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The Association Between Glucose Challenge Test, Obesity and Pregnancy Outcome in 6390 Non-Diabetic Women

Posted on: Sunday, 24 April 2005, 03:00 CDT

Abstract

Objective: To evaluate the association between obesity, glucose challenge test (GCT) and pregnancy outcome.

Methods: A prospective cohort study of 6854 consecutive gravid patients screened for gestational diabetes (GDM) using 50-gram GCT, at 24-28 weeks' gestation was performed. A screening value ≥ 130 mg/dl was followed by 100 gr oral GTT. Patients who were diagnosed with GDM were excluded. For purpose of analysis patients were categorized by prepregnancy BMI and by different GCT thresholds. Maternal outcome was defined by rate of preeclampsia, gestational age at delivery, cesarean section (CS) rate and the need for labor induction. Neonatal outcome was defined by fetal size (macrosomia/LGA), arterial cord pH, respiratory complications and neonatal intensive care unit (NICU) admission.

Results: Overall, a positive GCT result (GCT ≥ 130 mg/dl) was identified in 2541/6854 (37%) women. GDM was further diagnosed in 464/6854 (6.8%) of subjects. In both groups of screening results (> 130 mg/dl and < 130 mg/dl), the obese women were significantly older, gained more weight during pregnancy and had a lower rate of nulliparity in comparison to the non obese women. The obese women had higher rates of macrosomia, LGA and induction of labor. No difference was found in mean birth weight, the total rate of cesarean section, preterm delivery, 5 minute Apgar score ≤ 7, mean arterial cord pH, NICU admission and a need for respiratory support in comparison to non obese women in both groups of screening results. A gradual increase in the rate of macrosomia, LGA and cesarean section was identified in both obese and non-obese women in relation to increasing GCT severity categories.

Conclusion: Fetal size and cesarean section rate are associated with the degree of carbohydrate intolerance (screening results). Furthermore, obesity remains the main contributor impacting fetal size.

Keywords: Glucose challenge test, obesity, pregnancy outcome

Introduction

It has been suggested that even minor degrees of increased glucose intolerance during pregnancy in women without gestational diabetes (GDM) are related in a continuous and graded pattern with significantly increased incidence of macrosomia, cesarean section, preeclampsia (PET), and increased need for NICU admission, as well as greater length of maternal and neonatal hospital stay [1-6]. In addition, the association between obesity, higher rate of pregnancy complications and increased glucose intolerance has been suggested [7-15].

However, a paucity of data exists concerning the correlation between different levels of increased carbohydrate intolerance with pregnancy outcome in both obese and normal weight non-diabetic gravid women. Thus, we sought to determine if there are differences in pregnancy outcome with different glucose challenge test (GCT) thresholds.

Materials and methods

Subjects

A prospective study of 6854 consecutive gravid women, between January 1999 to December 2000 was performed. The study population was drawn from maternal health clinics in the metropolitan area of San Antonio, Texas, serving economically compromised inner-city residents. All patients underwent a 50-gram glucose challenge test at 24-28 weeks gestation. A screening value of > 130 mg/ dl was considered positive and it was followed by a 3-hour 100 gr oral glucose tolerance test (OGTT). Gestational diabetes mellitus was diagnosed using the Carpenter-Coustan criteria [16]. GDM subjects were excluded from the study. Women with a prepregnancy body mass index (BMI: weight in kilograms divided by the square of the height in meters) of 27.3 or more were considered obese [17-19]. Total pregnancy weight gain was based on the prepregnancy weight and the last weight measured within a week before delivery.

Pregnancy outcome

For purpose of analysis, pregnancy outcome was compared between women with negative (GCT < 130 mg/dl) and positive screening results in obese and non-obese women. Subjects were further stratified by screening test results in categories of 10 mg/dl increments. For each GCT category, the rate of cesarean section, macrosomia (denned by birth weight 4000 grams or greater), and large for gestational age (LGA), defined as birth weight in the 90th percentile or greater, was assessed for obese and non-obese women. Neonatal outcome was denned by fetal size, arterial cord pH (measured in all neonates in blood drawn from double clamped segments of the umbilical cord), rate of respiratory complications and neonatal intensive care unit (NICU) admission. Neonatal respiratory outcomes included the presence or absence of hyaline membrane disease and transient tachypnea (defined as respiratory distress in infants born near term that lasted for about three days). The diagnosis of hyaline membrane disease was based on the criteria of Corbet et al. [20]. Maternal outcome was characterized by rate of preeclampsia (PET), denned as systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg and proteinuria (at least 300 mg/dl or at least 1 + on a dipstick) on at least two occasions at least 6 hours apart after the 20th week of gestation; gestational age at delivery; cesarean section (CS) rate; and, the need for labor induction. Spontaneous preterm birth was defined as occurring at less than 37 gestation weeks.

