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New Study Shows Mothers Pass on Allergies to Offspring in the Womb

Researchers from Singapore find that maternal antibodies responsible for triggering allergic reactions can cross the placenta and enter a developing foetus, hinting at why infants exhibit allergies early in life.

A team of researchers from Singapore’s Agency for Science, Technology and Research (A*STAR), KK Women’s and Children’s Hospital (KKH) and Duke-NUS Medical School have found that mothers can pass allergies onto offspring while they are developing in the womb.

Their study, recently published in Science, demonstrated that immunoglobulin E (IgE), the key antibody responsible for triggering allergic reactions, can cross the placenta and enter the foetus. Once inside, the antibody binds to foetal mast cells, a type of immune cell that releases chemicals to trigger allergic reactions.

The team utilised an animal model, following the National Advisory Committee for Laboratory Animal Research (NACLAR) guidelines. Mice were exposed to ragweed pollen, a common allergen, prior to pregnancy. After birth, new-born mice who had mothers that were sensitive to the pollen exhibited an allergic reaction at the time of their first exposure to it, unlike adult mice, who required two exposures. This sensitivity was shown to be allergen-specific, as the offspring did not react to dust mites, another common allergen. Additional laboratory studies showed that maternal IgE can bind to human foetal mast cells, suggesting that they may cross the placenta in humans in a similar manner.

The experimental studies were backed up with cellular tests and imaging, which showed maternal IgE bound to fetal mast cells, triggering the mast cells to release chemicals in reaction to an allergen, a process called degranulation.

This study further showed that the IgE transfer across the placenta requires the help of another protein, FcRN (Neonatal Fc Receptor). Mice with FcRN knocked out lacked maternal IgE attached to their mast cells, and did not develop allergies after birth.

“Allergies begin very early in life,” said Associate Professor Ashley St. John, an immunologist at Duke-NUS’ Emerging Infectious Diseases Programme and a senior co-author of the study. “Infants experience allergic responses closely linked with the mother’s allergic response in ways that cannot only be explained by genetics. This work emphasises one way that allergic responses can pass from the mother to the developing foetus and shows how allergies can then persist after birth.”

The study findings potentially open new intervention strategies to limit such transfer to minimise the occurrence of neonatal allergies. Currently, between 10 to 30 percent of the world’s population are affected by allergies. This number is set to continue rising and a solution preventing allergies being passed from mother to child could potentially reduce those numbers.

“Our research has really exciting findings that may explain the high incidence of early onset atopic dermatitis (eczema) in children of mothers with clinically proven eczema, which parallel findings in our local birth cohort findings,” said Professor Jerry Chan, Senior Consultant, Department of Reproductive Medicine at KKH, Senior National Medical Research Council Clinician Scientist, and Vice Chair of Research with the Obstetrics and Gynaecology Academic Clinical Programme at the SingHealth Duke-NUS Academic Medical Centre.

“From a clinical point of view, developing a further understanding in placental transfer of IgE, and the mechanism of foetal mast cell activation would be key to developing strategies to reduce the chance of eczema or other allergies from being transferred from mother to baby.”

The authors aim to better understand the mechanism of IgE transfer through the placenta, how IgE binding to mast cells in foetal skin modulate their functions and how it could affect skin physiology after birth in further studies. [APBN]