Counterpoint: enough evidence to treat? The American College of Obstetricians and Gynecologists guidelines.

In the US, the most common practice for gestational diabetes mellitus (GDM) screening is a 2-step process: an initial 1-h (50 g) glucose tolerance test (GTT) done at 24 –28 weeks, followed by a confirmatory 3-h (100 g) GTT (fasting, 1-h, 2-h, and 3-h measurements) (1 ). On the assumption of a 1% rate of pre-GDM and the fact that 10% of pregnant women will be of “low risk” and thus not require screening, approximately 3.6 10 women undergo GDM screening per year in the US (2 ). A diagnosis of GDM is then made if 2 values on the 3-h GTT are above reference limits [Carpenter and Coustan criteria: fasting, 95 mg/dL ( 5.27 mmol/L); 1 h, 180 mg/dL ( 9.99 mmol/L); 2 h, 155 mg/dL ( 8.60 mmol/L); 3 h, 140 mg/dL ( 7.77 mmol/L)]. With the current American College of Obstetricians and Gynecologists (ACOG) diagnostic criteria, approximately 7% of pregnant women are diagnosed with GDM ( 250 000 women per year). Although there was a time when many experts questioned whether GDM was a “disease” that warranted treatment, data from 2 randomized clinical trials (RCTs) that demonstrated both maternal and neonatal benefit from treatment for GDM have largely quieted this argument (3, 4 ). Although the National Institute of Child Health and Human Development (NICHD) Maternal Fetal Medicine Units Network (MFMU) mild GDM treatment trial did not report differences between groups in the primary composite outcome (stillbirth or neonatal death, hypoglycemia, hyperbilirubinemia, increased cord blood C-peptide, and birth trauma) or between any of the individual outcomes in the composite, there were statistically significant differences in several secondary outcomes, such as macrosomia [number needed to treat (NNT) 12], shoulder dystocia (NNT 40), cesarean delivery (NNT 15), and preeclampsia (NNT 34). The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study demonstrated a continuous association of maternal glucose concentrations with adverse pregnancy outcomes (e.g., cesarean delivery, birth weight 90th percentile, clinical neonatal hypoglycemia, and fetal hyperinsulinemia) (5 ). The HAPO study used a 1-step 75-g GTT (fasting, 1-h, and 2-h measurements). On the basis of the HAPO results, an expert group, the International Association of Diabetes and Pregnancy Study Group (IADPSG), has suggested that GDM screening be performed with the 1-step 75-g GTT and a diagnosis of GDM be made if one or more values are above designated reference thresholds [fasting, 92 mg/dL ( 5.11 mmol/L); 1 h, 180 mg/dL ( 9.99 mmol/L); 2 h, 153 mg/dL ( 8.49 mmol/L)] (6 ). These thresholds for GDM diagnosis are much lower than current diagnostic criteria used for GDM in the US and recommended by the ACOG. If these thresholds are adopted, it is estimated that the overall prevalence of GDM will be 17.8% in the US ( 640 000 women per year). This change in the standard of practice has been proposed by the IADPSG and has been endorsed by the American Diabetes Association, but not by ACOG. There is one fundamental reason why the evidence is insufficient to change our current practice: The HAPO study was observational in design and cannot provide information regarding the effectiveness of treatment of women with “increased” glucose concentrations that are lower than current thresholds for GDM diagnosis. It is unknown whether treatment (nutritional modification and glucose monitoring) for women with this level of glycemia would (a) decrease glucose concentrations and/or (b) improve perinatal outcomes. Certainly there are some (rare) situations in which an observational study can provide information regarding treatment effectiveness (7, 8 ), but the medical literature is replete with examples of a therapy that was 1 Larry C. Gilstrap Center for Perinatal and Women’s Health Research, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Health Science Center at Houston (UTHealth), Houston, TX. * Address correspondence to the author at: UTHEALTH–University of Texas Medical School at Houston, 6431 Fannin, Suite 3.286, Houston, TX 77030. Fax 713-500-7860; e-mail [email protected]. Received April 23, 2012; accepted May 1, 2012. Previously published online at DOI: 10.1373/clinchem.2011.179085 2 Nonstandard abbreviations: GDM, gestational diabetes mellitus; GTT, glucose tolerance test; ACOG, American College of Obstetricians and Gynecologists; RCT, randomized clinical trial; NICHD, National Institute of Child Health and Human Development; MFMU, Maternal Fetal Medicine Units Network; NNT, number needed to treat; HAPO, Hyperglycemia and Adverse Pregnancy Outcome (study); IADPSG, International Association of Diabetes and Pregnancy Study Groups; ACHOIS, Australian Carbohydrate Intolerance Study in Pregnant Women. Clinical Chemistry 58:7 1098–1100 (2012) Point/Counterpoint