Education and debate

Should we screen for gestational diabetes? The case for screening for gestational diabetes

^a Department of Obstetrics and Gynaecology, Imperial College School of Medicine at St Mary's Hospital, London W2 NY1, ^b Department of Endocrinology, Imperial College School of Medicine at Hammersmith Hospital, London W12 0NN

Correspondence to: Professor Beard

	Introduction

Top Introduction Identifying future diabetics Effects on the child Demonstrating benefit Who should be screened? References

Screening for gestational diabetes is imperative but we need to refocus away from short term improvements in obstetric outcomes to more important medium and long term health benefits. Today 5% of United Kingdom¹ and 12% of United States² total healthcare expenditure is spent on diabetes and its complications. There is a global epidemic of non-insulin dependent diabetes, and radical preventive measures are required if morbidity and mortality from diabetes are to fall. We would ask whether we can afford not to screen for gestational diabetes.

	Identifying future diabetics

Top Introduction Identifying future diabetics Effects on the child Demonstrating benefit Who should be screened? References

Detecting gestational diabetes identifies women at risk of future non-insulin dependent diabetes.^{3 4} The success of treating non-insulin dependent diabetes is severely hampered by the high percentage of diabetic complications present at diagnosis,⁵ so earlier diagnosis is important in preventing complications.⁶ Half of all people with non-inuslin dependent diabetes are clinically undiagnosed, and diagnosis takes, on average, seven years from onset of the disorder.⁷

The rate of progression to non-insulin dependent diabetes mellitus after a pregnancy where the woman has had gestational diabetes depends predominantly on ethnicity and the degree of glucose intolerance both in pregnancy and immediately afterwards.⁸ Other contributing factors are weight during pregnancy and subsequent weight gain, age, parity, and family history.^{8 9} In high risk populations, such as Hispanic American women, about 40% of women with gestational diabetes develop diabetes within six years, which rises to 70% among those with impaired glucose tolerance (by World Health Organisation criteria) after birth.¹⁰ In white Europeans the rate of progression to diabetes is slower—20-40% within 20 years.¹¹ Identifying women who are at risk while they are still young provides an opportunity to identify the disease in subsequent pregnancies and to modify the natural history of non-insulin diabetes mellitus.

The onset of non-insulin dependent diabetes in women can be delayed by weight control and exercise, the benefits being greatest among obese women with a family history of diabetes.¹² Whether further benefit can be obtained with a change of lifestyle or drugs is currently being evaluated in the United States. If this study does show that intervention can delay diabetes in these women the long term benefits of screening for gestational diabetes will be further established.

	Effects on the child

Top Introduction Identifying future diabetics Effects on the child Demonstrating benefit Who should be screened? References

The consequences of gestational diabetes on the health of the child have until recently received little attention. The recent explosion of studies underlining the importance of the intrauterine environment for future adult chronic diseases¹³ has challenged the sceptics' view that in pregnancy lesser degrees of maternal glucose intolerance, not justifying treatment of the non-pregnant woman, are irrelevant.¹⁴ The concept that diabetes begets diabetes through an intrauterine effect on the fetal pancreas,¹⁵ additional to any genetic effect, is strongly supported by animal and human epidemiological studies.^{16 17}

In support of this hypothesis are studies within the Pima population, where children of a diabetic mother are at greater risk of diabetes and childhood obesity than older siblings born before their mother become diabetic.¹⁸ Maternal carbohydrate metabolism may also influence future human fetal insulin secretion and function as suggested by the studies on black and white American adolescents. Those born to diabetic mothers have greater insulin resistance and are more likely to be glucose intolerant during puberty.¹⁹ The literature supports an effect of maternal hyperglycaemia on an infant's future susceptibility to abnormalities of carbohydrate metabolism.¹⁶ However, the critical threshold of hyperglycaemia is currently not known.

Poor maternal diabetic control is associated with an increased risk of large for gestational age infants.²⁰ In certain ethnic groups up to half of all pregnancies where gestational diabetes is present have evidence of accelerated fetal growth.²¹ The apparent paradox of low birth weight associated with an increased risk of future diabetes and high birth weight with a decreased risk²² has distracted attention from the knowledge of the potential harm in later life of accelerated intrauterine fetal growth associated with gestational diabetes. In a high risk population with a 5% prevalence of gestational diabetes up to half the infants above the 90th birthweight percentile theoretically could be from a diabetic pregnancy. In such populations both high and low birth weights are associated with an increased risk of diabetes in later life.²³ By contrast, when the prevalence of gestational diabetes is low (0.5-1%) at most only 5-10% of all infants above the 90th birthweight percentile could be the result of maternal diabetes. Thus in low risk populations this argument for universal screening is not so strong.

