Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00614094 |
| Other study ID # |
2007043 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
January 31, 2008 |
| Last updated |
July 8, 2008 |
| Start date |
December 2007 |
| Est. completion date |
July 2008 |
Study information
| Verified date |
July 2008 |
| Source |
Oklahoma State University Center for Health Sciences |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Institutional Review Board |
| Study type |
Observational
|
Clinical Trial Summary
The purpose of this retrospective pilot study is to assess the association of maternal
hypoglycemia during the one hour glucose tolerance test with decreased placental weight and
identifiable placental pathology. We hypothesize that a decreased one hour glucose tolerance
test is a risk factor for decreased placental weight, an increased fetal to placental weight
ratio, and other identifiable placental pathology.
Description:
There have been several studies linking hyperglycemia during pregnancy to adverse perinatal
outcomes such as macrosomia, fetal cardiac defects, and shoulder dystocia. However, there
have only been a few studies addressing the effects of hypoglycemia on perinatal outcomes.
Several of these studies have shown an increased risk of intrauterine growth restriction
(IUGR) with maternal hypoglycemia particularly during the glucose tolerance test (GTT).3-6
However, many of these studies have not taken into account comorbid factors or have
conflicting findings.3-6 IUGR is defined as infant birth weights below the tenth percentile
when the baby is otherwise genetically normal. The purpose of this retrospective pilot study
is to assess the association of maternal hypoglycemia during the one hour glucose tolerance
test with decreased placental weight and identifiable placental pathology. We hypothesize
that a decreased one hour glucose tolerance test is a risk factor for decreased placental
weight, an increased fetal to placental weight ratio, and other identifiable placental
pathology.
Abell et al. found that maternal hypoglycemia during the one hour GTT was associated with
decreased birth weights and intrauterine growth restriction (IUGR). However, this study made
no comment on the effect of confounding factors such as tobacco use, history of gestational
diabetes, or maternal BMI. Both Sokol et al and Langer et al revealed a link between
decreased maternal response during the third trimester GTT and IUGR, although in the Sokol
study, each pregnancy had one known risk factor for gestational diabetes. Conversely,
several more recent papers have reported that maternal hypoglycemia is not predictive of
IUGR or poor perinatal outcomes. -8 Consequently, the effect maternal hypoglycemia during
the oral GTT is unclear. The placenta is viewed as a reflection of the intrauterine
environment during pregnancy. Therefore, we wish to examine hypoglycemia during the oral one
hour GTT as a risk factor for decreased placental weight, increased fetal weight to
placental weight ratio, and an increased incidence of abnormal placental pathology.
A normal term placenta weighs approximately 450 grams, which is on average, one sixth of the
fetal weight.9 Increased maternal substrate availability of vital fetal nutrients, such as
glucose, has been known to result in large for gestational age infants, such as occurs with
gestational diabetics.10 This may also be reflected in the increased placental weights
linked with large for gestational age infants.11 Conversely, IUGR and small for gestational
age infants may have decreased placental weights, possibly due to decreased substrate
availability secondary to maternal hypoglycemia. 12 Increased fetal to placental weight
ratios of 1.5 or greater above the average value for a particular gestational age are also
indicative of an IUGR infant.
Identifying a possible indicator for an increased risk of decreased placental weight, which
may in turn indicate an increased risk for IUGR, is vitally important when considering the
outcomes of IUGR infants. These infants are at great risk for hypoglycemia, sepsis, seizure,
stillbirth, respiratory distress, and meconium aspiration. Long term outcomes include poor
school performance, hyperactivity, hypertension, and cardiovascular disease.2 Study
Population Inclusion/Exclusion Criteria Our study population will consist of women younger
than 35, who delivered a term infant either by vaginal delivery or cesarean section at Tulsa
Regional Medical Center between July 1, 2005 and July 31, 2007. This time range was selected
in order to have an adequate number of recent charts to review. (Women 35 and older are
considered "advanced maternal age" and may be at increased risk of placental pathology for
that reason, so they are excluded.) We expect to collect approximately 350 usable charts,
with perhaps only 35 of those from patients with blood sugars in the "low" or experimental
category. A power analysis using these assumptions is provided at the end of this protocol.
All placentas are sent to pathology on a routine basis. A term infant is defined as delivery
at 37 weeks or greater.
The study population will consist of a typical resident clinic patient population from the
OSU OB-Gyn clinic. The ethnicities of the study population include African-American,
Caucasian, Hispanic, American Indian, and Asian women. The population included in the study
must have a one hour glucose tolerance test result equal to or less than 88 mg/dl. These
results are equal to a range in the fifth percentile or less.3 We used 50 grams of oral
glucola at 24 weeks or greater for our glucose tolerance test.
We will exclude women with the following comorbid conditions, due to the fact that such
conditions manifest placental pathology and may affect placental weight: insufficient
gestational dates, multiple gestation, hypothyroidism, hyperthyroidism, heart disease,
tobacco use, drug use, history of or current gestational diabetes, history of IUGR,
chromosomal abnormalities, congenital malformations, preexisting diabetes, any autoimmune
disease, hypertensive disorders, abnormal maternal screen, pulmonary disease, previous
gastric bypass, any disease process that results in decreased gastrointestinal absorption,
HIV, intrauterine amniotic infection, history of placental abruption, thrombophilia, body
mass index (BMI) greater than 40 or BMI less than 19.8.13
Early Termination Criteria N/A
Methods/Procedures Diagnosis
The diagnosis of maternal hypoglycemia after a one hour glucola screen will be defined as a
one hour plasma glucose measurement of equal to or less than 88 mg/dl. The glucose screen
will be performed at 24 weeks gestation or greater, as calculated by last menstrual period
and ultrasound. The one hour GTT results will be obtained from the patient's chart. A
decreased placental weight will be defined as a weight equal to or below one standard
deviation of the mean placental weight according to gestational age (Table 1). The control
group of this population will have a one hour GTT result greater than 88mg/dl. In this
study, we will assess placental weight, birth weight, the placenta to birth weight ratio,
and placental pathology as described in Table 2. All placental findings were assessed by a
single pathologist blinded to the patient's one hour GTT results.
Data Collection The collaborating investigators and research assistants will collect age,
height, weight at initial visit, date of delivery, infant birth weight, one hour GTT result,
smoking and drug use status, placental weight and pathology results, and any of the above
mentioned exclusion criteria only from any patient chart. (Height and weight are needed to
calculate BMI.) Research assistants will be utilized to aid in the collection of this data
from clinic and hospital records. These assistants will be OSU medical students employed by
the work study program and will have basic human research and HIPAA training.
Analysis The two populations will be compared for various response variables. Whenever the
response variable is meaningfully numeric and continuous in nature, two population t-tests
will be used to compare the means of the two groups. When the response is categorical in
nature, contingency tables will be created and Chi Squares tests utilized to compare the
proportion of responses for the two groups. All analyses will be conducted with the use of
PC SAS Version 9 (SAS Institute, Cary, NC).
Confidentiality The records reviewed will be kept in the Houston Park medical records
department or Tulsa Regional Medical Center health information management department. Both
these facilities are locked or under security supervision at all times. All study records
will be de-identified by conversion to numbers before review, analysis, or interpretation.
J. Martin Beal, D.O., Sarah McCoy, Ph.D., and Elsa Vadakekut, D.O. will have access to these
numbers which will be kept locked in the OSU Ob/Gyn office, which is separate from both
medical records departments. All documents linking patient names to charts will be destroyed
after the data collection is complete.
