SLE occurs in women of childbearing age and can cause multisystem and multiorgan damage. Because of the specificity of the population, the problem of fertility cannot be avoided. Due to the specificity of the disease and the risk of combined pregnancy, there are no authoritative guidelines for the diagnosis and treatment of these problems at home and abroad.
1. Basis for successful pregnancy
The level of treatment for SLE has been greatly improved, and the obstetric monitoring and treatment environment is constantly improving, but it is still very important for SLE patients to have a stable condition before pregnancy. Unstable disease, especially the presence of LN and high titers of antiphospholipid antibodies, increases the risk of maternal hypertension and preterm delivery. pregnancy outcome and timing in SLE patients are associated with a stable period from 4 to 6 months prior to conception. Under conditions of stable disease (at least 6 months, with medication regimen having been adjusted in advance), the frequency of pregnancy failure in SLE patients can approach normal pregnancy.
As far as the condition of pregnancy is concerned, the criteria for judging the stability of SLE should be.
① Maintenance of a smaller hormonal dose (prednisone <15 mg/d) without immunosuppressive agents (e.g., cyclophosphamide, methotrexate, etc.) or discontinued for at least 6 months;
(ii) No clinical damage to the heart, lungs, kidneys, central nervous system and other important organ systems, and the disease is stable for more than 6 months to 1 year;
(iii) Stable renal function [creatinine ≤ 140 μmol/L; normal blood pressure; urine protein quantification (24 h) ≤ 3 g] in those with LN. If the above conditions are met, pregnancy can be planned. Negative anti-dsDNA antibodies and normal complement C3 and C4 should not be used as mandatory indicators and should be assessed dynamically (some patients with long-term abnormal anti-dsDNA antibodies and complement C3 and C4, while other indicators are completely normal, may also plan pregnancy). Contraception should be used for those who do not meet the target. Contraception should not be preferred to combination oral contraceptives, which can aggravate the disease and increase the risk of thrombosis.
Before pregnancy, SLE patients should have routine blood, urine, urine protein quantification (24h) (when urine protein is positive), blood biochemistry, Coomb’s test, anti-cardiolipin antibody (ACL), lupus anticoagulant, anti-β2-glycoprotein Ⅰ (GPⅠ), anti-dsDNA antibody, anti-SSA antibody, anti-SSB antibody and complement C3 and C4 tests, among which routine blood, urine and ACL are particularly important. Pregnancy in SLE patients should be performed under the supervision of rheumatologists, obstetricians and gynecologists, and nephrologists.
2. Timing of pregnancy
The timing of pregnancy is crucial for a successful pregnancy. In all cases, the physician should prefer to initiate communication with the patient and family, emphasizing the high risk of pregnancy, pregnancy complications, and the possibility of pregnancy failure; SLE patients have the same fertility as healthy women, but SLE patients have fewer children than expected, which is mainly related to the lack of confidence in pregnancy and pregnancy miscarriage.
Immunosuppressive drugs should be discontinued for more than 6 months in SLE patients who plan to become pregnant. Unplanned pregnancies while taking immunosuppressants also often bother doctors. This is because these drugs may cause stillbirths or neonatal malformations. Some unplanned pregnancies in patients taking immunosuppressive drugs (e.g., cyclophosphamide) can result in miscarriage and preterm delivery; however, there have been instances of normal deliveries of full-term fetuses with healthy newborns.
Although there have been successful pregnancies and deliveries with immunosuppressive drugs, the drugs are teratogenic and pregnancy with drugs (immunosuppressive drugs) is not yet encouraged. The author believes that under current medical conditions, a more aggressive attitude should be taken towards the chances of pregnancy than before. For infertile SLE patients with stable disease and no SLE comorbidities, ovulation induction and in vitro fertilization can be attempted, and precedents of healthy fetuses being born by in vitro fertilization in SLE patients are not uncommon. Patients who have had perinatal fetal loss also have a good chance of success in subsequent pregnancies.
