A significant concern in pregnancies complicated by glucose intolerance is fetal overgrowth. Both maternal adiposity1 and glucose values2 have been linked to neonatal birth weight. The Hyperglycemia and Adverse Pregnancy Outcome study recently reported a continuous relationship between increasing maternal blood glucose and adverse outcomes, including macrosomia.3 This latter association forms the basis for treatment strategies in pregnancies complicated by diabetes.4 Indeed, most women diagnosed with gestational diabetes are treated through nutritional counseling and diet, and insulin is typically added if blood sugar remains elevated after a trial of dietary therapy.5 These interventions are intended to reduce fetal size and associated outcomes such as cesarean and traumatic vaginal delivery, by lowering maternal glucose values.
In pregnant women with overt diabetes, self-monitoring of blood glucose has been associated with both improved control of diabetes6 and improved neonatal morbidity and mortality.7 Use of such monitors enables physicians to track maternal metabolic status and better target insulin therapy. These advantages are also important in the management of women with insulin-treated gestational diabetes, and have been linked to a reduction in macrosomia and large for gestational age neonates.8,9 However, the use of blood glucose self-monitoring devices in the management of women with diet-treated gestational diabetes remains controversial. The American College of Obstetricians and Gynecologists has written that “Whether daily testing is essential for women with GDM [gestational diabetes mellitus] has not been proven.”5 The American Diabetes Association recommends self-monitoring of blood glucose in these women,10 but the utility of daily blood glucose self-monitoring in women diagnosed with mild glucose intolerance has not been firmly established.11,12 Our purpose was to compare pregnancy outcomes in women with diet-treated gestational diabetes who were monitored weekly using office-based fasting glucose testing with those who received blood glucose self-monitoring meters and instructed to check glucose levels four times per day.
MATERIALS AND METHODS
This was a retrospective cohort study of women with diet-treated gestational diabetes who were delivered between January 1, 1991, and March 31, 2001. Between January 1, 1991, and December 31, 1996, pregnant women cared for at Parkland Memorial Hospital, Dallas, Texas, underwent selective screening for gestational diabetes using a 50-g oral glucose beverage between 24 and 28 weeks of gestation. Risk factors for screening included family history of diabetes, personal history of gestational diabetes, and prior delivery of a stillborn, malformed, or macrosomic neonate. Beginning January 1, 1997, all pregnant women were routinely screened for gestational diabetes between 24 and 28 weeks of gestation. Only women who had risk factors for gestational diabetes (family history of diabetes, prior gestational diabetes or prior delivery of a stillborn, malformed or macrosomic neonate) are included in this analysis to correct for any potential differences between those diagnosed after selective or universal screening. Throughout the study period, women with glucosuria, a random serum glucose concentration of 130 mg/dL or greater (all antepartum women had serum glucose measured on presentation for prenatal care), a previous history of gestational diabetes, or symptoms such as polydipsia or polyuria were screened immediately using a 50-g oral glucose screening test.
Those women whose serum glucose exceeded 140 mg/dL (but not more than 200 mg/dL) 1 hour after ingesting a 50-g oral glucose tolerance beverage (Allegiance Healthcare Corp., McGaw Park, IL) were given a 100-g, 3-hour oral glucose tolerance test after an overnight fast. Women with two or more abnormal values according to the National Diabetes Data Group thresholds were diagnosed with gestational diabetes.13 Women whose serum glucose exceeded 200 mg/dL after the 50-g glucose screen underwent a fasting capillary blood glucose measurement, and those women with a glucose value less than 105 mg/dL underwent a 100-g glucose tolerance test. All women who had a negative 3-hour test result before 24 weeks of gestation were tested again between 24 and 28 weeks. Women diagnosed with gestational diabetes are managed in a special morning obstetrics clinic held weekly at Parkland Hospital and receive dietary counseling, which includes instructions regarding daily caloric intake (35 kilocalories per kilogram of ideal body weight) and food types to avoid. Diet counseling or weight gain recommendations did not change during the study period.
Between January 1, 1991, and March 31, 2001, women with diet-treated gestational diabetes underwent monitoring of serum fasting glucose during each office visit. Starting January 1, 1998, such women were routinely given an Accucheck Advantage or Advantage II blood glucose meter (Boehringer Mannheim Corp, Indianapolis, IN) upon diagnosis. Women given these meters were instructed to test their capillary blood glucose four times per day (preprandially, including a morning fasting value and before bedtime). All women with persistent fasting glucose of 105 or greater were initiated on insulin and excluded from analysis.
Pregnancy outcomes for all women delivered at Parkland Hospital are routinely entered into a computerized database. Nurses attending each delivery complete an obstetric data sheet, and research nurses assess the data for consistency and completeness before electronic storage. Historical and antepartum information about women with gestational diabetes was entered into a separate research database and linked electronically to pregnancy outcomes and blood glucose monitor data.
Women with diet-treated gestational diabetes managed with weekly (in-office) serum glucose measurements were compared with women given home blood glucose meters. Those delivered of singleton, cephalic pregnancies were included in the analysis (noncephalic gestations were excluded from analysis because noncephalic presentation may affect delivery outcomes independent of gestational diabetes). The Institutional Review Board of the University of Texas Southwestern Medical Center determined that this study was exempt in accordance with federal regulations. For the purposes of this analysis, macrosomia was defined as any neonate with a birth weight of 4,000 g or greater. Large for gestational age (LGA) was defined using 90th percentile birth weight for gestational age distribution for our population.14
Statistical analysis was performed using SAS 9.1 (SAS Institute, Cary, NC). Statistical analyses performed included χ2, Student t test, and multiple logistic regressions. Results are presented as mean±standard deviation, frequency (percent), and odds ratios with 95% confidence intervals. Values of P<.05 were considered statistically significant.
A total of 990 women with risk factors for gestational diabetes (family history of diabetes, personal history of gestational diabetes, or prior delivery of a stillborn, malformed, or macrosomic neonate) were diagnosed with diet-treated gestational diabetes mellitus. Of these women, 675 were monitored using office-based serum glucose levels every 1 to 2 weeks. The remaining 315 were given home blood glucose meters and instructed to check their capillary glucose four times per day, before each meal and before bed. Table 1 includes demographic characteristics and the results of glucose diagnostic tests for those women monitored weekly compared with those monitored four times per day. Women performing blood glucose self-monitoring were older and more likely Hispanic than those monitored weekly. Those performing daily monitoring had higher mean 50-g glucose challenge test results, but the 100-g glucose tolerance test results were similar between the two groups. Listed in Table 2 are pregnancy outcomes for both groups. There were no significant differences in intrapartum outcomes between the two groups.
Neonatal outcomes are compared in Table 3. Neonates of women who performed self-monitoring of blood glucose weighed an average of 154 g less (3,536 g compared with 3,690 g, P<.001). Similarly, the incidence of macrosomia (more than 4,000 g) or large for gestational age neonates was less in women using blood glucose meters when compared with those monitored during office visits. This difference persisted after adjustment for maternal demographic variables and gestational age at diagnosis (odds ratio 1.48, 95% CI 1.07–2.05, P=.02). No other neonatal outcome differences were identified between the two monitoring protocols.
Shown in Figure 1 are the average fasting glucose values according to gestational age between the two monitoring schemes. Women without blood glucose meters had only fasting glucose values determined at weekly clinic appointments, whereas women using blood glucose self-monitoring checked their capillary glucose an average of 3.7±0.7 times per day. Even though women monitored daily had higher average fasting glucose levels (P=.02), there was no significant difference in the rate of improvement of these glucose values during pregnancy. Shown in Figure 2 is the weekly weight gain until delivery for each group. Women who performed blood glucose self-monitoring gained significantly less weight (per week) after diagnosis than those whose fasting glucose was evaluated at each office visit (median 0.56, interquartile range 0.22–1.08 lb per week compared with 0.74, interquartile range 0.33–1.17 lb per week, P=.009).
