American Journal of Obstetrics
and Gynecology Founded in 1920
Clinical Opinion Screening recommendations for gestational diabetes mellitus Larry Cousins, MD: Laxmi Baxi, MD,b Ronald Chez, MD,c Donald Coustan, MD,d Steven Gabbe, MD,. Joseph Harris, MD,r Mark Landon, MD,. David Sacks, MD,g and Shailini Singh, MDh San Diego, Los Angeles, and Bellflower, California, New York, New York, Tampa, Florida, Providence, Rhode Island, Columbus, Ohio, and Washington, D.C. As a result of extensive experiences in multiple centers and a review of the current literature, we conclude that a plasma glucose level obtained 1 hour after a 50 gm oral glucose challenge is the "best" gestational diabetes mellitus screening test. This universal screening is performed at least once during pregnancy. The screening threshold should be no higher than 140 mg!dl, or an unacceptable loss in sensitivity occurs. Universal screening for gestational diabetes mellitus is justified by morbidity reduction, cost, and protocol simplicity and ease. (AM J OBSTET GVNECOL 1991 ;165:493-6.)
Key words: Gestational diabetes, screening Gestational diabetes mellitus is the most common metabolic complication that affects pregnant women. The frequency of gestational diabetes mellitus and its associated maternal, perinatal, and long-term morbidity emphasize the importance of an appropriate screening method. The clinician who attempts to determine how best to screen patients for gestational diabetes mellitus is confronted with conflicting information and recommendations. This article summarizes the information that forms the basis for the authors' recommendations about screening for gestational diabetes mellitus. Significance of gestational diabetes mellitus Gestational diabetes mellitus is defined as carbohydrate intolerance with onset or recognition during pregnancy.' It is important to identify a pregnant woman with gestational diabetes mellitus because ges-
From the Sharp Perinatal Center, San Diego," the Department of Obstetrics and Gynecology, Columbia Presbyterian Hospital, New York..' the Department of Obstetrics and Gynecology, University of Florida, Tampa,' the Department of Obstetrics and G.vnecology, Women and Infants Hospital, Providence," the Department of Obstetrics and Gynecology, The Ohio State University School ofMedicine, Columbus,' the Department of Obstetrics and Gynecology, King! Drew Medical Center, Los Angeles,! the Department of Obstetrics and Gynecology, Kaiser Hospital, Bellflower,K and the Division of Perinatology, Washington Hospital Center, Washington, D.C: Reprint requests: Larry Cousins, MD, Sharp Perinatal Center, Sharp MemorialHospital, 8010 Frost St., San Diego, CA 92123. 6fI !29992
tational diabetes mellitus is common and is associated with significant metabolic alterations, increased perinatal and maternal morbidity, and exaggerated longterm morbidity among the mothers and their offspring. Perinatal mortality is significantly increased in gestational diabetic pregnancies if the metabolic abnormality is not recognized or if it is recognized but not treated properly? In addition to an increased risk of intrauterine fetal death, commonly reported perinatal morbidity associated with gestational diabetes mellitus includes an increased incidence of macrosomia, birth trauma, neonatal hypoglycemia, hyperbilirubinemia, hypocalcemia, and polycythemia.' Although recent studies report enviable results regarding perinatal morbidity in cases of gestational diabetes mellitus.' 5 there is evidence that maternal and perinatal morbidity and mortality is significantly increased in women with gestational diabetes mellitus when compared with nondiabetic pregnant women."' 7 Short-term maternal morbidity includes an increased incidence of chronic hypertension, hydramnios, and cesarean section. 7 Gestational diabetes mellitus also has long-term morbidity implications for the mother and her offspring. Data from human and animal studies suggest that female fetuses exposed to chronic hyperglycemia may suffer subclinical islet cell injury.s Women with gestational diabetes mellitus have an increased likelihood of remaining carbohydrate intolerant after pregnancy,9 a significantly increased risk of type II (non-insulin-dependent) diabetes later in life, and a predisposition to
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obesity, hyperlipidemia, atherosclerotic vascular disease, and increased systolic blood pressure and mortality.'o The offspring of women with gestational diabetes mellitus have a higher incidence of childhood obesity," type II diabetes during childhood and later in life, II and intellectual and motor impairment. ' 2 Screening methods for gestational diabetes mellitus
