You are on page 1of 8

C URR ENT C ONC EP TS

Current Concepts

G ESTATIONAL D IABETES M ELLITUS
SIRI L. KJOS, M.D.,
AND

THOMAS A. BUCHANAN, M.D.

G

ESTATIONAL diabetes mellitus is defined as glucose intolerance that is first detected during pregnancy.1 This simple definition belies the complexity of a condition that spans a spectrum of glycemia, pathophysiology, and clinical effects and for which there is a wide diversity of opinion regarding detection and clinical management. There is convincing evidence that mild maternal hyperglycemia is a risk factor for fetal morbidity,2 but that morbidity occurs only in a minority of cases. Failure to recognize and treat the condition will result in unnecessary morbidity in some pregnancies, whereas overly aggressive approaches to detection and treatment will result in unneeded interventions in many others. We will review current recommendations for the detection and treatment of gestational diabetes, with an emphasis on risk stratification to minimize both undertreatment and overtreatment of individual women.
DETECTION OF GESTATIONAL DIABETES

The risks to the fetus increase in a continuous fashion with increasing maternal glycemia.2-4 Thus, there is no threshold of glycemia that discriminates clearly between low-risk and high-risk pregnancies. The diagnostic criteria for gestational diabetes could be set high to identify only very-high-risk pregnancies (and miss some at-risk pregnancies) or low to identify all at-risk pregnancies (and many no-risk pregnancies). The latter approach was adopted by the Fourth International Workshop-Conference on Gestational Diabetes Mellitus1 and is described below.
Screening

Screening procedures identify pregnant women who are at sufficient risk to warrant a diagnostic test, the oral glucose-tolerance test. Screening of all pregnant women by measurement of serum or plasma glucose between 24 and 28 weeks of gestation has been recommended widely.5,6 However, some wom-

en have clinical characteristics that indicate such a low risk of gestational diabetes that screening may not be warranted.1,7,8 Other women have high-risk characteristics that warrant screening early in pregnancy. Accordingly, screening for gestational diabetes should include an assessment of the clinical characteristics of all pregnant women to determine the risk of gestational diabetes (Table 1) and serum glucose screening in women who do not have a low-risk clinical profile (Table 2).1 The initial clinical assessment should be made at the first antepartum visit. Women with high-risk clinical characteristics should then undergo glucose screening as soon as possible. A 50-g oral glucosechallenge test9-11 is usually recommended for this purpose, followed by an oral glucose-tolerance test if the serum glucose concentration at screening is sufficiently high (Table 2).1 However, if the suspicion of overt hyperglycemia is very high (e.g., if polyuria and polydipsia are present), measurement of serum glucose during fasting may be sufficient to confirm the diagnosis of diabetes (Table 3). Women who are found to be at average or low clinical risk (Table 1) at the initial clinical evaluation should be reassessed between 24 and 28 weeks of gestation, along with women at high risk who have not already received a diagnosis of gestational diabetes by that time. At 24 to 28 weeks, women with low-risk clinical characteristics (Table 1) do not need further testing.1 The risk in these women is low,7,8,10 although the effect of not performing glucose screening has not been evaluated thoroughly. Women with any clinical characteristic placing them at risk (average or high risk in Table 1) should undergo glucose testing. In most populations, a two-step testing procedure will limit the number of full glucose-tolerance tests that are performed; step 1 is the 50-g, one-hour glucosechallenge test (Table 2), and step 2 an oral glucosetolerance test performed in women whose one-hour glucose-challenge test indicates an increased risk of gestational diabetes. The frequency of positive screening tests and their specificity for the detection of gestational diabetes vary according to the cutoff point selected for the serum glucose concentration at one hour (Table 2). In some groups (e.g., some Native American peoples), the rates of diabetes and gestational diabetes are so high that proceeding directly to the full oral glucose-tolerance test may be appropriate.1
Diagnosis

From the Department of Obstetrics and Gynecology (S.L.K., T.A.B.) and the Department of Medicine (T.A.B.), University of Southern California School of Medicine, Los Angeles. Address reprint requests to Dr. Kjos at 1240 N. Mission Rd., Rm. L1017, Los Angeles, CA 90033, or at skjos@hsc.usc.edu. ©1999, Massachusetts Medical Society.

The diagnosis of gestational diabetes is based on the results of an oral glucose-tolerance test, except in women with severe hyperglycemia (Table 3), who should be considered to have type 1 or type 2 diabetes and treated accordingly. There is no agreement about the conduct or interpretation of the oral glucose-tolerance test in pregnant women. The apVol ume 341 Numb e r 23 ·

1749

The New England Journal of Medicine Downloaded from nejm.org on March 17, 2011. For personal use only. No other uses without permission. Copyright © 1999 Massachusetts Medical Society. All rights reserved.

