Maternal and perinatal conditions and the risk of developing celiac disease during childhood

Fredinah Namatovu, Cecilia Olsson, Marie Lindkvist, Anna Myléus, Ulf Högberg, Anneli Ivarsson, Olof Sandström, Fredinah Namatovu, Cecilia Olsson, Marie Lindkvist, Anna Myléus, Ulf Högberg, Anneli Ivarsson, Olof Sandström

Abstract

Background: Celiac disease (CD) is increasing worldwide, which might be due to the changing environmental and lifestyle exposures. We aimed to explore how conditions related to maternity, delivery and the neonatal period influence CD onset during childhood.

Methods: Using Sweden's national registers we had access to information on 1 912 204 children born between 1991 and 2009, 6 596 of whom developed CD before 15 years of age. Logistic regression analyses were performed to determine how CD is associated with maternity, delivery and the neonatal period.

Results: Regardless of sex, a reduction in CD risk was observed in children born to mothers aged ≥35 years (odds ratio [OR] 0.8; 95 % confidence interval [CI] 0.7-0.9) and with high maternal income (OR 0.9; 95 % CI 0.8-0.9). Being a second-born child, however, was positively associated with CD. Among boys, elective caesarean delivery increased the risk of CD (OR 1.2; 95 % CI 1.0-1.4), while maternal overweight (OR 0.9; 95 % CI 0.8-0.9), premature rupture of the membrane (OR 0.4; 95 % CI 0.2-0.8) and low birth weight showed a negative association. Girls had an increased CD risk compared to boys and in girls the risk was increased by repeated maternal urinary tract infections (OR 1.1; 95 % CI 1.0-1.2).

Conclusions: Elective caesarean delivery and repeated maternal urinary tract infections during pregnancy are associated with increased risk of CD onset during childhood, suggesting the role of dysbiosis during early life. High maternal age and high income reduced the risk of CD, which might be due to infant-feeding practices and life style.

Keywords: Caesarean; Celiac disease; Children; Delivery; Elective; Income; Infections; Perinatal; Pregnancy; Register.

