Bodmer-Roy, Sonja MD; Morin, Lucie MD; Cousineau, Jocelyne MD, PhD; Rey, Evelyne MD, MSc
The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) proposed in 2010 new criteria for the diagnosis of gestational diabetes mellitus (GDM).1 These include performing a 75-g oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation without a screening test and using lower thresholds: 92 mg/dL (5.1 mmol/L) for fasting plasma glucose, 180 mg/dL (10 mmol/L) 1-hour postglucose load, and 153 mg/dL 2-hour postglucose load (8.5 mmol/L). Only one abnormal value on the OGTT is needed to diagnose GDM. These recommendations are based on the results of the Hyperglycemic Adverse Pregnancy Outcome study, an international multicenter study, which quantified the risk of adverse pregnancy outcomes related to maternal hyperglycemia.2 The new IADPSG cutoffs identify women with a relative risk of 1.75 for a newborn birth weight above the 90th percentile and approximately 1.5 for other major adverse maternal or neonatal outcomes such as primary cesarean delivery, prematurity, and preeclampsia.
Because adoption of these new criteria would imply an increase in the number of women diagnosed with GDM, it will further burden the health care system. However, these drawbacks are acceptable and justified if maternal and neonatal health are improved.
The goal of this retrospective study was to estimate, in our population, the incidence of gestational GDM by IADPSG criteria, and to study the maternal and neonatal outcomes in women fulfilling these criteria but who were nondiabetic by Canadian Diabetes Association criteria.
MATERALS AND METHODS
This is a retrospective observational study involving women followed at the Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada, between November 1, 2008, and October 31, 2010. The study protocol was approved by the research ethics committee of the institution (#3276).
In our institution, the diagnosis of GDM is usually established by a two-step approach: first, a nonfasting 50-g 1-hour screening test is performed in all nondiabetic women. Results of less than 137 mg/dL (7.6 mmol/L; local threshold) are considered normal, whereas those greater than 184 mg/dL (10.2 mmol/L) are considered abnormal and diagnostic of GDM. If the results are inconclusive, ie, between 137 mg/dL (7.6 mmol/L) and 184 mg/dL (10.2 mmol/L), a 75-g 2-hour OGTT is then performed. The OGTT thresholds are as follows: fasting glucose 96 mg/dL (5.3 mmol/L), 1-hour 191 mg/dL (10.6 mmol/L), and 2-hour 160 mg/dL (8.9 mmol/L) in accordance with the criteria proposed by the Canadian Diabetes Association in 2008.3 Gestational glucose intolerance is defined by one abnormal value on the OGTT and GDM by two abnormal values.3 Women with gestational glucose intolerance are treated in the same way as women with GDM. These tests are performed at the first prenatal visit in high-risk women and between 24 and 28 weeks of gestation in all nondiabetic women. A 75-g OGTT may also be performed without a prior 50-g screening test if preferred by the treating physician.
To evaluate the incidence of GDM, all 50-g screening tests and OGTT results performed at our center on pregnant women during the study period were extracted from the laboratory computerized system database. We then identified the women who would have been classified as abnormal according to the IADPSG criteria but normal according to the Canadian Diabetes Association criteria: fasting glucose value 92 or greater and less than 96 mg/dL (5.1 and less than 5.3 mmol/L, respectively) 1-hour 180 or greater and less than 191 mg/dL (10 and less than 10.6 mmol/L, respectively), and 2-hour 153 or greater and less than 160 mg/dL (8.5 and less than 8.9 mmol/L, respectively). To estimate the rate of GDM according to the IADPSG criteria in women with a normal 50-g screening test, we used data from a previous study performed in our institution: 28.9% of women with a screening test result between 110 and 137 mg/dL (6.1 and 7.6 mmol/L) had GDM according to IADPSG criteria.4
To study maternal and neonatal outcomes, we compared two groups: group 1 included women considered to have GDM according to IADPSG criteria but who did not fulfill the current Canadian Diabetes Association criteria (GDM or gestational glucose intolerance). During the study period these women were not considered as having GDM and as such had no glucose monitoring or treatment for GDM. Because we did not have the resources to review all the charts of women without GDM according to both criteria, the comparison group, group 2, was constituted as follows: for each woman in group 1, we randomly selected one woman with a normal OGTT according to IADPSG and Canadian Diabetes Association criteria and one woman with a 50-g screening test result less than 110 mg/dL (these women were chosen to avoid false-negative GDM and to get a control group equivalent to women without GDM in the Hyperglycemic Adverse Pregnancy Outcome study). For both groups, the exclusion criteria were: multiple gestations, OGTT performed before 12 weeks, delivery in another hospital, major fetal malformation, or GDM diagnosed after the initial test. Maternal and neonatal medical records were reviewed to collect information about baseline maternal characteristics, pregnancy evolution, and maternal and neonatal complications.
