mycophenolic-acid and Abnormalities--Drug-Induced

Most biological agents are safe to use in pregnancy. Biologic agents may be divided into 4 risk categories: minimal, uncertain, moderate, and high. Treatment options should be individualized to each patient's disease activity, response to medication, and adverse effects. Hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine A, and low-dose aspirin are considered safe. Glucocorticoids may increase the risk of gestational diabetes and gestational hypertension/preeclampsia. Nonsteroidal medication should only be used during the first trimester and for a short period during the second trimester. Limited experience with tumor necrosis factor-α inhibitor medications suggests minimal risk. Methotrexate, mycophenolate, and leflunomide are contraindicated during pregnancy.

Topics: Abnormalities, Drug-Induced; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Autoimmune Diseases; Azathioprine; Biological Products; Cyclophosphamide; Cyclosporine; Female; Fetal Growth Retardation; Glucocorticoids; Humans; Hydroxychloroquine; Immunosuppressive Agents; Leflunomide; Methotrexate; Mycophenolic Acid; Pregnancy; Pregnancy Complications; Premature Birth; Rituximab; Sulfasalazine; Tumor Necrosis Factor Inhibitors

Topics: Abnormalities, Drug-Induced; Antibiotics, Antineoplastic; Azathioprine; Female; Humans; Immunosuppressive Agents; Infant, Low Birth Weight; Male; Methotrexate; Mycophenolic Acid; Paternal Exposure; Pregnancy; Pregnancy Complications; Pregnancy Outcome

The determination that an exposure is a human teratogen is a complex process involving the application of the principles of teratology, epidemiology, biology, and clinical medicine. Shepard suggested that the "rare exposure/rare defect" or "case report method", the astute clinician model, was one approach for establishing teratogenicity. The purpose of this article is to review selected exposures with the goal of identifying principles that lead to a working proposal for the application of this approach.. We selected three known exposures--penicillamine, fluconazole and mycophenolate mofetil--for detailed review. These agents were chosen because their evidence for causation arises mostly from clinical observations in the context of biologic plausibility.. All three agents were originally detected based on astute observations by clinicians reporting on individual cases of a distinctive pattern of malformation or, in the case of penicillamine distinctive phenotype, after the rare exposure. All three have varying degrees of biologic evidence that support the hypothesis that each represents a human teratogen. All three meet Shepard's criteria for "proof.". The basic premise of this approach depends on the rarity of both the exposure and the outcome. We propose guidelines for utilization of this approach in the determination of human teratogenicity.

Topics: Abnormalities, Drug-Induced; Antifungal Agents; Antirheumatic Agents; Congenital Abnormalities; Evidence-Based Medicine; Female; Fetus; Fluconazole; Humans; Immunosuppressive Agents; Infant, Newborn; Mycophenolic Acid; Penicillamine; Practice Guidelines as Topic; Pregnancy; Teratogens

Mycophenolate mofetil (MMF) (CellCept) is an immunosuppressant drug that is teratogenic in rats and rabbits. Reports of malformations in 13 offspring of women exposed to MMF in pregnancy raise concern that MMF is also a human teratogen. We report an additional child with malformations following prenatal exposure to MMF and review the other 13 reports. We identified a Cambodian male born at 31 weeks' gestation to a mother who had been treated for lupus nephritis with MMF from before conception to 12 weeks' gestational age. He had bilateral moderate-to-severe microtia, external auditory canal atresia, bilateral conductive hearing loss, mild microcephaly, and apparently normal development. Among the 14 MMF-exposed offspring now reported, the underlying maternal conditions were kidney transplantation (7), lupus nephritis (4), liver transplantation (1), heart transplantation (1), and recurrent erythema multiforme (1). All were exposed in early pregnancy. The most distinctive malformation was moderate-to-severe microtia or anotia (12), with external auditory canal atresia in 9. Other common craniofacial malformations and minor anomalies included orofacial clefts (7), hypertelorism (3), coloboma (3), and micrognathia (3). Six had cardiovascular malformations, of which three were either conotruncal or aortic arch defects. MMF dose, reported in 12 patients, was <1 g/day in 4 and 1 g or more/day in 8; no correlation between dose and phenotype severity was apparent. While case reports have limited value in identifying human teratogens, the unusual distribution of malformations among the 14 reported exposed offspring identifies a phenotype suggesting that MMF is likely a human teratogen.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Fatal Outcome; Female; Humans; Immunosuppressive Agents; Maternal-Fetal Exchange; Mycophenolic Acid; Pregnancy; Teratogens; Young Adult

