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



Status:Suspended
Conditions:Women's Studies
Therapuetic Areas:Reproductive
Healthy:No
Age Range:18 - 50
Updated:8/26/2018
Start Date:January 2001
End Date:June 2020

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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.

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.

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
We found this trial at
1
site
Aurora, Colorado 80045
Principal Investigator: Henry Galan, MD
Phone: 303-724-6501
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mi
from
Aurora, CO
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