Maternal Hypoglycemia During One Hour Glucose Tolerance Test as a Risk for Decreased Placental Weight and Placental Pathology

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.