VA=

Cheryl Levitt,

----- ------ --------- ---- - -I

MD, CCFP

Screening for Ge stational Diab etes, Diagnosis and Control: A Review SUMMARY

RESUME

Gestational diabetes mellitus is a relatively Le diabete gestationnel est une complication relativement courante de la grossesse. L'incidence varie de 1.6% a common complication of pregnancy. The 13 %, selon les criteres utilises pour evaluer la tolerance incidence varies from 1.6% to 13%, au glucose dans les etudes oiu on a utilise le depistage depending on the criteria used for systematique. L'epreuve d'hyperglycemie provoquee evaluating glucose tolerance in studies produit de nombreux resultats faux-positifs; les patientes ainsi identifiees sont alors soumises a d'autres epreuves where universal screening was employed. de tolerance au glucose provoquee par voie orale qui The glucose-challenge screening test deviennent penibles. Le diagnostic etiquette de produces many false-positive results; the nombreuses patientes enceintes comme etant a "haut patients thus identified are then subjected risque" et les expose a une foule d'interventions. to further unpleasant oral L'auteur passe en revue la litterature afin d'examiner la glucose-tolerance tests to make the base des pratiques systematiques de depistage. Il presente aussi les recommandations du Deuxieme coldiagnosis. The diagnosis labels many loque international sur le diabete gestationnel. L'article pregnant patients as "high risk" and discute de depistage, diagnostic et controle, risques et exposes them to a cascade of benefices et, enfin, de la litterature recente. interventions. The author examines the basis in the literature for universal screening practices. The recommendations of the Second International Workshop-Conference on Gestational Diabetes Mellitus are presented. The author discusses risks and benefits of alternative screening approaches, diagnosis, control, and reviews the current literature. (Can Fam Physician 1988; 34:1957-1962.) Key words: gestational diabetes mellitus, pregnancy, screening Dr. Levitt is an Assistant Professor in the Department of Family Medicine, Faculty of Medicine, McGill University, and Education Co-ordinator at the Herzl Family Practice Centre, Sir Mortimer B. Davis - Jewish General Hospital, Montreal. Requests for reprints to: Dr. C. Levitt, Herzl Family Practice Centre, 5750 Cote des Neiges, Montreal, Que. H3S 1Y9 CAN. FAM. PHYSICIAN Vol. 34: SEPTEMBER 1988

Gestational diabetes mellitus is defined as carbohydrate intolerance of variable severity with onset or first recognition during the present pregnancy (Diabetes 1979; 28:1039. Diabetes Care 1980; 3:499). The definition applies irrespective of whether or not insulin is used for the treatment or [whether] the condition persists after pregnancy. It does not exclude the possibility that the glucose intolerance may have antedated the pregnancy. I

PREGNANCY is a diabetogenic state characterized by an exaggerated rate and amount of insulin release, in conjunction with an apparent decrease in sensitivity to insulin action at the cellular level. 2, 3 Patients with gestational diabetes are unable to produce the compensatory hyperinsulinism required to offset these contra-insulin factors.4 In 1979, a classification of diabetes and other categories of glucose intolerance was developed by an international 1957

workshop sponsored by the National Diabetes Data Group of the National Institutes of Health.5 It was concluded that "gestational diabetes (should) be restricted to women in whom glucose intolerance develops or is discovered in pregnancy." In 1980, the American Diabetes Association Workshop-Conference on Gestational Diabetes Mellitus recommended universal screening for abnormal glucose metabolism in pregnancy.6 A variety of screening tests with different combinations of glucose load and different time intervals from the application of glucose load to the glucose determination had been proposed.8" 0 This WorkshopConference concluded that a variety of screening tests was acceptable. Despite the recommendations of the participants in these workshops, there still appeared to be some controversy in the literature7 relating to the classification of diabetes mellitus in pregnancy. Schwartz and his associates pointed out that the wide range of definitions in current use made meaningful discourse almost impossible. The Second International Workshop-Conference on Gestational Diabetes Mellitus (2nd IWCGDM) was convened in Chicago, on October 25, 1984, as an invitational meeting sponsored by the American Diabetes Association, The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Diabetic Pregnancy Study Group of the European Associates for Study of Diabetes. The meeting was called to collate existing information about gestational diabetes mellitus and to use ''state of the art" appraisals to achieve consensus on definitions, prognoses, and strategies for screening, diagnosis, and intervention. The conference achieved a consensus definition and classification of diabetes mellitus in pregnancy (Chart 1). Schwartz, who represented the American Academy of Pediatrics at the 2nd IWCGDM, and colleagues'7 also identified problems associated with the conversion of the data from blood-glucose levels to plasma-glucose levels, for both fasting plasma glucose and the glucose-tolerance test, and cited the incorrect or incompletely established extrapolation of the criteria in some refer-

