MANAGEMENT OF MATERNAL

AUTOIMMUNE DISEASES IN
PREGNANCY

PRESENTER :DR ET MUKEBA

SUPERVISOR: DR MCNEIL
2024/02/23rd
AUTOIMMUNITY: The presence of autoantibodies
(antibodies against autoantigens) or auto reactive (self
reactive) lymphocytes without the induction of any
pathological changes

In autoimmune diseases, the body’s immune system

starts acting abnormally by misinterpreting healthy
tissue as being foreign invaders, and gradually attacks
it
75% of autoimmune diseases occur in women, most
frequently during their Childbearing years.

Men and women are affected differently.

The causes of these differences in Symptoms, severity

of disease, incidence, remission and other factors are
not clear.
The female immune system must be actively adapted
during pregnancy in order to maintain its defensive
capacity and, at the same time, protect the fetus from
immunological rejection.

Immunological change may influence, in various ways,

women with an autoimmune disease who are
conceiving.
Systemic Lupus Erythematosus
SLE is a multisystem autoimmune disease with a
strong female predilection with production of
pathogenic auto antibodies directed against nucleic
acids.

It is a connective tissue disease

The exact patho-aetiology of SLE remains elusive.
Almost 90 percent of SLE cases develop in women.

Its prevalence in those of childbearing age

approximates 1 case in 500.

Prevalence of SLE is approximately 28-150/100.000

Identification of antinuclear antibodies (ANA) is the
best screening test.

Antibodies to double stranded DNA (dsDNA) and to

Smith (Sm) antigens are relatively specific for SLE.

The decline in levels of complement during pregnancy

has been associated with poor pregnancy outcomes
 Lupus and Pregnancy
During pregnancy, lupus improves in a third of
women, remains unchanged in a third, and worsens in
the remaining third.

In any pregnancy, the clinical condition can worsen or

f lare without warning .
Effect of SLE on pregnancy
. Maternal
Preeclampsia and its complications
Preterm birth
Lupus nephritis
Thrombosis
Maternal death
Longer hospital stay
Foetal
1. 1st trimester
Spontaneous miscarriages(16%)
2. 2nd trimester
CCHB( Prev child 17%)
3. 3th trimester
IUGR
Foetal death(17,5% if CCHB)
4. Neonate
Neonatal death
Neonatal cutaneous lupus(2%)
The predictors of APO include active maternal
disease, nephritis, proteinuria, HPT,
thrombocytopenia, and presence of (aPLs), especially
lupus anticoagulant.
Lupus Nephritis
The kidneys are affected in one-third of patients at the
time of SLE diagnosis.

50% of individuals with SLE will have kidney

involvement.
Renal damage occurs because of inflammation
associated with immune-complex deposition and
complement activation.

Laboratory features of lupus nephritis include

increased levels of anti-dsDNA antibodies, elevated
serum creatinine, and the presence of urinary red-cell
casts.
Lupus Versus PreeclampsiaEclampsia
Chronic hypertension complicates up to 30 percent of
pregnancies in women with SLE

SLE-specific predictors for preeclampsia include active

or history of lupus nephritis, presence of aPLs,
thrombocytopenia, declining complement levels, and
mutations in complement regulatory proteins
Difficult to differentiate preeclampsia in SLE from
lupus nephritis.

Both conditions can manifest with increasing

proteinuria, deteriorating renal function,
hypertension, and thrombocytopenia, and can even
coexist.
Lupus nephritis is treated with immunosuppression,
and severe preeclampsia/eclampsia requires delivery.

Last, central nervous system involvement with SLE

may culminate in convulsions similar to those of
eclampsia.
Anti-Ro/La Antibodies and Neonatal Lupus Syndromes
A form of passively acquired fetal autoimmunity from
maternal antibodies that cross the placenta.

