Features of pregnancy management and prevention of complications in patients with SLE

Rayana B. Chidigova, Rayana A. Yandarova, Bella Sh. Parsho-eva, Daniil Yu. Zavarzin. Features of pregnancy management and prevention of complications in pa-tients with SLE. Cardi-ometry; Issue No. 30; February 2024; p. 98-102; DOI: 10.18137/ cardiometry.2024.30.98102; Available from:

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease affecting mainly women, especially those of childbearing age. Assessing the potential of the body of women with this diagnosis before pregnancy is vital, since it allows you to maximize the chances of a successful pregnancy and the risks for both the mother and the child[1]. Thus, data from two systematic reviews and meta-analyses have shown that active lupus nephritis (LN) is associated with poor pregnancy outcomes for both mother and child. These outcomes include exacerbation of LN in the mother, gestational hypertension and preeclampsia, as well as prematurity of the newborn, intrauterine growth retardation and spontaneous miscarriages.

Assessment of the body’s potential before pregnancy is mandatory for all women with SLE, this allows patients to be divided into different risk profile groups. An interdisciplinary approach is important to determine the best approach to care through collaborative decision-making. As a rule, women of childbearing age with SLE can be divided into 3 groups, namely: inactive or calm course of the disease, active course of the disease and course of SLE with severe organ dysfunction or previously severe organ damage [2].

The assessment of the disease activity is carried out using clinical, laboratory and histological parameters. Experts have noted that the onset of pregnancy with an active disease is closely correlated with adverse outcomes for the mother and fetus. Women with SLE need to receive comprehensive recommendations from specialists before pregnancy in order to ensure remission of the disease, as well as to get good prospects for a safe and successful outcome.

MATERIALS AND METHODS

In the process of preparing this work, an array of data was studied demonstrating the theoretical and practical study of the problem under consideration. When writing the study, comparative and analytical research methods were used.

RESULTS

Systemic lupus erythematosus (SLE) is a chronic systemic immune–mediated disease affecting mainly women of childbearing age [3]. Pregnancy in women diagnosed with SLE presents a higher risk of complica- tions compared to the general population. One study identified and described obstetric and neonatal outcomes in pregnant women with lupus. Based on the analysis of 59 pregnancies and 52 newborns, experts determined the following: in 58% of cases, pregnancy proceeded smoothly. Exacerbation was registered in 25% of cases, gestosis – in 3%, fetal development delay – in 12%, gestational loss – in 10%, premature birth – in 10%, postpartum complications – in 20%, small for gestational age newborns – in 17% of cases. affairs. According to the results of the study, it was determined that the majority of pregnancies in women with lupus have favorable obstetric and neonatal outcomes [4]. However, the fundamental factors in this case are prenatal counseling, adequate interdisciplinary follow-up and optimized treatment of the disease.

Another study noted that SLE can negatively affect the development of pregnancy. Thus, a study of a sample of pregnant women (n=116 people) revealed preeclampsia in 3% of cases, fetal growth restriction in 12% in 12%, termination of pregnancy and premature birth in 10% of cases, and severe consequences after childbirth in 20% [5].

In the recent period, there has been a positive trend in overall survival, an increase in the number of pregnancies and favorable obstetric and perinatal outcomes. The reason for this is the increased access of women to specialist counseling before conception and interdisciplinary monitoring throughout pregnancy.

However, it must be remembered that SLE carries a significant risk of obstetric and perinatal complications, the pathogenesis of which is mainly associated with uteroplacental insufficiency, the inflammatory condition underlying the disease, as well as the possibility of penetration of autoantibodies to immunoglobulin G (IgG) of the mother through the placental bloodstream and binding to fetal tissue [6].

Obstetric complications include the risk of termination of pregnancy, premature birth, and fetal death; hypertensive complications include preeclampsia (PE), eclampsia (E) and/or hemolysis, increased activity of liver enzymes, low platelet count syndrome (LPCS); other complications include gestational diabetes, fetal growth retardation (FGR), higher the rate of infections, thromboembolic complications, cesarean section and postpartum complications, including infections, bleeding and exacerbations of lupus [7].

Researchers, both theorists and practitioners, describe many predictors of complications and adverse pregnancy outcomes in SLE, namely: lupus nephritis, damage to other organs (lungs, heart, central nervous system), interruption of drug treatment, antiphospholipid syndrome, etc. [8] In newborns whose mother has a history of SLE, there is an increased risk of the risk of developing a number of complications – prematurity, low birth weight, etc.

