AUTOIMMUNE DISEASES IN PREGNANCY

Dr Max MongelliDepartment of Obstetrics & Gynaecology

Nepean HospitalUniversity of Sydney

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 disordersTransient 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 PurpuraITP

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

Concluding Remarks

For rare autoimmune diseases limited data to guide decision-making Occasionally antibodies found incidentally without any clinical features Indication for close monitoring rather than treatment Notify pediatrician if neonatal morbidity is a possibility