Prenatal Antibiotics and Breast Milk / Neonatal IgA

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Prenatal Exposure Delayed Effects, Antibiotic Prophylaxis, Dysbiosis, Neonatal Infection, Breast Milk; Noxious Influence, Affecting Fetus

Intervention / Treatment
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* Drug: Antibiotics


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| breast milk IgA | concentration of IgA in breast milk | until 12 months of neonatal life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fecal IgA | concentration of IgA in neonatal feces | until 12 months of neonatal life | 
| breast milk microbiota | Composition of microbiota in breast milk and analysis of fractions coated or uncoated by IgA | until 12 months of neonatal life | 
| fecal microbiota | Composition of microbiota in breast milk and analysis of fractions coated or uncoated by IgA | until 12 months of neonatal life | 
| maternal CCL28 | concentration of CCL28 in maternal serum and breast milk | until 12 months of neonatal life | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgA, Prenatal antibiotics, breast milk, feces, neonatal immune system