Gestational Diabetes: Opportunities to Improve Maternal and Child Health | Lancet PDF

Personal View Gestational diabetes: opportunities for improving maternal and child health Ponnusamy Saravanan, on behalf of the Diabetes in Pregnancy Working Group* of the Maternal Medicine Clinical Study Group, Royal College of Obstetricians and Gynaecologists, UK Gestational diabetes, the most c...

Personal View Gestational diabetes: opportunities for improving maternal and child health Ponnusamy Saravanan, on behalf of the Diabetes in Pregnancy Working Group* of the Maternal Medicine Clinical Study Group, Royal College of Obstetricians and Gynaecologists, UK Gestational diabetes, the most common medical disorder in pregnancy, is defined as glucose intolerance resulting in Lancet Diabetes Endocrinol hyperglycaemia that begins or is first diagnosed in pregnancy. Gestational diabetes is associated with increased 2020; 8: 793–800 pregnancy complications and long-term metabolic risks for the woman and the offspring. However, the current *Members listed in appendix diagnostic and management strategies recommended by national and international guidelines are mainly focused on Department of Populations, Evidence, and Technologies, short-term risks during pregnancy and delivery, except the Carpenter-Coustan criteria, which were based on the risk Warwick Medical School, of future incidence of type 2 diabetes post-gestational diabetes. In this Personal View, first, we summarise the evidence University of Warwick, for long-term risk in women with gestational diabetes and their offspring. Second, we suggest that a shift is needed in Coventry, UK the thinking about gestational diabetes; moving from the perception of a short-term condition that confers increased (Prof P Saravanan PhD); and Department of Diabetes, risks of large babies to a potentially modifiable long-term condition that contributes to the growing burden of Endocrinology, and childhood obesity and cardiometabolic disorders in women and the future generation. Third, we propose how the Metabolism, George Eliot current clinical practice might be improved. Finally, we outline and justify priorities for future research. Hospital, Nuneaton, UK (Prof P Saravanan) Introduction typically diagnosed by an oral glucose tolerance test done Correspondence to: Prof P Saravanan, Department of Gestational diabetes is increasingly prevalent and between 24 weeks and 28 weeks of gestation.1–4 Studies13,14 Populations, Evidence, and estimated to affect more than 20 million livebirths (about now recognise that the onset of gestational diabetes Technologies, Warwick Medical one in six) worldwide. Of these, more than 90% of cases might occur as early as 16–20 weeks, and earlier maternal School, University of Warwick, are expected to occur in South and southeast Asia.1 hyperglycaemia (9–10 weeks)13 and fetal hyperinsulinaemia Coventry CV4 7AL, UK [email protected] Gestational diabetes has long been a controversial (14–20 weeks)14 are associated with later development of diagnosis, with variations in the screening procedures and gestational diabetes and a baby deemed large for See Online for appendix diagnostic criteria between different countries.2–4 In view of gestational age. As a result, several ongoing studies are these variations, the term hyper­glycaemia in pregnancy addressing the value of screening, diagnosing, and has sometimes been used in the definition, which includes managing gestational diabetes in early pregnancy. gestational diabetes, pre-gestational diabetes (pre-existing Screening criteria and glucose thresholds for type 1 and type 2 diabetes), and overt diabetes diagnosed diagnosing gestational diabetes vary between different in pregnancy. Manage­ ment of women with severe countries.1–4 Screening strategies currently recommended hyperglycaemia improves adverse pregnancy outcomes.5 and offered include: universal screening using a two-step Additionally, management of women with milder degrees strategy (used in USA and Canada);15,16 selective risk factor of hyperglycaemia could also reduce the rates of gestational screening (used in the UK);2 and universal screening hypertension and pre-eclampsia.6 The link between using a one-step strategy in countries with high-risk and maternal glucose concentration and neonatal outcomes low-medium risk populations.17–21 Frequently, in many attributed to fetal hyper­ insulinaemia such as large for low-resource settings (eg, sub-Saharan Africa), testing is gestational age (birthweight >90th centile), neonatal not routinely available partly because the oral glucose adiposity, and neonatal hypoglycaemia is continuous.7 tolerance test is cumbersome and labour-intensive.22 Gestational diabetes is typically perceived to be an acute Consequently, the American Diabetes