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MANAGING LUPUS
IN PREGNANCY
A Practical Approach
Sidney Erwin T. Manahan, MD, FPCP, FPRA
Medical Specialist (Rheumatology)...
OBJECTIVES
• Describe adverse events
observed in SLE patients who
become pregnant
• Discuss the management of
lupus pregna...
1997 ACR Classification Criteria
• Malar rash
• Discoid rash
• Photosensitivity
• Oral ulcers
• Arthritis
• Serositis
• Re...
SYSTEMIC LUPUS ERYTHEMATOSUS
2012 SLICC Classification Criteria
CLINICAL
• Acute cutaneous
• Chronic cutaneous
• Oral ulce...
Pregnancy/ Fetal Loss in SLE
43%
17%
0%
10%
20%
30%
40%
50%
1960-65 2000-03
Clark CA, Spitzer KA, Laskin CA. Decrease in p...
Adverse Events During Pregnancy
Maternal
Mortality
Odds Ratio 20
Lupus
Flares
Frequency
27-70%
Cesarean
Section
Odds Ratio...
The Health Care Team
Expertise in
• High-risk pregnancies
• Systemic Lupus Erythematosus
• Neonatal medicine
Care should b...
Risk Factors for POOR
Pregnancy Outcomes
• Active disease within 6 months
prior to conception
• Active disease during preg...
Domains in Managing Lupus in Pregnancy
Pre-pregnancy Pregnancy
Choice of Therapy Anti-Phospholipid Syn
Yang H,Liu H, Xu D, et al. Pregnancy-related SLE: clinical features, outcome and risk factors
of disease flares – a case c...
Before Conception
1
2
3
4
Monitor organ involvement
Target disease remission; Delay pregnancy if
high disease activity OR ...
Risk factors for Flares
during Pregnancy
TYPE OF FLARE RISK FACTORS
Mucocutaneous Anti-Ro, previous involvement
Articular ...
Before Conception
1
2
3
4
Monitor organ involvement
Target disease remission; Delay pregnancy if
high disease activity OR ...
CONTRAINDICATIONS
to Pregnancy
• Severe pulmonary HPN (PAP >50mmHg)
• Advanced heart failure
• Severe restrictive lung dis...
Before Conception
1
2
3
4
Monitor organ involvement
Target disease remission; Delay pregnancy if
high disease activity OR ...
When Do We Allow?
• No evidence of active disease >6 months
• Prednisone <10mg/d
• May take Hydroxychloroquine
• No contra...
Following Conception
Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al.
Understanding and Managing Pregnancy ...
Flares During Pregnancy
New onset lupus
during pregnancy
(n 41)
Flare of lupus
during pregnancy
(n 41)
Non pregnant
SLE pa...
WHAT causes these findings?
Facial flush / Melasma
Palmar erythema
Post partum hair loss
Photosensitive rash
Malar rash
Al...
WHAT causes these findings?
ESR 18-46mm/hr <20 weeks
30-70mm/hr >20 weeks
ESR Increased
Hgb >11 during 1st 20 weeks
Hgb >1...
Hypertension, Proteinuria in Pregnancy?
Features Lupus nephritis Pre-eclampsia
Hypertension Onset any time Onset after 20 ...
SLE Disease Activity Indices(SLEDAI)
in Pregnancy (SLEPDAI)
Feature Score
Seizure 8
Psychosis 8
Organic Brain syndrome 8
V...
Follow up of the
Pregnant SLE Patient
OBSTETRICIAN
• Monthly until week 20
• Every 2 weeks until week 28
• Weekly until de...
Lab Evaluation in Pregnant SLE Patients
First Visit
• CBC with platelet count
• PT/ PTT
• Anti-Phospholipid Abs
• Anti-Ro/...
Specific Investigations
ULTRASOUND
• Screen for fetal anomalies – between week 16-20
• Monitoring fetal growth – every 4 w...
Following Conception
Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al.
Understanding and Managing Pregnancy ...
Up to 30% may develop pre-eclampsia
Risk factors for Pre-
eclampsia in SLE
• Pre-existing hypertension
• Anti-phospholipid...
Following Conception
Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al.
