Dr. Alka Pandey

1. Dr. Alka Pandey
Associate Prof. PMCH,
Deptt. Of OB & GY
Patna
Pregnancy
in
SLE

2. Pregnancy in SLE
Systemic Lupus Erythematosus (SLE) is a rare,
multisystem, chronic autoimmune disease in
which the tissues are damaged by autoantibodies
and immune complex.

3. •The disease affects women and men in a ratio
of 10:1
•Prevalence of SLE in women of childbearing
years is around 1 in 500.
Incidence

4. Exact cause remains unknown
It has been proposed that an environmental trigger such as
ultraviolet light or a viral infection; for example, the Epstein-
Barr virus combined with a genetic predisposition, forms the
basis of the disease process.
Pathophysiology

5. The disease is characterised by immune complex
deposition which causes inflammation in vascular beds.
There is polyclonal B-cell activation which is thought to
result in antinuclear antibody production.
There is also an associated impairment of T-cell
regulation and deficiencies in complement which leads to
a failure to remove these immune complexes.

6. Patients who are antinuclear antibody negative are very unlikely to have SLE.
Patient is classified of having SLE if any of 4 or more of following criteria is met.
Diagnostic Criteria

8. •Pregnancy related complications are common with SLE.
•SLE flare can occur during pregnancy.
•Fetal outcome is poor.
•Safety of drugs during pregnancy has to be kept in mind.
Why SLE is important in Pregnancy?

9. Pre-pregnancy challenge
Information gathering
•Past and current disease activity
•Preexisting organ damage
•Serological profile
•Medication history
•Additional medical disorders
•Past obstetric history
•Baseline blood pressure, urinalysis.

10. Initial evaluation should be based on thorough history taking and
physical examination along with careful BP measurement.
Evaluation
Investigations during first visit:
• Routine urine analysis
• CBC, ESR,
Serum creatinine 24 hour urinary total protein,(Creatinine clearance
test if possible)
• Anti-ds-DNA (raised level indicates active SLE or impending flare.)

11. •Anti-Ro(SS-A) and Anti-La(SS-B), Anti-Phospholipid Antibodies (Anti cardoilipin
Ab & Lupus anticoagulant).
• Serum C3 &C4 level (low C3 indicates active SLE or impending flare in over
80% of patients.)
• Fasting blood glucose if at high risk
• Serum lipids if patient is nephrotic or on steroids
• Coombs’ test
• Hepatitis B & C serology, Anti HIV screening, Syphilis serology
LFT
Evaluation

12. Investigations for assessment of disease activity
Organ /System Complication/manifestation/investigation
Cardiac Pulmonary hypertension, valvular heart disease, cardiomyopathy: assess with
echocardiography
Respiratory Pulmonary fibrosis: may need to consider chest X-ray, CT lung function tests if
there is underlying restrictive respiratory involvement.
Renal Urine dipstick and protein: creatinine ratio to screen for and to quantify any
underlying proteinuria.
Document and quantify presence of haematuria, hypertension and/or renal
impairment (lupus nephritis).
Renal function tests to assess pre-existing renal dysfunction
Haematology/
Immunology
Thrombosis: assessment of risk and need for anticoagulation. Full blood count
to determine any anaemia, neutropenia or thrombocytopenia.
Autoantibody profile: antiphospholipid (aPL), anticardiolipin (aCL) lupus
anticoagulant (LA), anti-dsDNA and anti-La antibodies, complement C3/C4
levels.

13. Stratification of women into these three groups enables an overall
approach to management, with adjustment for individual
situations.
Pre-pregnancy challenge : appropriate counseling
1.SLE in remission, or stable
low disease activity:
medication should be
reviewed and adjusted as
necessary; pregnancy can
be planned
2. SLE with active
disease: those
women should be
encouraged to
postpone pregnancy
and use effective
contraception.
Pregnancy should be
planned on
remission.
3. Severe impairment of
organ function and/or
preexisting severe organ
damage : pregnancy
should be discouraged;
alternatives, including
adoption and surrogacy
should be discussed.

