As active rheumatic and musculoskeletal disease during pregnancy increases the risk for pregnancy loss, preterm birth, and maternal illness, ongoing management with pregnancy-compatible medications can improve these outcomes. Selecting and taking these medications can be challenging for rheumatologists and patients due to limited knowledge about potential risks and benefits.

Following successful kidney transplantation, recipients usually regain fertility. Post-engraftment pregnancies should be planned and the teratogenic mycophenolic acid should be replaced with azathioprine before conception. To avoid unintentional pregnancies, pre-conception counseling is mandatory in women of reproductive age who are scheduled for a kidney transplant. Counseling should be repeated after transplantation. Female recipients should receive advice to use long-acting reversible contraception and avoid pregnancy for a minimum of 1 year following transplantation. Conception should be deferred even longer in female recipients with moderate to severe proteinuria, uncontrolled hypertension or reduced graft function and be very carefully discussed in highly HLA-sensitized patients. The recipient wishes, values and acceptance of pregnancy-related risk should receive attention. Assisted fertilization increases the risk of pre-eclampsia, but still result in live births. Pregnancy management in kidney transplant recipients should be provided by a multidisciplinary team consisting of a nephrologist, a midwife and an obstetrician with expertise in high-risk pregnancies. Until measurement of unbound fraction of calcineurin inhibitors becomes clinically available, we recommend to adjust calcineurin inhibitor dose according to whole blood trough level, even though it overestimates the effective drug concentration during pregnancy. If nephrotoxicity is suspected, the calcineurin inhibitor dose should be reduced. Breastfeeding should be accepted after kidney transplantation since infant immunosuppressive drug exposure via breastmilk is extremely low. The prevalence of congenital malformations in children fathered by male recipients, including patients on mycophenolic acid therapy at the time of conception, is at level with the general population.

Pediatric patients often have poor pregnancy outcomes. Systemic lupus erythematosus predominantly impacts women in their second to fourth decade of life, with childhood-onset disease being particularly aggressive. Reproductive issues are an important clinical consideration for pediatric patients with systemic lupus erythematosus (SLE), as maintaining good disease control and planning a pregnancy are important for maternal and fetal outcomes. In this clinical review, we will consider the safety of medications in managing childhood-onset SLE during conception, pregnancy, and breastfeeding. The developing fetus is at highest risk for teratogenicity from maternal medications during the period of critical organogenesis, which occurs between the first 3-8 weeks following conception. Medications known to be teratogenic, leading to a specific pattern of malformations, include mycophenolic acid, methotrexate, and cyclophosphamide. These should be discontinued prior to a planned pregnancy or as soon as pregnancy is suspected. Hydroxychloroquine is safe and should be continued throughout pregnancy and breastfeeding in those without contraindications to it. Azathioprine and calcineurin inhibitors are felt to be compatible with pregnancy in usual doses and may be used prior to and throughout pregnancy and lactation. Non-fluorinated corticosteroids including methylprednisolone and prednisone are inactivated by the placenta and can be used if needed for maternal indication during gestation. Addition of aspirin may be considered around the 12th week of gestation for prevention of pre-eclampsia. Illustrative cases are presented that demonstrate management of adolescents with childhood-onset SLE through conception, pregnancy, and breastfeeding.

Kidney transplantation offers best hope to women with end-stage renal disease who wish to become pregnant. Pregnancy in a kidney transplant recipient continues to remain challenging due to side effects of immunosuppressive medication, risk of deterioration of allograft function, risk of adverse maternal complications of preeclampsia and hypertension, and risk of adverse fetal outcomes of premature birth, low birth weight, and small for gestational age infants. The factors associated with poor pregnancy outcomes include presence of hypertension, serum creatinine greater than 1.4 mg/dL, and proteinuria. The recommended maintenance immunosuppression in pregnant women is calcineurin inhibitors (tacrolimus/cyclosporine), azathioprine, and low dose prednisone; and it is considered safe. Sirolimus and mycophenolate mofetil should be stopped 6 weeks prior to conception. The optimal time to conception continues to remain an area of contention. It is important that counseling for childbearing should start as early as prior to getting a kidney transplant and should be done at every clinic visit after transplant. Breast-feeding is not contraindicated and should not be discouraged. This review will help the physicians in medical optimization and counseling of renal transplant recipients of childbearing age.

