1. Pregnancy in patients with lupus requires careful management by an obstetrician and rheumatologist due to the high risk nature. 2. Patients with active lupus or kidney disease are more likely to have complications and it is recommended to avoid pregnancy until the disease is well controlled. 3. With proper management of medications and disease activity, many lupus patients can have successful pregnancies and deliveries. Close monitoring is important throughout the pregnancy and postpartum period.

1. OPTIMIZING LUPUS
MANAGEMENT IN PREGNANCY
Dr. AbdelAzeim Elhefny
Prof of Internal Medicine, Rheumatology & Immunology
Ain Shams University

2.  Lupus is a chronic, multi-system autoimmune disease
that occurs mainly in women of childbearing age.
 SLE pregnancies are considered high risk & require carful
collaboration of the obstetrician & rheumatologist .
•The obstetrician has to be experienced in managing high-
risk pregnancies.
• Delivery should be at a hospital containing a Neonatal ICU

4.  Although patients with lupus are as fertile as women in
the general population, their pregnancies may be
associated with complications.
 Many lupus patients can have a successful pregnancy; if
managed properly.
In the next few minutes I will try to answer these 2Qs:-
1. Who will have a difficult pregnancy?
2. How can you avoid/ decrease the severity of the complications?

5.  It is strongly recommended that lupus pt. should avoid
pregnancy until at least six months after the lupus disease
activity, especially kidney disease, has been completely under
control.
Pregnancy is inadvisable in the presence of:-
uncontrolled hypertension, Proteinuria > 1 g/d
progressive renal impairment,
severe neurologic, cardiopulmonary involvement,
severe thrombocytopenia, and
during the use of teratogenic medications.

6.  The frequency of lupus exacerbation by preg. ranges
from 6% in women in remission for at least 6 months
before preg., to >60% in pts. with active disease at
the time of conception.
 Disease flares may also occur in association with
hormone manipulation for IVF in lupus pt..
 Patients who discontinue hydroxychloroquine prior
to, or during pregnancy are more likely to have
exacerbations of their disease.
(Clowse et al., 2007).

7.  With lupus exacerbation, there are increased rates
of:-
 HTN, PE, HELLP, preterm delivery, unplanned CS,
 postpartum hemorrhage,
 hypercoagulability with arterial & venous thrombosis,
or placental infarctions (esp. with aPL -ab).
 IUGR and neonatal deaths [20%].

8. Pre-
Eclampsia
HELLP
Syndrome
Active Lupus
Nephritis
Timing in pregnancy After 20 wk
of gestation
After 20 wk of
gestation
All gestational ages
Complement (C3, C4) N N Typically decreased
Thrombocytopenia In sever dis/+ present Present
Neutropenia Absent Absent Present
Active urine sediment -- Absent Present
Proteinuria +++ 86% +++
Other organ involvement Absent Absent Present
Anti-ds DNA Absent Absent Present
ANA antibodies Absent Absent Present
Hemolysis with a micro-
angiopathic blood smear
Absent Present
(RBC fragments)
Absent
Abnormal liver function In sever dis/+ Present
(AST, LDH, Bil)
Absent
Serum uric acid >5.5 mg/dl Absent < 5.5 mg/dl
Hypertension >140/90 mmHg present > 82% Variable
Elevation in creatinine In sever complicated cases Commonly present
Differentiation of Pre-eclampsia, HELLP syndrome &
Active LN during pregnancy.

9. If the pt is receiving MMF (cellcept):
Discontinue and switch to azathioprine at
least 3 months prior to conception

10. Hydroxychloroquine
may protect
against
Onset
of LN
Lupus
flare
Relapses
of
LN
ESRD
Vascular
thrombosis

11. Rarely indicated nowadays because of advances in patients
monitoring and availability of effective treatment, but can be
one of optional lines of therapy when there is:-
 sever lupus flare with major organ involvement not responding to
aggressive management,
 sever uncontrolled hypertension and
 vasculitis affecting major organs
(Samadirad et al., 2012).

12.  If the mother and her baby are healthy at the time of labor,
many lupus patients are able to have a successful vaginal
delivery.
 However, if the mother/baby is under stress, or in the event of
preterm labor, a caesarian section might be the safest and the
fastest method of delivery.
 Women taking steroids usually require an increased dose (also
known as a stress dose) during labor. ???

