The need for a disease-specific prospective pregnancy registry for multiple sclerosis (MS).

Multiple sclerosis (MS) is the most commonly acquired neurological disorder affecting young adults of reproductive age with an approximately 3:1 female to male ratio. Although pregnancy is not contraindicated in MS, data are limited regarding pregnancy outcome among MS patients, and the safety or risk to the fetus associated with most maternal MS treatments, such as disease modifying therapies (DMTs), during pregnancy is unknown. We review available epidemiological and registry data on MS and pregnancy and discuss the need to initiate a North American Multiple Sclerosis Pregnancy Registry that will prospectively identify pregnancies in women with MS, obtain information on the disease, and its treatment during gestation and lactation and follow the children to determine their health status.

Breast-feeding after transplantation.

Transplantation affords recipients the potential for a full life and, for some, parenthood. Female transplant recipients must continue to take immunosuppression during pregnancy and breast-feeding. This article reviews case and series reports regarding breast-feeding in those taking transplant medications. Avoidance of breast-feeding has been the customary advice because of the potential adverse effects of immunosuppressive exposure on the infant. Subsequent studies have demonstrated that not all medication exposure translates to risk for the infant, that the exposure in utero is greater than via breast milk and that no lingering effects due to breast-feeding have been found to date in infants who were breast-fed while their mothers were taking prednisone, azathioprine, cyclosporine, and/or tacrolimus. Thus, except for those medications where clinical information is inadequate (mycophenolic acid products, sirolimus, everolimus, and belatacept), the recommendation for transplant recipients regarding breast-feeding has evolved into one that is cautiously optimistic.

Immunosuppressive drugs and fetal outcome.

Successful pregnancies have been reported in all types of solid-organ transplant recipients on a variety of immunosuppressive regimens. Immunosuppression is essential to maintain the transplanted organ and maternal health, thus the safety of these medications continues to be studied. This article reviews information in the literature and data from the National Transplantation Pregnancy Registry (NTPR) in the United States related to immunosuppressive medication and pregnancy. Although most maintenance immunosuppressive regimens have not been shown to affect the outcome of posttransplant pregnancies, mycophenolic acid products are associated with an increased incidence of spontaneous abortion and an increase in the incidence and a specific pattern of birth defects. When counseling transplant recipients about the prospect and safety of pregnancy, the health of the mother, her graft, and the developing fetus must all be taken into account.

Complex chimerism: pregnancy after solid organ transplantation.

Thousands of women with organ transplantation have undergone successful pregnancies, however little is known about how the profound immunologic changes associated with pregnancy might influence tolerance or rejection of the allograft. Pregnant women with a solid organ transplant are complex chimeras with multiple foreign cell populations from the donor organ, fetus, and mother of the pregnant woman. We consider the impact of complex chimerism and pregnancy-associated immunologic changes on tolerance of the allograft both during pregnancy and the postpartum period. Mechanisms of allograft tolerance are likely dynamic during pregnancy and affected by the influx of fetal microchimeric cells, HLA relationships (between the fetus, pregnant woman and/or donor), peripheral T cell tolerance to fetal cells, and fetal minor histocompatibility antigens. Further research is necessary to understand the complex immunology during pregnancy and the postpartum period of women with a solid organ transplant.

Breastfeeding and tacrolimus: is it a reasonable approach?

Successful pregnancy after transplantation has become more common and more recipients are choosing to breastfeed their infants, despite the controversy surrounding the safety of breastfeeding while the mother is taking immunosuppressive medications, such as tacrolimus. Data collected to date by the National Transplantation Pregnancy Registry have not revealed specific problems related to breastfeeding; however, individual circumstances must be considered when counseling transplant recipients regarding breastfeeding. Bramham et al. reported on a series of transplant recipients who were maintained on tacrolimus during pregnancy and lactation and concluded that women should not be discouraged from breastfeeding while on tacrolimus. Recently, other authors have also supported the option of breastfeeding while recipients are maintained on tacrolimus. Herein, we review the Bramham article and discuss the key issues to be considered regarding the compatibility of breastfeeding and immunosuppression.

Safety considerations: breastfeeding after transplant.