mended that these diagnostic criteria be All patients with gestational diabetes used, but the concerns expressed by are at significant risk for foetal macrosomia. The condition may result Schwartz still apply. It is therefore recin significant injury to the infant due ommended that physicians acquaint themselves with the methodology and to brachial plexus injury or bony standards being used in their own hostrauma... The infant of the mother with gestational diabetes is at inpitals, in order to correlate their results with those of the literature. creased risk (up to 25 %) for several For the purpose of discussion, I shall other neonatal morbidities including hypoglycemia, hyperglycemia, present current recommendations for the detection, screening, and control of polycythemia and hyperbilirubinemia. 1, 13-17 pregnant women with gestational diabetes as presented by the 2nd IWCGDM. Studies by investigators who have I shall then discuss the recommenda- used universal screening but different tions in relation to the current litera- and variable criteria for the evaluation ture. of glucose tolerance have reported an overall incidence of gestational diabeDetection and Screening tes mellitus varying from 1.6%The 2nd IWCGDM recommended 13%.18-21 Macrosomia (a birthweight of 4000 g or more) occurred in that: and 10%16 of the infants All pregnant women should be 9%4.10 over 2500 g at birth. This figweighing screened for glucose intolerance ure was significantly increased in gessince selective screening based on tational diabetics with normal fasting clinical attributes or past obstetrical plasma levels, to 20%, and in Type-i history has been shown to be inade- diabetics to 25% 2 10 Macrosomia is quate. I associated with an increased incidence A number of studies8' 10-12 indicate of labour augmentation by oxytocin, that screening only those patients with shoulder dystocia, Caesarean secpositive risk factors would result in ap- tion, 13 14 and meconium aspiraproximately 50% of all patients with tion,'13 16 but no increase in birth asgestational diabetes mellitus being phyxiation or infant mortality has been missed. found in macrosomic infants compared with those of normal size.10' 16 The perinatal morbidity seems to be related Risks of to the birthing process itself'4 16 and is Gestational Diabetes associated with the known increase in Infant morbidity Caesarean section rates. Not only are The current literature demonstrates Caesarean sections being performed in conclusively that gestational diabetes emergencies for cephalopelvic dispromellitus is associated with a significant portion associated with macrosomia, increase in morbidity to the new- but they are also done electively, to preborn. 13-16 After reviewing the litera- vent the morbidity associated with the ture and the presentations, the 2nd birthing process. The study that comIWCGDM concluded that: pares macrosomic babies born in

Chart 1 Classification Criteria for Gestational Diabetes Mellitus Definition during pregnancy Gestational Diabetes Mellitus: carbohydrate intolerance of varying severity with onset or first recognition during the current pregnancy.

Classification after pregnancy 1. Postpartum evaluation with 75 g oral glucose-tolerance test. 2. If glucose tolerance is normal at this time, classify as "previous abnormality of glucose tolerance (gestational diabetes mellitus)". for 9 ences. The O'Sullivan values8 3. If glucose is abnormal at this time, classify as "impaired glucose tolerfasting blood-glucose levels and the ance" or "diabetes mellitus in non-pregnant adult" according to the criteglucose-tolerance test are the most fre- ria of the National Diabetes Data Group or the World Health Organization. quently referenced in the American literature. The 2nd IWCGDM recom- Source: See reference 1. 1958

