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Pediatric Drugs

, Volume 20, Issue 6, pp 511–521 | Cite as

Pharmacological Approach to Managing Childhood-Onset Systemic Lupus Erythematosus During Conception, Pregnancy and Breastfeeding

  • Nicole Bitencourt
  • Bonnie L. BermasEmail author
Therapy in Practice
  • 170 Downloads

Abstract

Pediatric patients often have poor pregnancy outcomes. Systemic lupus erythematosus predominantly impacts women in their second to fourth decade of life, with childhood-onset disease being particularly aggressive. Reproductive issues are an important clinical consideration for pediatric patients with systemic lupus erythematosus (SLE), as maintaining good disease control and planning a pregnancy are important for maternal and fetal outcomes. In this clinical review, we will consider the safety of medications in managing childhood-onset SLE during conception, pregnancy, and breastfeeding. The developing fetus is at highest risk for teratogenicity from maternal medications during the period of critical organogenesis, which occurs between the first 3–8 weeks following conception. Medications known to be teratogenic, leading to a specific pattern of malformations, include mycophenolic acid, methotrexate, and cyclophosphamide. These should be discontinued prior to a planned pregnancy or as soon as pregnancy is suspected. Hydroxychloroquine is safe and should be continued throughout pregnancy and breastfeeding in those without contraindications to it. Azathioprine and calcineurin inhibitors are felt to be compatible with pregnancy in usual doses and may be used prior to and throughout pregnancy and lactation. Non-fluorinated corticosteroids including methylprednisolone and prednisone are inactivated by the placenta and can be used if needed for maternal indication during gestation. Addition of aspirin may be considered around the 12th week of gestation for prevention of pre-eclampsia. Illustrative cases are presented that demonstrate management of adolescents with childhood-onset SLE through conception, pregnancy, and breastfeeding.

Notes

Compliance with Ethical Standards

Conflict of interest

Drs Bitencourt and Bermas report no conflicts of interest.

Funding

No funding was received for the preparation of this manuscript.

References

  1. 1.
    Mina R, Brunner HI. Pediatric lupus: are there differences in presentation, genetics, response to therapy, and damage accrual compared with adult lupus? Rheum Dis Clin North Am. 2010;36(1):53–80, vii–viii.PubMedGoogle Scholar
  2. 2.
    Tucker LB, Uribe AG, Fernandez M, et al. Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case–control study within LUMINA, a multiethnic US cohort (LUMINA LVII). Lupus. 2008;17(4):314–22.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Malabarey OT, Balayla J, Klam SL, Shrim A, Abenhaim HA. Pregnancies in young adolescent mothers: a population-based study on 37 million births. J Pediatr Adolesc Gynecol. 2012;25(2):98–102.PubMedGoogle Scholar
  4. 4.
    Chen XK, Wen SW, Fleming N, Demissie K, Rhoads GG, Walker M. Teenage pregnancy and adverse birth outcomes: a large population based retrospective cohort study. Int J Epidemiol. 2007;36(2):368–73.PubMedGoogle Scholar
  5. 5.
    Finer LB, Zolna MR. Declines in unintended pregnancy in the United States, 2008–2011. N Engl J Med. 2016;374(9):843–52.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Clark CA, Spitzer KA, Nadler JN, Laskin CA. Preterm deliveries in women with systemic lupus erythematosus. J Rheumatol. 2003;30(10):2127–32.PubMedGoogle Scholar
  7. 7.
    United States National Library of Medicine. ToxNet: Toxicology Data Network. LACTMED. https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm. Updated August 4, 2018. Accessed 8 Aug 2018.
  8. 8.
    Ulug P, Oner G, Kasap B, Akbas EM, Ozcicek F. Evaluation of ovarian reserve tests in women with systemic lupus erythematosus. Am J Reprod Immunol. 2014;72(1):85–8.PubMedGoogle Scholar
  9. 9.
    Silva CA, Leal MM, Leone C, et al. Gonadal function in adolescents and young women with juvenile systemic lupus erythematosus. Lupus. 2002;11(7):419–25.PubMedGoogle Scholar
  10. 10.
    Rygg M, Pistorio A, Ravelli A, et al. A longitudinal PRINTO study on growth and puberty in juvenile systemic lupus erythematosus. Ann Rheum Dis. 2012;71(4):511–7.PubMedGoogle Scholar
  11. 11.
    Brunner HI, Bishnoi A, Barron AC, et al. Disease outcomes and ovarian function of childhood-onset systemic lupus erythematosus. Lupus. 2006;15(4):198–206.PubMedGoogle Scholar
  12. 12.
    Huong DL, Amoura Z, Duhaut P, et al. Risk of ovarian failure and fertility after intravenous cyclophosphamide. A study in 84 patients. J Rheumatol. 2002;29(12):2571–6.PubMedGoogle Scholar
  13. 13.
    Cortes-Hernandez J, Ordi-Ros J, Paredes F, Casellas M, Castillo F, Vilardell-Tarres M. Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies. Rheumatology (Oxford). 2002;41(6):643–50.Google Scholar
  14. 14.
    Clowse ME, Magder LS, Witter F, Petri M. The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum. 2005;52(2):514–21.PubMedGoogle Scholar
  15. 15.
    Buyon JP, Kim MY, Guerra MM, et al. Predictors of pregnancy outcomes in patients with lupus: a cohort study. Ann Intern Med. 2015;163(3):153–63.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Saavedra MA, Miranda-Hernandez D, Sanchez A, et al. Pregnancy outcomes in women with childhood-onset and adult-onset systemic lupus erythematosus: a comparative study. Rheumatol Int. 2016;36(10):1431–7.PubMedGoogle Scholar
  17. 17.
    Silva CA, Hilario MO, Febronio MV, et al. Pregnancy outcome in juvenile systemic lupus erythematosus: a Brazilian multicenter cohort study. J Rheumatol. 2008;35(7):1414–8.PubMedGoogle Scholar
  18. 18.
    Webster WS, Freeman JA. Prescription drugs and pregnancy. Expert Opin Pharmacother. 2003;4(6):949–61.PubMedGoogle Scholar
  19. 19.
    Henderson E, Mackillop L. Prescribing in pregnancy and during breast feeding: using principles in clinical practice. Postgrad Med J. 1027;2011(87):349–54.Google Scholar
  20. 20.
    Rowe H, Baker T, Hale TW. Maternal medication, drug use, and breastfeeding. Pediatr Clin N Am. 2013;60(1):275–94.Google Scholar
  21. 21.
    Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. BMJ. 2003;327(7411):368.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Nielsen GL, Sorensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case–control study. BMJ. 2001;322(7281):266–70.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Nakhai-Pour HR, Broy P, Sheehy O, Berard A. Use of nonaspirin nonsteroidal anti-inflammatory drugs during pregnancy and the risk of spontaneous abortion. CMAJ. 2011;183(15):1713–20.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Edwards DR, Aldridge T, Baird DD, Funk MJ, Savitz DA, Hartmann KE. Periconceptional over-the-counter nonsteroidal anti-inflammatory drug exposure and risk for spontaneous abortion. Obstet Gynecol. 2012;120(1):113–22.PubMedGoogle Scholar
  25. 25.
    Daniel S, Koren G, Lunenfeld E, Bilenko N, Ratzon R, Levy A. Fetal exposure to nonsteroidal anti-inflammatory drugs and spontaneous abortions. CMAJ. 2014;186(5):E177–82.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Ofori B, Oraichi D, Blais L, Rey E, Berard A. Risk of congenital anomalies in pregnant users of non-steroidal anti-inflammatory drugs: a nested case–control study. Birth Defects Res B Dev Reprod Toxicol. 2006;77(4):268–79.PubMedGoogle Scholar
  27. 27.
    van Gelder MM, Roeleveld N, Nordeng H. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and the risk of selected birth defects: a prospective cohort study. PLoS One. 2011;6(7):e22174.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Daniel S, Matok I, Gorodischer R, et al. Major malformations following exposure to nonsteroidal antiinflammatory drugs during the first trimester of pregnancy. J Rheumatol. 2012;39(11):2163–9.PubMedGoogle Scholar
  29. 29.
