AUTOIMMUNE DISEASES IN PREGNANCY

Dr Max Mongelli
Department of Obstetrics & Gynaecology
University of Sydney
Australia
Autoimmune disorders:

 More common among pregnant women

 Abnormal antibodies can cross the placenta and
affect the fetus
 Pregnancy affects autoimmune diseases in
different ways
Most common conditions:
 Thyroid Disease
 Crohn’s Disease
 SLE
 Myasthenia Gravis
 Immune Thrombocytopenic Purpura
 Rheumatoid Arthritis
 Pemphigoid Gestationis
Thyroid Disease in Pregnancy

 Graves’ Disease
 Hashimotos’ Disease
Graves’ Disease
 Hyperthyroidism
 Goitre
 Ophthalmopathy
 Pretibial myxedema
 Antibodies to TSH receptor
Hashimotos’ Thyroiditis
 “Chronic autoimmune thyroiditis”
 Most common cause of hypothyroidism
 Gradual thyroid failure or goitre
 Autoimmune destruction of thyroid gland
 Sex ratio 7:1
 Antibodies against TG, TPO, TSH receptor
Diagnosis of Hyperthyroidism in
Pregnancy

 TSH < 0.01

 Raised free T4
 +/- raised free T3
 Difficult to ascertain cause in pregnancy
Causes of Hyperthyroidism in Pregnancy

 Graves’ Disease
 Gestational Transient Thyrotoxicosis - HCG
mediated
 Molar pregnancy
 Familial gestational thyrotoxicosis
Hyperthyroidism in Pregnancy
Increased risk of -

 Miscarriage
 Premature labour
 Low birth weight
 Stillbirth
 Pre-eclampsia
 Heart failure
Hypothyroidism in Pregnancy

 Usually subclinical rather than overt

 PET and PIH
 Placental abruption
 Non-reassuring CTG
 Preterm delivery
 Increased risk of C/S
 PPH
Thyroid Peroxidase (TPO) Antibodies

 Increased risk of miscarriage

 Increased risk of preterm delivery
 20% develop hypothyroidism if untreated
 Risks may be reduced by T4 therapy
T4 therapy in pregnancy:

 Hypothyroid women need more T4

replacement
 As much as 50% dose increase
 Aim at normalising the TSH levels
 Important for normal fetal cognitive
development
Postpartum Thyroiditis:
 Occurs in 5-10% of all pregnancies
 May occur after delivery or pregnancy loss
 May decrease milk volume
 Transient hyperthyroidism followed by
transient hypothyroidism
 May recur in subsequent pregnancies
 Risk may be reduced by selenium
supplements
Crohn’s Disease
Crohn’s Disease: effect of pregnancy.

 Pregnancy has no effect on disease activity

 Perianal disease not worsened by vaginal
delivery
 Fistulas may occur during pregnancy
 Elective c/s controversial
Crohn’s Disease: effect on pregnancy.

 Increased risk of preterm delivery and IUGR

 Comparable to effect of moderate smoking
 Higher risk if disease active at conception
 Careful monitoring during pregnancy
Systemic Lupus Erythematosus
SLE features associated with high maternal
and fetal risks – pregnancy relatively
contraindicated:

 Severe pulmonary hypertension

 Restrictive lung disease
 Heart failure
 History of severe HELLP or PET
 Stroke within previous 6/12
 Lupus flare within previous 6/12
SLE complications in pregnancy:

 Disease exacerbation
 Miscarriage, stillbirth
 IUGR, preterm labour
 Neonatal lupus
 Drugs and breast-feeding
Neonatal Lupus:
 Occurs in up to 2% of mothers with SLE
 Targets skin and cardiac tissue,rarely other tissues
 Congenital partial or complete heart block
 Heart block detected in utero
 Complete heart block: PNM of 44%
 Rash: erythematous annular lesions
 Rash clears within 6/12
 Maternal dexamethasone may prevent progression
of heart block
 Neonatal pacemaker if HR<55
Antiphospholipid antibodies

 Anti-cardiolipin
 Lupus anticoagulant
 Increased risk of miscarriage
 Risk may be reduced with aspirin +
heparin
Investigations for SLE in pregnancy:

