Diabetes Care in Pregnancy

Introduction

Prevalence

Risk associated with uncontrollable diabetes in pregnancy

Diagnosis and classification of disorders of hyperglycaemia in pregnancy

Screening for gestational diabetes (GDM)

Preconception counselling and education

Management of diabetes during pregnancy

Dietary therapy during pregnancy

Insulin therapy during pregnancy

Oral hypoglycaemic agents in pregnancy

Timing of delivery

Management during labour or caesarean section

Postpartum

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(See Strength of Recommendations Taxonomy (SORT) for explanation of Grade A-C)

SEMDSA 2017 Recommendations

Classification and Diagnosis The WHO classification of hyperglycaemia first detected in pregnancy has changed, and now includes “gestational diabetes” and “diabetes mellitus in pregnancy/overt diabetes” The diagnostic criteria for gestational diabetes has changed. We currently adopt the IADPSG criteria

Screening Pregnant women considered at high-risk for diabetes should be offered a 75 g 2-hour OGTT at their first visit (Grade B) and a further test at 24-28 weeks if the first test is normal (Grade A)

Referral Diabetes in pregnancy is a high-risk condition and must be referred to specialist diabetes centres for management (Grade C)

Preconception Preconception counselling should occur (Grade A), and an HbA1C <6.5% (Grade B) should be achieved for at least three months just prior to conception to minimise the incidence of congenital anomalies Folate (5 mg/day) should be taken from three months preconception to 12 weeks of gestation (Grade A). Hypertensive patients should achieve an acceptable BP of <130/80 mm Hg and discontinue ACE inhibitors and ARB therapies (Grade A) Statin therapy should be discontinued (Grade A)

Pharmacological management of diabetes during pregnancy Insulin is the preferred therapy for diabetes in pregnancy. Both human (Grade A) and some analogue insulins (Grade B) may be given during pregnancy as multiple daily injections, striving for normoglycaemia Non-insulin oral agents: both metformin and glibenclamide may be prescribed/continued during pregnancy under specialist supervision (Grade B)

Timing of delivery For pre-existing type 1 and type 2 diabetes, and diabetes in pregnancy/overt diabetes  Uncomplicated pregnancy- aim for elective delivery between 37-38 weeks gestation (Grade B) Complicated pregnancy- aim for delivery prior to 37 weeks gestation (Grade B) Gestational diabetes and Uncomplicated pregnancy- safe to continue pregnancy to 39-40 weeks gestation (Grade B)  Complicated pregnancy- delivery prior to 40 weeks is advocated (Grade C)

Postpartum care All neonates born to mothers with diabetes should be delivered in a tertiary care centre and be assessed by a neonatologist (Grade A) All patients with hyperglycaemia in pregnancy and normoglycaemia post-delivery should be reassessed with a 2-hour OGTT at 6 weeks postpartum (Grade A). Annual screening for diabetes should be performed if the result is normal (Grade B) Patients with pre-existing type 1 or type 2 diabetes may resume their pre-conception oral and/or insulin therapy Patients with overt/gestational diabetes with persistent hyperglycaemia immediately postpartum should be managed accordingly

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INTRODUCTION

There has been a major revision since the 2012 guideline to the classification and diagnosis of hyperglycaemia which is detected for the first time in pregnancy.

Great strides have been made in the management of diabetes mellitus in pregnancy in recent years. As a result of the epidemic of obesity, more young women are being diagnosed with gestational diabetes and overt diabetes in pregnancy. This section serves to classify the different types of diabetes in pregnancy, the current and proposed criteria for diagnosis, and the principles of management. A diabetes-obstetrics healthcare team should, ideally, be responsible for the comprehensive management of these women. Excellent care throughout (and, in certain cases, prior to) pregnancy ensures a successful outcome in the vast majority of these pregnancies.