2 mmol/liter) 14–18 20–25 ~80 ~90 *Recommendations are adapted from Metzger et al. ‡Values are measured at any time except during the oral glucose-challenge test or oral glucose-tolerance test. At present there are no data on perinatal or maternal outcomes to support the use of those criteria. three-hour test. multiply by 0. repeat at 24–28 History of glucose intolerance weeks if no diagnosis Previous infant with macrosomia of gestational diabetes Current glycosuria mellitus by that time Average risk Between 24 and 28 weeks of The patient fits neither the low. 2011. black. one-hour and two-hour values from the 100-g. DIAGNOSIS TIME OF MEASUREMENT OF DIABETES DURING PREGNANCY. most of these women and their infants are not at risk for glucose-related morbidity (Fig.1 Use of those criteria increased the percentage of pregnant women classified as having gestational diabetes from 4 percent (according to the criteria of the National Diabetes Data Group5) to 7 percent in a group that consisted predominantly of white women. risk of fetal macrosomia and cesarean delivery in the absence of specific treatment. SERUM OR PLASMA GLUCOSE SCREENING GESTATIONAL DIABETES MELLITUS WITH THE 50-g ORAL GLUCOSE-CHALLENGE TEST. 100-g test with use of criteria developed to quantify the risk of subsequent diabetes in the mother. The serum glucose cutoff points for the 75-g.17 The Fourth International WorkshopConference on Gestational Diabetes Mellitus1 (Table 3). CLINICAL SCREENING FOR GESTATIONAL DIABETES MELLITUS.16 The incidence rates may be different in other races and ethnic groups. the World Health Organization. ‡The percentage may vary according to race or ethnic group and the glucose-tolerance-test criteria used for diagnosis.1 †Assessment is performed at the initial antepartum visit and repeated at 24 to 28 weeks of gestation in patients in whom gestational diabetes has not been diagnosed.16 However. For personal use only. or Indigenous Australian. three-hour oral glucose-tolerance test. diagnostic testing may be performed without prior glucose screening.1 †Venous serum or plasma glucose concentration is measured by methods with high precision and appropriate quality control. The data are most convincing for an association with preeclampsia20.8 mmol/liter) »130 mg/dl (7. No other uses without permission.1 Two or more of the values must be met or exceeded for a diagnosis of gestational diabetes to be made with the use of either test. incorporating lower glucose concentrations. 1).* RECOMMENDATION FOR SERUM OR PLASMA GLUCOSE SCREENING TABLE 3. two-hour glucose-tolerance tests in pregnant women.14 identify additional pregnant women with an increased 1750 · Dec em b er 2 . ANTEPARTUM IMPLICATIONS AND TREATMENT proach recommended in 1979 by the National Diabetes Data Group5 was based on a three-hour. South or East Asian. Pacific Islander. without regard to the time of the last meal. †Values shown are for a 100-g. TABLE 2.05551.13. ‡Low-risk races and ethnic groups are those other than Hispanic.* GLUCOSE CONCENTRATION DIABETES MELLITUS TYPE GESTATIONAL DIABETES MELLITUS† RISK CATEGORY AND CLINICAL CHARACTERISTICS† 1 OR 2 High risk (one or more of the following) At initial antepartum visit or Marked obesity as soon as possible thereDiabetes in first-degree relative after.16 The more inclusive criteria (Table 3) were adopted by the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. Native American. §Abnormal values should be present on at least two occasions.1 with venous serum or plasma glucose concentrations measured by methods with high precision and appropriate quality control. two-hour oral glucose-tolerance test are identical to the fasting.21 and more controversial for an association with pregnancy-induced The New England Journal of Medicine Downloaded from nejm. All rights reserved.12 Other criteria.18 and the European Diabetic Pregnancy Study Group19 have proposed different criteria for interpreting the results of 75-g. .15. 19 9 9 Implications Antepartum morbidity in women with gestational diabetes is limited to an increased frequency of hypertensive disorders. In women with very-high-risk clinical characteristics. Copyright © 1999 Massachusetts Medical Society.The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne TABLE 1. which can be performed at any time of day.* PROPORTION OF WOMEN WITH POSITIVE TEST‡ FOR SERUM GLUCOSE CUTOFF POINT† SENSITIVITY GESTATIONAL DIABETES MELLITUS‡ FOR percent »140 mg/dl (7. To convert values for glucose to millimoles per liter. milligrams per deciliter Random‡§ After overnight fast§ One hour after test Two hours after test Three hours after test »200 »126 — — — — 95 180 155 140 *Diagnoses are based on recommendations of the Fourth International Workshop-Conference on Gestational Diabetes.nor the gestation high-risk profile Low risk (all of the following) Not required Age <25 yr Belongs to low-risk race or ethnic group‡ No diabetes in first-degree relatives Normal prepregnancy weight and weight gain during pregnancy No history of abnormal blood glucose concentrations No prior poor obstetrical outcomes *Data are from Metzger et al.org on March 17.1 Serum or plasma glucose is measured one hour after the glucose challenge.