14. •Severe lupus flares within the previous 6 months.
•Severe restrictive lung disease
•Heart failure.
•Chronic renal failure
•Stroke within the previous 6 months.
•Previous severe preeclampsia or HELLP syndrome despite therapy
with aspirin and heparin.
•Severe pulmonary hypertension (Estimated systolic PAP >50mm Hg
or symptomatic)
Contraindications to pregnancy

15. Factors affecting pregnancy outcomes in SLE
•Disease activity
• Lupus nephritis
• Anti-Ro/anti-La antibodies
• Antiphospholipid syndrome
• Cardiac/lung involvement

16. Appropriate Medications
European League Against Rheumatism task force overarching
principles include
•The importance of family planning.
•The aim to prevent or suppress disease activity in the
mother whilst minimizing harm to the fetus.
•The balancing of risks of medication against risks of
untreated disease.
•Importance of multidisciplinary input when making
decisions about treatment.

17. Medications
•Medications which are safe throughout pregnancy and during
lactation to maintain remission and/or treat flare are HCQ.,
Azathioprine, Cyclosporine, and Tacrolimus.
•The aim should be to use steroid-sparing immuno-
suppressants. Corticosteroids are safe to control active disease
symptoms in low dose.
•Antihypertensive medication for PIH or PET may include
labetalol, methyldopa, nifedipine and hydralazine.

18. SLE patients suffer from different kinds of pregnancy related
complications more frequently than non-SLE women do.
There are two main problems;
Firstly -- increased pregnancy related complication due to
SLE &
Secondly -- SLE disease flares due to pregnancy

19. •Pregnancy related hypertension
• Preeclamsia
• Eclamsia
• HELLP syndrome
• Ante-partum haemorrhage
• IUGR
• Pre-maturity, Abortion & Still birth
• Gestational diabetes (increased by prednisone used for SLE Rx)
Common pregnancy related complications
Antenatal Challenge

20. • Infection
• Deep vein thrombosis
• Pulmonary embolism
• Cerebro-vascular accident (stroke)
• Pulmonary hypertension
Other Maternal Complications of Lupus Pregnancy

21. Flare may be defined as unpredictable bouts of the disease after a
period of remission.
Flare increases maternal morbidity, risk of premature delivery and
fetal loss.
Therapeutic issues are also important concern.
Antenatal Challenge : Maternal Lupus Flares

22. •Flares can occur throughout pregnancy so close follow up is
required.
•Flares are generally mild with pregnant women experiencing
arthritis, fatigue and cutaneous manifestations.
•Exacerbation of SLE with major organ involvement such as the
CNS and kidneys, may occur in upto 5% and 46% respectively.
• A fall of ≥25% in serum complement levels during pregnancy
may suggest lupus flare.

23. Pregnancy changes SLE activity
Clinical features Facial flush Photosensitive rash
Palmar erythema Oral or nasal ulcers
Arthralgias Inflammatory arthritis
Fatigue Fatigue, lethargy
Mild edema Moderate to severe edema
Mild resting dyspnea Pleuritis, pericarditis
Laboratory features Mild anemia Immune hemolytic anemia
Mild thrombocytopenia Thrombocytopenia
Leukopenia, lymphopenia
Mild increased ESR Increased inflammatory marker levels
Physiologic proteinuria Proteinuria>300 mg/day
Active urinary sediment
Difference between pregnancy and lupus flare

24. Differentiating lupus flare from preeclampsia
Features suggestive of
preeclampsia
Features suggestive of lupus flare Features that may be
common to both
Severe headache Onset <20 weeks (more suggestive off
SLE)
Hypertension
Visual symptoms (including
flashing lights)
Active urinary sediment/cellular casts Worsening proteinuria
Epigastric or right upper
quadrant tenderness
Hematuria Edema
Clonus (>2 beats) Low/falling complement levels Renal impairment
Abnormal LFTs High/increasing anti-dsDNA antibodies Thrombocytopenia
Rising uric acid level Evidence of flare involving other
organs
Signs of hemolysis
Falling angiogenic factors (eg,
PIGF, VEGF)

