Early maternal obesity shapes offspring development through immune mechanisms: a systematized review

In recent years, rates of maternal obesity before conception have continued to rise globally. Maternal obesity in early pregnancy may alter intrauterine immune mechanisms, impact fetal metabolic programming, and increase the risk of later-life obesity. This study aimed to review the literature on changes in immune parameters and weight-related outcomes in offspring reported in human and animal studies of maternal obesity. A systematized literature search was conducted using PubMed and Web of Science for relevant human and animal studies published between 2010 and 2025. Study screening was facilitated using Rayyan. The risk of bias was assessed using SYRCLE for animal studies and LEGEND for human studies. Fifteen studies reporting birth weight outcomes showed conflicting findings, with three reporting higher birth weight, three reporting lower birth weight in offspring of mothers with versus without obesity, eight reporting no significant association, and one study did not report a p-value. These discrepancies may reflect heterogeneity in study models (e.g., Sprague-Dawley rats, C57BL/6J mice, and rhesus macaques), dietary compositions (e.g., cafeteria diet, Western-style diet, and high-fat diet), and species (animal versus human studies). In animal studies, gene expression analyses across different species and sample sources consistently showed upregulation of TLR2, ARG1, VEGF, TNF, and NF-κB, but variable trends for TNF-α, IL-10, IL-6, TLR4, TRAF6, STAT3, and MCP-1(CCL2). In human studies, placental gene expression of IL-1β, MCP-1 (CCL2), CXCR2, STAT3, P38-MAPK, and IL-8 varied across studies, while blood levels of IL-6, CRP, microRNAs, and antibodies also showed inconsistency. Placental macrophage and neutrophil counts were increased in humans, whereas animal studies consistently reported increased placental macrophage counts. Maternal pre-pregnancy or first trimester obesity showed inconsistent effects on offspring birth weight; however, it is associated with alterations in multiple immune parameters and may induce placental inflammation via the macrophage TLR2-NF-κB-p38 signaling pathway.