Mycophenolate mofetil (MFM) is an immunosuppressant agent used in organ transplantation, rheumatoid arthritis and lupus nephritis. Experimental data show that doses roughly equivalent to those used clinically in transplant patients may cause fetal resorption and malformations in pregnant rats and rabbits. There are limited data regarding the use of MFM in pregnant women. The human experience is based on 9 case reports, 1 case series, and 2 registry data. The most frequent structural anomalies described in 12 newborns exposed to MFM were as follows: microtia (11); auditory canal atresia (8); cleft lip and palate (6); micrognathia (4); hypertelorism (4); ocular coloboma (3); short fingers (2) and hypoplasic nails (2). The distinctive and unique phenotype associated with MFM exposure during pregnancy (EMFO tetrada: Ear, Mouth, Fingers, Ocular/Organ malformation) raised the hypothesis that MFM may be a real teratogenic drug. Appropriate recommendations to prevent this possible new embryopathy are given.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adult; Animals; Consumer Product Safety; Embryo, Mammalian; Female; Humans; Immunosuppressive Agents; Infant, Newborn; Mycophenolic Acid; Practice Guidelines as Topic; Pregnancy; Rabbits; Rats; Registries; Risk Assessment; Teratogens

Myfortic is a new formulation of mycophenolic acid (MPA) utilizing enteric coated mycophenolate sodium (EC-MPS) that may have fewer gastrointestinal side effects.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Contraindications; Delayed-Action Preparations; Female; Gastric Acid; Humans; Hydrogen-Ion Concentration; Immunosuppressive Agents; IMP Dehydrogenase; Intestinal Absorption; Male; Mycophenolic Acid; Pregnancy; Prodrugs; Skin Diseases; Tablets, Enteric-Coated

We present a case of living, related-donor kidney transplantation during the first trimester of pregnancy. The patient received mycophenolate mofetil (MMF), tacrolimus, and prednisone throughout the entire pregnancy. This is the first reported case of use of MMF during pregnancy. The mother did well, except for mild preeclampsia and mild renal insufficiency at term. The baby girl was born prematurely at week 353/7. The only possible teratogenic effects detected included hypoplastic nails and short fifth fingers. No chromosomal abnormalities were found. The child is growing and developing normally. Although we do not recommend the use of mycophenolate mofetil during pregnancy based on this experience, it is reassuring to know that a successful outcome can be expected in mothers treated with MMF during pregnancy.

Topics: Abnormalities, Drug-Induced; Adult; Drug Therapy, Combination; Female; Fingers; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Mycophenolic Acid; Nails, Malformed; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Tacrolimus

Immunosuppressive drugs and their active metabolites can cross the placental barrier and enter fetal circulation. The adverse effects on the fetus include chromosomal aberrations, structural malformations, organ-specific toxicity and intrauterine growth retardation. The aim of our study was to investigate the impact of "safe" and "contraindicated" immunosuppressive drugs on birth defects in juvenile Wistar rats after exposure of pregnant female rats to these drugs.. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients. The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy.. Treatment with mycophenolate mofetil and everolimus turned out to be toxic. We have noticed a significantly reduced number of live births in all pregnant rats exposed to these drugs in combination with calcineurin inhibitors and prednisone. Malformations and histological changes of fetal organs were confirmed after mycophenolate mofetil exposure during pregnancy.. Mycophenolate mofetil turned out to be more toxic when used with tacrolimus than with cyclosporin (delivery of live offspring was possible only in the latter group). Everolimus in combination with cyclosporin effectively suppressed the fetal maturation in utero, but did not contribute to the development of malformations.

Topics: Abnormalities, Drug-Induced; Animals; Cyclosporine; Everolimus; Female; Immunosuppressive Agents; Mycophenolic Acid; Prednisone; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Tacrolimus

Exposure to teratogenic drugs during pregnancy is associated with a wide range of embryo-fetal anomalies and sometimes results in recurrent and recognizable patterns of malformations; however, the comprehension of the mechanisms underlying the pathogenesis of drug-induced birth defects is difficult, since teratogenesis is a multifactorial process which is always the result of a complex interaction between several environmental factors and the genetic background of both the mother and the fetus. Animal models have been extensively used to assess the teratogenic potential of pharmacological agents and to study their teratogenic mechanisms; however, a still open issue concerns how the information gained through animal models can be translated to humans. Instead, significant information can be obtained by the identification and analysis of human genetic syndromes characterized by clinical features overlapping with those observed in drug-induced embryopathies. Until now, genetic phenocopies have been reported for the embryopathies/fetopathies associated with prenatal exposure to warfarin, leflunomide, mycophenolate mofetil, fluconazole, thalidomide and ACE inhibitors. In most cases, genetic phenocopies are caused by mutations in genes encoding for the main targets of teratogens or for proteins belonging to the same molecular pathways. The aim of this paper is to review the proposed teratogenic mechanisms of these drugs, by the analysis of human monogenic disorders and their molecular pathogenesis.

Topics: Abnormalities, Drug-Induced; Angiotensin-Converting Enzyme Inhibitors; Animals; Female; Fetal Diseases; Fetus; Fluconazole; Humans; Isoxazoles; Leflunomide; Mutation; Mycophenolic Acid; Phenotype; Pregnancy; Teratogenesis; Teratogens; Thalidomide; Warfarin

Topics: Abnormalities, Drug-Induced; Allografts; Consumer Product Safety; Drug Approval; Drug Industry; Female; Government Agencies; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Organ Transplantation; Patient Safety; Pregnancy; Risk Assessment; Risk Factors; Sex Factors

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.

Topics: Abnormalities, Drug-Induced; Fathers; Female; Humans; Infant, Newborn; Male; Mycophenolic Acid; Paternal Exposure; Pregnancy; Pregnancy Outcome; Premature Birth; Registries; Transplantation

Mycophenolic acid (MPA) is an immunosuppressive agent that acts as a selective, non-reversible inhibitor of the enzyme inosine-5'-monophosphate dehydrogenase (IMPDH). Malformations have been described in children after maternal exposure to mycophenolate. However, the causal link is unclear in most cases because women had been treated with a combination of drugs and birth defects may have other causes. Therefore, it is important to study the action of this drug and its main metabolite on embryonic tissue. We studied the teratogenic potential of MPA and its major metabolite, the mycophenolic acid glucuronide (MPAG) in the rat whole-embryo culture. A total of 147 day 9.5 embryos were cultivated for 48 h in the standard medium containing 85 % serum. We tested MPA at concentrations of 0.1; 0.25; 0.5; 0.75 mg/l (0.31; 0.78; 1.56; 2.34 μM) and MPA glucuronide at concentrations of 3; 10; 30; 100 mg/l (6.04; 20.14; 60.43; 201.43 μM). Both substances are highly protein bound, and MPA glucuronide might displace MPA from protein binding. Therefore, we examined whether the effects of MPA can be enhanced when studied in combination with the glucuronide. Furthermore, the focus was on additional endpoints to the standard evaluation of cultivated embryos, such as development of cranial nerves [trigeminal nerve (V), facial nerve (VII), glossopharyngeal nerve (IX), vagus nerve (X)] after staining with an antibody against 2H3 neurofilament. Ultrastructural changes were evaluated by electron microscopy. At a concentration of 0.75 mg MPA/l medium, all embryos showed dysmorphic changes. Embryos exposed to 0.25 mg MPA/l medium showed impaired development of nerves, and at 0.1 mg/l, no effects were detectable. Concentration-dependent ultrastructural changes, such as signs of apoptosis, were found by electron microscopy. The examination of the metabolite in this assay showed that at a concentration of 100 mg MPAG/l, the embryos exhibited distinct malformations. This is probably caused by MPA, which was detectable at 0.6 % in the material used for our experiments. The combination of the parent compound (0.03; 0.1; 0.25 mg/l) with its metabolite MPAG (3 mg/l) did not cause enhanced toxicity under our experimental conditions. IMPDH, the target enzyme of MPA, could be detected in rat embryos on day 9.5 of embryonic development as well as at the end of the culture period 48 h later. In summary, MPA impairs embryonic development at low, therapeutically relevant concentrations, but the g