Several studies report the association of premature birth with certain risk factors, namely: high activity of the disease at conception, positive antiphospholipid antibodies, APS, exacerbations, obstetric abortion in the anamnesis, thromboembolic complications, lupus nephritis, etc. [9]. Approximately a quarter of pregnancies (25%) had exacerbations of SLE, with the most frequent manifestations being skin and joint manifestations, which is consistent with the literature data [10].

Although most pregnant women with SLE have favorable obstetric and perinatal outcomes, these women continue to represent a risk group for obstetric complications. To improve obstetric and perinatal outcomes, it is important to conduct systematic preventive work, as well as plan pregnancy in the remission phase of the disease, in order to ensure adequate multidisciplinary monitoring of pregnancy and optimal treatment of the disease. Delivery should be planned in a differentiated mode [11].

The researchers point out that given the inherent risks of infertility (for example, menstrual irregularities and premature ovarian failure) associated with cyclophosphamide, a mycophenolic acid analog (MPAA) regimen is the preferred initial therapy for proliferative lupus nephritis. It is also strongly recommended that all women of childbearing age with SLE be consulted on fertility issues, especially on the adverse effects associated with age and the use of alkylating agents [12]. In cases where MPAA-based therapy is prescribed, a risk assessment program and risk reduction strategies are conducted to ensure its safe use and to raise awareness among healthcare professionals and patients about teratogenic problems associated with MPAA during pregnancy [13].

According to experts, assisted reproductive treatments, such as in vitro fertilization protocols and ovulation induction methods, can also be considered in patients with stable or inactive disease [14].

In order to exclude unplanned pregnancy, especially during active illness and when taking teratogenic drugs, women with SLE should receive advice

Issue 30. February 2024 | Cardiometry | 99

on contraceptive methods. There are many options available, such as the intrauterine device (IUD), progestin-only contraception (POC) in pill form, etc. The choice of the method of contraception will ultimately depend on the patient’s preferences, taking into account the pros and cons of each option and balanced by the thrombotic risk profile. The risk of thrombosis depends on the history of active thrombotic episodes, current disease activity, and common risk factors (e.g. smoking, obesity, and family history of hormone-dependent malignancies) [15].

The use of a copper IUD can be considered in all patients with SLE without any gynecological contraindications, whereas a levonorgestrel-based IUD may be an option if the benefits of hormone release (for example, reducing excessive menstrual bleeding) outweigh the thrombotic risk. When considering the use of these non-estrogenic contraceptives, it is necessary to take into account the rare but potential side effects that may occur in the patient.

The division of women with SLE into groups according to the symptoms and complexity of the course of the disease is the first step towards developing a systematic approach to management. This requires the ability to identify high-risk patients and plan a safe and timely pregnancy, taking into account the preferences and values of the patients [16].

Patients with SLE and concomitant severe disorders or organ damage should be informed about the risks of disease progression that can lead to organ failure, as well as possible pregnancy-related problems for both mother and child. Experts have confirmed the conclusions that problems in the postpartum period in patients with SLE are not related to pregnancy as such, but rather to the sum of negative factors accompanying the development of the disease, as well as the patient’s lack of understanding of the degree of activity of the development of autoimmune pathology.

In light of these results, women with SLE and severe damage to target organs should be informed of the high risks associated with maintaining pregnancy. Such patients should be encouraged to consider alternative options, such as adoption [17].

Patients who have been diagnosed with an active form of SLE, but severe organ damage has not been noted, should be advised to wait for the onset of remission and only after 6 months of its course consider the possibility of pregnancy. This will minimize the adverse effects of pregnancy on both the mother and the child [18]. Postponing pregnancy planning will increase the likelihood of a favorable pregnancy outcome in the future. Also, such patients should be given general advice on preparing for conception, including discussion of appropriate methods of contraception.

Patients with an inactive form of the disease are informed that this is the safest period for pregnancy planning. Before starting pregnancy, all patients with SLE are strongly recommended to be screened for antibodies to antiphospholipid syndrome (APS). The activity of the disease should be constantly monitored throughout pregnancy. It is also recommended that patients regularly undergo the necessary tests. It is extremely important to stop taking teratogenic drugs such as MPAA and switch to non-teratogenic therapy such as calcineurin inhibitor or azathioprine. During this period, specialists monitor the activity of the disease development in patients and advise on contraceptive methods [19].