    Nezvalova-Henriksen K, Spigset O, Nordeng H. Effects of ibuprofen, diclofenac, naproxen, and piroxicam on the course of pregnancy and pregnancy outcome: a prospective cohort study. BJOG. 2013;120(8):948–59.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Koren G, Florescu A, Costei AM, Boskovic R, Moretti ME. Nonsteroidal antiinflammatory drugs during third trimester and the risk of premature closure of the ductus arteriosus: a meta-analysis. Ann Pharmacother. 2006;40(5):824–9.PubMedGoogle Scholar
  31. 31.
    Alano MA, Ngougmna E, Ostrea EM Jr, Konduri GG. Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn. Pediatrics. 2001;107(3):519–23.PubMedGoogle Scholar
  32. 32.
    Cuzzolin L, Dal Cere M, Fanos V. NSAID-induced nephrotoxicity from the fetus to the child. Drug Saf. 2001;24(1):9–18.PubMedGoogle Scholar
  33. 33.
    Townsend RJ, Benedetti TJ, Erickson SH, et al. Excretion of ibuprofen into breast milk. Am J Obstet Gynecol. 1984;149(2):184–6.PubMedGoogle Scholar
  34. 34.
    Lebedevs TH, Wojnar-Horton RE, Yapp P, et al. Excretion of indomethacin in breast milk. Br J Clin Pharmacol. 1991;32(6):751–4.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Voltaren package insert.Google Scholar
  36. 36.
    Jamali F, Stevens DR. Naproxen excretion in milk and its uptake by the infant. Drug Intell Clin Pharm. 1983;17(12):910–1.PubMedGoogle Scholar
  37. 37.
    Ostensen M, Matheson I, Laufen H. Piroxicam in breast milk after long-term treatment. Eur J Clin Pharmacol. 1988;35(5):567–9.PubMedGoogle Scholar
  38. 38.
    Kozer E, Costei AM, Boskovic R, Nulman I, Nikfar S, Koren G. Effects of aspirin consumption during pregnancy on pregnancy outcomes: meta-analysis. Birth Defects Res B Dev Reprod Toxicol. 2003;68(1):70–84.PubMedGoogle Scholar
  39. 39.
    Roberge S, Nicolaides K, Demers S, Hyett J, Chaillet N, Bujold E. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am J Obstet Gynecol. 2017;216(2):110e116–120e116.Google Scholar
  40. 40.
    CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet. 1994;343(8898):619–29.Google Scholar
  41. 41.
    Schramm AM, Clowse ME. Aspirin for prevention of preeclampsia in lupus pregnancy. Autoimmune Dis. 2014;2014:920467.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Stuart MJ, Gross SJ, Elrad H, Graeber JE. Effects of acetylsalicylic-acid ingestion on maternal and neonatal hemostasis. N Engl J Med. 1982;307(15):909–12.PubMedGoogle Scholar
  43. 43.
    Sibai BM, Caritis SN, Thom E, Shaw K, McNellis D. Low-dose aspirin in nulliparous women: safety of continuous epidural block and correlation between bleeding time and maternal-neonatal bleeding complications. National Institute of Child Health and Human Developmental Maternal-Fetal Medicine Network. Am J Obstet Gynecol. 1995;172(5):1553–7.PubMedGoogle Scholar
  44. 44.
    Benigni A, Gregorini G, Frusca T, et al. Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension. N Engl J Med. 1989;321(6):357–62.PubMedGoogle Scholar
  45. 45.
    Datta P, Rewers-Felkins K, Kallem RR, Baker T, Hale TW. Transfer of low dose aspirin into human milk. J Hum Lancet. 2017;33(2):296–9.Google Scholar
  46. 46.
    Clark JH, Wilson WG. A 16-day-old breast-fed infant with metabolic acidosis caused by salicylate. Clin Pediatr (Phila). 1981;20(1):53–4.PubMedGoogle Scholar
  47. 47.