Background. Inflammatory bowel disease (IBD) affects patients in their young reproductive years. Women with IBD require maintenance therapies during pregnancy and breastfeeding. However, physician management of IBD during pregnancy and breastfeeding has not been well characterized. Objective. To characterize physician perceptions and management of IBD during pregnancy and breastfeeding. Methods. A cross-sectional survey of Canadian physicians who are involved in the care of women with IBD was conducted. The survey included multiple-choice and Likert scale questions about perceptions and practice patterns regarding the management of IBD during pregnancy and breastfeeding. Results. 183 practicing physicians completed the questionnaire: 97/183 (53.0%) gastroenterologists; 75/183 (41.0%) general practitioners; and 11/183 (6.0%) other physicians. Almost half (87/183, 47.5%) of the physicians felt comfortable managing pregnant IBD patients. For specified IBD medications, proportions of physicians who indicated they would continue them during pregnancy were as follows: sulfasalazine, 47.4%; oral mesalamine, 67.0%; topical mesalamine, 70.3%; oral prednisone, 68.0%; topical prednisone, 78.0%; oral budesonide, 61.6%; topical budesonide, 75.0%; ciprofloxacin, 15.3%; metronidazole, 31.4%; azathioprine, 57.1%; methotrexate, 2.8%; infliximab, 55.6%; adalimumab, 78.1%. Similar proportions of physicians would continue these medications during breastfeeding. A higher proportion of gastroenterologists than nongastroenterologists indicated appropriate use of these IBD medications during pregnancy and breastfeeding. Conclusions. Physician management of IBD during pregnancy and breastfeeding varies widely. Relative to other physicians, responses of gastroenterologists more frequently reflected best practices pertaining to medications for control of IBD during pregnancy and breastfeeding. There is a need for further education regarding the management of IBD during pregnancy and breastfeeding.

Inflammatory bowel diseases are chronic conditions that frequently affect patients during their childbearing years. Considering the characteristics of disease and the medications used to treat it, several issues arise in the care of these patients when they attempt or achieve conception. We review the most current evidence concerning fertility and pregnancy outcomes in patients with inflammatory bowel diseases. With the exception of those women who undergo pelvic surgery, patients with inflammatory bowel diseases have no decreased fertility. Sulfasalazine decreases fertility in men. When looking at obstetrical outcomes, active disease at conception is associated with an increased risk of preterm delivery and low birth weight. While most medications used to treat inflammatory bowel diseases are low risk, some precautions need to be taken and the risk-to-benefit ratio needs to be considered on an individualized basis. In general, aminosalicylates and thiopurines should be continued, but methotrexate is contraindicated. Anti-tumour necrosis factor agents are considered safe to continue but full monoclonal antibodies do cross the placenta. As a general rule, the it is important to counsel women that conception is optimal when disease is in remission, as adverse obstetrical outcomes are directly associated with disease activity. Clinicians need to educate patients before, during and after conception, emphasizing treatment compliance.

Pregnancy can pose a challenge to the physician caring for women with rheumatoid arthritis (RA). While many women with RA experience a spontaneous improvement in joint pain and inflammation during pregnancy, in others it remains active and they continue to need ongoing therapy. It is important to tailor the treatment regimen so that the disease is stabilized prior to conception and to use medications that are safe throughout pregnancy and lactation. The use of immunomodulating medications considered low risk during pregnancy allows for optimal outcomes. NSAIDs should be avoided in the third trimester. Corticosteroids may be used throughout pregnancy in the lowest effective dose. Antimalarial agents, sulfasalazine and azathioprine are safe options, but methotrexate and leflunomide are contraindicated as they are teratogenic and must, therefore, be withdrawn before a planned pregnancy. The risk for some of the newer biological therapies for RA is not necessarily their proven teratogenicity, but the absence of proven safety for the fetus. As such, it is recommended that abatacept, rituximab and tocilizumab be withheld prior to pregnancy; however, tumour necrosis factor inhibitors and anakinra may be continued until conception. In this review, we provide an overview of the RA treatment issues pre-conception, during pregnancy and in the post-partum period with respect to breastfeeding, and we provide guidelines for drugs that may be used relatively safely for RA management in pregnant women. Where available, pre-conception guidelines for men using these medications for RA are also discussed.

