In this prospective observational cohort study we aim to study the potential clinical consequences of antibiotic use in early life, by focussing on the incidence of eczema, as well as food allergy, upper respiratory tract infections (URTI), lower…
ID
Source
Brief title
Condition
- Gastrointestinal conditions NEC
- Allergic conditions
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is the incidence of eczema in antibiotic
treated children versus healthy controls. Besides that, the incidence of food
allergy, URTI, LRTI and GITI will be monitored. This will illustrate whether
early antibiotic treatment may influence the developing immune system.
Objective evaluation will be done by measuring vaccination response, length and
weight (weight/growth curves) and recall doctor*s diagnoses from the GP
(primary care visits for URTI, LRTI, GITI, food allergy, atopic dermatitis).
Even so, usage of medication will be determined by checking pharmacist*s
medication records and by asking the parents to report antibiotic treatment of
their child on the monthly checklists.
Secondary outcome
The secundary outcomes of the study are potential differences in the
development of intestinal microbiota (i.e. microbiota composition) in infants
exposed to antibiotic therapy in early life (first 2 weeks) versus infants that
did not receive antibiotic treatment during that period.
The samples are subjected to microbiota composition profiling by means of a
PCR-based interspace profiling technique (IS-pro, IS-Disgnostics, Amsterdam).
Composition of faecal samples will be analyzed by targeting bacterial groups
that are present (e.g. Bifidobacteria, Enterobacteriaceae, Streptococci,
Lactobacilli, Bacteroides, Proteobacteria) and by pyrosequencing technique at
the University of Wageningen (head Prof. J. Knol). .
Background summary
Evidence is growing that an aberrant microbiota composition can have clinical
effects. It is yet unknown to what extend the neonatal use of antibiotics can
have a detrimental effect on the gastrointestinal microbiota, for how long this
gastrointestinal imbalance will remain, to what extend the microbiota will
normalize and what the effects are on the developing immune system. Several
studies showed distinct associations between aberrant colonization patterns and
reduced microbial diversity and an increased risk of developing atopic Th2 type
diseases on one hand, such as allergy, wheezing and asthma, and
auto-inflammatory Th1 diseases on the other hand, like inflammatory bowel
disease (IBD), diabetes and obesity
Answering these questions can be important, since there is evidence that
manipulation of the infant microbiota by using pre-or probiotics can restore
ecological balance of the microbiota. Future studies should demonstrate if
development of allergic diseases might be influenced by (restoring) the
ecological intestinal microbiota balance. Also, targeted intervention may have
beneficial effects on gastrointestinal imbalance due to early antibiotic
exposure.
Study objective
In this prospective observational cohort study we aim to study the potential
clinical consequences of antibiotic use in early life, by focussing on the
incidence of eczema, as well as food allergy, upper respiratory tract
infections (URTI), lower respiratory tract infections (LRTI) and
gastrointestinal infections (GITI) in the first year of life. Also, vaccination
response will be measured at 1 year of age. Differentiation will be made
between a group of neonates who received antibiotics in the first days of their
life, and control infants who were not exposed to antibiotics in the neonatal
period.
Besides that, the perturbations in the gastrointestinal microbiota due to
antibiotic use in early life will be studied, since it is hypothesized that
altered microbiota may be an important underlying mechnism for impediments in
the developing immune system.
Study design
At baseline, parents have to fill out an (online) questionnaire containing
questions on key events family history, family composition, co morbidity and
medication. They have to complete daily checklists, on which they tick off the
presence of 8 symptoms.
A total of 8 faecal samples need to be collected at specific time points during
the first year of life. Also, at the age of 2 years, a fecal sample needs to be
collected. All parents will be offered collection vials for easy collection of
the fecal samples.
Participation will end around the 1st birthday of the infant after a scheduled
outpatient consultation. At that time instruction will be given for the fecal
sample collection around the 2nd birthday of their child.
When the child has reached the age of 4-5 years old, parents will be approached
for an online questionnaire concerning allergic disorders, gastro-intestinal
disorders and general health and growth. In addition, permission will be asked
to approach the general practitioner for doctor diagnosed conditions as
mentioned above. Moreover, parents will be asked to collect one more fecal
sample.
Participants will be recruited at the maternity ward or neonatal ward of the
St. Antonius Hospital, Meander Medisch Centrum Amersfoort as well as the
Tergooi Hospitals Blaricum/Hilversum and Gelre Hospitals Apeldoorn. In total
150 couples of whom their baby is suspected to suffer from a perinatal
infection are recruited (antibiotic treated group). Newborns with a low
probability of neonatal infection (no treatment but 24-48 hours of observation)
and healthy newborns, born in the hospital, will be included to form the
control group (in total 300 couples recruited).
During the study period, parents are free in their choice of breastfeeding
and/or feeding formula as well as their feeding regime; no specific formula
feeds and/or regime will be provided by the research group.
Study burden and risks
See page 12 of the protocol.
Potential side-effects: The study involves collection of faecal samples, one
blood sampling and information gathering by requesting parents to fill out
checklists. No negative side-effects of the study content are expected.
Unwanted effects and other risks: Unwanted effects and other risks are not to
be foreseen.
Inconveniences and risks related to study related procedures: During this study
there are no procedures which would pose any risk to the participants. Blood
sampling (on the back of the hand) may be inconvenient shortly, but doesn*t
cause increased risk for the participant (compared to blood sampling in
adults). A local anesthetic will be used to relieve the inconvenience.
Strains for the parents: The main strain for the parents is ticking off of the
weekly checklist (max 10 minutes every week). Former studies showed that
parents quickly do this 'out of habit' and don't encounter this as a strain.
Collecting the faecal samples takes ~5 minutes per sample.
Koekoekslaan 1
Nieuwegein 3430 EM
NL
Koekoekslaan 1
Nieuwegein 3430 EM
NL
Listed location countries
Age
Inclusion criteria
Term born babies (i.e. > 36 weeks gestational age)
(Short) stay on maternal ward OR admission to neonatal ward because of antibiotic treatment
Signed informed consent by the parents
Exclusion criteria
Prematurity (i.e. gestational age < 36 weeks)
Congenital illness or malformations
Maternal probiotic use (well considered) < last 6 weeks of pregnancy
Severe perinatal infections for which neonatal intensive care transfer is needed
Insufficient knowledge of the Ducht language (by the parents)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02536560 |
| CCMO | NL37233.100.11 |