Understanding and Managing Pregnancy ...
Risks from Medications Used
in Pregnancy
• Concerns over teratogenic risks lead
to women not taking meds during
pregnancy ...
Gaps in Medication Use
During Pregnancy
• Only half of all pregnancies are
planned and, as a result, many women
are alread...
ACR Reproductive
Health Summit
The GREATEST RISKS to the outcome
of the mother and the fetus comes from
• Uncontrolled dis...
What medications to give?
US FDA CLASSIFICATION
A
Studies in pregnant women failed to
demonstrate a risk to the fetus
B
No...
Towards Better
Understanding of
Medication Use in
Pregnancy
FDA
Amendments
Act of 2007
Medications in Pregnancy
LOW RISK NO DATA HIGH RISK
Steroids
Hydroxychloroquine
Azathioprine
Ciclosporin
Tacrolimus
Aspiri...
Medications When Breast Feeding
LOW RISK NO DATA HIGH RISK
Steroids
Hydroxychloroquine
Aspirin
Heparin or LMWH
IVIG
Azathi...
Anti-Phospholipid Syndrome (APS)
NON CRITERIA FEATURES
• Thrombocytopenia
• Hemolytic Anemia
• Livedo reticularis
• Cardia...
2006 Sydney (modified Sapporo) Criteria
Pregnancy
Morbidity
Vascular
Thrombosis
• Arterial thrombosis (e.g. stroke)
• Veno...
Nuances of aPL Testing
Anti-Phospholipid
Pregnancy
Morbidity
Vascular
Thrombosis
Lupus anticoagulant (LAC)  
Anti-Cardio...
TREATMENT
THROMBOSIS
VENOUS EVENT
Warfarin to target INR 2-3
? Long term treatment
ARTERIAL EVENT
Warfarin to target INR 3...
SUMMARY
• Pregnant SLE patients are high risk
for having multiple adverse events
• Care of the pregnant SLE patient
should...
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Managing Lupus in Pregnancy

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Slide set used during the 7th Post Graduate Symposium of the Northern Mindanao Medical Center held 3 October 2015 in Cagayan De Oro City.

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Managing Lupus in Pregnancy

  1. 1. MANAGING LUPUS IN PREGNANCY A Practical Approach Sidney Erwin T. Manahan, MD, FPCP, FPRA Medical Specialist (Rheumatology) Department of Medicine East Avenue Medical Center
  2. 2. OBJECTIVES • Describe adverse events observed in SLE patients who become pregnant • Discuss the management of lupus pregnancies • Discuss briefly the management of Anti-Phospholipid Syndrome (APS) in pregnancy
  3. 3. 1997 ACR Classification Criteria • Malar rash • Discoid rash • Photosensitivity • Oral ulcers • Arthritis • Serositis • Renal disorder • Neurologic disorder • Hematologic disorder • Immunologic disorder • Anti-nuclear antibodies SYSTEMIC LUPUS ERYTHEMATOSUS • Chronic Inflammatory Autoimmune Disorder • Predominantly affecting women in their reproductive years Hochberg MC. Updating the ACR revised criteria for the classification of SLE. Arthritis Rheum 1997; 40: 1725.
  4. 4. SYSTEMIC LUPUS ERYTHEMATOSUS 2012 SLICC Classification Criteria CLINICAL • Acute cutaneous • Chronic cutaneous • Oral ulcers • Non-scarring alopecia • Synovitis • Serositis • Renal • Neurologic • Hemolytic anemia • Leucopenia / Lymphopenia • Thrombocytopenia IMMUNOLOGIC • ANA • Anti-dsDNA • Anti-Sm • Anti-Phospholipid • Low complement • Direct Coomb’s test Petri M, Orbai AM, Alarcon GS, et al. Derivation and vallidation of the SLICC Classification Criteria for SLE. Arth & Rheum 2012; 64 (8): 2677-86.
  5. 5. Pregnancy/ Fetal Loss in SLE 43% 17% 0% 10% 20% 30% 40% 50% 1960-65 2000-03 Clark CA, Spitzer KA, Laskin CA. Decrease in pregnancy loss rates in patients with SLE over a 40-year period. J Rheumatol 2005; 32 (9): 1709-12.