CAN. FAM. PHYSICIAN Vol. 34: SEPTEMBER 1988

1978-1980 with those born in 1965-1967 shows that the increase in Caesarean section rate does not significantly reduce the risk of fetal asphyxia and trauma. 16 Boyd and colleagues suggested that a possible explanation for their findings is the technical difficulties inherent in the delivery ofan excessively large infant, even through an abdominal incision. Factors, other than gestational diabetes, found to be associated with fetal macrosomia are multiparity and maternal age over 35 yrs; pre-pregnant weight exceeding 70 kg; ponderal index (weight/height) in the upper tenth percentile; height exceeding 169 cm; weight gain during pregnancy exceeding 20 kg (44 lbs); or delivery seven days or more post term.'6

Maternal morbidity Some studies have found a correlation between women with gestational diabetes, operative delivery associated with fetal macrosomia, and subsequent overt diabetes.'3' 21-23 This correlation has recently been confirmed by Tallarigo and colleagues, who found that there was a significant correlation between toxemia and Caesarean section and the two-hour plasma-glucose level on the glucose-tolerance test.24

Controversies over Screening Criteria The glucose-challenge test (GC7) The criteria for screening for gestational diabetes mellitus is based on the O'Sullivan study that involved screening all pregnant women at their first antenatal visit by means of a single bloodglucose estimate made after an oral glucose load.8 Some of the literature refers to this test as a "glucose-challenge test" (GCT) The 2nd IWCGDM endorsed these criteria as follows: Pregnant women who have not been identified as having intolerance before the 24th week, should have a screening glucose load between the 24th and 28th week consisting of 50 g oral glucose given without regard to the time of the last meal or the time of day. Venous plasma glucose is measured one hour later. A value of >140 mg/dL (7.8 mmol/L) is recommended as a threshold to indicate the need for a full diagnostic glucose tolerance test. This latter procedure will identify the majority CAN. FAM. PHYSICIAN Vol. 34: SEPTEMBER 1988

of women with gestational diabetes mellitus. ' Debates on the sensitivity as compared to the specificity of the GCT have resulted in many researchers experimenting with different screening criteria.6 There is controversy over the value of > 140 mg/dL (7.8 mmol/L). O'Sullivan8 recommended a level of > 130 mg/dL (7.2 mmol/L), because ... higher screening blood levels will reduce the number of blood tests (OGTTs) and increase the proportionate yield but will miss many cases of gestational diabetes. Nevertheless, a level of 150 mg/dL (8.3 mmol/L) was found to be a costeffective method of screening for gestational diabetes without decreasing the sensitivity substantially below that found at a level of 130 mg/dL (7.2 mmol/L). Although the threshold of 150 mg/dL (7.2 mmol/L) fulfils these criteria, it ...does not include the costs of additional days in hospital due to maternal or neonatal morbidity secondary to undiagnosed gestational diabetes.25 The level of 150 mg/dL (8.3 mmol/L) is used extensively in the literature. The ideal level for screening after a one-hour GCT may be academic now, as Merkatz and colleagues'8 demonstrated that a two-hour GCT was more effective than a one-hour test, although he used a 75 g glucose load carried out with fasting prior to the test. A level of 120 mg/dL (6.6 mmol/L) was the upper level ofnormal. His data suggest that as many as one in four women who screen positive at two hours would be missed on a one-hour test. Similarly, a recent study compared a one-hour to a twohour GCT, both after ingestion of a 50 g glucose load.26 The two-hour screen definitely reduced significantly the number of OGTTs required, as well as the cost per case of gestational diabetes mellitus identified, compared with the one-hour screen. In this study, however, the patients fasted for three hours prior to the one-hour test and the twohour test. The cut-off for the two-hour test was > 118 mg/dL (6.6 mmol/L). The two-hour test saved 33.7% of OGTTS, and the study suggests that if institutions currently using a one-hour screen with a 150 mg/dL (8.3 mg/dL) threshold switched to a two-hour

