Running title: Childhood allergy prevention behaviours

\(\mathrm{Maja\ Pawellek,\ MSc}^{\mathrm{1,2,\ *}}\),\(\mathrm{Angela\ Koninger,\ MD}^{2,3}\mathrm{,\ }\mathrm{Michael\ Melter,\ MD}^{\mathrm{1,2}}\mathrm{,\ }\mathrm{Michael\ Kabesch,\ MD}^{\mathrm{1,2}}\),\(\mathrm{Christian\ Apfelbacher,\ PhD}^{2,4}\mathrm{,\ }\mathrm{Susanne\ Brandstetter,\ PhD}^{\mathrm{1,2}}\)& KUNO-Kids study group
  1. University Children’s Hospital Regensburg (KUNO), Regensburg, Germany
  2. Member of the Research and Development Campus Regensburg (WECARE), Hospital St. Hedwig of the Order of St. John, Regensburg, Germany
  3. University Department of Gynecology and Obstetrics, Hospital St. Hedwig of the Order of St. John, University Medical Center Regensburg, Regensburg, Germany
  4. Institute of Social Medicine and Health Systems Research, Otto von Guericke University Magdeburg, Magdeburg, Germany
* Corresponding author: Maja.Pawellek@klinik.uni-regensburg.de
Word count: 1058
Number of tables and figures: 2

Disclosure of interest

The authors report no conflict of interest.

Funding

This study was supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Grant FOR 2959 „HELICAP“, BR 5081/2-1.