  6. 6. Adverse Events During Pregnancy Maternal Mortality Odds Ratio 20 Lupus Flares Frequency 27-70% Cesarean Section Odds Ratio 1.7 Preterm Labor Odds Ratio 2.4 Pre- eclampsia Odds Ratio 3.0 Premature Birth Frequency 39.4% Abortion Frequency 16% Stillbirth Frequency 3.6% Neonatal Death Frequency 2.5% IUGR Odds Ratio 2.6 Neonatal Lupus Congenital Heart Block 1-2% of Ro+ Clowse ME, Jamison M, Myers E, et al. A national study of the complication of lupus in pregnancy. Am J Obstet Gynecol 2008; 199 (2): 127.31-e6. Smyth A, Oliveira GH, Lahr BR, et al. A systematic review and metaanalysis of pregnancy outcomes in patients with SLE and lupus nephritis. Am Soc Nephrol 2010; 5 (11): 2060-8.
  7. 7. The Health Care Team Expertise in • High-risk pregnancies • Systemic Lupus Erythematosus • Neonatal medicine Care should be performed in a controlled setting Stojan G, Baer AN. Flares of SLE during pregnancy and the puerperium: prevention, diagnosis and management. Expert Rev Clin Immunol 2012; 8 (5): 439-53. Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490. Lateef A, Petri M. Managing lupus patient during pregnancy. Best Pract Res Clin Rheumatol 2013; 27 (3): doi: 10.1016.
  8. 8. Risk Factors for POOR Pregnancy Outcomes • Active disease within 6 months prior to conception • Active disease during pregnancy • SLE onset during pregnancy • Anti-phospholipid syndrome • Hypocomplementemia • Presence of anti-dsDNA • Thrombocytopenia • Chronic hypertension • Pre-existing renal disease • First trimester proteinuria Stojan G, et al. Flares of SLE during pregnancy and the puerperium: prevention, diagnosis and management. Expert Rev. Clin Immunol 2012; 8(5): 439-453.
  9. 9. Domains in Managing Lupus in Pregnancy Pre-pregnancy Pregnancy Choice of Therapy Anti-Phospholipid Syn
  10. 10. Yang H,Liu H, Xu D, et al. Pregnancy-related SLE: clinical features, outcome and risk factors of disease flares – a case control study. PLoS ONE 2014; 9(8): 3104375 14% 32% 5% 37% 49% 5% 20% 49% 24% 2% 42% 54% 7% 12% 10% 10% 0% 6% 58% 0% 0% Pre/eclampsia Abortion Neonatal death Preterm birth Live birth Maternal death Severe organ damage New onset SLE during pregnancy (n 41) Flare of SLE during pregnancy (n 41) Stable SLE in preganancy (n 73) Outcomes in Pregnant SLE Patients
  11. 11. Before Conception 1 2 3 4 Monitor organ involvement Target disease remission; Delay pregnancy if high disease activity OR SLEDAI>8 Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490. Check for autoantibody profile Determine anti-PL, anti-Ro/ La
  12. 12. Risk factors for Flares during Pregnancy TYPE OF FLARE RISK FACTORS Mucocutaneous Anti-Ro, previous involvement Articular Anti-dsDNA Hematologic Anti-PL, Coombs+, previous involvement Renal Anti-dsDNA, Low C3/C4, previous involvement CNS Previous involvement Vascular Previous involvement Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490.
  13. 13. Before Conception 1 2 3 4 Monitor organ involvement Target disease remission; Delay pregnancy if high disease activity OR SLEDAI>8 Identify organ damage Look into contraindications to pregnancy Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490. Check for autoantibody profile Determine anti-PL, anti-Ro/ La
  14. 14. CONTRAINDICATIONS to Pregnancy • Severe pulmonary HPN (PAP >50mmHg) • Advanced heart failure • Severe restrictive lung disease • Chronic renal failure (sCrea >2.8mg/dl) Consider DEFERRING Pregnancy When • Current use of CTX, MMF, LEF • Active renal or CNS disease <6 months • Recent major thrombosis (i.e. stroke) <2 years Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490. Lateef A, Petri M. Managing lupus patients during pregnancy. Best Prac Res Clin Rheumatol 2013; 27 (3): doi:10/1016.
