# Early Pregnancy Immune Signatures May Distinguish Aneuploid Miscarriage from Euploid Pregnancy Loss and Live Birth

## TL;DR

The study finds immune cell patterns in early pregnancy that may help distinguish between miscarriages caused by chromosomal abnormalities and other outcomes.

## Contribution

The study identifies specific immune cell differences in early pregnancy that may predict aneuploid miscarriage, offering new biomarkers for clinical use.

## Key findings

- Basophils were highest in aneuploid miscarriage cases, distinguishing them from euploid miscarriage and live birth.
- Th9 cells were lower in aneuploid miscarriages compared to euploid miscarriages.
- Th17 levels were higher in live births compared to both miscarriage groups.

## Abstract

Pregnancy loss affects ~15% of couples and often results from embryonic chromosomal abnormalities. Early peripheral biomarkers that signal abnormal development could improve counseling and clinical decision-making. Here, we analyzed early-pregnancy peripheral blood from patients who conceived via assisted reproduction without preimplantation aneuploidy testing. Samples were collected ≤12 weeks’ gestation for complete blood counts with differentials and multiparameter flow cytometry to quantify major lymphocyte subsets (total T, B, cytotoxic T cells, T helpers (Th), Th1, Th2, Th9, Th17, and regulatory T cells (Treg)). Participants were followed until pregnancy resolution (live birth, euploid or aneuploid miscarriage), and immune profiles were compared by outcome using the Kruskal–Wallis test. Exploratory discriminative analyses were performed with significantly different immune cell quantities. Basophils were highest in the aneuploid miscarriage group (n = 26), distinguishing them from both euploid miscarriage (n = 27) and live birth (n = 91). Th9 cells were lower in aneuploid miscarriages compared to euploid miscarriages. Th17 levels were higher in live births compared with both miscarriage groups. Additional aneuploidy-type-specific immune differences were observed. These alterations may reflect maternal immune recognition of a non-viable conceptus and localized immune activation at the fetal–maternal interface. If validated in larger cohorts, these early peripheral markers may help identify pregnancies at risk for miscarriage, particularly those involving chromosomal abnormalities.