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

Project 1A) To Determine Whether the Transplacental Gradients for 6 Polyols and Mannose Are Altered in IUGR Pregnancies Compared to Normal Pregnancies. Project 1B) To Determine the Relative Contributions of Transplacental Transport vs. Production by the Conceptus of Both Myoinositol (Major Polyol) and Mannose in IUGR and Normal Pregnancies Using Stable Isotopic Methodology.

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.

Study Overview

• Status: Terminated
• Conditions: Pregnancy; IUGR
• Intervention / Treatment: Drug: Placebo; Drug: Mannose; Drug: Myoinositol

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part 1: Measurements of maternal and fetal concentrations; 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.	Drug: Placebo; placebo
Active Comparator: Part 2: Stable Isotope Studies; 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.	Drug: Mannose; A primed constant infusion containing the stable isotopes of mannose and myoinositol is administered through a peripheral IV.; Other Names: D-[U-13C]; Drug: Myoinositol; A primed constant infusion containing the stable isotopes of mannose and myoinositol is administered through a peripheral IV.; Other Names: D-[U-13C]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Measured at time of cesarean delivery
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.	Measured at time of cesarean delivery
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.	Measured at time of cesarean delivery
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.	Measured at time of cesarean delivery

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Henry Galan, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2001
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: March 12, 2015
• First Submitted That Met QC Criteria: March 18, 2015
• First Posted (Estimate): March 24, 2015

Study Record Updates

• Last Update Posted (Actual): November 11, 2021
• Last Update Submitted That Met QC Criteria: October 13, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Pregnancy; IUGR
• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Fetal Growth Retardation; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Inositol
• Other Study ID Numbers: 01-517

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No