All rights reserved. there appears to be a weak positive correlation between the degree of maternal glycemia and birth weight3.7 mmol per liter]25). The group with the highest glucose concentrations (Positive by GDM and NDDG). hypertension. women with hypertension. polycythemia. and hypocalcemia have been reported with varying frequency in the infants of women with gestational diabetes. 50-g glucose screening test and a three-hour. who were treated to reduce their glucose concentrations.16. Accordingly. with care providers unaware of the women’s serum glucose concentrations. No other uses without permission.24.22 Careful monitoring of blood pressure.24. including pregnancies in women with untreated gestational diabetes. it is prudent to offer such women special counseling and targeted ultrasound examinations to detect fetal anomalies.. particularly during the second half of gestation. initial fasting serum glucose concentrations above 120 mg per deciliter [6.32-35 and associated complications of labor and delivery15. A simplistic view of macrosomia is that it results from the delivery of excess glucose to the fetus as a consequence of maternal hyperglycemia.16.23-25 but the increase appears to be limited to infants whose mothers have severe hyperglycemia (e.32-35 Macrosomia15. Historically. Several large clinical studies demonstrated no excess perinatal mortality when these measures were instituted at term in women with gestational diabetes and otherwise uncomplicated pregnancies who were treated by diet or at 32 to 34 weeks of gestation in women treated with insulin. maternal glycemia accounts for only a small fraction of the variance in the birth weights of the infants of mothers with gestaVol ume 341 Numb e r 23 · 4t The New England Journal of Medicine Downloaded from nejm. “Screen Negative” indicates a one-hour serum glucose value of less than 140 mg per deciliter (7. The dominant antepartum clinical risks of gestational diabetes are to the fetus.C URR ENT C ONC EP TS Macrosomia No macrosomia Cesarean No cesarean Untreated 100 Treated 100 Untreated Treated Percentage of Pregnancies 80 60 40 20 0 Percentage of Pregnancies N Sc eg re at en iv e Po Scr si ee P tiv n h os e W iti or ve ks b ho y p GD O M Po nl si y tiv e an by d G N D D M D G 80 60 40 20 0 N Sc eg re at en iv e 4t Figure 1.34. and urinary protein excretion is recommended.5 The care providers were unaware of serum glucose concentrations for all pregnancies except those complicated by gestational diabetes as defined by the NDDG. For personal use only. Macrosomia. had the lowest proportion of infants with macrosomia but the highest rate of cesarean delivery. and the women were treated.30.34 or the frequency of macrosomia.31 Whether routine cardiotocography is beneficial or leads to unnecessary interventions in pregnant women with well-controlled diabetes is not known. Rates of Macrosomia and Cesarean Delivery in Relation to Maternal Serum Glucose Classification in the Toronto TriHospital Gestational Diabetes Project. Some studies have reported an increased frequency of major congenital anomalies. stillbirth was an important complication of diabetic pregnancies. maternal monitoring of fetal movements and fetal cardiotocography are often recommended in pregnancies complicated by gestational diabetes in order to detect fetuses at risk of intrauterine death. Po Scr si ee Po tiv n h s e W iti or ve ks b ho y p GD O M Po nl si y tiv e an by d G N D D M D G 1751 . The rates of macrosomia (birth weight >4000 g) and cesarean delivery rose with increasing degrees of maternal glycemia in the three untreated groups.35 are the most frequent and serious types of morbidity. The horizontal line in each panel is the rate of the complication in the lowest glucose category. and women who had had a previous stillborn infant.36 Indeed. 2011. jaundice.8 mmol per liter) on the 50-g test. the values for women in this category were known. respiratory distress syndrome.2-4 However.27-31 The rates of induction of labor and early delivery among women with nonreassuring or suspicious fetal heart-rate tracings were in the range of 9 to 13 percent.g.16. hypoglycemia. but not the stricter criteria of the National Diabetes Data Group (NDDG). Standard diagnostic criteria and treatment of hypertensive disorders are applicable to women with gestational diabetes.24. Copyright © 1999 Massachusetts Medical Society. but only a minority of pregnant women in each group had complications.org on March 17. “Positive by GDM 4th Workshop Only” indicates that the criteria for gestational diabetes mellitus of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus1 were met (see Table 3).2 Classifications are based on the results of a one-hour. 100-g oral glucose-tolerance test in all women.15. weight gain.26 As a result.

measurements of insulin in the amniotic fluid identify the minority of fetuses with hyperinsulinism. 19 9 9 nancies complicated by preexisting diabetes.44 and reducing the total intake for overweight women to 25 kcal per kilogram.7 mmol per liter) one and two hours. With each of these two approaches. Postprandial hyperglycemia is more closely related to fetal macrosomia than preprandial hyperglycemia in preg1752 · Decem b er 2 .3 Other maternal factors that may contribute to fetal macrosomia include obesity2.8 mmol per liter) while receiving dietary therapy. Copyright © 1999 Massachusetts Medical Society.17.46 Once nutritional therapy has been initiated.39. 2011. Dietary approaches that lower maternal serum glucose concentrations include limiting carbohydrate intake to 40 percent of total calories.45 One study found that women who obtained less than 40 percent of their total calories from carbohydrates had infants with lower birth weights and fewer cesarean deliveries than women with higher intakes. The American Diabetes Association42 recommends the provision of adequate calories and nutrients to meet the needs of pregnancy and to minimize maternal hyperglycemia. but that affects only a minority of infants overall (approximately 20 to 30 percent of infants whose mothers have gestational diabetes). No other uses without permission. One such approach uses serum fructosamine concentrations to identify women with low-risk pregnancies.33-35.3 and high serum concentrations of amino acids37. The rates of macrosomia and perinatal complications are low with both of these fetus-based approaches.4 Home blood glucose monitoring with memorycapable meters appears superior to monitoring with visually read strips in identifying women whose blood glucose concentrations remain elevated while they are receiving dietary therapy. .52 Measurements of the fetal abdominal circumference early in the third trimester are then used to identify the minority of fetuses at risk for macrosomia at term. some investigators have combined simple measures of maternal glycemia with fetal measurements to identify pregnancies at risk for perinatal morbidity.4.The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne tional diabetes.16 Antepartum Metabolic Treatment Antepartum treatment of women with gestational diabetes should be focused on the prevention of fetal complications.40 Fetal responses to maternal diabetes vary as well. excessive fetal growth in pregnancies complicated by gestational diabetes should be viewed as the result of a multifaceted maternal metabolic disturbance superimposed on varied fetal responses to that disturbance.24.50 although overly aggressive treatment without preselection for mothers with large fetuses51. after meals.49 Nonetheless. respectively. The net result is a frequency of macrosomia that is greater than in infants of nondiabetic pregnant women. and many of them require insulin therapy.2. Another approach uses measurements of fasting serum glucose obtained every one to two weeks to identify the majority of women who maintain glucose concentrations of less than 105 mg per deciliter (5.1.41 The excess rate of macrosomia associated with gestational diabetes is likely to decrease as the cutoff levels are lowered to include more pregnancies.org on March 17.53 Treatment based on maternal hyperglycemia alone has been estimated to be cost effective. Virtually all approaches have as their foundation a program of nutritional education and dietary treatment. the Fourth International WorkshopConference on Gestational Diabetes Mellitus1 recommended maintaining blood glucose concentrations at less than 95 mg per deciliter (5. Since there is not a maternal glycemic threshold for fetal risk. The most common approach and the one backed by the greatest clinical experience uses intensive monitoring to detect blood glucose concentrations that are indicative of increased fetal risk. although that practice has not been proved to be superior to preprandial monitoring alone.43 providing carbohydrates that have a low glycemic index. as evidenced by the differences in the frequency of macrosomia in the infants of women with gestational diabetes who belong to different racial and ethnic groups.15-17. Women in whom there are signs of fetal morbidity (according to approaches based on the characteris- The New England Journal of Medicine Downloaded from nejm. For personal use only.47.54 even though all women being treated must monitor their blood glucose concentrations.55 Since only a minority of fetuses of women with gestational diabetes are at risk for hyperglycemiarelated morbidity (Fig.38 and lipids.41 Thus.3 mmol per liter) before meals and less than 140 and 120 mg per deciliter (7.51. Some clinicians have used more strict glycemic targets.2-4 recommendations have focused on maintaining blood glucose concentrations in the normal range for pregnancy in all women. but neither approach has been compared directly with treatment based on maternal hyperglycemia alone for efficacy or cost effectiveness.56 In the remainder. two general approaches can be used to identify women whose fetuses are at sufficiently high risk to warrant more intensive treatment: frequent measurement of maternal blood glucose concentrations and assessments of fetal development. All rights reserved.8 and 6. Daily caloric needs for women of normal weight in the second half of pregnancy are 30 to 32 kcal per kilogram of body weight. blood glucose monitoring by patients and treatment with insulin are used only in the minority of pregnancies that have some evidence of fetal hyperinsulinism (20 percent of pregnancies complicated by gestational diabetes in one study56) or macrosomia (one third of pregnancies complicated by gestational diabetes in another study51).48 That observation led to recommendations for both preprandial and postprandial blood glucose monitoring in women with gestational diabetes. 1).52 may increase the rate of delivery of small-for-gestational-age infants.