Association and condition with short-term problems for the mother and the International Federation of Gynecology and Obstetrics her offspring, as glucose intolerance usually reverts back have modified their recommendations to include a single to normal after the pregnancy. However, in addition to or a two-step strategy according to the local resources.4,23 type 2 diabetes, recent studies8–10 suggest that gestational diabetes is also a risk factor for long-term maternal and Long-term implications of gestational diabetes offspring cardio­metabolic disease. In the knowledge that for the mother most cases of type 2 diabetes can be prevented or Among women with a previous history of gestational significantly delayed by lifestyle intervention and loss of diabetes, the lifetime risk of type 2 diabetes might be up to bodyweight between 10% and 15% can result in remission 20 times higher,8 and nearly 50% of these women will of type 2 diabetes,11,12 women with gestational diabetes and develop impaired glucose metabolism within 10 years of their families form a key high-risk group, for whom there having gestational diabetes.24,25 After 10–14 years of follow- is a compelling case for targeted intervention. up, the HAPO study,25 found that 52% of women with gestational diabetes (defined by the International Screening and diagnosis of gestational diabetes Association of Diabetes and Pregnancy Study Groups Although screening procedures and diagnostic criteria [IADPSG]26 and the 2013 WHO criteria)3 had developed vary between countries, gestational diabetes is most impaired glucose metabolism compared with 20% of www.thelancet.com/diabetes-endocrinology Vol 8 September 2020 793  Personal View women who had a normal glucose tolerance during testing women for glycaemic status every 1–3 years,2,4 in pregnancy (adjusted OR 3·4–3·6). In addition to the practice these women are often missed as they fall higher risk of diabetes, women with a history of gestational between primary and secondary care teams.8 None of diabetes also display a cluster of cardiovascular disease these international guidelines recommend screening for risk factors such as obesity (BMI ≥30 kg/m²), hypertension, other cardiovascular risk factors. Hence, a clear pathway and dyslipidaemia. This finding has translated into large for identifying and managing women with a previous observational cohort studies8,9,27 showing higher rates of history of gestational diabetes in the early postnatal period incident ischaemic heart disease independent from the is needed. A simple gestational diabetes recall register or onset of type 2 diabetes.9 In addition, a recent population- an appointment with a dedicated cardiovascular based study28 from Canada, has shown that women with coordinator might improve the follow-up of women with hyperglycaemia who did not meet the diagnostic gestational diabetes.31,32 Incentives for primary care teams thresholds for gestational diabetes still had a higher risk of could be another approach because many of these women cardiovascular disease, although some of those women can be managed in the community. This incentive should might have met the more stringent criteria by the IADPSG also incorporate a concerted effort to educate patients and and WHO. health-care professionals on the future risk of type 2 Taken together, these data highlight that gestational diabetes and cardiovascular disorders. NICE and inter­ diabetes and hyperglycaemia in pregnancy should be national guidelines should be updated to recognise treated as a pre-cardiovascular disease state and the gestational diabetes as a pre-cardiovascular disease. manage­ ment strategy should be to comprehensively identify and systematically treat cardiovascular risk factors Long-term implications of gestational diabetes beyond the prevention of type 2 diabetes. Although the for the offspring risk of incident type 2 diabetes is recognised and previous The combination of maternal obesity, excess gestational history of gestational diabetes is incorporated into the weight gain, and gestational diabetes contribute to the QDiabetes-2018 risk prediction algorithm,29 this development of accelerated fetal growth and accumu­ information has not been incorporated into cardiovascular lation of adipose tissue resulting in infants with higher disease risk calculators. Despite these findings, in the first birthweight that are classified as large for gestational year after a gestational diabetes pregnancy, only half of age.7,33–35 In addition, it should be recognised that excess women (58%) in the UK underwent any glucose testing adiposity in the offspring can be independent of and even less had a lipid test.8 No improve­ment was seen birthweight.36 The effects of an infant being large for in the numbers tested following