The primary outcome was the number of large-for-gestational age newborns, defined as a birth weight of 90th percentile or more according to a Canadian birth weight chart.5 The other main outcomes were: 1) delivery complications (assisted vaginal delivery or cesarean delivery in labor or shoulder dystocia or excessive bleeding (greater than 500 cc in vaginal delivery, greater than 1,000 cc in cesarean delivery, or documented immediate postpartum hemorrhage) or significant vaginal or perineal laceration6; 2) preeclampsia (defined according to the 2008 Society of Obstetricians and Gynecologists of Canada criteria)7; 3) prematurity (delivery before 37.0 weeks of gestation); 4) neonatal complications at delivery (5-minute Apgar score less than 7 or cord blood pH less than 7.2 or need for oxygen therapy for more than 12 hours after delivery); and 5) neonatal metabolic complications (hemoglobin level of 20 g/dL [200 g/L] or more or hypoglycemia needing medical intervention or phototherapy). Obesity was defined as a body mass index (BMI, calculated as weight (kg)/[height (m)]2) 30 or greater. If height was missing, women were considered obese if the first-trimester weight was 90 kg or more and nonobese if it was less than 70 kg. Other missing data were not adjudicated.
We calculated that 186 women in group 1 and 372 women in group 2 would be necessary to detect a difference in the incidence of large for gestational age between 16% (group 1) and 8% (group 2) (based on the Hyperglycemic Adverse Pregnancy Outcome study) with 80% power and α level of 0.05 (two-tailed). Statistical analyses were performed using SPSS 16.0. Continuous variables are expressed as mean±standard deviation and categorical variables as numbers and percentages. Results are presented as crude (odds ratio [OR]), adjusted OR, or mean difference with their 95% confidence interval (CI). The Student's t test, χ2, or Fisher's exact test were used when appropriate. The rates of large for gestational age, preeclampsia, and neonatal respiratory distress at birth were adjusted by logistic regression analyses for established clinical risk factors (in the case of large for gestational age: maternal obesity, age 35 years or older, and parity three or more; for preeclampsia: obesity, nulliparity, and chronic hypertension; for neonatal respiratory distress at birth: mode of delivery). The results were considered to be statistically significant if the P value <.05 (two-tailed).
During the study period, 5,601 women underwent a 50-g screening test, an OGTT, or both (Fig. 1). Among the 5,411 screening tests, 4,014 were considered normal and 195 abnormal. Among the 1,202 women with an inconclusive screening test, 53 did not proceed to do an OGTT. One hundred ninety women underwent a 75-g OGTT without a 50-g screening test. Five hundred ninety-nine of 1,339 OGTTs were considered abnormal according to the Canadian Diabetes Association criteria. Thus, 794 women (14.18%) had abnormal glucose tolerance according to the Canadian Diabetes Association criteria, 467 with GDM (272 abnormal OGTT and 195 abnormal screening test; 8.33%) and 327 with gestational glucose intolerance (5.84%). Among the 1,339 OGTTs, 219 were abnormal according to the IADPSG criteria but normal according to the Canadian Diabetes Association criteria. Considering that 28.9% of women with a 50-g screening test result less than 137 mg/dL (7.6 mmol/L) have GDM by the IADPSG criteria, the total number of GDMs according to the IADPSG criteria was estimated to be 1,541 out of 5,601 women, or 27.51% (95% CI 25.92–29.11).
From the 219 OGTTs identified as abnormal according to IADPSG criteria but not according to Canadian Diabetes Association criteria, 33 women were excluded from our analysis of maternal and neonatal outcomes: 12 had multiple pregnancies, nine OGTTs were performed before 12 weeks of gestation, seven delivered outside our center, three presented GDM later during pregnancy, and two neonates had major malformations. Maternal and neonatal outcomes of the 186 remaining women (group 1) were compared with those of 372 women without GDM according to both IADPSG and Canadian Diabetes Association criteria (group 2).
Group 1 presented higher rates of advanced maternal age, obesity, and previous GDM as well as higher first-trimester weight and BMI (Table 1). The other maternal characteristics, including previous large for gestational age and cesarean delivery, were similar between the groups.
Table 2 presents the main maternal and neonatal outcomes. The rate of large for gestational age was not statistically different between group 1 and group 2, before (OR 1.60, 95% CI 0.83–3.09; P=.16) and after adjustment for obesity, age 35 years or older, and parity three or greater (adjusted OR 1.58, 95% CI 0.79–3.13; P=.19). Among group 2, women with a normal screening test and those with a normal OGTT presented a statistically similar rate of large for gestational age after adjustment for obesity, age 35 years or older, and parity three or greater (4.2% compared with 7.7%, adjusted OR 1.69, 95% CI 0.67–4.23; P=.27).
The other main outcomes were not statistically different between the groups: delivery complications (OR 1.37, 95% CI 0.95–1.98; P=.10), prematurity (OR 1.10, 95% CI 0.53–2.27; P=.85), neonatal complications at delivery (OR 1.45, 95% CI 0.84–2.49; P=.20), and neonatal metabolic complications (OR 0.73, 95% CI 0.42–1.26; P=.29). Preeclampsia was more frequent in group 1 before (OR 2.50, 95% CI 1.06–5.89, P=.04) but not after adjustment for obesity, nulliparity, and chronic hypertension (adjusted OR 2.40, 95% CI 0.92–6.27; P=.07).