  15. 15. Before Conception 1 2 3 4 Monitor organ involvement Target disease remission; Delay pregnancy if high disease activity OR SLEDAI>8 Identify organ damage Look into contraindications to pregnancy Check for autoantibody profile Determine anti-PL, anti-Ro/ La Review treatment regimen Replace contraindicated meds with safer ones Wait for 2-3 months on new regimen to ensure disease control is maintained Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490.
  16. 16. When Do We Allow? • No evidence of active disease >6 months • Prednisone <10mg/d • May take Hydroxychloroquine • No contraindicated meds being taken >6mo • No evidence of active disease for 2-3 months if placed on a new regimen
  17. 17. Following Conception Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus . Autoimmune Dis 2015; 2015: Article ID 943490. 1 2 3 Monitor disease activity Differentiate symptoms of pregnancy vs SLE
  18. 18. Flares During Pregnancy New onset lupus during pregnancy (n 41) Flare of lupus during pregnancy (n 41) Non pregnant SLE patients (n 164) Mucocutaneous 20 (49%) 15 (37%) 98 (60%) Musculoskeletal 14 (34%) 3 (7%) 56 (34%) Renal 27 (66%) 35 (85%) 102 (62%) Cardiovascular 8 (20%) 9 (22%) 48 (29%) Pulmonary 9 (22%) 2 (5%) 26 (16%) Nervous system 7 (17%) 6(15%) 40 (24%) Gastrointestinal 10 (24%) 10 (24%) 30 (19%) Hematologic 25 (61%) 23(56%) 71 (44%) Yang H,Liu H, Xu D, et al. Pregnancy-related SLE: clinical features, outcome and risk factors of disease flares – a case control study. PLoS ONE 2014; 9(8): 3104375
  19. 19. WHAT causes these findings? Facial flush / Melasma Palmar erythema Post partum hair loss Photosensitive rash Malar rash Alopecia / lupoid hair Arthralgias, Myalgias Bland effusion of knees Synovitis Fatigue Mild edema Pleuritis Pericarditis Fever (T>38oC) Lymphadenopathy Yang H,Liu H, Xu D, et al. Pregnancy-related SLE: clinical features, outcome and risk factors of disease flares – a case control study. PLoS ONE 2014; 9(8): 3104375 Lateef A, Petri M. Managing lupus patients during pregnancy. Best Prac Res Clin Rheumatol 2013; 27 (3): doi:10/1016.
  20. 20. WHAT causes these findings? ESR 18-46mm/hr <20 weeks 30-70mm/hr >20 weeks ESR Increased Hgb >11 during 1st 20 weeks Hgb >10.5 beyond 20 weeks Hemoglobin <10.5 Mild thrombocytopenia in <8% Platelet <95,000 Proteinuria <300mg/24hours Proteinuria >300mg/24hours Rare hematuria from vaginal contamination Hematuria or cellular casts Anti-dsDNA Negative or stable Anti-dsDNA Rising Normal or increasing complement Low or >25%drop in complement Yang H,Liu H, Xu D, et al. Pregnancy-related SLE: clinical features, outcome and risk factors of disease flares – a case control study. PLoS ONE 2014; 9(8): 3104375 Lateef A, Petri M. Managing lupus patients during pregnancy. Best Prac Res Clin Rheumatol 2013; 27 (3): doi:10/1016.
  21. 21. Hypertension, Proteinuria in Pregnancy? Features Lupus nephritis Pre-eclampsia Hypertension Onset any time Onset after 20 weeks Proteinuria >300mg/d >300mg/d Urinary sediment Active Inactive Uric acid <5.5mg/dl >5.5mg/dl Anti-dsDNA level Rising Stable or negative 24 hr urine calcium >195mg/d <195mg/d Complement levels >25% drop Normal Other organs Active non-renal SLE CNS or HELLP Stojan G, Baer AN. Flares of SLE during pregnancy and the puerperium: prevention, diagnosis and management. Expert Rev Clin Immunol 2012; 8 (5): 439-53. Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490. Lateef A, Petri M. Managing lupus patient during pregnancy. Best Pract Res Clin Rheumatol 2013; 27 (3): doi: 10.1016.
