The Effects of Antibiotic Exposure in Early Infancy on Vaccine Responses

This prospective cohort study will include 200 term children born in Landspitali University Hospital in Iceland. The cohort will be divided into four groups according to antibiotic exposure of which one is the control group. Children's immune responses to live oral rotavirus vaccine as well as conventional vaccinations given at three, five and 12 months old will be determined by measuring salivary and serologic responses. Responses will be compared between the four groups. Stool samples will also be collected from participants and the composition of the microbiome compared between the four groups.

Study Overview

• Status: Active, not recruiting
• Conditions: Antibiotic Treatment; Immune Responses
• Intervention / Treatment: Other: Antibiotic treatment

Detailed Description

This prospective cohort study will evaluate the development of the immune system by means of evaluating the immune responses to oral rotavirus vaccine and the scheduled childhood vaccinations in Iceland, at the age of three, five and 12 months, in four different groups of term children born in Iceland.

The cohort will be divided into the following groups:

• Group A: Term children born with elective caesarean section (their mothers received intra-operative antibiotics).
• Group B: Term vaginally born children and their mothers received intra-partum antibiotics.
• Group C: Term vaginally born children that received systemic antibiotics during the first week of life for at least 48 hours.
• Group D: Term vaginally born children that had not received systemic antibiotics at the time of recruitment.

Parents of children born with elective caesarean section in Landspitali or born vaginally and their mothers received intra-partum antibiotics as well as parents of children in the Neonatal Intensive Care Unit receiving systemic antibiotics during the first week of life will be offered to take part in the study (Groups A, B and C). Parents of children coming to a five day old check up at the Children's Hospital in Landspitali will also be offered to take part in the study (Group D). Sample size calculations show that to detect a 30% difference in immune responses to vaccines with 80% power, 40 infants are needed for analysis in each group. To account for late exclusions due to antibiotic use or drop-out due to other reasons, 50 infants will be recruited to each group. Participants will receive vaccination with the oral live attenuated rotavirus vaccine, Rotarix, at six weeks old and again at three months old. Participants will receive vaccinations with Pentavac against diphtheria, tetanus, pertussis, haemophilus influenza type B and polio and Synflorix against pneumococci at their Health Care Centre according to scheduled childhood vaccinations in Iceland at three, five and 12 months old. Salivary and blood samples will be taken from participants just before the first vaccination with Rotarix at six weeks old and again at six months (four weeks after the second dose of Pentavac and Synflorix) and at 13 months old (four weeks after the third dose of Pentavac and Synflorix). Specific antibody levels against rotavirus, pertussis, diphtheria, tetanus, haemophilus influenzae type B, polio virus and pneumococci will be measured. Parents of participants will be given two stool sample kits and asked to take one from their child at six weeks old (before the first dose of rotavirus vaccine) and then another at three months old. In case of detection of differences in antibody response, these samples will be sent for microbiome analysis.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• Iceland
  • Reykjavik, Iceland, 101
    • Landspitali University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

• Group A: In total 50 term children born in Iceland during the time period 2022-2023, delivered with elective caesarean section (their mothers received intra-operative antibiotics).
• Group B: In total 50 term children born in Iceland during the time period 2022-2023, delivered vaginally and their mothers received intra-partum antibiotics.
• Group C: In total 50 term children born in Iceland during the time period 2022-2023, delivered vaginally and received systemic antibiotics during the first week of life for at least 48 hours.
• Control group (Group D): In total 50 term children born in Iceland during the time period 2022-2023, delivered vaginally and received no systemic antibiotics at the time of recruitment.

Description

Inclusion Criteria:

• All term children born in Iceland from 2022-2023

Exclusion Criteria:

• Children born with emergency caesarean section
• Children born before 36 weeks of gestation
• Children diagnosed with primary or secondary immunodeficiency
• Use of immunosuppressive drugs at recruitment or during the follow up period (excluding inhaled corticosteroids and short term oral corticosteroids (<3 consecutive days).
• Children with chromosomal, genetic or other congenital diseases or abnormalities
• Children with severe, chronic diseases or disabilities
• Informed consent not signed by parents

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; Term children born with caesarean section (their mothers received intra-operative antibiotics)	Other: Antibiotic treatment; Children will be assigned to groups according to antibiotic exposure in early life. No antibiotics will be given in the study.
Group B; Term vaginally born children and their mothers received intra-partum antibiotics	Other: Antibiotic treatment; Children will be assigned to groups according to antibiotic exposure in early life. No antibiotics will be given in the study.
Group C; Term vaginally born children that received systemic antibiotics during the first week of life for at least 48 hours	Other: Antibiotic treatment; Children will be assigned to groups according to antibiotic exposure in early life. No antibiotics will be given in the study.
Group D (Control group); Term vaginally born children that had not received systemic antibiotics at the time of recruitment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum antibody response to rotavirus	Serum IgA against rotavirus	2 years
Salivary antibody response to rotavirus	Salivary IgA levels against rotavirus	2 years
Serum antibody response to other microbes	Serum IgG against other microbes	2 years
Salivary antibody response to other microbes	Salivary IgG against other microbes	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composition of the microbiome	16s rRNA analysis of stool microbiome	3 years

Collaborators and Investigators

• Sponsor: Landspitali University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2022
• Primary Completion (Actual): February 28, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: October 6, 2023
• First Submitted That Met QC Criteria: October 6, 2023
• First Posted (Actual): October 12, 2023

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Children; Antibiotics; Rotavirus; Vaccinations; Immune Responses
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: e-INFANT-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No