Journal Article

Effect of prenatal antibiotics on breast milk and neonatal IgA and microbiome: a case-control translational study protocol

Silvestri, Alessandra, Fornasa, Giulia, Lutterotti, Martina, Melacarne, Alessia, Carlosama, Carolina, Fumagalli, Monica, Pietrasanta, Carlo, Ferrazzi, Enrico, D’Ambrosi, Francesco, Cetin, Irene, Rescigno, Maria, Ronchi, Andrea, Penna, Giuseppe, Mihula, Martin, Carbone, Elisa, Lizier, Michela, Mosca, Fabio, Pugni, Lorenza

2025

Overview

Background Up to 25–35% of women receive antibiotics (ABX) during pregnancy, but little is known about the consequences on a key mucosal interface such as the mammary gland, and on the development of the neonatal gut’s microbiota and IgA. We hypothesize that prenatal ABX negatively affect the immune functionality of mammary gland, the composition of breast milk microbiota, the development of neonatal fecal microbiota and the abundance of neonatal fecal IgA. Methods Case-control translational cohort study on women and neonates in the presence or absence ( N  = 41 + 41 pairs) of exposure to prenatal ABX for at least 7 consecutive days after 32 weeks of gestation. Results We will evaluate IgA concentration in breast milk and in neonatal feces up to one year after delivery. We will also evaluate clinical parameters, neurodevelopment and the composition of the IgA-coated and uncoated fractions of breast milk and fecal microbiota by means of magnetic-activated cell sorting (MACS) coupled with shotgun metagenomics. Finally, we will measure the concentration of the chemokine CCL28 on maternal serum and breast milk, as a marker of activity of the entero-mammary pathway. Conclusions Our results might support a data-driven evaluation of breast milk immune function in women exposed to prenatal ABX. Impact Breast milk IgA and microbiota are critical to determine the positive effects of breastfeeding in infants. This research protocol will investigate breast milk IgA, microbiota, and the IgA + / IgA − fractions of neonatal fecal microbiota upon exposure to prenatal antibiotics. Fecal IgA and microbiota in infants exposed or not exposed to prenatal antibiotics will be analyzed up to 1 year after birth. This research will clarify the impact of prenatal antibiotics on the immune function of breast milk. This, in turn, might support the selective evaluation of breast milk IgA/microbiota in mothers exposed to prenatal antibiotics, or in donor human milk.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Adult / Anti-Bacterial Agents - adverse effects / Antibiotics / Bacteria / Breastfeeding & lactation / Case-Control Studies / Chemokines / Feces / Feces - chemistry / Feces - microbiology / Female / Gastrointestinal Microbiome - drug effects / Gestational age / Humans / Immune system / Immunoglobulin A - metabolism / Infant, Newborn / Informed consent / Ligands / Medicine / Medicine & Public Health / Microbiota / Microbiota - drug effects / Milk, Human - chemistry / Milk, Human - immunology / Pediatric Surgery / Pediatrics / Plasma / Pregnancy / Prenatal Exposure Delayed Effects / Study Protocol / Translational Research, Biomedical / Womens health