Clinical trial NCT02536560: Intestinal Microbiota Composition After Antibiotic Treatment in Early Life
Official title: "Intestinal Microbiota Composition After Antibiotic Treatment in Early Life. The INCA Study"
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Microbiota
Eczema
Atopy
Keywords: intestinal microbiota
antibiotics
infant
allergy
Lead sponsor: Agentschap NL
Sponsor class: OTHER_GOV
Collaborators: name: Danone Global Research & Innovation Center
name: Amsterdam UMC, location VUmc
First posted: 2015-09-01
Enrollment: 450
Sex: ALL
Minimum age (years): 1
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy newborns born in the hospital, observed for low probability of neonatal infection will be compared to newborns exposed to antibiotic therapy in early life (first 1-2 weeks) by investigating potential differences in intestinal fecal microbiota composition

Brief summary: In this prospective observational cohort study the potential clinical consequences of antibiotic use in early life and perturbations in the gastrointestinal microbiota composition due to that antibiotic use are studied. It is hypothesized that altered microbiota may be an important underlying mechanism for impediments in the developing immune system.

Differentiation will be made between a group of neonates who received antibiotics in the first week of life, and control infants who were not exposed to antibiotics in the neonatal period.

Detailed description: Healthy newborns born in the hospital, observed for low probability of neonatal infection will be compared to newborns exposed to antibiotic therapy in early life (first 1-2 weeks).

Infants are recruited from the maternity wards and neonatal wards of four teaching hospitals in the Netherlands. In total 150 infants, treated with antibiotics because of (a high suspicion of) a perinatal infection during the first week of life, will be recruited. The control group comprises 300 healthy newborns, born in the hospital and needing clinical observation for 24-48 hours for several reasons like maternal comorbidity, low probability of neonatal infection, blood sugar monitoring, meconium containing amniotic fluid, or delivery by caesarean section.

Differences in clinical outcomes between antibiotic treated infants and controls are investigated. Incidence of atopic dermatitis (eczema), food allergy, upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI), gastrointestinal infections (GITI) and excessive crying are evaluated, prospectively assessed by parental reports and retrospectively assessed by doctor's diagnoses. The clinical endpoints will be linked to the developing intestinal microbiota during the first year of life.

Potential differences in intestinal fecal microbiota composition and diversity can be determined at eight time points during the first year of life, as sampling moments include: day one (T1), day two (T2), one week (T3), two weeks (T4), one month (T5), three months (T6), six months (T7), one year (T8).

Eligibility criteria: Inclusion Criteria:

1. Term-born babies (≥ 36 weeks gestational age)
2. (Short) stay on maternal ward or admission to neonatal ward because of antibiotic treatment
3. Signed informed consent by the parents

Exclusion Criteria:

1. Congenital illness or malformations
2. Severe perinatal infections for which transfer to the neonatal intensive care unit is needed
3. Maternal probiotic use ≤ six weeks before delivery
4. Insufficient knowledge of the Dutch language.

Primary outcomes:
measure: Clinical endpoints
timeFrame: Participants will be followed during their first year of life
Secondary outcomes:
measure: Microbiota composition
timeFrame: Samples will be taken at eight time points during the participant's first year of life
measure: Vaccine response
timeFrame: around 1 year of age
measure: Doctor's diagnosis
timeFrame: Participants will be followed during their first year of life
Other outcomes:
measure: infant height
timeFrame: Participant's height is monitored during the first year of life
measure: infant weight
timeFrame: Participant's weight is monitored during the first year of life
measure: coughing
timeFrame: the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life
measure: wheezing
timeFrame: the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life
measure: fever >38 degrees Celsius
timeFrame: the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life
measure: runny nose
timeFrame: the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life
measure: glue ear
timeFrame: the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life
measure: rash
timeFrame: the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life
measure: diarrhea
timeFrame: the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life
measure: >3 crying hours a day
timeFrame: the symptom is daily reported as present or not present (by the parents, on the calendar list), during the infant's first year of life
measure: prescribed antibiotics
timeFrame: Participants will be followed during their first year of life and prescription of antibiotic courses will be monitored
measure: allergic sensitization
timeFrame: around 1 year of age
Locations:
city: Apeldoorn
country: Netherlands
facility: Gelre Hospitals
state: Gelderland
city: Amersfoort
country: Netherlands
facility: Meander Medical Centre
state: Utrecht
city: Blaricum
country: Netherlands
facility: Tergooi Hospital
state: Utrecht
city: Nieuwegein
country: Netherlands
facility: St Antonius Hospital
state: Utrecht
Study officials:
affiliation: St Antonius Hospital Nieuwegein, the Netherlands
name: Arine M Vlieger, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kamphorst K, Vlieger AM, Oosterloo BC, Garssen J, van Elburg RM. Neonatal Antibiotics and Food Allergy Are Associated With FGIDs at 4-6 Years of Age. J Pediatr Gastroenterol Nutr. 2022 Jun 1;74(6):770-775. doi: 10.1097/MPG.0000000000003428. Epub 2022 Feb 24.
citation: Oosterloo BC, Van't Land B, de Jager W, Rutten NB, Klopping M, Garssen J, Vlieger AM, van Elburg RM. Neonatal Antibiotic Treatment Is Associated With an Altered Circulating Immune Marker Profile at 1 Year of Age. Front Immunol. 2020 Jan 10;10:2939. doi: 10.3389/fimmu.2019.02939. eCollection 2019.
citation: Kamphorst K, Oosterloo BC, Vlieger AM, Rutten NB, Bunkers CM, Wit EC, van Elburg RM. Antibiotic Treatment in the First Week of Life Impacts the Growth Trajectory in the First Year of Life in Term Infants. J Pediatr Gastroenterol Nutr. 2019 Jul;69(1):131-136. doi: 10.1097/MPG.0000000000002360.
citation: Rutten NB, Rijkers GT, Meijssen CB, Crijns CE, Oudshoorn JH, van der Ent CK, Vlieger AM. Intestinal microbiota composition after antibiotic treatment in early life: the INCA study. BMC Pediatr. 2015 Dec 9;15:204. doi: 10.1186/s12887-015-0519-0.