Key words

allergy prevention; early childhood; pregnancy; trend analyses
To the Editor,
Early childhood allergy prevention (ECAP) behaviours encompass a wide range of parental behaviours with regard to children’s exposure to or avoidance of allergens, including maternal and child nutrition or modification of the living environment. The paradigm shift in allergy prevention from avoidance to exposure has questioned many measures formerly presumed efficacious and resulted in a revised guideline on childhood allergy prevention in Germany in 2014. This guideline specifies not only the behaviours recommended for allergy prevention (e.g. breastfeeding and early introduction of solid food), but also discourages most measures promoting avoidance of allergens. A new revision has been currently published. We are not aware of studies investigating whether and to what extent families in Germany engage in ECAP behaviours and if there are secular trends. Therefore, we observed prevalences and trends in ECAP behaviours of mothers in Germany over a period of five years (2015 to 2020).
We used data from a prospective birth cohort in Regensburg (Germany), the KUNO Kids health study4. All mothers who gave consent and participated with their newborn child in the study for at least one year (recruited until March 2020, with data collection until March 2021) were included. Sociodemographic and ECAP data were collected directly after birth of the child, at the age of four weeks, 6 months and 1 year, respectively, using standardized computer-assisted personal interviews (CAPI) and paper-based self-report questionnaires. The study has been approved by the Ethics Committee of the University of Regensburg (reference number: 14-101-0347 and 19-1646-101).
ECAP behaviours considered in our analyses were: fish in mothers’ diet during pregnancy, during feeding with breast milk, as part of solid food during the child’s first year of life (≥1 /<1 per week); smoking during pregnancy (yes/no); allergy prevention related avoidance of specific foods in mother’s diet during feeding with breast milk, in the child’s diet during first year of life (fish, meat, dairies, wheat, hen egg, nuts (incl. peanuts), soy, citruses, other fruit or vegetable, other foods: yes (any)/no); duration of predominant breastfeeding (no breastfeeding/<4 /≥4 months); regular feeding of hypoallergenic (HA) infant milk; age of introduction of solid foods (<4 /4-6 />6 months); feeding of farm milk (yes (cow milk not boiled/boiled/goat milk)/no); allergy prevention related measures for reducing house dust mites (removal of carpets, frequent cleaning, use of specific vacuum cleaners, mattress encasing, allergy mattress, allergy pillow/blanket: yes (any)/no); exposure to tobacco smoke by smoking of parents or in the child’s home (yes/no); removal of pets (any fury pets, cats: yes/no); avoidance of pets (yes/no); regular (≥1 per week) contact with hay (yes/no). Children whose mother, father or sibling had an allergic disease (self-reported diagnosis of food allergy, allergic rhinitis, allergic conjunctivitis, bronchial asthma or atopic dermatitis) were defined as at-risk for allergy.
Crude prevalence estimates and 95% confidence intervals (CIs) were calculated for ECAP behaviours, in the total sample and stratified for allergy risk status. Multivariate imputation by chained equations (MICE) was applied to handle missing data. In order to analyse trends over time, two independent cross-sectional data sets were prepared (cohort 1: born 2015 to mid-2017; cohort 2: born mid-2017 to 2020). Adjusted logistic regression modelling was used for estimating change in ECAP behaviours over time, for the total sample and stratified for allergy risk status. Results were adjusted for multiple testing using the Hommel method. All analyses were performed according to an a priori specified analysis plan, using SPSS and R.
Baseline characteristics of N=1662 mothers included in our analyses are shown in table 1. N=1442 mothers dropped out before the 1-year assessment.
Prevalences of ECAP behaviours: 23.7% (CI: 21.5-25.9) of mothers renounced specific foods in their diet during feeding with breast milk, 40.1% (CI: 37.7-42.4) in their child’s diet during the first year of life. 67.9% (CI: 65.6-70.1) of mothers were predominantly breastfeeding at least 4 months and 92% (CI: 91-94) introduced solid foods between the 4th and 6th month. 43.5% (CI: 40.3-46.7) of children who were not predominantly breastfed were fed with hypoallergenic (HA) infant milk. Weekly fish consumption was 51.9% (CI: 49.5-54.3) during pregnancy, 57.7% (CI: 55.1-60.3) during feeding with breast milk, and 64.6% (CI: 62.3-66.9) for the child during the first year of life. There was no smoking in the home of 90% (CI: 88.5-91.4) of children; 1.4% [CI: 0.9-2] of mothers smoked during pregnancy. 16.7% (CI: 14.9-18.5) of families took any measure against dust mites, 2.1% (CI: 1.5-2.8) deliberately kept their children away from pets. 6.4% (CI: 5.3-7.6) of children had regular contact with hay, 12.3% (CI: 10.7-13.9) received cow/goat milk directly from the farm. 57.6% (CI: 55.3-60) of the children were at risk for allergy. Prevalences stratified for children at-risk and not at-risk for allergies are presented in Figure 1 (b and c).
Trends of ECAP behaviours: Baseline characteristics of cohort 1 (2015-2017, N=893) and cohort 2 (2017-2020; N=769) differed only regarding parity (see table 1). Accordingly, trend analyses were adjusted for parity. There was no statistically significant upward or downward trend form 2015-2017 to 2017-2020 in any ECAP behaviour, neither in the total sample nor in the stratified samples.
Although the sample is characterized by a high proportion of highly educated women without migration background from an affluent area, the study yields findings with relevance for child health and allergy prevention. More than half of the children were at risk for allergy, emphasizing the relevance of ECAP. We found that some recommended ECAP behaviours were practiced in most families, in particular the early introduction of solids. However, allergen avoidance measures were also implemented – in both children at-risk and not at-risk for allergies. Remarkably, the prevalences of specific ECAP behaviours practiced in families did not change significantly from 2015 to 2020. In Germany, the paradigm shift in allergy prevention may not (yet) be reflected in young families’ lives. In contrast, a study from Australia comparing data from 2007-2011 with data from 2017-2019 showed an increase in adherence to recommended behaviours following guideline revision. This might be due to more specific recommendations in the Australian guideline, especially concerning infant feeding practices, or due to the longer time period considered in that study. There is a need for easy access to evidence-based allergy prevention information alongside specific education and counselling for families with and without risk of allergy. Paediatricians, gynaecologists and midwives could play a crucial role in communicating recommendations for allergy prevention to families.

