Patients with rheumatic diseases are a high-risk group for pregnancy. With the development of diagnostic techniques for rheumatic immune diseases, more and more patients with rheumatic diseases are being diagnosed and many young women are facing pregnancy problems. Rheumatic diseases and pregnancy are discussed below.
I. Factors leading to adverse pregnancy outcomes in patients with rheumatic diseases
1. Factors of the disease itself: such as disease recurrence, disease activity and complications arising from the disease.
2, drug factors: rheumatic immune diseases require a variety of immunosuppressive drugs or hormone therapy, for pregnancy, azathioprine, hydroxychloroquine and prednisone are safe to use during pregnancy, but drugs such as mortification, which has certain teratogenic effects, such as small ear malformation and toxic damage to the cardiovascular system. Therefore, the application of such drugs during pregnancy will certainly lead to adverse outcomes.
3. Sex hormone changes: such as estrogen. Estrogen receptors α and β play an important role in the action of estrogen. Studies have found that anti-estrogen receptor alpha antibodies are found in about 45% of lupus patients, but anti-estrogen receptor beta antibodies are not found in lupus patients, and studies have also found that anti-estrogen receptor alpha antibodies are associated with lupus activity.
4. Autoantibodies: Certain autoantibodies are associated with infertility. For example, the combination of anti-brewer’s yeast antibodies and anti-coagulant antibodies is of high value for predicting infertility. In addition, anti-thyroid-related antibodies are considered to be an independent risk factor for infertility.
II. Characteristics of pregnancy in different rheumatic diseases
1. Rheumatoid arthritis: In the past, it was widely believed that patients with rheumatoid arthritis would experience significant improvement in joint symptoms after pregnancy. But a study found that this was not the case, it found that the rate of joint symptom relief in pregnant patients had dropped from 90% in the past to 48%, and half of the patients would have disease activity during pregnancy. In addition, the study found that: patients with rheumatoid arthritis who were negative for anti-cyclic citrulline antibodies and rheumatoid factor were more likely to be in remission after pregnancy; patients taking hormones showed no significant change in disease remission during pregnancy compared to those not taking them; and rheumatoid arthritis activity was strongly associated with low birth weight infants, who had an increased incidence of metabolic disease and cardiovascular disease in adulthood.
2. Systemic lupus erythematosus: these patients have the following characteristics at the time of pregnancy.
(1) Disease activity scores and impairment index scores peak at 24 weeks of gestation.
(2) A high rate of recurrence of the disease during pregnancy, mostly in the middle of pregnancy, with mostly mild relapses.
(3) activity of the disease in the first months of pregnancy increases the risk of miscarriage fourfold, and activity of the disease during pregnancy increases the incidence of miscarriage and preterm delivery eightfold
(4) Lupus patients with renal impairment have a significantly higher risk of eclampsia, fetal growth restriction, miscarriage, and preterm delivery during pregnancy. In patients presenting with renal impairment, Scr levels have a significant impact on pregnancy outcome, with blood creatinine at 125-180 umol/L, a 60% risk of preterm delivery, 40% risk of eclampsia, 5% perinatal mortality, and 2% progression to end-stage renal disease. Since lupus nephritis is so terrible in pregnancy, how should we treat it? One of the current consensus is hormones, but the adverse consequences of hormone therapy such as uncontrolled disease, infection, preterm delivery and diabetes cannot be ignored. Recent studies have found that tacrolimus can be used in such patients to treat relapses of lupus nephritis and is relatively safe.
3. Antiphospholipid antibody syndrome: The mechanism of this disease is still quite complicated so far. The mechanisms responsible for adverse pregnancy outcomes are as follows.
(1) thrombotic factors.
(2) Pulmonary thrombotic factors leading to placental meconium cell damage.
(3) inflammatory effects.
(4) Complement activation.
For a rare but serious complication of antiphospholipid antibody syndrome and catastrophic antiphospholipid antibody syndrome, the disease is often precipitated by an underlying event, such as HELLP syndrome. This complication often manifests clinically as damage to the skin, liver, kidneys, and cardiovascular and neurological systems. For the treatment of antiphospholipid antibody syndrome, traditional treatment includes aspirin and low molecular heparin, but this traditional treatment is not effective in some patients, so in this case it is essential to look for risk factors in advance, such as positive serology for antiphospholipid antibodies, previous history of deep vein thrombosis, autoimmune disease or lupus anticoagulant carriers. In addition to the above treatments, hydroxychloroquine has a role in antiphospholipid antibody syndrome, and studies have found that oral administration of such drugs for less than 12 months has negligible potential for retinal toxicity or cardiotoxicity.
4. Systemic sclerosis and vasculitis: Because of the relatively late age of onset of these diseases and the relative civilization of the disease during pregnancy, studies are rare. However, the adverse pregnancy outcome caused by such diseases is similar to other rheumatic immune diseases.
Third, several common complications of pregnancy in patients with rheumatic diseases
Pre-eclampsia: The imbalance between angiogenic and anti-angiogenic factors is the pathogenesis of these diseases. For this complication, the only effective treatment and delivery. However, this also leads to a high rate of preterm birth. In addition, aspirin and low-molecular heparin have been shown to be effective. Some recent studies have found that statins have the potential to treat this condition because of their anti-angiogenic factor effect, but specific clinical studies are still ongoing.
2. Intrauterine growth restriction: This complication is thought to be associated with placental malfunction. Early and regular Doppler ultrasonography or detection of factors such as Sflt-1 and PIGF can be used to terminate the occurrence of intrauterine growth restriction in a timely manner.
Fourth, the preparation before pregnancy
1, is prenatal consultation and comprehensive assessment: including age, previous pregnancy and outcome, degree of organ involvement, current disease status and frequency of recent recurrence, current treatment, and any pregnancy requiring discontinuation of medications.
2. Any change in treatment regimen prior to pregnancy should be maintained for 2-3 months to ensure that the change in regimen will keep the disease in remission.
3. Hydroxychloroquine is not recommended to be discontinued during pregnancy to avoid high relapse rate of lupus during pregnancy. In case of disease relapse before pregnancy, pregnancy should be considered after the disease has been stable for at least 3 months. For patients with re-relapse of lupus kidney, conception should be achieved again after normalization of renal function and absence of proteinuria or urine protein <1g/24 hours. For patients with pre-pregnancy renal lesions, it is recommended that a small amount of aspirin be given from the first trimester to prevent the development of eclampsia in pregnancy. Doppler ultrasonography of the placenta during pregnancy is necessary to predict and prevent intrauterine growth restriction and eclampsia. Relevant studies recommend starting standardized and regular this examination after 25 weeks of gestation.
In conclusion, patients with rheumatic diseases are high-risk pregnancy patients, and the existence of pregnancy characteristics, complications during pregnancy and prenatal preparation in different rheumatic diseases require our utmost attention.