25. Lupus flares should be treated with the appropriate steroid (usually
prednisolone) dose.
Azathioprine and cyclosporine can be used in pregnancy with
active SLE.
Cytotoxic drugs such as cyclophosphamide and methotrexate
should be avoided during first trimester except in rare
circumstances such as pulmonary alveolar haemorrhage or class IV
nephritis due to SLE as these are teratogenic.
More safety data are needed for the use of mycophenolate mofetil.
Treatment for Lupus Flares

27. Lupus Pregnancy, Nephritis and Eclampsia
Lupus nephritis is an important risk factor for both maternal and
fetal complications.
Positive associations are identified between preterm birth,
hypertension, preeclampsia and lupus nephritis.
If woman has proteinuria, hypertension, renal function
decreased at the beginning of pregnancy and a history of lupus
nephritis she is likely to have a flare of lupus nephritis.
Decrease in complement, even within the normal range, should
alert the clinician to a possible flare of SLE more when associated
with an increase in anti-dsDNA

28. 1. After 20 weeks usually when on 20mg/day prednisone
2. First Pregnancy.
3. Pre-eclampsia in prior pregnancy
4. Twins or multifetal gestation
1. History of lupus nephritis &/or hypertension
2. History of anti-phospholipid antibody syndrome
Risk factors for Pre-eclampsia in SLE:

29. Lupus nephritis and preeclampsia must be
differentiated because treatment is different.
Preeclampsia requires early delivery .
Lupus nephritis requires immunosuppressive
treatment.

30. Clinical measures Preeclampsia Lupus nephritis
Time >20 weeks >20 weeks
Hypertension Present Often Present
Urine active sediment Rare Common
Onset of proteinuria Abrupt, after 20 weeks Abrupt or gradual, anytime
Uric acid >4.9mg/dl <4.9mg/dl
C3 and C4 Usually normal Usually low or decreasing
Complement products Normal Usually higher
Anti-DNA Negative or stable Positive or increasing
Lupus activity No Yes
Urine calcium <195 mg/day >195 mg/day
Thrombocytopenia Yes (HELLP) 20% of SLE
Liver function test May be elevated (HELLP) Usually normal
Kidney biopsy Glomeruloendotheliosis SLE nephritis
sFlt-1/PIGF ratio Higher Normal

31. Anti-phospholipid Antibody Syndrome
•If antiphospholipid syndrome is present there is increased risk of
thrombosis and fetal loss.
•It is to be treated with low dose aspirin and low molecular weight heparin.
•Obstetric APS has a higher thrombotic risk.
•Smoking and alcohol consumption should be stopped.
•Low dose of steroids has been evaluated and found useful in refractory APS.
•IVIG improves pregnancy complications.
•Pravastatin suggests a beneficial role in those women with preeclampsia
•HCQ immunomodulator can have beneficial effects not only in the
treatment of thrombotic APS but also in the prevention of pregnancy
complications.

32. •Prematurity, fetal loss, neonatal lupus syndrome.
•Intrauterine growth retardation.
•Reduced liquor.
•Fetal distress.
•Pre-mature rupture of membranes.
•Risk factors for premature delivery are anti-phospholipid
antibodies, active SLE at conception, SLE flare, renal disease,
high blood pressure.
Antenatal challenge : fetal complications

33. Antenatal / Post Natal Challenge : fetal complications
Neonatal lupus syndrome is an unusual condition due to the
passage of maternal antibodies (specially Anti-Ro/SSA and Anti-
La/SS-B) to unborn fetus.
The main features are
•Congenital heart block (CHB)
•Transient cutaneous lupus lesions
•Cytopenias, hepatic and other systemic
manifestations

34. Antenatal / Postnatal challenge : Neonatal Lupus
Complete heart block is a more serious form of NLS,
affecting 2% of newborns of anti-Ro-positive
women and requires placing of a permanent
pacemaker.
Recurrence rate is 16-20% after a first NLS event.
NLS with CHB – leads to 20% mortality.

