Fetal Growth and Placental Function in Pregnancies Complicated by Diabetes
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Preterm delivery
研究概览
简要总结
Diabetic pregnancies are often complicated by placental dysfunction with reduced transfer of oxygen from the mother to the fetus, which may compromise fetal growth and organ development. In diabetic pregnancies, hyperinsulinemia and hyperglycemia very often leads to fetal macrosomia. The combination of reduced placental oxygen transfer and increasing fetal demand due to fetal overgrowth may possess a particular risk of adverse pregnancy outcome.
Current methods in the antenatal identification of placental dysfunction relies on estimates of fetal size and fetal wellbeing using ultrasound including Doppler flows measurements. These measurements are only indirect estimates of placental function, as no clinical method exists to assess placental function directly. In diabetic pregnancies, the estimates are further limited due to fetal overgrowth and unreliable Doppler. In addition, in diabetic pregnancies, intrauterine fetal weight estimates by ultrasound are inaccurate because of asymmetric fetal growth. Therefore, new accurate methods to assess placental function, fetal oxygenation and fetal growth in this particular group of high-risk pregnancies is highly needed. Early and precise identification of pathology in diabetes pregnancy may lead to an improved outcome in the offspring, as precise identification of pathology facilitates important obstetric decisions in regards to maternal antidiabetic treatment and timing of delivery. Resent research indicates that MRI is useful for this purpose.
It is well described, that preeclampsia is associated with an increased maternal risk of cardiovascular disease later in life. Recent studies suggest, that pregestational subclinical cardiovascular dysfunction, in particular left ventricular dysfunction, may increase the risk of preeclampsia and fetal growth restriction during pregnancy. Cardiac MRI is a sensitive method to detect subclinical maternal cardiac dysfunction, which may be used in identification of high-risk pregnancies. In addition, the longitudinal design of this study allows for the investigation of cardiovascular changes during pregnancies in normal pregnancies and pregnancies complicated by diabetes.
The overall aim of this study is to improve the antenatal fetal and maternal monitoring in diabetes pregnancies. Early and precise identification of pregnancy pathology provides a better basis for important obstetric decisions regarding antidiabetic treatment, monitoring intervals and timing of delivery, which leads to a better outcome for the mother and offspring.
Hypothesis
Project A:
Placental function and fetal oxygenation in diabetic pregnancies estimated by T2* weighted placental and fetal MRI
Aim: To investigate placental function and fetal oxygenation by longitudinal T2* weighted placental MRI and the association with pregnancy complications.
Hypothesis:
- Diabetic pregnancies are characterized by placental hypoxia (low T2* value)
- Diabetic pregnancies are characterized by fetal hypoxia (low T2* value)
- Fetal and placental hypoxia is a risk factor of placental related complications in pregnancy such as low birth weight, preterm delivery, acute cesarean sections and preeclampsia.
Project B: Fetal growth and the growth of selected fetal organs in diabetic pregnancies estimated by longitudinal MRI volumetry
Aim: To investigate growth velocity of the fetus and selected fetal organs and the correlation with pregnancy complications.
Hypothesis:
- Diabetic pregnancies are characterized by accelerated fetal growth in the third trimester
- Diabetic pregnancies are characterized by asymmetric growth (reduced brain/liver-volume ratio)
- Abnormal fetal growth is associated with dysregulated maternal diabetes.
- Abnormal fetal growth is a risk factor of pregnancy complications such as; macrosomia, preterm delivery and acute cesarean sections.
Project C:
Maternal cardiac function in diabetic pregnancies estimated by MRI
Aim: To investigate maternal cardiac function and the correlation with pregnancy complications such as preeclampsia and fetal growth restriction.
Hypothesis:
- Maternal cardiac function is altered in diabetes pregnancies when compared to normal pregnancies.
- Impaired cardiac function (left ventricular dysfunction) is a risk factor of preeclampsia and fetal growth restriction.
