Paediatric infections in the first 3 years of life after maternal anti-TNF treatment during pregnancy.
Adult
Age of Onset
Anti-Inflammatory Agents
/ therapeutic use
Antirheumatic Agents
/ therapeutic use
Arthritis, Rheumatoid
/ drug therapy
Child Development
/ drug effects
Child, Preschool
Cohort Studies
Denmark
/ epidemiology
Female
Finland
/ epidemiology
Humans
Infant
Infant, Newborn
Infections
/ chemically induced
Inflammatory Bowel Diseases
/ drug therapy
Pregnancy
Pregnancy Complications
/ drug therapy
Prenatal Exposure Delayed Effects
/ chemically induced
Psoriasis
Risk Assessment
Spondylitis, Ankylosing
/ drug therapy
Sweden
/ epidemiology
Tumor Necrosis Factor-alpha
/ antagonists & inhibitors
Young Adult
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
31
03
2020
revised:
26
04
2020
accepted:
26
06
2020
pubmed:
25
7
2020
medline:
15
12
2020
entrez:
25
7
2020
Statut:
ppublish
Résumé
Most anti-tumour necrosis factor (anti-TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections. To assess the risk of paediatric infections after maternal anti-TNF treatment. Population-based cohort study in Denmark, Finland and Sweden 2006-2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti-TNF, and 9346 children to women with non-biologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years. Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23-1.67) for anti-TNF and 1.14 (1.07-1.21) for non-biologic systemic treatment, and 1.29 (1.11-1.50) and 1.09 (1.02-1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti-TNF, 1.19 (1.11-1.29), and for non-biologic systemic treatment, 1.10 (1.07-1.13). There was no difference among anti-TNF agents, treatment in the third trimester, or between mono/combination therapy with non-biologic systemic treatment. Both anti-TNF and non-biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, or with combination treatment, and were not persistent during the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare-seeking behaviour. This may in turn shift the risk-benefit equation towards continuation of treatment even in the third trimester.
Sections du résumé
BACKGROUND
Most anti-tumour necrosis factor (anti-TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections.
AIMS
To assess the risk of paediatric infections after maternal anti-TNF treatment.
METHODS
Population-based cohort study in Denmark, Finland and Sweden 2006-2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti-TNF, and 9346 children to women with non-biologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years.
RESULTS
Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23-1.67) for anti-TNF and 1.14 (1.07-1.21) for non-biologic systemic treatment, and 1.29 (1.11-1.50) and 1.09 (1.02-1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti-TNF, 1.19 (1.11-1.29), and for non-biologic systemic treatment, 1.10 (1.07-1.13). There was no difference among anti-TNF agents, treatment in the third trimester, or between mono/combination therapy with non-biologic systemic treatment.
CONCLUSIONS
Both anti-TNF and non-biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, or with combination treatment, and were not persistent during the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare-seeking behaviour. This may in turn shift the risk-benefit equation towards continuation of treatment even in the third trimester.
Substances chimiques
Anti-Inflammatory Agents
0
Antirheumatic Agents
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
843-854Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
Références
Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46-54; e42; quiz e30.
Kvien TK, Uhlig T, Odegard S, Heiberg MS. Epidemiological aspects of rheumatoid arthritis: the sex ratio. Ann N Y Acad Sci. 2006;1069:212-222.
Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford). 2014;53:650-657.
Ritchlin CT, Colbert RA, Gladman DD. Psoriatic Arthritis. N Engl J Med. 2017;376:2095-2096.
Han J, Lee J, Han K, et al. Epidemiology and medication trends in patients with psoriasis: a nationwide population-based cohort study from Korea. Acta Derm Venereol. 2018;98:396-400.
Nørgaard M, Larsson H, Pedersen L, et al. Rheumatoid arthritis and birth outcomes: a Danish and Swedish nationwide prevalence study. J Intern Med. 2010;268:329-337.
Broms G, Granath F, Linder M, Stephansson O, Elmberg M, Kieler H. Birth outcomes in women with inflammatory bowel disease: effects of disease activity and drug exposure. Inflamm Bowel Dis. 2014;20:1091-1098.
Broms G, Haerskjold A, Granath F, Kieler H, Pedersen L, Berglind IA. Effect of maternal psoriasis on pregnancy and birth outcomes: a population-based cohort study from Denmark and Sweden. Acta Derm Venereol. 2018;98:728-734.
Luu M, Benzenine E, Doret M, et al. Continuous anti-TNFalpha use throughout pregnancy: possible complications for 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.
Bernatsky S, Habel Y, Rahme E. Observational studies of infections in rheumatoid arthritis: a metaanalysis of tumor necrosis factor antagonists. J Rheumatol. 2010;37:928-931.
Targownik LE, Bernstein CN. Infectious and malignant complications of TNF inhibitor therapy in IBD. Am J Gastroenterol 2013;108(12):1835-1842, quiz 1843.
Leombruno JP, Einarson TR, Keystone EC. The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: meta and exposure-adjusted pooled analyses of serious adverse events. Ann Rheum Dis. 2009;68:1136-1145.