Organ transplant is an effective treatment for end-stage organ failure. For women, restoration of organ function can restore fertility and the ability to successfully carry a pregnancy. Posttransplant pregnancies have been reported among recipients of all types of solid organ transplants via case and center reports plus registry data. Stable graft function is dependent on prevention of rejection, currently accomplished by using maintenance immunosuppressant medications, to which the fetus is exposed in utero. Common among neonatal outcomes in transplant recipients are preterm and low-birth-weight infants. Emotional, nutritional, and immunologic benefits of breastfeeding have been well-documented and could be valuable for these newborns. Concern must be directed at the effects of the child's exposure to immunosuppressive agents excreted into the breast milk. Breastfeeding could be considered in transplant recipients if it can be shown that the level of exposure does not result in risks to the newborn, immediately and throughout childhood. Despite concerns of health care professionals, some recipients have chosen to breastfeed. Breastfeeding after transplant must be approached with consideration of many issues, and the potential risks require further study. This review focuses on benefits of breastfeeding, common immunosuppressive agents used in organ transplant recipients, a summary of the reports of women who have breastfed their infants while on immunosuppressive therapy and the published studies on breastfeeding and immunosuppressive agents. Recommendations are provided to guide health care professionals to help mothers receiving immunosuppressive agents to make informed choices about breastfeeding their infants.

Outcomes of pregnancies fathered by solid-organ transplant recipients exposed to mycophenolic acid products.

CONTEXT-In women, exposure to mycophenolic acid products during pregnancy results in an increase in both miscarriages and birth defects in the live born. OBJECTIVE-To describe the outcomes of pregnancies fathered by transplant recipients who were being maintained on mycophenolic acid products at the estimated time of conception and compare these pregnancies with pregnancies in the general population. METHODS- Data were collected by the National Transplantation Pregnancy Registry via questionnaires, telephone interviews, and medical records. RESULTS -One hundred fifty-two male transplant recipients with exposure to mycophenolic acid products fathered 205 pregnancies (208 outcomes, including 3 pairs of twins). Pregnancy outcomes included 194 live births with a prematurity rate of 10.8%, 14 spontaneous abortions, and no therapeutic abortions or stillbirths. Among the live births, 6 malformations were reported, for an incidence of 3.1%. No pattern of malformations was identified. CONCLUSION-The outcomes of pregnancies fathered by transplant recipients treated with mycophenolic acid products appear similar to outcomes in the general population.

Pregnancy after solid organ transplantation: a guide for obstetric management.

Successful pregnancy outcomes are possible among all solid organ transplant recipients. Patients should be fully counseled regarding the potential adverse fetal outcomes, including prematurity and low birth weight. Transplant recipients are at an increased risk for both maternal and neonatal complications and should be seen by a high-risk obstetrician in conjunction with their transplant teams. Ideally, preconception counseling begins during the pretransplantation evaluation process. Initiating contraception early after transplantation is ideal, and long-acting reversible methods such as intrauterine devices and subdermal implants may be preferred. Pregnancy should be avoided for at least 1 year after transplantation to limit the potential risks of early pregnancy that may adversely affect both allograft function and fetal well-being. Hypertension, diabetes, and infection should be monitored and treated to minimize fetal risks during pregnancy. Maintenance of current immunosuppression is usually recommended, with the exception of mycophenolic acid products, which (when possible) should be discontinued before conception and replaced with an alternative medication. Throughout pregnancy, immunosuppression must be maintained at appropriate dosing to avoid graft rejection. During labor and delivery, cesarean delivery should be performed for obstetric reasons only. A multidisciplinary team should manage pregnant transplant recipients before, during, and following pregnancy. Breastfeeding and long-term in utero exposure to immunosuppressants for offspring of transplant recipients continue to require further investigation but have been encouraged by recent reports. Continued reporting of post-transplantation pregnancy outcomes to the National Transplantation Pregnancy Registry is highly encouraged.

Pregnancy after lung transplant.

