Transplacental Gradients and Transport in Intrauterine Growth Restricted (IUGR) Pregnancies Compared to Normal Pregnancies.

University of Colorado Denver (CU Denver)

Status: Terminated

Conditions: IUGR; Pregnancy

Treatments: Drug: Mannose; Drug: Placebo; Drug: Myoinositol

Study type: Interventional

Funder types: Other

Identifiers

NCT02397291

01-517

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 2 patient groups, including a placebo group

Part 1: Measurements of maternal and fetal concentrations

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Part 2: Stable Isotope Studies

Active Comparator group

Description:

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.

Treatment:

Drug: Myoinositol

Drug: Mannose