Cohort profile: Finnish Health and Early Life Microbiota (HELMi) longitudinal birth cohort

Katri Korpela, Evgenia Dikareva, Eveliina Hanski, Kaija-Leena Kolho, Willem M de Vos, Anne Salonen, Katri Korpela, Evgenia Dikareva, Eveliina Hanski, Kaija-Leena Kolho, Willem M de Vos, Anne Salonen

Abstract

Purpose: HELMi (Health and Early Life Microbiota) is a longitudinal, prospective general population birth cohort, set up to identify environmental, lifestyle and genetic factors that modify the intestinal microbiota development in the first years of life and their relation to child health and well-being.

Participants: The HELMi cohort consists of 1055 healthy term infants born in 2016-2018 mainly at the capital region of Finland and their parents. The intestinal microbiota development of the infants is characterised based on nine, strategically selected, faecal samples and connected to extensive online questionnaire-collected metadata at weekly to monthly intervals focusing on the diet, other exposures and family's lifestyle as well as the health and growth of the child. Motor and cognitive developmental screening takes place at 18 months. Infant's DNA sample, mother's breast milk sample and both parent's spot faecal samples have been collected.

Findings to date: The mean age of the mothers was 32.8 (SD 4.1) and fathers/coparents 34.8 (5.3) years at the time of enrolment. Seventeen percentage (n=180) of the infants were born by caesarean section. Just under half (49%) were firstborns; 50.7% were males. At 3 months of age, 86% of the babies were exclusively breastfed and 2% exclusively formula-fed.

Future plans: The current follow-up from pregnancy to first 24 months will be completed in March 2020, totalling to over 10 000 biological samples and over 50 000 questionnaire entries. The results are expected to identify environmental and host factors that affect early gut microbiota development and health, and hence give indications of how to prevent or reverse microbiota perturbations in infancy. This prospective cohort will be followed up further to identify how the early microbiota relates to later health outcomes, especially weight gain, infections and allergic and other chronic diseases.

Trial registration number: NCT03996304; Pre-results.

Keywords: birth cohort; early life exposures; intestinal microbiota development; longitudinal follow-up; paediatrics.

Conflict of interest statement

Competing interests: All authors declare support from Valio Ltd, Finnish Red Cross Blood Service, Dupont Nutrition and Health and Oriola Ltd in the form of a grant that has partially funded the study.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Consort diagram.
Figure 2
Figure 2
Infographic illustrating the type and frequency of biological samples and questionnaires collected in the HELMi cohort during the first 2 years. Each horizontal line depicts sample and data collection point in relation to age that is indicated on the central bar. The colours refer to the type of sample or data collected, the numbers in the parenthesis to the total number of entries per family. ASQ-3, Ages & Stages Questionnaires, Third Edition; BDI-II, Beck Depression Inventory II; BSID-III, Bayley Scale of Infant Development III; ECBQ, Early Childhood Behaviour Questionnaire; ITSEA, Infant Toddler Social Emotional Assessment; PSI, Parenting Stress Index.
Figure 3
Figure 3
Parent’s age (A) and BMI (B) distribution and their correlation between the parents within a family. Data are plotted on hexagonal bins, which are shaded according to the count of the data points in the aggregate. In addition, histograms of the maternal and paternal values are plotted on the top and right, respectively. BMI, body mass index.
Figure 4
Figure 4
(A) Infant birth mode (VD; CD) and (B) breastfeeding rates at 3 months in the HELMi cohort. CD, caesarean delivery; VD, vaginal delivery.