A variety of methods have been proposed to screen for gestational diabetes mellitus. The Second International Workshop-Conference recommended screening with a 50 gm oral glucose load followed I hour later by a glucose determination in blood. I A recent survey has confirmed that the I-hour oral 50 gm glucose challenge is the preferred method of screening for gestational diabetes mellitus. 13 Ninety-six percent of maternal-fetal medicine subspecialists and 84% of fellows of the American College of Obstetricians and Gynecologists (ACOG) use this method in their practice. The 50 gm oral glucose load may be administered to patients in the fasting or fed state." A I-hour period is more efficient for screening than a 2-hour window, but it has been suggested that a 2hour blood determination may improve specificity.'5 A 2-hour postprandial plasma glucose level has been suggested for screening nonpregnant individuals for diabetes. Random blood glucose screening seems desirable because it does not inconvenience patients and might be more cost-efficient. Lind ' 6 has determined 99% cutoff values of 100 mg / dl within 2 hours of a meal compared with 101 mg / dl >2 hours after a meal. However, few women with gestational diabetes mellitus have been identified by means of 2-hour postprandial or random glucose levels, so that appropriate cutoff values have not been established ; therefore it has not been possible to determine the clinical utility of these methods. Glycosylated serum protein levels have been correlated with glycemic control in nonpregnant individuals, which led investigators to examine whether such tests might be effective in screening for gestational diabetes mellitus. Glycosylated hemoglobin measurements have been most studied, and they do not appear to be helpful in the detection of gestational diabetes mellitus. 17 When compared with glycosylated hemoglobin levels, the I-hour 50 gm glucose challenge had greater specificity, sensitivity, and predictive value for a positive diagnosis. 17 Similarly, neither glycosylated albumin nor protein I S has been of value in the diagnosis of gestational diabetes mellitus. In view of the preceding information we recommend screening for gestational diabetes with a plasma glucose level 1 hour after a 50 gm oral glucose load. Sensitivity and specificity considerations
An ideal screening test should have high sensitivity (proportion of cases with the disease under consider-
September 1991 Am J Obstet Gynecol
ation correctly identified) and high specificity (proportion of patients without the disease correctly identified). The choice of a threshold for screening is based on the degree of sensitivity desired and the amount of specificity to be sacrificed. In gestational diabetes mellitus this translates into the number of 3-hour 100 gm oral glucose tolerance tests one is willing to perform to detect a given proportion of gestational diabetes mellitus cases in the population. To accurately assess these test functions an ideal study would include both the screening test and the gold standard diagnostic test on all subjects. Only the study of O'Sullivan et al. 19 fulfills these criteria. In that study of 752 pregnant women, a venous whole-blood glucose level> 130 mg/dl that was obtained 1 hour after a 50 gm glucose challenge was 79% sensitive and 87 % specific for gestational diabetes mellitus . In a population-based study of 6214 pregnant women'o evaluated by venous plasma and the hexokinase method of glucose analysis, the diagnostic test was performed if the 50 gm I-hour screening value was > 130 mg/d1. Although it is possible that cases of gestational diabetes went undetected because of screening values 30 years (the current ACOG screening recommendation) to > 25 years, while the cost per case diagnosed increased by only I %! Thus no advantage is gained from a maternal age threshold for screening of 30 years, and the threshold could be decreased to 25 years with no increase in cost. Screening patients exclusively on the basis of age fails to consider other risk factors. For instance, an obese 25-year-old gravid patient with a family history of diabetes has a risk of gestational diabetes mellitus equivalent to that of a nonobese 34-year-old woman without a family history?2 Furthermore, gestational diabetes mellitus of a severity that poses increased risk of perinatal morbidity and mortality is likely to be found among both young and older gravid patients. 22 Ethnicity also affects the incidence of gestational diabetes. For example Navajo Indian women, Mexican women, women of Indo-Chinese descent, Chinese women with high prepregnancy ponderal indices, Saudi Arabian women, and black and Mexican teenagers have increased rates of gestational diabetes mellitus. The issues of frequency and timing of glucose testing during pregnancy are linked to the issues of reliability of the individual tests and metabolic changes that are dependent on gestational age. Existing data 22.23 suggest that glucose intolerance increases as gestation advances. Women with elevated glucose levels at screening and normal glucose tolerance test results early in pregnancy are at increased risk for the development of gestational diabetes mellitus later in pregnancy when compared with patients who have initially normal screening values?2 Sequential screening, glucose tolerance testing,"3 or both 22 increase the yield of gestational diabetes mellitus identifications. Universal screening for gestational diabetes mellitus, without regard to maternal age, is the most appropriate
Screening for gestational diabetes mellitus
