# IMMUNE RESPONSES IN THE MOTHER-INFANT DYAD INDUCED BY FETAL SURGERY, AND ASSOCIATIONS WITH PREMATURITY

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2021 · $238,341

## Abstract

Over 300,000 neonates worldwide die in their first month of life due to a congenital birth defect. Thanks to
advancements in diagnostic technology and imaging, the field of fetal surgery was developed to treat some of
these conditions in utero. Results have demonstrated improved short and long-term outcomes following
surgery, especially for those fetuses diagnosed with congenital diaphragmatic hernia, lower urinary tract
obstruction and spina bifida. However, over 30% of the surgical cases will have preterm labor, leading to
complications related to neonatal prematurity. The cause of this surgery-induced preterm birth is unknown;
however, disruption in fetal-maternal tolerance may lead to immune activation and inflammation of the
maternal and fetal immune systems. Maintaining immunologic tolerance is essential during pregnancy, as a
women shares only half of her genetic material with the fetus. Previous work has demonstrated that fetal
surgery leads to an increase in maternal cells identified in cord blood. Animal studies have also shown that in
utero intervention leads to the activation of maternal cells against fetal (paternal) antigen. Based on this
previous data, we hypothesize that surgical trauma following in utero intervention results in mixing of maternal
and fetal cells leading to activation of systemic (adaptive maternal immunity) and regional (fetal placental
macrophages) immune responses that disrupt fetal-maternal tolerance, which can result in preterm birth.
These hypotheses will be addressed in the experiments of the following Specific Aims: 1) to determine whether maternal T cells specific to fetal antigen are activated and expand after in utero intervention; and 2) to determine whether placental macrophages (Hofbauer Cells) and histology in the maternal-fetal interface exhibit increased activation and inflammation in surgical cases born preterm (<37 weeks) compared to term. Should this exploratory study reveal activation of maternal and/or fetal immune responses following in utero surgery, modalities aimed at therapeutically suppressing these acute responses may prolong gestation, significantly benefiting newborns diagnosed with a congenital anomaly.

## Key facts

- **NIH application ID:** 10113537
- **Project number:** 5R21AI151208-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Elizabeth Ann Lieser Enninga
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $238,341
- **Award type:** 5
- **Project period:** 2020-02-24 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113537

## Citation

> US National Institutes of Health, RePORTER application 10113537, IMMUNE RESPONSES IN THE MOTHER-INFANT DYAD INDUCED BY FETAL SURGERY, AND ASSOCIATIONS WITH PREMATURITY (5R21AI151208-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10113537. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*