PREVALENCE 

The prevalence of diabetes mellitus (diabetes) in pregnancy has been increasing worldwide, with the vast majority being due to gestational diabetes and the remainder due to disease predating the pregnancy i.e. pregestational diabetes. A global prevalence estimate of hyperglycaemia in pregnancy is 16.9%.^1,2 To date, there remains a paucity of data regarding the prevalence of gestational diabetes in Africa.³

RISKS ASSOCIATED WITH UNCONTROLLABLE DIABETES IN PREGNANCY  

Uncontrolled diabetes during pregnancy poses numerous risks for the mother and foetus /neonate (Table I). In addition, diabetes in pregnancy increases the risk of obesity and type 2 diabetes in the offspring later in life.⁴

Table I. Maternal, foetal/neonatal complications

Maternal	Foetal	Neonatal
Pre-eclampsia	Miscarriage	Respiratory distress syndrome
Polyhydramnios	Stillbirth	Hypoglycaemia
Pre-term delivery	Macrosomia	Hyperbilirubinemia
Acceleration of vascular disease	Congenital anormalities	Hypocalcemia

DIAGNOSTIC AND CLASSIFICATION OF DISORDERS OF HYPERGLYCAEMIA IN PREGNANCY

SEMDSA endorses and adopts the guideline on the diagnostic criteria and classification of hyperglycaemic disorders first detected in pregnancy as published by the World Health Organisation in 2013.⁸

This guideline:

• Takes into consideration new evidence from the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study.
• Proposes a new classification for hyperglycaemia first detected in pregnancy.
• Removes the ambiguity with regard to fasting plasma glucose values in the 1999 WHO guideline.

Any known type of diabetes mellitus that existed prior to pregnancy should continue to be referred to as such (e.g. type 1 diabetes, type 2 diabetes, LADA etc.  (Refer to: Definition and Classification of Diabetes Mellitus). Hyperglycaemia detected for the first time in pregnancy, and at any stage of pregnancy, should be classified as either:

• Diabetes mellitus in pregnancy (also referred to as “overt” diabetes by the IASDPG), or
• Gestational diabetes mellitus (GDM).

This consensus distinguishes between “overt” diabetes in pregnancy and lesser degrees of hyperglycaemia (GDM) for the following reasons:

• Overt diabetes during pregnancy, whether symptomatic or not, is associated with significant risk of adverse perinatal outcomes
• A detailed assessment for the presence of diabetes-related complications is recommended at diagnosis of overt diabetes (but not GDM), especially complications which can affect pregnancy or be aggravated by it, such as retinopathy and renal impairment
• During pregnancy a more intensive monitoring and treatment of hyperglycaemia is recommended and pharmacotherapy is much more likely to be required to control the hyperglycaemia for patients with overt diabetes
• Following the pregnancy there is a need for closer follow-up and ongoing monitoring and treatment of women with overt diabetes.

Classification of diabetes in pregnancy⁸

Pre-existing diabetes

Type 1, type 2 or other form of diabetes that was diagnosed before the pregnancy, with or without complications of diabetes

Hyperglycaemia first detected in pregnancy

Diabetes mellitus in pregnancy (also referred to as “overt diabetes”): Identification of, diabetes for the first time in pregnancy, using the (conventional) 2006 WHO criteria for diabetes in non-pregnant adults. 8 Gestational diabetes: Defined as any degree of glucose intolerance with onset or first recognition during pregnancy⁵ that is not clearly overt diabetes, with resolution post-delivery

The diagnostic criteria are summarised below:

Diagnosis of hyperglycaemia first detected at any stage of pregnancy⁸

Glucose Test	Gestational diabetes	Diabetes mellitus in pregnancy /overt diabetes
Fasting plasma glucose (FPG)	≥ 5.1- 6.9 mmol/l	≥ 7.0 mmol/l; or
One hour post-glucose load (75g) plasma glucose	≥ 10.0 mmol/l	Not applicable
Two hours post-glucose load (75g) plasma glucose	≥ 8.5-11 mmol/l	≥ 11.1 mmol/l

One or more of these criteria must be satisfied for the diagnosis of GDM to be made.