screen, sensitivity would be increased by approximately 17 % without increasing the cost per case of gestational diabetes identified. Studies have also concluded that universal screening is cost effective.26'27 The feasibility and cost of a universal screening program have been shown to compare favourably with screening tests employed for other diseases during pregnancy.27 Random blood sugar sampling Random blood glucose measurement is not a sufficiently sensitive method for detecting gestational diabetes as presently defined,28 yet it had been proposed as a method of effective screening for gestational diabetes mellitus. 29, 30 The oral glucose-tolerance test (OGMT The 2nd IWCGDM endorsed the criteria for diagnosis of gestational diabetes mellitus as those based on the study done by O'Sullivan and Mahan in 1964.9 The test is performed in the morning after an overnight fast for at least 8 hours but not more than 14 hours and after at least 3 days of unrestricted diet (.150 g carbohydrate) and physical activity. A 100 g oral glucose load is given in a volume of at least 400 ml fluid. Venous plasma glucose is measured at 1, 2, and 3 hours. The subject should remain seated and not smoke throughout the test. Definitive diagnosis requires that two or more ofthe following venous plasma levels be met or exceeded: fasting, 105 mg/dL (5.8 mmol/L 1 hour, 190 mg/dL (10.6 mmol/L) 2 hours, 165 mg/dL (9.2 mmol/L) 3 hours, 145 mg/dL (8.1 mmol/L).' These levels are based on glucose de-

terminations

performed

by

an

autoanalyser. The 75 g glucose tolerance test, which is currently used in non-pregnant states, is under evaluation at present for the diagnosis of gestational diabetes mellitus.It may eventually replace the lOOg and 50g glucose after sufficient experience during pregnancy has been secured and the normal limits have been defined in comparison to more established diagnostic procedures for gestational diabetes mellitus. I The National Diabetes Data Group5 commented that certain members of 1 959

their group believed that greater attention should be paid to pregnant subjects whose plasma glucose levels at the twohour point during the OGTT were between 120 mg/dL (6.7 mmol/L) and 164 mg/dL (9.1 mmol/L). They recommended that such values define a class called "impaired gestational glucose tolerance". The results obtained by Tallarigo and colleagues24 indicate that there is significant correlation between infant weight, macrosomia, toxemia, and Caesarean section in women with a plasma level between 120 mg/dL and 164 mg/dL (6.7 mmol/L-9. 1 mmol/L) at two hours following a 100 g glucose load, given for the diagnostic OGTT. This study suggested that even the limited degrees of maternal hyperglycemia that currently stand in the normal range may affect the outcome of pregnancy. Leikin and colleagues31 have found that the women who tested positive by GCT (level 140 mg/dL or 7.8 mmol) and were found to have a negative OGTT still had a significantly higher frequency of fetal macrosomia. These studies suggest that even stricter criteria must be employed for identifying problems relating to glucose tolerance.

Optimum Time for Screening There does not appear to be consensus about the optimum time for performing the screening test. Lavin and colleagues27 showed that repeat testing of those patients with positive GCTs but negative OGTTs did not result in a higher proportion of identified cases of gestational diabetes. Merkatz and colleagues'8 demonstrated a higher incidence of positive screens at 24-28 weeks. More recently, a study that looked specifically at the optimum timing of the screening test showed highest yield at 27-31 weeks, and a retest at 33-36 weeks appeared to be cost effective if the women were 33 years of age or older, had a positive screen at 27-31 weeks gestation or were obese (> 120% ideal body weight). These specifications were adopted to avoid missing the additional one per cent of pregnant women who would go on to develop diabetes. 12

Optimum Age for Screening The incidence of abnormal glucose tolerance increases with age. '0 Granat and colleagues confirmed the definitive increase in glucose intolerance in a high-risk population over the age of 30 years.36 O'Sullivan found that in those patients under the age of 25, the perinatal mortality is virtually the same as that of the non-diabetic population.37 Other studies have found, however, that a number of cases may escape detection if this approach is adopted.'10 18,38 Mestman'° found nine per cent of women under the age of 20 years were positively diagnosed as having gestational diabetes, and in McFarland's study38 the corresponding figure was five per cent. If the purpose of screening is to identify women likely to develop gestational diabetes, it would appear prudent to screen pregnant women of all age groups.

