New guidance on the management of diabetes and its complications in pregnancy has been issued by the UK health watchdog, the National Institute for Health and Care Excellence (NICE).
This is the first update on this topic since 2008 and, most important, since the landmark multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study was published (N Engl J Med. 2008;358:1991-2002), explained Rudy Bilous, MD, from Newcastle University and James Cook Hospital, Middlesbrough, United Kingdom, who presented the new guidelines at the Diabetes UK Professional Conference in London last week.
HAPO, published in 2008, was the first study to conclusively establish a relationship between elevated maternal glucose concentrations and undesirable perinatal outcomes in women not previously diagnosed with diabetes.
As well as advising on gestational diabetes, the new NICE guidelines also address the management of type 1 and type 2 diabetes both preconception, during pregnancy and birth, and after delivery, as well as neonatal care, said Dr Bilous, a diabetologist who chaired the NICE panel for the guidance.
"The one major change is that we've clarified, using good evidence, the fasting [plasma] glucose criterion for diagnosing gestational diabetes mellitus," he told Medscape Medical News, adding that he believes this to be the most controversial part of the new recommendations.
NICE has opted for a 5.6-mmol/L (101-mg/dL) cutoff to diagnose gestational diabetes (using the one-step approach, a single fasted 75-g 2-hour oral glucose tolerance test [OGTT], which is common practice in Europe), whereas other organizations, including the International Association of Diabetes in Pregnancy Study Group (IADPSG) and the World Health Organization (WHO) have plumped for a cutoff of 5.1 mmol/L (92 mg/dL).
This means the NICE guidance will result in fewer women being diagnosed with gestational diabetes than would be using WHO/IADPSG recommendations, but still many more than would currently be identified using existing American College of Obstetrics and Gynecology (ACOG) guidance.
"We've also clarified and tidied up a lot of other aspects of care for women with diabetes. We've looked at the evidence about contraception, target [plasma glucose] ranges during pregnancy, the management of gestational diabetes after pregnancy, and the timing of delivery, which is another area of contention," Dr Bilous said.
"So I think the new guidance has clarified a lot of areas of uncertainty around the original  guidance, and hopefully people will find it helpful."
Asked to comment, cochair of the session, Rahat Maitlan, MD, from King's College Hospital, London, United Kingdom, told Medscape Medical News the new guidance is very useful.
"These are the first UK diabetes in pregnancy guidelines utilizing the HAPO data to inform clinical recommendations," she said. The IADPSG had issued its guidance, which was adopted by the WHO and American Diabetes Association (ADA), after HAPO, and "the diabetes community at large has eagerly anticipated the outcome from NICE."
On the issue of the cutoff point for diagnosis of gestational diabetes, Dr Maitland believes that NICE has pitched this "about right." As it stands, the new NICE guidance will still result in a large increase in the number of gestational diabetes cases diagnosed in the United Kingdom, she pointed out. Currently, her clinic diagnoses gestational diabetes at 6 mmol/L, and "our clinic is absolutely saturated already." Using the even-lower cutoff proposed by IADPSG would result in unmanageable numbers of women falling into the category of gestational diabetes, she said.
Planning Pregnancy Is Important: Avoid if HbA1c is 10% or Higher
The NICE committee was asked to review all the evidence around contraception in women with diabetes, "most of which is noncontroversial but is an update," Dr Bilous explained. "Most contraception is okay in women with [both forms of] diabetes; nothing is contraindicated, although a bit of extra care is required with combined hormonal contraceptive methods."
One of the "key things" that has emerged, however, is "that we must talk to girls and younger women, from adolescence, about unplanned pregnancy and what pregnancy would mean [for a person with diabetes]," he stressed.
In an ideal world, contraception should be used until good blood glucose control is achieved (the same HbA1c target as for type 1 diabetes — ie, < 6.5%) before contemplating pregnancy, and all medication and monitoring should undergo review before and during pregnancy.
Essentially, any reduction in HbA1c toward the target "reduces pregnancy risk," he observed, noting also that NICE has recommended — "and this is controversial" — that pregnancy be avoided in patients whose HbA1c is 10% or higher.
However, one audience member observed that the world is in fact far from ideal and many women with diabetes do not plan their pregnancies. This issue needs to be addressed — it is vital that public awareness of this risk is increased — for example, by including a character who is diabetic and then gets pregnant into a soap-opera storyline, he suggested.
Dr Bilous agreed wholeheartedly, as did Helen Murphy, MD, from Cambridge University, United Kingdom, who also presented the rather-disheartening results of the first national UK audit of the management of diabetes in pregnancy to the Diabetes UK meeting.
Not Doing Enough to Lower Risks in Pregnant Diabetic Women
Although Dr Murphy reported some good news — more women are taking folic acid prepregnancy, and there are some improved infant outcomes for women with type 2 diabetes, including fewer preterm deliveries, large-for-gestational-age babies, and NICU admissions, there remains much work to do, she said.
Importantly, the proportion of women with type 2 diabetes who are getting pregnant has increased by as much as 45% since the last audit 10 years ago, and yet there has been "no change in serious adverse outcomes," notably major congenital abnormality rates, she explained. In addition, there has been no improvement in glucose control or in infant outcomes for those women with type 1 diabetes.
"We are not doing enough to lower risks [in diabetic women] in contrast to those of the general pregnant patient population," she added.
Dr Maitland said the new audit figures for major congenital anomaly rates are "quite disappointing," because there has been no reduction achieved over the past 10 years.
"Obtaining the audit data is an important step and starting point, but now we need to understand how to improve management to positively influence clinical outcomes."
Once Pregnant: Monitoring and When to Measure HbA1c
The NICE guidance recommends that, once pregnant, women with type 1 diabetes should be offered blood ketone monitoring equipment.
And during pregnancy, patients with type 1 diabetes or those with type 2 (or gestational diabetes on multiple daily injections) should aim for blood glucose targets of > 4.0 mmol/L. Fasting levels should be < 5.3 mmol/L, 1-hour postmeal values < 7.8 mmol/L, and 2-hour postmeal values < 6.4 mmol/L.
There was also much discussion about long-acting insulin, Dr Bilous observed, noting "we came up with NPH as first choice, but if a woman is already using another long-acting insulin and control is satisfactory, they do not need to change [medication]."
On the issue of the use of continuous glucose monitoring (CGM) during pregnancy, for the time being the recommendation is to "not offer CGM," unless there is problematic severe hypoglycemia, unstable blood glucose levels, or a need to understand glucose variability, Dr Bilous explained. If CGM is employed in pregnancy, women must have access to 24-hour support, he noted.
HbA1c should be measured at the first antenatal appointment to determine risk level and should be measured in all women at the diagnosis of gestational diabetes mellitus "to detect those with possible type 2 diabetes."
"Another area of controversy" is whether to measure HbA1c in the second and third trimesters, which we say can be 'considered,' " Dr Bilous said.
The reason this poses a difficulty is that, barring the risk for macrosomia and stillbirth, there are few data relating HbA1c at this stage of pregnancy to outcomes, he explained.
Gestational Diabetes Diagnosis: 70% of Those Affected Will Need Medication
On the controversial issue of diagnosing gestational diabetes, there remains a split between various international organizations.
The more traditional, and still more common, practice in the United States — recommended by the American Congress of Obstetricians and Gynecologists (ACOG) and the US National Institutes of Health — is the 2-step approach, a nonfasted 1-hour, 50-g glucose challenge followed by a diagnostic fasted 3-hour, 100-g OGTT only for those women who exceed a designated glucose cutoff. Currently, the ACOG diagnoses gestational diabetes at a blood glucose level of 135 mg/dL to 140 mg/dL (7.5 to 7.8 mmol/L).
The 2-step method has the advantage of convenience, because women don't have to fast. However, the 1-step method identifies more gestational diabetes cases.
The new NICE guidance recommends the 1-step approach, as does the IADPSG and the WHO. The ADA has said that either the 1- or 2-step approach can be used, as more research is needed to determine which is best.
NICE recommends diagnosing gestational diabetes if fasting glucose is > 5.6 mmol/L and/or 2-hour glucose is > 7.8 mmol/L.
The 75-g OGTT can be used at the first antenatal appointment if the women has had prior gestational diabetes or at 24 to 28 weeks' gestation if there is any other risk factor (eg, glycosuria), Dr Bilous said. In addition, any woman of a nonwhite ethnic background should be offered a screening for gestational diabetes.
Another possibility for women who have had prior gestational diabetes is to consider capillary blood glucose monitoring at the first appointment instead of the 75-g OGTT, which he acknowledged "is unpleasant."
Prior to screening, it is vitally important to explain to women that although some of those diagnosed with gestational diabetes will respond to a change in diet and exercise, "70% will need oral agents and/or insulin," Dr Bilous explained.
For those who are diagnosed with gestational diabetes, they "should be seen in a specialist clinic within a week of a positive diagnosis…to teach them about monitoring and blood glucose targets." All women with gestational diabetes should be referred to a dietician and recommended to eat foods with a low glycemic-index value. They should be advised to exercise and offered a trial on lifestyle advice if fasting plasma glucose is < 7.0 mmol/L.
Metformin should be offered if targets are not met within 2 weeks or metformin plus insulin if fasting plasma glucose is > 7.0 mmol/L or be considered insulin if fasting plasma glucose is 6 to 6.9 mmol/L and macrosomia and/or polyhydramnios are evident. Glyburide can be considered if women are intolerant of metformin or resistant to insulin.Mismatch Between Different Organizations
One audience member questioned why NICE had opted for a different diagnostic threshold from the WHO and IADPSG and commented that this could prove to be "troublesome."
Dr Bilous explained that extensive economic analysis of the impact of the IADPSG guidelines on the provision of care for women with gestational diabetes was included for the first time in these new NICE recommendations, but NICE is constrained by the fact its modeling can take into account only what happens around pregnancy and its complications and doesn't incorporate information on the future outcome of the baby. If that were the case, "we might have a different set of criteria," he explained.
"Given those constraints…it is different, but I don't make too much apology for that, because I believe that IADPSG was done for physiologic reasons but it didn't really take into account what the implications would be for all of us in clinical services.
"We have huge numbers in the UK, where we would be diagnosing gestational diabetes with all of the cost implications of that, without really being able to demonstrate the cost benefit for the population as a whole. Until we can get a firm handle on whether we can reduce the risk to future health of the babies by doing something different, that's the best we've got," he stressed.
Session cochair Stephanie Amiel, MD, from Kings College Hospital, London, United Kingdom, agreed: The new NICE guidance is "a fantastic piece of work. The balance between evidence and pragmatism…has been refreshing," she observed.
Timing of Delivery and Postnatal Care
Another hot topic in the new guidance relates to the timing and mode of delivery for pregnant women with diabetes, which should be discussed with all pregnant women with diabetes in the third trimester, Dr Bilous said.
Those with type 1 or type 2 diabetes and no complications are advised to have an elective birth between weeks 37 and 38 of pregnancy. Birth should be considered before week 37, however, for those with type 1 or 2 diabetes and metabolic or fetal/maternal complications, he noted.
Those with gestational diabetes should be advised to give birth no later than 40 weeks (+ 6 days), and elective birth should be offered prior to this. For women with gestational diabetes with maternal or fetal complications, "you can deliver earlier, and this is really standard practice," he explained.
The new NICE guidance also covers postnatal care, with Dr Bilous observing, "We couldn't find a single study where they had tested women to show that their glucose returned to normal."
NICE recommends that for women with gestational diabetes whose glucose levels are normal after birth, lifestyle advice should be offered, as should a fasting plasma glucose test at 6 to 13 weeks after birth and an HbA1c test not later than 13 weeks after the woman has given birth. But "do not offer routine OGTT," he observed.
OGTT should be offered only to those with fasting plasma glucose of 6.0 to 6.9 mmol/L; for levels lower than this, lifestyle advice should be offered, and the woman should have an annual screening test for diabetes.
If fasting plasma glucose is > 7.0 mmol/L, a repeat test, OGTT, or HbA1c test should be offered. For those having an HbA1c test, if < 5.7% they should be given lifestyle advice and have annual screening; for 5.7% to 6.4% an OGTT should be offered; and for 6.5% or greater, a repeat HbA1c assessment.
Five Research Recommendations
Finally, the NICE guidance also issued 5 research recommendations:
What are the roles of continuous subcutaneous insulin infusion (CSII) and CGM in helping women achieve targets prepregnancy?
What is the optimum screening time for gestational diabetes?
What are the barriers that women experience that prevent them from achieving blood glucose targets?
How can fetuses at risk of intrauterine death be identified?
What are the best long-term pharmacologic interventions for women with gestational diabetes to prevent the development of type 2 diabetes?
And as well as the new NICE guidelines for healthcare professionals, the agency has also issued guidance for the public, Dr Bilous concluded.
National Institute for Health and Care Excellence. Guideline
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Cite this: UK NICE Alters Threshold for Diagnosis of Gestational Diabetes - Medscape - Mar 19, 2015.