One-step or 2-step testing for gestational diabetes: which is better?

In the United States, the common approach to detecting gestational diabetes mellitus is the 2-step protocol recommended by the American College of Obstetricians and Gynecologists. A 50 g, 1-hour glucose challenge at 24 to 28 weeks' gestation is followed by a 100 g, 3-hour oral glucose tolerance test when a screening test threshold is exceeded. Notably, 2 or more elevated values diagnose gestational diabetes mellitus. The 2-step screening test is administered without regard to the time of the last meal, providing convenience by eliminating the requirement for fasting. However, depending upon the cutoff used and population risk factors, approximately 15% to 20% of screened women require the 100 g, 3-hour oral glucose tolerance test. The International Association of Diabetes and Pregnancy Study Groups recommends a protocol of no screening test but rather a diagnostic 75 g, 2-hour oral glucose tolerance test. One or more values above threshold diagnose gestational diabetes mellitus. The 1-step approach requires that women be fasting for the test but does not require a second visit and lasts 2 hours rather than 3. Primarily because of needing only a single elevated value, the 1-step approach identifies 18% to 20% of pregnant women as having gestational diabetes mellitus, 2 to 3 times the rate with the 2-step procedure, but lower than the current United States prediabetes rate of 24% in reproductive aged women. The resources needed for the increase in gestational diabetes mellitus are parallel to the resources needed for the increased prediabetes and diabetes in the nonpregnant population. A recent randomized controlled trial sought to assess the relative population benefits of the above 2 approaches to gestational diabetes mellitus screening and diagnosis. The investigators concluded that there was no significant difference between the 2-step screening protocol and 1-step diagnostic testing protocol in their impact on population adverse short-term pregnancy outcomes. An accompanying editorial concluded that perinatal benefits of the 1-step approach to diagnosing gestational diabetes mellitus "appear to be insufficient to justify the associated patient and healthcare costs of broadening the diagnosis." We raise several concerns about this conclusion. The investigators posited that a 20% improvement in adverse outcomes among the entire pregnancy cohort would be necessary to demonstrate an advantage to the 1-step approach and estimated the sample size based on that presumption, which we believe to be unlikely given the number of cases that would be identified. In addition, 27% of the women randomized to the 1-step protocol underwent 2-step testing; 6% of the study cohort had no testing at all. A subset of women assigned to 2-step testing did not meet the criteria for gestational diabetes mellitus but were treated as such because of elevated fasting plasma glucose levels, presumably contributing to the reduction in adverse outcomes but not to the number of gestational diabetes mellitus identified, increasing the apparent efficacy of the 2-step approach. No consideration was given to long-term benefits for mothers and offspring. All these factors may have contributed to obscuring the benefits of 1-step testing; most importantly, the study was not powered to identify what we understand to be the likely impact of 1-step testing on population health.

Prenatal Care Adherence and Neonatal Intensive Care Unit Admission or Stillbirth among Women with Gestational and Preexisting Diabetes Mellitus.

OBJECTIVE: To determine if there was an association between prenatal care adherence and neonatal intensive care unit (NICU) admission or stillbirth, and adverse perinatal outcomes in women with preexisting diabetes mellitus (DM) and gestational DM (GDM). MATERIALS AND METHODS: This is a retrospective cohort study among women with DM and GDM at a Diabetes in Pregnancy Program at an academic institution between 2006 and 2014. Adherence with prenatal care was the percentage of prenatal appointments attended divided by those scheduled. Adherence was divided into quartiles, with the first quartile defined as lower adherence and compared with the other quartiles. RESULTS: There were 443 women with DM and 499 with GDM. Neonates of women with DM and lower adherence had higher rates of NICU admission or stillbirth (55 vs. 39%; p = 0.003). A multivariable logistic regression showed that the lower adherence group had higher likelihood of NICU admission (adjusted odds ratio: 1.61 [1.03-2.5]; p = 0.035). Those with lower adherence had worse glycemic monitoring and more hospitalizations. Among those with GDM, most outcomes were similar between groups including NICU admission or stillbirth. CONCLUSION: Women with DM with lower adherence had higher rates of NICU admission and worse glycemic control. Most outcomes among women with GDM with lower adherence were similar.