the publication of updated gestational age as a result of gestational diabetes extends National Institute for Health and Care Excellence beyond the immediate concerns of birth injury and guidelines (NICE). In addition, women who missed post- neonatal hypoglycaemia to childhood obesity; the rising natal testing seem to be at a higher risk of cardiovascular rate of which is a global concern.37–39 Current estimates disease.30 Although inter­national guidelines recommend show that by the age of 2 years, one in ten children in the USA have obesity and more than half will have obesity by Panel: Long-term complications of gestational diabetes the age of 35 years.40 This persistence of obesity into early adulthood is likely to increase the risk of type 2 diabetes Complications for the women and cardiovascular disease. The long-term complications Hypertension8 in women and their offspring following gestational Type 2 diabetes8,24,25 diabetes are summarised in panel. Vascular dysfunction41 Early life exposures are known to influence long-term Non-alcoholic fatty liver disease42,43 health of the offspring, as encompassed by the Dyslipidaemia8,24,25 Developmental Origins of Health and Disease concept— Chronic inflammation41,44 ie, exposure to some environmental factors during crucial Chronic kidney disease45,46 periods of development might have pronounced Ischaemic heart disease8,9 consequences on later health.56 Human observational Complications for the offspring studies have shown an association between exposure to Childhood obesity10,25 maternal hyper­glycaemia, obesity, and disordered glucose Excess abdominal adiposity47 regulation in children and adolescents.10,50,57 Such Metabolic syndrome48,49 conditioning in girls could increase the propensity to Hyperinsulinaemia50 gestational diabetes, thus resulting in a vicious cycle of Disordered glucose regulation in adolescents27 cardiometabolic disorders (figure). Proposed mechanisms Higher blood pressure51,52 derived from studies in animals and humans include Possible early onset of cardiovascular disease53 altered gene expression through epigenetic mechanisms Possible attention-deficit hyperactivity disorder and leading to altered cellular signalling58 or disturbances in autism spectrum disorders52,54,55 the develop­ ment of central fetal pathways controlling appetite and energy balance.59 794 www.thelancet.com/diabetes-endocrinology Vol 8 September 2020  Personal View Therefore, solutions are needed to mitigate these fetal programming effects by developing interventions to Gestational diabetes prevent gestational diabetes among women at risk, and better management of hyperglycaemia is also needed. The Maternal glucose, lipids, inflammatory response approach must include optimisation of cardiometabolic health of the offspring to reduce the risk of childhood and adult obesity and the associated individual and population- level cardiometabolic consequences. Fetal insulin Epigenetic DNA modifications Fetal macrosomia affecting offspring energy balance and metabolism Preventing gestational diabetes Meta-analyses of lifestyle intervention studies designed to prevent gestational diabetes showed that interventions can reduce hyperglycaemia, gestational weight gain, caesarean Child and adult, obesity diabetes, and delivery, and might reduce gestational diabetes, but cardiovascular disease without consistently improving perinatal outcomes.60,61 Similarly, pharmacological interventions have failed to prevent babies being born large for gestational age.62 Figure: Developmental programming and gestational diabetes However, many multicentre studies did not show a Metabolic consequences of maternal gestational diabetes might increase the reduction in gestational diabetes, perhaps because partici­ risk of obesity, diabetes, and cardiometabolic disorders in the child and adult, pants did not adhere to trial protocols; interventions started leading to a transgenerational cycle of gestational diabetes and higher cardiometabolic susceptibility. too late in pregnancy; women most at risk of gestational diabetes were not targeted (selective screening picks up only 10–15% of women at risk of gestational diabetes followed this recom­ mendation because of insufficient entered in the trials); or a one size fits all approach was interventional evidence, clinical capacity, and concerns used for different ethnic groups.35 Lifestyle inter­ventions about increasing medicalisation during pregnancy. An could be effective if selectively targeting the correct risk ongoing randomised controlled trial identifies women groups; however, risk assessment is based on clinical risk with gestational diabetes using an oral glucose tolerance alone2,63 and is not sufficiently sensitive. Improving the test early in the pregnancy (