An Australian study suggests maternal prebiotic supplementation could reduce the increased risk of food allergy, allergen sensitisation, and atopic eczema linked to intrapartum antibiotics, although larger trials are needed.
Maternal prebiotic supplementation may protect infants from developing allergic disease after exposure to antibiotics during labour, according to Australian researchers, who say the findings point to a potential strategy for reducing one of the unintended consequences of essential obstetric care.
An exploratory analysis of a randomised controlled trial was published this week in Allergy, the European Journal of Allergy and Clinical Immunology.
It found that intrapartum antibiotics were associated with markedly higher risks of allergen sensitisation, IgE-mediated food allergy, and atopic eczema by one year of age, but only among mothers who had not received prebiotic supplementation. Among women given prebiotics, those associations disappeared.
The findings add to growing evidence that microbial disruption around the time of birth may influence immune development, while raising the possibility that maternal prebiotics could help preserve immune tolerance in infants exposed to medically indicated antibiotics.
“Microbial metabolites generated in the maternal gut, such as short-chain fatty acids, can cross the placental barrier, and modulate foetal immune development through epigenetic regulation, cytokine production, and the maturation of regulatory T cells,” the researchers wrote.
“Disruptions in microbial exposures during the perinatal period can impair immune system maturation, promoting allergic sensitisation and chronic inflammation.
A study by Du and colleagues found that lower maternal gut microbial diversity and a reduced abundance of beneficial short-chain fatty-acid-producing bacteria during pregnancy were associated with an increased risk of infant eczema.”
The Australian study analysed 568 mother-infant pairs enrolled in a double-blind randomised trial of galacto-oligosaccharide and fructo-oligosaccharide supplementation from 18 to 20 weeks’ gestation until six months after birth.
All infants had a first-degree relative with allergic disease, placing them at elevated risk of developing allergy.
Antibiotic exposure was common. More than 80% of mothers received antibiotics during the intervention period, including 13.7% during labour, while one in five infants received antibiotics during their first six months of life.
Among women in the placebo group, intrapartum antibiotic exposure was associated with a 3.6-fold higher risk of infant allergen sensitisation, a 5.7-fold increased risk of IgE-mediated food allergy, and a 6.4-fold increased risk of medically diagnosed atopic eczema.
In contrast, no statistically significant increase in any of these outcomes was observed among women randomised to receive prebiotics.
The researchers found no similar associations for antibiotic exposure earlier in pregnancy, during lactation, through routine caesarean prophylaxis or via direct antibiotic treatment of the infant, suggesting labour may represent a particularly vulnerable period for immune programming.
They proposed that antibiotics administered during labour may disrupt the establishment of the infant microbiome at a critical stage of immune development.
Prebiotics, by promoting the growth of beneficial gut bacteria and the production of immunomodulatory metabolites, may help maintain microbial resilience despite antibiotic exposure, the researchers said.
The analysis also offers a possible explanation for the original trial’s primary findings. Although maternal prebiotic supplementation did not reduce allergic disease across the study population as a whole, its benefits may have been concentrated in the subgroup exposed to intrapartum antibiotics, masking a protective effect when all participants were analysed together.
The authors emphasised that the findings should not be interpreted as a reason to avoid intrapartum antibiotics, which remained a cornerstone of preventing serious maternal and neonatal infection, particularly group B streptococcal disease.
Instead, they argue the results support further investigation into interventions that may mitigate antibiotic-induced disruption of early microbial colonisation without compromising infection prevention.
The researchers acknowledged several important limitations, including that the analysis was exploratory and the subgroup of women receiving intrapartum antibiotics was relatively small, resulting in wide confidence intervals around several risk estimates.
No microbiome samples were collected from mothers, breast milk, or infants, meaning the proposed biological mechanisms remain speculative. The cohort also consisted largely of Caucasian families with a strong history of allergic disease, limiting the generalisability of the findings.
Even so, the results aligned with previous observational studies linking intrapartum antibiotics with increased risks of eczema, allergen sensitisation, and food allergy, while providing the first evidence that maternal prebiotic supplementation may modify those associations, the researchers said.
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Although the evidence was not yet sufficient to recommend routine maternal prebiotic supplementation for allergy prevention, the findings identified a potentially modifiable pathway that could become increasingly relevant as efforts continue to balance effective infection prevention with preservation of the infant microbiome.
“In conclusion, antibiotics can be lifesaving and should always be used when clinically indicated,” the researchers wrote.
“However, our findings reinforce that maternal intrapartum antibiotic administration is associated with an increased risk of infant allergen sensitisation, IgE-mediated food allergy, and medically diagnosed atopic eczema.
“Notably, there was no increased risk of infant allergic disease associated with intrapartum antibiotic exposure among mothers randomised to prebiotic supplementation, suggesting that prebiotics may represent a potential strategy to mitigate downstream immune responses.
“Future allergy prevention trials could further optimise maternal prebiotic interventions, especially for women at high risk of intrapartum antibiotic exposure.”