org on March 17.53.82.75 as children and young adults. To minimize such iatrogenic morbidity. usually with insulin. For personal use only.72.57-59 and perinatal morbidity. The associations have been reported not only in the offspring of women with type 1 or type 2 diabetes.90. This observation suggests that the two approaches are clinically equivalent with regard to the most serious types of perinatal morbidity. No other uses without permission. but that waiting allows more time for accelerated fetal growth.81.1 Moreover.72.63-65 Some of the increase may be due to an increase in the number of infants with macrosomia.85.50. The observation that weight gain and an additional pregnancy increase the risk of diabetes after gestational diabetes102 suggests that insulin resistance may accelerate the decline in beta-cell function that leads to diabetes.4 mmol per liter) in women whose fetuses have been identified as being at risk for macrosomia by fetal ultrasonography. treatment of women with a history of gestational diabetes should include Vol ume 341 Numb e r 23 · 1753 The New England Journal of Medicine Downloaded from nejm. the rates of cesarean delivery among women with gestational diabetes are more than double those for nondiabetic women.71.66 However.74 No interventions to prevent these longterm complications have been tested.60 The preprandial target of 105 mg per deciliter is higher than currently recommended. Nonetheless.1 Women with gestational diabetes have a 17 to 63 percent risk of nongestational diabetes within 5 to 16 years after the index pregnancy. 23 percent) than did waiting for labor to begin spontaneously by 41 completed weeks of gestation.95-101 but its cause is unknown in the majority. Other options for intensifying treatment include the dietary modifications mentioned above and aerobic exercise. and fetal growth characteristics should all be considered in designing insulin treatment.62 Route and Timing of Delivery women whose labor was induced.61. and blood glucose concentrations and appropriate diet and physical activity to minimize the likelihood that obesity will develop.83. All rights reserved.59 Optimal insulin regimens have not been determined. 2011. the route of delivery in well-treated women should be based on the same maternal and fetal considerations that apply to nondiabetic pregnant women. the target glucose concentrations.94 The beta-cell defect may be due to pancreatic autoimmunity in a small minority of women. In that regard.80-83 or soon after 80.12. Copyright © 1999 Massachusetts Medical Society. and tailoring of regimens to achieve blood glucose targets in individual patients is recommended.C URR ENT C ONC EP TS tics of the fetus) or in whom blood glucose concentrations exceed targets (according to glucose-based or fetus-based approaches) are treated more intensively.67 routine induction of labor at 38 completed weeks of gestation resulted in earlier delivery (39 vs.53. unblinded study of women with insulin-treated diabetes (93 percent of whom had gestational diabetes).84.68. excess macrosomia has been eliminated with insulin by reducing preprandial blood glucose concentrations to approximately 80 mg per deciliter (4.76-83 The risk of diabetes is particularly high in women who have marked hyperglycemia during9.80. testing of fetal lung maturation is not recommended after 38 weeks of gestation in cases in which there are reliable estimates of gestational age and good maternal glycemic control.58.51.86 Physiologic testing of women with gestational diabetes has revealed a limited capacity of pancreatic beta cells to increase insulin secretion in compensation for insulin resistance. 31 percent among women in whom labor was not induced) nor the frequency of shoulder dystocia (0 percent vs. the strength of the indication for preterm delivery should determine whether assessment of pulmonary maturity would alter the clinical management of individual cases. knowledge that the mother has gestational diabetes16 or has been treated with insulin51 can increase the chances of cesarean section.51 Thus. 3 percent) was higher. AFTER THE PREGNANCY Gestational diabetes is not in itself an indication for cesarean delivery.87-93 Poor insulin secretion during pregnancy is predictive of diabetes after delivery. neither the rate of cesarean delivery (25 percent.84 and women whose gestational diabetes was diagnosed before 24 weeks of gestation.1 Before 38 weeks.81. The timing of delivery.69 Accordingly. the timing of measurements of blood glucose. vs. 40 weeks) and a smaller proportion of infants who were large for gestational age (10 percent vs. insulin treatment to achieve postprandial blood glucose concentrations of less than 140 mg per deciliter resulted in a lower average level of glycemia and better perinatal outcomes than treatment to maintain preprandial blood glucose concentrations of less than 105 mg per deciliter in women who were not selected according to fetal characteristics.16.83 pregnancy.62 which was associated with perinatal outcomes similar to the outcomes in insulintreated women in one small study. Surfactant-deficient respiratory distress syndrome is rare in term infants of mothers with gestational diabetes.76. who have no circulating antibodies to islet-cell antigens. women who are obese. weight. but also in the offspring of women with gestational diabetes. Accordingly. should take into account fetal growth patterns as well as the risks associated with the induction of labor and premature delivery. . Among There is epidemiologic evidence that persons exposed to maternal diabetes in utero have an increased risk of obesity70-74 and abnormal glucose tolerance71. Insulin therapy decreases the frequency of fetal macrosomia50. in the absence of maternal or fetal jeopardy.74. Recommendations for the care of the children include regular evaluations of height. In one randomized.79.

40:Suppl 2:74-8. Chen E. 38. Sivan E. Naylor CD. Brustman L. Farine D. Neonatal morbidities in gestational diabetes mellitus. Roberts R. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Gare DJ. 40:Suppl 2:197-201.116:901-4. Fotheringham N. Influence of diagnostic criteria on the incidence of gestational diabetes and perinatal morbidity. Am J Obstet Gynecol 1995. Magee MS. Impact of increasing carbohydrate intolerance on maternal fetal outcomes in 3637 women without gestational diabetes: the Toronto Tri-Hospital Gestational Diabetes Project. Am J Obstet Gynecol 1973. Diabetes Care 1995. Obstet Gynecol 1989. Diabetes Care 1998.21:Suppl 2:B33B42.21:Suppl 2:B79-B84. 12. 14.72:841-6. population. Diabetes Care 1999. 19 9 9 The New England Journal of Medicine Downloaded from nejm. Torchia MG. Clin Obstet Gynecol 1991. Sermer M. Cousins L. 1754 · Dec em b er 2 . 17. All rights reserved. Biophysical profile scoring in the management of the diabetic pregnancy. Am J Obstet Gynecol 1998. Naylor CD. Metzger BE.21: Suppl 2:B113-B117. Am J Obstet Gynecol 1982. Homko CJ. Maternal age and screening for gestational diabetes: a population-based study. Jang HC.161:646-53.34:Suppl 2:50-4.103-105 The copper-medicated intrauterine device is a highly effective contraceptive that is metabolically neutral. intensively monitored gestational diabetes. Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. Knopp RH. Congenital malformations in offspring of women with hyperglycemia first detected during pregnancy. Cordero JF. Diabetic Pregnancy Study Group of the European Association for the Study of Diabetes. Erickson JD. 9. Supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-46374) and the General Clinical Research Center Branch. 29. et al. Hackett JR. Gestational diabetes mellitus: a survey of perinatal complications in the 1980s.165:493-6. 23. Gestational diabetes mellitus. Metzger BE. and by a research grant from the Juvenile Diabetes Foundation International. Am J Obstet Gynecol 1995. O’Sullivan JB. Gabbe SG. Joffe GM. Glycemic control in gestational diabetes mellitus — how tight is tight enough: small for gestational age versus large for gestational age? Am J Obstet Gynecol 1989.173:146-56. 36. women with a history of gestational diabetes should use effective contraception to minimize the chance that they will become pregnant with untreated hyperglycemia. Herny HM.337:1591-6.org on March 17. Influence of pregnancy on the 75-g OGTT: a prospective multicenter study. Yao JFF. Am J Obstet Gynecol 1991. Farine D. Cesarean delivery in relation to birthweight and gestational glucose tolerance: pathophysiology or practice style? JAMA 1996. Coustan DR. 2nd ed. For personal use only. Obstet Gynecol 1988. Antepartum surveillance in diabetic pregnancies: predictors of fetal distress in labor. and neonatal birthweight ratio in pregnancy. American Diabetes Association. Songster G. Diabetes mellitus in pregnancy and the risk for specific birth defects: a population-based case-control study.28: 1039-57. Prediction of infant birth weight by GDM screening tests: importance of plasma triglyceride. Carr SR. Diabetes 1991. Khoury MJ. which increases the risk of birth defects in their infants. Jung KB. Berkowitz K. Riley SF. Sacks DA. Fetal surveillance in the pregnancy complicated by diabetes mellitus. Reece EA. 37. Walstab JE. Anyaegbunam A. Friedman S.18:1550-6. Mahan CM. Dandrow RV. The relationship between large-for-gestationalage infants and glycemic control in women with gestational diabetes. 1977:191-7. Gestational diabetes and perinatal mortality rate. Manning FA. JAMA 1993. Screening for gestational diabetes with the one-hour 50-g glucose test. Diabetes 1991. Forsythe AB.85:1-9. Merlob P. Charles D. Diabetes mellitus: report of a WHO study group. Chen E. 5. Pedersen J. O’Sullivan JB. 40. by a Clinical Investigator Award from the American Diabetes Association.73:557-61. 3. Bar J. 34. Persson B. Landon MB. Diabetes 1964. 32. 33. Sheedy MT. Blood glucose concentrations should be reassessed after delivery and at least every three years thereafter in keeping with the recommendation of the American Diabetes Association for the detection of diabetes in high-risk subjects. J Perinatol 1992. Levine RJ. 16. Mahan CM. Bonet B. Sermer M.21:Suppl 2:B27-B32. Walden CE. WHO Tech Rep Ser 1985. the use of a contraceptive containing only progestin during breastfeeding increased the rate of diabetes by a factor of nearly three.70:89-93. 28. 19.106 In contrast.269:609-15. Xiang A. Lange IR. Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus. Nelson C. 11. Kalkhoff RK. glucose tolerance. 10. Gestational diabetes mellitus: influence of race on disease prevalence and perinatal outcome in a U. Victor MR. Am J Obstet Gynecol 1988. Diabetes 1991. Benedetti TJ. Schoenfeld A. Abu-Fadil S. Divon M. 27. 41. 20:1582-8. Maternal serum triglyceride. Merkatz R. 2. Min Y-K. Diabetes Care 1998. Benedetti TJ. The relationship between abnormal glucose tolerance and hypertensive disorders of pregnancy in healthy nulliparous women. Coustan DR.40: Suppl 2:99-105.40:Suppl 2:8-13. Diabetes Care 1997. Becerra JE. Langer O. 24. Leung A. Metzger BE. Idem.40:Suppl 2:25-9. Increased macrosomia and perinatal morbidity independent of maternal obesity and advanced age in Korean women with GDM. Langer O. Diabetes Care 1995. Baltimore: Williams & Wilkins. Widness JA. Buchanan TA. Johnson JM. Diabetes 1991. N Engl J Med 1997. Organizing Committee.104 an effect that was not explained by breast-feeding itself. Cho NH. Diabetes Care 1998. 39.22:Suppl 1:S74-S76.172:607-14. Am J Obstet Gynecol 1995.40:Suppl 2:61-6. Greenspoon JS. et al. The Toronto Tri-Hospital Gestational Project: a preliminary review. Diabetes 1985. Cho NH. Chez R. 13.103 More frequent testing is warranted in women who have impaired fasting or postchallenge blood glucose concentrations.34:535-43. Sacks DA. 30. Diabetes 1991. Hod M. Obstet Gynecol 1987. Biphasic effects of maternal metabolism on fetal growth: quintessential expression of fuel-mediated teratogenesis.159:1478-83. REFERENCES 1. National Diabetes Data Group. Diabetes Care 1992.116: 895-900. Beischer NA. Hanson U. Henry OA. maintenance of normal weight. Greenspoon JS. Metzger BE. Am J Obstet Gynecol 1997. et al. Copyright © 1999 Massachusetts Medical Society. 20. Sermer M. The pregnant diabetic and her newborn: problems and management. Antepartum fetal surveillance in gestational diabetes mellitus. 15. 42. Criteria for screening tests for gestational diabetes. Charles D. No other uses without permission. 25. Wolde-Tsadik G. O’Sullivan JB. Abu-Fadil S. Merkatz IR. Phillips PR. Coustan DM. Nyirjesy P. 26. Esterlitz JR. Dooley SL.173:1532-9. 6.21:Suppl 2:B161-B167. 31.83. 4. Han IK.13:278-85. et al. et al. and avoidance of drugs that induce insulin resistance). Baxi L. Schaefer UM. Screening recommendations for gestational diabetes mellitus. Levy J. 35. 8. Hod M. Sermer M. Divon MY. Walden CE. Rotondo L. Screening criteria for high-risk gestational diabetic patients.727:7-113. Naylor CD. Pediatrics 1990.18:1442-5. Do the current standards for glucose tolerance testing in pregnancy represent a valid conversion of O’Sullivan’s original criteria? Am J Obstet Gynecol 1989. 22.103 Finally. Toward universal criteria for gestational diabetes: the 75-gram glucose tolerance test in pregnancy. Mazze R. Carpenter MW. Ovadia J. Kjos SL. Knopp RH.174:1032-7. 2011. Abu-Fadil S.177:1165-71. Antepartum management protocol: timing and mode of delivery in gestational diabetes. Hypertension in women with gestational diabetes. Criteria for the oral glucose tolerance test in pregnancy.The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne measures to minimize insulin resistance (exercise.12:229-33. Lind T. Paul RH. Naylor CD. Diabetes Care 1998. Sacks DA. 21. Carpenter MW. Metzger BE. Magee MS. Harman CR. 161:638-41. The interrelationship between ethnicity and gestational diabetes in fetal macrosomia. Mahan CM. Diabetes Care 1998. Girz BA.S. Am J Obstet Gynecol 1973. 18. Impact of maternal fuels and nutritional state on fetal growth.275:1165-70. . Diabetes 1979.144:768-73. Sykora K. 7. Selective screening for gestational diabetes mellitus. Sudden fetal death in women with well-controlled. Dandrow RV. Karten GJ. Long-term treatment with low-dose combination oral contraceptives does not appear to increase the risk of diabetes after gestational diabetes. Diabetes 1991. Medearis AL. Peled Y. Nolan CJ. Kjos SL.15:1605-13. National Center for Research Resources (M01-RR-43).