References

    1. Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013;62(1):43–52. doi: 10.1136/gutjnl-2011-301346.
    1. Namatovu F, Sandstrom O, Olsson C, Lindkvist M, Ivarsson A. Celiac disease risk varies between birth cohorts, generating hypotheses about causality: evidence from 36 years of population-based follow-up. BMC Gastroenterol. 2014;14:59. doi: 10.1186/1471-230X-14-59.
    1. Lohi S, Mustalahti K, Kaukinen K, Laurila K, Collin P, Rissanen H, Lohi O, Bravi E, Gasparin M, Reunanen A, et al. Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther. 2007;26:1217–1225. doi: 10.1111/j.1365-2036.2007.03502.x.
    1. Ivarsson A, Persson LA, Nystrom L, Ascher H, Cavell B, Danielsson L, Dannaeus A, Lindberg T, Lindquist B, Stenhammar L, et al. Epidemic of coeliac disease in Swedish children. Acta Paediatr. 2000;89(2):165–171. doi: 10.1111/j.1651-2227.2000.tb01210.x.
    1. Parra-Medina R, Molano-Gonzalez N, Rojas-Villarraga A, Agmon-Levin N, Arango MT, Shoenfeld Y, Anaya JM. Prevalence of Celiac Disease in Latin America: A Systematic Review and Meta-Regression. Plos One. 2015;10(5):e0124040. doi: 10.1371/journal.pone.0124040.
    1. Kang JY, Kang AH, Green A, Gwee KA, Ho KY. Systematic review: worldwide variation in the frequency of coeliac disease and changes over time. Aliment Pharmacol Ther. 2013;38(3):226–245. doi: 10.1111/apt.12373.
    1. Kondrashova A, Mustalahti K, Kaukinen K, Viskari H, Volodicheva V, Haapala AM, Ilonen J, Knip M, Maki M, Hyoty H, et al. Lower economic status and inferior hygienic environment may protect against celiac disease. Ann Med. 2008;40(3):223–231. doi: 10.1080/07853890701678689.
    1. Olsson C, Stenlund H, Hornell A, Hernell O, Ivarsson A. Regional variation in celiac disease risk within Sweden revealed by the nationwide prospective incidence register. Acta Paediatr. 2009;98(2):337–342. doi: 10.1111/j.1651-2227.2008.01086.x.
    1. Marques AH, O’Connor TG, Roth C, Susser E, Bjorke-Monsen AL. The influence of maternal prenatal and early childhood nutrition and maternal prenatal stress on offspring immune system development and neurodevelopmental disorders. Front Neurosci. 2013;7:120. doi: 10.3389/fnins.2013.00120.
    1. Odaka Y, Nakano M, Tanaka T, Kaburagi T, Yoshino H, Sato-Mito N, Sato K. The influence of a high-fat dietary environment in the fetal period on postnatal metabolic and immune function. Obesity (Silver Spring) 2010;18(9):1688–1694. doi: 10.1038/oby.2009.513.
    1. Jakobsson HE, Abrahamsson TR, Jenmalm MC, Harris K, Quince C, Jernberg C, Bjorksten B, Engstrand L, Andersson AF. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut. 2014;63(4):559–566. doi: 10.1136/gutjnl-2012-303249.
    1. Vangay P, Ward T, Gerber JS, Knights D. Antibiotics, pediatric dysbiosis, and disease. Cell Host Microbe. 2015;17(5):553–564. doi: 10.1016/j.chom.2015.04.006.
    1. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, van den Brandt PA, Stobberingh EE. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006;118(2):511–521. doi: 10.1542/peds.2005-2824.
    1. Andreas NJ, Kampmann B, Mehring Le-Doare K. Human breast milk: A review on its composition and bioactivity. Early Hum Dev. 2015;91(11):629–635. doi: 10.1016/j.earlhumdev.2015.08.013.
    1. Decker E, Engelmann G, Findeisen A, Gerner P, Laass M, Ney D, Posovszky C, Hoy L, Hornef MW. Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children. Pediatrics. 2010;125(6):e1433–1440. doi: 10.1542/peds.2009-2260.
    1. Roberts SE, Williams JG, Meddings D, Davidson R, Goldacre MJ. Perinatal risk factors and coeliac disease in children and young adults: a record linkage study. Aliment Pharmacol Ther. 2009;29(2):222–231. doi: 10.1111/j.1365-2036.2008.03871.x.
    1. Marild K, Stephansson O, Montgomery S, Murray JA, Ludvigsson JF. Pregnancy Outcome and Risk of Celiac Disease in Offspring: A Nationwide Case–control Study. Gastroenterology. 2012;142(1):39–45.e3. doi: 10.1053/j.gastro.2011.09.047.
    1. Adlercreutz EH, Wingren CJ, Vincente RP, Merlo J, Agardh D. Perinatal risk factors increase the risk of being affected by both type 1 diabetes and coeliac disease. Acta Paediatr. 2015;104(2):178–184. doi: 10.1111/apa.12836.
    1. Ludvigsson JF, Otterblad-Olausson P, Pettersson BU, Ekbom A. The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research. Eur J Epidemiol. 2009;24(11):659–667. doi: 10.1007/s10654-009-9350-y.
    1. Walker-Smith JA, Guandalini S, Schmitz J, Shmerling DH, Visakorpi JK. Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child. 1990;65(8):909–911. doi: 10.1136/adc.65.8.909.
    1. Dickson BC, Streutker CJ, Chetty R. Coeliac disease: an update for pathologists. J Clin Pathol. 2006;59(10):1008–1016. doi: 10.1136/jcp.2005.035345.
    1. Strachan DP, Taylor EM, Carpenter RG. Family structure, neonatal infection, and hay fever in adolescence. Arch Dis Child. 1996;74(5):422–426. doi: 10.1136/adc.74.5.422.
    1. WHO statistical information system. Available from: Accessed 16 Nov2014 at []
    1. Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, Shamir R, Troncone R, Giersiepen K, Branski D, Catassi C, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136–160. doi: 10.1097/MPG.0b013e31821a23d0.
    1. Al-Sahab B, Lanes A, Feldman M, Tamim H. Prevalence and predictors of 6-month exclusive breastfeeding among Canadian women: a national survey. BMC Pediatr. 2010;10:20. doi: 10.1186/1471-2431-10-20.