    Ballard PL, Ballard RA. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am J Obstet Gynecol. 1995;173(1):254–62.PubMedGoogle Scholar
  48. 48.
    Bonanno C, Wapner RJ. Antenatal corticosteroid treatment: what’s happened since Drs Liggins and Howie? Am J Obstet Gynecol. 2009;200(4):448–57.PubMedGoogle Scholar
  49. 49.
    Benediktsson R, Calder AA, Edwards CR, Seckl JR. Placental 11 beta-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure. Clin Endocrinol (Oxf). 1997;46(2):161–6.Google Scholar
  50. 50.
    Burton PJ, Waddell BJ. Dual function of 11beta-hydroxysteroid dehydrogenase in placenta: modulating placental glucocorticoid passage and local steroid action. Biol Reprod. 1999;60(2):234–40.PubMedGoogle Scholar
  51. 51.
    Rodriguez-Pinilla E, Martinez-Frias ML. Corticosteroids during pregnancy and oral clefts: a case–control study. Teratology. 1998;58(1):2–5.PubMedGoogle Scholar
  52. 52.
    Pradat P, Robert-Gnansia E, Di Tanna GL, et al. First trimester exposure to corticosteroids and oral clefts. Birth Defects Res A Clin Mol Teratol. 2003;67(12):968–70.PubMedGoogle Scholar
  53. 53.
    Hviid A, Molgaard-Nielsen D. Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ. 2011;183(7):796–804.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Bay Bjorn AM, Ehrenstein V, Hundborg HH, Nohr EA, Sorensen HT, Norgaard 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(2):73–80.PubMedGoogle Scholar
  55. 55.
    Yildirim Y, Tinar S, Oner RS, Kaya B, Toz E. Gestational diabetes mellitus in patients receiving long-term corticosteroid therapy during pregnancy. J Perinat Med. 2006;34(4):280–4.PubMedGoogle Scholar
  56. 56.
    Leung YP, Kaplan GG, Coward S, et al. Intrapartum corticosteroid use significantly increases the risk of gestational diabetes in women with inflammatory bowel disease. J Crohns Colitis. 2015;9(3):223–30.PubMedGoogle Scholar
  57. 57.
    Fisher JE, Smith RS, Lagrandeur R, Lorenz RP. Gestational diabetes mellitus in women receiving beta-adrenergics and corticosteroids for threatened preterm delivery. Obstet Gynecol. 1997;90(6):880–3.PubMedGoogle Scholar
  58. 58.
    Cowchock FS, Reece EA, Balaban D, Branch DW, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol. 1992;166(5):1318–23.PubMedGoogle Scholar
  59. 59.
    Katz FH, Duncan BR. Letter: entry of prednisone into human milk. N Engl J Med. 1975;293(22):1154.PubMedGoogle Scholar
  60. 60.
    Greenberger PA, Odeh YK, Frederiksen MC, Atkinson AJ Jr. Pharmacokinetics of prednisolone transfer to breast milk. Clin Pharmacol Ther. 1993;53(3):324–8.PubMedGoogle Scholar
  61. 61.
    Ost L, Wettrell G, Bjorkhem I, Rane A. Prednisolone excretion in human milk. J Pediatr. 1985;106(6):1008–11.PubMedGoogle Scholar
  62. 62.
    Cooper SD, Felkins K, Baker TE, Hale TW. Transfer of methylprednisolone into breast milk in a mother with multiple sclerosis. J Hum Lancet. 2015;31(2):237–9.Google Scholar
  63. 63.
    Costedoat-Chalumeau N, Amoura Z, Duhaut P, et al. 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(11):3207–11.PubMedGoogle Scholar
  64. 64.
    Klinger G, Morad Y, Westall CA, et al. Ocular toxicity and antenatal exposure to chloroquine or hydroxychloroquine for rheumatic diseases. Lancet. 2001;358(9284):813–4.PubMedGoogle Scholar
  65. 65.
    Law I, Ilett KF, Hackett LP, et al. Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers. Br J Clin Pharmacol. 2008;65(5):674–9.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Matz GJ, Naunton RF. Ototoxicity of chloroquine. Arch Otolaryngol. 1968;88(4):370–2.PubMedGoogle Scholar
  67. 67.
    Villegas L, McGready R, Htway M, et al. Chloroquine prophylaxis against vivax malaria in pregnancy: a randomized, double-blind, placebo-controlled trial. Trop Med Int Health. 2007;12(2):209–18.PubMedGoogle Scholar
  68. 68.
    Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation. 2012;126(1):76–82.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Clowse ME, Magder L, Witter F, Petri M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum. 2006;54(11):3640–7.PubMedGoogle Scholar
  70. 70.
    Koh JH, Ko HS, Kwok SK, Ju JH, Park SH. Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus. Lupus. 2015;24(2):210–7.PubMedGoogle Scholar
  71. 71.
    Kroese SJ, de Hair MJH, Limper M, et al. Hydroxychloroquine use in lupus patients during pregnancy is associated with longer pregnancy duration in preterm births. J Immunol Res. 2017;2017:2810202.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Costedoat-Chalumeau N, Amoura Z, Huong DL, Lechat P, Piette JC. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases. Review of the literature. Autoimmun Rev. 2005;4(2):111–5.PubMedGoogle Scholar
  73. 73.
    Polifka JE, Friedman JM. Teratogen update: azathioprine and 6-mercaptopurine. Teratology. 2002;65(5):240–61.PubMedGoogle Scholar
  74. 74.
    Norgard B, Pedersen L, Christensen LA, Sorensen HT. Therapeutic drug use in women with Crohn’s disease and birth outcomes: a Danish nationwide cohort study. Am J Gastroenterol. 2007;102(7):1406–13.PubMedGoogle Scholar
  75. 75.
    Shim L, Eslick GD, Simring AA, Murray H, Weltman MD. The effects of azathioprine on birth outcomes in women with inflammatory bowel disease (IBD). J Crohns Colitis. 2011;5(3):234–8.PubMedGoogle Scholar
  76. 76.
    Francella A, Dyan A, Bodian C, Rubin P, Chapman M, Present DH. The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study. Gastroenterology. 2003;124(1):9–17.PubMedGoogle Scholar
  77. 77.
    Langagergaard V, Pedersen L, Gislum M, Norgard B, Sorensen HT. Birth outcome in women treated with azathioprine or mercaptopurine during pregnancy: a Danish nationwide cohort study. Aliment Pharmacol Ther. 2007;25(1):73–81.PubMedGoogle Scholar
  78. 78.
    Sau A, Clarke S, Bass J, Kaiser A, Marinaki A, Nelson-Piercy C. Azathioprine and breastfeeding: is it safe? BJOG. 2007;114(4):498–501.PubMedGoogle Scholar
  79. 79.
    Gardiner SJ, Gearry RB, Roberts RL, Zhang M, Barclay ML, Begg EJ. Exposure to thiopurine drugs through breast milk is low based on metabolite concentrations in mother-infant pairs. Br J Clin Pharmacol. 2006;62(4):453–6.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Christensen LA, Dahlerup JF, Nielsen MJ, Fallingborg JF, Schmiegelow K. Azathioprine treatment during lactation. Aliment Pharmacol Ther. 2008;28(10):1209–13.PubMedGoogle Scholar
  81. 81.
    Bar Oz B, Hackman R, Einarson T, Koren G. Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis. Transplantation. 2001;71(8):1051–5.PubMedGoogle Scholar
  82. 82.
    Paziana K, Del Monaco M, Cardonick E, et al. Ciclosporin use during pregnancy. Drug Saf. 2013;36(5):279–94.PubMedGoogle Scholar
  83. 83.
    Giudice PL, Dubourg L, Hadj-Aissa A, et al. Renal function of children exposed to cyclosporin in utero. Nephrol Dial Transplant. 2000;15(10):1575–9.PubMedGoogle Scholar
  84. 84.
    Nulman I, Sgro M, Barrera M, Chitayat D, Cairney J, Koren G. Long-term neurodevelopment of children exposed in utero to ciclosporin after maternal renal transplant. Paediatr Drugs. 2010;12(2):113–22.PubMedGoogle Scholar
  85. 85.