References

    1. Renz H, Brandtzaeg P, Hornef M. The impact of perinatal immune development on mucosal homeostasis and chronic inflammation. Nat Rev Immunol 2011;12:9–23. 10.1038/nri3112
    1. Nylund L, Satokari R, Salminen S, et al. . Intestinal microbiota during early life - impact on health and disease. Proc Nutr Soc 2014;73:457–69. 10.1017/S0029665114000627
    1. Stiemsma LT, Michels KB. The role of the microbiome in the developmental origins of health and disease. Pediatrics 2018;141:e20172437 10.1542/peds.2017-2437
    1. Tanaka M, Nakayama J. Development of the gut microbiota in infancy and its impact on health in later life. Allergol Int 2017;66:515–22. 10.1016/j.alit.2017.07.010
    1. Olin A, Henckel E, Chen Y, et al. . Stereotypic Immune System Development in Newborn Children. Cell 2018;174:1277–92. 10.1016/j.cell.2018.06.045
    1. Cox LM, Yamanishi S, Sohn J, et al. . Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 2014;158:705–21. 10.1016/j.cell.2014.05.052
    1. Francino MP. Early development of the gut microbiota and immune health. Pathogens 2014;3:769–90. 10.3390/pathogens3030769
    1. Hill CJ, Lynch DB, Murphy K, et al. . Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort. Microbiome 2017;5:4 10.1186/s40168-016-0213-y
    1. Scheepers LE, Penders J, Mbakwa CA, et al. . The intestinal microbiota composition and weight development in children: the KOALA Birth Cohort Study. Int J Obes 2015;39:16–25. 10.1038/ijo.2014.178
    1. Subbarao P, Anand SS, Becker AB, et al. . The Canadian Healthy Infant Longitudinal Development (CHILD) Study: examining developmental origins of allergy and asthma. Thorax 2015;70:998–1000. 10.1136/thoraxjnl-2015-207246
    1. Stewart CJ, Ajami NJ, O’Brien JL, et al. . Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 2018;562:583–588. 10.1038/s41586-018-0617-x
    1. Bisgaard H. The Copenhagen Prospective Study on Asthma in Childhood (COPSAC): design, rationale, and baseline data from a longitudinal birth cohort study. Ann Allergy Asthma Immunol 2004;93:381–9. 10.1016/S1081-1206(10)61398-1
    1. Yang HJ, Lee SY, Suh DI, et al. . The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods. BMC Pulm Med 2014;14:109 10.1186/1471-2466-14-109
    1. Wacklin P, Mäkivuokko H, Alakulppi N, et al. . Secretor genotype (FUT2 gene) is strongly associated with the composition of Bifidobacteria in the human intestine. PLoS One 2011;6:e20113 10.1371/journal.pone.0020113
    1. Korpela K, Salonen A, Virta LJ, et al. . Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat Commun 2016;7:10410 10.1038/ncomms10410
    1. Official Statistics of Finland (OSoF): Väestön koulutusrakenne. ISSN=1799-4586. 2016. Helsinki: Tilastokeskus [referred: 25.8.2018]
    1. Haahtela T, von Hertzen L, Makela M, et al. . Allergy Programme Working G. Finnish Allergy Programme2008-2018time to act and change the course. Allergy 2008;63:634–45.
    1. Jousilahti P, Haahtela T, Laatikainen T, et al. . Asthma and respiratory allergy prevalence is still increasing among Finnish young adults. Eur Respir J 2016;47:985–7. 10.1183/13993003.01702-2015
    1. The Social Insurance Institution Kela: Statistics on reimbursements for prescription medicines. 2018. (Accessed 9 Mar 2018).
    1. Virta LJ, Kaukinen K, Collin P. Incidence and prevalence of diagnosed coeliac disease in Finland: results of effective case finding in adults. Scand J Gastroenterol 2009;44:933–8. 10.1080/00365520903030795
    1. Official Statistics of Finland (OSoF). Perinatal statistics - parturients, deliveries and newborns. Helsinki: National Institute for Health and Welfare (THL) (Referred: 8 Dec 2018).
    1. Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease-revised guidelines from CDC, 2010. MMWR 2010;59:1–32. Available at
    1. Erkkola M, Salmenhaara M, Kronberg-Kippilä C, et al. . Determinants of breast-feeding in a Finnish birth cohort. Public Health Nutr 2010;13:504–13. 10.1017/S1368980009991777
    1. The Organisation for Economic Co-operation and Development (OECD) database: Breastfeeding rates. 2009. (Accessed 24 Aug 2018).
    1. Milani C, Lugli GA, Turroni F, et al. . Evaluation of bifidobacterial community composition in the human gut by means of a targeted amplicon sequencing (ITS) protocol. FEMS Microbiol Ecol 2014;90:n/a–503. 10.1111/1574-6941.12410
    1. Jayaprakash B, Adams RI, Kirjavainen P, et al. . Indoor microbiota in severely moisture damaged homes and the impact of interventions. Microbiome 2017;5:138 10.1186/s40168-017-0356-5

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi