Intestinal Microbiota Composition After Antibiotic Treatment in Early Life

• Conditions: Eczema; Microbiota; Atopy

• Registration Number: NCT02536560
• Lead Sponsor: Agentschap NL

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).

Study Timeline

• Study Start: 2012-01
• Status Verified: 2015-08
• Study First Submitted: 2015-08-21
• Study First Submitted QC: 2015-08-28
• Last Update Submitted: 2015-08-28
• Study First Posted: 2015-09-01
• Last Update Posted: 2015-09-01
• Primary Completion: 2016-04
• Study Completion: 2016-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 450

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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).

Trial Locations

Locations (4)

Gelre Hospitals; 🇳🇱 Apeldoorn, Gelderland, Netherlands

Meander Medical Centre; 🇳🇱 Amersfoort, Utrecht, Netherlands

Tergooi Hospital; 🇳🇱 Blaricum, Utrecht, Netherlands

St Antonius Hospital; 🇳🇱 Nieuwegein, Utrecht, Netherlands