35. •Fetal echo should be done to diagnose heart block
•Fetal heart rate should be auscultated and recorded every
1-2 weeks and referred to fetal cardiology service if fetal
heart rate below 110bpm is detected.
•If incomplete heart block, myocarditis, ascites, or hydrops
is identified, then therapy with steroids, HCQ 400mg/day
should be considered.
•Hydrops in a fetus with CHB is an extremely poor
prognostic sign, with a mortality rate of 83%-100%.

36. Antenatal challenge : Antenatal Care
•Women should be seen in the first trimester by both
obstetrician and rheumatologist.
•Same as normal non-SLE antenatal care; but more
concentration should be given to identify early disease
flares;
•Search for SLE related pregnancy complications and
regular monitoring of fetal conditions.
•Patients suffering from active disease, should be kept
under special observation.

37. Antenatal challenge : Management of pregnancy
Review every 4 weeks from 16-28 weeks, every 2 weeks from
28-34 weeks and every week from 34 weeks.
Each visit should be documented- the presence or absence of
flare or preeclampsia symptoms, blood pressure, dipstick
urinalysis, symphysial-fundal height, and fetal heart rate.
Low dose aspirin and low molecular weight heparin should
be started.

38. History and clinical examinations should be focused on identification of
disease flares and pregnancy related complications.
Follow up at subsequent visit:
Laboratory assessment includes:
• CBC, ESR
• Routine urine analysis
• Serum creatinine, Urinary protein:creatinine ratio
• FBG/Modified OGTT 24 to 28 weeks
• Anti-dsDNA and C3 {At the end of each trimester}
• Biophysical profile (BPP) scoring from 28 weeks
• Women detected to have either anti-Ro or anti-La antibodies should be offered
serial foetal echocardiograms between 16-24 weeks of gestation.

39. • Measurement of the crown-rump length in the 1st trimester.
• Level II scan at 16-22 weeks of gestation.
• Growth scan every month, at every 15 days if there is pre-eclampsia.
• Fetal echo at 22 weeks gestation. for women with anti-SSA/anti-SSB
antibodies to exclude congenital heart block.
• Bilateral uterine notch between 23-25 weeks is risk factor for
development of early onset PET and gestational hypertension.
• NST, Biophysical profile, Doppler velocimetry of the fetal umbilical artery,
beginning at 26-28 weeks and continuing weekly until birth.
Evaluation of fetal growth and vitality

40. Avoiding sun exposure is very important to prevent flares.
Mother should take low salt diet containing adequate
amount of vitamins and minerals.
General Advice

41. General Advise
Treatment when there is no sign of flares or complications:
Drugs those can be used safely during pregnancy
1. Folic acid (this is recommended)
2. Hydroxychloroquine
3. Low dose Aspirin(75mg/d ) if antiphospholipid antibodies are
present, in high risk patient or presence of nephritis for
prevention of pre-eclampsia,
There are many controversies of using steroid in this group of patients
to prevent flares as flare prophylaxis. Use of steroid increases the risk of
fetal cleft palate, IUGR, PROM, DM, pre-eclamsia.

42. Women with previous hypertension, preeclampsia, and/or renal
disease should have more frequent blood pressure and
urinalysis checks.
Proteinuria on dipstick analysis would necessitate confirmation
and quantification by either PCR or 24 hrs collection of urine.
Women on steroids, or those with previous gestational diabetes,
should have screening for gestational diabetes, ideally at 16
weeks, and if negative, again at 26-28 weeks.

43. Intrapartum challenge : Managing labour
•Multi disciplinary team is required in a tertiary care center.
•Obstetrician, rheumatologist, nephrologist, fetal
cardiologist, fetal medicine specialist, neonatologist & mid
wife must be in the team.

44. Intrapartum challenge : Managing labour
•Women with SLE have an increased risk of preterm delivery.
•If the fetus is of 24 – 34 weeks of gestation two maternal
intramusuclar steroid injections should be given to aid fetal
lung maturation.
•If the gestational age <32 weeks magnesium sulfate may
have fetal neuroprotective benefits.
•Normal vaginal delivery should be tried.
•Cesarean section is an additional risk factor for VTE, carries
risks of bleeding and infection, and has implications for
future pregnancies.

