because of the damage of the atrioventricular node by anti-SS-A or anti-SS-B antibodies, or both. The reported prevalence of CHB in the offspring of an anti-SS-A-positive woman is 1% to 2%. The recurrence rate in a patient with antibodies, who has a previous child affected, is approximately 10 times higher.19-21 The incidence of neonatal lupus in an offspring of a mother with anti-SS-A antibodies is estimated at approximately 1% to 2%.22

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The outcome of pregnancies in women with Sjögren syndrome can be excellent with use of a multidisciplinary management approach involving an obstetrician who specializes in high-risk pregnancies, a rheumatologist, and a pediatrician.11

Prenatal Management

Women with Sjögren syndrome planning to conceive must undergo good counseling regarding all specific risks and complications involved, medications that are contraindicated during pregnancy, and whether the patient is in the best condition to get pregnant according to underlying disease activity and complications. Ideally, the disease should be well under control three to six months before conception.

Antenatal Management

One of the most dreaded complications of pregnancy in patients with Sjögren syndrome is CHB. A woman is at risk of delivering a baby affected by CHB if she is anti-SS-A positive.11 Frequent surveillance by serial echocardiograms and obstetric sonograms between 16 to 20 weeks of gestation and thereafter is required for at-risk pregnancies. The goals are early diagnosis and early treatment of incomplete CHB, thus improving the outcome for the fetus.23 The rationales for management are 1) to decrease maternal autoantibodies and then to decrease their placental transfer and 2) to decrease the inflammation once it occurs before it leads to permanent fibrosis and irreversible CHB.24 Maternal treatment with fluorinated corticosteroids such as dexamethasone or betamethasone, can reduce the antibody-mediated inflammatory damage of nodal tissue because they are not inactivated by placental hydroxylase.25 However, there is no definite evidence about whether steroids effectively decrease the titers of anti-SS-A or anti-SS-B antibodies or reverse the CHB.25-27 However, dexamethasone has been reported to reverse carditis and incomplete CHB, and to improve fetal hemodynamics.23,25,27-29 Hence, dexamethasone treatment is recommended if the block is recent or incomplete, or if there is evidence of cardiac failure.25,30,31 Maternal risks of fluorinated steroids include infection, osteoporosis, osteonecrosis, and glucose intolerance. Specific fetal risks include intrauterine growth restriction, oligohydramnios, and possibly adrenal suppression.31 The alternative therapies, as evidenced by a few case reports, include plasmapheresis,31 intravenous immunoglobulins, and b-sympathomimetics.32 In most cases, complete heart block requires a pacemaker implantation in the infant, preferably in the neonatal period.11


Women with Sjögren syndrome are likely to experience more complications during pregnancy. Studies show a high incidence of poor fetal outcomes for these patients. Women with this underlying autoimmune disorder must undergo prenatal counseling explaining all the risks involved and the need to control the disease well before conception. These high-risk pregnancies can be optimally managed by a multidisciplinary approach involving a high-risk obstetrician, a rheumatologist, and a pediatrician.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.


Kathleen Louden, ELS, of Louden Health Communications provided editorial assistance.

How to Cite this Article

Gupta S, Gupta N. Sjögren syndrome and pregnancy: A literature review. Perm J 2017;21:16-047. DOI:

