1. 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

2. Disclosures Research Grants: Bayer Consultant/Advisor:
UCB , Inova diagnostics , Medimmune / AstraZeneca
Speakers’ Bureau:
UCB , GSK , Inova diagnostics

3. Lupus in pregnancy clinic – St Thomas’ Hospital

4. Connective Tissue Disorders and Pregnancy
St Thomas’ Hospital
Systemic Lupus Erythematosus >1000
Antiphospholipid syndrome >1000
Sjögren’s Syndrome
Rheumatoid arthritis
Vasculitis
Mixed Connective Tissue disease
Systemic sclerosis/scleroderma

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

8. 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:

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

10. 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

14. SLE with and without Lupus Nephritis
SLE + Nephritis
(43)
SLE – Nephritis
(64)
Maternal Outcome
Pre-eclampsia
12 (28.6%)
10 (16.9%)
Thrombus
1 (1.7%)
Flare
14 (41.2%)
22 (37.3%)
Neonatal Outcome
IUD
1 (2.9%)
1 (1.7%)
NND
1 (2.9%)
Gestation
36.7± 4.2
38.2 ± 3.0
Prematurity due to PET in 50% <34 in both + and - nephritis and 40% and 30% in <37 respectively
% <34/40
8 (19%)
2 (3%)
% <37/40
13 (30%)
7 (11%)
Birth Weight (g)
2715 ± 862
2963 ± 717
%<10th Centile SGA
14 (33%)
14 (23.3%)
Bramham K et al. J Rheumatol 2011;38:

15. Increasing proteinuria
Physiological
Pre-eclampsia
Nephritic flare

16. Nephritic flare / Pre-eclampsia
To help distinguish between PET and a flare of lupus (esp. lupus nephritis).
PET
Flare of lupus
Proteinuria ++
> 0.3g/ day or PCR > 30
(in lupus nephritis)
Casts in MSU
Absent
Present (if lupus nephritis)
RBC in MSU
Present if nephritic
Hypertension
If sBP > 20mmHg or dBP > 10mmHg above booking BP
May be present
Involvement of skin and joints No
Malar rash, photosensitive rash or evidence of arthritis
Seizures
Present in eclampsia
Present if there is neurological involvement
Urate
Elevated
Not elevated unless CKD
Albumin
Low
Very low if nephrotic syndrome
LFT
May be deranged
Rarely deranged in a flare of SLE
C3 and C4
Unchanged from baseline in early pregnancy
Anti-dsDNA
Unchanged

17. Early Diastolic Notching
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

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

20. Neonatal lupus
3 weeks
3 months

21. 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

22. 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

24. 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
+ HCQ
HCQ
Unaffected 8 27
Cardiac NL 7
0/8=0% 7/34=20.6%
Izmirly et al, Circulation 2012, 126:76-82. 24