14.  Passively transmitted autoantibodies occur
in some babies born to lupus mothers with
anti-Ro/ anti-La antibodies
 The risk for positive auto antibodies in
the child is ~ 10%; while risk of NLE
is only ~ 1% of them.
 The most serious complication is complete
heart block, in approximately 2 % of NLE.
 Isolated skin rash, thrombocytopenia,
abnormal LFT occurs in about 2%.

15.  The recurrence rate of NLE is about 10 folds in subsequent pregnancies.
 Maternal use of hydroxychloroquine (HCQ) reduced the rates of CHB
and isolated cardiomyopathy .
 Fetal echocardiography is recommended in cases of suspected fetal
dysrhythmia or myocarditis, especially in mothers with positive anti-
Ro/SSA and/or anti-La/SSB antibodies.
 Treatment of CHB (intrauterine diagnosis)
 Dexamethasone (4 mg/day) or betamethasone is given to the mother
(crosses the placenta)
 In refractory cases; Plasmapheresis, & pacemaker implantation if needed

16.  Some women will experience
exacerbations of SLE in the PP
 Pts at greater risk of disease flares
in 3m. PP:-
 Those who have active disease at
conception
 those with significant end-organ
damage,
 they have a poorer prognosis .
 Thus, periodic assessment of
disease activity is indicated
postpartum.
The following laboratory tests are
recommended :
• Urinalysis, urine P/C ratio
• Renal function .
• CBC + DD WBC
• anti-dsDNA level
• Complement (CH50, or C3 and C4)

17.  Particular care should be taken prior to prescribing any estrogen OCs to
lupus patients who also suffer from APS, to avoid hypercoagulability
 Use of combination OCs is contraindicated in pts with active LN.
 Women with SLE/APS have other methods of birth control,
including:-
 progestin-only pills,
an intrauterine device, condoms, a diaphragm,
an injection (eg, Depo Provera), or
a surgical procedure.
http://www.health.am/gyneco/more/contraception-in-the-lupus-patient/P3/#ixzz2U8nqu6An

18.  Patients with SLE and aPL Abs. appear to be at increased
risk for spontaneous miscarriage compared with those
without (39%Vs. 18 %) .
 Fetal loss typically occurs after 10 weeks gestation .
 Thus, all pregnant lupus patients should be screened for
the presence of LAC and aCL Abs. for early detection &
management; to avoid further complications.

19. Recommendations
9. Prevention & treatment of APS-related morbidity
should be a therapeutic goal, therapy is the same for
primary APS.
Von Vollenhoven et al. AnnRheum Dis 2014; 73:958

20. 12
12

22. Treatment of APS
(Handa et al., 2006)
&/or VTE
Vascular
thrombosis
Hydroxychloroquine, has antithrombotic &
lipid lowering effects.
Nor Vascular
thrombosis
Therapeutic
anticoagulant dose
prophylactic
dose

24. Andreoli L, et al. Ann Rheum Dis 2017;76:476–485

25. 1. Methotrexate
2. leflunomide
3. Mycophenolate
4. Cyclophosphamide 1st trimester
5. ACE-I/ARBs –2/3rd trimesters
Skorpen, et al. The EULAR points to consider for use of anti-rhuematicdrugs before pregnancy, and during
pregnancy and lactation. Ann Rheum Dis 2016.

26.  Drugs for the prevention and management of SLE flares
during pregnancy:-
 HCQ , SSZ, oral GC, AZA, colchicine, ciclosporin A &
tacrolimus.
 Moderate-to-severe flares can be managed with additional
strategies:-
 IV pulse steroid, IVIG or plasmapheresis.
 Even 2nd - 3rd trimester CYC in severe, refractory cases??
 During lactation NSAIDs, celecoxib & warfarin are safe.

27.  The majority of pregnancies in women with lupus result in a healthy mother
and baby
 To optimize the pregnancy outcome:
 Acknowledge the deep desire in your patients to have a healthy baby and
use that to help them make good choices
 Identify high risk pregnancy and wait for disease control
 Avoid the bad meds (MTX, MMF, CYC) by discussing contraception
 Continue HCQ
 Use AZA to prevent lupus flare; Tacro, Cyclosporin, or IVIg can also be used.
 Use prednisone in the least effective dose for the shortest possible period.

