Fetal Toxicity of Immunosuppressive Drugs in Pregnancy
Abstract
:1. Introduction
2. Glucocorticoids
3. Calcineurin Inhibitors (CNIs)
3.1. Cyclosporine
3.2. Tacrolimus
4. Nucleotide Synthesis Inhibitors
4.1. Azathioprine
4.2. Mycophenolate Salts
4.3. Leflunomide
5. Alkylating Agents
5.1. Cyclophosphamide
5.2. Chlorambucil
6. Mammalian Target of Rapamycin (mTOR) Inhibitors
7. Monoclonal Antibodies
7.1. Rituximab (RTX)
7.2. Eculizumab
7.3. TNF-Inhibitors
7.4. Belimumab
8. Proteasome Inhibitors
Bortezomib
9. Tyrosine Kinase Inhibitors (TKIs)
10. Fusion Proteins
11. Hydroxychloroquine (HCQ)
12. Methotrexate
13. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Levitz, M.; Jansen, V.; Dancis, J. The transfer and metabolism of corticosteroids in the perfused human placenta. Am. J. Obstet. Gynecol. 1978, 132, 363–366. [Google Scholar] [CrossRef]
- Brown, R.W.; Chapman, K.E.; Edwards, C.R.; Seckl, J.R. Human placental 11 beta-hydroxysteroid dehydrogenase: Evidence for and partial purification of a distinct NAD-dependent isoform. Endocrinology 1993, 132, 2614–2621. [Google Scholar] [CrossRef] [PubMed]
- Brown, R.W.; Diaz, R.; Robson, A.C.; Kotelevtsev, Y.V.; Mullins, J.J.; Kaufman, M.H.; Seckl, J.R. The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. Endocrinology 1996, 137, 794–797. [Google Scholar] [CrossRef] [PubMed]
- Chambers, C.D.; Tutuncu, Z.N.; Johnson, D.; Jones, K.L. Human pregnancy safety for agents used to treat rheumatoid arthritis: Adequacy of available information and strategies for developing post-marketing data. Arthritis Res. Ther. 2006, 8, 215. [Google Scholar] [CrossRef] [PubMed]
- Bay Bjørn, A.M.; Ehrenstein, V.; Hundborg, H.H.; Nohr, E.A.; Sørensen, H.T.; Nørgaard, M. Use of corticosteroids in early pregnancy is not associated with risk of oral clefts and other congenital malformations in offspring. Am. J. Ther. 2014, 21, 73–80. [Google Scholar] [CrossRef] [PubMed]
- Goedhart, G.; Vrijkotte, T.G.; Roseboom, T.J.; van der Wal, M.F.; Cuijpers, P.; Bonsel, G.J. Maternal cortisol and offspring birthweight: Results from a large prospective cohort study. Psychoneuroendocrinology 2010, 35, 644–652. [Google Scholar] [CrossRef] [PubMed]
- Bloom, S.L.; Sheffield, J.S.; McIntire, D.D.; Leveno, K.J. Antenatal dexamethasone and decreased birth weight. Obstet. Gynecol. 2001, 97, 485–490. [Google Scholar]
- Reynolds, R.M. Programming effects of glucocorticoids. Clin. Obstet. Gynecol. 2013, 56, 602–609. [Google Scholar] [CrossRef]
- Moisiadis, V.G.; Matthews, S.G. Glucocorticoids and fetal programming part 1: Outcomes. Nat. Rev. Endocrinol. 2014, 10, 391–402. [Google Scholar] [CrossRef]
- Stirrat, L.I.; Sengers, B.G.; Norman, J.E.; Homer, N.Z.M.; Andrew, R.; Lewis, R.M.; Reynolds, R.M. Transfer and Metabolism of Cortisol by the Isolated Perfused Human Placenta. J. Clin. Endocrinol. Metab. 2018, 103, 640–648. [Google Scholar] [CrossRef]
- McCalla, C.; Nacharaju, V.L.; Muneyyirci-Delale, O.; Glasgow, S.; Feldman, J.G. Placental 11β-hydroxysteroid dehydrogenase activity in normotensive and pre-eclamptic pregnancies. Steroids 1998, 63, 511–515. [Google Scholar] [CrossRef]
- Ponticelli, C.; Moroni, G. Immunosuppression in pregnant women with systemic lupus erythematosus. Expert Rev. Clin. Immunol. 2015, 11, 549–552. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rusnak, F.; Mertz, P. Calcineurin: Form and function. Physiol. Rev. 2000, 80, 1483–1521. [Google Scholar] [CrossRef] [PubMed]
- Liao, W.; Lin, J.X.; Leonard, W.J. IL-2 family cytokines: New insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr. Opin. Immunol. 2011, 23, 598–604. [Google Scholar] [CrossRef] [PubMed]
