PAIGAN 1: Prenatal Antibiotics and Breast Milk / Neonatal IgA

Sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05813184

Collaborator

Humanitas Hospital, Italy (Other)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

In this biological study, we 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

Condition or Disease	Intervention/Treatment	Phase
Prenatal Exposure Delayed Effects Antibiotic Prophylaxis Dysbiosis Neonatal Infection Breast Milk; Noxious Influence, Affecting Fetus	Drug: Antibiotics

Detailed Description

In a human cohort of women and their neonates, we 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, we 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, we 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:

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

Study Design

Study Type:

Observational

Anticipated Enrollment :

82 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Effect of Prenatal Antibiotics on Breast Milk Immune Function and on the Development of Neonatal Intestinal Immune System: the Role of IgA

Anticipated Study Start Date :

Apr 30, 2023

Anticipated Primary Completion Date :

Apr 30, 2025

Anticipated Study Completion Date :

Oct 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Control Women not exposed to antibiotics throughout the entire duration of pregnancy
Prenatal antibiotics Women exposed to antibiotics for at least 7 days from the 32nd week of gestation	Drug: Antibiotics Any antibiotic therapy administered > 7 days

Arm

Intervention/Treatment

Control

Women not exposed to antibiotics throughout the entire duration of pregnancy

Prenatal antibiotics

Women exposed to antibiotics for at least 7 days from the 32nd week of gestation

Drug: Antibiotics

Any antibiotic therapy administered > 7 days

Outcome Measures

Primary Outcome Measures

breast milk IgA [until 12 months of neonatal life]
concentration of IgA in breast milk

Secondary Outcome Measures

fecal IgA [until 12 months of neonatal life]
concentration of IgA in neonatal feces
breast milk microbiota [until 12 months of neonatal life]
Composition of microbiota in breast milk and analysis of fractions coated or uncoated by IgA
fecal microbiota [until 12 months of neonatal life]
Composition of microbiota in breast milk and analysis of fractions coated or uncoated by IgA
maternal CCL28 [until 12 months of neonatal life]
concentration of CCL28 in maternal serum and breast milk

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

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), and 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 and the administration of antibiotics to neonates after birth, within the first week of life.