Maternal iron deficiency, preterm birth, and disrupted microbial inheritance: a proposed double-hit hypothesis
Year: 2026
Type: article
Abstract: The maternal microbiome is the infant’s primary microbial inheritance, transmitted mainly through the maternal gut, vaginal delivery, breast milk, and skin-to-skin contact. Maternal iron deficiency (ID), with anemia, is a common and modifiable nutritional condition associated with impaired immune function and increased preterm birth (PTB) risk, whereas evidence for ID without anemia remains limited. It may influence maternal microbial ecology; however, its potential effect on maternal-to-infant microbial transmission remains unexplored. This review, conducted across PubMed, Embase, and Web of Science (January 2000–June 2026), proposes a double-hit hypothesis defined by the source and biological context of disruption rather than by a strictly temporal sequence. The first hit comprises potentially altered maternal-origin microbial and immunologic inputs from the vaginal, gut, and breast milk ecosystems; the second hit comprises PTB and neonatal intensive care (NICU)-associated disruption of early microbial succession. Human evidence directly linking ID to vaginal dysbiosis is limited to a single study, evidence relating maternal iron status to milk lactoferrin is inconsistent, and the contribution of vaginal communities to persistent infant gut colonization remains uncertain whereas vaginal exposure may have transient ecological or immunologic effects. No study has simultaneously evaluated maternal iron biomarkers, vaginal community state type (CST), breast milk composition, maternal gut microbiome and longitudinal infant gut microbiota. The proposed framework is therefore hypothesis-generating and identifies testable pathways through which maternal ID may alter maternal microbial and immunologic inputs, while also being associated with an increased risk of PTB. PTB, together with the resulting prematurity-related vulnerability and subsequent postnatal exposures, may further disrupt early infant microbiome development.
Authors: Fouzia Zahid Ali Khan, Syed Arham Ali
Language: English
Topic: Infant Nutrition and Health
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223362785