Injury to the developing fetal cardiac conduction

pathway by these antibodies can lead to permanent
damage.
The cardiac manifestations include conduction
defects, structural abnormalities, cardiomyopathy, and
congestive cardiac failure and complete heart block
(CHB).
Affecting up to 2% of exposed pregnancies.

70% survivors require pacemaker insertion.

Management During Pregnancy

All pregnant women with SLE should be closely

monitored during pregnancy.

Multidisciplinary team approach with rheumatologist,

maternal fetal medicine subspecialist and pediatrician
from preconception to postpartum.
Obstetrical management
Baseline laboratory testing early in pregnancy plus
serial assessment of autoantibodies, complement
levels, complete blood count, and serum chemistry.

Clinical and laboratory evidence of a flare can be used

to adjust treatment.
Pharmacological Treatment

There is no cure for SLE, and complete remissions are

rare.
Arthralgia can be managed by nonsteroidal anti-
inflammatory drugs (NSAIDs).

NSAIDs should be discontinued by 32 weeks- higher

risk of premature closure of the ductus arteriosus.
Aspirin (Antiplatelet agents) is considered safe for use
during pregnancy.

Hydroxychloroquine has multiple proven benefits in

SLE and continued use throughout pregnancy is
strongly recommended.

Reduction in disease activity, lower risk of flares, and

reduced risk of heart block in at-risk pregnancies.
Heparin remains the anticoagulant of choice during
pregnancy, LMWH is easier to use and has similar
efficacy and safety to unfractionated heparin.

Warfarin is teratogenic and should be avoided during

pregnancy, especially during the first trimester.
Corticosteroids
Typically, corticosteroids are recommended when SLE
is not controlled with HCQ alone.
 Prednisone or hydrocortisone are preferred.
The dosage should be minimized to reduce the risk of
dose-dependent adverse effects.
Teratogenic medications to be avoided include
methotrexate, and cyclophosphamide .

Azathioprine has a good safety record during

pregnancy .
Its recommended daily oral dose is 2 mg/kg.
Postpartum management

The incidence of relapse or flare of SLE symptoms is

increased.

NSAIDs for mild joint pain.

Patients who require lifelong anticoagulation can be
transitioned back to warfarin after delivery.
Those that do not require lifelong anticoagulants
continued on low-molecular-weight heparin for 6
weeks after delivery.

Breastfeeding should be encouraged.

NSAIDS, HCQ, and corticosteroids are considered
compatible with breastfeeding by the American
Academy of Pediatrics.
Contraception
People taking potentially teratogenic medications
should avoid pregnancy.
Long-acting reversible contraception methods are
appropriate for many patients with SLE.
Intrauterine contraceptive devices (IUDs) are safe and
effective choices
 ANTI PHOSPHOLIPID SYNDROME
(APS) is an acquired autoimmune disorder that
manifests clinically as recurrent venous or arterial
thrombosis and/or fetal loss.

APS is classified as primary or secondary, depending

on its association with other autoimmune disorders.
APS - hypercoagulability associated to vascular
thrombosis and/or obstetric morbidity.

Caused by the presence of antiphospholipid

antibodies such as lupus anticoagulant, anti-β-2-
glycoprotein 1, and/or anticardiolipin antibodies.
5% of the general obstetrical population have
antiphospholipid antibodies.

Antibody-induce aggregation of platelets results in

thrombocytopenia

An interaction with the endothelium results in an

imbalance between thromboxane and prostaglandin E2.

Endothelial damage induces platelet aggregation

Complications
Arterial thrombosis (stroke, migraine).
Deep vein thrombosis developing may result in
pulmonary hypertension
15% will develop pre eclampsia
Thrombotic microangiopathy
IUGR and preterm labour
 Management
Precounselling to discuss the effects of APS on
pregnancy and the possible complications.

Medication adjustment and screening for pre-existing

hematological or renal involvement.