Topics: Abnormalities, Drug-Induced; Animals; Cranial Nerves; Dose-Response Relationship, Drug; Drug Therapy, Combination; Embryo Culture Techniques; Embryo, Mammalian; Embryonic Development; Glucuronides; Immunosuppressive Agents; IMP Dehydrogenase; Mycophenolic Acid; Rats; Teratogens; Toxicity Tests

We report on a case of a multiple congenital anomalies in a newborn infant whose mother was on allopurinol treatment through the pregnancy. The pattern of congenital anomalies that was noted in our patient was similar to the pattern described in a number of published reports following mycophenolate mofetil [CellCept®] treatment during pregnancy. The anomalies present in our patient include: diaphragmatic hernia, unilateral microtia and absence of external auditory canal, micrognathia, microphthalmia, optic nerve hypoplasia, hypoplasia of the corpus callosum, unilateral renal agenesis, pulmonary agenesis, and cleft lip and palate. Since both allopurinol and mycophenolate mofetil act by disrupting purine biosynthesis and given the similarities in anomalies seen after prenatal exposure, we suggest that allopurinol should also be considered a teratogen.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Allopurinol; Antimetabolites; Female; Humans; Infant, Newborn; Kidney Calculi; Male; Mycophenolic Acid; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Purines; Teratogens

Topics: Abnormalities, Drug-Induced; Adult; Ear; Female; Humans; Immunosuppressive Agents; Infant, Newborn; Kidney Transplantation; Male; Mycophenolic Acid

Mycophenolate mofetil (MMF) has become a major therapeutic option in the management of patients undergoing transplantation, as well as in the treatment of autoimmune conditions. Case reports have suggested that MMF use during pregnancy is associated with a specific pattern of congenital malformations. Because many pregnancies are unplanned, it is imperative to assess the teratogenic risk of MMF. Using the Organization of Teratology Information Specialists network, we prospectively identified and followed pregnant women exposed to MMF during pregnancy to update this teratogenic potential. Ten cases were identified and all received the drug during embryogenesis at the recommended doses (500 to 1500 mg daily). There were four miscarriages and one elective abortion due to fear of teratogenesis. None of the five live births had malformations. It is possible that, similar to other human teratogens discovered first by case reports, the absolute risk from MMF may be smaller than originally calculated based on case reports. Because the major malformations phenotypic of MMF may be visualized in utero (e.g., microtia, cleft palate, congenital diaphragmatic hernia, and cardiac malformation), diagnostic imaging should be performed.

