Autoimmune diseases in pregnancyAbdullah Al-Harthy
• For years, women with potentially serioussystemic autoimmune diseases have beenadvised not to get pregnant.• We now know that, with careful medical andobstetric management, most of these womencan have successful pregnancies.
Autoimmune disease•inappropriate immune response of the bodyagainst substances and tissues normallypresent in the body•In other words, the immune systemmistakes some part of the body as a pathogenand attacks its own cells•The treatment of autoimmune diseases istypically with immunosuppression medicationwhich decreases the immune response.
Objectives:• Why Rheumatic Diseases Important inPregnancy ?• effect of rheumatic diseases in the mother onfertility• discuss the maternal and fetal effects ofpregnancy
Risk of Transmission From Mother to FetusFetal Outcome USE OF RHEUMATIC DRUGS DURING PREGNANCY ANDLACTATION DVT vs. Back pain
Why Rheumatic DiseasesImportant in Pregnancy ?Rheumatic diseases often affect womenduring their childbearing years, whenpregnancy is an expected event.Careful medical and obstetric prepared tohandle the possible complications.Effect on Fetal Outcome .
Effect of rheumatic diseases in the motheron fertility• SLE, RA, the vasculitides and thespondyloarthropathies are not known todirectly affect fertility. Although SLE patientsare as fertile as the general population .• There is a reported reduced fertility rate inpatients with active disease who are treatedwith high dose corticosteroid therapy, asmenstrual irregularities and anovulatorycycles may occur.
Effect of rheumatic diseases in the motheron fertility• End-stage renal failure secondary tolupus nephritis can result inamenorrhoea.• Amenorrhoea in renal patients may alsobe due to ovarian failure secondary tocyclophosphamide or it may be ofautoimmune origin.
Discuss the maternal and fetal effects ofpregnancySYSTEMIC 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 nephritismay co-exist in pregnancy, it is essential to differentiateisolated pre-eclampsia from renal lupus during pregnancy, asmanagement will be very different depending on thediagnosis. Pre-eclampsia can be defined as blood pressure over 140/90or the rise of 30 mmHg systolic or 15 mmHg diastolic incombination with proteinuria (>300 mg/24 h) and oedema atgreater than 20 weeks gestation proteinuria is more likely to be due to pre-eclampsia thanlupus nephritis. Lupus nephritis is more likely if there is apositive urinary sediment
Discuss the maternal and fetal effects ofpregnancyAnti-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 thatthrombocytopenia may occur for a variety of reasons inpregnancy. Although APS, lupus or HELLP are the best knownassociations in patients with rheumatic diseases, it should notbe forgotten that approximately 9% of healthy womendevelop mild thrombocytopenia for non-autoimmunereasons.• Isolated anti-platelet antibodies can cause an idiopathicthrombocytopenia. Thrombocytopenia associated with APSmay worsen in pregnancy or due to treatment with heparin.
Discuss the maternal and fetal effects ofpregnancy• 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
• Wells score or criteria: (possible score −2 to 9)• Active cancer (treatment within last 6 months or palliative): +1point• Calf swelling ≥ 3 cm compared to asymptomatic calf (measured10 cm below tibial tuberosity): +1 point• Swollen unilateral superficial veins (non-varicose, insymptomatic 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 lowerextremities: +1 point• Recently bedridden ≥ 3 days, or major surgery requiring regionalor general anesthetic in the past 12 weeks: +1 point• Alternative diagnosis at least as likely: −2 points
• Those with Wells scores of two or morehave a 28% chance of having DVT, thosewith a lower score have 6% odds.Alternatively, Wells scores can becategorized as high if greater than two,moderate if one or two, and low if lessthan one, with likelihoods of 53%, 17%,and 5% respectively
Causes of Back Pain in Pregnant• Pregnancy back pain typically happens where the pelvis meetsthe spine, at the sacroiliac joint.• Weight gain . During a healthy pregnancy, women typically gainbetween 25 and 35 pounds. The spine has to support thatweight. That can cause lower back pain. The weight of thegrowing baby and uterus also puts pressure on the bloodvessels and nerves in the pelvis and back.• Posture changes. Pregnancy shifts The center of gravity.• Hormone changes. During pregnancy, your body makes ahormone called relaxin that allows ligaments in the pelvic areato relax and the joints to become looser in preparation for thebirth process. The same hormone can cause ligaments thatsupport the spine to loosen, leading to instability and pain.• Muscle separation.• Stress
• sciatica is used to describe a symptom ratherthan a specific disease. Some use it to meanany pain starting in the lower back and goingdown the leg.• Spinal disc herniation• Spinal stenosis• Pregnancysciatica
Risk of Transmission From Mother toFetusSLE and Sjögrens syndrome are the most widelyrecognized rheumatic diseases in whichpathogenic antibodies can pass from mother toinfant through the transmission of anti-Roand/or anti-La across the placenta duringpregnancy The prevalence of these auto-antibodies in SLE patient is about35% but transmission of IgG antibodies across the placentabetween weeks 16 and 32 gestation occurs in about 5% ofmothers. Neonatal transmission usually resolves within the first 6 monthsof life, as maternal antibodies are destroyed in the infant.