Statistical analysis

Comparison between the groups and subgroups were performed with Student's ?-test for continuous data and chi-square or Fisher's exact test for categorical data. The odds ratio (OR) and 95% confidence interval (CI) were calculated where appropriate. Multivariate logistic regression analysis for fetal macrosomia and PET as dependent variables and possible predictors was calculated by controlling for related variables.

Results

Patient characteristics

The maternal age in the study group ranged from 16 to 42 years. Approximately 84% were Hispanic, mostly Mexican American, 10% were Caucasians, 4% African American and another 2% from other ethnic origins.

A positive GCT result (GCT ≥ 130 mg/dl) was identified in 2541/6854 (37%) women. GDM was further diagnosed in 464/6854 (6.8%). For purpose of analysis, patients were stratified by screening results (> 130 mg/dl and < 130 mg/dl), and maternal size (obese, non- obese).

In both groups of screening results, the obese women were significantly older, gained more weight and had a lower rate of nulliparity in comparison to non-obese women (Table I). In addition, obese women with positive screening results (> 130 mg/ dl) were significantly older, had higher rates of multiparty, more perinatal visits and gained more weight during pregnancy in comparison to obese women with negative screening results (< 130 mg/ dl). Non- obese women with positive screening results were significantly older and had higher rates of multiparty in comparison to non-obese women with negative screening results (Table I).

Pregnancy outcome

In both groups of screening results (> 130 mg/dl and < 130 mg/ dl), the obese women had higher rates of macrosomia, LGA and induction of labor. No difference was found in mean birth weight, the total rate of cesarean section, preterm delivery, 5minute Apgar score ≤ 7, mean arterial cord pH, NICU admission, stillbirth rate and a need for respiratory support in comparison to non-obese women.

Further comparison by maternal weight revealed that both obese and non-obese women with positive screening results had higher rates of macrosomia and LGA in comparison to obese and non-obese women with negative screening results. All other pregnancy outcome measures were comparable between obese and non-obese women regardless of screening results (Table II).

Multivariate logistic regression analysis for the risk of macrosomia revealed that the only contributing variables were obesity (O.R 2.9, 95% CI 2.2-4.7) and maternal age (O.R 1.8% 95% CI 2.3-5.4). Nulliparity (p = 0.3), maternal weight gain during pregnancy (p = 0.5), previous macrosomia (p = 0.09), ethnicity (p = 0.7), gestational age at screening (p = 0.2), number of prenatal visits (p = 0.3), and GCT results (p = 0.07), were nonsignificant.

Table I. Selected maternal characteristics in obese and non obese women stratified by glucose challenge test results.

Table II. Selected pregnancy outcome measures in obese and non obese women stratified by glucose challenge test results.

Overall, the rate of PET was 6.7%. In obese women the rate was 8.2% and in non-obese 5.1% (p < 0.001). A logistic regression revealed that prepregnancy obesity (O.R 3.9, 95% CI 2.3-6.7) and nulliparity (O.R 3.6, 95% CI 2.8-4.6) were independent contributors. Maternal age (p = 0.7), maternal weight gain during pregnancy (p = 0.3), gestational age at screening (p = 0.3), ethnicity (p =0.6) number of prenatal visits (p = 0.4) and GCT result (p = 0.08) were non-significant.

GCT threshold categorization and pregnancy outcome

An increase in the rate of macrosomia, LGA and cesarean section was identified in both obese and non-obese women in relation to increased GCT severity categories (by 10 mg/dl increments) (Table III). For obese women, a comparison between GCT < 140 and GCT > 140 revealed that the macrosomia rate was 13.9% and 22.5%, respectively (O.R. 1.64 95% CI 1.1-2.9). Obese women with GCT < 110 and GCT > 110 had cesarean sectio\n rates of 10.6% and 24.3%, respectively (O.R 2.2 95% CI 1.2-4.2). A comparison between obese women with GCT < 120 and GCT > 120 revealed an LGA rate of 13.6% and 24.7%, respectively (O.R 1.1, 95% CI 0.5-2.5).

For non-obese women, a comparison between GCT < 140 and GCT > 140 resulted in a macrosomia rate of 8.9% and 13.2%, respectively (O.R 1.54 95% CI 1.2-2.0). For a threshold of GCT < 130 and GCT > 130, the cesarean section rate was 12.2% and 19.1%, respectively (O.R 3.1 95% CI 2.2-3.9) while a GCT < 130 and GCT > 130 revealed that the rate of LGA was 12.5% and 20.7%, respectively (O.R 1.7, 95% CI 1.2- 2.3).

Table III. Stratification by GCT severity for the risk of macrosomia, LGA and cesaraean section in obese and non obese women.

Discussion

In the current study we evaluated pregnancy outcomes in a cohort of 6390 non-diabetic pregnant women in relation to maternal size (obese and nonobese) and glucose tolerance status. The key findings in our study were: 1) Pre-pregnancy obesity is a significant contributor to fetal size; 2) Increased fetal weight and cesarean section rates in both obese and non-obese women are associated with higher degrees of carbohydrate intolerance; 3) Neither maternal obesity nor increased glucose intolerance are related to preterm deliveries; and 4) Obesity rather than weight gain during pregnancy and glucose intolerance are the main contributors for increased rates of preeclampsia.