Insulin Delivery Method and Admission for Glycemic Control in Pregnant Women with Type 1 Diabetes Mellitus.

OBJECTIVE: To determine if there was a difference in glycemic control admissions or perinatal outcomes in women with type 1 diabetes mellitus (DM) treated with multiple daily injections (MDIs) versus continuous subcutaneous insulin infusion (CSII). MATERIALS AND METHODS: This was a retrospective cohort study of women with type 1 DM with a singleton gestation who delivered between 2006 and 2014 at a tertiary hospital and received care at a dedicated DM clinic. Women who used MDI were compared with those who used CSII. The primary outcome was glycemic control admission during pregnancy. Secondary outcomes included adverse perinatal outcomes. RESULTS: There were a total of 156 women; 107 treated with MDI and 49 with CSII. Women treated with MDI had higher rates of glycemic control admissions versus those treated with CSII (68.2 vs. 30.6%, p < 0.001). Adjusting for age, ethnicity, public insurer, duration of DM, first recorded hemoglobin A1c (HbA1c), and DM comorbidities, the likelihood of admission remained higher in women on MDI versus CSII (AOR 5.9 [1.7-20.6]). Women treated with MDI had higher rates of postprandial hypoglycemia. Other perinatal outcomes were similar between the groups. CONCLUSION: Women with type 1 DM treated with MDI were more likely to have glycemic control admissions and postprandial hypoglycemia than those treated with CSII.

Stillbirth, Inflammatory Markers, and Obesity: Results from the Stillbirth Collaborative Research Network.

BACKGROUND: Obesity is associated with increased risk of stillbirth, although the mechanisms are unknown. Obesity is also associated with inflammation. Serum ferritin, C-reactive protein, white blood cell count, and histologic chorioamnionitis are all markers of inflammation. OBJECTIVE: This article determines if inflammatory markers are associated with stillbirth and body mass index (BMI). Additionally, we determined whether inflammatory markers help to explain the known relationship between obesity and stillbirth. STUDY DESIGN: White blood cell count was assessed at admission to labor and delivery, maternal serum for assessment of various biomarkers was collected after study enrollment, and histologic chorioamnionitis was based on placental histology. These markers were compared for stillbirths and live births overall and within categories of BMI using analysis of variance on logarithmic-transformed markers and logistic regression for dichotomous variables. The impact of inflammatory markers on the association of BMI categories with stillbirth status was assessed using crude and adjusted odds ratios (COR and AOR, respectively) from logistic regression models. The interaction of inflammatory markers and BMI categories on stillbirth status was also assessed through logistic regression. Additional logistic regression models were used to determine if the association of maternal serum ferritin with stillbirth is different for preterm versus term births. Analyses were weighted for the overall population from which this sample was derived. RESULTS: A total of 497 women with singleton stillbirths and 1,414 women with live births were studied with prepregnancy BMI (kg/m2) categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30.0 + ). Overweight (COR, 1.48; 95% confidence interval [CI]: 1.14-1.94) and obese women (COR, 1.60; 95% CI: 1.23-2.08) were more likely than normal weight women to experience stillbirth. Serum ferritin levels were higher (geometric mean: 37.4 ng/mL vs. 23.3, p < 0.0001) and C-reactive protein levels lower (geometric mean: 2.9 mg/dL vs. 3.3, p = 0.0279), among women with stillbirth compared with live birth. Elevated white blood cell count (15.0 uL × 103 or greater) was associated with stillbirth (21.2% SB vs. 10.0% live birth, p < 0.0001). Histologic chorioamnionitis was more common (33.2% vs. 15.7%, p < 0.0001) among women with stillbirth compared with those with live birth. Serum ferritin, C-reactive protein, and chorioamnionitis had little impact on the ORs associating stillbirth with overweight or obesity. Adjustment for elevated white blood cell count did not meaningfully change the OR for stillbirth in overweight versus normal weight women. However, the stillbirth OR for obese versus normal BMI changed by more than 10% when adjusting for histologic chorioamnionitis (AOR, 1.38; 95% CI: 1.02-1.88), indicating confounding. BMI by inflammatory marker interaction terms were not significant. The association of serum ferritin levels with stillbirth was stronger among preterm births (p = 0.0066). CONCLUSION: Maternal serum ferritin levels, elevated white blood cell count, and histologic chorioamnionitis were positively and C-reactive protein levels negatively associated with stillbirth. Elevated BMIs, both overweight and obese, were associated with stillbirth when compared with women with normal BMI. None of the inflammatory markers fully accounted for the relationship between obesity and stillbirth. The association of maternal serum ferritin with stillbirth was stronger in preterm than term stillbirths.