The American College of Obstetricians and

Gynecologists recommends to start low-dose aspirin at
12–28 weeks, ideally before 16 weeks of gestation to
decrease the risk of preeclampsia
Treatment
Specific
LDA therapy (100-150 mg nocte) is recommended as
prevention for IUGR as it enhances placentation in
early pregnancy by alterating prostacyclin-
thromboxane imbalance.
Anticoagulants (invidualised)

Prevents placental thrombosis can be started

preconceptionally
APS with continued poor pregnancy outcome.

Despite LDA and LMWH can be treated with a double

dose of LMWH, hydroxychloroquine and prednisone 5
mg daily in the first trimester and the use of
intravenous immunoglobuline (IVIG).
The mode and timing of delivery should
individualised, and will be influenced by the
development of pre-eclampsia and IUGR.

LMWH can be stopped the day before induction or

caesarean section, It should be restarted 12 hours after
delivery depending on the bleeding risk and continued
for six weeks.
Aspirin should be discontinued at 36 weeks’ gestation.

Postpartum oestrogen-containing contraception is

contraindicated due to the risk of thrombosis.

Long-acting reversible contraceptives such as The

copper IUCD are preferable
Rheumatoid arthritis (RA)

Rheumatoid arthritis (RA) is a common autoimmune

disease affecting approximately 1% of the world’s
population.

RA disease is characterized by a symmetric,

polyarthritis of the small joints of the hands and feet,
but almost any joint can become involved.
Immunological dysfunction, and infiltrating T cells
secrete cytokines to cause inflammation,polyarthritis,
and systemic symptoms.

The cardinal feature is inflammatory synovitis that

usually involves the peripheral joints.

 The worldwide prevalence is 0.5 to 1 percent, women

are affected three times more often than men, and
peak onset is from 25 to 55 years .
DIAGNOSIS
Effect of pregnancy on RA
Improvement of symptoms in 60% of women.
20% will go into remission.

Symptoms may be exacerbated by the withdrawal of

disease-modifying anti-rheumatic drugs(DMARDs).

Postpartum 47% will have an exacerbation as T-cell

immunity is re-established.
Effect of RA on pregnancy

Hypertension and pre-eclampsia .

Preterm labour, preterm rupture of membranes,

antepartum haemorrhage, IUGR and SGA babies.

Delivery may be difficult if the mother’s hip joints or

lumbar spine are affected, and the femur.
 Management

Medication should be adjusted preconceptionnlly and

in pregnancy to control and avoid harmful side effects.

Physiotherapy to maintain joint mobility

Specific aspects of the management : Should be
used for a limited time.
Paracetamol for analgesia
Prednisone use at limited time due to risk of
gestational diabetes and preterm labour.
Sulfasalazine at 2000mg dly with folic acid.
Hydrochloroquine, Azathioprine and Cyclosporine
can be used.
Intrapartum management
Aim for vaginal delivery
Hydrocortisone 100 mg 1M 6-hourly if taking
taking>7.5 mg prednisolone for >2 weeks in pregnancy
Postpartum management
Inform patients not to breastfeed and to use
contraception when taking methotrexateor Ciclosporin

Hydroxychloroquine and NSAIDs can potentially

displace bilirubin, so discontinue if baby jaundiced
 Immune Thrombocytopenic Purpura
The primary form—termed idiopathic (ITP)—is
usually caused by a cluster of IgG antibodies directed
against platelet glycoproteins.

Platelets are destroyed prematurely in the

reticuloendothelial system, especially the spleen.
Incidence of ITP in the general population, estimated
to be 3 in 100,000 adults
chronic thrombocytopenia appear in association with
SLE, lymphomas, leukemias, and several systemic
diseases.

