High-quality evidence has demonstrated the association of maternal hyperglycemia with adverse perinatal outcomes and the ability of treatment of gestational diabetes mellitus (GDM) to reduce these adverse outcomes.1–3 However, international consensus is still lacking on the best diagnostic testing strategy for GDM. In much of the United States, screening and diagnosis for GDM involves a two-step approach with an initial 50-g glucose screen followed by a 3-hour oral glucose tolerance test using the Carpenter-Coustan criteria.4 However, in other parts of the world, a one-step approach of a 2-hour 75-g oral glucose tolerance test, recommended by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG), is used.2,4
In 2013, the Eunice Kennedy Shriver National Institute of Child Health and Human Development Consensus Development consensus conference concluded that although there are clear benefits to international standardization with regard to the one-step approach, there was not sufficient evidence to adopt a one-step IADPSG approach.5 The conference also called for well-conducted cohort studies to assess the effect of each diagnostic strategy on clinical outcomes. Two large-cohort studies were published since the consensus conference that demonstrated contradictory results both for their primary outcome of large-for-gestational-age neonates as well as for select secondary outcomes, including the total rate of cesarean delivery, primary cesarean delivery, macrosomia, and neonatal intensive care unit admission.6,7
At Northwestern University, the IADPSG criteria were used for GDM diagnosis after the publication of the Hyperglycemia and Adverse Pregnancy Outcomes study1 until the consensus conference recommendation,5 whereupon the Carpenter-Coustan two-step strategy was used. This circumstance within one large-volume institution provided the opportunity to compare maternal and neonatal outcomes associated with each strategy. Therefore, the objective of this study was to compare maternal and neonatal outcomes using the two different approaches (ie, the IADPSG and Carpenter-Coustan) for GDM diagnosis. The primary outcome of our analysis was the rate of cesarean delivery during each of the screening strategy epochs. Our hypothesis was that the rate of cesarean delivery would be higher during the IADPSG epoch.
MATERIAL AND METHODS
This was a retrospective cohort study of women with a singleton pregnancy delivering between December 2010 and February 2015 at Northwestern Memorial Hospital. The IADPSG criteria were used in our institution from December 2010 until June 2013; Carpenter-Coustan criteria were used from July 2013 onward, with the cutoff of 135 mg/dL used as the abnormal screening threshold for the 1-hour glucose challenge during the Carpenter-Coustan epoch. Throughout the entire study duration, women at increased risk for GDM based on American College of Obstetricians and Gynecologists criteria4 were screened at the first prenatal visit with a hemoglobin A1C. Women were included in this cohort if they were at least 18 years of age, had a singleton nonanomalous gestation, and delivered at 37 0/7 weeks of gestation or greater. Women with pregestational diabetes either with a documented diagnosis of type 1 or type 2 diabetes or with hemoglobin A1C of 6.5% or greater at the first prenatal visit were excluded. If a woman had more than one pregnancy during the study period, only the first pregnancy was included so as to not violate the assumption of independence.
Institutional guidelines for women diagnosed with GDM did not change throughout the course of the study: women with GDM received medical nutritional therapy as first-line intervention. Fasting and 1-hour postprandial venous blood glucoses were measured weekly. Adjuvant medication, with insulin typically being first line, was initiated in the case of failure of 2 weeks of medical nutritional therapy, defined as consistently having fasting venous blood glucoses of at least 95 mg/dL or a 1-hour postprandial venous blood glucose of at least 140 mg/dL. If medications were initiated, the patient was provided a glucometer and recorded blood glucoses four times daily on average (one fasting and three postprandial values). Adherence with treatment was assessed by review of the weekly blood glucose log as well as periodic evaluation of the hemoglobin A1C. Fetal growth assessment was done at 30–32 weeks of gestation and at 37–38 weeks of gestation. Timing of delivery was at the discretion of the obstetric care provider, but was typically before 41 weeks of gestation for women with GDM controlled by diet and during the 39th week of gestation for women with GDM requiring medical treatment, either with insulin or oral hypoglycemic agents.