Topics: Abnormalities, Drug-Induced; Adult; Female; Humans; Immunosuppressive Agents; Mycophenolic Acid; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Young Adult

There is very little data linking the use of immunomodulating agents following solid organ transplantation in pregnant women with specific congenital anomalies in the offspring. Here we report on a late preterm infant with multiple, nonsyndromic, congenital anomalies including microtia/anotia, cleft lip and palate, micrognathia, ocular hypertelorism, microphthalmia and cataracts, complex congenital heart disease, rib anomalies, and intestinal malrotation. The similarity of the complex anomalies in our case to other reported cases suggests that the abnormalities are likely due to mycophenolate mofetil alone or in combination with other immunosuppressive medications taken by the mother during pregnancy.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Female; Humans; Immunosuppressive Agents; Infant, Newborn; Maternal Exposure; Maternal-Fetal Exchange; Mycophenolic Acid; Pregnancy; Prenatal Exposure Delayed Effects

A newborn female infant born to a woman on immunosuppressive medications including mycophenolate mofetil (MMF) for a renal graft secondary to lupus nephritis presented with congenital diaphragmatic hernia (CDH) and additional findings of microtia, esophageal atresia with tracheoesophageal fistula, cleft palate, congenital heart defect, digital anomalies, and dysmorphic facial features. Pulmonary hypoplasia resulted in death at day 2 of life. She was presumed to have Fryns syndrome based on diagnostic criteria established for this recessive disorder with prominent features including CDH, facial anomalies, and nail hypoplasia. In retrospect, this infant's findings are more likely the result of teratogenic exposure to MMF, as more recent data have emerged linking aural atresia, digital anomalies, and dysmorphic features to this drug. To date, this is the only human report of CDH in an infant with prenatal exposure to MMF, although the manufacturer's package insert alludes to animal studies with a broad spectrum of malformations, including CDH. Thus, a teratogenic exposure can mimic a known Mendelian genetic syndrome, and caution is urged in presuming a genetic etiology for infants with potential teratogenic exposure to relatively new drugs with limited published animal data.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Autopsy; Ear; Fatal Outcome; Female; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Immunosuppressive Agents; Infant, Newborn; Mycophenolic Acid; Pregnancy; Radiography; Syndrome; Teratogens

Mycophenolate mofetil (MMF) is an immunosuppressive agent that has now been recognized as teratogenic in humans. A pattern of malformations from in utero exposure to MMF has recently been described, and includes cleft lip and palate, microtia and atresia of the external auditory canal. We present a nulliparous mother who had taken MMF for recurrent erythema multiforme for the first 5 weeks of her pregnancy, and developed a spontaneous miscarriage during the seventh week of pregnancy. For her second pregnancy, she took MMF on her own accord for four days in the seventh week after her last menstrual period. The newborn had bilateral microtia, absence of the external auditory canals, and right iris and chorioretinal coloboma, consistent with the pattern recognized as part of the MMF embryopathy phenotype. As the newborn was not exposed to other immunosuppressive agents in utero, we believe that the phenotype described to be the result of the teratogenic effect of MMF. The spontaneous miscarriage in the first pregnancy may be due to the higher dose and longer duration of MMF exposure. The second pregnancy, with MMF exposure of 4 days, proceeded to term with the resultant phenotype. We conclude that the effect and severity of the embryopathy may be dependent on the dose, timing, and duration of MMF exposure. The manufacturer and the United States Food and Drug Administration have now disseminated information regarding the teratogenic risk of MMF. Women should be fully counseled and advised about contraception during the course of treatment with MMF.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adult; Child, Preschool; Coloboma; Dose-Response Relationship, Drug; Ear Canal; Ear, External; Erythema Multiforme; Female; Humans; Immunosuppressive Agents; Iris; Maternal Exposure; Mycophenolic Acid; Pregnancy; Time Factors

Topics: Abnormalities, Drug-Induced; Female; Fetus; Humans; Immunosuppressive Agents; Mycophenolic Acid; Organ Transplantation; Pregnancy; Pregnancy Complications

Topics: Abnormalities, Drug-Induced; Adult; Craniofacial Abnormalities; Female; Fetus; Heart Failure; Heart Transplantation; Humans; Immunosuppressive Agents; Maternal Exposure; Mycophenolic Acid; Pregnancy

ABSTRACTQUESTION One of my female patients conceived 2 years after renal transplant while using mycophenolate mofetil. She only realized she was pregnant at 14 weeks of gestation. How should I advise her?ANSWER Several recent case series show increased malformation rates with mycophenolate mofetil. Specifically, the repeated occurrence of phenotypic presentations of ear malformations, cleft lip and palate, and other malformations suggest that this is not by chance alone.

