\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Early childhood allergy prevention behaviours: trends in Germany from
2015 to 2020}



\author[1]{Maja Pawellek}%
\author[2]{Angela Köninger}%
\author[1]{Michael Melter}%
\author[1]{Michael Kabesch}%
\author[2]{Christian Apfelbacher}%
\author[1]{Susanne Brandstetter}%
\affil[1]{Universitatsklinikum Regensburg}%
\affil[2]{Krankenhaus Barmherzige Bruder Regensburg}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


Early childhood allergy prevention behaviours: trends in Germany from
2015 to 2020

\section*{Running title: Childhood allergy prevention
behaviours}

{\label{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

\begin{enumerate}
\tightlist
\item
  University Children's Hospital Regensburg (KUNO), Regensburg, Germany
\item
  Member of the Research and Development Campus Regensburg (WECARE),
  Hospital St. Hedwig of the Order of St. John, Regensburg, Germany
\item
  University Department of Gynecology and Obstetrics, Hospital St.
  Hedwig of the Order of St. John, University Medical Center Regensburg,
  Regensburg, Germany
\item
  Institute of Social Medicine and Health Systems Research, Otto von
  Guericke University Magdeburg, Magdeburg, Germany
\end{enumerate}

* Corresponding author: Maja.Pawellek@klinik.uni-regensburg.de

Word count: 1058

Number of tables and figures: 2

\subsection*{}

{\label{section}}

\subsection*{}

{\label{section-1}}

\subsection*{Disclosure of interest}

{\label{disclosure-of-interest}}

The authors report no conflict of interest.

\subsection*{Funding}

{\label{funding}}

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

\subsection*{Key words}

{\label{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 study\textsuperscript{4}. 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 /\textless{}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/\textless{}4 /[?]4 months); regular feeding of
hypoallergenic (HA) infant milk; age of introduction of solid foods
(\textless{}4 /4-6 /\textgreater{}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 4\textsuperscript{th} and 6\textsuperscript{th} 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.

\subsection*{Acknowledgments}

{\label{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 Br\selectlanguage{ngerman}üder 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.

\subsection*{Authors' contributions}

{\label{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.

\subsection*{Tables and Figures}

{\label{tables-and-figures}}

Table 1: Baseline characteristics of participating mothers\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& \textbf{Total sample (N=1662)} & \textbf{Total sample (N=1662)} &
\textbf{Cohort 2015-2017 (N=893)} & \textbf{Cohort 2015-2017 (N=893)} &
\textbf{Cohort 2017-2020 (N=769)} & \textbf{Cohort 2017-2020
(N=769)}\tabularnewline
\midrule
\endhead
\textbf{Characteristic} & \textbf{N} & & \textbf{N} & & \textbf{N}
&\tabularnewline
Age (years), \emph{Mean (SD)} & 1647 & 32.61 (4.1) & 887 & 32.56 (4.1) &
760 & 32.67 (4.1)\tabularnewline
Marital status, \emph{N (\%)} & 1629 & & 872 & & 757 &\tabularnewline
Married, living together with husband & & 1333 (81.83\%) & & 704
(80.73\%) & & 629 (83.09\%)\tabularnewline
Unmarried, living together with partner & & 271 (16.64) & & 153
(17.55\%) & & 118 (15.59\%)\tabularnewline
Living without partner/divorced/widowed & & 25 (1.53\%) & & 15 (1.72\%)
& & 10 (1.32\%)\tabularnewline
Migration background (country of birth other than Germany), \emph{N
(\%)} & 1631 & 149 (9.14\%) & 874 & 88 (10.07\%) & 757 & 61
(8.06\%)\tabularnewline
Education, \emph{N (\%)} & 1626 & & 871 & & 755 &\tabularnewline
No degree or less than 10 years of schooling & & 107 (6.58\%) & & 64
(7.35\%) & & 43 (5.70\%)\tabularnewline
Ten years of schooling & & 494 (30.38\%) & & 249 (28.59\%) & & 245
(32.45\%)\tabularnewline
University entrance level & & 1025 (63.04\%) & & 558 (64.06\%) & & 467
(61.85\%)\tabularnewline
Employment before birth, \emph{N (\%)} & 1627 & 1481 (91.03\%) & 871 &
802 (92.08\%) & 756 & 679 (89.81\%)\tabularnewline
Primiparous, \emph{N (\%)} & 1644 & 1048 (63.75\%) & 882 & 536 (60.77\%)
& 762 & 512 (67.19\%)*\tabularnewline
\bottomrule
\end{longtable}

* T-Test and Wilcoxon rank sum test (W) were used for comparing
participant characteristics between the two cohorts: \emph{W} =362923
(\emph{p} =0.016) for number of children.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Figure 1: ECAP prevalences and 95\% CIs in both cohorts (2015-2017,
2017-2020) for the total sample (A), children at-risk (B) and not
at-risk (C) for allergies. Results from trend analyses (logistic
regression): A: 0.17\textless{}\emph{OR} \textless{}1.31
(adjusted\emph{p} =0.928); B: 0\textless{}\emph{OR} \textless{}1.2
(adjusted\emph{p} =0.994); C: 0.41\textless{}\emph{OR} \textless{}1.52
(adjusted\emph{p} : 0.443\textless{}\emph{p} \textless{}0.978)

\selectlanguage{english}
\FloatBarrier
\end{document}