28.  http://www.health.am/gyneco/more/contraception-in-the-
lupus-patient/P3/#ixzz2U8nqu6An

32.  Lupus. 2014 Oct;23(12):1242-5. doi: 10.1177/0961203314528062.
 Contraception in patients with systemic lupus erythematosus and antiphospholipid syndrome.
 Sammaritano LR1. Author information
 Abstract
 Contraceptive choice in patients with systemic lupus erythematosus (SLE) and antiphospholipid
syndrome (APS) is challenging but important. Long-acting forms of contraception such as the
progesterone intrauterine device (IUD) or subdermal implant are preferable for most patients.
Estrogen-containing hormonal contraceptives may be used in stable, inactive SLE patients but are
contraindicated in patients with positive antiphospholipid antibodies (aPL).The levonorgestrel IUD
is a good alternative for many APS patients and often decreases menstrual blood loss. It is prudent
to avoid depot medroxyprogesterone acetate (DMPA) in corticosteroid-treated or other patients at
risk for osteoporosis because of the inhibition of ovulation. Effective and safe contraception in
patients with SLE and APS permits planning for pregnancy during inactive disease and while on
pregnancy-compatible medications, preventing a poorly timed pregnancy that may jeopardize
maternal and/or fetal health.
 ©The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

33.  IV UFH — Initial dosing of IV UFH consists of an IV UFH bolus of 80 units/kg, followed by a
continuous infusion of 18 units/kg per hour [ 7].The infusion is titrated every six hours to achieve a
therapeutic activated partial thromboplastin time (aPTT).Once the target aPTT level is achieved, it
should be rechecked once or twice daily. IV UFH can be transitioned to SC UFH or SC LMWH if long-
term or outpatient anticoagulant therapy is planned [ 1 ].
 SC UFH — A reasonable initial dose of SC UFH is 17,500 units every 12 hours.The dose is then
titrated to achieve a therapeutic aPTT, defined as the aPTT ratio) of 1.5 to 2.5.This corresponds to a
heparin level of 0.3 to 0.7 units/mL when measured by an anti-Xa assay [ 1 ].
 The first aPTT is generally measured six hours after the second dose. Most adjustments should be
an increase or decrease of 10 to 30 percent.The aPTT may be measured six hours after the second
injection that follows each dose adjustment. Once a stable dose is achieved, theaPTT may be
measured after three to four days of treatment and then every few weeks. During the last10 weeks
of the pregnancy, more frequent monitoring is warranted.
 Many clinicians prefer to begin with IV UFH and then transition to SC UFH in order to achieve a
rapid therapeutic effect for treatment.The transition is traditionally done after the patient has
received IV UFH for 5 to 10 days [ 11 ].

34.  In this situation, the first aPTT can be checked six hours after the first SC UFH dose
and then six hours after every dose adjustment until a stable dose that produces
the desired therapeutic level is achieved. Once a stable dose of SC UFH is achieved,
the aPTT may be initially checked once or twice daily for three to four days and
then every few weeks. During the last 10 weeks of the pregnancy, more frequent
monitoring is warranted.
 Labor and delivery —Treatment with SC LMWH should be discontinued at least
24 hours prior to delivery if the delivery time is predictable (eg, induction of labor,
planned cesarean section).This allows the effect of heparin to resolve, which is
particularly important for patients who desire neuraxial anesthesia because
anticoagulation during insertion (or removal) of a neuraxial anesthesia catheter
increases the risk for spinal hematoma.

35.  The clinician may be unwilling to tolerate even a short interval without
anticoagulant therapy in rare circumstances, such as a patient with reduced
cardiopulmonary reserve and a recent PE. A temporary inferior vena cava (IVC)
filter can be inserted in this situation, or delivery can proceed despite full
anticoagulation
 In cases in which preterm delivery is anticipated (eg, triplets, preterm rupture of
membranes, significant cervical dilation, preeclampsia, growth restriction), it is
common to discontinue SC LMWH or SC UFH at 36 weeks of gestation. IV UFH is
then used instead.
 After delivery —A heparin regimen (SC LMWH, IV UFH, or SC UFH) should be
restarted 12 hours after a cesarean delivery or 6 hours after a vaginal birth,
assuming that significant bleeding has not occurred.Options for long-term
anticoagulant therapy include SC LMWH, SC UFH, or an oral vitamin K antagonist

36.  In women who received heparin or LMWH antepartum
because of prior late fetal loss or recurrent embryonic losses,
we continue anticoagulation postpartum.
 Unfractionated heparin (5000 units every 12 hours) is
administered beginning 12 hours post-cesarean delivery and
four to six hours post-vaginal birth if there is no significant
bleeding, and either continued or replaced
with warfarin (stopping the heparin when the INR is
therapeutic 2-3 ) for six weeks [ 37,38 ].We also continue low
dose ASA postpartum for six weeks.

