Autoimmune diseases in pregnancyAbdullah Al-Harthy

• For years, women with potentially serious systemic autoimmune diseases have been advised not to get pregnant.

• We now know that, with careful medical and obstetric management, most of these women can have successful pregnancies.

Autoimmune disease

•inappropriate immune response of the body against substances and tissues normally present in the body

• In other words, the immune system mistakes some part of the body as a pathogen and attacks its own cells

•The treatment of autoimmune diseases is typically with immunosuppression medication

which decreases the immune response .

Objectives:

• Why Rheumatic Diseases Important in Pregnancy ?

• effect of rheumatic diseases in the mother on fertility

• discuss the maternal and fetal effects of pregnancy

Risk of Transmission From Mother to FetusFetal Outcome USE OF RHEUMATIC DRUGS DURING PREGNANCY AND

LACTATION DVT vs. Back pain

Why Rheumatic Diseases Important in Pregnancy ?

Rheumatic diseases often affect women during their childbearing years, when pregnancy is an expected event.

Careful medical and obstetric prepared to handle the possible complications.

Effect on Fetal Outcome .

Effect of rheumatic diseases in the mother on fertility

• SLE, RA, the vasculitides and the spondyloarthropathies are not known to directly affect fertility. Although SLE patients are as fertile as the general population .

• There is a reported reduced fertility rate in patients with active disease who are treated with high dose corticosteroid therapy, as menstrual irregularities and anovulatory cycles may occur.

Effect of rheumatic diseases in the mother on fertility

• End-stage renal failure secondary to lupus nephritis can result in amenorrhoea.

• Amenorrhoea in renal patients may also be due to ovarian failure secondary to cyclophosphamide or it may be of autoimmune origin.

Discuss the maternal and fetal effects of pregnancy

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) (a) Flares :  many patients used to stop all their therapy upon

discovering that they were pregnant, which may have contributed to an increased risk of flare in pregnancy.

(b) Hypertension : 25% of pregnancies in women with SLE are complicated by hypertensive disorders and there is also a higher rate of caesarean sections

(c) Renal Lupus : kidney is one of the major target organs and up to 60% of patients experience focal or diffuse renal involvement Proteinuria without the presence of red cells or casts in the urine can be difficult to distinguish from pre-eclampsia. features: proteinuria greater than 500 mg/24 h, haematuria, red cell casts and hypertension. 

(d) Pre-eclampsia : pre-eclampsia and lupus nephritis may co-exist in pregnancy, it is essential to differentiate isolated pre-eclampsia from renal lupus during pregnancy, as management will be very different depending on the diagnosis.

Pre-eclampsia can be defined as blood pressure over 140/90 or the rise of 30 mmHg systolic or 15 mmHg diastolic in combination with proteinuria (>300 mg/24 h) and oedema at greater than 20 weeks gestation

proteinuria is more likely to be due to pre-eclampsia than lupus nephritis. Lupus nephritis is more likely if there is a positive urinary sediment

antiphospholipids Syndrome (APLS)in SLE patient presented with CLOT

coangulation defectlivedo reticularis

obstetric complication - recurrent miscarriage & IUGRthrombocytopenia

Discuss the maternal and fetal effects of pregnancy

Anti-phospholipid Syndrome (a) Thrombosis : All women are in a prothrombotic state during

pregnancy and for 6 weeks postpartum and so are at increased risk of deep vein thrombosis, pulmonary emboli and stroke , A higher pregnancy success rate has been shown in women with APS and recurrent miscarriages taking low dose aspirin in pregnancy

(b) Pre-eclampsia : Pre-eclampsia is most common in pregnancies where the mother has APS. In patients with APS, it often recurs and may present as very early onset pre-eclampsia (<20 weeks)

 Patients with APS also have an increased incidence and severity of the HELLP syndrome than the general population,  with or without pre-eclampsia or eclampsia. 

• (c) Thombocytopenia :It should be noted that thrombocytopenia may occur for a variety of reasons in pregnancy. Although APS, lupus or HELLP are the best known associations in patients with rheumatic diseases, it should not be forgotten that approximately 9% of healthy women develop mild thrombocytopenia for non-autoimmune reasons.

• Isolated anti-platelet antibodies can cause an idiopathic thrombocytopenia. Thrombocytopenia associated with APS may worsen in pregnancy or due to treatment with heparin.

Discuss the maternal and fetal effects of pregnancy

• Rheumatoid Arthritis• RA has been known to improve during pregnancy for many years.

Several studies have shown significant improvement in 75–95% of pregnant women with RA. The improvement By Blood plasma Expansion .

• Or If It Get worst mainly by patient when she stoped her medications

DVT vs. Back pain

Wells score or criteria

• Wells score or criteria: (possible score −2 to 9)• Active cancer (treatment within last 6 months or palliative): +1

point • Calf swelling ≥ 3 cm compared to asymptomatic calf (measured

10 cm below tibial tuberosity): +1 point • Swollen unilateral superficial veins (non-varicose, in

symptomatic leg): +1 point • Unilateral pitting edema (in symptomatic leg): +1 point • Previous documented DVT: +1 point • Swelling of entire leg: +1 point • Localized tenderness along the deep venous system: +1 point • Paralysis, paresis, or recent cast immobilization of lower

extremities: +1 point • Recently bedridden ≥ 3 days, or major surgery requiring regional

or general anesthetic in the past 12 weeks: +1 point • Alternative diagnosis at least as likely: −2 points

• Those with Wells scores of two or more have a 28% chance of having DVT, those with a lower score have 6% odds. Alternatively, Wells scores can be categorized as high if greater than two, moderate if one or two, and low if less than one, with likelihoods of 53%, 17%, and 5% respectively

Causes of Back Pain in Pregnant• Pregnancy back pain typically happens where the pelvis meets

the spine, at the sacroiliac joint. • Weight gain . During a healthy pregnancy, women typically gain

between 25 and 35 pounds. The spine has to support that weight. That can cause lower back pain. The weight of the growing baby and uterus also puts pressure on the blood vessels and nerves in the pelvis and back.