Fouda GG, Martinez DR, Swamy GK, Permar SR. The Impact of IgG transplacental transfer on early life immunity. Immunohorizons. 2018;2:14-25.
Berthelsen BG, Fjeldsoe-Nielsen H, Nielsen CT, Hellmuth E. Etanercept concentrations in maternal serum, umbilical cord serum, breast milk and child serum during breastfeeding. Rheumatology (Oxford). 2010;49:2225-2227.
Mariette X, Förger F, Abraham B, et al. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018;77:228-233.
Julsgaard M, Christensen LA, Gibson PR, et al. Concentrations of adalimumab and infliximab in mothers and newborns, and effects on infection. Gastroenterology. 2016;151:110-119.
Zelinkova Z, de Haar C, de Ridder L, et al. High intra-uterine exposure to infliximab following maternal anti-TNF treatment during pregnancy. Aliment Pharmacol Ther. 2011;33:1053-1058.
Mahadevan U, Martin CF, Sandler RS, et al. 865 PIANO: a 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic. Therapy. Gastroenterology. 2012;142(5):S-149.
Chaparro M, Verreth A, Lobaton T, et al. Long-term safety of in utero exposure to anti-TNFalpha drugs for the treatment of inflammatory bowel disease: results from the Multicenter European TEDDY Study. Am J Gastroenterol. 2018;113:396-403.
Tsao NW, Lynd LD, Sayre EC, Sadatsafavi M, Hanley G, De Vera MA. Use of biologics during pregnancy and risk of serious infections in the mother and baby: a Canadian population-based cohort study. BMJ Open. 2019;9:e023714.
Vinet E, De Moura C, Pineau CA, Abrahamowicz M, Curtis JR, Bernatsky S. Serious infections in rheumatoid arthritis offspring exposed to tumor necrosis factor inhibitors: a cohort study. Arthritis Rheumatol. 2018;70:1565-1571.
Langhoff-Roos J, Krebs L, Klungsøyr K, et al. The Nordic medical birth registers-a potential goldmine for clinical research. Acta Obstet Gynecol Scand. 2014;93:132-137.
Wettermark B, Zoëga H, Furu K, et al. The Nordic prescription databases as a resource for pharmacoepidemiological research-a literature review. Pharmacoepidemiol Drug Saf. 2013;22:691-699.
Ludvigsson JF, Andersson E, Ekbom A, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.
Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sorensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol. 2015;7:449-490.
[26]Welfare FIfHa. Care Register for Health Care. 2016.
Wadström H, Eriksson JK, Neovius M, Askling J, on behalf of theARTIS* Study Group. How good is the coverage and how accurate are exposure data in the Swedish Biologics Register (ARTIS)? Scand J Rheumatol. 2015;44:22-28.
Schmitt-Egenolf M. PsoReg-the Swedish registry for systemic psoriasis treatment. The registry's design and objectives. Dermatology. 2007;214:112-117.
Sorup S, Benn CS, Poulsen A, Krause TG, Aaby P, Ravn H. Simultaneous vaccination with MMR and DTaP-IPV-Hib and rate of hospital admissions with any infections: a nationwide register based cohort study. Vaccine. 2016;34:6172-6180.
Miller JE, Hammond GC, Strunk T, et al. Association of gestational age and growth measures at birth with infection-related admissions to hospital throughout childhood: a population-based, data-linkage study from Western Australia. Lancet Infect Dis. 2016;16:952-961.
Esteve-Sole A, Deya-Martinez A, Teixido I, et al. Immunological changes in blood of newborns exposed to anti-TNF-alpha during pregnancy. Front Immunol. 2017;8:1123.
Kattah MG, Milush JM, Burt T, et al. Anti-TNF and thiopurine therapy in pregnant IBD patients does not significantly alter a panel of B-cell and T-cell subsets in 1-year-old infants. Clin Transl Gastroenterol. 2018;9:143.
Khashu M, Narayanan M, Bhargava S, Osiovich H. Perinatal outcomes associated with preterm birth at 33 to 36 weeks' gestation: a population-based cohort study. Pediatrics. 2009;123:109-113.
Ludvigsson JF, Lu D, Hammarstrom L, Cnattingius S, Fang F. Small for gestational age and risk of childhood mortality: a Swedish population study. PLoS Medicine. 2018;15:e1002717.
Jarnerot G, Into-Malmberg MB, Esbjorner E. Placental transfer of sulphasalazine and sulphapyridine and some of its metabolites. Scand J Gastroenterol. 1981;16:693-697.
Jharap B, de Boer NKH, Stokkers P, et al. Intrauterine exposure and pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease. Gut. 2014;63:451-457.
Matro R, Martin CF, Wolf D, Shah SA, Mahadevan U. Exposure concentrations of infants breastfed by women receiving biologic therapies for inflammatory bowel diseases and effects of breastfeeding on infections and development. Gastroenterology. 2018;155:696-704.
Niewiesk S. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Front Immunol. 2014;5:446.