Patients with liver failure have menstrual cycle irregularities or amenorrhea. Liver transplantation restores menstrual pattern among women with cirrhosis in childbearing years. It is now accepted that a planned pregnancy is possible among liver transplant recipients at least 1 year after liver transplantation, with stable allograft function and under immunosuppressive regimens, to minimize the risks of preterm delivery and pregnancy-induced hypertension. After 1 year, the risk of graft loss decreases and is not related to pregnancy. It is a high-risk pregnancy which requires a specific and regular multidisciplinary joint follow-up (obstetrician, hepatologist, and anaesthesiologist), which leads in most cases to successful outcome for mother and child. But, early prevention and multidisciplinary management of the most common complications (pregnancy-induced hypertension, preeclampsia, and fetal growth restriction) is essential. The prematurity rate, maternal morbidity and mortality are higher than in the general population. Usual immunosuppressive treatments (corticoids, cyclosporine, tacrolimus, azathioprine or mycophenolate mofetil) may require dose adaptation during pregnancy. Immunosuppressive drugs are not teratogenic, but breast feeding is not allowed.

The aim of this article is to critically review available data regarding the safety of immunomodulators and biological therapies during pregnancy and breast-feeding in women with inflammatory bowel disease. Methotrexate and thalidomide can cause congenital anomalies and are contraindicated during pregnancy (and breast-feeding). Although thiopurines have a Food and Drug Administration (FDA) rating D, available data suggest that these drugs are safe and well tolerated during pregnancy. Although traditionally women receiving azathioprine or mercaptopurine have been discouraged from breast-feeding because of theoretical potential risks, it seems that these drugs may be safe in this scenario. Treatment with cyclosporine for steroid-refractory ulcerative colitis (UC) during pregnancy can be considered safe and effective, and the use of this drug should be considered in cases of severe UC as a means of avoiding urgent surgery. Breast-feeding is contraindicated for patients receiving cyclosporine. Biological therapies appear to be safe in pregnancy, as no increased risk of malformations has been demonstrated. Therefore, the limited clinical results available suggest that the benefits of infliximab and adalimumab in attaining response and maintaining remission in pregnant patients might outweigh the theoretical risks of drug exposure to the fetus. Stopping therapy in the third trimester may be considered, as it seems that transplacental transfer of infliximab is low prior to this. Certolizumab differs from infliximab and adalimumab in that it is a Fab fragment of an antitumor necrosis factor alpha monoclonal antibody, and therefore it may not be necessary to stop certolizumab in the third trimester. The use of infliximab is probably compatible with breast-feeding.

Young women with inflammatory bowel disease (IBD) pose a unique set of challenges. These women and their treating physicians must make difficult choices in matters regarding conception, pregnancy, and breastfeeding. This review highlights recent evidence and management issues that arise when taking care of women with IBD in terms of fertility, outcomes, and medication safety in pregnancy and breastfeeding. Ultimately, treatment must be individualized for each patient based on the available evidence and the woman's preferences.

Crohn's disease commonly affects women of childbearing age. Available data on Crohn's disease and pregnancy show that women with Crohn's disease can expect to conceive successfully, carry to term and deliver a healthy baby. Control of disease activity before conception and during pregnancy is critical, to optimize both maternal and fetal health. Generally speaking, pharmacological therapy for Crohn's disease during pregnancy is similar to pharmacological therapy for nonpregnant patients. Patients maintained in remission by way of pharmacological therapy should continue it throughout their pregnancy. Sulfasalazine, mesalazine and corticosteroids are safe, azathioprine and 6-mercaptopurine are reasonably safe with few discordant data, infliximab seems safe as well, whereas methotrexate is contraindicated during pregnancy. During breastfeeding, mesalazine and prednisone are considered safe, azathioprine/6-mercaptopurine, budesonide and infliximab probably safe and methotrexate is contraindicated.

