INCA: Intestinal Microbiota Composition After Antibiotic Treatment in Early Life

Sponsor

Agentschap NL (Other)

Overall Status

Unknown status

CT.gov ID

NCT02536560

Collaborator

Danone Research (Industry), Amsterdam UMC, location VUmc (Other)

450

Enrollment

Locations

Duration (Months)

112.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Microbiota Eczema Atopy

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).

Study Design

Study Type:

Observational

Anticipated Enrollment :

450 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

"Intestinal Microbiota Composition After Antibiotic Treatment in Early Life. The INCA Study"

Study Start Date :

Jan 1, 2012

Anticipated Primary Completion Date :

Apr 1, 2016

Anticipated Study Completion Date :

Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Antibiotics 150 infants, (because of hospital protocol) treated with antibiotics because of a perinatal infection during the first week of life
Controls 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

Outcome Measures

Primary Outcome Measures

Clinical endpoints [Participants will be followed during their first year of life]
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. Data are prospectively assessed by parental reports (calendar lists).

Secondary Outcome Measures

Microbiota composition [Samples will be taken at eight time points during the participant's first year of life]
Fecal bacterial composition and diversity is determined at eight time points during the first year of life, from birth on. Sampling points 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). Potential differences in microbiota composition and diversity will be determined by use of 16S-23S ribosomal ribonucleic acid (rRNA) gene analysis (IS-pro).
Vaccine response [around 1 year of age]
Immunoglobulin G antibodies against Tetanus toxoid, Diphtheria toxoid, Haemophilus influenza type B, and the capsular polysaccharides of the pneumococcal 10-valent conjugate vaccine will be determined. Antibody concentrations will be determined from blood samples. Measured in international units per milliliter or microgram per milliliter.
Doctor's diagnosis [Participants will be followed during their first year of life]
Diagnoses are defined by selected International Classification system of Primary Care (ICPC) codes, diagnosticated during the first year of life. These include: dyspnea (R02), wheezing (R03), cough (R05), acute upper tract infection (R74), acute bronchi(oli)tis (R78), pneumonia (R81), asthma like symptoms (R96), breath problems [R04], sneeze [R07], other symptoms of the nose [R08], symptoms of the throat [R21], abnormal sputum [R25], concern about respiratory illness [R27], acute laryngitis [R77], influenza [R88], other infections of the airways [R83], and other respiratory diseases [R99], infectious diarrhea (D70), vomiting (D10), susceptible gastro-intestinal infection (D73), other symptoms/complaints of the skin (S21), dry skin/ flaking (S21.01), infantile colic (A14).

Other Outcome Measures

infant height [Participant's height is monitored during the first year of life]
Individual height is monitored during the first year of life. Parents report the most recently measured height of the child on the calendar lists. (height is measured in centimeters)
infant weight [Participant's weight is monitored during the first year of life]
Individual weight is monitored during the first year of life. Parents report the most recently measured weight of the child on the calendar lists. (weight is measured in kilograms)
coughing [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]
Parental reported symptom on calendar list (yes/no). Description: The child coughs several times a day and/or has coughing. Regularly there are signs of cold. Cough because of choking does not have to be recorded.
wheezing [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]
Parental reported symptom on calendar list (yes/no). Description: During expiration the parents notice a whistling, wheezy sound coming from the lower airways of the child. During expiration the child is trying to squeeze the air outwards. Wheezing coming from or through the nose does not have to be recorded.
fever >38 degrees Celsius [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]
Parental reported symptom on calendar list (yes/no). Description: Clear from itself, whereby it is important that parents use a rectal thermometer, measure twice and the temperature is >38 degrees Celsius on both occasions.
runny nose [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]
Parental reported symptom on calendar list (yes/no). Description: Signs of cold with white/yellow/green mucus running from the nose.
glue ear [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]
Parental reported symptom on calendar list (yes/no). Description: The child seems to have earache and/or grasps its ear (the ear frequently is high-colored or bends) and/or glue egresses from the ear.
rash [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]
Parental reported symptom on calendar list (yes/no). Description: More than one day existing skin-redness (spots, rash, pimples) on the face, arms or legs, trunk. Disease-symptoms are not necessarily present. The rash can be eczema; eczema mostly is red, scaly and may itch. Infants cheeks are affected mostly. When children grow up, elbow and knees are preferred sites.
diarrhea [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]
Parental reported symptom on calendar list (yes/no). Description: Watery or mucous defecation, more than three times a day, that continues more than one day.
>3 crying hours a day [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]
Parental reported symptom on calendar list (yes/no). Description: Clear from itself, whereby the total crying episodes add up to more than three hours a day (24 hours) in total.
prescribed antibiotics [Participants will be followed during their first year of life and prescription of antibiotic courses will be monitored]
Any prescribed (systemic) antibiotic treatments during the first year of life are investigated. Measured as number of antibiotic courses during the first year of life, [1] parental reported (on the calendar list) and [2] checked via pharmacist's medication records.
allergic sensitization [around 1 year of age]
(serum) allergen antibodies to food and inhalant allergens are determined. Measured in kilo unit.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Hour to 7 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Term-born babies (≥ 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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gelre Hospitals	Apeldoorn	Gelderland	Netherlands	7334 DZ
2	Meander Medical Centre	Amersfoort	Utrecht	Netherlands	3813 TZ
3	Tergooi Hospital	Blaricum	Utrecht	Netherlands	1261 AN
4	St Antonius Hospital	Nieuwegein	Utrecht	Netherlands	3430 EM