The association of stillbirth with depressive symptoms 6-36 months post-delivery.

BACKGROUND: Stillbirths (≥ 20 weeks' gestation), which account for about 1 in 200 US pregnancies, may grieve parents deeply. Unresolved grief may lead to persistent depression. METHODS: We compared depressive symptoms in 2009 (6-36 months after index delivery) among consenting women in the Stillbirth Collaborative Research Network's population-based case-control study conducted 2006-08 (n = 275 who delivered a stillbirth and n = 522 who delivered a healthy livebirth (excluding livebirths < 37 weeks, infants who had been admitted to a neonatal intensive care unit or who died). Women scoring > 12 on the Edinburgh Depression Scale were classified as currently depressed. Crude (cOR) and adjusted (aOR) odds ratios and 95% confidence intervals [CI] were computed from univariate and multivariable logistic models, with weighting for study design and differential consent. Marginal structural models examined potential selection bias due to low follow-up. RESULTS: Current depression was more likely in women with stillbirth (14.8%) vs. healthy livebirth (8.3%, cOR 1.90 [95% CI 1.20, 3.02]). However, after control for history of depression and factors associated with both depression and stillbirth, the stillbirth association was no longer significant (aOR 1.35 [95% CI 0.79, 2.30]). Conversely, for the 76% of women with no history of depression, a significant association remained after adjustment for confounders (aOR 1.98 [95% CI 1.02, 3.82]). CONCLUSIONS: Improved screening for depression and referral may be needed for women's health care. Research should focus on defining optimal methods for support of women suffering stillbirth so as to lower the risk of subsequent depression.

Counterpoint: Establishing consensus in the diagnosis of GDM following the HAPO study.

The International Association of Diabetes in Pregnancy Study Groups (IADPSG) recommended a new protocol of 1-step testing with a 75 g oral glucose tolerance test for gestational diabetes in 2010. Since that time, these recommendations have been carefully scrutinized and accepted by a variety of organizations, but challenged or rejected by others. In the current review, we present more details regarding the background to the development of the IADPSG recommendations and seek to place them in context with the available epidemiologic and randomized controlled trial data. In this "counterpoint," we also provide specific rebuttal for errors of fact and disputed contentions provided by Long and Cundy in their 2013 article in Current Diabetes Reports.

Predicting the need for medical therapy in patients with mild gestational diabetes.

OBJECTIVE: The enforcement of a one-step gestational diabetes mellitus (GDM) diagnosis would capture more patients with milder forms of glucose intolerance thereby increasing the incidence. We propose to identify characteristics predicting the need for medical therapy in such patients. STUDY DESIGN: Retrospective chart review of patients with mild GDM, defined as a fasting plasma glucose (FPG) < 95 mg/dL on the 3-hour 100-g oral glucose tolerance test (OGTT). Patients requiring medical therapy for glucose control were compared with diet-controlled patients. A predictive model was constructed with variables of significance. RESULTS: Included were 143 patients requiring medical therapy and 224 diet-treated patients. Mean FPG on 3-hour OGTT, prepregnancy body mass index (BMI), and BMI at 26 to 30 weeks were all significantly higher in patients requiring therapy. Combining several variables produced a predictive model with 76% sensitivity, 52% specificity, 48% positive predictive value, and 78% negative predictive value. CONCLUSIONS: Antenatal factors (alone or in combination) do not allow for prediction of the possible need for therapy in mild GDM patients.

Prediction of abnormal postpartum glucose tolerance testing in mild gestational diabetes mellitus.

