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Lupus and Pregnancy

Lupus and Pregnancy. Prof. Munther A Khamashta MD FRCP PhD Director: Graham Hughes Lupus Research Laboratory The Rayne Institute, St Thomas Hospital ( Dubai Hospital Rheumatology Department ). Challenges in Obstetrics & Gynaecology , Kuwait, February 2017. Disclosures.

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Lupus and Pregnancy

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  1. Lupus and Pregnancy Prof. Munther A Khamashta MD FRCP PhDDirector: Graham Hughes Lupus Research Laboratory The Rayne Institute, St Thomas Hospital ( Dubai Hospital Rheumatology Department ) Challenges in Obstetrics & Gynaecology, Kuwait, February 2017

  2. Disclosures

  3. Lupus in pregnancy clinic – St Thomas’ Hospital

  4. Connective Tissue Disorders and Pregnancy St Thomas’ Hospital 1987-2015 • Systemic Lupus Erythematosus >1000 • Antiphospholipid syndrome >1000 • Sjögren’s Syndrome 90 • Rheumatoid arthritis 50 • Vasculitis 30 • Mixed Connective Tissue disease 20 • Systemic sclerosis/scleroderma 15

  5. SLE: heterogeneous multi-system progressive autoimmune disease.Many patients fluctuate/cycle. No established treatment algorithm Flares Time Remission Long Quiescent 10-15% Barr et al. ARTHRITIS & RHEUMATISM. Vol. 42, No. 12, December 1999, pp 2682–2688. Petri et al. Lupus (1999) 8, 685-691 Petri. RHEUMATIC DISEASE CLINICS OF NORTH AMERICA. VOLUME 26 - NUMBER 2 MAY 2000 Relapse Remitting 50-60% Chronic Active 20-25%

  6. What makes a pregnancy “high risk”? • Renal involvement • Antiphospholipid syndrome • Previous poor obstetric history • Cardiac involvement • Pulmonary hypertension • Restrictive lung disease (FVC < 1 litre) • Active disease. • Extractable nuclear antigens (Ro, La) Ateka-Barrutia O, Khamashta MA. Lupus. 2013;22:1295-308

  7. Pregnancy and Lupus Potential problems • Lupus flare: 40-50% • Miscarriages or stillbirths: 20-25% • Premature birth of the infant: 25% • Pre-eclampsia: 15-20% • Neonatal lupus: 1-3% (Ro-positive) Ruiz-Irastorza G, Khamashta MA. European journal of clinical investigation. 2011;41:672-8

  8. Renal involvement / hypertension • Increased risk of PET / IUGR / preterm delivery • Even quiescent lupus nephritis increases risk of fetal loss, especially if hypertensive or proteinuric • Risk of deterioration is higher with higher serum creatinine • Chance of successful outcome is lower with higher serum creatinine • Delay pregnancy for 6 months after renal flare

  9. SLE with and without Lupus Nephritis SLE + Nephritis (43) SLE – Nephritis (64) Maternal Outcome Pre-eclampsia 12 (28.6%) 10 (16.9%) Thrombus 0 1 (1.7%) Flare 14 (41.2%) 22 (37.3%) Neonatal Outcome IUD 1 (2.9%) 1 (1.7%) NND 1 (2.9%) 0 Gestation 36.7± 4.2 38.2 ± 3.0 % <34/40 8 (19%) 2 (3%) % <37/40 13 (30%) 7 (11%) 2963 ± 717 Birth Weight (g) 2715 ± 862 %<10th Centile SGA 14 (33%) 14 (23.3%) Bramham K et al. J Rheumatol 2011;38:1906-13

  10. Increasing proteinuria • Physiological • Pre-eclampsia • Nephritic flare

  11. Nephritic flare / Pre-eclampsia

  12. Mid-trimester uterine artery Doppler screening as a predictor of pre-eclampsia • In high-risk women better than clinical risk assessment • Positive predictive values up to 60% • Negative predictive values up to 92% Coleman, McCowan & North Ultrasound Obstet Gynecol 2000 Normal Early Diastolic Notching

  13. NEONATAL LUPUS Passively Acquired Autoimmunity MATERNAL CIRCULATION PLACENTAL TRANSPORT FETAL CIRCULATION anti-Ro/La Abs FcRn anti-Ro/La Abs CLINICAL FEATURES Congenital AV block/Cardiomyopathy CARDIAC CUTANEOUS • Risk 2% if no affected childIn utero 18-28 wks • Unique to the fetus • Permanent, high morbidity/mortality • Risk 5% • Birth →6 wks, UV-provoked • Resembles adult SCLE • Transient, rare scarring

  14. Neonatal lupus 3 weeks 3 months

  15. Congenital Heart Block • Appears in utero (18-28 weeks) • Fetal bradycardia • 50-60% of those who survive need pacemakers in early infancy (others in early teens) • Currently no treatment to prevent recurrence Recurrence rate 1 in 5 Brito-zeron p et al.Nat Rev Rheumatol 2015,11:301-12

  16. Experience of IVIG use (animal model) Fetal:maternal ratios of Ro and La antibodies were lower in IVIG group (p<0.001) Tran HB et al, Arthritis Rheum 2004

  17. Restriction of Analysis to 42 Pregnancies Following a Child with Cardiac NL in Two Recent Prospective Studies of IVIG, no Recurrences of Cardiac NL Occurred in Fetuses Exposed to Hyroxychloroquine 0/8=0% 7/34=20.6% Izmirly et al, Circulation 2012, 126:76-82.

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