Glycosylated hemoglobin Measurements of glycosylated hemoglobin have not been shown to be sensitive diagnostic indicators for gestational diabetes. ' The glycosylated hemoglobin (HbA1) is not a useful screening test alone or in combination with the glucose-challenge test to identify gestational diabetes.32-34 It has been demonstrated, however, that some GCT positive and OGTT negative women who have macrosomic babies have abnormally elevated glycosylated hemoglobins.35 It is therefore suggested that the glycosylated hemoglobin test be performed on all women who screen positive for gestational diabetes, and if an elevated result is obtained, maternal and fetal surveillance is recommended. Postpartum Considerations In addition, an elevation in the HbAl The 2nd IWCGDM commented that: from a previous level is a worrisome inThe evidence that gestational diabedication of poor sugar control. HbA1 tes is associated with an increased level is not a reliable predictor of risk for later overt diabetes mellitus birthweight, but may be of value as a in the mother appears to be estabpost-partum screen for unrecognized lished beyond doubt. Women in diabetes and may help to discriminate whom gestational diabetes mellitus between a constitutionally large but is diagnosed should be followed otherwise normal newborn and a large postpartum at periodic intervals by infant of a diabetic mother. 1960

appropriate techniques to detect diabetes early in its course particularly in relation to future pregnancies. They should be evaluated at the first postpartum visit by a two-hour OGTT with 75 g of glucose. Those with normal oral glucose tolerance at this time should be designated as "previous abnormality of glucose tolerance (gestational diabetes mellitus)". Those with abnormal postpartum oral glucose tolerance should be designated as "impaired glucose tolerance" in accordance with the criteria of the National Diabetes Data Group or the World Health Organization . . . Presentations at the (2nd) Workshop-Conference provided evidence that obesity and impaired carbohydrate tolerance may develop in the offspring as the long-term sequelae of neonatal macrosomia. Long-term prospective evaluations will be necessary to document those possibilities. ' A normal post-partum screen does not rule out diabetes mellitus. Indeed it is very common for the OGTT to become normal after delivery.'9 Spontaneous improvements in carbohydrate metabolism have been reported, sometimes favoured by weight-reduction programs.39 Post partum, patients should avoid using oral contraceptive agents, as deterioration in glucose tolerance has been reported in those gestational diabetics who have been prescribed estrogen-progesterone agents. '9

Control Identification of gestational diabetics and the subsequent labelling and intense monitoring of these patients is a cause of concern for physicians caring for these women: the available screening and diagnostic tests are notoriously non-specific, the labelling puts undue stress on the mother, and the monitoring may result in a cascade40 of interventions that are of questionable benefit to the mother and the infant. The 2nd IWCGDM suggested: While randomized controlled studies of all these parameters have not been published, it appears likely that early detection and subsequent strict metabolic control of pregnant women with gestational diabetes should decrease the frequency of significant neonatal risks. ' CAN. FAM. PHYSICIAN Vol. 34: SEPTEMBER 1988

Scherger4' contends that it is not yet clear that all pregnant women should be screened with 50 g glucose load, thus questioning the value and effectiveness of early intervention. Tight control of blood sugars during pregnancy does not guarantee that macrosomy will not occur. In a symposium interview ,42 Huff refers to studies in his centre which have shown that women presenting at the clinic at 36 weeks gestation who are found to have gestational diabetes have infants of significantly greater weight and higher fetal mortality than do women who are identified as diabetic prior to their 36th week of pregnancy and put on a diet. It is understandably difficult to accept labelling about 13% of pregnant women as gestational diabetics and subjecting them to intense surveillance, as this approach may precipitate obstetrical interventions (ultrasound, nonstress tests, induction of labour, Caesarean section), all of which carry their own risks and consequences. The purpose of antenatal care, however, is to assist the physician to anticipate and predict adverse consequences that may occur during pregnancy and labour, and post partuin. The inevitable cascade of interventions is always considered acceptable in high-risk situations, where the benefits outweigh the risks. Gestational diabetes puts the pregnant woman at risk for complications during pregnancy and labour, and post partum. The onus is on the physician to identify these women, using currently acceptable, cost-effective criteria. It would appear that the reason for universal screening is to flag the cases of gestational diabetes mellitus. Women definitely diagnosed by means of an oral glucose-tolerance test as gestational diabetics may follow one of two distinct risk patterns. First, those patients who remain normoglycemi in the fasting state, or who maintain a normal two-hour postprandial serum glucose have a perinatal mortality rate as low as women in the general population. However, they are at risk for perinatal morbidity, maternal morbidity, and more complicated deliveries. To date, there is no conclusive study to support the tenet that dietary intervention will reduce the incidence of fetal macrosomia, pre-eclampsia, and Caesarean section in the pure gestational diabetic with normal fasting blood sugars. Nevertheless, it seems prudent, at this time, to propose universal screening, strict CAN. FAM. PHYSICIAN Vol. 34: SEPTEMBER 1988

