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DOI: 10.23648/UMBJ.2018.29.11354

УДК 618.2:616-097:618.3-06

 

БЕРЕМЕННОСТЬ И СИСТЕМНАЯ КРАСНАЯ ВОЛЧАНКА

Р.Н. Степанова

ФГБОУ ВО «Орловский государственный университет им. И.С. Тургенева», г. Орел, Россия

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Системная красная волчанка (СКВ) – аутоиммунное заболевание, поражающее многие органы и системы человека. При СКВ образуется большое количество антител к антигенам собственных клеток, вследствие чего развивается иммунокомплексный воспалительный процесс, поражающий сердце, кожу, почки, легкие, суставы, нервную систему. При СКВ утрачивается фундаментальное свойство иммунной системы – толерантность к аутоантигенам, в результате продуцируются антитела, атакующие нормальные ткани собственного организма, что сопровождается развитием аутоиммунных заболеваний. У больных СКВ появляются такие клинические манифестации, как множественный тромбоз, в т.ч. ТЭЛА, заболевания ЦНС, livedo reticularis, лабильная гипертензия, привычный выкидыш. СКВ поражает людей всех рас, мужчин и женщин, однако у последних она доминирует и особенно часто развивается у женщин репродуктивного возраста. Распространенность СКВ среди женщин репродуктивного возраста – 1:500. Почти 90 % больных волчанкой – женщины. Причины развития СКВ неизвестны. В настоящее время общепризнано, что такие осложнения гестации, как привычный аборт, преэклампсия и эклампсия, преждевременная отслойка плаценты, ДВС- и HELLP-синдромы, тромбозы, задержка внутриутробного роста плода, мертворождаемость, ассоциируются с аутоиммунными заболеваниями у матери. Механизм, которым СКВ отягощает течение беременности и ухудшает ее исходы для матери, плода, новорожденного, остается нерасшифрованным. Возможно, к этому причастны сосудистые поражения плаценты, имеющие природу, сходную с волчаночными поражениями сосудов при СКВ. Репродуктивные потери у пораженных СКВ матерей, особенно при клинически активной волчанке, могут достигать 45 %. В статье анализируется литература, касающаяся проблем взаимовлияния СКВ и беременности, клинического течения волчанки у беременной женщины, материнского и перинатального исхода гестации, частоты развития неонатального люпуса.

Ключевые слова: системная красная волчанка, осложнения беременности, исходы беременности, неонатальный люпус.

Литература

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2.    Hom D., Graham R., Modrek B. Association of systemic lupus erythematosus with C8 orf 13-BLK and ITGAM-ITGAX. N. Engl. J. Med. 2008; 358: 900–909.

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5.    Zhonghua Nei Ke. Close association of herpes zoster reactivation and systemic lupus erythematosus diagnosis. Open Rheumatol. J. 2008; 2: 89–98.

6.    Lockshin M.D., Sammaritano L.R. Rheumatic disease. In: Barron W.M., eds. Medical Disorders during pregnancy. 3-d ed. St. Louis: Mosby; 2000: 355.

7.    Степанова Р.Н. Беременность и аутоиммунные заболевания. Российский вестник акушера-гинеколога. 1997; 1: 50–52.

8.    Zwahr C., Räte K., Brietzke W. Letaler Ausgang bei lupus erythematosus viscerale und Gravidität. Zbl Gynäkol. 1983; 105: 300–307.

9.    Day C.J., Lipkin G.W. Lupus nephritis and pregnancy in the 21st century. Oxford J. Nephrol Dialys Transplantat. 2009; 24 (2): 344–347.

10. Dudley D.J., Branch D.W. New approaches to recurrent pregnancy loss. Clinical Obstet Gynecol. 1989; 32 (3): 520–532.

11. Scott J.R., Rote N.S., Branch D.W. Immunologic aspects of recurrent abortion and fetal death. Obstet. Gynecol. 1987; 70: 645–656.

12. Степанова Р.Н. Беременность и аберрации иммунитета. М.: Спутник-плюс; 2013. 136.

13. Hanly J.G., Gladman D.D., Rose T.H. Lupus Pregnancy. A prospective study of placental changes. Artritis Rheumatol. 1988; 31: 358–366.

14. Guzman L., Avalos E., Orliz R. Placental abnormalities in systemic lupus erythematosus. J. Rheumatol. 1987; 14: 924–929.

15. Рыбина А.Н., Белинская А.М., Черепкова Н.В. Морфологические изменения в плацентах рожениц с системной красной волчанкой. Материалы IV съезда акушеров-гинекологов России. М.; 2008: 221–222.

16. Baguley E., Maclachlan N., Hughes G. SLE and pregnancy. Clin Exp Rheum. 1988; 6: 183–185.

17. Varner M.W., Meehan R.T., Syrop G. Pregnancy in patients with lupus erythematosus. Am. J. Obstet Gynecol. 1983; 145: 1025–1040.

18. El-Roeiy A., Myers S.A., Gleicher N. The prevalence of autoantibodies and lupus anticoagulant in healthy pregnant women. Obstet Gynecol. 1990; 75: 390–396.

19. Cowchock S., Smith J., Gocial B. Antibodies to phospholipids and nuclear antigens in patients with repeated abortion. Am. J. Obstet Gynecol. 1986; 155: 1002–1010.

20. Farnam J., Lavastida M., Grant J. Antimiclear antibodies in the serum normal pregnant women. J. Allergy Clin Immunol. 1984; 73: 596–599.

21. Сперанский А.И., Купавцева О.А. АНФ-ассоциированные болезни. Медицинский вестник. 2008; 12–13: 16.

22. Степанова Р.Н., Макарова О.М. Антинуклеарные аутоантитела (АНА) при привычной потере плода. Курский научно-практический вестник «Человек и его здоровье». 2010; 1: 97–99.

23. Harger J.H., Rabin B.S., Marchere S.G. The prognostic value of antinuclear antibodies in women with recurrent pregnancy losses. Obstet Gynecol. 1989; 73 (3): 419–424.

24. Rosenberg A.M., Bingham M.C., Fong K.C. Antinuclear antibodies during pregnancy. Obstet Gynecol. 1986; 68: 560–562.

25. El-Roeiy A., Gleicher N. Definition of normal autoantibody levels in an apparently healthy population. Obstet Gynecol. 1988; 72: 596–602.

26. Petri M., Golbus M., Anderson R. Antinuclear antibody lupus anticoagulant and anticardiolipin antibody in women with habitual abortion. Arthritis Rheumatol. 1987; 30: 601–606.

27. Patton P.E., Coulam E.B., Bergstralh E. The prevalence of antibodies in pregnant and nonpregnant women. Am. J. Obstet Gynecol. 1987; 157: 345–350.

28. Hughes G.R.V. Autoantibodies in lupus and its variants: experience of 1000 patients. Brit. Med. J. 1984; 289: 339–342.

29. Степанова Р.Н. Беременность и аутоиммунные нарушения. Акушер-гинеколог. 1996; 1: 6–9.

30. Donaldson J.M., Espiner E.A. Disseminated lupus erythematosus presenting as chorea. Arch Neurol. 1971; 25: 240–244.

31. Asherson R.A. Pulmonary hypertension in systemic lupus erythematosus. Brit. Med. J. 1983; 287: 1024–1025.

32. Cunningham F.G., Leveno K.J., Bloom S.L., eds. Williams Obstetrics. NI – Toronto: Mc Graw-Hill; 2005. 1441.

33. Bobrie G., Liote F., Houiller B. Pregnancy in lupus nephritis and related disorders. Am. J. Kidney Dis. 1987; IX: 339–343.

34. Devoe L.D., Taylor R.L. Systemic lupus erythematosus in pregnancy. Am. J. Obstet Gynecol. 1979; 135: 473–479.

35. Houser M.T., Fish A.J., Tagatl G.E. Pregnancy and systemic lupus erythematosus. Am. J. Obstet Gynecol. 1980; 138: 409–413.

36. Gladman D.D., Tandon A., Ibañez D., Urowitz M.B. The effect of lupus nephritis on pregnancy outcome and fetal and maternal complications. J. Rheumatol. 2010; 37 (4): 754–758.

37. Donaldson L.B., Alvarez de R.R. Furter observations on lupus erythematosus associated with pregnancy. Am. J. Obstet Gynecol. 1962; 83: 1461–1473.

38. Buyon J.P., Kim M.Y., Guerra M.M., Laskin C.A., Petri M. Predictors of Pregnancy Outcomes in Patients With Lupus: A Cohort Study. Ann Intern Med. 2015; 163 (3): 153–163.

39. So-Young Kim, Jung-Hyun Lee. Prognosis of Neonates in Pregnant Women with Systemic Lupus Erythematosus. Yonsei Med. J. 2008; 49 (4): 515–520.

40. Gimovsky M.L., Montoro M., Paul R.H. Pregnancy outcome in women with systemic lupus erythematosus. Am. J. Obstet Gynecol. 1984; 63: 686–692.

41. Yan Yuens, Krizova A., Ouimet J., Pope J. Pregnancy outcome in systemic lupus erythematosus (SLE) in improving. Open Rheumatol. J. 2008; 2: 89–98.

42. Clowse M.E., Magder L.S., Wittur F., Petri M. The impact of increased lupus activity on obstetric outcome. Arthritis Rheum. 2005; 52 (20): 514–521.

43. Götestam Skorpen C., Hoeltzenbein M., Tincani A., Fischer-Betz R. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann. Rheum. Dis. 2016; 75 (5): 795–810.

44. Clowse M.E., Jamison M., Mgers E., James A. A navigational study of the complications of lupus in pregnancy. Am. J. Obstet Gynecol. 2008; 199 (126): 1271–1276.

45. Scott J.R. Risks to the children born to mothers with autoimmune diseases. Lupus. 2002; 11: 655–659.

46. So-Young Kim, Jung-Hyun Lee. Prognosis of Neonates in Pregnant Women with Systemic Lupus Erythematosus. Yonsei Med. J. 2008; 49 (4): 515–520.

47. Tseng C.E., Buyon J.P. Neonatal lupus syndrome. Rheum. Dis. Clin. North. Am. 1997; 23: 31–35.

48. Котлукова Н. Синдром неонатальной волчанки. Медгазета. 2002; 60: 60–61.

49. Le Thi Huong D., Wechsler B., Vauthier-Brouzes D. The second trimester Doppler ultrasound examination is the best predictor of late pregnancy outcome in systemic lupus erythematosus and/or the antiphospholipid syndrome. Rheumatology. 2006; 45 (3): 332–338.

50. Scog A. Outcome and growth of infants fetaly exposed to heart block-associated maternal anti Ro52/SSA autoantibodies. Pediatrics. 2008; 121: 803–809.

51. Sangle S., D′Cruz D.P., Hughes G.R. Livedo reticularis and pregnancy morbidity in patients negative for antiphospholipid antibodies. Ann. Rheum. Dis. 2005; 64: 147–153.

52. Julkunen H., Jouhikeinen T., Kaaja R. Fetal outcomes in lupus pregnancy. Lupus. 1993; 2: 125–131.

53. Reichlin M. Systemic lupus erythematosus. J. Reprod. Med. 1998; 43: 355–360.

54. Ruiz-Irastorza G., Khamasutra M.A., Hughes G.R. Systemic lupus erythematosus and antiphospholipid syndrome during pregnancy. Int. Med. Ass. J. 2000; 2: 462–469.

55. Richards D.S., Wagman A.J., Cabaniss M.L. Ascites not due to congestive heart failure in a fetus with lupus-induced heart block. Obstet Gynecol. 1990; 76: 957–959.

56. Lateef A., Petri M. Management of pregnancy in systemic lupus erythematosus. Nat. Rev. Rheumatol. 2012; 8 (12): 710–718.

57. Jara L.J., Medina G., Cruz-Dominguez P., Navarro C. Risk factors of systemic lupus erythematosus flares during pregnancy. Immunol. Res. 2014; 60 (2–3): 184–189.

58. Petri M., Daly R.P., Pushparajah D.S. Healthcare costs of pregnancy in systemic lupus erythematosus: retrospective observational analysis from a US health claims database. J. Med. Econ. 2015; 18 (11): 967–973.