Maternal characteristics and pregnancy outcomes were compared between the two GDM diagnostic epochs. Medical records were abstracted for sociodemographic and clinical characteristics, including maternal age, body mass index at the time of delivery, race and ethnicity, obstetric history, prior medical history, and obstetric course. Data were derived directly from clinical data entered by physicians and used in the care of patients. Furthermore, missing variables were abstracted by the first four authors (A.P., K.S., T.C., and A.B.).
The primary outcome was the rate of cesarean delivery during each of the epochs as we hypothesized that obstetric care provider decision-making regarding route of delivery would be affected by the label of GDM. Secondary outcomes included the rate of primary cesarean delivery, large-for-gestational-age (LGA) neonate (defined as a birth weight greater than the 90th percentile for gestational age and sex8), shoulder dystocia (defined as the application of additional obstetric maneuvers after failure of gentle downward traction on the fetal head to enable delivery of the fetal shoulders9 as determined by the delivering obstetrician), postpartum hemorrhage, hypertensive disease of pregnancy (preeclampsia or gestational hypertension), neonatal intensive care unit (NICU) admission, neonatal respiratory distress syndrome, neonatal hypoglycemia (defined as a glucose level of less than 40 mg/dL), neonatal hyperbilirubinemia (defined as a total serum or plasma bilirubin level greater than the 95th percentile on the hour-specific Bhutani nomogram),10 and perinatal death.
All analyses were performed with Stata 12.0. All tests were two-tailed and P<.05 was used to define significance. Univariable comparisons were performed using Student t test, χ2, Fisher exact test, and Mann-Whitney U test as appropriate. Multivariable logistic regression was used to estimate whether the type of GDM diagnostic testing strategy was associated with the rate of GDM as well as with the primary and secondary outcomes. Covariates entered into the regressions were those that in univariable analysis differed between the two epochs at a level of P<.05. Approval for this study was obtained before its initiation from the Northwestern University institutional review board (STU00200748).
During the study period, a total of 23,509 women met inclusion criteria; 14,074 (60%) pregnancies occurred during the IADPSG epoch, and 9,435 (40%) pregnancies occurred during the Carpenter-Coustan epoch. Maternal and neonatal characteristics are shown in Table 1. Although the actual differences were small, women who were screened using the IADPSG criteria were statistically significantly younger (31.6±5.2 years compared with 31.7±5.1 years, P=.031), were more likely to be non-Hispanic white (50.9% compared with 50.7%, P=.003), and had lower rates of chronic hypertension (1.6% compared with 2.0%, P=.006) and thyroid disease (5.3% compared with 6.3%, P=.003). The incidence GDM diagnosis was 8.3% (1,167) and 7.5% (715) during the IADPSG and the Carpenter-Coustan epochs, respectively (P=.042).
Maternal and neonatal outcomes are depicted in Table 2. The primary outcome, the rate of cesarean delivery, was significantly higher in women diagnosed by the IADPSG criteria rather than Carpenter-Coustan testing. Secondary outcomes of primary cesarean delivery, shoulder dystocia, and NICU admission also were higher among women diagnosed during the IADPSG epoch. In contrast, the rate of hypertensive disease of pregnancy was higher during the Carpenter-Coustan epoch. The rates of LGA, postpartum hemorrhage, neonatal respiratory distress syndrome, neonatal hypoglycemia, neonatal hyperbilirubinemia, and perinatal death did not differ between the two groups. A subgroup analysis including only women who were diagnosed with GDM was done to compare cesarean delivery rates between the two epochs. It showed similar rates of total (39.1% compared with 37.5%, P=.594) as well as primary (27.3% compared with 27.0%, P=.903) cesarean delivery during the IADPSG and the Carpenter-Coustan epochs.
After adjusting for potential confounding variables (maternal age, race, ethnicity, chronic hypertension, and thyroid disease) in multivariable regressions, odds of all cesarean delivery, primary cesarean delivery, shoulder dystocia, and NICU admission remained significantly higher during the IADPSG epoch, whereas the odds of hypertensive disease of pregnancy remained lower during the IADPSG epoch (Table 3).