dietary control, and careful monitoring to identify the women at risk for fetal and maternal morbidity. Secondly, there are some patients who are found, on glucose tolerance testing, to have fasting hyperglycemia, or who develop the condition while being monitored in the first group. They are insulin dependent, Type I, diabetes mellitus cases, and as such their risk for perinatal mortality increases significantly.37 These patients require closer medical and obstetrical surveillance. In such cases the physician would intervene more aggressively with serial ultrasound, weekly non-stress tests, patient home glucose monitoring, and induction of labour at term, as it has been shown that actively insulin-treated diabetic patients have a significantly reduced infant mortality (from 11.8% to

4.5%).43

Recommendations As a result of this review I make the following recommendations: * All pregnant women should be universally screened for gestational diabetes mellitus. * The screening should take the form of a glucose-challenge test given between 27 and 31 weeks gestation. * The glucose challenge test should be performed randomly without considering the time of day or of the previous meal, two hours after ingestion of a 50 g glucose load. There is good evidence to indicate that a two-hour test level (>118 mg/dL (6.6 mmol/L)) is more effective than the currently commonly employed one-hour screen, and is costeffective. * An OGTT, 100 g load, should be used to test all those patients who test positive by the GCT. Women who have positive test results by the O'Sullivan criteria should be diagnosed gestational diabetics and carefully managed. In addition, those women who have two-hour levels .120 mg/dL (6.7 mmol/L) OGTT should be monitored for fetal macrosomia and put on a restrictive diabetic diet. * The patients who test positive on screening and have negative OGTTS should be carefully monitored for fetal macrosomia and put on dietary surveillance. * The HbA 1 test should be used as an adjunct to monitoring diagnosed gestational diabetics. It should also be used post partum when a macrosomic baby is born to a normal mother.

* Therapeutic strategies (dietary, fetal surveillance, maternal serial plasmaglucose testing, identification of complications with subsequent obstetrical management) as recommended by the 2nd IWCGDM should continue to apply: Control of plasma glucose within the normal range for pregnancy must be the goal of therapy in gestational diabetes mellitus. If dietary management does not consistently maintain the fasting plasma levels below 105 mg/dL (5.8 mmol/L) and/or the two hour postprandial plasma glucose below 120 mg/dL (6.7 mmol/L) on two or more occasions within a two-week interval, insulin therapy is initiated in many centers. I * Post-partum gestational diabetics and those normal women who have had macrosomic babies should have a 75g OGTT, at the first post-natal visit, to detect whether they have impaired glucose tolerance.

Conclusions The family physician attempting to practice "low tech", "low interventionist" obstetrics may find the recommendations of the 2nd IWCGDM and of many of the publications following it difficult to accept. Universal screening for gestational diabetes produces a large number of false-positive results. These women are then subjected to a great deal of stress and further unpleasant testing. The evidence, however, appears to be overwhelmingly in favour of universal screening, which has been found cost effective. Recent studies indicate that the previously recommended levels for the diagnosis of gestational diabetes mellitus are too high, and that women who screen positive on GCT and are found to have negative OGTTs are still at risk for fetal macrosomia. The two-hour GCT may replace the one-hour test, as it appears to be more sensitive. Careful surveillance of, and dietary intervention in, all women identified as at risk for overt diabetes, pre-eclampsia, fetal macrosomia, and consequent traumatic delivery is indicated. These women should then be observed for post-partum glucose tolerance.

