Clinical trial NCT05813184: Prenatal Antibiotics and Breast Milk / Neonatal IgA
Official title: Effect of Prenatal Antibiotics on Breast Milk Immune Function and on the Development of Neonatal Intestinal Immune System: the Role of IgA
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Prenatal Exposure Delayed Effects
Antibiotic Prophylaxis
Dysbiosis
Neonatal Infection
Breast Milk; Noxious Influence, Affecting Fetus
Keywords: IgA
Prenatal antibiotics
breast milk
feces
neonatal immune system
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
Collaborators: name: Humanitas Hospital, Italy
First posted: 2023-04-14
Enrollment: 82
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: pregnant women exposed or not exposed to antibiotics in the last trimester of pregnancy

Brief summary: In this biological study, the investigators will evaluate the levels of breast milk IgA, neonatal fecal IgA, and the composition of breast milk and fecal microbiota throughout the first 12 months of life in neonates born to mothers treated or not treated with prenatal antibiotics for at least 7 days after the 32nd weeks of gestation

Detailed description: In a human cohort of women and their neonates, the investigators aim to evaluate the absolute amount of IgA in maternal breast milk and in neonatal feces in the presence (N=41 mother/infant pairs) or in the absence (N=41 mother/infant pairs) of exposure to prenatal ABX during the last period of pregnancy. Moreover, the investigators aim to evaluate, both in maternal breast milk and in neonatal feces, the composition of microbiota, and the proportion and composition of the IgA-coated and not-IgA- coated fractions of microbiota, by means of fluorescence-activated cell sorting (FACS) coupled with 16S rRNA sequencing of bacteria. Finally, the investigators will measure the concentration of the chemokine CCL28 on maternal serum and breast milk, as a soluble marker of activity of the entero-mammary pathway that is known to drive the migration of IgA producing plasma- cells from maternal mesenteric lymph nodes to the mammary gland.

All the analysis will be performed in mother-infant dyads with exclusive breastfeeding. Breast milk/serum/feces collection and analysis will be repeated at the following timepoints:

1. during the first week of neonatal life
2. at 1 month of life
3. at 3 months of life
4. at 8-12 months of life (or at the time of breastfeeding interruption), after the introduction of solid food in the infant's diet.

Eligibility criteria: Inclusion Criteria:

* expression of written informed consent
* an antibiotic treatment (any molecule) for at least 7 days consecutively after the 32 weeks of pregnancy (or the absence of exposure to any systemic antibiotic treatment during pregnancy for the control group)
* the intention to breastfeed their neonates as long as possible during the first year of life

Exclusion Criteria:

* absence of written informed consent
* the intention to formula feed exclusively (or the presence of significant maternal concerns about breastfeeding)
* a maternal antibiotic treatment shorter than 7 days
* the presence of pre-existing maternal immune-mediated disorders (including immunodeficiencies and chronic infectious diseases)
* a delivery at a gestational age \< 34 weeks
* the administration of antibiotics to neonates after birth, within the first week of life.

Primary outcomes:
measure: breast milk IgA
timeFrame: until 12 months of neonatal life
Secondary outcomes:
measure: fecal IgA
timeFrame: until 12 months of neonatal life
measure: breast milk microbiota
timeFrame: until 12 months of neonatal life
measure: fecal microbiota
timeFrame: until 12 months of neonatal life
measure: maternal CCL28
timeFrame: until 12 months of neonatal life
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Study officials:
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Carlo Pietrasanta, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: