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Published in: Digestive Diseases and Sciences 6/2016

01-06-2016 | Original Article

The Effect of Maternal Peripartum Anti-TNFα Use on Infant Immune Response

Authors: Sarah Sheibani, Russell Cohen, Sunanda Kane, Marla Dubinsky, Joseph A. Church, Uma Mahadevan

Published in: Digestive Diseases and Sciences | Issue 6/2016

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Abstract

Background

Infliximab (IFX) and adalimumab (ADA) cross the placenta in the third trimester and can be detectable in infants for up to 12 months.

Aim

The aim of this study was to determine whether in utero IFX or ADA exposure results in an impaired immune response in infants, as measured by immunoglobulin levels and antibody responses to routine primary immunizations.

Methods

Infants who were exposed to in utero anti-TNFα agents were prospectively evaluated. Immunoglobulin levels (IgG, IgM, IgA) and antibodies to standard vaccinations, including tetanus toxoid (tetanus) and Haemophilus influenza type b (Hib), were measured in infants of at least 6 months of age.

Results

Twelve infants were prospectively studied: 10 exposed to in utero IFX and 2 exposed to ADA with at least one dose administered in the third trimester. Immunoglobulin levels were available on 10/12 patients, with all showing adequate immunoglobulin levels, except for low IgM levels in 5 (50 %) infants. Adequate responses to both the tetanus and Hib vaccines were seen in 11 of 12 (92 %) infants.