 Physical examination and BP

 FBC, renal function
 Anti-Ro/SSA abs and anti-La/SSB abs
 LA and aCL assays
 Anti-dsDNA abs
 Complement
Myasthenia Gravis
Myasthenia Gravis:

 Typically presents with fluctuating skeletal

muscular weakness
 May be ocular or generalised
 May have antibodies to the AChR
 10-15% have a thymoma
 Respiratory muscle involvement may lead
to respiratory failure
Myasthenia Gravis in Pregnancy:

 Pregnancy has a variable effect on the

course of MG
 Post-partum exacerbations in 30%
 Infections can trigger exacerbations
 Steroids can cause transient worsening
 MgSO4 is contraindicated
Myasthenia Gravis – Effect on the Fetus

 Transplacental passage of IgG anti-AChR

 Neuromuscular junction disorders
Transient neonatal MG in 10-20%
 Decreased FM’s and breathing
 Polyhydramnios
 Arthrogryposis multiplex congenita
Myasthenia Gravis – Labour & Delivery

 First stage of labour not affected

 Second stage: expulsive efforts may
weaken
 Assisted vaginal delivery may be indicated
 Pre-labour anaesthetic assessment
indicated
Immune Thrombocytopenic Purpura
ITP
ITP – Diagnostic Criteria:

 Isolated thrombocytopenia
 No drugs or other conditions that may
affect platelet count
 Exclude HIV, Hep C, SLE
ITP – Pathology:

 Increased platelet destruction

 Inhibition of platelet production at
megakaryocyte level
 Mediated by IgG Abs against platelet
membrane glycoproteins
 Usually a chronic condition
ITP – Clinical Features:

 Petechiae, purpura, easy bruising

 Epistaxis, menorrhagia, bleeding from
gums
 GIT bleeding, hematuria: rare
 Intracranial hemorrhage – very rare
ITP and Pregnancy
 May affect fetus in up to 15% of cases
 Neonatal count may drop sharply several days after
birth
 Difficult to differentiate from gestational
thrombocytopenia
 Epidurals safe if count > 50000
 Prednisone +/- IVIG if count < 50000
 Manage delivery according to standard obstetric
practice
 Avoid NSAIDS post-partum
Gestational Thrombocytopenia

 Incidence about 5%
 Occurs late in pregnancy
 Mild (>70 000)
 No fetal neonatal thrombocytopenia
 Postpartum resolution
Rheumatoid Arthritis
Rheumatoid Arthritis in Pregnancy

 Affects 1-2% of the general population

 More common in women
 RA in pregnancy is a common challenge
 Sex hormones have effects on disease activity
 70-80% of cases improve during pregnancy
 Post-partum flare common
Effect of Pregnancy on RA

 Minimal effects on fetal morbidity and

mortality
 Steroids may increase risk of IUGR and
PPROM
 Active disease correlates with lower birth
weights
Treatment of RA in Pregnancy

 Avoid NSAIDS and high dose aspirin

 Low-dose aspirin safe
 Use lowest doses of prednisone
 Sulfasalazine, hydroxychloroquine in
refractory cases
RA Medications and Breast-feeding –
Avoid:
 Aspirin
 Azathioprine
 Cyclosporin
 Cyclophosphamide
 Methotrexate
 Chlorambucil
 High dose prednisone
Pemphigoid Gestationis
Pemphigoid Gestationis

 Blistering disease associated with increased fetal risk

 Incidence 1:1700 to 1: 50000 pregnancies
 Associated with HLA-DR3 and HLA-DR4
 Caused by IgG1 against basement membrane of skin
 Bullous pemphigoid antigen 2
 Eosinophilic infiltration
Pemphigoid Gestationis – Fetal Risks
 Preterm delivery in 1/3 of cases
 SGA in 1/3 of cases
 Worse prognosis if onset in 1st or 2nd
trimesters
 Neonatal pemphigoid in up to 10%
 Mild disease that resolves in weeks
Autoimmune Diseases in Pregnancy: Conclusions

Isolated antibodies without clinical features or history may not

be an indication to start treatment

Sometimes identified following adverse outcomes – eg stillbirth

and lupus anticoagulant

Some conditions are mixed or not classified, and difficult to treat

as there may not be clear guidelines