”Safe” medications should be continued throughout pregnancy. Low-dose aspirin and heparin should be used aggressively in the presence of positive antiphospholipid antibodies. Maintenance of hydroxychloroquine has been shown to be safe, to significantly reduce prednisone dosage, to reduce SLE progression, fetal loss, fetal growth restriction, and fetal distress, and to be safe during lactation. In a large number of studies for the treatment of SLE, hydroxychloroquine was not found to be associated with an increased risk of congenital defects, spontaneous abortion, intrauterine death, preterm birth or a reduced number of live births, and also reduced the risk of maternal lupus cardiomyopathy.
3. Follow-up of patients during pregnancy is the key to success
Patients with SLE have a higher risk of developing gestational hypertension, preeclampsia, and eclampsia than the healthy population. Poor pregnancy outcomes include miscarriage, preterm delivery, stillbirth, fetal growth restriction, intrauterine distress, and low birth mass infants. lN, infection, pulmonary embolism, and pulmonary hypertension may lead to fatal outcomes. Adrenocortical failure due to abrupt discontinuation of glucocorticoids is also frequently seen in pregnant patients.
When disease activity in pregnancy is present, prompt evaluation, decisive management and, if necessary, immediate termination of the pregnancy are warranted. In nephrotic syndrome, full-term delivery is possible in those with normal or mildly impaired renal function, however, the expected delivery date should not be exceeded; if renal function continues to deteriorate, blood pressure is unsatisfactorily controlled, or fetal distress is present, the pregnancy should be terminated. Planned application of adrenocorticotropic hormones to promote fetal lung maturation prior to termination can help reduce the incidence of neonatal respiratory distress syndrome.
Those with platelet counts < 20 x 109/L are at risk and require aggressive management; intravenous administration of immunoglobulin may be the preferred option. If the platelet count is < 50 x 109/L and there is a tendency to bleed, then cesarean section should also be performed to end the delivery. Patients at high risk of pre-eclampsia and thrombosis should be treated prophylactically with aspirin and heparin; treatment with plain heparin or low-molecular heparin combined with aspirin may reduce the rate of pregnancy loss.
However, high doses of aspirin (>3 g/d) lead to prolonged overdue pregnancies and deliveries, and also increase the complications of delivery bleeding. In addition, patients with SLE combined with pregnancy are prone to depression and targeted psychological interventions are necessary.
After pregnancy, if disease activity occurs, those who were previously maintained on small doses of prednisone (5-15 mg orally daily) before pregnancy should be doubled to a maximum of 60 mg orally/d during pregnancy; in severe cases, 60-100 mg of methylprednisolone daily, or shock therapy should be used. If the condition is severe during pregnancy and endangers maternal life, the combined use of azathioprine, cyclophosphamide or cyclophosphamide should be used after timely termination of pregnancy. Intravenous immunoglobulin infusion is a good choice for those with severe disease.
The puerperium is a high-risk period for SLE patients with risk of thromboembolism, especially for antiphospholipid antibody-positive patients, who should be closely monitored for the first 4 d postpartum, especially in patients with recent disease activity or previous history of severe disease. Low relative molecular mass heparin should be used to prevent thrombosis until 4 to 6 weeks postpartum. Patients with a previous history of thrombosis may resume the amount of anticoagulant applied before delivery 2-3d postpartum. Patients on long-term heparin need calcium and vitamin D supplementation until the end of lactation.
Establishing close contact between rheumatology and obstetrics is the greatest guarantee for pregnancy in SLE patients. The author’s hospital has established a green channel for pregnancy in SLE patients. A senior specialist in the outpatient clinic is responsible for the management of pregnancy in SLE patients and actively liaises with the relevant departments. The relevant departments have their own responsibilities and cooperate with each other to solve all problems related to SLE and pregnancy. Since the establishment of the green channel, both the rheumatology and obstetrics departments have increased their confidence and level of management of such problems.
In such cases, decisive decisions should be made while being meticulous and cautious. Especially for the family members of such patients, it is important to achieve a good explanation and reach a consensus on the treatment and prognosis of each different stage. It would be a boon to SLE patients’ pregnancy if similar partnerships were established in all general hospitals in a relatively short period of time.