protocol. This recommendation is based on two lines of reasoning. The first is that gestational diabetes mellitus should be diagnosed because of the potentially preventable morbidity and mortality associated with this problem. In addition, adding complexity to test administration and interpretation leads to patient and physician error and noncompliance!· In the population-based study previously described ,'o 22% of pregnant women were under the age of 25 and had no risk factors for gestational diabetes; thus they would not have been screened. If a protocol requires historic risk factor evaluation, a decision must be made for each patient. Each decision point increases the possibility of error and takes the physician'S time to consider the risk(s) and to explain to each patient why she does nor does not need screening. It would be more efficient and less error prone to use universal screening, in which a clerk would schedule the test automatically at 24 to 28 weeks' gestation and would ,provide each patient with a written explanation. As a result of our study information, we recommend screening all pregnant women for gestational diabetes mellitus at least once during pregnancy. Testing between 24 and 28 weeks' gestation is late enough to demonstrate glucose intolerance but early enough to allow appropriate interventions. Patients with gestational diabetes mellitus risk factors may benefit from earlier screening. Patients with initially elevated screens that are followed by normal glucose tolerance tests may benefit from repeat testing later in pregnancy. Oral glucose tolerance testing methods
If a patient's I-hour 50 gm glucose screening level shows abnormality, she should be tested with the definitive diagnostic test, a 100 gm 3-hour glucose tolerance test.!. 19 The patient is instructed to consume at least 150 mg of carbohyd rate daily for the 3 days before the oral glucose tolerance test. The patient who is to have a 3-hour oral glucose tolerance test should take nothing by mouth overnight for at least 8 to 10 hours before the test.!.·5On the morning of the test the patient may drink water but should not ingest caffeine or food or liquid containing calories. It is also best that the patient not smoke for 12 hours before the test. Ideally, the patient should rest for approximately 30 minutes before the test. During that time period she may read, listen to the radio, and /or converse, but she should not move around . A heparin lock may be placed to avoid repeated needle sticks. After the fasting sample is drawn, the patient drinks 100 gm of a glucose solution. For consistency, the timing clock is started as the patient begins to drink. The drinking should be completed within 5 minutes?' Subsequent blood samples are taken 1, 2, and 3 hours after the patient has drunk the glucose solution. During that time the patient should not move around or smoke.
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When the test has been completed, the patient may eat or drink to minimize rebound hypoglycemia. The rigorousness of the preceding methods does not apply when the patient has a I-hour 50 gm glucose screen. Then the patient need not fast, be prepared by purposeful rest or diet before the test or be purposely isolated from activity. If the patient is a smoker, it is preferable that she not smoke a cigarette within 2 hours before the test. In summary, we recommend: (1). Universal screening of prenatal patients for gestational diabetes mellitus should be done at least once during pregnancy. All prenatal patients should be screened, regardless of age, ethnicity or the presence of other risk factors for diabetes.. (2) A I-hour plasma glucose level after a 50 gm oral glucose challenge should be used for screening. (3) A screening threshold level no higher than 140 mg/dl should be used. (4) A "positive" screen should be followed up with the diagnostic 3-hour oral glucose tolerance test. We gratefully acknowledge the valuable assistance of Ms. Vickie Carreiro and Ms. Terry Esler in the preparation of this manuscipt. REFERENCES 1. Summary and recommendations of the second international workshop-conference on gestational diabetes mellitus. Diabetes 1985;34(suppl 2): 123. 2. O'Sullivan jB, Charles 0, Mahan C, et al. Gestational diabetes and perinatal mortality rate. AMj OB5TET GYNECOL 1973;116:901. 3. Oh W. Neonatal outcome and care. In: Reece EA, Coustan DR, eds. Diabetes mellitus in pregnancy. New York: Churchill Livingstone, 1988. 4. Langer 0, Anyaegbunam A, Brustman L, et al. Management of women with abnormal oral glucose tolerance test value reduces adverse outcome in pregnancy. AM j OBSTET GYNECOL 1989;161:593. 5. jacobsonj, Cousins LM. A population-based study of maternal and perinatal outcome in gestational diabetic patients. AM j OBSTET GYNECOL 1989; 161 :981. 6. Wheeler F, Gollmar C, Deeb S. Diabetes and pregnancy in South Carolina: prevalence, perinatal mortality and neonatal morbidity in 1978. Diabetes Care 1982;5:561. 7. Cousins LM. Pregnancy complications among diabetic women: review 1965-1985. Obstet Gynecol Surv 1987;42:140. 8. Freinkel N, Metzger RL, Phelps RL, et al. Gestational diabetes mellitus: a syndrome with phenotypic and genotypic heterogeneity. Horm Metab Res 1986;18:427.