Family physicians who recognize that routine screening criteria may not be sensitive enough to identify all the women at risk for gestational diabetes and its complications may choose to 1961

place all their pregnant patients on stricter dietary management. Some studies in this area are going on in the United States and Europe and may prove the effectiveness of this intervenU tion.

Acknowledgements The author wishes to thank Dr. M. Klein for his invaluable editorial advice and Mrs. A. Continelli for her help in preparing the manuscript.

References 1. Second International Workshop-Conference on Gestational Diabetes. Summary and Recommendations. Diabetes 1985: 34(Suppl 2): 123-6. 2. Spellacy WN. Maternal and foetal metabolic interrelationships. In: Sutherland HW, Stowers JM, eds. Carbohydrate metabolism in pregnancy and the newborn. Livingstone, Edinburgh: Churchill 1975;42. 3. Yen SSC. Endocrine regulation of metabolic homeostasis during pregnancy. Clin Obstet Gynecol 1973; 16:130. 4. Gabbe S, Mestman JH, Freeman RK, Anderson GV, Lowensohn RI. Management and outcome of class A diabetes mellitus. Am J Obstet Gynecol 1977; 5:465-9. 5. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979; 28: 1039-57. 6. Freinkiel N, Josimovich J. Conference Planning Committee: American Association Workshop - Conference on Gestational Diabetes: summary and recommendations. Diabetes Care 1980; 3:499-501. 7. Schwartz ML, Brenner WE. Need for adequate and consistent diagnostic classifications for diabetes mellitus diagnosed during pregnancy. Am J Obstet Gynecol 1982; 143:119-24. 8. O'Sullivan JB, Mahan CM, et al. Screening criteria for high-risk gestational diabetic patient. Am J Obstet Gynecol 1973; 116:895-900. 9. O'Sullivan JB, Mahan CM. Criteria for the oral glucose tolerance test in pregnancy. Diabetes 1964; 13:278-85. 10. Mestman JH. Outcome of diabetes screening in pregnancy and perinatal morbidity in infants of mothers with mild impairment in glucose tolerance. Diabetes Care 1980: 3:447-52. 11. Lavin JP, Barden TP, Miodovnik M. Clinical experience with a screening program for gestational diabetes. Am J Obstet Gynecol 1981; 141:491-4.

1962

12. Jovanovic L, Peterson CM. Screening for gestational diabetes: optimum timing and criteria for retesting. Diabetes 1985; 34:21-3. 13. Li DF, Wong VC, Ma HK. Foetal macrosomia: demographic analysis and perinatal performance in a Chinese population. Asia-Oceania J Obstet Gynecol 1986; 12:569-73. 14. Modanlou HD, Dorchester WL, Thorosian A, Freeman RK. Macrosomia: maternal, foetal, and neonatal implications. Obstet Gynaecol 1980; 55:420-4. 15. Widness J, Cowett RM, Coustan DR, Carpenter MW, Oh W. Neonatal morbidities in infants of mothers with glucose intolerance in pregnancy. Diabetes 1985; 34:61-5. 16. Boyd ME, Usher RH, McLean FH. Foetal macrosomia: prediction, risks, proposed management. Obstet Gynaecol 1983; 61:715-22. 17. Metzger BE, Bybee DE. Gestational diabetes mellitus: correlations between the phenotypic and genotypic characteristics of the mother and abnormal glucose tolerance during the first postpartum. Diabetes 1985; 34:111-5. 18. Merkatz IR, Method A. Pilot community-based screening program for gestational diabetes. Diabetes Care 1980; 3:453-7. 19. Mestman JH, Anderson GV, Barton P. Carbohydrate metabolism in pregnancy. Am J Obstet Gynaecol 1971; 109:41-5. 20. Gillmer MDG, Oakley NW, Beard RW, Nithyanantham R, Cawston M. Screening for diabetes during pregnancy. Br J Obstet Gynaecol 1980; 87:377-82.