Sivan E. Hartling SG. Hofmann HMH. Arredondo F. Rizzo T. Johnston CLW. For personal use only. Diabetes Care 1998. Drexel H. Pettitt DJ. Am J Obstet Gynecol 1993. Reed GF. Reece EA. Diabetes 1985. Silverman BL. Buchanan TA.111:792800. Gavin LA. Knopp RH. Ward WK. Pregnancy in the diabetic patient: timing and mode of delivery. Trigo E.168:1139-45. The effects of carbohydrate restriction in patients with diet-controlled gestational diabetes. Prevalence and etiology of respiratory distress in infants of diabetic mothers: predictive value of fetal lung maturation tests. Berlin.40:Suppl 2:121-5. All rights reserved. Is self-monitoring of blood glucose necessary in the management of gestational diabetes mellitus? Diabetes Care 1998. Bichler A. Kjos SL. Obstet Gynecol 1972. Henry OA. Metzger BE. Bevier W. Coustan DR. Amini SB. Effect of dietary carbohydrate on the glucose and insulin response to mixed caloric intake and exercise in both nonpregnant and pregnant women. Yen SS. Utility of fetal measurements in the management of gestational diabetes. Placek PJ. lunch.C URR ENT C ONC EP TS 43. Incidence and risk factors associated with abnormal postpartum glucose tolerance in women with gestational diabetes. Kjos S. Buchanan TA. Benedetti T. 78. Raisys V. 44. Gestational diabetes: predictors of subsequent disordered glucose metabolism. 46. Plasma glucagon and the insulin:glucagon ratio in gestational diabetes. Diabetes 1991. Therapeutic results of insulin therapy in gestational diabetes mellitus. Benedetti TJ. Mestman JH. Steel JM. Baird HR. Buchanan TA. Mestman JH. Maternal glycemic criteria for insulin therapy in gestational diabetes mellitus. Insulin resistance and impaired insulin secretion in subjects with histories of gestational diabetes mellitus. de Veciana M. 84. 2011. 163:898-903. Peterson CM. Lee WP. Assessment of costs and benefits of management of gestational diabetes mellitus. Insulin sensitivity and B-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes. Kjos SL. Clapp JF III. birth weight. Phelps RL. 73. Kjos SL. Gestational diabetes: factors influencing the rates of subsequent diabetes. Drury MI. Numb e r 23 · 1755 . Recent patterns in cesarean delivery in the United States. Jovanovic-Peterson L. Catalano PM. Montoro M. Diabetes Care 1998. Obstet Gynecol 1983. Binder C. 21:Suppl 2:B123-B130. Foley ME. Cho NH. Xiang A. 49. Management of diabetes mellitus and pregnancy: a survey of obstetricians and maternal-fetal specialists. Elective delivery of infants with macrosomia in diabetic women: reduced shoulder dystocia versus increased cesarean delivery.162:1174-7. 77.162:1008-14. Sims EAH. Damm P. 79. Diabetes 1991. Diabetes 1985. 91. 61. Am J Obstet Gynecol 1971. Follow-up of women with previous GDM: insulin. Diabetes Care 1988. Irvine WJ. Bennett PH. 81. 53. Exercise in gestational diabetes: an optional therapeutic approach? Diabetes 1991. Bergman RN. Kuhl C. Combs CA. Montoro M. 55. Molsted-Pedersen L. Obstet Gynecol 1998. Long-term implications of gestational diabetes for the mother. Knowler WC. and breast-feeding in Pima Indians. Catalano PM. Silverman BL. Bernstein GS. Am J Obstet Gynecol 1990. Bewsher PD. Buchanan TA. Fisher PM. operative delivery. Buchanan TA.163:93-8. Long-term effects of the intrauterine environment. Aleck KA. Diabetes Care 1998. Follow-up studies of 360 subjects with abnormal carbohydrate metabolism during pregnancy. Peterson CM. Henry MJ. Stabler M. 69. 70. Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy. Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus. Magee MS. Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes. Montoro M. et al.15:607-27. Kjos SL. Peterson CM. Am J Obstet Gynecol 1992. Baird HR. Silverman BL. Purstner P. Predicting future diabetes in Latino women with gestational diabetes: utility of early postpartum glucose tolerance testing. Clarke BF. Henry OA. 59. 1979:425-35. The Santa Barbara County Health Care Services program: birth weight change concomitant with screening for and treatment of glucose-intolerance of pregnancy: a potential cost-effective intervention? Am J Perinatol 1997. Am J Obstet Gynecol 1990. 65. Diabetes 1976. 67.34:Suppl 2:97-100.168:783-6.21:Suppl 2:B138-B141. Maternal postprandial glucose levels and infant birth weight: the Diabetes in Early Pregnancy Study. Copyright © 1999 Massachusetts Medical Society. 47. Buchanan TA. Peters RK. 54. Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. Walther FJ. The significance of pancreatic islet cell antibody and abnormal glucose tolerance during pregnancy. Major CA. N Engl J Med 1995. et al. et al. et al. Serum fructosamine and amniotic fluid insulin levels in patients with gestational diabetes and healthy control subjects. Diabetes Care 1995. Bennett PH. 90. eds. Metzger BE. Pettitt DJ. Kjos SL.167:607-16.165:914-9. Am J Physiol 1993. Am J Obstet Gynecol 1993. et al. Diabetes Care 1992.44: 586-91. The insulin response to glucose infusion in gestational diabetes. 