1. Pregnancy and other Rheumatological Diseases Dr Subramanian R, MD PDF JSS Medical College Mysore

2. Case Scenarios Case A 23 yr old patient 3 months amenorrhoea Diagnosed case of vasculitis Had renal involvement 1 year back Currently on low dose steroids and azathioprine Skin lesions in the lower limbs : biopsy s/o vasculitis Case B 25 yr old patient 2 nd pregnancy, in her 7 th month Diagnosed as Rheumatoid arthritis 4 years of disease Previous pregnancy 2 years back Currently on hydroxychloroquine Has mild joint pains in the hands with early morning stiffness

3. Outline Common connective tissue disorders and vasculitis in pregnancy Outcome of pregnancy Problems that need to be anticipated Safety of the drugs Future pregnancies

4. Autoimmune disorders Connective tissue disorders Rheumatoid arthritis Seronegative spondyloarthritides Undifferentiated connective tissue diseases (UCTD) Mixed connective tissue diseases (MCTD) Polymyositis– dermatomyositis (PM–DM) Vasculitides Wegener’s granulomatosis Churg–Strauss syndrome Microscopic polyangitis Polyarteritis nodosa Takayasu arteritis Behcet ‘s disease

5. Flares Drugs Mode of delivery

6. Organ involvement Inflammation of blood vessels and organ ischemia Abortions, IUGR Drugs Flares of the disease

7. RA and pregnancy Majority of pregnancies in women with RA are without complication – the mother has a decrease in her arthritis pain – the baby is born healthy 75% of women experienced improvement in their disease during pregnancy (range 54–86%) and 90% of women reported a relapse in disease within 3 months of delivery Ostensen M, Villiger PM. The remission of rheumatoid arthritis during pregnancy. Semin Immunopathol 2007;29:185–91 Nelson JL, Ostensen M. Pregnancy and rheumatoid arthritis. Rheum Dis Clin North Am 1997;23:195–212

9. Pregnancy suppresses disease activity?

10. Upregulation of T regs inhibits the generation of TH 17

11. Pregnancy outcomes for women with Rheumatoid arthritis Scand J Rheumatol 2010;39:99–108

12. Premature delivery and Preeclampsia risk for preterm birth, however does seem to be increased for women with RA one out of every four women with RA delivered early compared to 1 in 10 women without RA Preeclampsia and caesarean section rates have been shown to be higher in mothers with RA Having increased RA activity and using disease-modifying anti-rheumatic drugs (DMARDs) and steroid medications increases the risks for these complications

13. Influence of treatment change Women may change or cease treatment during or after pregnancy for a variety of reasons, including improvement in symptoms and fear of harming the fetus

14. Subsequent pregnancy previous experience postpartum was not predictive of deterioration after the current pregnancy

15. Ankylosing spondylitis Compared to pregnant women with RA, women with AS generally experience unchanged or increased disease activity – increased morning stiffness – spinal tenderness – pain at night and need for non-steroidal medications during pregnancy

16. …contd AS associated with small joint disease,psoriasis, or ulcerative colitis have improvement Postpartum flares are also common, especially during the first 3 months after delivery The postpartum flare is independent of level of disease activity during pregnancy, period of lactation, or the return of menses Disease activity during the year following delivery seems to return to the same level as before conception There appears to be no increase in frequency of miscarriage, premature labour, or delivery complications in this population of women

17. …contd Of note, women with AS experience a similar increase in Tregs during pregnancy as women with RA However, Tregs in pregnant woman with AS secrete less IL-10 and have lower suppression of INF-g and TNFa secretion by effector T cells This may account for the difference in disease activity experienced during pregnancy among women with AS and RA

18. Pregnancy other connective tissue disorders and vasculitis Outcome of pregnancy depends on – organ involvement – Status of immunosuppressive drugs – Previous pregnancy related complications – Comorbidities

19. Scleroderma and pregnancy Successful pregnancy could be achieved with good outcomes both in the mother and infant Percentage RR95% CIP value Long standing SSc 42 2.8 1.23 – 6.37 < 0.05 Other subjects 15

21. …contd Scleroderma disease activity does not change in pregnancy Raynaud’s phenomenon may improve with pregnancy secondary to a physiological increase in cardiac output Gastroesophageal reflux disease (GERD) worsens, especially during the latter part of pregnancy

22. …contd Scleroderma renal crisis is a feared complication during pregnancy Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers are life-saving treatments for scleroderma renal crisis – renal atresia, pulmonary hypoplasia, and foetal death Prior episode of renal crisis is not a strict contraindication for future pregnancy, but it is recommended that a woman wait several years until her disease is stable before trying to conceive

23. Pulmonary hypertension is another serious complication and is associated with 50% maternal mortality, and most vigilance is required 48 to 72 hours after delivery

24. Vasculitides Vasculitides can occur at any age but are generally more frequent in men and in women beyond their reproductive period Planning conception at a time of disease inactivity usually allows women with Wegener granulomatosis (WG), polyarteritis nodosa (PAN), or Churg-Strauss syndrome to remain well during pregnancy

26. They are at risk of deterioration during pregnancy and the first 6 weeks after delivery should conception occur when the disease is inadequately treated or newly active In Takayasu arteritis (TA), severe aortic valvular disease and aortic aneurysm are risk factors for maternal morbidity and fatality; therefore, pregnancy is discouraged in these patients

27. Pregnancy effects Hypertensive disease is more common in women with WG and renal involvement than in normal pregnant women Pregnancy complications and cesarean section were significantly higher in BD patients than in controls, as with most other vasculitides, particularly TA and WG

30. Other diseases UCTD Polymyositis and dermatomyositis MCTD

31. What to do when disease is active in pregnancy ? Trimester Fetal status Drugs Organ involvement Safe pregnancy Abortion, early delivery IUGR, abnormalities High dose steroids / Azathioprine, IVIG Major or minor

32. Autoantibodies and pregnancy Anti-thyroid antibodies (ATAs) have been suggested to be independent markers of ‘at-risk’ pregnancy Euthyroid women with recurrent miscarriage have increased levels of autoantibodies either against thyroglobulin (aTG) or thyroid peroxidase (TPO) while the probability of abortion in women with ATA has been shown to be greater than in controls

33. the prevalence of ATA has been reported to be 15–20% in normal pregnant women, compared with 20–25% in women with recurrent miscarriages Anti-laminin antibodies : IgG anti-laminin antibodies have been associated with infertility and recurrent first-trimester miscarriages in humans

35. Conclusion With careful planning, most women with inflammatory rheumatological diseases can have successful pregnancies It is important that conception occur when the disease has been inactive for at least 6 months and while the mother is taking non- teratogenic drugs