Acknowledgments

We would like to thank all participating parents as well as the members of the KUNO-Kids study group:
Andreas Ambrosch (Institute of Laboratory Medicine, Microbiology and Hygiene, Barmherzige Brüder Hospital, Regensburg, Germany), Petra A. Arndt (ZNL Transfercenter of Neuroscience and Learning, University of Ulm, Ulm, Germany), Andrea Baessler (Department of Internal Medicine II, Regensburg University Medical Center, Regensburg, Germany), Mark Berneburg (Department of Dermatology, University Medical Centre Regensburg, Regensburg, Germany), Stephan Böse-O’Reilly (University Children’s Hospital Regensburg (KUNO), Hospital St. Hedwig of the Order of St. John, Regensburg, Germany), Romuald Brunner (Clinic of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Bezirksklinikum Regensburg (medbo), Regensburg, Germany), Sara Fill Malfertheiner (Clinic of Obstetrics and Gynecology St. Hedwig, University of Regensburg, Regensburg, Germany), André Franke (Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany), Sebastian Häusler (Clinic of Obstetrics and Gynecology St. Hedwig, University of Regensburg, Regensburg, Germany), Iris Heid (Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany), Stefanie Heinze (Bavarian Health and Food Safety Authority (LGL) Munich, Germany), Wolfgang Högler (Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria), Sebastian Kerzel (Department of Pediatric Pneumology and Allergy, University Children’s Hospital Regensburg (KUNO), Hospital St. Hedwig of the Order of St. John, Regensburg, Germany), Michael Koller (Center for Clinical Studies, University Hospital Regensburg, Regensburg, Germany), Michael Leitzmann (Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany), Áine Lennon (Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, University of Regensburg, Regensburg, Germany), David Rothfuß (City of Regensburg, Coordinating Center for Early Interventions, Regensburg, Germany), Wolfgang Rösch (Department of Pediatric Urology, University Medical Center, Regensburg, Germany), Bianca Schaub (Pediatric Allergology, Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany), Stephan Weidinger (Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany) and Sven Wellmann (Department of Neonatology, University Children’s Hospital Regensburg (KUNO), Hospital St. Hedwig of the Order of St. John, Regensburg, Germany).
The HELICAP research group (FOR 2959) is funded by the German Research Foundation (DFG) - project number 409800133. HELICAP is an association of leading scientists at four locations in Germany. In addition to the Otto von Guericke University Magdeburg, the University of Education Freiburg, the University of Regensburg and the Medical University Hannover are involved in the interdisciplinary research group HELICAP. Members of the HELICAP steering group are Prof. Dr. Christian Apfelbacher, Prof. Dr. Eva Maria Bitzer, Dr. Susanne Brandstetter, Dr. Janina Curbach, Prof. Dr. Marie-Luise Dierks and Prof. Dr. Markus Antonius Wirtz.

Authors’ contributions

Maja Pawellek drafted the statistical analysis plan, performed data analysis, interpreted the study findings, drafted the manuscript, critically evaluated the manuscript, and approved the final manuscript as submitted. Angela Köninger contributed to data collection, critically evaluated the manuscript, and approved the final manuscript as submitted. Michael Melter contributed to data collection, critically evaluated the manuscript, and approved the final manuscript as submitted. Michael Kabesch contributed to the design of the study and to data collection. He critically evaluated the manuscript and approved the final manuscript as submitted. Christian Apfelbacher contributed to the design of the study, critically evaluated the statistical analysis plan and the manuscript. He approved the final manuscript as submitted. Susanne Brandstetter designed the study, and contributed to the statistical analysis plan, data analysis, interpretation of study findings and manuscript writing. She critically evaluated the manuscript and approved the final manuscript as submitted.

Tables and Figures

Table 1: Baseline characteristics of participating mothers