OBJECTIVE: To describe the liikelihood of women with gestational diabetes mellitus (GDM)--who are at increased risk for developing overt diabetes--undergoing postpartum testing, and the patient characteristics associated with abnormal postpartum glucose tolerance testing (GTT) in mild GDM. STUDY DESIGN: This was a retrospective chart review that included mild GDM patients, defined as those with fasting plasma glucose levels < 95 mg/dL on a 3-hour 100-g oral glucose tolerance test (OGTT). Patients who underwent postpartum testing were assessed and predictive factors for abnormal results evaluated. RESULTS: Mild GDM was diagnosed in 414 (39.6%) women, 201 (48.6%) of whom completed a postpartum 2-hour 75-g OGTT. Abnormal testing was seen in 69 (34.3%), with diabetes in 6 (3%); those with abnormal testing had been diagnosed with GDM at an earlier gestational age, had higher 1-hour 50-g OGTT values, and were also more likely to require pharmacologic therapy. Combining several variables produced a predictive model with positive and negative predictive values of 50% and 84%, respectively. CONCLUSION: Antenatal factors (alone or in combination) do not allow for prediction of abnormal postpartum OGTT results in mild GDM patients. Patients with mild GDM are at a slightly decreased postpartum risk of developing diabetes and prediabetes as compared to other patients with GDM.

Impact of an intensive follow-up program on the postpartum glucose tolerance testing rate.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a strong risk factor for the development of diabetes. We assessed the impact of a 1-year intensive follow-up demonstration program, using direct nurse and outreach worker case management, aimed at increasing compliance with postpartum oral glucose tolerance testing (OGTT). STUDY DESIGN: During the year of implementation, a nurse or bilingual outreach worker contacted patients to encourage attendance at their scheduled postpartum 2-h 75-g OGTT and assisted in overcoming obstacles to testing. All patients with GDM seen in our specialty clinic the previous year served as a control group for comparison. RESULTS: One hundred eighty-one patients treated during the year prior to implementation were compared to the 207 in the demonstration program. Baseline characteristics were similar in both groups. After the program's implementation, postpartum OGTT adherence increased from 43.1 to 59.4 % (p < 0.01, hazard ratio 1.59; 95 % confidence interval 1.20-2.12). Had the program been in place the previous year, we calculated that 12 additional cases of diabetes or prediabetes would have been detected, increasing the total number from 33 to 45 such cases. CONCLUSION: Implementation of direct nurse and outreach worker case management leads to a modest, but important increase in adherence to postpartum OGTT testing.

A population-based case-control study of stillbirth: the relationship of significant life events to the racial disparity for African Americans.

Stillbirths (fetal deaths occurring at ≥20 weeks' gestation) are approximately equal in number to infant deaths in the United States and are twice as likely among non-Hispanic black births as among non-Hispanic white births. The causes of racial disparity in stillbirth remain poorly understood. A population-based case-control study conducted by the Stillbirth Collaborative Research Network in 5 US catchment areas from March 2006 to September 2008 identified characteristics associated with racial/ethnic disparity and interpersonal and environmental stressors, including a list of 13 significant life events (SLEs). The adjusted odds ratio for stillbirth among women reporting all 4 SLE factors (financial, emotional, traumatic, and partner-related) was 2.22 (95% confidence interval: 1.43, 3.46). This association was robust after additional control for the correlated variables of family income, marital status, and health insurance type. There was no interaction between race/ethnicity and other variables. Effective ameliorative interventions could have a substantial public health impact, since there is at least a 50% increased risk of stillbirth for the approximately 21% of all women and 32% of non-Hispanic black women who experience 3 or more SLE factors during the year prior to delivery.

Gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus, defined as diabetes diagnosed during pregnancy that is not clearly overt diabetes, is becoming more common as the epidemic of obesity and type 2 diabetes continues. Newly proposed diagnostic criteria will, if adopted universally, further increase the prevalence of this condition. Much controversy surrounds the diagnosis and management of gestational diabetes. CONTENT: This review provides information regarding various approaches to the diagnosis of gestational diabetes and the recommendations of a number of professional organizations. The implications of gestational diabetes for both the mother and the offspring are described. Approaches to self-monitoring of blood glucose concentrations and treatment with diet, oral medications, and insulin injections are covered. Management of glucose metabolism during labor and the postpartum period are discussed, and an approach to determining the timing of delivery and the mode of delivery is outlined. SUMMARY: This review provides an overview of current controversies as well as current recommendations for gestational diabetes care.

Hyperglycemia and adverse pregnancy outcomes.