    Thomas AG, Burrows L, Knight R, Panico M, Lapinski R, Lockwood CJ. The effect of pregnancy on cyclosporine levels in renal allograft patients. Obstet Gynecol. 1997;90(6):916–9.PubMedGoogle Scholar
  86. 86.
    Moretti ME, Sgro M, Johnson DW, et al. Cyclosporine excretion into breast milk. Transplantation. 2003;75(12):2144–6.PubMedGoogle Scholar
  87. 87.
    Kainz A, Harabacz I, Cowlrick IS, Gadgil SD, Hagiwara D. Review of the course and outcome of 100 pregnancies in 84 women treated with tacrolimus. Transplantation. 2000;70(12):1718–21.PubMedGoogle Scholar
  88. 88.
    Nevers W, Pupco A, Koren G, Bozzo P. Safety of tacrolimus in pregnancy. Can Fam Physician. 2014;60(10):905–6.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Webster P, Wardle A, Bramham K, Webster L, Nelson-Piercy C, Lightstone L. Tacrolimus is an effective treatment for lupus nephritis in pregnancy. Lupus. 2014;23(11):1192–6.PubMedGoogle Scholar
  90. 90.
    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(4):563–7.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Coscia LA, Armenti DP, King RW, Sifontis NM, Constantinescu S, Moritz MJ. Update on the teratogenicity of maternal mycophenolate mofetil. J Pediatr Genet. 2015;4(2):42–55.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Anderka MT, Lin AE, Abuelo DN, Mitchell AA, Rasmussen SA. Reviewing the evidence for mycophenolate mofetil as a new teratogen: case report and review of the literature. Am J Med Genet A. 2009;149A(6):1241–8.PubMedGoogle Scholar
  93. 93.
    Perez-Aytes A, Ledo A, Boso V, et al. In utero exposure to mycophenolate mofetil: a characteristic phenotype? Am J Med Genet A. 2008;146A(1):1–7.PubMedGoogle Scholar
  94. 94.
    Sifontis NM, Coscia LA, Constantinescu S, Lavelanet AF, Moritz MJ, Armenti VT. Pregnancy outcomes in solid organ transplant recipients with exposure to mycophenolate mofetil or sirolimus. Transplantation. 2006;82(12):1698–702.PubMedGoogle Scholar
  95. 95.
    Hoeltzenbein M, Elefant E, Vial T, et al. Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services. Am J Med Genet A. 2012;158A(3):588–96.PubMedGoogle Scholar
  96. 96.
    Al Maimouni H, Gladman DD, Ibanez D, Urowitz MB. Switching treatment between mycophenolate mofetil and azathioprine in lupus patients: indications and outcomes. Arthritis Care Res (Hoboken). 2014;66(12):1905–9.PubMedGoogle Scholar
  97. 97.
    Fischer-Betz R, Specker C, Brinks R, Aringer M, Schneider M. Low risk of renal flares and negative outcomes in women with lupus nephritis conceiving after switching from mycophenolate mofetil to azathioprine. Rheumatology (Oxford). 2013;52(6):1070–6.Google Scholar
  98. 98.
    Weber-Schoendorfer C, Chambers C, Wacker E, et al. Pregnancy outcome after methotrexate treatment for rheumatic disease prior to or during early pregnancy: a prospective multicenter cohort study. Arthritis Rheumatol. 2014;66(5):1101–10.PubMedGoogle Scholar
  99. 99.
    Bawle EV, Conard JV, Weiss L. Adult and two children with fetal methotrexate syndrome. Teratology. 1998;57(2):51–5.PubMedGoogle Scholar
  100. 100.
    Lewden B, Vial T, Elefant E, et al. Low dose methotrexate in the first trimester of pregnancy: results of a French collaborative study. J Rheumatol. 2004;31(12):2360–5.PubMedGoogle Scholar
  101. 101.
    Visser K, Katchamart W, Loza E, et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis. 2009;68(7):1086–93.PubMedGoogle Scholar
  102. 102.
