Clinical trial NCT03001167: Microbiome, Antibiotics, and Growth Infant Cohort
Official title: Early Life Antibiotics, Gut Microbiome Development, and Risk of Childhood Obesity
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity, Childhood
Antibiotic Side Effect
Keywords: Microbiome
Antibiotics
Growth
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: University of Minnesota
name: University of Pennsylvania
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2016-12-22
Enrollment: 509
Sex: ALL
Maximum age (years): 96
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Our study population will be comprised of children born at Pennsylvania Hospital between 2016-2018 and subsequently, followed in the Children's Hospital of Philadelphia (CHOP) Care Network or one of four other local primary care pediatric practices.

Brief summary: This cross-disciplinary study will assemble and longitudinally follow a large, diverse birth cohort to determine the relationships between early life antibiotic exposure, microbiome development, growth, antibodies, and immunostimulation.

Detailed description: Perinatal and infant antibiotic exposures are common and have been linked to changes in the gut microbiome, which plays a central role in health and disease. Childhood obesity is an epidemic and animal models have linked antibiotic induced changes in the microbiome with increased adiposity. Infants become colonized with trillions of bacteria in the first few hours of life. During this time period, their nascent immune system develops tolerance to commensal microbes

The primary objectives are to measure the impact of common perinatal and early childhood antibiotic exposures on the structure and function of the developing gut microbiome. To determine the association between common perinatal and early childhood antibiotic exposures and weight/adiposity gain in a large birth cohort of children. To determine mechanisms for the association between microbiome changes over time and the rate of weight/adiposity gain in a large birth cohort of children. To determine the normal developmental pattern by which healthy children develop antibodies in their blood against the microbes that naturally colonize their intestines. To determine the association between immunostimulation and protection from persistent colonization in humans.

Eligibility criteria: Inclusion Criteria (if not specified, applies to child):

* Born at Pennsylvania Hospital
* Recruited at \<120 hours of age
* Born at ≥36 0/7 weeks gestation
* Birth weight ≥2000 grams
* Parents plan to receive well-child care in the Children's Hospital of Philadelphia (CHOP) network, Society Hill Pediatrics, Center City Pediatrics, Penn Medicine or South Philly Pediatrics
* Biological mother is the legal guardian, or the child is born from a surrogacy with guardianship immediately transferred in hospital

Exclusion Criteria (if not specified, applies to child):

* Child in neonatal intensive care unit (NICU) for \>120 cumulative hours
* Biological mother NOT legal guardian, except surrogacy where guardianship is transferred at birth
* Biological mother NOT primary caretaker, except surrogacy where guardianship is transferred at birth
* Biological mother \< 18 years of age
* Child has culture confirmed (blood or cerebrospinal fluid cultures) infection
* Biological mother is non-English speaking

Primary outcomes:
measure: cumulative microbial diversity
timeFrame: 24 months
measure: weight trajectory adjusted for time varying length
timeFrame: 24 months
Secondary outcomes:
measure: total number of individual bacterial taxa
timeFrame: 24 months
measure: expression levels of bacterial gene categories
timeFrame: 24 months
measure: fat stores in the upper arm/extremity
timeFrame: 24 months
measure: fat stores in the upper back/trunk
timeFrame: 24 months
measure: supine length trajectory
timeFrame: 24 months
measure: determine the association between immunostimulation and protection from persistent colonization in humans
timeFrame: 24 months
measure: Use autologous serum antibodies to "tag" fecal microbes
timeFrame: 24 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Jeffrey S Gerber, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Dan Knights, PhD
role: PRINCIPAL_INVESTIGATOR
References: