Managing a patient exposed to a teratogenic drug at different stages of pregnancy

Pregnancy-related information provided by leaflets usually contains inadequate data to interpret risks of teratogenicity; and in the absence of data, prescribing information often recommends discontinuing use in anticipation of and during pregnancy. In contrast, individual information on drug risk assessment addresses three different clinical perspectives: 1) looking for drugs of choice or planning pregnancy under medication; 2) assessment of drugs’ risk after exposure during an unplanned pregnancy; 3) assessment of causality in cases of adverse pregnancy outcomes in association with drug exposure. Unfortunately, for many women with chronic rheumatic diseases, discontinuation of all medication leaves an unacceptable risk of disease reactivation. Although, for the majority of drugs, human data are still insufficient to rule out developmental risks it is possible to distinguish antirheumatic drugs of choice with apparently low or negligible risks from those with scarce data or controversies on their safety and those with evidenced risk for the unborn.

Vasculitis in pregnancy

A growing number of women with vasculitis are becoming pregnant, largely the result of improved patient outcomes in vasculitis as a whole. Given such pregnancies are infrequent, there is a paucity of outcomes data from which to guide care. Women with vasculitis have higher rates of pregnancy loss and pre-term birth than the general population, and active disease contributes to negative results for the mother and foetus. Pregnancies have been reported in a variety of vasculitis types, with Takayasu arteritis and Behçet’s disease more commonly observed. The majority of pregnancies in women with vasculitis can result in favorable outcomes for both the mother and baby; planning prior to conception, well-controlled disease, the use of pregnancy compatible medications and close follow up with a multidisciplinary team are key to a successful pregnancy.

Pregnancy and obstetric complications in women with autoimmune diseases

For most women, pregnancy is suspected when the symptoms of early pregnancy develop—these include breast soreness or tenderness, fatigue, nausea, and missed menses. Human chorionic gonadotropin (hCG) is first detectable using sensitive tests in the urine and blood of pregnant women 8–10 days after conception (day 22–24 of a 28-day menstrual cycle). Concentrations of hCG rise rapidly in early pregnancy, peak at 9–10 weeks, and decline thereafter to a nadir at 20 weeks. Understanding embryo-foetal development and maternal physiological accommodation to pregnancy is required for the optimal management of pregnancy in women with autoimmune diseases. This chapter reviews the important developmental and physiologic aspects of normal pregnancy and both common and unique obstetric complications associated with selected rheumatic conditions.

Infection in a pregnant patient on immunosuppressive treatment

Patients on immunosuppressive therapies have greater susceptibility to a broad range of infections and pose a special challenge during pregnancy and lactation. Anti-microbials must be given with due consideration to side-effects, drug-drug interactions, and importantly safety to the growing foetus and the breastfeeding baby. This chapter further elucidates on modes of transmission and prevention of some infections which can significantly impact materno-foetal outcomes. Systemic autoimmune diseases must be kept under good control during pregnancy since untreated disease carries its own risks to both the mother and the developing foetus. Whilst infections are an important complication of immunosuppressive drugs used for many autoimmune rheumatic diseases, their clinical manifestations may be masked or absent among immunosuppressed individuals.

Prevention of postpartum venous thromboembolism (VTE)

Venous thromboembolism (VTE) is a leading cause of maternal mortality in developed countries. The baseline pregnancy-associated VTE (PA-VTE) risk is further increased by additional maternal, pregnancy, and delivery characteristics. In a recently developed risk prediction model for postpartum VTE, emergency caesarean section, stillbirth, postpartum haemorrhage, pre-eclampsia/eclampsia, infection, and medical comorbidities were the strongest VTE predictors. While the evidence base supporting optimal strategies for reducing the risk of postpartum VTE in general is weak, for women with prior VTE it appears that this risk may be reduced by up to 75% with low-molecular-weight heparin (LMWH). VTE prevention in women with more common VTE risk factors is a knowledge gap in 2020, with widely varying international guideline recommendations. However, there is no debate surrounding the requirement to perform systematic VTE risk assessment in pregnant and postpartum women.

