IUGR, Pregnancy
Conditions
Keywords
Pregnancy, IUGR
Brief summary
The purpose of this study is to determine whether the transplacental gradients for 6 polyols and mannose are altered in intrauterine growth restricted (IUGR) pregnancies compared to normal pregnancies and b) to determine the relative contributions of transplacental transport vs production by the conceptus of both inositol (the major polyol) and mannose in IUGR and normal pregnancies using stable isotopic methodology.
Detailed description
The purposes of this study fall in 2 categories: 1) information important to an understanding of normal pregnancies and the roles of polyols and trace carbohydrates in human fetal nutrition and metabolism and 2) determination of the impact of the small IUGR placenta upon the delivery of polyols and trace carbohydrates to the fetus. Stable isotopes of D-mannose, D-glucose and myoinositol are used to determine the contributions of placental transport of these carbohydrates from the maternal circulation to the fetus vs their synthesis in the fetus and placental tissues. The IUGR pregnancies compare the transport and synthesis of these compounds vs a classification of clinical severity based upon Doppler velocimetry data. The investigators anticipate that, (just as the investigators have shown for glucose) the fetal enrichment of mannose m+6 will be \ equal to the maternal enrichment. Thus, without any appreciable dilution of fetal mannose m+6 there is no evidence of fetal production of mannose. This will be further confirmed by the infusion of D-\[1-13C\]glucose into the maternal circulation. Our previous studies have shown that the fetal enrichment will equal the maternal enrichment. Thus, confirmation will be obtained by comparing the enrichment of fetal mannose m+1 with the fetal enrichment of glucose m+1. The mannose enrichment should be 10% or less of the glucose enrichment. These findings would establish unequivocally that fetal requirements for mannose are met primarily by transplacental transport, not fetal production from glucose. Conversely, the investigators anticipate demonstrating that the fetal enrichment of myoinositol m+6 is significantly less than the maternal enrichment demonstrating minimal transplacental flux of myoinositol with very little dilution of fetal enrichment by myoinositol production from glucose. This will receive further confirmation by comparing the fetal enrichment of myoinositol m+1 with the fetal enrichment of glucose m+1. For example if the fetal enrichment of myoinositol m+1 is 70% of the fetal enrichment of glucose m+1, then 70% of fetal plasma myoinositol is derived from fetal plasma glucose. This would establish that fetal myoinositol requirements are met by fetal production from glucose rather than by transplacental transport.
Interventions
DRUGMannose
A primed constant infusion containing the stable isotopes of mannose and myoinositol is administered through a peripheral IV.
DRUGMyoinositol
A primed constant infusion containing the stable isotopes of mannose and myoinositol is administered through a peripheral IV.
DRUGPlacebo
placebo
Sponsors
University of Colorado, Denver
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Normal pregnancy = normal fetal growth by ultrasound, absence of congenital anomalies and no maternal complications. * IUGR = fetal abdominal circumference \< 2 Standard Deviations for gestational age * Scheduled for elective Cesarean section for clinical indications. * Age 18-50
Exclusion criteria
* Presence of maternal infection, chromosomal abnormalities or congenital anomalies * Multiple pregnancies * Emergency Cesarean sections * Diagnosed with Diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maternal Enrichment of Mannose | Measured at time of cesarean delivery | The infusion of D-\[U-13C\]mannose and \[U-13C\]myoinositol into the maternal circulation is used to establish the degree of transplacental flux of these 2 carbohydrates and to determine if there is evidence of fetal and/or placental production of either of these substrates. |
| Fetal Enrichment of Mannose | Measured at time of cesarean delivery | The infusion of D-\[U-13C\]mannose and \[U-13C\]myoinositol into the maternal circulation is used to establish the degree of transplacental flux of these 2 carbohydrates and to determine if there is evidence of fetal and/or placental production of either of these substrates. |
| Maternal Enrichment of Myoinositol | Measured at time of cesarean delivery | The infusion of D-\[U-13C\]mannose and \[U-13C\]myoinositol into the maternal circulation is used to establish the degree of transplacental flux of these 2 carbohydrates and to determine if there is evidence of fetal and/or placental production of either of these substrates. |
| Fetal Enrichment of Myoinositol | Measured at time of cesarean delivery | The infusion of D-\[U-13C\]mannose and \[U-13C\]myoinositol into the maternal circulation is used to establish the degree of transplacental flux of these 2 carbohydrates and to determine if there is evidence of fetal and/or placental production of either of these substrates. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Control Group At the time of the elective cesarean section, a blood sample of 0.5 ml will be obtained from a maternal heated hand vein at the time the umbilical cord is clamped. Then, the umbilical cord will be doubly clamped to isolate a segment. The umbilical artery and vein will be sampled for 0.5 ml of blood. There are no stable isotopes infused. Heating the maternal hand vein allows it to be arterialized. These patients are separate from those required for the stable isotope studies listed below.