In the current study we found that the risk of preeclampsia, the rate of induction of labor, macrosomia and LGA increased in obese women, as previously reported by others [1,2,12,21-23]. As expected, the increase in fetal weight was more prominent in women with abnormal GCT results in both obese and non-obese subjects. Moreover, obese women had higher rates of macrosomia and LGA, even though the mean birthweight was comparable between obese and non-obese subjects and no increased rate of preterm labor was identified among these obese subjects in comparison to non-obese. This controversy may be explained by the theoretical disguise effect of calculated mean birthweight over analysis of birthweight in terms of LGA and SGA ratio in a given studied population.

Previous studies have demonstrated that increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of macrosomia and other pregnancy complications [1,3]. Macrosomia occurred more often in infants of obese mothers and significantly more often in those who were obese and had abnormal GCT results. It has been suggested that even limited degrees of glucose intolerance may affect the outcome of pregnancy and fetal size [1-5]. Assuming that the glucose intolerance during pregnancy is a continuum, increased maternal weight contributes to the development of insulin resistance and affects fetal size. We found that obesity rather than the GCT levels are the most important predictors of macrosomia as reflected in the logistic regression model. The large sample size enabled us to categorize the GCT results into several increment groups and to evaluate the predictive value for diagnosis of macrosomia, LGA and cesarean section in each category. We found that for non-obese women a significant increase in the rates of macrosomia, LGA and cesarean section was identified above the GCT category of 130-140 mg/dl. For obese subjects, a significant increase in the rate of macrosomia was identified from the GCT category of 130-140 mg/dl, for LGA in the GCT category of 120-130 mg/dl and for cesarean section above the GCT category of 110-120 mg/dl (Table III).

The rate of preterm delivery in our study was not influenced by the presence of maternal obesity or increased glucose intolerance (GCT). Our findings are not consistent with several studies that suggested an increased rate of preterm birth in relation to increased glucose intolerance [24,25]. However, our data concurred with several studies that support our findings [3,12,26,27]. This inconsistency can be explained, in part by physicians' response to positive GCT screening results with aggressive measures [28].

It has been suggested that the risk of cesarean section is higher among obese women [1,2,9,10,12,30]. In our study the overall rate of both primary (elective) and non-elective cesarean section was not increased in obese women. However, we found an increased cesarean section rate in association with increased GCT results. When we stratified the patients by maternal size, we found that in non- obese women only with a GCT threshold > 130 mg/dl, was there an increased cesarean section rate. In contrast, obese women had an increase in cesarean section rates in the presence of a normal GCT result (> 110 mg/dl). This may be due, in part, to a self- fulfilling prophesy, i.e., the physician responds to obesity, abnormal screening results, and the possibility of fetal macrosomia with a cesarean section delivery. The higher cesarean section rate in obese women is of particular concern because this group is exposed to higher perioperative morbidity, including higher rate of preoperative infections, blood loss, anesthetic complications, and prolonged hospitalization [31,32].

We found that there is increased risk for PET in obese women. Maternal obesity, both in itself and as part of the insulin resistance syndrome, is an important risk factor for the development of preeclampsia. Our finding is in agreement with a recent meta- analysis [33] that demonstrated that the risk of preeclampsia typically doubled with each 5-7 kg/m^sup 2^ increase in prepregnancy body mass index. This relationship persisted after exclusion of women with chronic hypertension, diabetes mellitus or multiple gestations, and after adjustment for other confounders.

Previously, the association between maternal obesity and abnormal glucose intolerance was measured in relation to perinatal mortality [1,12,13]. Since perinatal mortality rates are relatively low, outcome evaluation should address fetal morbidity. In our study, we measured short-term outcome criteria such as mean arterial pH, 5 minute Apgar score below 7, stillbirth and the need for admission for NICU and respiratory complications. All these measures were not related to either maternal obesity or abnormal GCT results. Finally, our studied population is heavily weighted toward the Hispanic populations, thus, our findings may be limited to this sub- population.

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YARIV YOGEV1, ODED LANGER1, ELLY M.J. XENAKIS2, & BARAK ROSENN1

1 Department of Obstetrics and Gynecology, St. Luke's-Roosevelt Hospital Center, University Hospital of Columbia University, New York, and 2 Department of Obsterics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, USA

(Received 20 February 2004; revised 21 April 2004; accepted 27 April 2004)

Correspondence: Y. Yogev M.D., Department of Obstetrics and Gynecology, St. Luke's-Roosevelt Hospital Center, 1000 Tenth Avenue, Suite 11A, New York, NY 10019, USA. Tel: 1-212-523-5750. Fax: 1-212- 523-8066. E-mail: ilanit@dlylaw.co.il

Copyright CRC Press Jan 2005

Source: Journal of Maternal - Fetal & Neonatal Medicine

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