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Impact of anti-TNFα exposure in utero on the development of immune systems of exposed children – a controlled, multicentre observational study


Authors: Ďuricová D. 1;  Dvořáková E. 1;  Hradský O. 2;  Mitrová K. 1,2;  Durilová M. 3;  Koželuhová J. 4;  Kohout P. 5;  Zárubová K. 2;  Bronský J. 2;  Hradská N. 6;  Bronská E. 7;  Adamcová M. 7;  Machková N. 1;  Hrubá V. 1;  Bortlík M. 1,8,9;  Lukáš M. 1;  Malíčková K. 1,10
Authors‘ workplace: Klinické a výzkumné centrum pro střevní záněty ISCARE I. V. F., a.  s., Praha 1;  Pediatrická klinika 2. LF UK a FN Motol, Praha 2;  Klinika dětské chirurgie 2. LF UK a FN Motol, Praha 3;  Gastroenterologické a hepatologické oddělení, I. interní klinika LF UK a FN v Plzni 4;  Interní klinika 3. LF UK a Thomayerovy nemocnice, Praha6 Privátní ordinace PLDD, Litovel 5;  Privátní ordinace PLDD, Praha 7;  Interní klinika 1. LF UK a ÚVN, Praha 8;  Farmakologický ústav 1. LF UK a VFN, Praha 9;  Ústav lékařské bio­chemie a laboratorní dia­gnostiky, 1. LF UK a VFN, Praha 10
Published in: Gastroent Hepatol 2018; 72(6): 479-485
Category:
doi: https://doi.org/10.14735/amgh2018479

Overview

Background:

Data on safety of in utero exposure to anti-tumor necrosis factor (TNF) α on long-term childhood development are sparse. Our aim was to assess the impact of in utero exposure to anti-TNFα on the postnatal development of immune systems of exposed children.

Methods:

Children (≥ 12 months of age) born to mothers with inflammatory bowel disease (IBD) (2007–2016) treated with anti-TNFα during pregnancy in three centres were included. Unexposed children of non-IBD mothers who came for mandatory check-up to the general pediatrician served as a control group. A predefined questionnaire was distributed by the pediatricians to collect data on the perinatal period, infectious complications, antibiotic use, and vaccination.

Results:

We included 72 exposed and 69 unexposed children (median age 35 months and 50 months, respectively). No significant difference in infectious complications ≤ 1st year of life (23.9 vs. 17.4%, p = 0.36) or during the whole follow-up (p = 0.32) was found between exposed infants and controls. Concomitant immunosuppressive therapy during pregnancy and anti-TNFα levels in cord blood did not increase the infection rate ≤ 1st year of life (p > 0.05). Protective titers of antibodies to vaccination were found in > 95% of exposed children except for H. influenzae and mumps vaccines. However, these two vaccines had the lowest serologic response in the control group, too.

Conclusions:

Treatment with anti-TNFα during pregnancy seemed to be safe with regard to postnatal development of the immune systems of exposed children.

Key words: inflammatory bowel disease – anti-TNFα – gravidity – infections – vaccination

Submitted: 22. 11. 2018

Accepted: 28. 11. 2018


Sources

1. Burisch J, Munkholm P. The epidemiology of inflam­matory bowel dis­ease. Scand J Gas­troenterol 2015; 50(8): 942–951. doi: 10.3109/ 00365521.2015.1014407.

2. van der Woude CJ, Ardizzone S, Bengtson MBet al. The second European evidenced-based consensus on reproduction and pregnancy in inflam­matory bowel dis­ease. J Crohns Colitis 2015; 9(2): 107–124. doi: 10.1093/ecco-jcc/jju006.

3. Julsgaard M, Christensen LA, Gibson PR et al. Concentrations of adalimumab and infliximab in mothers and newborns, and ef­fects on infection. Gastroenterol 2016; 151(1): 110–119. doi: 10.1053/j.gastro.2016.04.002.

4. Bortlik M, Duricova D, Machkova 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(3): 495–501. doi: 10.1097/01.MIB.0000440984.86659.4f.

5. de Lima A, Zelinkova Z, van der Ent C et al. Tailored anti-TNF ther­apy dur­­ing preg­nancy in patients with IBD: maternal and fetal safety. Gut 2016; 65(8): 1261–1268. doi: 10.1136/gutjnl-2015-309321.

6. Chapar­ro M, Ver­reth A, Lobaton T et al. Long-term safety of in utero exposure to anti-tnfα drugs for the treatment of inflam­matory bowel dis­ease: results from the multicenter European TEDDY Study. Am J Gastroenterol 2018; 113(3): 396–403. doi: 10.1038/ajg.2017.501.

7. Mahadevan U, Martin CF, Sandler RS et al. PIANO: A 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to im­munomodulators and bio­logic ther­a­­-py (Abstract 865). Gastroenterol 2012; 142 (5 Suppl 1): S149.

8. Kanis SL, de Lima-Karagian­nis, van der Ent C et al. Anti-TNF levels in cord blood at birth are as­sociated with anti-TNF type. J Crohns Colitis 2018; 12(8): 939–947. doi: 10.1093/ecco-jcc/jjy058.

9. Mahadevan U, Martin CF, Kane SV et al. Do infant serum levels of bio­logic agents at birth cor­relate with risk of adverse outcomes? Results from the PIANO Registry. Gastroenterol 2016; 150 (4 Suppl 1): S91–S92.

10. Zinke M, Dis­selhoff J, Gartner B et al. Im­munological persistence in 4–6 and 7–9 year olds previously vaccinated in infancy with hexavalent DTPa-HBV-IPV/Hib. Hum Vaccin 2010; 6(2): 189–193.

11. Beaulieu DB, Ananthakrishnan AN, Martin C et al. Use of bio­logic ther­apy by pregnant women with inflam­matory bowel dis­ease does not af­fect infant response to vaccines. Clin Gastroenterol Hepatol 2018; 16(1): 99–105. doi: 10.1016/j.cgh.2017.08.041.

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Paediatric gastroenterology Gastroenterology and hepatology Surgery

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