Thrombotic complications in pregnant patients with rheumatic disease

Rheumatic disease and pregnancy are both associated with increased rates of venous thromboembolism. In pregnancy, the highest risk is in the later stages of pregnancy and postpartum. The management of anticoagulation to provide thromboprophylaxis, for treatment of acute thromboembolism or for prevention of secondary recurrence can cause issues throughout pregnancy for the clinician and patient, particularly around the time of delivery. In those with rheumatic disease, this can be complicated by the presence of antiphospholipid antibodies, which are associated with venous, arterial, and microvascular thromboembolism and obstetric complications. We discuss the management of thrombotic conditions during pregnancy and the post-natal period and considerations that the clinicians should be aware of.

Adjustment of therapy before/during pregnancy and lactation

Treatment with medications during pregnancy and lactation is a challenge and needs to balance the risk of untreated maternal disease against any possible harm to the foetus or child. Indications for treatment are control of disease activity and ensuring a healthy pregnancy and healthy child outcomes. Administration of the following drugs is compatible with pregnancy: non-steroidal anti-inflammatory drugs (non-selective COX inhibitors until gestational week 32), glucocorticoids (preferentially at low dose), antimalarials, sulfasalazine, azathioprine (AZA), cyclosporine, tacrolimus, colchicine, and intravenous immunoglobulin. Methotrexate, mycophenolate mofetil, and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Among biologics tumour necrosis factor (TNF) inhibitors are best studied and appear reasonably safe preconceptionally, during pregnancy, and lactation; for other biologics foetal safety has not yet been established. The pregnancy compatibility of medications administered for comorbidities must be assessed. Except for cyclophosphamide other immunosuppressives are compatible with fatherhood.

Advanced renal disease/renal impairment

There is an increased incidence of chronic kidney disease (CKD) in patients with underlying rheumatic disease. For a proportion of patients, CKD is diagnosed for the first time in pregnancy through routine antenatal blood and urine testing. Pregnancy places increased physiological demand on the kidneys, and women with CKD have increased risks of adverse pregnancy outcomes, including pre-eclampsia (PET), pre-term delivery, and low birth weight babies. These risks increase incrementally with declining baseline renal function. Thorough pre-conception counselling and regular antenatal review by teams specializing in the care of renal and/or rheumatological conditions is recommended to mitigate these risks and optimize outcome for mother and baby. This chapter describes, through case-based discussion, the investigation and management of abnormal renal function presenting in pregnancy, pre-pregnancy counselling for women with CKD, and the principles of antenatal care for women with impaired renal function.

Ankylosing spondylitis in pregnancy

Ankylosing spondylitis (AS), now called axial spondyloarthritis (axSpA) shows no tendency to improve spontaneously during pregnancy but remains stable or active. An aggravation of symptoms occurs often around mid-gestation. Treatment with medications is needed in many pregnant patients and has to be modified according to stage of pregnancy. Vaginal delivery is possible in most women with axSpA, however, disease-related and iatrogenic reasons or patient preferences increase the rate of surgical delivery. AS typically affects individuals in the 3rd decade of life and is in its radiographic form predominant in men with a male to female ratio of 2–3:1 whereas the non-radiographic form has an equal gender distribution.

Vaccination before or during pregnancy

In general, live attenuated vaccines are contraindicated in pregnancy and with immunosuppression, especially biologics. Prior to pregnancy and initiation of immunosuppressive therapy, attempts should be made to administer recommended vaccines to protect the health of both the woman and child. There is limited safety and efficacy data for many inactivated, toxoid, and subunit/conjugate vaccines in the setting of pregnancy and biologic therapy. In addition, vaccines in general may have diminished immunogenicity if administered during biologic therapy. This chapter focuses on the current recommendations, immunogenicity, and contraindications for vaccination of women of child-bearing age with rheumatic diseases who may be taking or considering initiation of disease-modifying antirheumatic drugs (DMARDs).