  22. 22. SLE Disease Activity Indices(SLEDAI) in Pregnancy (SLEPDAI) Feature Score Seizure 8 Psychosis 8 Organic Brain syndrome 8 Visual disturbance 8 Cranial nerve disorder 8 Lupus Headache 8 CVA 8 Vasculitis 8 Arthritis 4 Myositis 4 Urinary casts 4 Hematuria 4 Feature Score Proteinuria 4 Pyuria 4 Rash 2 Alopecia 2 Mucosal ulcers 2 Pleurisy 2 Pericarditis 2 Low complement 2 Anti-dsDNA increasing 2 Fever 1 Thrombocytopenia 1 Leucopenia 1 Buyon JP, et al. Assessing disease activity in SLE patients during pregnancy. Lupus 1999; 8(8): 677-84.
  23. 23. Follow up of the Pregnant SLE Patient OBSTETRICIAN • Monthly until week 20 • Every 2 weeks until week 28 • Weekly until delivery RHEUMATOLOGIST • Support the obstetrician during prenatal care • Every 4-6 weeks
  24. 24. Lab Evaluation in Pregnant SLE Patients First Visit • CBC with platelet count • PT/ PTT • Anti-Phospholipid Abs • Anti-Ro/ La/ Sm • Anti-dsDNA titers/ C3/ C4/ CH50 • Chemistry (include BUA) • Urinalysis, 24 hour urine protein or urine protein/ creatinine ratio in a single sample Quarterly Visits • CBC with platelet count • Anti-ds DNA titers/ C3/ C4/ CH50 • Chemistry (include BUA) • Urinalysis, 24 hours urine protein or urine protein/ creatinine ratio in a single sample Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490 Lateef A, Petri M. Managing lupus patient during pregnancy. Best Pract Res Clin Rheumatol 2013; 27 (3): doi: 10.1016.
  25. 25. Specific Investigations ULTRASOUND • Screen for fetal anomalies – between week 16-20 • Monitoring fetal growth – every 4 weeks FOR ANTI-RO+ MOTHERS • Fetal echocardiography every week from week 16-26 and biweekly thereafter until delivery FOR PRE-ECLAMPSIA • Uterine artery doppler study – Week 20 then every 4 weeks • Fetal umbilcal artery doppler velocimetry – Week 26 then weekly Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490 Lateef A, Petri M. Managing lupus patient during pregnancy. Best Pract Res Clin Rheumatol 2013; 27 (3): doi: 10.1016.
  26. 26. Following Conception Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus . Autoimmune Dis 2015; 2015: Article ID 943490. 1 2 3 Monitor disease activity Differentiate symptoms of pregnancy vs SLE Consider low-dose Aspirin To reduce risks of pre-eclampsia esp in those with lupus nephritis
  27. 27. Up to 30% may develop pre-eclampsia Risk factors for Pre- eclampsia in SLE • Pre-existing hypertension • Anti-phospholipid syndrome • Obesity • Anti-dsDNA • Anti-RNP • Low Complement • Thrombocytopenia Consider low dose ASA (40- 160mg/d) before 16 weeks AOG in high risk patients • Preeclampsia (RR 0.6 95% CI 0.27- 0.83) • Severe preeclampsia (RR 0.3 95% CI 0.11-0.69) Schramm AM, Clowse MEB. Aspirin for the prevention of pre-eclampsia in lupus pregnancy. Autoimmune Dis 2014; 2014: ID 920467.
