Pregnancy implications for systemic lupus erythematosus and the antiphospholipid syndrome
Highlights
► Patients with SLE and APS can have successful pregnancies when properly assisted. ► Multidisciplinary approach and pre-gestational counselling are key points to favourable outcome. ► Optimal timing: pregnancy should start during stable remission of maternal disease. ► Teratogenic drugs should be withdrawn, while “safe” drugs should be continued throughout pregnancy. ► Autoantibodies that may negatively affect pregnancy outcome should be screened in each patient.
Introduction
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a remitting and relapsing trend. SLE mainly affects young females during their reproductive years, therefore pregnancy is a topic of major interest. In early times, pregnancy was discouraged in women affected by SLE, because it was reported that the disease could become more aggressive during pregnancy, putting both the mother and the foetus at high risk. In the last 30 years, the management of the disease has greatly improved, and the approach to pregnancy along with it. SLE patients can successfully carry out a pregnancy, as long as timing and management of gestation are planned in close contact with doctors. In fact, pregnancy should be still considered a high risk period during the course of SLE, with a large number of potential complications that can influence maternal and foetal health. In particular, many SLE patients carry antiphospholipid antibodies (aPL), which are well-known risk factors for thrombotic events and pregnancy morbidity [1]. The antiphospholipid syndrome (APS) may present also as a primary form (PAPS), without any underlying systemic autoimmune disease such as SLE. Such patients are at risk for either a first obstetric failure or a recurrence of pregnancy loss.
In any case, preconception counselling is essential in order to estimate the chance of both foetal and maternal problems, related to either disease activity, serologic profile or organ involvement as contraindication to pregnancy. In addition, the checklist must include some epidemiologic items that are relevant to any pregnancy (age, smoking, arterial hypertension, diabetes mellitus, previous obstetric history, previous thrombosis) [2]. The counselling and the follow-up during and after pregnancy should be preferably performed by a multidisciplinary team joined by rheumatologists, obstetricians, neonatologists and also other medical specialties (nephrology, neurology, cardiology, haematology, etc.) when indicated [3].
When talking about her productive plans, any patient will ask the following questions: “Will my baby be healthy?”, “Will my disease worsen during pregnancy?”, “Will medications harm my baby?”. Therefore, the following issues must be discussed with a patient who desires a pregnancy:
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Disease activity during pregnancy and post-partum period and its possible effects on foetal outcome;
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Obstetrical maternal complications;
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Autoantibodies able to interfere with pregnancy outcome (in particular aPL and anti-Ro/SSA and anti-La/SSB antibodies);
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Drugs compatible or not with pregnancy, drugs to be added during pregnancy.
Section snippets
Lupus flares during pregnancy
An important aspect of pregnancy in lupus patients is the risk of the occurrence of disease flares.
It is not simple to quantify the incidence of such complications because many clinical studies were performed using individual definitions of flare. In recent times, many efforts were done to create a “pregnancy-version” of existing activity indexes, such as ECLAM, SLEDAI, SLAM and LAI, aiming at making studies more comparable [4]. The literature reports discordant results from prospective,
Definition of APS and aPL
The antiphospholipid syndrome (APS) is a systemic autoimmune disorder defined by the occurrence of venous and arterial thromboses, often multiple, and pregnancy morbidity (abortions, foetal deaths, premature births), in the presence of antiphospholipid antibodies (aPL) [1]. APS can be found in patients having neither clinical nor laboratory evidence of another definite autoimmune condition (primary APS) or it may be associated with other diseases, mainly systemic lupus erythematosus (SLE). aPL
Compatibility of drugs with pregnancy
One of the critical issue in the management of a pregnancy in SLE/APS patients is to choose the right medication to treat the mother without harming the foetus. The pregnancy categories used by the United States Food and Drug Administration (FDA) are often not very helpful for the clinician for various reasons. Warnings may come from evidence that is mostly based on animal data, or restrictions may be generated by the lack of information in humans, rather than by a demonstrated teratogenicity.
Contraception, fertility and assisted reproduction
Speaking of contraception with SLE/APS patients goes beyond the simple need of avoiding unwanted pregnancies. Several conditions may require an effective contraception: early stage of the disease, very active disease, severe organ involvement or damage, use of embryotoxic/fetotoxic drugs. Therefore, contraceptive counselling is essential in the rheumatologic practice, but in the “real life” most women do not receive any information about this issue [110], [111]. A common misconception among
The offspring of SLE/APS patients
A major source of anxiety for women with SLE/APS who wish to become pregnant is the possible impact of maternal disease and medications on the offspring, in terms of physical and mental development of the child. Older and recent studies have focused on several different aspects of the issue: physical growth, neuropsychological development, effect of drugs on the infant’s immune system, and development of autoimmune features in children [132], [133].
First of all, it should be emphasized that
Concluding remarks
SLE and APS are chronic systemic diseases that affect young women during their childbearing age. Great improvement has been done in the past few decades in the approach to pregnancy. Maternal counselling is the key point. Women should be aware that pregnancy is possible and can be satisfactorily managed in terms of both maternal and neonatal outcome. To this purpose, some “minimal requirements” are needed: i) optimal timing: pregnancy should start in a period of stable remission of maternal
Acknowledgements
Dr. Andreoli is supported by the project “Dote Ricercatore e Dote Ricerca Applicata ai sensi dell’accordo regionale per lo sviluppo del capitale umano nel sistema universitario Lombardo sottoscritto tra Regione Lombardia e Università Lombarde il 20-10-2009” (Università degli Studi di Brescia).
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2018, Journal of AutoimmunityCitation Excerpt :In contrast, the presence of high levels of Th17 cells, a third set of CD4+ T helper cells, are found in preeclampsia and recurrent pregnancy loss [25]. There are contradictory results in the literature regarding whether lupus flares are more common in pregnancy [26]; this is likely due to the fact that most clinical studies were performed using differing definitions of SLE disease flare in addition to the challenges in differentiating flares from other pregnancy related complications [27]. Some degree of disease activity is thought to be present in 40–50% of SLE pregnancies [12], with the most common manifestations including lupus nephritis, cutaneous disease, arthritis, and hematologic disease [12].
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2016, Journal of AutoimmunityCitation Excerpt :However, whether these complications should be attributed to Belimumab, or to the assumption of concomitant drugs or active disease itself is not clarified yet [132]. The current suggestion is to interrupt this medication about 4 months before conception [5], switching to an immunosuppressant compatible with pregnancy. The suspension has to be applied also to Rituximab (RTX), another biological DMARD that has been used in SLE/APS patients with refractory disease.