详细描述
Maternal diabetes is an increasing problem among pregnant women worldwide. The incidence of diabetes in pregnancy has increased by 50% during the last 20 years, which is related to increased maternal BMI and higher maternal age. In Denmark the current incidence of gestational diabetes is approximately 6%. Maternal diabetes is a serious complication of pregnancy, and it is associated with an increased risk of maternal and neonatal complications such as preeclampsia, abnormal fetal growth, fetal asphyxia, still birth, caesarian section and premature delivery. In addition, diabetes is associated adverse long term consequences in the mother and the offspring such as increased risk of diabetes and cardiovascular disease.
These complications may be related to impaired fetal oxygenation, which is a result of increased oxygen demand of the macrosomic fetus and impaired fetal supply of oxygen due to placental dysfunction. The diabetic placenta is characterized by immaturity and maternal vascular malperfusion which leads to a reduced transport of oxygen from the mother to the fetus. At the same time, there are adaptive changes such as peripheral vascular hyperplasia, which tends to normalize the oxygen transport capacity. However, in a number of diabetic pregnancies this process remains inadequate to meet the increasing metabolic demand of the growing fetus. This explains why diabetic pregnancies have an increased risk of chronic intrauterine hypoxia and asphyxia in labor.
Current antenatal care in pregnancies complicated by diabetes focus on keeping maternal glucose level stable by the use of either diet or insulin treatment. It has been demonstrated that maternal glucose control is directly related to placental development and adverse obstetric outcomes. Placental function or fetal oxygenation cannot be assessed directly by current clinical methods. In antenatal care screening for placental dysfunction focus on ultrasound estimates of fetal size and ultrasound Doppler measurement of fetal and umbilical blood flow. Small fetal size and specific circulatory changes are indirect signs of placental dysfunction. Unfortunately, in diabetic pregnancies, screening for placental dysfunction is limited by fetal macrosomia and unreliable Doppler flow measurements and therefore new methods to directly assess placental function and fetal growth in this particular group of high risk pregnancies is highly needed in order to ensure rational obstetric decisions on when and how to deliver these high-risk fetuses.
It is well described, that preeclampsia is associated with an increased maternal risk of cardiovascular disease later in life. Women with GDM has a substantially increased risk of both preeclampsia and cardiovascular disease and GDM may be recognized as an early marker of atherosclerosis . Recent studies suggest, that pregestational subclinical cardiovascular dysfunction, in particular left ventricular dysfunction, may increase the risk of preeclampsia and fetal growth restriction during pregnancy. Therefore, early identification of maternal cardiovascular dysfunction is highly important, as prophylactic treatment with aspirin before gestational week 16 may reduce the risk of preeclampsia by more than 50%. Cardiac MRI is a sensitive method to detect subclinical maternal cardiac dysfunction, which may be used in identification of high-risk pregnancies. In addition, the longitudinal design of this study allows for the investigation of cardiovascular changes during pregnancies in normal pregnancies and pregnancies complicated by diabetes.
The overall aim of this study is to improve the antenatal fetal and maternal monitoring in diabetes pregnancies. Early and precise identification of pregnancy pathology provides a better basis for important obstetric decisions regarding antidiabetic treatment, monitoring intervals and timing of delivery, which leads to a better outcome for the mother and offspring.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Age >18 years
- •Singleton pregnancy
排除标准
- •Fetal malformation or abnormal karyotype
- •Maternal height from spine to chest > 43 cm (for technical reasons)
- •Sever claustrophobia or any other contradictions to MRI
- •Women who do not read or understand Danish
结局指标
主要结局
Preterm delivery
时间窗: At birth
Delivery before gestational age 37+0
Preeclampsia
时间窗: 30 weeks before birth or 5 weeks after birth
Any degree of preeclamsia / eclampsia og HELLP
Cesarean sections
时间窗: At birth
Any elective or acute cesarean section
Abnormal birth weight
时间窗: At birth
Birth weight below or above normal index for gestational age (-22% - +22%)
Placental pathology
时间窗: Within 1 year after birth
Any abnormal placenta pathology
次要结局
未报告次要终点
研究者
Sidsel Linneberg Rathcke
MD, PhD student
Aalborg University Hospital