- Eberhardt, W.; Nasrullah, U.; Pfeilschifter, J. Activation of renal profibrotic TGFβ controlled signaling cascades by calcineurin and mTOR inhibitors. Cell Signal. 2018, 52, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Venkataramanan, R.; Koneru, B.; Wang, C.C.; Burckart, G.J.; Caritis, S.N.; Starzl, T.E. Cyclosporine and its metabolites in mother and baby. Transplantation 1988, 46, 468–469. [Google Scholar] [CrossRef] [PubMed]
- Pávek, P.; Fendrich, Z.; Staud, F.; Malákova, J.; Brozmanová, H.; Láznícek, M.; Semecký, V.; Grundmann, M.; Palicka, V. Influence of P-glycoprotein on the transplacental passage of cyclosporine. J. Pharm. Sci. 2001, 90, 1583–1592. [Google Scholar] [CrossRef]
- Janssen, N.M.; Genta, M.S. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy and lactation. Arch. Intern. Med. 2000, 160, 610–619. [Google Scholar] [CrossRef]
- Durst, J.K.; Rampersad, R.M. Pregnancy in Women with Solid-Organ Transplants: A Review. Obstet. Gynecol. Surv. 2015, 70, 408–418. [Google Scholar] [CrossRef]
- Gotestam Skorpen, C.; Hoeltzenbein, M.; Tincani, A.; Fischer-Betz, R.; Elefant, E.; Chambers, C.; da Silva, J.; Nelson-Piercy, C.; Cetin, I.; Costedoat-Chalumeau, N.; et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann. Rheum. Dis. 2016, 75, 795–810. [Google Scholar] [CrossRef] [Green Version]
- Ling, Y.; Huang, Y.; Chen, C.; Mao, J.; Zhang, H. Low dose Cyclosporin A treatment increases live birth rate of unexplained recurrent abortion–initial cohort study. Clin. Exp. Obstet. Gynecol. 2017, 44, 230–235. [Google Scholar] [PubMed]
- Thiagarajan, K.M.; Arakali, S.R.; Mealey, K.J.; Cardonick, E.H.; Gaughan, W.J.; Davison, J.M.; Moritz, M.J.; Armenti, V.T. Safety considerations: Breastfeeding after transplant. Prog. Transplant. 2013, 23, 137–146. [Google Scholar] [CrossRef] [PubMed]
- Constantinescu, S.; Pai, A.; Coscia, L.A.; Davison, J.M.; Moritz, M.J.; Armenti, V.T. Breast-feeding after transplantation. Best Pract. Res. Clin. Obstet. Gynaecol. 2014, 28, 1163–1173. [Google Scholar] [CrossRef] [PubMed]
- Hebert, M.F.; Zheng, S.; Hays, K.; Shen, D.D.; Davis, C.L.; Umans, J.G.; Miodovnik, M.; Thummel, K.E.; Easterling, T.R. Interpreting tacrolimus concentrations during pregnancy and postpartum. Transplantation 2013, 95, 908–915. [Google Scholar] [CrossRef] [PubMed]
- Zheng, S.; Easterling, T.R.; Hays, K.; Umans, J.G.; Miodovnik, M.; Clark, S.; Calamia, J.C.; Thummel, K.E.; Shenn, D.D.; Davis, C.L.; et al. Tacrolimus placental transfer at delivery and neonatal exposure through breast milk. Br. J. Clin. Pharmacol. 2013, 76, 988–996. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kainz, A.; Harabacz, I.; Cowlrick, I.S.; Gadgil, S.D.; Hagiwara, D. Review of the course and outcome of 100 pregnancies in 84 women treated with tacrolimus. Transplantation 2000, 70, 1718–1721. [Google Scholar] [CrossRef] [PubMed]
- Nevers, W.; Pupco, A.; Koren, G.; Bozzo, P. Safety of tacrolimus in pregnancy. Can. Fam. Physician 2014, 60, 905–906. [Google Scholar]
- Bramham, K.; Chusney, G.; Lee, J.; Lightstone, L.; Nelson-Piercy, C. Breastfeeding and tacrolimus: Serial monitoring in breast-fed and bottle-fed infants. Clin. J. Am. Soc. Nephrol. 2013, 8, 563–567. [Google Scholar] [CrossRef]
- Armenti, V.T.; Moritz, M.J.; Davison, J.M. Breastfeeding and tacrolimus: Is it a reasonable approach? Expert Rev. Clin. Immunol. 2013, 9, 623–626. [Google Scholar] [CrossRef]