  28. 28. Following Conception Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus . Autoimmune Dis 2015; 2015: Article ID 943490. 1 2 3 Monitor disease activity Differentiate symptoms of pregnancy vs SLE Consider low-dose Aspirin To reduce risks of pre-eclampsia esp in those with lupus nephritis Treat for APAS Will discuss later
  29. 29. Risks from Medications Used in Pregnancy • Concerns over teratogenic risks lead to women not taking meds during pregnancy and lactation • Actual estimated risk for major malformations from meds <5% • Background rate for congenital anomalies ranges from 1-5% Koren G, Bologa M, Long D, et al. Perception of teratogenic risks by pregnant women exposed to druugs and chemical during the fist trimester. Am J Obstet Gynecol 1989; 160: 1190-4. Koren G, Pastuszak A. Prevention of unnecessary pregnancy terminations by counselling women on drug, chemical and radiation exposure during the first trimester. Teratology 1990; 41: 657-61. Loebstein R, Addis A, et al. Pregnancy outcomes following gestational exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob Agents Chemother 1998; 42: 1336-9 Bird TM, Hobbs CA, et al. National rates of birth defects among hospitalized newborns. Birth Def Res Clin Mol Teratol 2006: 76: 762-9
  30. 30. Gaps in Medication Use During Pregnancy • Only half of all pregnancies are planned and, as a result, many women are already taking medications when they become pregnant • In 2006, US Data shows that in >6 Million pregnancies >90% were taking at least 1 medication 50% were taking 3-4 medications Finer LB, Zolna MR. Unintended pregnancies in the US 2006. Contraception 2011; 84: 478-85
  31. 31. ACR Reproductive Health Summit The GREATEST RISKS to the outcome of the mother and the fetus comes from • Uncontrolled disease activity • Disease flares during pregnancy • Disease flares during the post partum period Kavanaugh A, Cush JJ, Ahmed MS, et al. Proceedings from the ACR Reproductive Health Summit: The management of fertility, pregnancy and lactation in women with autoimmune and systemic inflammatory diseases. Arthritis Care Res 2015; 67 (3): 313-25.
  32. 32. What medications to give? US FDA CLASSIFICATION A Studies in pregnant women failed to demonstrate a risk to the fetus B No studies in pregnant women but animal studies failed to show risk OR No studies in pregnant women but animal studies show a risk C No studies in pregnant women but animal studies show an adverse event but benefits outweigh risks in humans OR No studies in humans and animals D Evidence of fetal risk in humans but benefits outweigh risks X Evidence of fetal risk in humans or animals and risks outweighs benefits US FDA Pregnancy Categories: http://chemm.nlm.nih.gov/pregnancycategories.htm
  33. 33. Towards Better Understanding of Medication Use in Pregnancy FDA Amendments Act of 2007
  34. 34. Medications in Pregnancy LOW RISK NO DATA HIGH RISK Steroids Hydroxychloroquine Azathioprine Ciclosporin Tacrolimus Aspirin Heparin or LMWH IVIG TNF-inhibitors* Rituximab Belimumab Tofacitinib Tocilizumab Ustekinumab Methorexate Leflunomide Mycophenolate MMF Cyclophosphamide Warfarin * Generally safe in 1st and 2nd trimester; drug specific recommendations: Mabs – discontinue before 30 weeks and avoid live vaccine in infant until 6 months , ETN – discontinue 4 weeks before dellivery, certolizumab can be continued. Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490. Kavanaugh A, Cush JJ, Ahmed MS, et al. Proceedings from the ACR Reproductive Health Summit: The management of fertility, pregnancy and lactation in women with autoimmune and systemic inflammatory diseases. Arthritis Care Res 2015; 67 (3): 313-25.
  35. 35. Medications When Breast Feeding LOW RISK NO DATA HIGH RISK Steroids Hydroxychloroquine Aspirin Heparin or LMWH IVIG Azathioprine Ciclosporin Tacrolimus Rituximab Belimumab Tofacitinib Tocilizumab TNF-inhibitors Methorexate Leflunomide Mycophenolate MMF Cyclophosphamide Warfarin Ramires de Jesus G, Mendoza-Pinto C, Ramires de Jesus N, et al. Understanding and Managing Pregnancy in Patients with Lupus. Autoimmune Dis 2015; 2015: Article ID 943490. Kavanaugh A, Cush JJ, Ahmed MS, et al. Proceedings from the ACR Reproductive Health Summit: The management of fertility, pregnancy and lactation in women with autoimmune and systemic inflammatory diseases. Arthritis Care Res 2015; 67 (3): 313-25.