45. If a woman is taking long-term oral steroids, she will require
intravenous hydrocortisone to cover the physiological stress
of labour and delivery (50-100mg IV hydrocortisone 8
hourly).
Women receiving standard prophylactic doses of LMWH
should discontinue it at the onset of spontaneous labour, or
24 hours before induced labor or elective cesarean section.

46. •During the postpartum period, the mother should be
watched for infection and disease exacerbation.
Treatment of any underlying pregnancy-induced
hypertension.
• Risk assessment and prophylaxis regimen for thrombosis,
particularly in women with APS or who have a previous
history of thrombosis or nephrotic syndrome.
Post-partum challenge: flare, other risks, and follow-up

47. •If a women is taking long-term oral steroids, IV
hydrocortisone in labour and delivery, her usual dose of
prednisolone should be doubled for 2-3 days.
•She should be called for follow up after 4-6 weeks after
being discharged from hospital.
•All women who received antenatal LMWH should continue
this for 6 weeks postpartum as there is increased risk of VTE.
Post-partum challenge: flare, other risks, and follow-up

48. Majority of drugs are excreted in human milk in variable amounts.
From neonatal perspective, maternal intake of prednisolone less than or up to 30
mg/day, warfarin, cyclosporine in standard doses and weekly chloroquine for
malaria prophylaxis are considered safe.
If the dose of prednisolone is greater than 30 mg/day, feeding should be avoided
for 4 hours after ingestion of the morning dose of steroid.
By this time the blood levels are quite low and very limited amounts are secreted
into the milk.
However, breastfeeding is contraindicated if mother is on cyclophosphamide,
azathioprine, hydroxychloroquine for SLE.
Post-partum challenge: Breastfeeding

49. •Barrier methods are the safest method for contraception.
•Low dose estogen or progesterone only pills are relatively safe.
•High dose estrogen containing pill should be avoided.
•OCP should be avoided in antiphospholipid syndrome, other
thromboembolic diseases, highly active disease, migraine, Raynaud’s
phenomenon.
•Use of intrauterine devices is controversial because it causes
infections like endometritis, PID etc.
Post-partum challenge: Contraception

50. Fetal complications that can lead to delivery of handicapped
baby or fetal demise.
Continuation of pregnancy is endangering maternal life.
If mother gets pregnant during treatment of SLE with
Methotrexate, Cyclophosphamide
Medical Termination of Pregnancy is indicated
Medical termination of pregnancy

51. •Pregnancies should be planned during periods of disease quiescence for at
least six months prior to conception.
• Preconception assessment is essential in women with SLE to determine
whether pregnancy may pose an unacceptably high maternal or fetal risk, to
initiate interventions to optimize disease activity, and to adjust medications to
those with the best safety profile during pregnancy.
•Primigravidas and women with a history of lupus nephritis or active nephritis
are at highest risk of flare. Higher rates of complications such as preeclampsia,
preterm birth, fetal loss, growth restriction, and neonatal lupus syndromes are
seen in lupus pregnancy
•Collaboration between a rheumatologist and an obstetrician is important.
•Continuation of hydroxychloroquine reduces the risk of SLE flares.
Summary & Recommendations

52. •Women with SLE are at higher risk of preeclampsia and prophylactic use
of low-dose aspirin is recommended.
•Lupus nephritis flares during pregnancy can mimic preeclampsia.
•Women with risk factors or poor prognostic indicators may require more
frequent maternal-fetal monitoring.
•In patients with positive anti-Ro/SSA and/or anti-La/SSB, increased
surveillance for CHB in fetus is appropriate.
•Treatment should not be withheld due to pregnancy. Risk and benefits
of treatment during pregnancy must be weighed against the risk of SLE
activity having a deleterious effect on the mother and the fetus.
Summary & Recommendations

53. Thank
you