The purpose of this study was to analyze pregnancy outcomes in female lung transplant recipients. Data were collected from the National Transplantation Pregnancy Registry via questionnaires, interviews, and hospital records. Twenty-one female lung recipients reported 30 pregnancies with 32 outcomes (1 triplet pregnancy). Outcomes included 18 live births, 5 therapeutic abortions, and 9 spontaneous abortions. No stillbirths or ectopic pregnancies were reported. Mean (SD) interval from transplant to conception was 3.6 (3.3) years (range, 0.1-11.3 years). Comorbid conditions during pregnancy included hypertension in 16, infections in 7, diabetes in 7, preeclampsia in 1, and rejection in 5 women. Ten of the 21 recipients received a transplant because of cystic fibrosis and accounted for 12 pregnancy outcomes (7 live births, 3 spontaneous abortions, and 2 therapeutic abortions). At last recipient contact, 13 had adequate function, 2 had reduced function, 5 recipients had died (2 with cystic fibrosis), and 1 recipient had a nonfunctioning transplant. Mean gestational age of the newborn was 33.9 (SD, 5.2) weeks, and 11 were born preterm (<37 weeks). Mean birthweight was 2206 (SD, 936) g and 11 were low birthweight (<2500 g). Two neonatal deaths were associated with a triplet pregnancy; one fetus spontaneously aborted at 14 weeks and 2 died after preterm birth at 22 weeks. At last follow-up, all 16 surviving children were reported healthy and developing well. Successful pregnancy is possible after lung transplant, even among recipients with a diagnosis of cystic fibrosis.

Pregnancy after cardiac transplantation.

More women are reporting pregnancy following heart transplantation. Although successful outcomes have been reported for the mother, transplanted heart, and newborn, such pregnancies should be considered high risk. Hypertension, preeclampsia, and infection should be treated. Vaginal delivery is recommended unless cesarean section is obstetrically necessary. Most outcomes are live births, and long-term follow-up of children show most are healthy and developing well. Maternal survival, independent of pregnancy-related events, should be part of prepregnancy counseling.

Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation.

With the constant advent of new developments and modifications in immunosuppressive regimens, clinicians are responsible for providing pregnancy counseling to all pre and posttransplant recipients of childbearing age. As individual physicians and centers accrue experience with these major therapeutic decisions, it is critical that both positive and negative outcomes be reported in appropriate settings-symposia, meetings, publications, and registries. The NTPR has acquired experience with 2000 pregnancy outcomes in female transplant recipients. For the NTPR's largest group, female kidney recipients, 71-76% of the pregnancies produce a livebirth. For the other organs combined, the livebirth likelihood ranges from 50-86%. The incidence of birth defects in the liveborn appears similar to the general population, except for pregnancies with MPA exposure that have a 23% incidence of birth defects. Long-term follow-up of the offspring of transplant recipients has provided reassurance after 20 years of observation. The continued recording of data in registries such as the NTPR is essential for assessing the safety of pregnancy in solid organ transplant recipients. Key benefits of the NTPR are the personal contact between registry staff and participants, the wide range of pregnancy-related variables that are analyzed, and the opportunity for health-care providers to obtain information that helps them care for transplant recipients on a case-by-case basis.

Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation.

With the constant advent of new developments and modifications in immunosuppressive regimens, clinicians are responsible for providing pregnancy counseling in all pre- and post-transplant recipients of childbearing age. As individual physicians and centers accrue experience with these major therapeutic decisions, it is critical that both positive and negative outcomes be reported in appropriate settings-symposia, meetings, publications, and registries. Future analyses from the NTPR are directed at potential effects of newer immunosuppressive regimens, not only from immediate exposure, but also from continued exposures such as may occur from breastfeeding. As the registry study design allows for contact between registry staff and recipients and their health care providers, efforts are ongoing to analyze long-term outcomes of parent and child. Continued close collaboration among specialists will help to better identify potential pregnancy risks in these populations, particularly as new immunosuppressive agents are developed. Therefore, centers are encouraged to report all pregnancy exposures in transplant recipients to the NTPR.

Pregnancy after transplantation.