21. Dandrow RV, O'Sullivan JB. Obstetrics hazards of gestational diabetes. Am J Obstet Gynecol 1966; 96:1144. 22. Mestman JH, Anderson GV, Guadalupe V. Follow-up study of 370 subjects with abnormal carbohydrate metabolism during pregnancy. Obstet Gynecol 1972; 39:421-5. 23. O'Sullivan JB. Gestational diabetes. N Engl J Med 1961; 264:1082-5. 24. Tallarigo L, Giampietro 0, Penno G, Miccoli R, Grigori G, Navalesi R. Relation of glucose tolerance to complications of pregnancy in non-diabetic women. N Engl J Med 1986; 315:989-1026. 25. Marquette GP, Klein VR, Repke JT, Niebyl JR. Cost-effective criteria for glucose screening. Obstet Gynecol 1985; 66:181-3. 26. Weiner CP, Fraser MM, Burns JM, Schnorr D, Harrig J, Whitaker LA. Costefficacy of routine screening for diabetes in pregnancy: 1-h versus 2-h specimen. Diabetes Care 1986; 9:255-9.

27. Lavin JP. Screening of high-risk and general populations for gestational diabetes: clinical application and cost analysis. Diabetes 1985; 34(Suppl 2):24-7. 28. Jowett NI, Samanta AK, Burden AC. Screening for diabetes in pregnancy: is a random blood glucose enough? Diabetic Med 1987; 4:160-3. 29. Stangenberg M, Persson B, Nordlinder E. Random capillary blood glucose and conventional selection criteria for glucose tolerance testing during pregnancy. Diabetes Research 1985; 2:29-33. 30. Lind T. Antenatal screening using random blood glucose values. Diabetes 1985; 34(Suppl 2):17-20. 31. Leiken EL, Jenkins JH, Pomerantz GA, Klein L. Abnormal glucose screening tests in pregnancy: a risk factor for foetal macrosomia. Obstet Gynaecol 1987; 69:570-3. 32. O'Shaughnessy R, Russ R, Zuspan F. Glycosylated hemoglobins and diabetes mellitus in pregnancy. Am J Obstet Gynecol 1979; 135:783-90. 33. Cousins L, Dattel BJ, Hollingsworth DR, Zettner A. Glycosylated hemoglobin as a screening test for carbohydrate intolerance in pregnancy. Am J Obstet Gynecol 1984; 150:455-60. 34. Shah BD, Cohen AW, May C, Gabbe SG. Comparison of glycohemoglobin determination and the one-hour oral glucose screen in the identification of gestational diabetes. Am J Obstet Gynecol 1982; 144:774-7. 35. Frisoli G, Naranjo L, Shebab N. Glycohemoglobins in normal and diabetic pregnancy. Am J Perinatol 1985; 2:183-8. 36. Granat M, Sharf M, Cooper A. Glucose intolerance during pregnancy. Obstet Gynaecol 1979; 53:157-61. 37. O'Sullivan JB, Charles D. Gestational diabetes and perinatal mortality rate. Am J Obstet Gynecol 1973; 116:901-4. 38. McFarland KF, Case CA. Relationship of maternal age on gestational diabetes. Diabetes Care 1985; 8:598-600. 39. O'Sullivan JB, Hurwitz D. Spontaneous remissions in early diabetes mellitus. Arch Intern Med 1966; 117:69. 40. Klein M. Canadian family practice accoucheur. Can Fam Physician 1986; 32:533-40. 41. Scherger JE, Hudson TW. Routine screening for gestational diabetes reconsidered. J Fam Pract (editorial) 1985; 21:177-8. 42. Coustan DR. (moderator) Symposium: managing gestational diabetes. Contemporary Ob/Gyn 1976; 8:119-42. 43. O'Sullivan JB, Gellis SS. Potential diabetic and her treatment in pregnancy. Obstet Gynecol 1966; 27:683-9.

CAN. FAM. PHYSICIAN Vol. 34: SEPTEMBER 1988