Feeding the Preterm Gut Microbiota - Impact of Infant-feeding on Preterm Gut Microbiota Development (FEEDMI)

Preterm infants are especially vulnerable to gut microbiota disruption and dysbiosis since their early gut microbiota is less abundant and diverse. Several factors may influence infants' microbiota such as mother's diet, mode of delivery, antibiotic exposure and type of feeding. The main goal of this observational study is to evaluate the impact of different types of feeding (breast milk, donor human milk and preterm formulas) on the intestinal microbiota of preterm infants hospitalized in the neonatal intensive care unit (NICU) of Maternidade Alfredo da Costa (MAC). Furthermore, the influence of mode of delivery and the mother's diet, among others factors, on vertical microbiota transmission will be evaluated. After delivery, mothers will be asked to collect their own fecal samples and will be invited to complete a semi-quantitative food frequency questionnaire. Stool samples will be collected from premature infants every 7 days. DNA will be extracted from fecal samples and different bacterial genus and species will be analyzed.

Study Overview

• Status: Unknown
• Conditions: Very Preterm Infants
• Intervention / Treatment: Other: Infant-feeding

Detailed Description

Meconium and the additional 3 fecal samples will be collected from preterm infants by the nursing team of MAC Neonatology Unit. Fecal samples will be collected every 7 days, during 21 days, from diapers into sterile tubes. Mothers will be asked to collect their own fecal samples with an appropriate stool collection kit (EasySampler®) and will be invited to complete a semi-quantitative food frequency questionnaire, previously validated for the Portuguese population.

Infant-feeding profile (breast milk, donor human milk or formula) of preterm infants will be recorded every day to select the most representative (>50 %) type of infant-feeding received during the 7 days prior to each fecal sample collection.

Additionally, detailed clinical data will be collected during the preterm infant enrollment in the study. Personal clinical data includes sociodemographic information and clinical intrapartum and postpartum outcomes, such as newborn's weight, days of antibiotic exposure, number of total days of hospitalization and others outcomes related to the preterm clinical evolution.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Sara Brito, MD; Phone Number: +351 964278547; Email: sarabri@gmail.com
• Study Contact Backup: Name: Conceição Calhau, PhD; Phone Number: +351 218 803 000; Email: ccalhau@nms.unl.pt

Study Locations

• Portugal
  • Lisbon, Portugal, 1050-010
    • Recruiting
    • Maternidade Dr. Alfredo da Costa, Centro Hospitalar de Lisboa Central
    • Contact: Sara Brito, MD; Phone Number: +351 964 278 547; Email: sarabri@gmail.com;
    • Contact: Juliana Morais, BsC; Phone Number: +351 362711106; Email: ju_morais17@hotmail.com
    • Principal Investigator: Sara Brito, MD
    • Sub-Investigator: Manuela Cardoso, BsC
    • Sub-Investigator: Teresa Tomé, MD
    • Sub-Investigator: Israel Macedo, MD
  • Lisbon, Portugal, 1169-056
    • Active, not recruiting
    • NOVA Medical School, Universidade Nova de Lisboa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Very preterm infants born with less than 32 weeks recruited at the NICU of Maternidade Dr. Alfredo da Costa, Centro Hospitalar de Lisboa Central, Lisbon, Portugal

Description

Inclusion Criteria:

• To be eligible for enrolment, preterm infants must have been admitted to the NICU in less than 24 hours of life, have been born with less than 32 weeks with absence of malformations or metabolic diseases.

Exclusion Criteria:

• non applicable

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Very Preterm Infants; Newborn infants with less than 32 weeks admitted in the NICU.	Other: Infant-feeding; Preterm infants hospitalized in the NICU can be feed by three different types of infant feeding, such as breast milk, donor human milk and/or formulas.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline intestinal microbiota composition of preterm infants at 7, 14 and 21 days.	The intestinal microbiota profile of preterm infants will be evaluated over time.	The first fecal sample (meconium) of preterm infants will be collected. Afterwards, fecal samples will be collected every 7 days, during 21 days.
Changes from baseline intestinal microbiota composition of preterm infants in relation to infant-feeding profile (breast milk, donor human milk or formula) at 7,14 and 21 days.	Infant-feeding profile (breast milk, donor human milk or formula) will be recorded every day to select the most representative type of infant-feeding (> 50 %) received during the 7 days prior to each fecal sample collection.	Infant-feeding type of preterm infants before the first, second, third and fourth collection will be recorded during these 21 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal intestinal microbiota composition, analyzed by RT-PCR.	Mother's will be asked to collect their own fecal samples for gut microbiota analysis by RT-PCR. An appropriate stool collection kit will be provided (EasySampler Stool Collection kit).	Maternal fecal samples will be collected after delivery up to 1 week.
Changes in maternal gut microbiota in relation to clinical variables described below	Changes in intestinal microbiota profile of preterm infants' mothers will be evaluated in relation to mode of delivery, mother's gestational age, dietary pattern during pregnancy, weight gain in gestation and antibiotic exposure.	Clinical variables will be collected daily, until study completion an average of 2 years.

Collaborators and Investigators

• Sponsor: Universidade do Porto
• Collaborators: Center for Health Technology and Services Research; Universidade Nova de Lisboa; Maternidade Dr. Alfredo da Costa

Publications and helpful links

General Publications

• Morais J, Marques C, Teixeira D, Durao C, Faria A, Brito S, Cardoso M, Macedo I, Pereira E, Tome T, Calhau C. Extremely preterm neonates have more Lactobacillus in meconium than very preterm neonates - the in utero microbial colonization hypothesis. Gut Microbes. 2020 Nov 9;12(1):1785804. doi: 10.1080/19490976.2020.1785804. Epub 2020 Jul 13.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2017
• Primary Completion (Anticipated): December 30, 2018
• Study Completion (Anticipated): December 30, 2018

Study Registration Dates

• First Submitted: July 19, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 2, 2018
• Last Update Submitted That Met QC Criteria: September 28, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: preterm infants; breast milk; formula; intestinal microbiota; donor human milk
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: FEEDMI

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