Topics: Abnormalities, Drug-Induced; Animals; Female; Graft Rejection; Humans; Immunosuppressive Agents; Mycophenolic Acid; Organ Transplantation; Pregnancy; Pregnancy Trimester, First; Pregnancy, Animal; Pregnancy, High-Risk; Prenatal Care; Rabbits; Rats; Risk Assessment; Sensitivity and Specificity; Teratogens; Transplantation Immunology

Mycophenolate mofetil (MMF) is a widely prescribed immunosuppressive agent after solid organ transplantation. Potential teratogenic effects after in utero exposure to MMF in experimental studies and clinical observations in humans has been postulated in recent literature. However, a specific pattern of malformation has not been identified yet. We present a newborn patient, born to a recipient of renal transplantation, who became pregnant while taking MMF as immunosuppressive therapy. The newborn exhibited cleft lip and palate, bilateral microtia and atretic external auditory canals, chorioretinal coloboma, hypertelorism, and micrognathia. An extensive review of the literature documented six other cases with similar malformations after in utero exposure to MMF. A consistent pattern of malformations comprising cleft lip and palate, microtia and external auditory canals could be observed in five of the six cases. A different malformative pattern observed in one of the patients could be attributed to a different agent rather than MMF. The possible teratogenic effects of other immunosuppressive drugs, such as tacrolimus and prednisone, to which this patient was also exposed, are discussed herein. In addition, the differential diagnosis with other dysmorphic syndromes that can present with a similar phenotype, such as CHARGE syndrome, 18q deletion and hypertelorism-microtia-clefting (HMC) syndrome, is presented. We conclude that in utero exposure to MMF can cause a characteristic phenotype and propose the existence of a mycophenolate-associated embryopathy whose main features are: cleft lip and palate, microtia with atresia of external auditory canal, micrognathia and hypertelorism. Ocular anomalies, corpus callosum agenesis, heart defects, kidney malformations, and diaphragmatic hernia may be part of the phenotypic spectrum of MMF embryopathy. The human teratogenicity of MMF is reinforced by this report, and the current contraceptive recommendations about its use in fertile women are stressed.

Topics: Abnormalities, Drug-Induced; Adult; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Maternal Exposure; Maternal-Fetal Exchange; Mycophenolic Acid; Phenotype; Prednisone; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Tacrolimus; Ultrasonography

Topics: Abnormalities, Drug-Induced; Craniofacial Abnormalities; Female; Humans; Immunosuppressive Agents; Infant, Newborn; Mycophenolic Acid; Pregnancy; Prenatal Exposure Delayed Effects

Immunosuppressants are teratogenic in mice, rats, and rabbits and cause prenatal growth restriction in humans. As yet, there has been no proven teratogenicity in humans.. We present a chromosomally normal fetus with severe acrofacial dysostosis and orofacial clefts. These were bilateral transverse and oblique clefts and defects of the midface. In addition, there were preaxial limb anomalies with digitalization of thumbs and internal cardiovascular, gastrointestinal, and urogenital malformations. The mother had been treated with high doses of the immunosuppressant mycophenolate mofetil in early pregnancy for systemic lupus erythematosus.. Mycophenolate mofetil may have contributed to or even caused acrofacial dysostosis phenotype and extensive clefting.

Topics: Abnormalities, Drug-Induced; Adolescent; Craniofacial Abnormalities; Female; Fetal Diseases; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects

Mycophenolate mofetil (MMF) has proved to be a major addition to the therapeutic options for the treatment of multisystem autoimmune disorders. The majority of the autoimmune rheumatological diseases are more prevalent in women and they are often first diagnosed during childbearing age. MMF use during pregnancy is associated with an increased risk of malformations and first-trimester pregnancy loss. The most frequent malformations include external ear and other facial malformations such as cleft palate and lip. Therefore MMF should be avoided during pregnancy and safe contraceptive methods provided.