 Approximately 2 percent of thrombocytopenic

patients have positive serological tests for lupus
 Pregnancy
Effect of pregnancy on ITP
None
Effect of ITP on the mother
Relates to platelet count.
Effect of ITP on the fetus/neonate
Antiplatelet IgG may cross the placenta leading to
thrombocytopenia in 10-30% + Risk of neonatal (ICH)
is 2%.
Management

Prepregnancy
Obstetricians and haematologists
Advise women with refractory ITP and severe
thrombocytopenia to avoid pregnancy
Optimize therapy and consider splenectomy
Counsel about maternal and fetal risks
Antenatal
Monitor platelet count every '2-4 weeks
Aim for safe platelet count for delivery (>80x10)
Treatment depends on platelet count and symptoms

Intrapartum
Inform anaesthetists and paediatricians of delivery
Aim for vaginal birth
 Platelet count -<80x10%/l, avoid regional anaesthesia
Platelet count <50x10%/ platelets should be available (use
only if active bleeding)
Postpartum

Repair perineal trauma.

Any wouind sites should be observed closely
Thrombosis prophylaxis with LMWH is safe if platelet
count is >50x109/
Obtain cord blood for neonatal platelet count.
In neonates with severe thrombocytopenia or
bleeding: Perform ultrasonography of brain
Myasthenia Gravis
Autoimmune mediated neuromuscular disorder

 The etiology is unknown, but genetic factors likely

play a role.

 80 to 90 percent demonstrate antibodies to the

acetylcholine receptors.
 Autoimmune production of IgG antibodies directed
toward receptors on the postsynaptic membrane at
neuromuscular junctions (NMJs).

MG occurs in about 0,3-2,8 out of 100 000 people and

is more common in women than men.
Women in remission who become pregnant while
taking corticosteroids or azathioprine should continue
these.

Acute onset or exacerbation of myasthenia gravis

Plasmapheresis and high dose IVIG are options for
emergencies .
Myasthenia Gravis and Pregnancy
Effect of pregnancy on myasthenia gravis
40% deteriorate, 30% improve, 30% worsen postpartum
Exacerbation less likely if prior thymectomy

Effect of MA on pregnancy and labour

Increased risk of preterm birth and low birth weight
Second stage--may be affected by weak maternal
expulsive
Transplacental anti-AchR passage may cause Neonatal
MG (affects 10-20% neonates)
 Management
Prepregnancy
Multidisciplinary consultation (obstetricians,
paediatrician, neurologists, and anaesthetists)

Advise postponing pregnancy until remission

Consider thymectomy in symptomatic patients

Discuss the risk of exacerbation in pregnancy and

postpartum.
Antenatal
Identify and treat infections promptly
Treatment with anti-acetylcholinesterase
(pyridostigmine/neostigmine).
In myasthenic crisis, assisted ventilation is required
Labour itself is not affected
Bearing down may be affected.
 Assisted delivery is more likely.

Magnesium sulphate should not be used.

Barbiturates or phenytoin can be used for eclampsia.
Prednisone is the immunosuppressant of choice.
Azathioprine and cyclosporine can also be used

In a crisis, plasma exchange or delivery of the baby can

improve the condition.
LEVEL OF CARE

As the autoimmune diseases constitute a complex

group of illnesses with regard to manifestion, course
and complications.

They should ideally be managed at a

tertiary/academic centre.
Conclusion
With the proper implementation of Preconception
counselling, strategy, Choice of the correct timing of
Conception, close monitoring of autoimmune
diseases.

Flares with tight control, and the Appreciation of the

value of Multidisciplinary management to Best
practice most young women can carry on successful
Pregnancies with favourable Outcome.
REFERENCES
Williams OBSTETRICS ,2 4 th E D I T I O N,F. Gary
Cunningham,Kenneth J.Leveno,Steven L. Bloom,2019

Green-top Guideline,No. 51,RCOG,2018.

Bramham K, Thomas M, Nelson-Piercy C, et al. First-trimester

low-dose prednisolone in refractory antiphospholipid antibody-
related pregnancy loss. Blood 2011;117(25):6948–51.

Empson M, Lassere M, Craig JC, et al. Recurrent pregnancy loss

with antiphospholipid antibody: a systematic review of
therapeutic trials. Obstet Gynecol 2002;
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