Conclusions

Infants exposed to anti-TNFα agents in utero demonstrate appropriate response to two commonly administered neonatal vaccines and show adequate immunoglobulin levels, except for IgM. Newborns with a history of exposure to anti-TNFα agents should follow a standard vaccination schedule for inactive vaccines.
Literature
1.
go back to reference Loftus E, Sandborn W. Epidemiology of inflammatory bowel disease. Gastroenterol Clin N Am. 2002;31:1–20.CrossRef Loftus E, Sandborn W. Epidemiology of inflammatory bowel disease. Gastroenterol Clin N Am. 2002;31:1–20.CrossRef
2.
go back to reference Bush MC, Patel S, Lapinksi RH, et al. Perinatal outcomes in inflammatory bowel disease. J Matern Fetal Neonatal Med. 2004;15:237–241.CrossRefPubMed Bush MC, Patel S, Lapinksi RH, et al. Perinatal outcomes in inflammatory bowel disease. J Matern Fetal Neonatal Med. 2004;15:237–241.CrossRefPubMed
3.
go back to reference Norgard B, Hundborg HH, Jacobsen BA, et al. Disease activity in pregnant women with Crohn’s disease and birth outcomes: a regional Danish Cohort study. Am J Gastroenterol. 2007;102:1947–1954.CrossRefPubMed Norgard B, Hundborg HH, Jacobsen BA, et al. Disease activity in pregnant women with Crohn’s disease and birth outcomes: a regional Danish Cohort study. Am J Gastroenterol. 2007;102:1947–1954.CrossRefPubMed
4.
go back to reference Reddy D, Murphy S, Kane S, et al. Relapse of inflammatory bowel disease during pregnancy: in-hospital management and birth outcomes. Am J Gastroenterol. 2008;103:1203–1209.CrossRefPubMed Reddy D, Murphy S, Kane S, et al. Relapse of inflammatory bowel disease during pregnancy: in-hospital management and birth outcomes. Am J Gastroenterol. 2008;103:1203–1209.CrossRefPubMed
5.
go back to reference Katz JA, Antoni C, Keenan GF, et al. Outcomes of pregnancy in women receiving infliximab for the treatment of Crohn’s disease and rheumatoid arthritis. Am J Gastroenterol. 2004;99:2385–2392.CrossRefPubMed Katz JA, Antoni C, Keenan GF, et al. Outcomes of pregnancy in women receiving infliximab for the treatment of Crohn’s disease and rheumatoid arthritis. Am J Gastroenterol. 2004;99:2385–2392.CrossRefPubMed
6.
go back to reference Mahadevan U, Cucchiara S, Hyams J, et al. The London position statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organization: pregnancy and pediatrics. Am J Gastroenterol. 2011;105:214–223.CrossRef Mahadevan U, Cucchiara S, Hyams J, et al. The London position statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organization: pregnancy and pediatrics. Am J Gastroenterol. 2011;105:214–223.CrossRef
7.
go back to reference Casanova MJ, Chaparro M, Domenech E, et al. Safety of thiopurines and anti-TNF drugs during pregnancy in patients with inflammatory bowel disease. Am J Gastroenterol. 2013;108:433–440.CrossRefPubMed Casanova MJ, Chaparro M, Domenech E, et al. Safety of thiopurines and anti-TNF drugs during pregnancy in patients with inflammatory bowel disease. Am J Gastroenterol. 2013;108:433–440.CrossRefPubMed
8.
go back to reference Mahadevan U, Martin C, Sandler RS, et al. PIANO: a 1000 patient prospective registry of pregnancy of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy. Gastroenterol. 2012;142:S-149. (abstract).CrossRef Mahadevan U, Martin C, Sandler RS, et al. PIANO: a 1000 patient prospective registry of pregnancy of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy. Gastroenterol. 2012;142:S-149. (abstract).CrossRef
9.
go back to reference Mahadevan U, Wolf D, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastro Hepatol. 2013;11:286–292.CrossRef Mahadevan U, Wolf D, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastro Hepatol. 2013;11:286–292.CrossRef
10.
go back to reference Julsgaard M, Christensen L, Gibson P. Adalimumab and infliximab level in neonates. Gastroenterology. 2015;148:S-108. (abstract).CrossRef Julsgaard M, Christensen L, Gibson P. Adalimumab and infliximab level in neonates. Gastroenterology. 2015;148:S-108. (abstract).CrossRef
11.
go back to reference Pasparakis M, Alexopoulou L, Episkopou V. Immune and inflammatory responses in TNFα-deficient mice: a critical requirement for TNFoL in the formation of primary B cell follicles follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J Exp Med. 1996;184:1397–1411.CrossRefPubMed Pasparakis M, Alexopoulou L, Episkopou V. Immune and inflammatory responses in TNFα-deficient mice: a critical requirement for TNFoL in the formation of primary B cell follicles follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J Exp Med. 1996;184:1397–1411.CrossRefPubMed
12.
go back to reference Wen L, Shinton SA, Hardy RR, et al. Association of B-1 B cells with follicular dendritic cells in spleen. J Immunol. 2005;174:6918–6926.CrossRefPubMed Wen L, Shinton SA, Hardy RR, et al. Association of B-1 B cells with follicular dendritic cells in spleen. J Immunol. 2005;174:6918–6926.CrossRefPubMed