Topics: Abnormalities, Drug-Induced; Adult; Animals; Contraindications; Craniofacial Abnormalities; Female; Humans; Immunosuppressive Agents; Lupus Nephritis; Maternal-Fetal Exchange; Mycophenolic Acid; Organ Transplantation; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Mycophenolate mofetil has been shown to have teratogenic properties in animal studies and clinical reports. We report a case of major fetal malformation likely caused by mycophenolate mofetil exposure in utero in a 36 year old patient with systemic lupus erythematosus. The diagnosis was made by ultrasonography at 22 weeks of gestation.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adult; Ear, External; Facies; Female; Fetus; Humans; Imaging, Three-Dimensional; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Nose; Pregnancy; Pregnancy Complications; Ultrasonography, Prenatal

After admitting a patient to our Neonatal Intensive Care with a severe anemia and an ear malformation, we ruled out any other cause than maternal medication use. Knowing she used mycophenolate mofetil during pregnancy, we looked for related articles. Two articles were found describing ear malformations, but no article was ever written about anemia caused by this medication. Consulting the international registers of drug effects through the National Institute for Public Health and the Environment, we found out that the anemia was never seen or reported before.

Topics: Abnormalities, Drug-Induced; Adult; Anemia, Neonatal; Ear, External; Female; Humans; Hydrops Fetalis; Immunosuppressive Agents; Infant, Newborn; Male; Mycophenolic Acid; Pregnancy; Pregnancy Complications

Animal and limited human studies have raised concerns as to the safety of in utero exposure to mycophenolate mofetil (MMF) and sirolimus (SRL) in transplant recipients. This study examined the outcomes of pregnancies with exposure to MMF or SRL from 30 female transplant recipients (39 pregnancies) who have reported pregnancies to the National Transplantation Pregnancy Registry.. Data were collected via questionnaires, phone interviews and medical records.. There were 18 kidney recipients reporting 26 pregnancies with exposure to MMF: 15 livebirths (LB), 11 spontaneous abortions (SA). Structural malformations were reported in four of the 15 children (26.7%) including: hypoplastic nails and shortened fifth fingers (one), microtia with cleft lip and palate (one), microtia alone (one), and neonatal death with multiple malformations (one). One kidney/pancreas (K/P) recipient reported one SA. Three liver recipients reported three pregnancies; two LB (no malformations), and one second trimester SA. Two heart recipients reported one LB (no malformations) and two SA. SRL exposures included seven recipients (four kidney, one K/P and two liver) reporting four LB (one infant whose mother was switched from MMF to SRL during late pregnancy had cleft lip and palate and microtia) and three SA.. A higher incidence of structural malformations was seen with MMF exposures during pregnancy compared to the overall kidney transplant recipient offspring, while no structural defects have as yet been reported with early pregnancy sirolimus exposures. Centers are encouraged to report all pregnancy exposures in transplant recipients.

Topics: Abnormalities, Drug-Induced; Adult; Female; Humans; Immunosuppressive Agents; Maternal Exposure; Maternal-Fetal Exchange; Mycophenolic Acid; Organ Transplantation; Pregnancy; Pregnancy Outcome; Registries; Sirolimus

Mycophenolate mofetil has teratogenic properties in rats and rabbits. Previous human studies have reported an increased rate of fetal losses with its use. We report a case of major fetal malformations due to mycophenolate mofetil.. The patient was treated with mycophenolate mofetil before conception and during the first trimester of pregnancy. The fetus had multiple malformations, specifically, facial dysmorphology and midline anomalies, including agenesis of the corpus callosum.. This case of fetal malformation attributable to mycophenolate mofetil must be taken into consideration when considering pregnancy in an organ-transplant recipient.

Topics: Abnormalities, Drug-Induced; Adult; Animals; Female; Fetus; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Pregnancy