The most severe complication of neonatal lupussyndrome is congenital heart block (CHB).Complete CHB is diagnosed when fetal bradycardia isidentified usually between 18 and 28 weeks. It is important to closely monitor these pregnanciesby serial Doppler echocardiography. Measurement of AV time intervals is a suggestedsurveillance instrument, as incomplete block mayprogress in utero or post-delivery and carries a 20%mortality rate. Permanent pacemakers are requiredby 67% of survivors with complete CHB.Dexamethasone or betamethasone may be given totry and reverse heart block, as it is able to cross theplacenta unlike prednisolone
Fetal Outcome• Fetal Loss : The risk is increased in women who have previouslyexperienced fetal loss, active renal disease at conception, maternal hypertensionand the presence of anti-phospholipid antibodies.• Recurrent fetal loss is also one of the criteria when diagnosing APS and thepresence of both lupus anticoagulant and anticardiolipin antibodies is associatedwith the highest risk of fetal loss.• Intrauterine Growth Restriction : In SLE patients,hypertension, active lupus and APS are significant predictive factors forIUGR.• Fetal loss in early pregnancy in APS can be due to failure of the placenta toimplant, due to the effect of anti-phospholipid antibodies on anionicphospholipids and the effect of B2-glycoprotein on trophoblasts. Thrombosisin APS is also thought to have a role in pregnancy loss due to uteroplacentalinsufficiency 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 underlyingcause, such as breathing difficulties, infection, jaundice, feedingdifficulties, developmental abnormalities and neonatal death.• Breathing difficulties are usually due to insufficient surfactant, which canbe reduced by a 48-h course of dexamethsone or betamethasone in caseswhere there is a high chance of premature delivery, such as activematernal disease or fetal distress.
USE OF RHEUMATIC DRUGS DURINGPREGNANCY AND LACTATION Pregnancy LactationNSAID Yes(avoid after 32 weeks(YesSulfasalazine Yes YesAntimalarials Yes YesCorticosteroids Yes YesCyclosporin Yes probably yesAzathioprine Yes probably yesMycophenolate No NoMethotrexate No NoCyclophosphamide No NoAnti-tumor necrosisfactor (TNF(No NoRituximab No NoWarfarin No(with caution, only afterfirst trimester(YesHeparin Yes Yes
POINTS TO REMEMBERAll women should undergo counseling beforeconception for their specific risk, depending on theircondition and the medications they are taking.Each woman’s rheumatic disease should be wellunder control for a period of at least 3-6 monthsbefore attempting pregnancy.Women with a low-risk profile can be managed withusual visits to the rheumatologist as a precaution.Those with a high-risk profile should be managed byboth the rheumatologist and obstetric team withexperience in high-risk pregnancies.
Summary• Pregnancies in women with rheumatic diseases require amulti-disciplinary, carefully monitored, coordinated approachbefore, during and after pregnancy to ensure the bestpossible success for mother and baby.• In contrast to SLE, APS, vasculitis and systemic sclerosis thereis little evidence for poor maternal or fetal outcomes in RA orother forms of inflammatory arthritis such as psoriasis andseronegative spondyloarthropathies.• Prior to pregnancy it is important to counsel the motherconcerning potential complications, establish disease activitycontrol, screen for hypertension and renal involvement,exclude pulmonary hypertension and make appropriatechanges to the womans therapy.
During pregnancy it is essential to monitor allaspects of disease activity such as renalinvolvement, as well as pregnancy complicationssuch 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 themother on postpartum issues such as breast-feeding and contraception, as well as to monitorfor and treat any postpartum flares as these arecommon in all the rheumatic diseases.
References• American college of rheumatology• http://arthritis-research.com• Medscape• Current Diagnosis & Treatment inRheumatology, Third Edition