62. Piper JM. 80. In: Sutherland HW. Hanson U.48:848-54. Taffel SM. O’Sullivan PS. Landon MB. Kjos SL.47:1302-10. 85. 82. 87. Carr S.21:Suppl 2:B91-B98. N Engl J Med 1983. Knowler WC.18:611-7.78:922-5. Diabetes Care 1998. Am J Obstet Gynecol 1994. Intensified versus conventional management of gestational diabetes. Prepregnancy weight and antepartum insulin secretion predict glucose tolerance five years after gestational diabetes mellitus. Morgan MA. Gestational diabetes mellitus and impaired glucose tolerance during pregnancy: long-term effects on obesity and glucose tolerance in the offspring. McFarland MB. 76. 93. Carpenter MW. Relationship of fetal macrosomia to maternal postprandial glucose control during pregnancy. et al. Green OC. 58.40: Suppl 2:165-71.169:611-5. Knowler WC. Am J Obstet Gynecol 1990.40:Suppl 2:182-5. Wolfe RR. Langer O. Gestational diabetes mellitus: heterogeneity of maternal age. Is exercise safe or useful for gestational diabetic women? Diabetes 1991.40:Suppl 2:172-4. 52. insulin secretion. Diabetes Care 1993. Obstet Gynecol 1990.19:10-4.150:836-42. Diabetes 1985. Vela P.21:Suppl 2:B118-B122. Paul RH. et al. Xiang AH.308:242-5. Kalkhoff RK. Cho NH. Sailer S. Diabetes 1995.264:E60-E67. Metzger BE. De Veciana M. Diabetes 1998. Impaired glucose tolerance in adolescent offspring of diabetic mothers: relationship to fetal hyperinsulinism. Buchanan TA. Diabetes 1991. O’Sullivan JB. et al. Peterson CM. Greenspoon JS. Persson B.5:461-83.17:275-83. 56. Khodiguian N. 50. 88. 60. Metabolic effects of hypocaloric diets in management of gestational diabetes. Elixhauser A. Am J Obstet Gynecol 1998. 57.21:Suppl 2:B99-B106. Imarah J. Percentage of carbohydrate and glycemic response to breakfast. and proinsulin responses to oral glucose load. Bernstein IM.21:Suppl 2:B142B149. Prevention of perinatal morbidity by tight metabolic control in gestational diabetes mellitus. Long-term prospective evaluation of offspring of diabetic mothers. 94. Buchanan TA. Berkus MD. Kjos SL. 96. Weiss PAM. Kuhl C. Porte D Jr. Kitzmiller JL. Diaz F.11:761-8. Mestman JH. 83. Incidence and significance of is- Vol ume 341 The New England Journal of Medicine Downloaded from nejm.62: 279-82. J Clin Lab Immunol 1980.16:1598-605. Montoro MN. Roston SM. Am J Obstet Gynecol 1990. 74. Holst JJ.91:600-4. Sutherland HW. Gestational diabetes mellitus: the prevalence of glucose intolerance and diabetes mellitus in the first two months post partum. 72. Diabetes Care 1998. 71. 45. Freinkel N. Xiang A. 92. Langer O. 89. Coustan DR. Bung P. Catalano PM. No other uses without permission. 34:Suppl 2:1-7. Peters RK. and birth trauma.40:Suppl 2:179-81.164:103-11. Jovanovic-Peterson L. 86. Conway DL. Langer O. Insulinrequiring diabetes in pregnancy: a randomized trial of active induction of labor and expectant management.15:1251-7. Diabetes Care 1998.75:635-40. Sachs L. Use of fetal ultrasound to select metabolic therapy for pregnancies complicated by mild gestational diabetes. Aleck KA. et al. 51.34:Suppl 2:119-22. Carr SR. and islet cell antibodies and the impact of maternal metabolism on pancreatic B-cell and somatic development in the offspring. 95.14:221-8. Does maternal diabetes delay fetal pulmonary maturity? Am J Obstet Gynecol 1993. Tyzbir ED. Anderson GV. Prophylactic insulin treatment of gestational diabetes reduces the incidence of macrosomia. C-peptide. Radvany R.39:421-5. Jovanovic-Peterson L. Diabetes 1991. Diabetologia 1980.org on March 17. Halter JB. Stowers JM. Long-term effects of the intrauterine environment. Cho NH. Guadalupe V. Beischer NA. Am J Obstet Gynecol 1984.34:861-9.21:Suppl 2:B107-B112. Tyzbir ED. Montoro MN. Rizzo TA. Metzger BE. Obstet Gynecol Clin North Am 1988. Homko CJ.25:16-23. MacDonald DW. Jovanovic-Peterson L. Stronge JM. Rodriguez DA.40:Suppl 2:136-41. 66. Vargo KM. Artal R. Carbohydrate metabolism in pregnancy and the newborn 1978. Beard JC. Am J Obstet Gynecol 1991. Bertelsen A. weight. Freinkel N. Tsai CC. Gunderson E. 75. 63. Baillieres Clin Obstet Gynaecol 1991.333:1237-41. 48. Main EK. Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes. 64. Morgan MA. Am J Obstet Gynecol 1991. Kjos SL. Diabetes 1999.4:83-5. 68.170:1036-47. Schaefer U. and dinner in women with gestational diabetes. Diabetes 1985. Gestational diabetogenesis: quantitative analyses of glucose-insulin interrelationship between normal pregnancy and pregnancy with gestational diabetes. Metzger BE. Xenakis EM. Gabbe SG. et al. Germany: Springer-Verlag. Major CA. Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women. Henry OA. Diabetes Care 1994. Langer O. Pettitt DJ. HLA antigens. Kitzmiller JL. et al.