	Demonstrating benefit

Top Introduction Identifying future diabetics Effects on the child Demonstrating benefit Who should be screened? References

The short term benefits of screening and treating gestational diabetes have focused on pregnancy outcome. In high risk populations, with a high background prevalence of diabetes combined with limited access to medical and perinatal care, perinatal mortality can be seen to improve after screening for and treatment of gestational diabetes.²⁴ Retrospective studies suggest a benefit on stillbirth rates after the introduction of screening and treating gestational diabetes in low risk populations,²⁵ but demonstrating a benefit on perinatal mortality in prospective trials has proved more difficult. In Western populations, with a low prevalence of diabetes, good access to medical care, and low perinatal mortality and morbidity rates, there are ethical constraints in mounting randomised trials with sufficient power to test whether treating gestational diabetes reduces perinatal morbidity. Prospective studies in these populations have therefore assessed pregnancy outcome using surrogate markers of diabetic control. These include macrosomia, need for caesarean section, and fetal hypoglycaemia. None of these end points are specific for diabetes and many are influenced by the practice of individual obstetricians, maternal obesity, age, and parity.

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These difficulties should not, however, detract from the fact that maternal hyperglycaemia is the cause of a diabetic fetopathy syndrome of Pedersen. With the knowledge that a baby showing evidence of this syndrome may well develop diabetes in later life, there is a good case for early detection and treatment of the mother. Evidence of increased visceral fat and enlargement of the liver, spleen, and heart may be apparent on ultrasound as early as 28 weeks' gestation. These accelerated growth patterns, associated with gestational diabetes, can be corrected with diet or insulin, which results in fewer large for gestational age infants and fewer operative deliveries.²⁶ To what extent, if any, abnormal fetal growth patterns due to hyperinsulinaemia reflect aberrant fetal cell programming and what influence this may have on the future insulin sensitivity and adult health remains speculative. To ignore such a link in the face of mounting animal evidence would, however, be short sighted.

	Who should be screened?

Top Introduction Identifying future diabetics Effects on the child Demonstrating benefit Who should be screened? References

Should all pregnant women be screened or only those at risk? The answer needs to reflect the ethnicity of the population, the availability of health care, and the economic and medicolegal expectations of the country. Once the decision has been made to screen a reproducible screening test needs to be chosen that is sensitive, specific, and easily applied.

The most universally researched screening test is the O'Sullivan test, which involves a one hour timed blood glucose sample after a 50 g oral glucose load, a value 7.8 mmol/l being positive.²⁷ This test has a 95% sensitivity and 85% specificity for detecting pregnancy induced glucose intolerance that occurs at 20-28 weeks' gestation. A first trimester test is advisable in high risk populations, in which more women will have gestational diabetes before 20 weeks. This can be done with either the 50 g oral glucose load ²⁸ or a timed plasma glucose value, which will identify women with glucose intolerance likely to require insulin treatment—namely, a fasting plasma glucose concentration >6 mmol or a 2 hour postprandial value >9 mmol/l.²⁰ Other screening tests—which include random glucose values, glucosuria, fructosamine, diurnal glucose profiles, and glucose responses to mixed meals—have been less extensively evaluated in pregnancy than the O'Sullivan test, which remains the gold standard. The sensitivity of purely clinical risk factors is poor, <70%, especially in multiethnic populations, since they do not include ethnicity.^{27 29}

The confirmational diagnostic test for gestational diabetes remains controversial. Gestational diabetes is usually diagnosed on the basis of an oral glucose tolerance test. However, the exact load administered (50, 75, or 100 g) varies between centres.³⁰ The need for one test and one set of diagnostic criteria is recognised. Epidemiologically the 75 g oral glucose tolerance test has the advantage that it is internationally used outside pregnancy. However, the diagnostic limits at which treatment is required still need to be defined.

A dogmatic stand against screening for gestational diabetes not only ignores the proved benefits of treatment on perinatal outcome but also denies affected mothers the possibility to reduce their own and their babies' risk of later diabetes.

	References

Top Introduction Identifying future diabetics Effects on the child Demonstrating benefit Who should be screened? References

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