- Piccoli, G.B.; Cabiddu, G.; Attini, R.; Gerbino, M.; Todeschini, P.; Perrino, M.L.; Manzione, A.M.; Piredda, G.B.; Gnappi, E.; Caputo, F.; et al. Outcomes of Pregnancies After Kidney Transplantation: Lessons Learned from CKD. A Comparison of Transplanted, Nontransplanted Chronic Kidney Disease Patients and Low-Risk Pregnancies: A Multicenter Nationwide Analysis. Transplantation 2017, 101, 2536–2544. [Google Scholar] [CrossRef]
- Piccoli, G.B.; Cabiddu, G.; Attini, R.; Gerbino, M.; Todeschini, P.; Perrino, M.L.; Manzione, A.M.; Piredda, G.B.; Gnappi, E.; Caputo, F.; et al. Pregnancy outcomes after kidney graft in Italy: Are the changes over time the result of different therapies or of different policies? A nationwide survey (1978–2013). Nephrol. Dial. Transplant. 2016, 31, 1957–1965. [Google Scholar] [CrossRef] [PubMed]
- Saavedra, M.A.; Sánchez, A.; Morales, S.; Ángeles, U.; Jara, L.J. Azathioprine during pregnancy in systemic lupus erythematosus patients is not associated with poor fetal outcome. Clin. Rheumatol. 2015, 34, 1211–1216. [Google Scholar] [CrossRef] [PubMed]
- Alami, Z.; Agier, M.S.; Ahid, S.; Vial, T.; Dautriche, A.; Lagarce, L.; Toutain, A.; Cherrah, Y.; Jonville-Bera, A.P. Pregnancy outcome following in utero exposure to azathioprine: A French comparative observational study. Therapie 2018, 73, 199–207. [Google Scholar] [CrossRef] [PubMed]
- EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients. Nephrol. Dial. Transplant. 2002, 17 (Suppl. 4), 50–55. [Google Scholar]
- McKay, D.B.; Adams, P.L.; Bumgardner, G.L.; Davis, C.L.; Fine, R.N.; Krams, S.M.; Martinez, O.M.; Murphy, B.; Pavlakis, M.; Tolkoff-Rubin, N.; et al. Reproduction and pregnancy in transplant recipients: Current practices. Progr. Transplant. 2006, 16, 127–132. [Google Scholar] [CrossRef]
- Shah, S.; Verma, P. Overview of Pregnancy in Renal Transplant Patients. Int. J. Nephrol. 2016, 2016, 4539342. [Google Scholar] [CrossRef]
- Kelly, G.E.; Sheil, A.G. Sister chromatid exchange in lymphocytes from renal transplant recipients with and without cancer. Br. J. Cancer 1983, 48, 797–801. [Google Scholar] [CrossRef] [Green Version]
- Erskine, I.A.; Mackay, J.M.; Fox, D.P. Monitoring patients on long-term drug therapy for genotoxic effects. Basic Life Sci. 1984, 29 Pt B, 895–905. [Google Scholar]
- Perez-Aytes, A.; Ledo, A.; Boso, V.; Sáenz, P.; Roma, E.; Poveda, J.L.; Vento, M. In utero exposure to mycophenolate mofetil: A characteristic phenotype? Am. J. Med. Genet. A 2008, 146, 1–7. [Google Scholar] [CrossRef]
- Hoeltzenbein, M.; Elefant, E.; Vial, T.; Finkel-Pekarsky, V.; Stephens, S.; Clementi, M.; Allignol, A.; Weber-Schoendorfer, C.; Schaefer, C. Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services. Am. J. Med. Genet. A 2012, 58, 588–596. [Google Scholar] [CrossRef]
- Martín, M.C.; Cristiano, E.; Villanueva, M.; Bonora, M.L.; Berguio, N.; Tocci, A.; Groisman, B.; Bidondo, M.P.; Liascovich, R.; Barbero, P. Esophageal atresia and prenatal exposure to mycophenolate. Reprod. Toxicol. 2014, 50, 117–121. [Google Scholar] [CrossRef] [PubMed]
- Coscia, L.A.; Armenti, D.P.; King, R.W.; Sifontis, N.M.; Constantinescu, S.; Moritz, M.J. Update on the Teratogenicity of Maternal Mycophenolate Mofetil. J. Pediatr. Genet. 2015, 4, 42–55. [Google Scholar] [PubMed] [Green Version]
- Klieger-Grossmann, C.; Chitayat, D.; Lavign, S.; Kao, K.; Garcia-Bournissen, F.; Quinn, D.; Luo, V.; Sermer, M.; Riordan, S.; Laskin, C.; et al. Prenatal exposure to mycophenolate mofetil: An updated estimate. J. Obstet. Gynaecol. Can. 2010, 32, 794–797. [Google Scholar] [CrossRef]
