The highest incidence of inflammatory bowel disease (IBD) is seen between the second and fourth decades of life, which is the most fertile age for women. Increased disease activity has been shown to effect female fertility and pregnancy outcomes, stressing the need for drugs that can safely induce and maintain clinical remission without harming either the mother or fetus.

Anti-TNF-α agents have been shown to be effective in both inducing and maintaining remission among IBD patients. This review highlights the results of previous studies conducted on pregnant women who were exposed to anti-TNF-α agents during the course of their pregnancy. The drugs reviewed include infliximab (IFX), adalimumab (ADA), certolizumab pegol (CZP) and golimumab (GMB). Of > 200 articles reviewed, 105 were included in the manuscript based on relevance. The keywords used were anti-TNF, infliximab, adalimumab, certolizumab, golimumab, biologics, pregnancy and inflammatory bowel disease.

Anti-TNF agents have been studied extensively during pregnancy from the early case reports to the more recent prospective Pregnancy in IBD and Neonatal Outcomes study. A comprehensive review of the literature has shown that biologics can be safely used during pregnancy. In view of this safety data, it is recommended to maintain therapy during pregnancy.

Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease of synovial joints, can lead to chronic pain and structural joint damage, as well as other organ involvement, especially if not adequately controlled. Because it can affect women in their reproductive years, care of pregnant women with RA requires a delicate balance of maintaining disease control while limiting potential toxicity to the fetus and neonate. While most women experience a substantial improvement in disease activity during pregnancy, for some women their RA remains active. It can even manifest itself for the first time during pregnancy or early in the post-partum period. Optimizing disease control prior to conception is key, but utilizing disease-modifying treatments effectively and safely throughout pregnancy and lactation requires open dialogue and shared decision making. This review provides evidence-based recommendations for use of disease-modifying antirheumatic drugs (DMARDs) and biologic response modifiers to guide rheumatologists in their care of pregnant and lactating women with RA and serves as a guide to counsel male patients with RA on family planning decisions.

Biologic therapies, including anti-tumor necrosis factor antibody therapy and anti-integrin antibodies, are currently approved for the treatment of and are increasingly being used in patients with moderate to severe inflammatory bowel disease, including Crohn disease and ulcerative colitis. Because patients who require these medications are often in their child-bearing years, knowledge of the safety of these medications before and after pregnancy is imperative. This article summarizes the available data regarding the use of biologic therapy during and after pregnancy, highlighting such issues as safety for mother and newborn, length of medication use during pregnancy, and breastfeeding after pregnancy while on biologic therapy.

The safety of anti-tumour necrosis factor (TNF) agents during pregnancy is a major concern for child-bearing women and physicians.

To assess the impact of anti-TNF therapy on adverse pregnancy and foetal outcomes in women with inflammatory bowel disease (IBD).

Pregnancies occurring during anti-TNF treatment or less than 3 months after its cessation in IBD patients followed in GETAID centres were recorded from January 2009 to December 2010. Ninety-nine pregnancies in women without anti-TNF treatment were identified from the CESAME registry. We compared pregnancy and neonatal outcomes by a case-control study.

In the 124 IBD patients followed, 133 pregnancies were reported. At the conception time, 23% of patients had active disease. Eighty-eight per cent (n = 117) of the 133 pregnancies followed until delivery resulted in 118 liveborns (one twin pregnancy). Complications were observed in 47 (35%) women and 24 (20%) newborns. In multivariate analysis, factors associated with pregnancy complications were: current smoking (P = 0.004), a B2 (stenotic) phenotype in CD women (P = 0.004), occurrence of a flare during pregnancy (P = 0.006) and a past history of complicated pregnancy (P = 0.007). Current smoking was the only factor associated with severe (i.e. potentially lethal) pregnancy complications (P = 0.02). Having IBD for more than 10 years prior to conception was associated with newborn complications (P = 0.007). No difference was found with the control group for any of the pregnancy and neonatal outcomes.