Islet cell antibodies and beta-cell function in gestational diabetic women: comparison to first-degree relatives of type 1 (insulin-dependent) diabetic subjects. Buchanan TA. 19 9 9 The New England Journal of Medicine Downloaded from nejm.org on March 17.The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne let cell antibodies in women with previous gestational diabetes. de Leiva A. Kjos SL. Obstet Gynecol 1994. The copper T380A intrauterine device in women with type II diabetes mellitus. Kuhl C.20:1183-97. Kjos SL. et al. Petersen JS.13:478-82.84:1006-9. 100. Ballagh SA. Copyright © 1999 Massachusetts Medical Society. Molsted-Pedersen L. Kjos LK.12:1009-14. Peters RK. Peters RK. Long-term diabetogenic effect of single pregnancy in women with previous gestational diabetes mellitus. Prevalence and predictive value of islet cell antibodies and insulin autoantibodies in women with gestational diabetes. Diabetes Care 1990. JAMA 1998. For personal use only. Schaefer U. Wein P.12:275-85.280:533-8. Xiang A. 99. Rowley MJ. contraception. Xiang A. Thomas D. La Cour M. Kuhl C. Mackay IR. Morales J. Damm P. Schaefer U. de Leiva A. 1756 · Dec em b er 2 . Sheedy MT. 2011. Corcoy R. Buschard K. Corcoy RM. Beischer NA. Am J Obstet Gynecol 1995. 104. Xiang A. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Bus- chard K. Diabetologia 1996. Morales J. Diabetes Care 1998. Hormonal choices after gestational diabetes: subsequent pregnancy.21:Suppl 2:B50-B57. Diabet Med 1994. Buchanan TA. Puig-Domingo M. GAD65 autoantibodies in women with gestational or insulin dependent diabetes mellitus diagnosed during pregnancy. Mauricio D. . 101. No other uses without permission. Balsells M. 97. Codina M. Diabetes Metab Rev 1996. Buchanan TA. Xiang A. 105.173:1563-9. 39:1329-33. 102. Prevalence of antibodies to glutamic acid decarboxylase in women who have had gestational diabetes. Balsells M. Dyrberg T. and hormone replacement. Oral contraception and the risk of type 2 diabetes in Latina women with prior gestational diabetes mellitus. All rights reserved. Peters RK. Zimmet P. Islet cell autoimmunity in women with gestational diabetes and risk of progression to insulin-dependent diabetes mellitus. 98. Diabet Med 1995. 106. Damm P. Lancet 1996. 103. Kjos SL. Mauricio D. Mishell DR Jr.347:227-30.11:558-63. Diabetes Care 1997.