There are several important findings in this analysis. Most notably, women with diet-treated gestational diabetes who performed blood glucose self-monitoring were less likely to deliver an oversized neonate. This decrease in macrosomia or large for gestational age neonates was not explained by differences in fasting glycemia between the two groups. However, we did identify a reduction in weekly maternal weight gain when blood glucose self-monitors were used. Finally, the decreased birth weight in neonates of women monitored daily did not translate into a reduction in the rate of cesarean delivery.
Improved maternal glycemic control is an attractive explanation for how daily use of blood glucose self-monitors resulted in fewer larger neonates. Indeed, John B. O’Sullivan and colleages15 first showed that intervening for gestational diabetes lowered blood sugar values and resulted in smaller neonates. Yet, in our study, women using daily monitors actually had higher fasting glucose levels despite similar rates of improvement between the two groups (Fig. 1). This finding is consistent with those of Langer and colleagues16 (1994), who reported a reduction in macrosomia related to intensity of glycemic monitoring, but failed to demonstrate differences in glucose values between intensive and conventional glycemic monitoring groups. Conversely, Homko and colleagues17 (2002) compared blood glucose self-monitoring to a clinic-based monitoring system in 58 women with gestational diabetes and were unable to show a significant difference in pregnancy or neonatal outcomes between the two groups. We report that daily self-monitoring of blood glucose resulted in fewer overgrown neonates.
Although glycemic control plays an important role in determining fetal size, excessive maternal weight gain and obesity also strongly influence neonatal birth weight, even in women without glucose intolerance.18–20 The majority of women in our study were obese at presentation for prenatal care, but those monitored daily gained significantly less weight per week than those monitored weekly during their clinic visits (median 0.56 compared with 0.74 lb per week, P=.009). Excessive maternal weight gain, defined as 0.66 lb per week or greater, in women with a body mass index more than 24 kg/m2 has previously been associated with an increased risk of large for gestational age neonates. Similar overweight women who gained less weight were not at an increased risk of delivering such overgrown neonates.21 Our results indicate that a reduction in maternal weight gain is beneficial, even in women who are already obese. The mechanism for this interaction is uncertain. Herrera et al22 (2006) described how long-chain polyunsaturated fatty acids accumulate in maternal fat deposits, and that increased lipolysis of excess fat during the third trimester liberates fatty acids that may ultimately contribute to fetal overgrowth.
Despite a reduction in macrosomia (more than 4,000 g) and large for gestational age neonates, the rate of cesarean delivery in our study did not differ. The absence of a reduction in the rate of cesarean delivery in women using daily monitoring is not unexpected. Beginning with the work of John B. O’Sullivan and colleagues15 more than 40 years ago, prospective studies of various interventions for gestational diabetes have not convincingly demonstrated a decrease in cesarean delivery rates in treated women despite decreases in neonatal birth weight.23,24 In fact, it has been suggested that the mere diagnosis of gestational diabetes may even increase the likelihood of a cesarean delivery.25 In this study, the modest effect on fetal size was not sufficient enough to result in a reduction in cesarean for dystocia.
We performed an analysis of women with diet-treated gestational diabetes assessed with weekly, office-based glucose monitoring compared with women with diet-treated gestational diabetes performing blood glucose self-monitoring. One of the strengths of the study now reported is the large, population-based sample of 990 women with diet-treated gestational diabetes. A possible weakness is that comparison of only fasting glucose levels may not reflect the full extent of glycemic control. There may have been differences in postprandial glucose levels that could partially explain our findings. As reported by Jovanovic et al,26 macrosomia has been most strongly associated with postprandial glucose measurements in women with insulin dependent diabetes. Additionally, some of the women who used a meter may have felt more motivated to participate in their own care, such that they were more compliant with respect to other counseling interventions. Nonetheless, our findings do suggest that more intense involvement of women with diet-treated gestational diabetes in their glycemic monitoring, with frequent feedback on the effect of diet choices, translates into a reduction in maternal weight gain and thus a decrease in overgrown neonates. In light of the findings of the Hyperglycemia and Adverse Pregnancy Outcome trial,3 in which even lower levels of hyperglycemia were associated with an increased risk of overgrown neonates, our study provides further rationale for blood glucose self-monitoring by women with mild or diet-treated gestational diabetes.
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