In our series, the safety profile of anti-TNF therapy during pregnancy and the neonatal period appears similar to control group of IBD women not treated with anti-TNF therapy.

IBD often affects patients during their peak reproductive years. Several drugs are available for the treatment of IBD and new drugs are continuously in the pipeline. As long-term administration of medications is often necessary, the safety of drug therapy during pregnancy and breast-feeding needs to be considered in daily clinical practice. The aim of this Review is to summarize the latest information concerning the safety of medications used to treat IBD during pregnancy and lactation, as well as their effect on fertility. Although only thalidomide and methotrexate are absolutely contraindicated during pregnancy and breast-feeding, alternatives to ciprofloxacin, natalizumab and sodium phosphate should also be considered for pregnant women. Breast-feeding is also discouraged while on treatment with ciclosporin, metronidazole and ciprofloxacin. However, therapy with 5-aminosalicylic acid preparations, glucocorticoids, thiopurines and TNF inhibitors are acceptable during pregnancy and lactation. Pregnant women who have symptomatic IBD or who require therapy should have the opportunity to discuss any associated risks to their pregnancy and infant with the appropriate consultants. By ensuring that the patient and her family are informed, the clinical outcome might be optimized.

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.

Anti-tumor necrosis factor (TNF) drugs are an effective therapeutic option in patients with inflammatory bowel disease (IBD). However, data regarding their safety during pregnancy and breastfeeding are scarce. The aim of this study was to critically review available data on the safety of anti-TNF therapy during pregnancy and breastfeeding in women with IBD.

Bibliographical searches (MEDLINE) up to January 2013.

The studies included provided data from 462 women with IBD exposed to anti-TNF agents during pregnancy. Although these drugs cross the placenta from the end of the second trimester, they are low-risk in the short term. The use of anti-TNF agents after the second trimester leads to intra-uterine exposure. An increase in infections has recently been observed in infants exposed to immunomodulators plus anti-TNF drugs in utero, thus raising concerns about the consequences for the development of the immune system. Accordingly, it has recently been suggested that anti-TNF drugs should be stopped during the second trimester. Certolizumab is a Fab fragment of an anti-TNF monoclonal antibody, and, therefore, it may not be necessary to stop it during pregnancy. Anti-TNF drugs have been detected in breast milk, although in miniscule amounts. Case reports do not suggest toxicity; however, the effects of exposure on the neonate merit further investigation.

Anti-TNF drugs can cross the placenta from the latter part of the second trimester of gestation, although they seem to be safe, at least in the short term. Miniscule amounts of anti-TNF drugs are transferred in breast milk; therefore, a deleterious effect of this exposure on the neonate, although unlikely, cannot be excluded.

Tumor necrosis factor (TNF)-α inhibitors are increasingly being used in inflammatory bowel disease (IBD). Because this chronic intestinal disorder often affects women of fertile age, it is essential to assess the effect of biologics on pregnancy outcome.

We performed a systematic review of the English-language literature to investigate if treatment with TNF-α blockers during pregnancy in women with IBD increases the risk of spontaneous abortions, preterm delivery, stillbirth, low birth weight, congenital malformations, or risk of infections in the offspring. Of 552 articles and abstracts reviewed, 58 articles or abstracts with unique content were identified and included in this systematic review. However, most presentations were case reports or case series supplied by a limited number of observational studies. No randomized controlled studies were available.

TNF-α inhibitors do not seem to affect either outcome of pregnancy in mothers with IBD, or the outcome in the offspring (congenital malformations and immunosuppression). Further, recent data have not identified any increased risk of infections in the first year of life in the offspring of mothers who received biologics, even in combination with immunomodulators (thiopurines).

From the present systematic review, no association was found between administration of TNF inhibitors for IBD during pregnancy and adverse pregnancy outcome or congenital abnormalities. Further, no increased relative risk of infections has been reported in the first year of life in offspring of mothers who received biologics. Biologics should be discontinued during pregnancy solely if the IBD is in remission using the same stopping criteria as for patients with IBD in general, as uncontrolled activity of IBD may expose the mother and child to a risk greater than those only potentially coming from the use of TNF-α inhibitors. In such cases, inoculation of the offspring with live vaccines is contraindicated until the biologic agent is no longer detectable in the child's circulation.