    1. Jones JR, Kogan MD, Singh GK, Dee DL, Grummer-Strawn LM. Factors Associated With Exclusive Breastfeeding in the United States. Pediatrics. 2011;128(6):1117–1125. doi: 10.1542/peds.2011-0841.
    1. Oakley LL, Renfrew MJ, Kurinczuk JJ, Quigley MA: Factors associated with breastfeeding in England: an analysis by primary care trust. BMJ Open. 2013;3(6):e002765.
    1. Akobeng AK, Thomas AG. Systematic review: tolerable amount of gluten for people with coeliac disease. Aliment Pharmacol Ther. 2008;27(11):1044–1052. doi: 10.1111/j.1365-2036.2008.03669.x.
    1. Vriezinga SL, Auricchio R, Bravi E, Castillejo G, Chmielewska A, Crespo Escobar P, Kolacek S, Koletzko S, Korponay-Szabo IR, Mummert E, et al. Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med. 2014;371(14):1304–1315. doi: 10.1056/NEJMoa1404172.
    1. Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Amarri S, Barbato M, Barbera C, Barera G, Bellantoni A, et al. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med. 2014;371(14):1295–1303. doi: 10.1056/NEJMoa1400697.
    1. Aronsson CA, Lee HS, Liu E, Uusitalo U, Hummel S, Yang J, Hummel M, Rewers M, She JX, Simell O, et al. Age at gluten introduction and risk of celiac disease. Pediatrics. 2015;135(2):239–245. doi: 10.1542/peds.2014-1787.
    1. Stordal K, White RA, Eggesbo M. Early feeding and risk of celiac disease in a prospective birth cohort. Pediatrics. 2013;132(5):e1202–1209. doi: 10.1542/peds.2013-1752.
    1. Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299(6710):1259–1260. doi: 10.1136/bmj.299.6710.1259.
    1. White LE, Merrick VM, Bannerman E, Russell RK, Basude D, Henderson P, Wilson DC, Gillett PM. The Rising Incidence of Celiac Disease in Scotland. Pediatrics. 2013;132(4):e924–931. doi: 10.1542/peds.2013-0932.
    1. Pozo-Rubio T, Olivares M, Nova E, De Palma G, Mujico JR, Ferrer MD, Marcos A, Sanz Y. Immune development and intestinal microbiota in celiac disease. Clin Dev Immunol. 2012;2012:654143. doi: 10.1155/2012/654143.
    1. Malmborg P, Bahmanyar S, Grahnquist L, Hildebrand H, Montgomery S. Cesarean section and the risk of pediatric Crohn’s disease. Inflamm Bowel Dis. 2012;18(4):703–708. doi: 10.1002/ibd.21741.
    1. Ponsonby AL, Catto-Smith AG, Pezic A, Dupuis S, Halliday J, Cameron D, Morley R, Carlin J, Dwyer T. Association between early-life factors and risk of child-onset Crohn’s disease among Victorian children born 1983–1998: a birth cohort study. Inflamm Bowel Dis. 2009;15(6):858–866. doi: 10.1002/ibd.20842.
    1. Marild K, Ye W, Lebwohl B, Green PH, Blaser MJ, Card T, Ludvigsson JF. Antibiotic exposure and the development of coeliac disease: a nationwide case–control study. BMC Gastroenterol. 2013;13:109. doi: 10.1186/1471-230X-13-109.
    1. McLean MH, Dieguez D, Jr, Miller LM, Young HA. Does the microbiota play a role in the pathogenesis of autoimmune diseases? Gut. 2015;64(2):332–341. doi: 10.1136/gutjnl-2014-308514.
    1. Romero R, Hassan SS, Gajer P, Tarca AL, Fadrosh DW, Nikita L, Galuppi M, Lamont RF, Chaemsaithong P, Miranda J, et al. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome. 2014;2(1):4. doi: 10.1186/2049-2618-2-4.
    1. Laparra JM, Sanz Y. Bifidobacteria inhibit the inflammatory response induced by gliadins in intestinal epithelial cells via modifications of toxic peptide generation during digestion. J Cell Biochem. 2010;109(4):801–807.
    1. Cinova J, De Palma G, Stepankova R, Kofronova O, Kverka M, Sanz Y, Tuckova L. Role of intestinal bacteria in gliadin-induced changes in intestinal mucosa: study in germ-free rats. PLoS One. 2011;6(1):e16169. doi: 10.1371/journal.pone.0016169.
    1. Olen O, Bihagen E, Rasmussen F, Ludvigsson JF. Socioeconomic position and education in patients with coeliac disease. Dig Liver Dis. 2012;44(6):471–476. doi: 10.1016/j.dld.2012.01.006.
    1. Wingren CJ, Bjorck S, Lynch KF, Ohlsson H, Agardh D, Merlo J. Coeliac disease in children: a social epidemiological study in Sweden. Acta Paediatr. 2012;101(2):185–191. doi: 10.1111/j.1651-2227.2011.02434.x.
    1. Whyte LA, Kotecha S, Watkins WJ, Jenkins HR. Coeliac disease is more common in children with high socio-economic status. Acta Paediatr. 2014;103(3):289–294. doi: 10.1111/apa.12494.
    1. Stenhammar L, Hogberg L, Ivarsson A, Laurin P, Myleus A, Falth-Magnusson K. Coeliac disease and socio-economic status. Acta Paediatr. 2014;103(8):e328. doi: 10.1111/apa.12665.
    1. Westin M, Ahs A, Brand Persson K, Westerling R. A large proportion of Swedish citizens refrain from seeking medical care--lack of confidence in the medical services a plausible explanation? Health Policy. 2004;68(3):333–344. doi: 10.1016/j.healthpol.2003.10.008.
    1. Welander A, Tjernberg AR, Montgomery SM, Ludvigsson J, Ludvigsson JF. Infectious disease and risk of later celiac disease in childhood. Pediatrics. 2010;125(3):e530–536. doi: 10.1542/peds.2009-1200.
    1. Myleus A, Hernell O, Gothefors L, Hammarstrom ML, Persson LA, Stenlund H, Ivarsson A. Early infections are associated with increased risk for celiac disease: an incident case-referent study. BMC Pediatr. 2012;12:194. doi: 10.1186/1471-2431-12-194.
    1. Ivarsson A, Persson LA, Nystrom L, Hernell O. The Swedish coeliac disease epidemic with a prevailing twofold higher risk in girls compared to boys may reflect gender specific risk factors. Eur J Epidemiol. 2003;18(7):677–684. doi: 10.1023/A:1024873630588.

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