History of Changes for Study: NCT04835935
Microbiome, Atopic Disease, Prematurity (MAP)
Latest version (submitted July 4, 2022) on
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Study Record Versions
Version A B Submitted Date Changes
1 April 5, 2021 None (earliest Version on record)
2 July 4, 2022 Study Status
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Study NCT04835935
Submitted Date:  April 5, 2021 (v1)

Open or close this module Study Identification
Unique Protocol ID: 181711
Brief Title: Microbiome, Atopic Disease, Prematurity (MAP)
Official Title: The Association Between Milk Feedings in the Preterm Population, the Microbiome and Risk of Atopic Disease
Secondary IDs:
Open or close this module Study Status
Record Verification: April 2021
Overall Status: Active, not recruiting
Study Start: June 1, 2019
Primary Completion: November 1, 2022 [Anticipated]
Study Completion: June 30, 2025 [Anticipated]
First Submitted: March 2, 2021
First Submitted that
Met QC Criteria:
April 5, 2021
First Posted: April 8, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
April 5, 2021
Last Update Posted: April 8, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Sydney Leibel
Responsible Party: Sponsor-Investigator
Investigator: Sydney Leibel
Official Title: Assoc Physician
Affiliation: University of California, San Diego
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary:

There is increasing recognition that the microbiome may be important in the development of allergic disease. Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. For unclear reasons, those infants born at 34 weeks and earlier are three times as likely to develop asthma. Factors such as formula feeding, C-section delivery and antibiotic exposure may play a role. Recent evidence has identified a "critical window" in early life where gut and breast milk microbial changes are most influential. The investigators propose a novel study to follow a cohort of premature babies in the NICU and after discharge home. The investigators aim to examine whether various exposures of babies in the NICU impact their milk and gut microbiome and lead to asthma and allergies.

Our specific aims are:

  1. To assess if there is a specific pattern of gut and/or breast milk microbiome over time that is affected by the type of nutrition a baby receives (donor vs maternal vs formula) or other exposures such as antibiotics.
  2. Assess whether there are patterns in the microbiome associated with the development of allergic sensitization patterns.
  3. Determine if early patterns of the microbiome and allergic sensitization predict allergic conditions (food allergies, allergic rhinitis, eczema, asthma) by 2 years of age.

The investigators will recruit approximately 50 subjects born at 34 weeks of gestation or earlier from two local level III NICU. These subjects will be followed over their NICU course with weekly stool, milk feed, and oral saliva collection as well as documentation of relevant events including prenatal history, delivery history, nutrition and breast feeding history and antibiotic courses. Further samples will be collected after discharge at research visits that will take place Rady Children's Hospital until 4-6 years of age. At these visits, standardized allergy questionnaires and a blood allergy panel will be obtained. Together this data will provide a unique opportunity to identify potential shifts in the microbiome associated with nutrition, asthma and allergy in preterm infants. Ultimately, the investigators may be able to discover ways to prevent the development of asthma and allergies during this early window of opportunity.

Detailed Description:
Open or close this module Conditions
Conditions: Atopy
Open or close this module Study Design
Study Type: Observational
Observational Study Model: Case-Control
Time Perspective: Prospective
Biospecimen Retention: Samples With DNA
Biospecimen Description: Stool, breast milk, saliva
Enrollment: 51 [Actual]
Number of Groups/Cohorts 2
Open or close this module Groups and Interventions
Groups/Cohorts Interventions
subject who developed atopic disease
microbiome pattern
microbiome pattern in neonatal period
subject who did not develop atopic disease
microbiome pattern
microbiome pattern in neonatal period
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Pediatric Atopic Disease
[ Time Frame: 2-3 years of age ]

Clinical diagnosis of any atopic disease among the participants during study follow up visit. These include any food allergies, allergic rhinitis, eczema, and asthma.
Secondary Outcome Measures:
1. Allergic sensitization patterns
[ Time Frame: 1-2 years ]

Allergic sensitization patterns among the participants will be measured by ImmunoCAP Multitest, which is a blood test that provides qualitative responses (positive or negative) for food and environmental allergens.
Other Outcome Measures:
1. Gut, oral and milk feed microbiome
[ Time Frame: birth to 1 year of age ]

