A pregnancy complicated by diabetes represents a significant challenge for healthcare professionals. Outcomes are significantly worse than in women without diabetes (Confidential Enquiry into Maternal and Child Health [CEMACH], 2007); however, careful pre-conception care and antenatal management may improve outcomes.
The population of women with diabetes in pregnancy is changing. In 2003, 27% of women with pre-existing diabetes complicating pregnancy had type 2 diabetes (CEMACH, 2007); by 2013 this proportion has risen to 44.9% (Health and Social Care Information Centre [HSCIC], 2014). The majority of these women will receive their diabetes management, and therefore all pre-conception care, in a primary care setting.
Most contraceptive services for women with diabetes are delivered in primary care, providing a further valuable opportunity to advise women that their pregnancies should be planned. Additionally, primary care delivers the management of early pregnancy, the majority of post-natal care, and long-term follow-up of those with previous gestational diabetes. Primary care health professionals thus have a very important role in influencing the outcomes of these pregnancies, as part of a wider multi-disciplinary team.
The new NICE guideline on diabetes and pregnancy, which was published in February 2015, therefore has particular relevance to primary care, especially with regard to recommendations for pre-conception care, early pregnancy, gestational diabetes and post-partum care (NICE, 2015). It is important to note that some of the medications recommended in the guideline are not licensed for use during pregnancy, and so the prescriber must be familiar with the rationale behind the recommendation and the safe and ethical way to prescribe in this situation.
In this article, we explore the implications for primary care of this new NICE guideline. The guideline has been eagerly awaited, not least by clinicians wishing to find out what definition of gestational diabetes (diabetes arising in pregnancy) would be adopted. Across the world, gestational diabetes has been defined, in recent years, by various diagnostic standards, with perhaps the most widely established ones being: the World Health Organization (WHO) Department of Noncommunicable Disease Surveillance (1999) criteria; and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel (2010) criteria. Clinicians in the UK were aware that the definition accepted by NICE for the UK would significantly affect, among other things, the number of women diagnosed with gestational diabetes.
Recommendations in the NICE guideline
It is well established that the risk of a major congenital malformation is correlated with HbA1c at conception (Guerin et al, 2007; Bell et al, 2012). Many other outcomes in pregnancy such as first-trimester miscarriage and risk of premature delivery are also related to glycaemic control in early pregnancy (NICE, 2015). Women should be encouraged to plan pregnancies and use contraception until the target HbA1c is achieved. Advice to avoid unplanned pregnancies should start at adolescence.
New recommendations from the guideline are that the type of contraception should be based on a woman’s preferences and risks, and this includes oral contraceptives, which can be used if there are no contraindications, as outlined in the UK Medical Eligibility Criteria for Contraceptive Use, 2009 (Faculty of Sexual and Reproductive Healthcare, 2009).
There is guidance on which topics should be included in pre-conception discussions, and this includes the reasons for the intensive glucose control pre-conception, the common risks of a pregnancy complicated by diabetes to the mother and baby, and the intensity of the antenatal schedule. Advice on glucose control prior to pregnancy should be given at each consultation after adolescence.
Pre-conception glucose control
An HbA1c <48 mmol/mol (<6.5%) is advised pre-conception if it is possible to achieve this without problematic hypoglycaemia. This contrasts with the advice in the previous NICE guideline on diabetes and pregnancy to achieve an HbA1c of 43 mmol/mol (6.1%) or less pre-conception (NICE, 2008). The National Diabetes in Pregnancy Audit of 2013 showed that only 5.1% of women with type 1 diabetes and 18.5% of women with type 2 diabetes achieved the 2008 target (HSCIC, 2014), based on first-trimester measurements. The new guidance also advises that any lowering towards this target will reduce the risk of congenital malformation.
When planning a pregnancy, all women with diabetes should be self-monitoring capillary blood glucose and should have monthly HbA1c tests. Women with type 1 diabetes should have a ketone meter and know when to test for ketones and how to interpret the results.
Metformin may be continued pre-conception and during pregnancy; however, all other oral agents should be stopped and insulin substituted. Metformin does not have a specific licence for this indication; however, there is strong evidence for its safety and effectiveness (NICE, 2015). Rapid-acting analogues (see Table 1) are licensed in pregnancy and are preferred over human soluble insulin. Isophane insulin is suggested as the basal insulin of choice; however, if women are already well controlled on long-acting analogues such as insulin detemir or insulin glargine then these may continue (see Table 2). Women who are planning a pregnancy should be offered attendance at a structured education programme as soon as possible.
Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and statins should be stopped pre-conception when possible. Alternative medication for the treatment of hypertension may be necessary; methyldopa and nifedipine are commonly used and, although the data are limited, are not thought to cause fetal adverse effects.
Retinal and renal assessments
Retinopathy may deteriorate or arise during pregnancy. The greatest risk factors are pre-existing severe retinopathy, poor glycaemic control and hypertension. Retinal screening should be performed pre-conception. If retinopathy is present, rapid optimisation of glucose levels may need to be deferred until after treatment; however, it is crucial that optimisation not be deferred if the woman is already pregnant. Renal assessment should also be performed pre-conception. Women with a creatinine level >120 µmol/L, a microalbumin level >30 mg/mol or an estimated glomerular filtration <45 mL/min/1.73 m2 should be referred to a nephrologist prior to pregnancy. The presence of nephropathy and microalbuminuria increase the risk of hypertension in pregnancy and of intrauterine growth restriction.
All women with diabetes should receive folic acid 5 mg from the pre-conception period until week 12 of pregnancy. The National Diabetes in Pregnancy Audit demonstrated that 42.6% of women with type 1 diabetes received the correct dose, compared with 24.7% of those with type 2 diabetes (HSCIC, 2014). This may reflect a greater emphasis on pre-conception care for women with type 1 diabetes. In any case, the figures indicate the magnitude of the improvement to pre-conception care that is necessary.
Glucose targets during pregnancy
Women should be advised to check capillary blood glucose levels while fasting, pre-meal, 1 hour post-meal and before bed if they are taking multiple daily insulin injections. Adequate numbers of test strips will be required to test seven or eight times a day.
The fasting glucose should be <5.3 mmol/L, while the target 1 hour postprandially is <7.8 mmol/L and the target 2 hours postprandially is <6.4 mmol/L. Achieving tight glycaemic control in the first trimester, when insulin requirements are lowest, puts a woman at increased risk of hypoglycaemia. She should be warned of this and be given a fast-acting form of glucose. She should also be provided with glucagon and family members instructed on its use. Although not covered in the guideline, it should be borne in mind that if hypoglycaemia is severe or there is unawareness, the women may need to be advised to stop driving and to notify the Driver and Vehicle Licensing Agency, in accordance with the agency’s guidance.
As is mentioned in the introduction, there are various definitions of gestational diabetes in use across the world, including: the WHO definition of 1999; and the IADPSG definition of 2010, which requires a fasting glucose ≥5.1 mmol/L, a 1-hour glucose ≥10.0 mmol/L or a 2-hour glucose ≥8.5 mmol/L. The latter definition has been adopted by organisations such as the American Diabetes Association (ADA, 2015) and, more recently, WHO itself (WHO, 2013). The new NICE guideline adopts neither of these and instead opts for a modified definition.
Gestational diabetes is diagnosed if the fasting glucose is ≥5.6 mmol/L or the 2-hour glucose is ≥7.8 mmol/L on a 2-hour 75-g oral glucose tolerance test. These figures are based on cost-effectiveness analysis. The definition will increase the number of women diagnosed with gestational diabetes in the UK.
The IADPSG recommends screening all pregnant women for gestational diabetes at 24–28 weeks gestation (IADPSG Consensus Panel, 2010). The new NICE guideline suggests screening women with risk factors for gestational diabetes, which are identified at booking (unchanged from the 2008 version):
- BMI >30 kg/m2.
- Previous macrosomic baby weighing ≥4.5 kg.
- Previous gestational diabetes.
- Family history of diabetes (first‑degree relative with diabetes).
- Minority ethnic family origin with a high prevalence of diabetes.
Women with risk factors should generally be screened at 24–28 weeks for gestational diabetes. The exception is women with previous gestational diabetes, who should either self-monitor blood glucose or have a 75-g oral glucose tolerance test soon after booking, with a repeat test at 24 weeks if this is normal. Glycosuria is also considered to be a reason to screen for gestational diabetes (using either 2+ on one occasion or 1+ on two occasions), and this is new for the 2015 NICE guideline.
If gestational diabetes is identified, women should be seen in combined diabetes ante-natal clinic within a week and the primary care team should be informed. Blood glucose targets for gestational diabetes should be the same as for pre-existing diabetes. Women should be given advice on dietary changes from a state-registered dietitian and advice on exercise. In addition, it is recommended that women with gestational diabetes take a fasting blood glucose level each day and also test 1 hour after every meal, if they are on diet and exercise therapy or are taking oral therapy or single-dose intermediate-acting or long-acting insulin.
If targets are not met, metformin should be commenced, and if capillary glucose levels remain outside targets, insulin should be added. However, if the fasting glucose is >7.0 mmol/L at diagnosis, immediate insulin should be offered. This should also be offered if the fasting glucose is between 6 and 6.9 mmol/L and a complication such as macrosomia is present.
New for 2015 is the recommendation to consider glibenclamide for women who are not well controlled on metformin but who do not wish to use insulin or who cannot tolerate metformin. Glibenclamide is not licensed for this indication, and it is advised that the prescriber takes full responsibility for this decision and obtains informed written consent.
Women with gestational diabetes will have their medication stopped at delivery and blood glucose levels should be checked post-partum in hospital to ensure they are normal. Those women whose glucose levels return to normal post-partum will need a fasting plasma glucose measurement taken between 6 and 13 weeks post-partum.
l Where the fasting glucose is less than 6.0 mmol/L, individuals should be informed that they are at moderate risk of diabetes in the future, and if it is between 6.1 and 6.9 mmol/L they should be informed that they are at a high risk of diabetes in the future. These women should be offered a 75-g oral glucose tolerance test.
l If the glucose is above 7.0 mmol/L, they should have tests to confirm the diagnosis of diabetes.
For those without persistent diabetes, preventative measures should be started, including advice on weight control, diet and exercise. Annual screening for diabetes should be commenced with the use of HbA1c or fasting glucose levels.
Finally, all women developing gestational diabetes should be informed that they are at high risk of the condition in future pregnancies, and, while not explicitly stated in the guideline, it would seem prudent to test these women pre-conception where possible.
Detecting undiagnosed type 2 diabetes in pregnancy
The guideline suggests that HbA1c should be tested at the time of diagnosis of gestational diabetes to detect those with undiagnosed type 2 diabetes; however, it is stated elsewhere in the guidance that HbA1c is a poor marker of glycaemic control in the second and third trimesters, which is when most gestational diabetes will be diagnosed. The ADA (2015) recommends a test to detect diabetes when a woman initially presents with a pregnancy; this approach has the advantage of detecting type 2 diabetes early in pregnancy to allow early intervention. This may represent a missed opportunity to improve outcomes for a proportion of high-risk women and their babies.
One of the key recommendations from the National Diabetes in Pregnancy Audit of 2013 was to improve pre-conception care for women with diabetes. The new NICE guideline contains recommendations of how this should be achieved. Primary care practitioners have a very important role in delivering pre-conception care and are likely to be champions for implementing these recommendations.
The proportion of women with gestational diabetes will increase as these recommendations are adopted With this there will be an increase in the prescriptions of glucose testing strips, insulin and medications outside their licensed indications. There will also be an increase in interventions to prevent type 2 diabetes following gestational diabetes and in post-partum surveillance for the development of type 2 diabetes. Primary care will be central to the delivery of these new recommendations.