Epigenetic alterations after fetal surgery

Principal investigators: Prof. Dr. M. Landolt, Prof. Dr. E. Grünblatt, PD U. Möhrlen, PD T. Burkhardt

Funding: Anna Mueller Grocholski Foundation

Duration of project: May 2019 – December 2021

Open spina bifida or myelomeningocele (MMC) is a devastating congenital defect of the CNS for which there is no cure. There are several problems which are associated with MMC: Hydrocephalus, paraparesis or paraplegia, neuropathic voiding problems of bladder and rectum, orthopaedic pathologies, endocrinologic, sexual, intellectual, and psychosocial abnormalities. Fetal surgical repair is one way to treat a MMC. It is possible between gestational weeks 20-26 but also constitutes a highly stressful event for both the mother and the fetus. Primary studies suggest that prenatal traumatic stress can have long-lasting effects on the child (fetal programming hypothesis). The mechanisms hereby are still unclear, epigenetics may play an important role.

This study aims to answer the following questions:

• Do newborns after fetal surgery for MMC show epigenetic alterations in genes that are involved in stress regulation (NR3C1, FKBP5)?
• With which medical and psychosocial variables are epigenetic alterations associated?
• At age 3 months, do infants after fetal surgery have a more difficult temperament compared to controls?

The study will include newborns after fetal surgery for MMC at the University Hospital Zurich and two control groups. One including healthy newborns and another including newborns after prenatal exposure to synthetic glucocorticoids (sGC) in pregnancy. Each group shall include n=30 newborns (i.e. total number of study participants: n=90). The saliva samples will then be collected between 24 and 72h postpartum. Six weeks and 3 months post-partum, the parents will receive the study questionnaires by mail.

Contact: markus.landolt@kispi.uzh.ch