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are safe options, but methotrexate and leflunomide are contraindicated as they are teratogenic and must, therefore, be withdrawn before a planned pregnancy.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.

Recommendations on breastfeeding under thiopurines are inconsistent due to limited data.To assess the risk of infections in offspring breastfed by mothers receiving azathioprine (AZA) for inflammatory bowel disease (IBD).Babies, who were breastfed from their mothers treated either with or without AZA were included from a local pregnancy-registry. Women were asked by structured personal interview on general development, infections, hospitalisations and vaccinations of their offspring.A group of 11 mothers taking AZA (median 150 mg/d) during pregnancy and lactation and another of 12 patients without using any immunosuppressive therapy breastfed 15 babies each for median 6 months and 8 months, respectively. Median age of children at time of interview was 3.3 and 4.7 years, respectively. All offspring showed age-appropriate mental and physical development. Infections were commonly seen childhood diseases. Similar rates were observed for most of the various infections between offspring with and without azathioprine exposure during breastfeeding. However, common cold more than two episodes/year and conjunctivitis were numerically more often reported in the group without AZA exposure. In an exploratory analysis no difference in the rate of hospitalisations was seen between exposed (0.06 hospitalisations/patient year) versus non-exposed children (0.12 hospitalisations/patient year, p=0.8)Our study which reports the largest number of babies breastfed with exposure to AZA suggests that breastfeeding does not increase the risk of infections.

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.

Thiopurines are widely used to maintain remission in inflammatory bowel disease. Treatment during pregnancy is generally recommended to improve the chance of a normal birth outcome, but advice concerning breastfeeding is conflicting. Aim To estimate the exposure of breastfed infants to 6-mercaptopurine, as a metabolite of azathioprine, from maternal milk.Eight lactating women with inflammatory bowel disease receiving maintenance therapy with azathioprine 75-200 mg daily were studied. Milk and plasma samples were obtained 30 and 60 min after drug administration and hourly for the following 5 h.The variation in the bioavailability of the drug was reflected in a wide range of peak plasma values of 6-mercaptopurine within the first 3 h. A similar curve, but with an hour's delay and at significantly lower concentrations varying from 2-50 microg/L, was seen in maternal milk. After 6 h an average of 10% of the peak values were measured.The major part of 6-mercaptopurine in breast milk is excreted within the first 4 h after drug intake. On the basis of maximum concentration measured, the infant ingests mercaptopurine of <0.008 mg/kg bodyweight/24 h. The findings confirm that breastfeeding during treatment with azathioprine seems safe and should be recommended, considering the extensive beneficial effects.

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 published studies there is a lack of data about the risks, management and how women with autoimmune hepatitis (AIH) decide on and are advised about pregnancy. The aim of this study was to investigate how women with AIH consider pregnancies, are advised and pharmacologically treated, as well as the outcome.A questionnaire was mailed to 128 women with AIH diagnosed during their fertile period and data from the Swedish National Birth Register was also used for matched controls.There was an 83% response rate to the questionnaires. Sixty-three pregnancies were reported by 35 women. 48% did not consult their doctors before getting pregnant. More than half of the women reduced or stopped the immune suppression during pregnancy or breastfeeding. Some women were advised to abstain from pregnancy or even to have an abortion. Caesarean sections were performed more frequently in the AIH group (16% compared with 6.5% in the control group p<0.01). There were no significant differences in the number of stillborn infants or infants with malformations. However, 30% of the patients experienced flare-up after delivery.In general, the outcome of pregnancy in women with AIH seems to be good. Current pharmacological treatment appears to be safe, including azathioprine during pregnancy and lactation. After delivery an active preparedness to increase pharmacotherapy should be considered.

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.