Longitudinal stool, oral swab and milk feed samples will be analyzed for paired microbiome and metabolome patterns. The bacterial and metabolomic profiles will be correlated with the allergic sensitization patterns and diagnosis of pediatric atopic disease in participants.
Open or close this module Eligibility
Study Population: Premature infants born at equal or less than 34 weeks gestational age.
Sampling Method: Non-Probability Sample
Minimum Age: 0 Days
Maximum Age: 7 Days
Sex: All
Gender Based:
Accepts Healthy Volunteers: No

Inclusion Criteria:

  • premature infant equal or less than 34 weeks of age

Exclusion Criteria:

  • hypoxic ischemic encephalopathy, congenital anomaly that affects gastrointestinal system, unable to follow up
Open or close this module Contacts/Locations
Locations: United States, California
Scripps Memorial Hospital - Rady NICU
San Diego, California, United States, 92037
University of California, San Diego - Jacobs NICU
San Diego, California, United States, 92093
Open or close this module IPDSharing
Plan to Share IPD: No
de-identified microbiome and metabolome data will be available.
Open or close this module References
Citations: Raciborski F, Tomaszewska A, Komorowski J, Samel-Kowalik P, Białoszewski AZ, Walkiewicz A, Lusawa A, Szymański J, Opoczyńska D, Drużba M, Borowicz J, Lipiec A, Kapalczynski WJ, Samoliński B. The relationship between antibiotic therapy in early childhood and the symptoms of allergy in children aged 6-8 years - the questionnaire study results. Int J Occup Med Environ Health. 2012 Sep;25(4):470-80. doi: 10.2478/S13382-012-0056-0. Epub 2012 Dec 3. PubMed 23212289
Silvers KM, Frampton CM, Wickens K, Pattemore PK, Ingham T, Fishwick D, Crane J, Town GI, Epton MJ; New Zealand Asthma and Allergy Cohort Study Group. Breastfeeding protects against current asthma up to 6 years of age. J Pediatr. 2012 Jun;160(6):991-6.e1. doi: 10.1016/j.jpeds.2011.11.055. Epub 2012 Jan 30. PubMed 22289356
Roduit C, Scholtens S, de Jongste JC, Wijga AH, Gerritsen J, Postma DS, Brunekreef B, Hoekstra MO, Aalberse R, Smit HA. Asthma at 8 years of age in children born by caesarean section. Thorax. 2009 Feb;64(2):107-13. doi: 10.1136/thx.2008.100875. Epub 2008 Dec 3. PubMed 19052046
Been JV, Lugtenberg MJ, Smets E, van Schayck CP, Kramer BW, Mommers M, Sheikh A. Preterm birth and childhood wheezing disorders: a systematic review and meta-analysis. PLoS Med. 2014 Jan 28;11(1):e1001596. doi: 10.1371/journal.pmed.1001596. eCollection 2014 Jan. Review. PubMed 24492409
Lynch SV, Wood RA, Boushey H, Bacharier LB, Bloomberg GR, Kattan M, O'Connor GT, Sandel MT, Calatroni A, Matsui E, Johnson CC, Lynn H, Visness CM, Jaffee KF, Gergen PJ, Gold DR, Wright RJ, Fujimura K, Rauch M, Busse WW, Gern JE. Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children. J Allergy Clin Immunol. 2014 Sep;134(3):593-601.e12. doi: 10.1016/j.jaci.2014.04.018. Epub 2014 Jun 4. PubMed 24908147
Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, Kuzeljevic B, Gold MJ, Britton HM, Lefebvre DL, Subbarao P, Mandhane P, Becker A, McNagny KM, Sears MR, Kollmann T; CHILD Study Investigators, Mohn WW, Turvey SE, Finlay BB. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med. 2015 Sep 30;7(307):307ra152. doi: 10.1126/scitranslmed.aab2271. PubMed 26424567
Jeurink PV, van Esch BC, Rijnierse A, Garssen J, Knippels LM. Mechanisms underlying immune effects of dietary oligosaccharides. Am J Clin Nutr. 2013 Aug;98(2):572S-7S. doi: 10.3945/ajcn.112.038596. Epub 2013 Jul 3. Review. PubMed 23824724
Neu J. Preterm infant nutrition, gut bacteria, and necrotizing enterocolitis. Curr Opin Clin Nutr Metab Care. 2015 May;18(3):285-8. doi: 10.1097/MCO.0000000000000169. Review. PubMed 25807349
Available IPD/Information:

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