Epigenetic Alterations in Stress Regulation Genes Among Newborns After Fetal Surgery for Myelomeningocele Repair: An Exploratory Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Methylation status at NRC3C1 and the FKBP5 gene
研究概览
简要总结
Open spina bifida or myelomeningocele (MMC) is a devastating congenital defect of the central nervous system for which there is no cure. The etiology of MMC remains poorly understood. Primary failure of neural tube closure at the caudal neuropore in the embryonic period results in exposure of the developing spinal cord to the uterine environment. Without protective tissue coverage, secondary destruction of the exposed neural tissue by trauma or amniotic fluid may occur throughout gestation. In order to protect the spinal cord from this secondary destruction, a fetal surgical repair can be performed between gestational weeks 20 and 26.
From a psychological point of view fetal repair of MMC constitutes a highly stressful event both for the mother and the fetus. To date, however, stress of mothers and children in case of prenatal surgery for MMC repair has never been studied. It is therefore unclear, if and to what extend the procedure and its consequences are associated with stress, and if there are short- or longer-term consequences.
The aims of this study are threefold:
- Do newborns after fetal surgery for MMC show epigenetic alterations in genes that are involved in stress regulation?
- 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?
详细描述
BACKGROUND AND AIMS:
Open spina bifida or myelomeningocele (MMC) is a devastating congenital defect of the central nervous system for which there is no cure. The etiology of MMC remains poorly understood. Primary failure of neural tube closure at the caudal neuropore in the embryonic period results in exposure of the developing spinal cord to the uterine environment. Without protective tissue coverage, secondary destruction of the exposed neural tissue by trauma or amniotic fluid may occur throughout gestation. In order to protect the spinal cord from this secondary destruction, a fetal surgical repair can be performed between gestational weeks 20 and 26.
From a psychological point of view fetal repair of MMC constitutes a highly stressful event both for the mother and the fetus. To date, however, stress of mothers and children in case of prenatal surgery for MMC repair has never been studied. It is therefore unclear, if and to what extend the procedure and its consequences are associated with stress, and if there are short- or longer-term consequences.
The aims of this study are threefold:
- Do newborns after fetal surgery for MMC show epigenetic alterations in genes that are involved in stress regulation?
- 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?
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Days 至 3 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Group 1: Newborns after successful fetal surgery for MMC, delivered by ECS (elective c-section) at weeks 350 -
- •Group 2: Healthy newborns after exposure to synthetic glucocorticoids for lung maturity during pregnancy, delivered by ECS between 350 - 400 weeks, matched for child sex with group
- •This group is needed to control for the effects of sGC exposure.
- •Group 3: Healthy newborns, uncomplicated pregnancy, delivered at term by ECS between 360 - 390 weeks (healthy controls). Matched for child sex with group
- •Exclusion Criteria for all 3 groups:
- •Multiple pregnancies
- •Apgar 5 min <=7, or significant postpartal health problems such as respiratory distress syndrome
- •General anaesthesia for ECS
- •Insufficient knowledge of German or English by the mother
- •Mother exposed to traumatic stress during pregnancy (other than fetal surgery)
- •Non-Caucasian origin
- •Egg donation
排除标准
- 未提供
结局指标
主要结局
Methylation status at NRC3C1 and the FKBP5 gene
时间窗: Day 2 - Day 3
Saliva DNA will be isolated using prepIT.L2P following manufacturer's protocol (PT-L2P; DNA Genotek Inc.). DNA concentration, A260/A280 and A260/A230 ratios for integrity and quality will be measured using the NanoDrop spectrophotometer (ThermoFisher, Switzerland). DNA methylation specific analysis for each selected gene (NR3C1 and FKBP5) will be conducted using the EpiTect Methyl II PCR assays (Qiagen) following the manufacturer's protocol.
次要结局
- Patient Health Questionnaire (PHQ)(Week 6 and month 3)