Tumor necrosis factor (TNF) inhibitors are useful in the treatment of numerous inflammatory and immunologic disorders. Since many of these conditions occur in women of childbearing age, safety during pregnancy and breastfeeding is of considerable importance.

This paper is a review of the literature on the safety of TNF inhibitors during pregnancy and breastfeeding published between 2001 and 2011.

TNF inhibitors do not appear to be associated with a high risk of teratogenicity or intrauterine death. However, a small magnitude increase in risk cannot be ruled out given the paucity of data on the subject. Although TNF inhibitor use may be associated with a higher rate of preterm delivery, this may in fact be due to an active, underlying disease. Therefore, the decision to use these medications should be made on a case-by-case basis. If the disease cannot be managed with first line agents, TNF inhibitors may be helpful in reducing the number of disease exacerbations. Nevertheless, when using TNF inhibitors, it is prudent to discontinue treatment around the third trimester when transfer across the placenta is greatest and to restart postpartum.

It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn's disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant.

Anti-TNFα treatments have modified the medical care, the course and the quality of life of the patients with autoimmune rheumatic, cutaneous or bowel inflammatory diseases. On the other hand, these treatments may have potential severe side effects during pregnancy (congenital malformations, fetal infections). Actually, many pregnancies have been reported during anti-TNFα exposures, with good maternal and neonatal outcomes. The introduction or the discontinuation of these treatments will always have to be discussed with the specialist of the chronic disease and, ideally, during a preconceptional counselling. In gynecology, anti-TNFα drugs may offer a new safe and effective approach to treating patients with recurrent miscarriages or unexplained or failed in vitro fertilization cycles. On the other hand, these treatments significantly increase the risk for serious infections or viral reactivations and may promote gynaecological malignancies. An adapted gynaecological survey is necessary.

Due to limited human pregnancy experience safety issues in regard to children exposed antenatally to biological drugs are still under debate. A survey of new published experience on biological agents during pregnancy is necessary to assist clinicians with adequate counseling and management of patients who desire children.

No controlled study has been published on use of TNFα inhibitors, rituximab, abatacept, tocilizumab or anakinra in pregnancy during the years 2009-2010. New case reports confirm that all monoclonal antibodies expose the child to the full adult dose when administered in late pregnancy with a risk for adverse effects in the newborn and perinatally. Data from a drug registry show that preconceptional and early first-trimester use of rituximab appears to confer no serious side effect to the child. Case reports on abatacept, tocilizumab or anakinra in pregnancy are not conclusive.

Differences in molecular structure of TNFα inhibitors may turn out to favor the use of agents that are not complete monoclonal antibodies in women who consider pregnancy. The very limited experience with abatacept, tocilizumab or anakinra in pregnancy allows no statement as to their compatibility with pregnancy. At present use of biological agents throughout pregnancy cannot be recommended.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are invalidating inflammatory affections, which evolve by relapse interrupted with clinical remission. Crohn's disease commonly affects young women in their reproductive years with a peak of incidence between 20 and 30. Infertility and sexual dysfunction are equivalent to that of the general population while they are increasing in patients with active IBD or after colorectal surgery. IBD are well controlled by medical treatments and the frequency of relapse during the pregnancy is similar to that of the non-pregnant IBD patients. The data concerning the risk of congenital malformations in IBD are contradictory. The risk of preterm delivery and low birth weight is significantly increased and correlated to the disease activity. When a medical treatment insures a quiescent disease before the pregnancy, it is advisable to continue it during the pregnancy because the benefits of controlled disease outweigh the risks of medication. IBD, possible perianal lesions and colorectal surgical interventions influence the mode of delivery, but the indication of caesarean section should primarily be governed by obstetric necessity. Preconceptional counseling seems desirable because of the risks during pregnancy, according to the disease activity, the surgical histories and the therapeutic agents.