In 90% of cases, women with rheumatoid arthritis suffer a disease flare within 3 months of delivery of their baby. Drug treatment is, therefore, required; however, such therapies have implications for mothers who decide to nurse their infants. Unfortunately, because of a paucity of data, little is known about the transfer of antirheumatic drugs into breast milk, and even less is known about whether small amounts of these agents ingested during nursing could harm the infant. Our review of the literature indicates that paracetamol, prednisone, antimalarial agents, sulfasalazine and most NSAIDs can safely be used by lactating mothers. Expert opinions differ regarding the use of azathioprine, ciclosporin, and methotrexate during lactation because of varying views on the potential for short-term and long-term adverse effects. Evidence regarding the transfer of leflunomide and biologic drugs into breast milk is insufficient; therefore, until more studies are conducted, the use of these drugs in breastfeeding mothers should be restricted. At present, many patients feel they have to choose between postpartum disease control and lactation. Extended studies of the transfer of antirheumatic drugs into breast milk and the resulting consequences are, therefore, urgently needed.

Traditionally, women receiving azathioprine have been discouraged from breastfeeding because of theoretical potential risks of neonatal bone marrow suppression, susceptibility to infection, and pancreatitis. The aims of this study were to measure the concentration of 6-mercaptopurine (6-MP) in breast milk of mothers receiving azathioprine and in the blood of their babies and to investigate any immunosuppressive effects on the babies. Women receiving azathioprine, who after appropriate counselling wished to breastfeed their babies, were approached for inclusion in the study. Breast milk samples were obtained from recruited women, and 6-MP levels were measured in each breast milk sample. Haemoglobin level, white cell and platelet counts, and 6-MP and 6-thioguanine nucleotides (6-TGN) levels were measured in the respective neonatal blood samples. Clinical signs of immunosuppression in the neonates were noted. Thirty-one breast milk samples were collected from ten women. Low concentrations of 6-MP (1.2 and 7.6 nanograms/ml, compared with therapeutic immunosuppressant level of 50 nanograms/ml in serum) were detected in two breast milk samples obtained from one woman. 6-MP was not detected in any of the other 29 samples. 6-MP and 6-TGN were undetectable in the neonatal blood. There were no clinical or haematological signs of immunosuppression in any of the ten neonates. We conclude that breastfeeding should not be withheld in infants of mothers receiving azathioprine.

Inflammatory bowel disease includes two primary disorders, ulcerative colitis and Crohn's disease. These diseases mainly affect young adults, with a peak occurrence between 15 and 25 years of age. The causes of these diseases are largely unknown, with current treatments targeted against the heightened inflammatory response witnessed in the intestinal mucosa of both conditions. With the peak age ranges for pregnancy and inflammatory bowel disease overlapping, it is important to weigh the benefits of treating a mother during pregnancy against the potential risks to the fetus and the course of the pregnancy. This review examines the current safety data on medications used in women with inflammatory bowel disease during pregnancy.

Care of pregnant women with multiple sclerosis (MS) is challenging because of the multiple physiological changes associated with pregnancy and the need to consider the impact of any intervention on the foetus. Pregnancy is associated with clinical MS stability or improvement, while the rate of relapse rises significantly during the first three months post-partum before coming back to its level prior to pregnancy. Gestational history has no influence on long-term disability and MS does not seem to influence pregnancy or the child's health. Apart from methotrexate and cyclophosphamide, most drugs used regularly to treat MS can safely be used by pregnant women. Intravenous steroids may be used with relative safety during pregnancy. Maternal use of azathioprine is not associated with an increased risk of congenital malformations, though impaired foetal immunity, intrauterine growth retardation and prematurity are occasionally observed. Cyclosporin is not teratogenic, but may be associated with growth retardation and prematurity. Pregnancy should be avoided in women treated with methotrexate because of its known abortifacient effects and risk of causing typical malformations. Cyclophosphamide is teratogenic in animals, but population studies have not conclusively demonstrated its teratogenicity in humans. Until information is available regarding safety, glatiramer acetate, mitoxantrone, interferon-beta-1a and interferon-beta-1b should be discontinued before an anticipated pregnancy. Women with MS are no more likely to experience delivery complications than are women without MS and the mode of delivery should be decided strictly on obstetrical criteria. Spinal, epidural and general anaesthesia can all be used safely in MS patients. Young women with MS who desire children can be reassured that their infants are not at increased risk of malformations, preterm delivery, low birth weight, or infant death. The progressive nature of the disease may motivate affected women to start or complete their families as soon as possible.