BACKGROUND: It is controversial whether maternal hyperglycemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes. METHODS: A total of 25,505 pregnant women at 15 centers in nine countries underwent 75-g oral glucose-tolerance testing at 24 to 32 weeks of gestation. Data remained blinded if the fasting plasma glucose level was 105 mg per deciliter (5.8 mmol per liter) or less and the 2-hour plasma glucose level was 200 mg per deciliter (11.1 mmol per liter) or less. Primary outcomes were birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide level above the 90th percentile. Secondary outcomes were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia. RESULTS: For the 23,316 participants with blinded data, we calculated adjusted odds ratios for adverse pregnancy outcomes associated with an increase in the fasting plasma glucose level of 1 SD (6.9 mg per deciliter [0.4 mmol per liter]), an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg per deciliter [1.7 mmol per liter]), and an increase in the 2-hour plasma glucose level of 1 SD (23.5 mg per deciliter [1.3 mmol per liter]). For birth weight above the 90th percentile, the odds ratios were 1.38 (95% confidence interval [CI], 1.32 to 1.44), 1.46 (1.39 to 1.53), and 1.38 (1.32 to 1.44), respectively; for cord-blood serum C-peptide level above the 90th percentile, 1.55 (95% CI, 1.47 to 1.64), 1.46 (1.38 to 1.54), and 1.37 (1.30 to 1.44); for primary cesarean delivery, 1.11 (95% CI, 1.06 to 1.15), 1.10 (1.06 to 1.15), and 1.08 (1.03 to 1.12); and for neonatal hypoglycemia, 1.08 (95% CI, 0.98 to 1.19), 1.13 (1.03 to 1.26), and 1.10 (1.00 to 1.12). There were no obvious thresholds at which risks increased. Significant associations were also observed for secondary outcomes, although these tended to be weaker. CONCLUSIONS: Our results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood serum C-peptide levels.

Gestational diabetes: evolving diagnostic criteria.

PURPOSE OF REVIEW: Gestational diabetes mellitus (GDM) is a common complication of pregnancy. There has been controversy and debate about how to optimally diagnose GDM and whether treatment modifies outcomes. We review the current controversies in both the screening and diagnosis of GDM and the benefits of treating GDM. RECENT FINDINGS: Three major studies have been published in the past 2 years that have evaluated these issues. The goal of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study was to determine the level of maternal glycemia at which adverse fetal/neonatal or maternal outcomes are impacted. Rather than a definitive cut-off, the study found that there was a continuous relationship between maternal glycemia and pregnancy outcomes. Two studies evaluated the effect of treating mild GDM on both maternal and neonatal outcomes. Each found a significant benefit with diagnosis and treatment. SUMMARY: Ideally, the results of the HAPO study will bring order to the current international confusion surrounding the diagnosis of GDM. Recently, the International Association of Diabetes and Pregnancy Study Groups recommended new screening criteria for GDM based on the HAPO study. Professional organizations around the world are currently considering these recommendations.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was performed in response to the need for internationally agreed upon diagnostic criteria for gestational diabetes, based upon their predictive value for adverse pregnancy outcome. Increases in each of the 3 values on the 75-g, 2-hour oral glucose tolerance test are associated with graded increases in the likelihood of pregnancy outcomes such as large for gestational age, cesarean section, fetal insulin levels, and neonatal fat content. Based upon an iterative process of decision making, a task force of the International Association of Diabetes and Pregnancy Study Groups recommends that the diagnosis of gestational diabetes be made when any of the following 3 75-g, 2-hour oral glucose tolerance test thresholds are met or exceeded: fasting 92 mg/dL, 1-hour 180 mg/dL, or 2 hours 153 mg/dL. Various authoritative bodies around the world are expected to deliberate the adoption of these criteria.

The use of oral antidiabetic medications in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance with onset or first recognition during pregnancy. When medical nutrition therapy is not successful in maintaining target glucose values during pregnancy complicated by GDM, medication is required. Insulin has been the traditional treatment under such circumstances. The use of oral antidiabetic medications in the management of gestational diabetes has increased over the past several years. Recent studies have shown the equivalence to insulin of both glyburide and metformin in terms of pregnancy outcomes in GDM. However, both agents have been shown to cross the placenta to the fetus, and thus they should be used with caution and patients counseled appropriately.