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AUTOIMMUNE DISEASES IN PREGNANCY


                Dr Max Mongelli
     Department of Obstetrics & Gynaecology
                Nepean Hospital
             University 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 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
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

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Autoimmune Disease in Pregnancy

  • 1. AUTOIMMUNE DISEASES IN PREGNANCY Dr Max Mongelli Department of Obstetrics & Gynaecology Nepean Hospital University of Sydney
  • 2. Autoimmune disorders:  More common among pregnant women  Abnormal antibodies can cross the placenta and affect the fetus  Pregnancy affects autoimmune diseases in different ways
  • 3. Most common conditions:  Thyroid Disease  Crohn’s Disease  SLE  Myasthenia Gravis  Immune Thrombocytopenic Purpura  Rheumatoid Arthritis  Pemphigoid Gestationis
  • 4. Thyroid Disease in Pregnancy  Graves’ Disease  Hashimotos’ Disease
  • 5. Graves’ Disease  Hyperthyroidism  Goitre  Ophthalmopathy  Pretibial myxedema  Antibodies to TSH receptor
  • 6. 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
  • 7. Diagnosis of Hyperthyroidism in Pregnancy  TSH < 0.01  Raised free T4  +/- raised free T3  Difficult to ascertain cause in pregnancy
  • 8. Causes of Hyperthyroidism in Pregnancy  Graves’ Disease  Gestational Transient Thyrotoxicosis - HCG mediated  Molar pregnancy  Familial gestational thyrotoxicosis
  • 9. Hyperthyroidism in Pregnancy Increased risk of -  Miscarriage  Premature labour  Low birth weight  Stillbirth  Pre-eclampsia  Heart failure
  • 10. Hypothyroidism in Pregnancy  Usually subclinical rather than overt  PET and PIH  Placental abruption  Non-reassuring CTG  Preterm delivery  Increased risk of C/S  PPH
  • 11. 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
  • 12. 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
  • 13. 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
  • 15. 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
  • 16. 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
  • 18. 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
  • 19. SLE complications in pregnancy:  Disease exacerbation  Miscarriage, stillbirth  IUGR, preterm labour  Neonatal lupus  Drugs and breast-feeding
  • 20. 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
  • 21. Antiphospholipid antibodies  Anti-cardiolipin  Lupus anticoagulant  Increased risk of miscarriage  Risk may be reduced with aspirin + heparin
  • 22. 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
  • 24. 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
  • 25. 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
  • 26. 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
  • 27. 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
  • 29. ITP – Diagnostic Criteria:  Isolated thrombocytopenia  No drugs or other conditions that may affect platelet count  Exclude HIV, Hep C, SLE
  • 30. ITP – Pathology:  Increased platelet destruction  Inhibition of platelet production at megakaryocyte level  Mediated by IgG Abs against platelet membrane glycoproteins  Usually a chronic condition
  • 31. ITP – Clinical Features:  Petechiae, purpura, easy bruising  Epistaxis, menorrhagia, bleeding from gums  GIT bleeding, hematuria: rare  Intracranial hemorrhage – very rare
  • 32. 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
  • 33. Gestational Thrombocytopenia  Incidence about 5%  Occurs late in pregnancy  Mild (>70 000)  No fetal neonatal thrombocytopenia  Postpartum resolution
  • 35. 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
  • 36. 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
  • 37. 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
  • 38. RA Medications and Breast-feeding – Avoid:  Aspirin  Azathioprine  Cyclosporin  Cyclophosphamide  Methotrexate  Chlorambucil  High dose prednisone
  • 40. 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
  • 41. 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
  • 42. 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