Table 3 presents other maternal and neonatal outcomes. We observed a higher rate of cesarean deliveries in group 1 as a result of a higher rate of repeat cesarean deliveries (OR 2.06, 95% CI 1.14–3.71; P=.02). This was not explained by a higher rate of large for gestational age because the groups have a statistically similar rate of large for gestational age in women having repeat cesarean delivery in labor (4.2% compared with 12.0%; OR 0.65, 95% CI 0.34–1.27; P=1.0). Neonatal respiratory problems at delivery were more frequent in group 1 before (OR 2.41 95% CI 1.15–5.05; P=.03) but not after adjustment for mode of delivery (vaginal delivery compared with cesarean delivery) (adjusted OR 2.07, 95% CI 0.97–4.39; P=.06). Clavicle fracture was a rare event, occurring in only two neonates in group 2 (0.5%).
In this study we observed that the IADPSG criteria would nearly double the number of women classified as GDM in our population. However, the women diagnosed with GDM by these criteria but considered nondiabetic by Canadian Diabetes Association criteria did not have worse pregnancy outcomes than those without GDM according to both criteria.
An increased rate of GDM is logical as the new IADPSG thresholds are lower than those of the Canadian Diabetes Association and because a one-step approach is used.8 An increase in the incidence of GDM from 1.06 to 3.6 times its current rate has been previously reported in several other studies from various countries.1,9–13 The varying degrees of increase are attributed to differences in population baseline characteristics and current local diagnostic criteria. In our center, the projected increase will result in almost one-third of all pregnant women being diagnosed with GDM, generating important strain on financial and human resources, namely physicians, nurses, dieticians, and patients.14,15
Contrary to previous studies, we did not observe a statistically significant increase in the rates of neonatal complications such as large for gestational age, prematurity, birth trauma, and metabolic complications in women diagnosed with GDM according to the IADPSG criteria but not to the Canadian Diabetes Association criteria.1,11,12 Our observed rate of large for gestational age was lower in both study groups than in the Hyperglycemic Adverse Pregnancy Outcome study.2 This discrepancy may be explained by differences between the populations' baseline characteristics. Women with a 50-g screening test of 110 mg/dL (6.1 mmol/L) or less may have decreased the rate of large for gestational age in our study. However, women with a screening test between 110 and 137 mg/dL could have contaminated the normal group, because the risk of having GDM by the IADPSG criteria is high (nearly 30%) in these women.4 Moreover, our normal group included women showing various degrees of glycemic response such as women with GDM in the Hyperglycemic Adverse Pregnancy Outcome study (categories 1–4).2
Our observations concerning cesarean deliveries and preeclampsia deserve comments. The increased rate of cesarean deliveries in group 1 was mostly the result of a higher rate of repeat cesarean deliveries. This cannot be explained by the incidence of large for gestational age because this rate was similar in women with repeat cesarean delivery of both groups. However, one possible explanation could be the fact that women in group 1 presented higher rates of advanced age and obesity. These parameters are associated with an increased rate of repeat and emergency cesarean deliveries in several studies including the Hyperglycemic Adverse Pregnancy Outcome study.16–19 We also observed that the rate of preeclampsia was not statistically different between the groups after adjustment for obesity, nulliparity, and chronic hypertension. Nulliparity and chronic hypertension were similar between the two groups. This suggests that obesity was a determining factor in the occurrence of preeclampsia. The risk of preeclampsia has been proven to increase according to BMI, even in nonobese women and independently of maternal glycemia.18,20,21 Advanced maternal age also increases the risk of preeclampsia.22
Our observations are subject to limitations. First, retrospective studies such as ours are subject to the quality of information available in the medical records. Information is often incomplete, especially in such areas as prepregnancy weight, the indication for repeat cesarean deliveries, dietary habits, or exercise. Second, our sample size does not permit the detection of slight differences in perinatal outcomes (type 2 error) in contrast to the Hyperglycemic Adverse Pregnancy Outcome study. Finally, our observations do not apply to first-trimester OGTTs, because we excluded these tests to standardize the study groups. Our observations could be used by centers contemplating the adoption of the IADPSG criteria, either in their decision-making process or to plan for the increase in resource use.
In conclusion, our observations suggest that an abnormal OGTT according to the IADPSG criteria but not according to the Canadian Diabetes Association criteria identifies women with particular characteristics such as advanced age and higher BMI but who are not at increased risk of perinatal complications. From the perspective of optimal use of scarce resources, we question whether our patients would be better served by the adoption of the IADPSG criteria. Randomized controlled trials with cost-effectiveness analyses are needed to prospectively evaluate the effect of applying the IADPSG criteria. Our conclusions are consistent with those of the American College of Obstetricians and Gynecologists published in September 2011.23
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