In this study we have shown that the use of IADPSG testing, compared with Carpenter-Coustan testing, for diagnosis of GDM was associated with an increase in the rate of GDM diagnosis, cesarean deliveries, shoulder dystocia, and NICU admission. These associations persisted after adjusting for potential confounders, suggesting they were not clearly attributable to differences in the patient population during the different epochs.
Several prior studies that assessed outcomes of different diagnostic testing for GDM performed the analysis by assessing outcomes of women who had been classified as normal by Carpenter-Coustan criteria but who would have been diagnosed with GDM if the IADPSG criteria had been used instead.11–14 However, these studies cannot account for the effect of obstetric care provider knowledge of GDM status in clinical decision-making nor for what outcomes would have been with treatment after the IADPSG diagnosis. In our search of the literature we found only two retrospective cohorts that compared the treatment effect on maternal and neonatal outcomes between groups who received Carpenter-Coustan compared with the IADPSG testing.6,7 Huang and Hsieh6 found that, compared with women who underwent Carpenter-Coustan testing, those who underwent the IADPSG testing had lower rates of LGA [6.3% compared with 7.8%, adjusted odds ratio (OR) 0.74, 95% CI 0.61–0.89], but had no change in the rate of cesarean delivery, NICU admission, or preeclampsia because it was underpowered to identify differences in many of these outcomes. A second before-and-after cohort study by Feldman and Tieu7 found no differences in rates of LGA neonates in a Carpenter-Coustan compared with the IADPSG epoch. They did, however, find that the use of IADPSG testing was associated with a higher rate of primary cesarean delivery (20% compared with 16%, adjusted OR 1.2, 95% CI 1.01–1.42).
The increase in the rate of primary cesarean delivery associated with the IADPSG testing observed by Feldman and Tieu7 as well as in our study parallels the increase in the frequency with which GDM was diagnosed during this epoch. Because the rates of LGA were similar between the two epochs, fetal size should not be the factor responsible for the higher odds of cesarean delivery during the IADPSG epoch. Rather, the mere application of the label of GDM may lead to a tendency toward cesarean delivery. This shift in obstetric practice style, regardless of fetal size, has been shown in earlier studies of GDM, even when GDM was treated and the rates of macrosomia and LGA were reduced.15–17 Similarly, a recent study demonstrated that knowledge of an ultrasonographic estimated fetal weight increases the risk of cesarean delivery, even above the effect of the fetal size itself.18 Because the incidence of LGA did not increase across epochs, our data corroborate the finding that obstetric care provider concern of potential adverse delivery outcomes related to fetal weight may influence decision-making beyond that supported by the clinical data.
Our study has several strengths. First, it is a large cohort that assessed the association of two different diagnostic strategies for GDM with perinatal outcomes. Our sample size allowed us to evaluate more uncommon outcomes such as shoulder dystocia. Another strength is that the management of pregnancies complicated by the diagnosis of GDM did not change at our institution over time and therefore should not account for differences between the two epochs.
Our study is not without limitations. First, we cannot rule out the presence of additional unmeasured confounders that may have contributed to the differences in the outcomes. One of these may be related to a joint publication by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine workshop released toward the end of the IADPSG epoch regarding strategies to prevent the first cesarean delivery,19,20 which may have affected practice during the later Carpenter-Coustan epoch. In addition, the rate of GDM during the IADPSG epoch in our patient population seems to be lower than previously reported by the Hyperglycemia and Adverse Pregnancy Outcomes study of 17.8%,1 although the range of GDM in the participating centers in the Hyperglycemia and Adverse Pregnancy Outcomes trial was 9.3–25.5%.21
In summary, in this large retrospective cohort study, we found that use of IADPSG testing, compared with Carpenter-Coustan testing, for GDM diagnosis, was associated with higher rates of overall cesarean delivery, primary cesarean delivery, shoulder dystocia, and NICU admission. Although the absolute risk difference is low, because more than 1.1 million cesarean deliveries are performed annually in the United States,22 the public health effect of even a marginal change may still be large. These data suggest that the more frequent diagnosis of GDM does not necessarily translate into better health outcomes and that randomized trials demonstrating outcome improvement should be undertaken before new testing strategies for GDM are used.
1. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002.
2. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477–86.
3. Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009;361:1339–48.
4. Gestational diabetes mellitus. Practice Bulletin No. 137. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;122:406–16.
5. Vandorsten JP, Dodson WC, Espeland MA, Grobman WA, Guise JM, Mercer BM, et al. NIH consensus development conference: diagnosing gestational diabetes mellitus. NIH Consens State Sci Statements 2013;29:1–31.
6. Hung TH, Hsieh TT. The effects of implementing the International Association of Diabetes and Pregnancy Study Groups criteria for diagnosing gestational diabetes on maternal and neonatal outcomes. PLoS One 2015;10:e0122261.
7. Feldman RK, Tieu RS, Yasumura L. Gestational diabetes screening: the International Association of the Diabetes and Pregnancy Study Groups compared with Carpenter-Coustan screening. Obstet Gynecol 2016;127:10–7.
8. Duryea EL, Hawkins JS, McIntire DD, Casey BM, Leveno KJ. A revised birth weight reference for the United States. Obstet Gynecol 2014;124:16–22.
9. Shoulder dystocia. Practice Bulletin No. 178. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129:e123–33.
10. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297–316.
11. Lapolla A, Dalfrà MG, Ragazzi E, De Cata AP, Fedele D. New International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosing gestational diabetes compared with former criteria: a retrospective study on pregnancy outcome. Diabet Med 2011;28:1074–7.
12. Bodmer-Roy S, Morin L, Cousineau J, Rey E. Pregnancy outcomes in women with and without gestational diabetes mellitus according to the International Association of the Diabetes and Pregnancy Study Groups criteria. Obstet Gynecol 2012;120:746–52.
13. Benhalima K, Hanssens M, Devlieger R, Verhaeghe J, Mathieu C. Analysis of pregnancy outcomes using the new IADPSG recommendation compared with the Carpenter and Coustan criteria in an area with a low prevalence of gestational diabetes. Int J Endocrinol 2013;2013:248121.
14. Ethridge JK Jr, Catalano PM, Waters TP. Perinatal outcomes associated with the diagnosis of gestational diabetes made by the international association of the diabetes and pregnancy study groups criteria. Obstet Gynecol 2014;124:571–8.
15. Goldman M, Kitzmiller JL, Abrams B, Cowan RM, Laros RK Jr. Obstetric complications with GDM. Effects of maternal weight. Diabetes 1991;40(suppl 2):79–82.
16. Naylor CD, Sermer M, Chen E, Sykora K. Cesarean delivery in relation to birth weight and gestational glucose tolerance: pathophysiology or practice style? Toronto Trihospital Gestational Diabetes Investigators. JAMA 1996;275:1165–70.
17. Langer O, Yogev Y, Most O, Xenakis EM. Gestational diabetes: the consequences of not treating. Am J Obstet Gynecol 2005;192:989–97.
18. Little SE, Edlow AG, Thomas AM, Smith NA. Estimated fetal weight by ultrasound: a modifiable risk factor for cesarean delivery? Am J Obstet Gynecol 2012;207:309.e1–6.
19. Spong CY, Berghella V, Wenstrom KD, Mercer BM, Saade GR. Preventing the first cesarean delivery: summary of a joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, and American College of Obstetricians and Gynecologists Workshop. Obstet Gynecol 2012;120:1181–93.
20. Safe prevention of the primary cesarean delivery. Obstetric Care Consensus No. 1. American College of Obstetricians and Gynecologists. Obstet Gynecol 2014;123:693–711.
21. Sacks DA, Hadden DR, Maresh M, Deerochanawong C, Dyer AR, Metzger BE, et al. Frequency of gestational diabetes mellitus at collaborating centers based on IADPSG consensus panel-recommended criteria: the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Diabetes Care 2012;35:526–8.
22. Martin JA, Hamilton BE, Osterman MJ, Driscoll AK, Mathews TJ. Births: final data for 2015. Natl Vital Stat Rep 2017;66:1.