    Thorne JC, Nadarajah T, Moretti M, Ito S. Methotrexate use in a breastfeeding patient with rheumatoid arthritis. J Rheumatol. 2014;41(11):2332.PubMedGoogle Scholar
  103. 103.
    American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001;108(3):776–89.Google Scholar
  104. 104.
    Enns GM, Roeder E, Chan RT, Ali-Khan Catts Z, Cox VA, Golabi M. Apparent cyclophosphamide (cytoxan) embryopathy: a distinct phenotype? Am J Med Genet. 1999;86(3):237–41.PubMedGoogle Scholar
  105. 105.
    Kirshon B, Wasserstrum N, Willis R, Herman GE, McCabe ER. Teratogenic effects of first-trimester cyclophosphamide therapy. Obstet Gynecol. 1988;72(3 Pt 2):462–4.PubMedGoogle Scholar
  106. 106.
    Paladini D, Vassallo M, D’Armiento MR, Cianciaruso B, Martinelli P. Prenatal detection of multiple fetal anomalies following inadvertent exposure to cyclophosphamide in the first trimester of pregnancy. Birth Defects Res A Clin Mol Teratol. 2004;70(2):99–100.PubMedGoogle Scholar
  107. 107.
    Vaux KK, Kahole NC, Jones KL. Cyclophosphamide, methotrexate, and cytarabine embropathy: is apoptosis the common pathway? Birth Defects Res A Clin Mol Teratol. 2003;67(6):403–8.PubMedGoogle Scholar
  108. 108.
    Zemlickis D, Lishner M, Erlich R, Koren G. Teratogenicity and carcinogenicity in a twin exposed in utero to cyclophosphamide. Teratog Carcinog Mutagen. 1993;13(3):139–43.PubMedGoogle Scholar
  109. 109.
    Kart Koseoglu H, Yucel AE, Kunefeci G, Ozdemir FN, Duran H. Cyclophosphamide therapy in a serious case of lupus nephritis during pregnancy. Lupus. 2001;10(11):818–20.PubMedGoogle Scholar
  110. 110.
    Hardin JA. Cyclophosphamide treatment of lymphoma during third trimester of pregnancy. Obstet Gynecol. 1972;39(6):850–1.PubMedGoogle Scholar
  111. 111.
    Berry DL, Theriault RL, Holmes FA, et al. Management of breast cancer during pregnancy using a standardized protocol. J Clin Oncol. 1999;17(3):855–61.PubMedGoogle Scholar
  112. 112.
    Durodola JI. Administration of cyclophosphamide during late pregnancy and early lactation: a case report. J Natl Med Assoc. 1979;71(2):165–6.PubMedPubMedCentralGoogle Scholar
  113. 113.
    Perricone R, De Carolis C, Kroegler B, et al. Intravenous immunoglobulin therapy in pregnant patients affected with systemic lupus erythematosus and recurrent spontaneous abortion. Rheumatology (Oxford). 2008;47(5):646–51.Google Scholar
  114. 114.
    Clark AL, Gall SA. Clinical uses of intravenous immunoglobulin in pregnancy. Am J Obstet Gynecol. 1997;176(1 Pt 1):241–53.PubMedGoogle Scholar
  115. 115.
    Kaaja R, Julkunen H, Ammala P, Teppo AM, Kurki P. Congenital heart block: successful prophylactic treatment with intravenous gamma globulin and corticosteroid therapy. Am J Obstet Gynecol. 1991;165(5 Pt 1):1333–4.PubMedGoogle Scholar
  116. 116.
    David AL, Ataullah I, Yates R, Sullivan I, Charles P, Williams D. Congenital fetal heart block: a potential therapeutic role for intravenous immunoglobulin. Obstet Gynecol. 2010;116(Suppl 2):543–7.PubMedGoogle Scholar
  117. 117.
    Gordon C, Kilby MD. Use of intravenous immunoglobulin therapy in pregnancy in systemic lupus erythematosus and antiphospholipid antibody syndrome. Lupus. 1998;7(7):429–33.PubMedGoogle Scholar
  118. 118.