SCREENING FOR THE GESTATIONAL DIABETES (GDM) 

Pregnant women with the risk factors listed below should undergo a two-hour 75 g oral glucose-tolerance test (OGTT) at first booking and if normal, a repeat test at 24-28 weeks gestation, to screen for GDM as proposed by IADPSG (International Association of the Diabetes and Study Pregnancy Groups):^5.6.7

• Repeated glycosuria
• Previous GDM
• Family history of diabetes (first-degree relative)
• History of stillbirths of unknown origin, previous congenital anomalies and suspicion of polyhydramnios in present pregnancy
• History of high-birth weight infant ≥ 4.5 kg
• Obesity (body mass index (BMI) > 30 kg/m²)
• History of polycystic ovarian syndrome
• History of unexpected perinatal death
• Women of South-Asian descent

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Note: Universal screening for gestational diabetes may be adopted in well-resourced settings.

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PRECONCEPTION COUNSELLING AND EDUCATION

Suitably trained educators should provide education on all aspects of diabetes and its management before and during pregnancy. Pregnancy should ideally be planned in the patient with diabetes and hence preconception counselling is particularly important.

The following topics must be covered:

• Contraception: Effective contraception must be used until optimal HbA_1C levels are achieved.
• Optimising glucose control
  • Preconception glycated haemoglobin (HbA_1C) must be as close to the normal range as possible without significant hypoglycaemia. Target HbA_1C ≤ 6.5%.^6,10
  • Four to seven home blood-glucose tests should be carried out daily; refer to targets below (Table II).
  • If there is suboptimal blood-glucose control on oral agents,refer for insulin therapy
  • Advice should be given on the management of hypoglycaemia
• Diet, exercise and structured education:
  • The patient should be referred to a dietitian for education on the ingestion of regular, small-to-moderate portions of low glycaemic-index carbohydrates
    • Weight-loss education should be provided if the body mass index (BMI) > 27 kg/m²
    • Regular exercise should be encouraged
    • Advice should be given on smoking cessation and abstinence from alcohol use
• Hypertension
  Chronic hypertensive patients should achieve a satisfactory blood pressure (BP<130/80 mm Hg) pre-conception.⁶
• Medications
  • Ensure folic acid supplementation
  • Review other medication: avoid angiotensin- converting enzyme (ACE) inhibitors, angiotensin-II receptor blockers (ARBs), statins and diuretics
  • Treat hypertension with methyldopa
• Screen for and refer diabetic complications e.g. retinopathy, nephropathy and cardiac disease
• Screen for human immunodeficiency virus (HIV) and immunity to the rubella virus
• Counsel on risks associated with pregnancy in individuals with diabetes (Table I)

MANAGEMENT OF DIABETES DURING PREGNANCY

The management of the pregnant diabetic women requires intensive specialist supervision. Referral to a centre with a diabetes-obstetric healthcare team (including a physician with a special interest in diabetes or endocrinology), obstetrician, paediatrician, dietitian and diabetes nurse educator) would be ideal.
The mainstay of the medical management of diabetes during pregnancy involves frequent monitoring of blood glucose levels with adjustment of diet and, in most cases, the addition and or adjustment of therapy to achieve normoglycaemia. 

Frequent self-monitoring, i.e. six point profiles, of capillary blood glucose must be performed in pregnancy at the following times: pre-meal, one/two hours postprandial, and late at night.^6,7 Continuous glucose monitoring systems (CGMS) should not be offered routinely in pregnant females with diabetes, and may be considered, if available, in the following circumstances:⁶

1. Problematic or severe hypoglycaemia
2. To gain information regarding glucose variability
3. Presence of unstable glucose levels

Patients must be followed closely to term: every two weeks until 32 weeks of gestation, and weekly thereafter until just before delivery.

Dietary therapy during pregnancy

All patients should be referred to a dietician for detailed dietary advice. The diet should comprise approximately 40% carbohydrate (complex, low-glycaemic index, high fibre),⁶ 40% fat (at least 50% unsaturated) and 20% protein. The daily meal plan should include three meals, plus three or four snacks. Dietary consistency (in amount and timing of food intake) must be maintained to facilitate tight glycaemic control without inducing hypoglycaemia. Regular, moderate intensity exercise is recommended for at least 30 minutes daily throughout pregnancy.¹¹Caution should prevail should any maternal or neonatal complications arise.

Insulin therapy during pregnancy

Insulin is the preferred therapy for diabetes in pregnancy. It is indicated in all patients in whom target blood glucose levels are not met (Table II).