- Kylat, R.I. What is the teratogenic risk of mycophenolate? J. Pediatr. Genet. 2017, 6, 111–114. [Google Scholar] [CrossRef] [PubMed]
- King, R.W.; Baca, M.J.; Armenti, V.T.; Kaplan, B. Pregnancy Outcomes Related to Mycophenolate Exposure in Female Kidney Transplant Recipients. Am. J. Transplant. 2017, 17, 151–160. [Google Scholar] [CrossRef] [PubMed]
- Midtvedt, K.; Bergan, S.; Reisæter, A.V.; Vikse, B.E.; Åsberg, A. Exposure to Mycophenolate and Fatherhood. Transplantation 2017, 101, e214–e217. [Google Scholar] [CrossRef] [PubMed]
- Brent, R.L. Teratogen update: Reproductive risks of leflunomide (Arava); A pyrimidine synthesis inhibitor: Counseling women taking leflunomide before orduring pregnancy and men taking leflunomide who are contemplatingfathering a child. Teratology 2001, 63, 106–112. [Google Scholar] [CrossRef]
- De Santis, M.; Straface, G.; Cavaliere, A.; Carducci, B.; Caruso, A. Paternal and maternal exposure to leflunomide: Pregnancy and neonatal outcome. Ann. Rheum. Dis. 2005, 64, 1096–1097. [Google Scholar] [CrossRef]
- Chambers, C.D.; Johnson, D.L.; Robinson, L.K.; Xu, R.; Lopez-Jimenez, J.; Mirrasoul, N.; Salas, E.; Luo, Y.J.; Jin, S.; Jones, K.L. Organization of Teratology Information Specialists Collaborative Research Group. Birth outcomes in Women Who Have Taken Leflunomide During Pregnancy. Arthritis Rheum. 2010, 62, 1494–1503. [Google Scholar] [CrossRef]
- Bérard, A.; Zhao, J.P.; Shui, I.; Colilla, S. Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes. Ann. Rheum. Dis. 2018, 77, 500–509. [Google Scholar] [CrossRef]
- Weber-Schoendorfer, C.; Beck, E.; Tissen-Diabaté, T.; Schaefer, C. Leflunomide—A human teratogen? A still not answered question. An evaluation of the German Embryotox pharmacovigilance database. Reprod. Toxicol. 2017, 71, 101–107. [Google Scholar] [CrossRef] [PubMed]
- Marchitti, S.A.; Brocker, C.; Stagos, D.; Vasiliou, V. Non-P450 aldehyde oxidizing enzymes: The aldehyde dehydrogenase superfamily. Expert Opin. Drug Metab. Toxicol. 2008, 4, 697–720. [Google Scholar] [CrossRef] [PubMed]
- Clowse, M.E.; Magder, L.; Petri, M. Cyclophosphamide for lupus during pregnancy. Lupus 2005, 14, 593–597. [Google Scholar] [CrossRef] [PubMed]
- Colla, L.; Diena, D.; Rossetti, M.; Manzione, A.M.; Marozio, L.; Benedetto, C.; Biancone, L. Immunosuppression in pregnant women with renal disease: Review of the latest evidence in the biologics era. J. Nephrol. 2018, 31, 361–383. [Google Scholar] [CrossRef] [PubMed]
- Kirshon, B.; Wasserstrum, N.; Willis, R.; Herman, G.E.; McCabe, E.R. Teratogenic effects of first-trimester cyclophosphamide therapy. Obstet. Gynecol. 1988, 72, 462–464. [Google Scholar]
- Pekar, O.; Molotski, N.; Savion, S.; Fein, A.; Toder, V.; Torchinsky, A. p53 regulates cyclophosphamide teratogenesis by controlling caspases 3, 8, 9 activation and NF-kappaB DNA binding. Reproduction 2007, 134, 379–388. [Google Scholar] [CrossRef] [PubMed]
- Grijalva-Flores, J.; Guerrero-Romero, F. Klippel-Feil syndrome in a boy exposed inadvertently to cyclophosphamide during pregnancy: A case report. Birth Defects Res. A Clin. Mol. Teratol. 2012, 94, 249–252. [Google Scholar]
- Rengasamy, P. Congenital Malformations Attributed to Prenatal Exposure to Cyclophosphamide. Anticancer Agents Med. Chem. 2017, 17, 1211–1227. [Google Scholar] [CrossRef]
- Murthy, R.K.; Theriault, R.L.; Barnett, C.M.; Hodge, S.; Ramirez, M.M.; Milbourne, A.; Rimes, S.A.; Hortobagyi, G.N.; Valero, V.; Litton, J.K. Outcomes of children exposed in utero to chemotherapy for breast cancer. Breast Cancer Res. 2014, 16, 500. [Google Scholar] [CrossRef]