Placebo: placebo | 19 |
| Study Group (IUGR) Prior to the elective cesarean section, 2 samples from the patient's heated hand vein are obtained to establish a baseline for the compounds. Next, a primed constant infusion containing the stable isotopes of mannose and myoinositol is begun in a peripheral IV of the mother. This is continued approximately 2 hours until the Cesarean section is complete and the umbilical cord samples are obtained. An additional 3 samples are obtained from the patient's heated hand vein: 1 at the start of the cesarean section, 1 at the time the fetus is delivered, and 1 at the time the umbilical cord samples are obtained.
Mannose: A primed constant infusion containing the stable isotopes of mannose and myoinositol is administered through a peripheral IV.
Myoinositol: A primed constant infusion containing the stable isotopes of mannose and myoinositol is administered through a peripheral IV. | 5 |
| Total | 24 |
Baseline characteristics
| Characteristic | Placebo/Control Group | Study Group (IUGR) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 5 Participants | 24 Participants |
| Region of Enrollment United States | 19 Participants | 5 Participants | 24 Participants |
| Sex: Female, Male Female | 19 Participants | 5 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 5 |
| other Total, other adverse events | 0 / 19 | 0 / 5 |
| serious Total, serious adverse events | 0 / 19 | 0 / 5 |
Outcome results
Primary
Fetal Enrichment of Mannose
The infusion of D-\[U-13C\]mannose and \[U-13C\]myoinositol into the maternal circulation is used to establish the degree of transplacental flux of these 2 carbohydrates and to determine if there is evidence of fetal and/or placental production of either of these substrates.
Time frame: Measured at time of cesarean delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Control Group | Fetal Enrichment of Mannose | 58.54 G/DL | Standard Deviation 20.1 |
| Study Group (IUGR) | Fetal Enrichment of Mannose | 76.50 G/DL | Standard Deviation 8.02 |
Primary
Fetal Enrichment of Myoinositol
The infusion of D-\[U-13C\]mannose and \[U-13C\]myoinositol into the maternal circulation is used to establish the degree of transplacental flux of these 2 carbohydrates and to determine if there is evidence of fetal and/or placental production of either of these substrates.
Time frame: Measured at time of cesarean delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Control Group | Fetal Enrichment of Myoinositol | 66.8 G/DL | Standard Deviation 17.25 |
| Study Group (IUGR) | Fetal Enrichment of Myoinositol | 59.4 G/DL | Standard Deviation 21.9 |
Primary
Maternal Enrichment of Mannose
The infusion of D-\[U-13C\]mannose and \[U-13C\]myoinositol into the maternal circulation is used to establish the degree of transplacental flux of these 2 carbohydrates and to determine if there is evidence of fetal and/or placental production of either of these substrates.
Time frame: Measured at time of cesarean delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Control Group | Maternal Enrichment of Mannose | 63.8429 G/DL | Standard Deviation 7.85 |
| Study Group (IUGR) | Maternal Enrichment of Mannose | 78.5 G/DL | Standard Deviation 1.97 |
Primary
Maternal Enrichment of Myoinositol
The infusion of D-\[U-13C\]mannose and \[U-13C\]myoinositol into the maternal circulation is used to establish the degree of transplacental flux of these 2 carbohydrates and to determine if there is evidence of fetal and/or placental production of either of these substrates.
Time frame: Measured at time of cesarean delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Control Group | Maternal Enrichment of Myoinositol | 58.543 G/DL | Standard Deviation 19.1 |
| Study Group (IUGR) | Maternal Enrichment of Myoinositol | 76.5 G/DL | Standard Deviation 6.55 |