1.    Tincani A, Andreoli L, Cavazzana I, et al. Novel aspects of Sjögren’s syndrome in 2012. BMC Med 2013 Apr 4;11:93. DOI:
    2.    Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, Bosch X. Primary Sjogren syndrome. BMJ 2012 Jun 14;344:e3821. DOI:
    3.    Goules AV, Skopouli FN. Prognostic factors and survival. In: Ramos-Casals M, Stone JH, Moutsopoulos HM, editors. Sjögren’s syndrome: diagnosis and therapeutics. London, United Kingdom: Springer; 2012. p 129-48.
    4.    Siamopoulou-Mavridou A, Manoussakis MN, Mavridis AK, Moutsopoulos HM. Outcome of pregnancy in patients with autoimmune rheumatic disease before the disease onset. Ann Rheum Dis 1988 Dec;47(12):982-7. DOI:
    5.    Skopouli FN, Papanikolaou S, Malamou-Mitsi V, Papanikolaou N, Moutsopoulos HM. Obstetric and gynaecological profile in patients with primary Sjögren’s syndrome. Ann Rheum Dis 1994 Sep;53(9):569-73. DOI:
    6.    Carvalheiras G, Faria R, Braga J, Vasconcelos C. Fetal outcome in autoimmune diseases. Autoimmun Rev 2012 May;11(6-7):A520-30. DOI:
    7.    Vitali C, Bombardieri S, Jonsson R, et al; European Study Group on Classification Criteria for Sjögren’s Syndrome. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002 Jun;61(6):554-8. DOI:
    8.    Mavragani CP, Moutsopoulos HM. The geoepidemiology of Sjögren’s syndrome. Autoimmun Rev 2010 Mar;9(5):A305-10. DOI:
    9.    Brito-Zerón P, Ramos-Casals M, Bove A, Sentis J, Font J. Predicting adverse outcomes in primary Sjogren’s syndrome: identification of prognostic factors. Rheumatology (Oxford) 2007 Aug;46(8):1359-62. DOI:
    10.    Reichlin M, Brucato A, Frank MB, et al. Concentration of autoantibodies to native 60-kd Ro/SS-A and denatured 52-kd Ro/SS-A in eluates from the heart of a child who died with congenital complete heart block. Arthritis Rheum 1994 Nov;37(11):1698-703. DOI:
    11.    Brucato A, Cimaz R, Caporali R, Ramoni V, Buyon J. Pregnancy outcomes in patients with autoimmune diseases and anti-Ro/SSA antibodies. Clin Rev Allergy Immunol 2011 Feb;40(1):27-41. DOI:
    12.    Julkunen H, Kaaja R, Kurki P, Palosuo T, Friman C. Fetal outcome in women with primary Sjögren’s syndrome. A retrospective case-control study. Clin Exp Rheumatol 1995 Jan-Feb;13(1):65-71. DOI:
    13.    De Carolis S, Salvi S, Botta A, et al. The impact of primary Sjogren’s syndrome on pregnancy outcome: our series and review of the literature. Autoimmun Rev 2014 Feb;13(2):103-7. DOI:
    14.    Sandhya P, Jeyaseelan L, Scofield RH, Danda D. Clinical characteristics and outcome of primary Sjogren’s syndrome: a large Asian Indian cohort. Open Rheumatol J 2015 Jun 26;9:36-45. DOI:
    15.    Takaya M, Ichikawa Y, Shimizu H, Uchiyama M, Moriuchi J, Arimori S. Sjögren’s syndrome and pregnancy. Tokai J Exp Clin Med 1991 Jul;16(2):83-8.
    16.    Priori R, Gattamelata A, Modesti M, et al. Outcome of pregnancy in Italian patients with primary Sjögren syndrome. J Rheumatol 2013 Jul;40(7):1143-7. DOI:
    17.    Hussein SZ, Jacobsson LT, Lindquist PG, Theander E. Pregnancy and fetal outcome in women with primary Sjogren’s syndrome compared with women in the general population: a nested case-control study. Rheumatology (Oxford) 2011 Sep;50(9):1612-7. DOI:
    18.    Miranda-Carús ME, Askanase AD, Clancy RM, et al. Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages. J Immunol 2000 Nov 1;165(9):5345-51. DOI:
    19.    Frassi M, Brucato A, Cavazzana I, et al. [Neonatal lupus: clinical features and risk of congenital cardiac heart block in newborns from mothers with anti Ro/SSA antibodies]. [Article in Italian]. Reumatismo 2001;53(4):298-304. DOI:
    20.    Brucato A, Franceschini F, Gasparini M, et al. Isolated congenital complete heart block: longterm outcome of mothers, maternal antibody specificity and immunogenetic background. J Rheumatol 1995 Mar;22(3):533-40.
    21.    Julkunen H, Kurki P, Kaaja R, et al. Isolated congenital heart block. Long-term outcome of mothers and characterization of the immune response to SS-A/Ro and to SS-B/La. Arthritis Rheum 1993 Nov;36(11):1588-98. DOI:
    22.    Brucato A, Frassi M, Franceschini F, et al. Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women. Arthritis Rheum 2001 Aug;44(8):1832-5. DOI:<1832::aid-art320>;2-c.
    23.    Rosenthal D, Druzin M, Chin C, Dubin A. A new therapeutic approach to the fetus with congenital complete heart block: preemptive, targeted therapy with dexamethasone. Obstet Gynecol 1998 Oct;92(4 Pt 2):689-91. DOI:
    24.    Yang CH, Chen JY, Lee SC, Luo SF. Successful preventive treatment of congenital heart block during pregnancy in a woman with systemic lupus erythematosus and anti-Sjögren’s syndrome A/Ro antibody. J Microbiol Immunol Infect 2005 Oct;38(5):365-9.
    25.    Saleeb S, Copel J, Friedman D, Buyon JP. Comparison of treatment with fluorinated glucocorticoids to the natural history of autoantibody-associated congenital heart block: retrospective review of the research registry for neonatal lupus. Arthritis Rheum 1999 Nov;42(11):2335-45. DOI:<2335::aid-anr12>;2-3.
    26.    Buyon J, Roubey R, Swersky S, et al. Complete congenital heart block: risk of occurrence and therapeutic approach to prevention. J Rheumatol 1988 Jul;15(7):1104-8.
    27.    Copel JA, Buyon JP, Kleinman CS. Successful in utero therapy of fetal heart block. Am J Obstet Gynecol 1995 Nov;173(5):1384-90. DOI:
    28.    Fesslova V, Mannarino S, Salice P, et al. Neonatal lupus: fetal myocarditis progressing to atrioventricular block in triplets. Lupus 2003;12(10):775-8. DOI:
    29.    Buyon JP, Clancy RM. Neonatal lupus: review of proposed pathogenesis and clinical data from the US-based Research Registry for Neonatal Lupus. Autoimmunity 2003 Feb;36(1):41-50. DOI:
    30.    Costedoat-Chalumeau N, Amoura Z, Le Thi Hong D, et al. Questions about dexamethasone use for the prevention of anti-SSA related congenital heart block. Ann Rheum Dis 2003 Oct;62(10):1010-2. DOI:
    31.    Buyon J, Roubey R, Swersky S, et al. Complete congenital heart block: risk of occurrence and therapeutic approach to prevention. J Rheumatol 1988 Jul;15(7):1104-8.
    32.    Kaaja R, Julkunen H. Prevention of recurrence of congenital heart block with intravenous immunoglobulin and corticosteroid therapy: comment on the editorial by Buyon et al. Arthritis Rheum 2003 Jan;48(1):280-1. DOI:


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