Successful pregnancy outcomes are possible after solid organ transplantation. While there are risks to mother and fetus, there has not been an increased incidence of malformations noted in the newborn of the transplant recipient. It is essential that there is closely coordinated care that involves the transplant team and an obstetrician in order to obtain a favourable outcome. Current data from the literature, as well as from reports from the National Transplantation Pregnancy Registry (NTPR), support the concept that immunosuppression be maintained at appropriate levels during pregnancy. At present, most immunosuppressive maintenance regimens include combination therapy, usually cyclosporin or tacrolimus based. Most female transplant recipients will be receiving maintenance therapy prior to and during pregnancy. For some agents, including monoclonal antibodies and mycophenolate mofetil, there is either no animal reproductive information or there are concerns about reproductive safety. The optimal (lowest risk) transplant recipient can be defined by pre-conception criteria which include good transplant graft function, no evidence of rejection, minimum 1 to 2 years post-transplant and no or well controlled hypertension. For these women pregnancy generally proceeds without significant adverse effects on mother and child. It is of note that the epidemiological data available to date on azathioprine-based regimens are favourable in the setting of a category D agent (i.e. one that can cause fetal harm). Thus, there is still much to learn regarding potential toxicities of immunosuppressive agents. The effect of improved immunosuppressive regimens which use newer or more potent (and potentially more toxic) agents will require further study.

This report summarizes experience with drugs prescribed for women with connective tissue disorders who either are anticipating childbearing, are pregnant or are breast-feeding. Principles of maintenance therapy are the same as when nonpregnant. Comparative trials of drugs during gestation are uncommon because of a lack of sufficient case numbers. It is difficult to distinguish between any additional risks from the medication, from any other drug and from the underlying disease. Symptoms of pregnancy may mimic side effects or toxic reactions to certain drugs. Each drug crosses the placenta, and any additional risk of spontaneous abortion, malformation or stillbirth is either negligible or unproven. Potential fetal problems with long-term intrauterine exposure to these drugs may include pancytopenia, immunosuppression, craniofacial abnormalities or restricted growth. These agents are transferred into breast milk in small quantities. Descriptions are provided of perinatal outcomes after in utero exposure to prednisone, aspirin, other nonsteroidal antiinflammatory drugs, antimalarials, gold salts, methotrexate, cyclophosphamide and azathioprine.

Pregnancies in women on dialysis and in women who have had renal transplant are no longer uncommon. Optimal obstetric outcomes require a multidisciplinary team approach, patient counseling, and clinicians who are knowledgeable and experienced in taking care of these patients. Counseling should begin before pregnancy, and all reproductive age women on dialysis and who have undergone renal transplant should receive family planning counseling. Preconceptional counseling should be provided to those patients who desire pregnancy. If the patient presents in early pregnancy, she should be informed about the maternal and fetal risks associated with her pregnancy. Prenatal care must include intensive surveillance for hypertension, preeclampsia, preterm labor, intrauterine growth restriction, anemia, infection, and renal allograft rejection. Aggressive treatment of complications is mandatory. There are limitations to our current knowledge about pregnancies in these patients. It is important for clinicians who provide care for these patients to be aware of these limitations when making obstetric management decisions. Cesarean section should be reserved for usual obstetric indications. Breast-feeding is not advised in patients taking cyclosporin or azathioprine. Transplant patients have unique gynecologic needs, so they should be encouraged to pursue follow-up gynecologic care after the pregnancy.

Women with ulcerative colitis (UC) are usually young and thus likely to undergo pregnancy. They should be advised to conceive when the disease is quiescent. Steroids and salicylates may be used normally during pregnancy, possibly without exceeding a dose of 2g/day for mesalazine. Azathioprine can be maintained if its indication is clear cut. Cyclosporin seems to be without additional risk in the pregnant woman, its use being limited to acute steroid-refractory disease, as an alternative to surgery.