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DOI: 10.23648/UMBJ.2018.29.11354 

PREGNANCY AND SYSTEMIC LUPUS ERYTHEMATOSUS

R.N. Stepanova

Orel State University named after I.S. Turgenev, Orel, Russia

e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many human organs and systems. In patients with SLE a large number of antibodies to the antigens of their own cells is formed. It leads to an immunocomplex inflammatory process, which affects heart, skin, kidneys, lungs, joints, and the nervous system. SLE contributes to the failure of a fundamental characteristic of the immune system, namely tolerance to autoantigens. As a result, antibodies that attack normal tissues in many parts of the body are produced. This process is accompanied by autoimmune disease development. Patients with
SLE demonstrate such clinical manifestations as multiple thrombosis, including pulmonary embolism (PE), CNS diseases, livedo reticularis, labile hypertension, habitual miscarriage. SLE affects people of all races, men and women, but it dominates in women and often develops in females of reproductive age.
SLE prevalence among women of reproductive age is 1:500. Nearly 90 % of patients diagnosed with lupus are women. The reasons for SLE development are unknown. Now it is generally accepted, that gestational complications such as habitual abortion, preeclampsia and eclampsia, premature placental abruption, disseminated intravascular coagulation (DIC) and HELLP syndromes, thromboses, intrauterine growth retardation, and stillbirth are associated with maternal autoimmune diseases. However, the mechanism how SLE interferes with pregnancy and worsens its outcomes for the mother, fetus, and newborn remains unidentified. Probably, vascular lesions of the placenta contribute to the process, as their nature is similar to the lupus vascular disease in patients with SLE. Reproductive loss in SLE mothers, especially in clinically active lupus, can reach 45 %. The article analyzes the literature on the problems of interaction between SLE and pregnancy, the lupus clinical course in pregnant women, the maternal and perinatal gestational outcome, and neonatal lupus frequency.

Keywords: systemic lupus erythematosus, pregnancy complications, pregnancy outcomes, neonatal lupus.

 

References

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2.   Hom D., Graham R., Modrek B. Association of systemic lupus erythematosus with C8 orf 13-BLK and ITGAM-ITGAX. N. Engl. J. Med. 2008; 358: 900–909.

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5.   Zhonghua Nei Ke. Close association of herpes zoster reactivation and systemic lupus erythematosus diagnosis. Open Rheumatol. J. 2008; 2: 89–98.

6.   Lockshin M.D., Sammaritano L.R. Rheumatic disease. In: Barron W.M., eds. Medical Disorders during pregnancy. 3-d ed. St. Louis: Mosby; 2000: 355.

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8.   Zwahr C., Räte K., Brietzke W. Letaler Ausgang bei lupus erythematosus viscerale und Gravidität. Zbl Gynäkol. 1983; 105: 300–307.

9.   Day C.J., Lipkin G.W. Lupus nephritis and pregnancy in the 21st century. Oxford J. Nephrol Dialys Transplantat. 2009; 24 (2): 344–347.

10. Dudley D.J., Branch D.W. New approaches to recurrent pregnancy loss. Clinical Obstet Gynecol. 1989; 32 (3): 520–532.

11. Scott J.R., Rote N.S., Branch D.W. Immunologic aspects of recurrent abortion and fetal death. Obstet. Gynecol. 1987; 70: 645–656.

12. Stepanova R.N. Beremennost' i aberratsii immuniteta [Pregnancy and immune aberrations]. Moscow: Sputnik-plyus; 2013. 136 (in Russian).

13. Hanly J.G., Gladman D.D., Rose T.H. Lupus Pregnancy. A prospective study of placental changes. Artritis Rheumatol. 1988; 31: 358–366.

14. Guzman L., Avalos E., Orliz R. Placental abnormalities in systemic lupus erythematosus. J. Rheumatol. 1987; 14: 924–929.