37.  Warfarin — Warfarin can be used for postpartum thromboprophylaxis, but NOT
antepartum thromboprophylaxis. It should be initiated at the same time or
after heparin is started because warfarin alone is associated with an increased
incidence ofVTE.The patient should receive both warfarin and heparin for at least
five days, and the heparin should not be stopped until the international normalized
ration (INR) is within the therapeutic range, usually 2 to 3 for 2 days.Warfarin is
safe during lactation because it does not accumulate in breast milk to a substantial
degree [
 evere renal failure (creatinine clearance <30 mL/min). In this situation, SC UFH is
preferred over SC LMWH. Elimination of UFH is both hepatic and renal, whereas
elimination of LMWH is nearly entirely renal.Thus, accumulation and bleeding
complications are more likely with LMWH. Renal failure is also a risk factor for
bleeding in patients taking warfarin
 Women with laboratory criteria for aPL and a prior history of arterial or venous

38.  Fetal warfarin syndrome (FWS) or warfarin embryopathy is
a well recognised complication following warfarin exposure
in pregnancy. The critical period for the development of
FWS has not been defined, although data suggests that
the risk period covers gestational weeks 6-12. The risk of
warfarin embryopathy following exposure during this
critical period could be as high as 30%, although more
recent reports suggest a risk of 6-10%. There is evidence to
suggest that the risk of FWS may be dose-dependant with
doses of >5mg carrying a higher risk.

39.  Aspirin — In addition to its antiplatelet effects, low dose aspirin (ASA) (50 to 100
mg) enhances leukocyte-derived interleukin-3 production, which stimulates
normal trophoblast growth and hormone expression [ 2 ]. For prevention of fetal
loss in women with APS, administration of low dose ASA alone has been
associated with an increased frequency of successful pregnancy outcome
 If the patient takes a nonsteroidal anti-inflammatory drug (NSAID) for pain in the
first two trimesters, it is best to wait at least three hours after the ASA dose before
taking the NSAID.
 Low dose ASA can be stopped anytime after 36 weeks of gestation, and, ideally,
should be stopped 7 to 10 days before delivery because some studies have
reported a slight increase in mostly minor perioperative bleeding
 Use of low dose ASA has not been associated with either premature closure of the
ductus arteriosus or increase in significant postpartum hemorrhage.

40.  Intravenous immune globulin — Intravenous gamma globulin (IVIG) (0.4 g/kg per
day for five days each month during the next attempted pregnancy) is one
alternative treatment that has been proposed; however, the efficacy of this
approach has not been demonstrated [ 21,54-56 ]. Use of IVIG should probably be
confined to research studies.
 Plasmapheresis - 1) three to four treatments per week starting at the 14th week of
pregnancy and continuing until cesarean delivery at 34 weeks; 2) another
performed a total of six exchanges beginning at the 24th week followed by
cesarean delivery at week 29. Both documented a reduction in antibody titers
following apheresis . 3)Weekly plasma exchanges were performed, but the patient
delivered in the 26th week due to fetal growth restriction and oligohydramnios.
The female infant weighed 730 g and survived.4) prednisone (10 mg/day) and
plasmapheresis for three sessions per week until LA activity was suppressed and

41.  Hydroxychloroquine —The antimalarial
drug hydroxychloroquine appears to reverse platelet
activation induced by human IgG aPL and reverse
thrombogenic properties of aPL in mice [ 62,63 ], and also
appears to depress aPL levels in humans [ 64 ].
 Labor and delivery — For women who are being treated with
anticoagulation, we suggest scheduled delivery at 39 weeks to
minimize anticoagulant exposure and to decrease the risk
that an anticoagulant dose will be given proximate to active
labor.