Throughout the entire prenatal period, patients should be regularly monitored for the condition of the mother and fetus by a multidisciplinary team [20]. In addition to routine ultrasound monitoring in the first (11-14 weeks of gestation) and second trimester (2024 weeks of gestation), pregnant women are recommended to conduct additional fetal monitoring in the third trimester.

DISCUSSION

Experts note the most increased risks of pregnancy against the background of lupus nephritis (LN). The occurrence of LN may be the first manifestation of SLE during pregnancy. Diagnosis of LN during pregnancy is rare in itself and is certainly a problem, since the symptoms of SLE tend to coincide with the symptoms of pregnancy [21]. LN can be diagnosed during pregnancy based on a set of signs, including clinical status, presence of autoantibodies, hypocomplementemia and in some cases, kidney biopsy, especially if the picture is atypical [22].

The management of a pregnant patient with newly diagnosed LN includes similar treatment principles for the management of patients with exacerbations of LN during pregnancy. Management is based on the importance of joint decision-making by both the patient and the doctor. Decisions are made after weighing the risk-benefit ratio of continuing pregnancy, as well as the efficacy and safety profile of treatment for both mother and child.

Progressive kidney disease can be a serious complication in this context. In addition, SLE itself can cause various obstetric complications, especially hypertension, preeclampsia and thromboembolic events, as well as fetal complications such as premature birth, miscarriages, intrauterine growth retardation and congenital heart block [23].

It is quite difficult to distinguish an exacerbation of LN from preeclampsia, especially in the second and third trimesters of pregnancy, even for an experienced clinician. The reason is that both of these conditions may have similar clinical manifestations: These are high blood pressure, an increase in serum creatinine, proteinuria and edema. It is believed that the conditions do not exclude each other and may even be present in the patient at the same time. Differentiation of both these conditions is of important therapeutic importance: for example, in preeclampsia, urgent delivery is necessary, whereas exacerbation of LN is treated with immunosuppression.

In general, the occurrence of LN can occur at any time throughout pregnancy with the preservation of extrarenal signs of lupus, whereas preeclampsia usually occurs in the middle of pregnancy, from about the 20th week of pregnancy [24].

Treatment of exacerbations of LN should not be postponed if they occur during pregnancy. The direction of management should be based on several considerations, including the severity and degree of organ damage, the duration of pregnancy during an exacerbation of LN, and the ratio of benefit and risk of continuing pregnancy while ensuring the well-being of the mother. The decision on whether to continue pregnancy or not should be made individually in accordance with the values and preferences of the patient after an in-depth discussion between the doctor and the patient [25].

In a young woman with severe exacerbation of LN in the early stages of pregnancy, the possibility of termination of pregnancy for medical reasons should be discussed. The main goal is to control the activity of the disease by early administration of immunosuppressants, while avoiding teratogenic side effects of therapy. Monitoring the activity of the disease at an early stage significantly increases the chances of a successful pregnancy outcome in the future.

If an exacerbation of LN occurred at a late stage of pregnancy in a patient who previously had difficulty conceiving, then it is necessary to direct forces to the treatment of the exacerbation itself. The goal of treatment is to try to restrain LN so that the pregnancy lasts as long as possible until the fetus reaches sufficient maturity for childbirth. Careful monitoring is necessary in the first 6 months after childbirth due to the high risk of exacerbation of LN during this period.

CONCLUSIONS

Systemic lupus erythematosus (SLE) is an archetypal multisystem autoimmune disease. Patients with systemic lupus erythematosus have immuno-mediat-ed inflammatory lesions of almost every organ system, so lupus can manifest itself in all areas of medicine. This well-known clinical heterogeneity leads to many difficulties, including diagnosis or standardization of treatment approaches.

Special attention from medical specialists should be paid to patients who have been diagnosed with this disease and who are planning pregnancy or are already expecting a child. The interdisciplinary model of medical care remains the cornerstone of the approach to ensuring accurate assessment and prognosis of the disease, identifying high-risk groups among women with SLE and drawing up a comprehensive and holistic pregnancy management plan for optimal results in the form of safe and timely pregnancy. This includes joint decision-making with patients, an effective two-way risk awareness process, fertility preservation measures, contraception if indicated, a systematic risk stratification process, phased pharmacological treatment and regular monitoring of mother and fetus.