15. Rybina A.N., Belinskaya A.M., Cherepkova N.V. Morfologicheskie izmeneniya v platsentakh rozhenits s sistemnoy krasnoy volchankoy [Morphological changes in the placenta of parturient women with systemic lupus erythematosus]. Materialy IV s’ezda akusherov-ginekologov Rossii [Proceedings of the 4th congress of obstetricians and gynecologists of Russia]. Moscow; 2008: 221–222 (in Russian).

16. Baguley E., Maclachlan N., Hughes G. SLE and pregnancy. Clin Exp Rheum. 1988; 6: 183–185.

17. Varner M.W., Meehan R.T., Syrop G. Pregnancy in patients with lupus erythematosus. Am. J. Obstet Gynecol. 1983; 145: 1025–1040.

18. El-Roeiy A., Myers S.A., Gleicher N. The prevalence of autoantibodies and lupus anticoagulant in healthy pregnant women. Obstet Gynecol. 1990; 75: 390–396.

19. Cowchock S., Smith J., Gocial B. Antibodies to phospholipids and nuclear antigens in patients with repeated abortion. Am. J. Obstet Gynecol. 1986; 155: 1002–1010.

20. Farnam J., Lavastida M., Grant J. Antimiclear antibodies in the serum normal pregnant women. J. Allergy Clin Immunol. 1984; 73: 596–599.

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22. Stepanova R.N., Makarova O.M. Antinuklearnye autoantitela (ANA) pri privychnoy potere ploda [Antinuclear autoantibodies (ANA) in women with habitual loss of fetus]. Kurskiy nauchno-prakticheskiy vestnik “Chelovek i ego zdorov'e”. 2010; 1: 97–99 (in Russian).

23. Harger J.H., Rabin B.S., Marchere S.G. The prognostic value of antinuclear antibodies in women with recurrent pregnancy losses. Obstet Gynecol. 1989; 73 (3): 419–424.

24. Rosenberg A.M., Bingham M.C., Fong K.C. Antinuclear antibodies during pregnancy. Obstet Gynecol. 1986; 68: 560–562.

25. El-Roeiy A., Gleicher N. Definition of normal autoantibody levels in an apparently healthy population. Obstet Gynecol. 1988; 72: 596–602.

26. Petri M., Golbus M., Anderson R. Antinuclear antibody lupus anticoagulant and anticardiolipin antibody in women with habitual abortion. Arthritis Rheumatol. 1987; 30: 601–606.

27. Patton P.E., Coulam E.B., Bergstralh E. The prevalence of antibodies in pregnant and nonpregnant women. Am. J. Obstet Gynecol. 1987; 157: 345–350.

28. Hughes G.R.V. Autoantibodies in lupus and its variants: experience of 1000 patients. Brit. Med. J. 1984; 289: 339–342.

29. Stepanova R.N. Beremennost' i autoimmunnye narusheniya [Pregnancy and autoimmune disorders]. Akusher-ginekolog. 1996; 1: 6–9 (in Russian).

30. Donaldson J.M., Espiner E.A. Disseminated lupus erythematosus presenting as chorea. Arch Neurol. 1971; 25: 240–244.

31. Asherson R.A. Pulmonary hypertension in systemic lupus erythematosus. Brit. Med. J. 1983; 287: 1024–1025.

32. Cunningham F.G., Leveno K.J., Bloom S.L., eds. Williams Obstetrics. NI – Toronto: Mc Graw-Hill; 2005. 1441.

33. Bobrie G., Liote F., Houiller B. Pregnancy in lupus nephritis and related disorders. Am. J. Kidney Dis. 1987; IX: 339–343.

34. Devoe L.D., Taylor R.L. Systemic lupus erythematosus in pregnancy. Am. J. Obstet Gynecol. 1979; 135: 473–479.

35. Houser M.T., Fish A.J., Tagatl G.E. Pregnancy and systemic lupus erythematosus. Am. J. Obstet Gynecol. 1980; 138: 409–413.

36. Gladman D.D., Tandon A., Ibañez D., Urowitz M.B. The effect of lupus nephritis on pregnancy outcome and fetal and maternal complications. J. Rheumatol. 2010; 37 (4): 754–758.

37. Donaldson L.B., Alvarez de R.R. Furter observations on lupus erythematosus associated with pregnancy. Am. J. Obstet Gynecol. 1962; 83: 1461–1473.