Table II. Target blood glucose levels during pregnancy as adopted by the Endocrine Society⁶

FPG	< 5.3 mmol/l
One hour postprandial	< 7.8 mmol/l
Two-hour postprandial	< 6.7 mmol/l

Multiple injections of short- and longer-acting insulins are recommended, i.e. short-acting human insulin, and intermediate-acting human neutral protamine Hagedorn (NPH) insulin, with the total dose of insulin varying from 0.7 U/kg-2U/kg (present pregnancy weight). Insulin requirements rise progressively as the pregnancy advances.
Frequent adjustments to insulin dosages must be made to achieve the target levels of blood glucose (Table II.)

Insulin analogues are deemed safe during pregnancy based on a growing body of evidence.^12,13 Short-acting analogues (Aspart and Lispro) are not known to adversely affect the outcomes of the pregnancy or the foetus. To date, there are no clinical trials assessing insulin glulisine in pregnancy and hence it is not recommended.

Long-acting insulin analogues (detemir or insulin glargine) may be continued in women with diabetes who have established good blood glucose control before pregnancy. It should, however, be noted that only insulin detemir is currently approved by the FDA (category B).^14,15

Oral hypoglycaemic agents in pregnancy

Although there is a lack of long-term safety data for oral hypoglycaemic agents (OHA) in pregnancy, both metformin and glibenclamide may be used in selected patients with type 2 diabetes, overt and GDM (category B). Offer metformin to patients with GDM who have not met glucose targets following 1-2 weeks of dietary and lifestyle manipulation. Consider glibenclamide, for women in whom blood glucose targets are not met with metformin and who decline insulin, or in those patients who are intolerant of metformin.^16,17

It is important to educate patients regarding the potential risks of each agent and to note that the majority (60-70%) will require supplemental insulin therapy at some point during the pregnancy.¹⁶

TIMING OF DELIVERY

Advise pregnant women with pregestational diabetes and no other complications to have an elective birth, either by induction of labour or caesarean section between 37 and 38 weeks of pregnancy. Consider elective birth prior to 37 weeks if there are metabolic or any maternal or foetal complications.⁷ The optimal timing of delivery in patients with GDM has not been evaluated in well-controlled trials.¹⁸

In controlled patients, whether on diet alone or diet and therapy, pregnancy may continue safely until 39-40 weeks.

If any maternal or foetal complications are present, earlier delivery is advised.

MANAGEMENT DURING LABOUR OR CAESAREAN SECTION

Glycaemic control during labour and birth is of utmost importance to avoid adverse neonatal outcomes. It is essential that capillary blood glucose is monitored hourly during labour and birth, ensuring that it is maintained between 4-7 mmol/l. Intravenous dextrose and insulin infusions should be prescribed at the onset of labour for all diabetic women whose glucose is not maintained between 4-7mmol/l.⁶ These infusions are also useful for glycaemic control during caesarian section.

POSTPARTUM

Women with diabetes in pregnancy should be advised to deliver at a hospital where advanced neonatal resuscitation skills are available. Numerous morbidities may present in babies born to women with diabetes (Table I). A neonatologist should assess newborns for any of these where clinically indicated.
Importantly, insulin requirements fall exponentially after delivery. Caution should be exercised in type I diabetic patients during this period, in order to avoid hypoglycaemia.
Type 2 diabetic women may resume their OHA immediately post-delivery and be reassured that these agents are safe during breastfeeding. Patients with overt diabetes/GDM and persistent hyperglycaemia immediately postpartum, should be managed accordingly. In those with normal glucose profiles post-delivery, their therapy should be stopped and they should undergo a 75g OGTT at six weeks to check for postpartum persistence of glucose intolerance. If normal, offer an annual HbA_1C test, given the high risk of developing type 2 diabetes in these patients. Lifestyle interventions (diet and exercise) and/or drug therapy, i.e. Metformin, may have a role in preventing future diabetes in such patients.^19,20

Contraception should be discussed and implemented. Most forms of contraception are safe and effective in women with diabetes.
Breastfeeding should be encouraged wherever possible both in women with overt or gestational diabetes.

Authors: Veronique Nicolau and Kenneth RL Huddle
Editor: Aslam Amod

References

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