Rheumatoid arthritis is a disease that is highly prevalent in women of childbearing age. A review is done about the characteristics of the placental barrier, the passage of drugs through it and the use of drugs during pregnancy: those which are potentially safe drugs, those drugs that can only be used if there is a life threatening condition for the mother, drugs that are contraindicated and those with insufficient data on safety and therefore should be avoided, the latter group comprises biological drugs. Also a review is done about the use of drugs during lactation, a period that a flare of rheumatoid arthritis can occur.

Inflammatory bowel disease (IBD), most commonly referring to Crohn's disease and ulcerative colitis, is a chronic and disabling condition with an increasing incidence in southern Europe. The etiology of IBD remains unknown, but the characteristic disproportionate inflammatory response in the gut may develop through various mechanisms at the cellular and subcellular level. Tumor necrosis factor (TNF) alpha is one crucial mediator of this abnormal immune response, and in recent years, biological therapies targeting TNFα have significantly improved the management of IBD refractory to conventional therapies. Infliximab is the best studied anti-TNFα agent, and is currently approved in the European Union for adults and children with Crohn's disease and adults with ulcerative colitis; adalimumab is indicated for Crohn's disease in adults but not children, while certolizumab was not approved in the European Union for Crohn's disease. Infliximab has confirmed efficacy in adults with Crohn's disease (including fistulizing disease) and ulcerative colitis, with benefits observed in both clinical remission and mucosal healing, it is similarly effective in children with Crohn's disease. Evidence suggests that early treatment with infliximab may improve the natural course of the disease. Adalimumab showed efficacy in adults with Crohn's disease and more limited data suggest efficacy in children with Crohn's disease. Although certolizumab pegol has also shown promising data in adults with Crohn's disease, data in children are lacking. Anti-TNFα agents are generally well tolerated, although careful monitoring for adverse events such as infections, infusion reactions, lymphomas and demyelinating diseases is warranted. A definitive causal relationship between anti-TNFα agents and various adverse events is difficult to establish, as the underlying disease and concomitant immunosuppression also predispose patients to such events. Infliximab has not been associated with an increased incidence of serious events, and adalimumab and certolizumab are also generally well tolerated in clinical trials. Both adalimumab and certolizumab pegol are associated with lower levels of drug antibodies compared with infliximab. Reactivation of latent tuberculosis is a potential risk with any anti-TNFα agent, and identification and treatment is required before initiating therapy. Although causal relationships are difficult to establish, caution is advised with anti-TNFα compounds in patients developing neurological symptoms suggestive of demyelinating disease, or in those at high risk of malignancy. Infliximab is also generally well tolerated in children; however, data are scarce for the other compounds. No increased risks associated with pregnancy have been observed for infliximab or adalimumab, but caution in pregnancy and during breast-feeding is currently advocated. In terms of future research, more long-term data are needed for both certolizumab pegol in Crohn's disease and adalimumab in ulcerative colitis. More research on the benefits of early biological treatment on disease progression is needed. In summary, the anti-TNFα inhibitors represent a momentous advance in the treatment of Crohn's disease and ulcerative colitis refractory to conventional treatments. They offer significant benefits in quality of life and mucosal healing, and may have the potential to change the evolution of the disease when given early.

Crohn disease and ulcerative colitis commonly affect women in their childbearing years. Fortunately, advances in the field of inflammatory bowel disease have made successful pregnancy outcomes a reality for many women. These advances have led to family planning as a common discussion between gastroenterologists and inflammatory bowel disease patients. Common discussion topics are fertility, conception, medication safety, pregnancy, delivery, and breastfeeding although there are limited available data. Education and patient awareness have become vital factors in successful pregnancy outcomes.