38. Buyon J.P., Kim M.Y., Guerra M.M., Laskin C.A., Petri M. Predictors of Pregnancy Outcomes in Patients with Lupus: A Cohort Study. Ann Intern Med. 2015; 163 (3): 153–163.

39. So-Young Kim, Jung-Hyun Lee. Prognosis of Neonates in Pregnant Women with Systemic Lupus Erythematosus. Yonsei Med. J. 2008; 49 (4): 515–520.

40. Gimovsky M.L., Montoro M., Paul R.H. Pregnancy outcome in women with systemic lupus erythematosus. Am. J. Obstet Gynecol. 1984; 63: 686–692.

41. Yan Yuens, Krizova A., Ouimet J., Pope J. Pregnancy outcome in systemic lupus erythematosus (SLE) in improving. Open Rheumatol. J. 2008; 2: 89–98.

42. Clowse M.E., Magder L.S., Wittur F., Petri M. The impact of increased lupus activity on obstetric outcome. Arthritis Rheum. 2005; 52 (20): 514–521.

43. Götestam Skorpen C., Hoeltzenbein M., Tincani A., Fischer-Betz R. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann. Rheum. Dis. 2016; 75 (5): 795–810.

44. Clowse M.E., Jamison M., Mgers E., James A. A navigational study of the complications of lupus in pregnancy. Am. J. Obstet Gynecol. 2008; 199 (126): 1271–1276.

45. Scott J.R. Risks to the children born to mothers with autoimmune diseases. Lupus. 2002; 11: 655–659.

46. So-Young Kim, Jung-Hyun Lee. Prognosis of Neonates in Pregnant Women with Systemic Lupus Erythematosus. Yonsei Med. J. 2008; 49 (4): 515–520.

47. Tseng C.E., Buyon J.P. Neonatal lupus syndrome. Rheum Dis. Clin. North. Am. 1997; 23: 31–35.

48. Kotlukova N. Sindrom neonatal'noy volchanki [Neonatal lupus syndrome]. Medgazeta. 2002; 60: 60–61 (in Russian).

49. Le Thi Huong D., Wechsler B., Vauthier-Brouzes D. The second trimester Doppler ultrasound examination is the best predictor of late pregnancy outcome in systemic lupus erythematosus and/or the antiphospholipid syndrome. Rheumatology. 2006; 45 (3): 332–338.

50. Scog A. Outcome and growth of infants fetaly exposed to heart block-associated maternal anti Ro52/SSA autoantibodies. Pediatrics. 2008; 121: 803–809.

51. Sangle S., D′Cruz D.P., Hughes G.R. Livedo reticularis and pregnancy morbidity in patients negative for antiphospholipid antibodies. Ann. Rheum. Dis. 2005; 64: 147–153.

52. Julkunen H., Jouhikeinen T., Kaaja R. Fetal outcomes in lupus pregnancy. Lupus. 1993; 2: 125–131.

53. Reichlin M. Systemic lupus erythematosus. J. Reprod. Med. 1998; 43: 355–360.

54. Ruiz-Irastorza G., Khamasutra M.A., Hughes G.R. Systemic lupus erythematosus and antiphospholipid syndrome during pregnancy. Int. Med. Ass. J. 2000; 2: 462–469.

55. Richards D.S., Wagman A.J., Cabaniss M.L. Ascites not due to congestive heart failure in a fetus with lupus-induced heart block. Obstet Gynecol. 1990; 76: 957–959.

56. Lateef A., Petri M. Management of pregnancy in systemic lupus erythematosus. Nat. Rev. Rheumatol. 2012; 8 (12): 710–718.

57. Jara L.J., Medina G., Cruz-Dominguez P., Navarro C. Risk factors of systemic lupus erythematosus flares during pregnancy. Immunol. Res. 2014; 60 (2–3): 184–189.

58.          Petri M., Daly R.P., Pushparajah D.S. Healthcare costs of pregnancy in systemic lupus erythematosus: retrospective observational analysis from a US health claims database. J. Med. Econ. 2015; 18 (11): 967–973.