- Kim, S.H.; Lee, I.C.; Baek, H.S.; Shin, I.S.; Moon, C.; Bae, C.S.; Kim, S.H.; Kim, J.C.; Kim, H.C. Induction of cytochrome P450 3A1 expression by diallyl disulfide: Protective effects against cyclophosphamide-induced embryo-fetal developmental toxicity. Food Chem. Toxicol. 2014, 69, 312–319. [Google Scholar] [CrossRef]
- Park, D.; Jeon, J.H.; Shin, S.; Joo, S.S.; Kang, D.H.; Moon, S.H.; Jang, M.J.; Cho, Y.M.; Kim, J.W.; Ji, H.J.; et al. Green tea extract increases cyclophosphamide-induced teratogenesis by modulating the expression of cytochrome P-450 mRNA. Reprod. Toxicol. 2009, 27, 79–84. [Google Scholar] [CrossRef] [PubMed]
- Park, D.; Yang, Y.H.; Choi, E.K.; Yang, G.; Bae, D.K.; Lee, S.H.; Kim, T.K.; Kyung, J.; Kim, D.; Choi, K.C.; et al. Licorice extract increases cyclophosphamide teratogenicity by upregulating the expression of cytochrome P-450 2B mRNA. Birth Defects Res. B Dev. Reprod. Toxicol. 2011, 92, 553–559. [Google Scholar] [CrossRef] [PubMed]
- Shotton, D.; Morie, W. Possible teratogenic effects of chlorambucil on human fetus. JAMA 1963, 186, 74–75. [Google Scholar] [CrossRef] [PubMed]
- Ostensen, M.; Ramsey-Goldman, R. Treatment of inflammatory rheumatic disorders in pregnancy: What are the safest treatment options? Drug Saf. 1998, 19, 38. [Google Scholar]
- Leslie, K.K.; Koil, C.; Rayburn, W.F. Chemotherapeutic drugs in pregnancy. Obstet. Gynecol. Clin. N. Am. 2005, 32, 627–640. [Google Scholar] [CrossRef] [PubMed]
- Avíles, A.; Neri, N. Hematological malignancies and pregnancy: A final report of 84 children who received chemotherapy in utero. Clin. Lymphoma 2001, 2, 173–177. [Google Scholar] [CrossRef] [PubMed]
- Ponticelli, C. The pros and the cons of mTOR inhibitors in kidney transplantation. Expert Rev. Clin. Immunol. 2014, 10, 295–305. [Google Scholar] [CrossRef]
- Fiocchi, R.; D’Elia, E.; Vittori, C.; Sebastiani, R.; Strobelt, N.; Eleftheriou, G.; Introna, M.; Freddi, C.; Crippa, A. First Report of a Successful pregnancy in an Everolimus-treated heart-transplanted patient: Neonatal disappearance of immunosuppressive drugs. Am. J. Trasplant. 2016, 16, 1319–1322. [Google Scholar] [CrossRef]
- Framarino dei Malatesta, M.L.; Corona, L.E.; De Luca, L.; Rocca, B.; Manzia, T.M.; Orlando, G.; Tisone, G.; Iaria, G. Successful pregnancy in a living-related kidney transplant recipient who received sirolimus throughout the whole gestation. Transplantation 2011, 91, e69–e71. [Google Scholar] [CrossRef]
- Carta, P.; Caroti, L.; Zanazzi, M. Pregnancy in a kidney transplant patient treated with everolimus. Am. J. Kidney Dis. 2012, 60, 329. [Google Scholar] [CrossRef]
- Yamamura, M.; Kojima, T.; Koyama, M.; Sazawa, A.; Yamada, T.; Minakami, H. Everolimus in pregnancy: Case report and literature review. Obstet. Gynaecol. Res. 2017, 43, 1350–1352. [Google Scholar] [CrossRef] [PubMed]
- Chakravarty, E.F.; Murray, E.R.; Kelman, A.; Farmer, P. Pregnancy outcomes after maternal exposure to rituximab. Blood 2011, 117, 1499–1506. [Google Scholar] [CrossRef] [PubMed]
- Calligaro, A.; Hoxha, A.; Ruffatti, A.; Punzi, L. Are biological drugs safe in pregnancy? Reumatismo 2015, 66, 304–317. [Google Scholar] [CrossRef] [PubMed]
- Ostensen, M. Safety issues of biologics in pregnant patients with rheumatic diseases. Ann. N. Y. Acad. Sci. 2014, 1317, 32–38. [Google Scholar] [CrossRef] [PubMed]
- Levy, R.A.; de Jesús, G.R.; de Jesús, N.R.; Klumb, E.M. Critical review of the current recommendations for the treatment of systemic inflammatory rheumatic diseases during pregnancy and lactation. Autoimmun. Rev. 2016, 15, 955–963. [Google Scholar] [CrossRef] [PubMed]