Over the past years, biological therapies, especially anti-TNF-α antibody therapy has emerged as a treatment approach in patients who have failed to achieve or maintain remission with tradional DMARDs. Women suffering from inflammatory arthritis may need to continue therapy throughout pregnancy and/or in the lactation period, hence the increased concern over the safety of antirheumatic drugs during pregnancy. Anti-TNF agents fall within the US FDA category B concerning fetal risk, indicating that no adequate and well-controlled studies have been conducted in pregnant or lactating women. However, in the last decade, numerous case series and registry data of pregnancies exposed to anti-TNF therapy have accumulated in the literature. According to these data, TNF inhibitor therapies appear to be safe in pregnancy, since no increased risk of malformations has been demonstrated. Ceasing therapy after conception should be considered, but treatment may be continued during pregnancy when indicated.The use of these agents is likely compatible with breast-feeding. The extent of fetal risk is not clarified for exposure to other biologics, such as Rituximab.

Disease modifying antirheumatic drugs are being increasingly utilized in the treatment of many autoimmune disorders. TNF-alpha antagonists have become the standard of care in treating many of these autoimmune diseases. Because these autoimmune disorders often affect women in their childbearing years, the safety of anti-TNF therapy in pregnancy becomes important.

We critically review the current literature on anti-TNF therapy safety in pregnancy. The available data regarding the anti-TNFs in the setting of pregnancy from 1999 to the present are reviewed.

Case reports and small case series have produced conflicting results, yet their results should only be viewed with cautious interest. Two database reviews suggest little to no risk of congenital anomalies, whereas a much larger independent review of the FDA database reveals congenital anomalies born to mothers who were exposed to anti-TNFs during pregnancy. An ongoing prospective registry (Organization of Teratology Information Services) suggests that about 7 - 10% of children born to mothers taking a TNF antagonist during pregnancy are born with congenital anomalies.

Whether or not these data represent a significant increase, or if a definitive pattern of birth defects exists, remains in question. All these sources have limitations, which are discussed. Further studies are needed to definitively determine the safety and role of anti-TNFs in pregnancy.

The socioeconomic burden of psoriatic arthritis (PsA) is considerable and not different from that of rheumatoid arthritis. Current treatment options do not always allow reaching the therapeutic objectives consisting of the remission of symptoms and prevention of the appearance of damage in the early stage of PsA or the blocking of PsA progression in the established cases.

After reviewing the current treatment choices, we examine the new drugs in clinical Phase II and III trials for PsA up to January 2010. Information was mainly obtained from the network of international clinical trial registries.

The current management of PsA includes NSAIDs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-alpha blocking agents. These last drugs are more effective than traditional DMARDs on symptoms/signs of inflammation, quality of life and function and can inhibit the progression of the structural joint damage. Recent advancement in the knowledge of the immunopathogenesis of PsA has permitted the development of novel drugs including new TNF-alpha blockers, IL-1, -6, -12, -23 and -17 inhibitors, co-stimulator modulation inhibitors, B-cell depleting agents, small molecules and receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand inhibitors.

The currently available anti-TNF-alpha blocking agents have revolutionized the management of PsA. However, there is a need for more effective and safer drugs.

Anti-TNFα medications have led to vast improvements in the treatment of inflammatory conditions, including rheumatoid arthritis and Crohn's disease. As these diseases often afflict women in their reproductive years, the safety of these drugs during pregnancy is an important issue. Prospectively collected data thus far appear to be reassuring; however an analysis of the FDA-reported anomalies has raised some questions. It appears that significant levels of these drugs cross the placenta as the pregnancy nears term, but little is passed through breast milk. Prior to using these medications during pregnancy, the risks and benefits of these drugs, other treatment options, and the ongoing inflammatory condition all must be carefully weighed by both doctor and patient.

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.

This review covers important questions that arise for physicians caring for women with inflammatory bowel disease. Fertility, pregnancy outcomes and the safety of medications in pregnancy and lactation are discussed.

This review covers important questions that arise for physicians caring for women with inflammatory bowel disease. Fertility, pregnancy outcomes and the safety of medications in pregnancy and lactation are discussed.