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9. Stowers jM, Sutherland HM, Kerridge DF. Long-range implications for the mother: the Aberdeen experience. Diabetes 1985;34(suppl): 106. 10. O'Sullivan jB. The interaction between pregnancy, diabetes and long-term maternal outcome. In: Reece EA, Coustan DR, eds. Diabetes mellitus in pregnancy. New York: Churchill Livingstone, 1988. 11. Pettitt Dj, Bennett PH, Knowler WC, et al. Gestational diabetes mellitus and impaired glucose tolerance in the offspring. Diabetes 1985;34: 119. 12. Rizzo T, Freinkel N, Metzger B, et al. Fuel mediated behavioral teratogenesis: correlations between maternal metabolism in diabetic pregnancies and Brazelton tests in the newborn [Abstract]. Diabetes 1988;37(suppl):86A. 13. Landon MB, Gabbe SG, Sachs L. Management of diabetes mellitus and pregnancy: a survey of obstetricians and maternal-fetal specialists. Obstet Gynecol 1990;75:635. 14. Coustan DR, Wid ness jA, Carpenter MW, et al. Should the fifty-gram I-hour plasma glucose screening test for gestational diabetes be administered in the fasting or fed state? AMj OBSTET GYNECOL 1986;154:1031. 15. Weiner CP, Fraser MM, Burns jM, et al. Cost efficiency of routine screening for diabetes in pregnancy: I-hour versus 2-hour specimen. Diabetes Care 1986;9:255. 16. Lind T. Antenatal screening using random blood glucose values. Diabetes 1985;34(suppI2):17. 17. Cousins L, Dattel BJ, Hollingsworth DR, et al. Glycosylated hemoglobin as a screening test for carbohydrate intolerance in pregnancy. AM J OB5TET GYNECOL 1984;150:455. 18. Ryan E, Stark R, Crockford PM, et al. Assessment of value of glycosylated albumin and protein in detection of gestational diabetes. Diabetes Care 1987;10:213. 19. O'Sullivan jB, Mahan CM, Charles D, et al. Screening criteria for high-risk gestational diabetic patients. AM j OBSTET GYNECOL 1973; 116:895. 20. Coustan DR, Nelson C, Carpenter MW, et al. Maternal age and screening for gestational diabetes: a populationbased study. Obstet Gynecol 1989;73:557. 21. Dooley SL, Keller JD, Metzger GE, et al. Screening for gestational diabetes (GDM): is the 140 mg/dL threshold appropriate? [Abstract 52]. In: Proceedings of the ninth annual meeting of the Society of Perinatal Obstetricians, New Orleans, Louisiana, February 2-4, 1989. New Orleans: Society of Perinatal Obstetricians, 1989. 22. Sacks DA, Abu-Fadil S, Karten Gj, et al. Screening for gestational diabetes with the I-hour 50 gm glucose test. Obstet Gynecol 1987;70:89. 23. Benjamin F, Wilson Sj, Deutsch S, et al. Effect of advancing pregnancy on the glucose tolerance test and on the 50 gm glucose load screening test for gestational diabetes. Obstet Gynecol 1986;68:362. 24. Lomasj, Anderson GM, Domnick-Pierre K, et al. Do practice guidelines guide practice? N Engl j Med 1989;321:1306. 25. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979;28: 1048. Additional references are available from Dr. Cousins on request.