  36. 36. Anti-Phospholipid Syndrome (APS) NON CRITERIA FEATURES • Thrombocytopenia • Hemolytic Anemia • Livedo reticularis • Cardiac valve vegetations • Renal thrombotic microangiopathy • Cognitive dysfunction • Catastrophic APS (CAPS) Lockshin MD. Anticoagulation in Management of Anti-Phospholipid Antibody Syndrome in Pregnancy. Clin Lab Med 2013; 33(2): 267-476. Asheron RA, et al. Catastrophic Antiphospholipid Syndrome: International Consensus Statement on classification and treatment guidelines. Lupus 2003; 12 (7): 530-4. Pregnancy Morbidity Vascular Thrombosis Anti-Phospholipid (aPL) Antibodies
  37. 37. 2006 Sydney (modified Sapporo) Criteria Pregnancy Morbidity Vascular Thrombosis • Arterial thrombosis (e.g. stroke) • Venous thrombosis (e.g. DVT, PTE) • Small vessel occlusion • >3 consecutive spontaneous abortions (REM) <10 weeks • >1 fetal death beyond 10 weeks • >1 premature birth <34 weeks due to severe pre-eclampsia, eclampsia or placental insufficiency Anti-Phospholipid (aPL) Antibodies Documented 12 weeks apart • Positive Lupus anticoagulant (LAC) • Anti-Cardiolipin (aCL) IgM / IgG (> 40 GPU/ MPU) • Anti-2 Glycoprotein I (a2GPI) IgM/ IgG (>40 units) Lockshin MD. Anticoagulation in Management of Anti-Phospholipid Antibody Syndrome in Pregnancy. Clin Lab Med 2013; 33(2): 267-476. Asheron RA, et al. Catastrophic Antiphospholipid Syndrome: International Consensus Statement on classification and treatment guidelines. Lupus 2003; 12 (7): 530-4.
  38. 38. Nuances of aPL Testing Anti-Phospholipid Pregnancy Morbidity Vascular Thrombosis Lupus anticoagulant (LAC)   Anti-Cardiolipin (aCL)   Anti-2 Glycoprotein I (a2GPI)   Giannalopoulos B, et al. How we diagnose the antiphospholipid syndrome. Blood 2009; 113: 985-994 Lockshin MD. Anticoagulation in Management of Anti-Phospholipid Antibody Syndrome in Pregnancy. Clin Lab Med 2013; 33(2): 267-476. Asheron RA, et al. Catastrophic Antiphospholipid Syndrome: International Consensus Statement on classification and treatment guidelines. Lupus 2003; 12 (7): 530-4. 59.6 42.3 11.4 OR Thrombosis LAC + aCL + 2GPI LAC + a2GPI LAC 34.3 5 OR Pregnancy Morbidity LAC + aCL + 2GPI aCL + a2GPI
  39. 39. TREATMENT THROMBOSIS VENOUS EVENT Warfarin to target INR 2-3 ? Long term treatment ARTERIAL EVENT Warfarin to target INR 3-4 OR Target INR 1.5-2.5 and ASA 325 mg/day Indefinitely PREGNANCY MORBIDITY WITHOUT PRIOR THROMBOSIS Heparin 5000 u SC BID + ASA 75-81mg/d Conception to 6-12 weeks postpartum WITH PRIOR THROMBOSIS Heparin 10000 u SC BID + ASA 75-81-100mg/d Conception to Indefinitely NO PRIOR EVENTS ?? ASA 81mg/d for SLE Patients (both pregnant / non-pregnant) Lim W. Antiphospholipid Syndrome. Hematology 2013; 675-80. Lockshin MD. Anticoagulation in Management of APS in Pregnancy. Clin Lab Med 2013; 33(2): 367-376. Lim W, Crowther MA, Eikelboom JW. Management of APAS: A Systematic Review. JAMA 2006; 295: 1050-57.
  40. 40. SUMMARY • Pregnant SLE patients are high risk for having multiple adverse events • Care of the pregnant SLE patient should be a collaborative effort • Care starts before conception until the post partum period with specific concerns needing to be addressed • APAS may complicate lupus pregnancies and is managed differently from non-pregnant patients

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