• Posture changes. Pregnancy shifts The center of gravity. • Hormone changes. During pregnancy, your body makes a

hormone called relaxin that allows ligaments in the pelvic area to relax and the joints to become looser in preparation for the birth process. The same hormone can cause ligaments that support the spine to loosen, leading to instability and pain.

• Muscle separation. • Stress

• sciatica is used to describe a symptom rather than a specific disease. Some use it to mean any pain starting in the lower back and going down the leg.

• Spinal disc herniation• Spinal stenosis• Pregnancy

sciatica

Risk of Transmission From Mother to Fetus

SLE and Sjögren's syndrome are the most widely recognized rheumatic diseases in which pathogenic antibodies can pass from mother to infant through the transmission of anti-Ro and/or anti-La across the placenta during pregnancy

The prevalence of these auto-antibodies in SLE patient is about 35% but transmission of IgG antibodies across the placenta between weeks 16 and 32 gestation occurs in about 5% of mothers.

Neonatal transmission usually resolves within the first 6 months of life, as maternal antibodies are destroyed in the infant.

The most severe complication of neonatal lupus syndrome is congenital heart block (CHB).

Complete CHB is diagnosed when fetal bradycardia is identified usually between 18 and 28 weeks.

It is important to closely monitor these pregnancies by serial Doppler echocardiography.

Measurement of AV time intervals is a suggested surveillance instrument, as incomplete block may progress in utero or post-delivery and carries a 20% mortality rate. Permanent pacemakers are required by 67% of survivors with complete CHB.

Dexamethasone or betamethasone may be given to try and reverse heart block, as it is able to cross the placenta unlike prednisolone

Fetal Outcome

• Fetal Loss : The risk is increased in women who have previously experienced fetal loss, active renal disease at conception, maternal hypertension and the presence of anti-phospholipid antibodies.

• Recurrent fetal loss is also one of the criteria when diagnosing APS and the presence of both lupus anticoagulant and anticardiolipin antibodies is associated with the highest risk of fetal loss.

• Intrauterine Growth Restriction : In SLE patients, hypertension, active lupus and APS are significant predictive factors for IUGR.

• Fetal loss in early pregnancy in APS can be due to failure of the placenta to implant, due to the effect of anti-phospholipid antibodies on anionic phospholipids and the effect of B2-glycoprotein on trophoblasts. Thrombosis in APS is also thought to have a role in pregnancy loss due to uteroplacental insufficiency from multiple placental thromboses and infarcts

• Premature Delivery : is common in patients with lupus, vasculitis, systemic sclerosis and especially antiphospholipid syndrome .

• There are several complications of prematurity, regardless of underlying cause, such as breathing difficulties, infection, jaundice, feeding difficulties, developmental abnormalities and neonatal death.

• Breathing difficulties are usually due to insufficient surfactant, which can be reduced by a 48-h course of dexamethsone or betamethasone in cases where there is a high chance of premature delivery, such as active maternal disease or fetal distress.

USE OF RHEUMATIC DRUGS DURING PREGNANCY AND LACTATION

 PregnancyLactationNSAIDYes

(avoid after 32 weeks)Yes

SulfasalazineYesYesAntimalarialsYesYes

CorticosteroidsYesYesCyclosporinYesprobably yes

AzathioprineYesprobably yesMycophenolateNoNoMethotrexateNoNo

CyclophosphamideNoNoAnti-tumor necrosis

factor (TNF)NoNo

RituximabNoNoWarfarinNo

(with caution, only after first trimester)

Yes

HeparinYesYes

POINTS TO REMEMBER

All women should undergo counseling before conception for their specific risk, depending on their condition and the medications they are taking.

Each woman’s rheumatic disease should be well under control for a period of at least 3-6 months before attempting pregnancy.

Women with a low-risk profile can be managed with usual visits to the rheumatologist as a precaution. Those with a high-risk profile should be managed by both the rheumatologist and obstetric team with experience in high-risk pregnancies.

Summary

• Pregnancies in women with rheumatic diseases require a multi-disciplinary, carefully monitored, coordinated approach before, during and after pregnancy to ensure the best possible success for mother and baby.

• In contrast to SLE, APS, vasculitis and systemic sclerosis there is little evidence for poor maternal or fetal outcomes in RA or other forms of inflammatory arthritis such as psoriasis and seronegative spondyloarthropathies.

• Prior to pregnancy it is important to counsel the mother concerning potential complications, establish disease activity control, screen for hypertension and renal involvement, exclude pulmonary hypertension and make appropriate changes to the woman's therapy.

During pregnancy it is essential to monitor all aspects of disease activity such as renal involvement, as well as pregnancy complications such as IUGR, thrombo-embolic disease and pre-eclampsia, particularly in patients with SLE, APS, vasculitis and systemic sclerosis.

After pregnancy it is essential to counsel the mother on postpartum issues such as breast-feeding and contraception, as well as to monitor for and treat any postpartum flares as these are common in all the rheumatic diseases.

References

• American college of rheumatology• http://arthritis-research.com• Medscape• Current Diagnosis & Treatment in

Rheumatology, Third Edition