    Tenti S, Cheleschi S, Guidelli GM, Galeazzi M, Fioravanti A. Intravenous immunoglobulins and antiphospholipid syndrome: how, when and why? A review of the literature. Autoimmun Rev. 2016;15(3):226–35.PubMedGoogle Scholar
  119. 119.
    Palmeira P, Costa-Carvalho BT, Arslanian C, Pontes GN, Nagao AT, Carneiro-Sampaio MM. Transfer of antibodies across the placenta and in breast milk from mothers on intravenous immunoglobulin. Pediatr Allergy Immunol. 2009;20(6):528–35.PubMedGoogle Scholar
  120. 120.
    Ton E, Tekstra J, Hellmann PM, Nuver-Zwart IH, Bijlsma JW. Safety of rituximab therapy during twins’ pregnancy. Rheumatology (Oxford). 2011;50(4):806–8.Google Scholar
  121. 121.
    Malek A. Ex vivo human placenta models: transport of immunoglobulin G and its subclasses. Vaccine. 2003;21(24):3362–4.PubMedGoogle Scholar
  122. 122.
    Klink DT, van Elburg RM, Schreurs MW, van Well GT. Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development. Clin Dev Immunol. 2008;2008:271363.PubMedPubMedCentralGoogle Scholar
  123. 123.
    Gasparoni A, Avanzini A, Ravagni Probizer F, Chirico G, Rondini G, Severi F. IgG subclasses compared in maternal and cord serum and breast milk. Arch Dis Child. 1992;67((Spec No 1)):41–3.PubMedPubMedCentralGoogle Scholar
  124. 124.
    Bragnes Y, Boshuizen R, de Vries A, Lexberg A, Ostensen M. Low level of Rituximab in human breast milk in a patient treated during lactation. Rheumatology (Oxford). 2017;56(6):1047–8.Google Scholar
  125. 125.
    Emmi G, Silvestri E, Squatrito D, et al. Favorable pregnancy outcome in a patient with systemic lupus erythematosus treated with belimumab: a confirmation report. Semin Arthritis Rheum. 2016;45(6):e26–7.PubMedGoogle Scholar
  126. 126.
    Danve A, Perry L, Deodhar A. Use of belimumab throughout pregnancy to treat active systemic lupus erythematosus: a case report. Semin Arthritis Rheum. 2014;44(2):195–7.PubMedGoogle Scholar
  127. 127.
    Bitter H, Bendvold AN, Ostensen ME. Lymphocyte changes and vaccination response in a child exposed to belimumab during pregnancy. Ann Rheum Dis. 2018.  https://doi.org/10.1136/annrheumdis-2018-213004.CrossRefPubMedGoogle Scholar
  128. 128.
    Auyeung-Kim DJ, Devalaraja MN, Migone TS, Cai W, Chellman GJ. Developmental and peri-postnatal study in cynomolgus monkeys with belimumab, a monoclonal antibody directed against B-lymphocyte stimulator. Reprod Toxicol. 2009;28(4):443–55.PubMedGoogle Scholar
  129. 129.
    Bullo M, Tschumi S, Bucher BS, Bianchetti MG, Simonetti GD. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists: a systematic review. Hypertension. 2012;60(2):444–50.PubMedGoogle Scholar
  130. 130.
    Nadeem S, Hashmat S, Defreitas MJ, et al. Renin angiotensin system blocker fetopathy: a midwest pediatric nephrology consortium report. J Pediatr. 2015;167(4):881–5.PubMedGoogle Scholar
  131. 131.
    Moretti ME, Caprara D, Drehuta I, et al. The fetal safety of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. Obstet Gynecol Int. 2012;2012:658310.PubMedGoogle Scholar
  132. 132.
    Bateman BT, Patorno E, Desai RJ, et al. Angiotensin-converting enzyme inhibitors and the risk of congenital malformations. Obstet Gynecol. 2017;129(1):174–84.PubMedPubMedCentralGoogle Scholar
  133. 133.
    Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006;354(23):2443–51.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Division of Rheumatic DiseasesUniversity of Texas Southwestern Medical CenterDallasUSA

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