- Kelly, R.J.; Höchsmann, B.; Szer, J.; Kulasekararaj, A.; de Guibert, S.; Röth, A.; Weitz, I.C.; Armstrong, E.; Risitano, A.; Patriquin, C.J.; et al. Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria. N. Engl. J. Med. 2015, 373, 1032–1039. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miyasaka, N.; Miura, O.; Kawaguchi, T.; Arima, N.; Morishita, E.; Usuki, K.; Morita, Y.; Nishiwaki, K.; Ninomiya, H.; Gotoh, A.; et al. Pregnancy outcomes of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: A Japanese experience and updated review. Int. J. Hematol. 2016, 103, 703–712. [Google Scholar] [CrossRef]
- Hallstensen, R.F.; Bergseth, G.; Foss, S.; Jæger, S.; Gedde-Dahl, T.; Holt, J.; Christiansen, D.; Lau, C.; Brekke, O.L.; Armstrong, E.; et al. Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn. Immunobiology 2015, 220, 452–459. [Google Scholar] [CrossRef] [Green Version]
- Ventura, S.J.; Hamilton, B.E.; Mathews, T.J.; Chandra, A. Trends in pregnancies and pregnancy rates by outcome: Estimates for the United States, 1976–96. Vital Health Stat. 21 2000, 56, 1–47. [Google Scholar]
- Hudson, M.; Flett, G.; Sinclair, T.S.; Brunt, P.W.; Templeton, A.; Mowat, N.A. Fertility and pregnancy in inflammatory disease. Int. J. Gynaecol. Obstet. 1997, 58, 229–237. [Google Scholar] [CrossRef]
- Kane, S. Trick or TREAT? More safety data of Infliximab during pregnancy. Am. J. Gastroenterol. 2018, 113, 1592–1593. [Google Scholar] [CrossRef] [PubMed]
- Hoxha, A.; Calligaro, A.; Di Poi, E.; Peccatori, S.; Favaro, M.; Del Ross, T.; Ramonda, R.; Grava, C.; Raffeiner, B.; Ravagni, P.; et al. Pregnancy and foetal outcomes following anti-tumor necrosis factor alpha therapy: A prospective multicentre study. Jt. Bone Spine 2017, 84, 169–173. [Google Scholar] [CrossRef] [PubMed]
- Luu, M.; Benzenine, E.; Doret, M. Continuous Anti-TNFα Use Throughout Pregnancy: Possible Complications fpr the Mother but Not for the Fetus. A Retrospective Cohort on the French National Health Insurance Database (EVASION). Am. J. Gastroenterol. 2018, 113, 1669–1677. [Google Scholar] [CrossRef]
- Flint, J.; Panchal, S.; Hurrell, A.; van de Venne, M.; Gayed, M.; Schreiber, K.; Arthanari, S.; Cunningham, J.; Flanders, L.; Moore, L.; et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: Standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2016, 55, 1693–1697. [Google Scholar] [CrossRef] [PubMed]
- Lau, A.G.; Clark, M.; Harrison, D.D.; Geldho, A.; Nissinen, R.; Sanders, M. Pregnancy outcomes in women exposed to golimumab. Arthritis Rheum. 2013, 65, S870–S871. [Google Scholar]
- Clowse, M.E.B.; Scheuerle, A.E.; Chambers, C.; Afzali, A.; Kimball, A.B.; Cush, J.J.; Cooney, M.; Shaughnessy, L.; Vanderkelen, M.; Förger, F. Pregnancy Outcomes After Exposure to Certolizumab Pegol: Updated Results from a Pharmacovigilance Safety Database. Arthritis Rheumatol. 2018, 70, 1399–1407. [Google Scholar] [CrossRef] [PubMed]
- Sandhu, V.K.; Wallace, D.J.; Weisman, M.H. Monoclonal antibodies, systemic lupus erythematosus, and pregnancy: Insights from an open-label study. J. Rheumatol. 2015, 42, 728–730. [Google Scholar] [CrossRef]
- Gelman, J.S.; Sironi, J.; Berezniuk, I.; Dasgupta, S.; Castro, L.M.; Gozzo, F.C.; Ferro, E.S.; Fricker, L.D. Alterations of the intracellular peptidome in response to the proteasome inhibitor bortezomib. PLoS ONE 2013, 8, e53263. [Google Scholar] [CrossRef]