The National Transplantation Pregnancy Registry (NTPR) was established in 1991 to study the outcomes of pregnancies in female transplant recipients and pregnancies fathered by male transplant recipients. Data from the NTPR have helped to endorse the reassurances from publications of smaller experiences that successful pregnancies are possible in the transplant population. In our last review for this journal (2000), we noted that important future issues would include the reassessment of prepregnancy guidelines, gestational and organ-specific problems, the role of new immunosuppressive drugs, and the long-term effects of pregnancy on both graft and child. Data collected by the NTPR over the last 7 years have addressed these issues, thus providing additional information for health care providers of transplant recipients of childbearing age. There has been some refinement of prepregnancy guidelines, but there is a need for additional data collection so that organ-specific outcomes and risks can further be identified. To date, the outcomes of the children followed have been encouraging, and specific remote effects have not been identified, but continued surveillance is still vital. Of special concern are the new immunosuppressive drugs, specifically for mycophenolate mofetil (CellCept, Roche Laboratories Inc., Nutley, New Jersey), where data reported to the NTPR and through postmarketing surveillance have shown an increased incidence of nonviable outcomes and a specific pattern and increased incidence of malformation in the newborn, which has resulted in a pregnancy category change. Newer information points to an increased need for vigilance among centers and continued monitoring of pregnancy outcomes in this population. As the first reported pregnancy after transplantation occurred in a kidney recipient 50 years ago, in March 1958, this review also highlights the first reported pregnancies in other solid organ recipients.

Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation.

With the constant advent of new developments and modifications in immunosuppressive regimens, clinicians are responsible for providing pregnancy counseling in all pre and post-transplant patients of childbearing age. As individual physicians and centers accrue experience with these major therapeutic decisions, it is critical that both positive and negative outcomes be reported in appropriate settings-symposia, meetings, publications, and registries. Future analyses from the NTPR are directed at potential effects of newer immunosuppressive regimens, not only from immediate exposure, but also from continued exposures such as may occur from breastfeeding. As the registry study design allows for contact between registry staff and recipients and their health care providers, efforts are ongoing to analyze long-term outcomes of parent and child. Continued close collaboration among specialists will help to identify potential pregnancy risks in these populations, particularly as new immunosuppressive agents are developed. Therefore, centers are encouraged to report all pregnancy exposures in transplant recipients to the NTPR. The 50th anniversary of the first post-transplant pregnancy (reported by Joseph Murray et al. (32)) that occurred in March of 2008 helped to raise awareness of the need for continued worldwide cooperation for data collection. Enhanced assessment of pregnancy safety is essential to the development of guidelines for counseling and management of pregnancy in the transplant population.

Nutrition, pregnancy, and transplantation.

One benefit of transplantation, along with the restoration of health, is the opportunity for successful pregnancies. A growing number of pregnancies have been reported among all types of solid-organ recipients. There is an increasing need for practice guidelines that include nutrition information in order to assist practitioners caring for and counseling these high-risk patients. In the transplant community, guidelines for managing pregnancies in transplant recipients have been evolving but lack specific nutrition recommendations. As for all pregnancies, there is a need to optimize nutrition for the mother and her infant, with additional consideration given to the transplant recipient's graft. This article reviews outcomes of posttransplant pregnancies and management guidelines, with special emphasis on nutrition in this unique population.

Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation.

From the first reports of pregnancy in each of the organ groups to the present, concerns varied and were specific to the type of transplant. Organ-specific issues still require additional attention and analyses. Lung recipients appear at greatest risk for poorer pregnancy outcomes. Given these ongoing concerns and the constant advent of new developments, clinicians are responsible for providing pregnancy counseling in all pre- and posttransplant recipients of childbearing age. As individual physicians and centers accrue experience with these major therapeutic decisions, it is critical that both positive and negative outcomes be reported in appropriate settings-symposia, meetings, publications, and registries. Future analyses from the NTPR are directed at potential effects of newer immunosuppressive regimens, not only from immediate exposure, but also from continued exposures such as may occur from breastfeeding. As the registry study design allows for contact between registry staff and recipients and their health care providers, efforts are ongoing to analyze long-term outcomes of parent and child. Continued close collaboration among specialists will help to identify potential pregnancy risks in these populations, particularly as new immunosuppressive agents are developed. Therefore, centers are encouraged to report all pregnancy exposures in transplant recipients to the NTPR. The 50th anniversary of the first posttransplant pregnancy (reported by Joseph Murray, et al. (11)) was in March 2008. With this important landmark event and with ongoing pregnancy issues concerning posttransplant pregnancy safety, this is an ideal time to raise the awareness of the need for continued worldwide cooperation for data collection. Enhanced assessment of pregnancy safety is essential to the development of guidelines for counseling and management of pregnancy in the transplant population.