13.
go back to reference Mamula P, Markowitz J, Piccoli D. Immune response to influenza vaccine in pediatric patients with inflammatory bowel disease. Clin Gastro Hepatol. 2007;5:851–856.CrossRef Mamula P, Markowitz J, Piccoli D. Immune response to influenza vaccine in pediatric patients with inflammatory bowel disease. Clin Gastro Hepatol. 2007;5:851–856.CrossRef
14.
go back to reference Fiorino G, Peyrin-Biroulet L, Naccarato P, et al. Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis. 2012;18:1042–1047.CrossRefPubMed Fiorino G, Peyrin-Biroulet L, Naccarato P, et al. Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis. 2012;18:1042–1047.CrossRefPubMed
15.
go back to reference Yeh S, Ward J, Partridge S. Safety and Immunogenicity of a pentavalent diphtheria, tetanus, pertussis, hepatitis B and polio combination vaccine in infants. Pediatr Infect Dis J. 2001;20:973–980.CrossRefPubMed Yeh S, Ward J, Partridge S. Safety and Immunogenicity of a pentavalent diphtheria, tetanus, pertussis, hepatitis B and polio combination vaccine in infants. Pediatr Infect Dis J. 2001;20:973–980.CrossRefPubMed
16.
go back to reference Kane S, Acquah L. Placental transport of immunoglobulins: a clinical review for gastroenterologist who prescribe therapeutic monoclonal antibodies to women during conception and pregnancy. Am J Gastroenterol. 2009;104:228–233.CrossRefPubMed Kane S, Acquah L. Placental transport of immunoglobulins: a clinical review for gastroenterologist who prescribe therapeutic monoclonal antibodies to women during conception and pregnancy. Am J Gastroenterol. 2009;104:228–233.CrossRefPubMed
17.
go back to reference Vasiliauskas EA, Church JA, Silverman N, et al. Case report: evidence for transplacental transfer of maternally administered infliximab to the newborn. Clin Gastroenterol Hepatol. 2006;4:1255–1258.CrossRefPubMed Vasiliauskas EA, Church JA, Silverman N, et al. Case report: evidence for transplacental transfer of maternally administered infliximab to the newborn. Clin Gastroenterol Hepatol. 2006;4:1255–1258.CrossRefPubMed
18.
go back to reference Zelinkova Z, de Haar C, de Ridder L, et al. High intra-uterine exposure to infliximab following maternal anti-TNF treatments during pregnancy. Aliment Pharmacol Ther. 2011;33:1053–1058.CrossRefPubMed Zelinkova Z, de Haar C, de Ridder L, et al. High intra-uterine exposure to infliximab following maternal anti-TNF treatments during pregnancy. Aliment Pharmacol Ther. 2011;33:1053–1058.CrossRefPubMed
19.
go back to reference Nesbitt A, Brown D, Stephens S. Placental transfer and accumulation in milk of the anti-TNF antibody TN3 in rats: immunoglobulin G1 verus PEGylated Fab. Am J Gastroenterol. 2006;101:S420–S470. (abstract).CrossRef Nesbitt A, Brown D, Stephens S. Placental transfer and accumulation in milk of the anti-TNF antibody TN3 in rats: immunoglobulin G1 verus PEGylated Fab. Am J Gastroenterol. 2006;101:S420–S470. (abstract).CrossRef
20.
go back to reference Martin PL, Oneda S, Treacy G. Effects of an anti-TNF-alpha monoclonal antibody, administered throughout pregnancy and lactation, on the development of the macaque immune system. Am J Reprod Immunol. 2007;58:138–149.CrossRefPubMed Martin PL, Oneda S, Treacy G. Effects of an anti-TNF-alpha monoclonal antibody, administered throughout pregnancy and lactation, on the development of the macaque immune system. Am J Reprod Immunol. 2007;58:138–149.CrossRefPubMed
21.
go back to reference Bortlik M, Duricova D, Machikova N, et al. Impact of anti-tumor necrosis factor alpha antibodies administered to pregnant women with inflammatory bowel disease on long-term outcome of exposed children. Inflamm Bowel Dis. 2014;20:495–501.CrossRefPubMed Bortlik M, Duricova D, Machikova N, et al. Impact of anti-tumor necrosis factor alpha antibodies administered to pregnant women with inflammatory bowel disease on long-term outcome of exposed children. Inflamm Bowel Dis. 2014;20:495–501.CrossRefPubMed
22.
go back to reference Cheent K, Nolan J, Shariq S, et al. Case report: fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn’s disease. J Crohns Colitis. 2010;4:603–605.CrossRefPubMed Cheent K, Nolan J, Shariq S, et al. Case report: fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn’s disease. J Crohns Colitis. 2010;4:603–605.CrossRefPubMed
Metadata
Title
The Effect of Maternal Peripartum Anti-TNFα Use on Infant Immune Response
Authors
Sarah Sheibani
Russell Cohen
Sunanda Kane
Marla Dubinsky
Joseph A. Church
Uma Mahadevan
Publication date
01-06-2016
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 6/2016
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3992-2

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