- Auyeung-Kim, D.J.; Devalaraja, M.N.; Migone, T.S.; Cai, W.; Chellman, G.J. Developmental and peri-postnatal study in cynomolgus monkeys with belimumab, a monoclonal antibody directed against B-lymphocyte stimulator. Reprod. Toxicol. 2009, 28, 443–455. [Google Scholar] [CrossRef]
- Cabañas-Perianes, V.; Macizo, M.; Salido, E. Management multiple myeloma during pregnancy: A case report and review’. Hematol. Oncol. 2016, 34, 108–114. [Google Scholar] [CrossRef]
- Iqbal, J.; Ali, Z.; Khan, A.U.; Aziz, Z. Pregnancy outcomes in patients with chronic myeloid leukemia treated with imatinib mesylate: Short report from a developing country. Leuk. Lymphoma 2014, 55, 2109–2113. [Google Scholar] [CrossRef] [PubMed]
- Pye, S.M.; Cortes, J.; Ault, P.; Haltfield, A.; Kantarjian, H.; Pilot, R.; Rosti, G.; Apperley, J.F. The effects of imatinib on pregnancy outcome. Blood 2008, 111, 5105–5108. [Google Scholar] [CrossRef] [PubMed]
- Cortes, J.E.; Abruzzese, E.; Chelysheva, E.; Guha, M.; Wallis, N.; Apperley, J.F. The impact of dasatinib on pregnancy outcomes. Am. J. Hematol. 2015, 90, 1111–1115. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barkoulas, T.; Hall, P.D. Experience with dasatinib and nilotinib use in pregnancy. J. Oncol. Pharm. Pract. 2018, 24, 121–128. [Google Scholar] [CrossRef] [PubMed]
- Abruzzese, E.; Trawinska, M.M.; Perrotti, A.P.; De Fabritiis, P. Tyrosine kinase inhibitors and pregnancy. Mediterr. J. Hematol. Infect. Dis. 2014, 6, e2014028. [Google Scholar] [CrossRef] [PubMed]
- Carman, W.J.; Accortt, N.A.; Anthony, M.S.; Iles, J.; Enger, C. Pregnancy and infant outcomes including major congenital malformations among women with chronic inflammatory arthritis or psoriasis, with and without etanercept use. Pharmacoepidemiol. Drug Saf. 2017, 26, 1109–1118. [Google Scholar] [CrossRef] [PubMed]
- Viktil, K.K.; Engeland, A.; Furu, K. Outcomes after anti-rheumatic drug use before and during pregnancy: A cohort study among 150,000 pregnant women and expectant fathers. Scand. J. Rheumatol. 2012, 41, 196–201. [Google Scholar] [CrossRef]
- Weber-Schoendorfer, C.; Oppermann, M.; Wacker, E.; Bernard, N.; Network of French Pharmacovigilance Centres; Beghin, D.; Cuppers-Maarschalkerweerd, B.; Richardson, J.L.; Rothuizen, L.E.; Pistelli, A.; et al. Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: A prospective multicentre cohort study. Br. J. Clin. Pharmacol. 2015, 80, 727–739. [Google Scholar] [CrossRef]
- Kumar, M.; Ray, L.; Vemuri, S.; Simon, T.A. Pregnancy outcomes following exposure to abatacept during pregnancy. Semin. Arthritis Rheum. 2015, 45, 351–356. [Google Scholar] [CrossRef]
- Ponticelli, C.; Moroni, G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin. Drug Saf. 2017, 16, 411–419. [Google Scholar] [CrossRef]
- Costedoat-Chalumeau, N.; Amoura, Z.; Duhaut, P.; Huong, D.L.; Sebbough, D.; Wechsler, B.; Vauthier, D.; Denjoy, I.; Lupoglazoff, J.M.; Piette, J.C. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: A study of one hundred thirty-three cases compared with a control group. Arthritis Rheum. 2003, 48, 3207–3211. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sperber, K.; Hom, C.; Chao, C.P.; Shapiro, D.; Ash, J. Systematic review of hydroxychloroquine use in pregnant patients with autoimmune diseases. Pediatr. Rheumatol. Online J. 2009, 7, 9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Clowse, M.E.; Magder, L.; Witter, F.; Petri, M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum. 2006, 54, 3640–3647. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moroni, G.; Doria, A.; Giglio, E.; Tani, C.; Zen, M.; Strigini, F.; Zaina, B.; Tincani, A.; de Liso, F.; Matinato, C.; et al. Fetal outcome Fetal outcome and recommendations of pregnancies in lupus nephritis nant women with systemic lupus erythematosus in the 21st century: A descriptive cohort study. A prospective multicenter study. J. Autoimmun. 2016, 74, 6–12. [Google Scholar] [CrossRef] [PubMed]
- Kroese, S.J.; de Hair, M.J.H.; Limper, M.; van Laar, J.M.; Derksen, R.H.W.M.; Fritsch-Stork, R.D.E. Hydroxychloroquine Use in Lupus Patients during Pregnancy Is Associated with Longer Pregnancy Duration in Preterm Births. J. Immunol. Res. 2017, 2017, 2810202. [Google Scholar] [CrossRef] [PubMed]
- Cimaz, R.; Brucato, A.; Meregalli, E.; Muscará, M.; Sergi, P. Electroretinograms of children born to mothers treated with hydroxychloroquine during pregnancy and breast-feeding: Comment on the article by Costedoat-Chalumeau et al. Arthritis Rheum. 2004, 50, 3056–3057. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Motta, M.; Tincani, A.; Faden, D.; Zinzini, E.; Lojacono, A.; Marchesi, A.; Frassi, M.; Biasini, C.; Zatti, S.; Chirico, G. Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation. J. Perinatol. 2005, 25, 86–89. [Google Scholar] [CrossRef]
- Sammaritano, L.R.; Bermas, B.L. Rheumatoid arthritis medications and lactation. Curr. Opin. Rheumatol. 2014, 26, 354–360. [Google Scholar] [CrossRef]
- Kavanaugh, A.; Cush, J.J.; Ahmed, M.S.; Bermas, B.L.; Chakravarty, E.; Chambers, C.; Clowse, M.; Curtis, J.R.; Dao, K.; Hankins, G.D.; et al. Proceedings from the American College of Rheumatology Reproductive Health Summit: The management of fertility, pregnancy, and lactation in women with autoimmune and systemic inflammatory diseases. Arthritis Care Res. (Hoboken) 2015, 67, 313–325. [Google Scholar] [CrossRef]
- Rajagopalan, P.T.; Zhang, Z.; McCourt, L.; Dwyer, M.; Benkovic, S.J.; Hammes, G.G. Interaction of dihydrofolate reductase with methotrexate: Ensemble and single-molecule kinetics. Proc. Natl. Acad. Sci. USA 2002, 99, 13481–13486. [Google Scholar] [CrossRef]
- Koch, M.; Schwab, S.; Meyer, E.; Montanari, E.; Bader, Y.; Ott, J.; Helmy, S. Management of uterine ectopic pregnancy–local vs. systemic methotrexate. Acta Obstet. Gynecol. Scand. 2018, 97, 824–829. [Google Scholar] [CrossRef] [PubMed]
Category | Human Fetus Risk | Drugs |
---|---|---|
A | No fetal risk | |
B | No risk of human fetus. Possible animal risk but human studies lacking. | Infliximab, Adalimumab, Golimumab, Certolizumab, Etanercept |
C | Human risk cannot be ruled out | Glucocorticoids, Cyclosporine, Tacrolimus, Azathioprine, Sirolimus, Everolimus, Rituximab, Eculizumab, Belimumab, Hydroxychloroquine |
D | Evidence of risk to human fetus | Mycophenolate, Cyclophos phamide, Chlorambucil, Bortezomib, Tyosine-kinase inhibitors |
X | Contraindication in pregnancy | Leflunomide, Methotrexate |
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Ponticelli, C.; Moroni, G. Fetal Toxicity of Immunosuppressive Drugs in Pregnancy. J. Clin. Med. 2018, 7, 552. https://doi.org/10.3390/jcm7120552
Ponticelli C, Moroni G. Fetal Toxicity of Immunosuppressive Drugs in Pregnancy. Journal of Clinical Medicine. 2018; 7(12):552. https://doi.org/10.3390/jcm7120552
Chicago/Turabian StylePonticelli, Claudio, and Gabriella Moroni. 2018. "Fetal Toxicity of Immunosuppressive Drugs in Pregnancy" Journal of Clinical Medicine 7, no. 12: 552. https://doi.org/10.3390/jcm7120552
APA StylePonticelli, C., & Moroni, G. (2018). Fetal Toxicity of Immunosuppressive Drugs in Pregnancy. Journal of Clinical Medicine, 7(12), 552. https://doi.org/10.3390/jcm7120552