Diabetes in pregnancy - Clinical review

Section 1: Epidemiology and aetiology

The diagnosis of diabetes in pregnancy is arbitrary, depending on where the cut-off is placed on the normal spectrum of glucose tolerance. About 2-5% of UK pregnancies are affected by diabetes.¹ This may be pre-existing type 1 or 2, or onset during pregnancy (gestational).

All adverse outcomes of pregnancy are increased by diabetes (see box 1); this relates to glycaemic control. The most important aim is to achieve maternal normoglycaemia.^2-6

In pregnancy, fasting levels of glucose decrease and normal serum levels following a meal increase. Glucose tolerance decreases progressively in each trimester, mostly because of anti-insulin hormones secreted by the placenta - human placental lactogen, glucagon and cortisol.

This underlies the increased insulin requirements of women with pre-existing diabetes and the development of abnormal glucose tolerance in gestational diabetes (GDM), where there is insufficient insulin secretion to compensate for the insulin resistance.2 Pre-existing diabetes may be insulin dependent or non-insulin dependent. GDM may be true or previously undiagnosed underlying type 2 diabetes.

Type 1 diabetes has a 0.5% prevalence in the UK and tends to present in young, lean children or young adults. Type 2 diabetes has a 3-4% prevalence in the UK, especially affecting older, overweight patients.

It is becoming more common as the prevalence of obesity and advanced age in pregnancy increases.3 In the UK, the prevalence of GDM is increased 11 times in women from India, eight times in those from south-east Asia, six times in Mediterranean and Arab women, and three times in African-Caribbean patients.³

Section 2: Making the diagnosis

The key feature of management is preconception counselling.^1,6 This aims to achieve good glycaemic control at an early stage and allows assessment for the presence of complications such as hypertension, and renal or eye disease (see box 2).

Glycaemic control can significantly reduce adverse outcomes including miscarriage, congenital malformation and stillbirth.

Contraindications to pregnancy include HbA1c >10%, IHD, untreated proliferative retinopathy and creatinine >250mmol/L.²

A pregnant woman with type 1 diabetes should be referred to the antenatal clinic. An early dating and viability scan is recommended.

GDM is asymptomatic and develops in the second or third trimester.

Antenatal diagnosis is usually with a 75g fasting glucose tolerance test at 28 weeks. If the woman has significant risk factors or previous GDM, this can be done at 18 weeks.⁶

Diagnosis is by a two-hour plasma glucose concentration >11.1mmol/L after 75g glucose tolerance test.

Risk factors are:^2,3

• BMI >30
• Previous macrosomic baby weighing >4.5kg
• Previous GDM
• Maternal age >35 years
• First-degree relative with diabetes
• South Asian, African-Caribbean or Middle Eastern ethnicity

Section 3: Managing the condition

All pregnancies complicated by diabetes are high risk and should be managed in a specialist antenatal clinic. Risks are related to glycaemic control at conception; GDM, which usually develops during the second trimester, has fewer risks.²

Women with pre-existing diabetes are entitled to free nuchal translucency screening at 11-13 weeks. Additional ultrasound scans are arranged to look at the fetal heart in detail and fetal growth from 28 weeks to detect macrosomia, polyhydramnios or intrauterine growth restriction.^1-3

All diabetic pregnant women will be taught to self-monitor their fasting and one-hour postprandial blood glucose levels.^1,6 They should aim for fasting blood glucose levels of 3.5-5.9mmol/L and one-hour postprandial blood glucose <7.8mmol/L.

GDM
Management of GDM involves regular exercise and a diet with reduced fat and controlled carbohydrate intake.⁴

Persistent hyperglycaemia (postprandial >7.8mmol/L and fasting >5.9mmol/L) are indications for the introduction of hypoglycaemic treatment.4,5 This may also be introduced if ultrasound shows macrosomia, defined as a birthweight >4.5kg. Insulin is a growth-promoting hormone, so babies of poorly controlled diabetic mothers tend to be large, with proportionally high abdomen to head ratios, enlarged organs and significant subcutaneous fat.

Macrosomia significantly increases the chance of assisted delivery and birth trauma.

Type 1 diabetes
Normal pregnancy is associated with an increase in insulin production and resistance, so women with type 1 diabetes often require increasing doses of insulin as their pregnancy progresses, especially between 28 and 32 weeks.⁵ Tight glycaemic control needs to be balanced against the risk of hypoglycaemia and the patient needs to be educated about this. Most maternal deaths in the UK caused by diabetes are due to hypoglycaemia.³

If diabetic ketoacidosis (DKA) is suspected during pregnancy, the patient should be admitted to a level two unit where obstetric and medical care are available. DKA has a fetal mortality rate of about 50%.³

Labour and birth
Most patients will be delivered by their due date (NICE recommends by 38 weeks),¹ with induction for vaginal delivery or by caesarean section.

During labour and birth, a sliding scale of insulin will often be used to maintain normoglycaemia around the time of delivery. This reduces the chance of neonatal hypoglycaemia.

Fetuses of diabetic mothers tend to mature more slowly and production of lung surfactant is often later, so steroids may be given if early elective birth is planned.

There is an increased chance of fetal distress, stillbirth and assisted delivery, so diabetic mothers are continuously monitored in labour. Delivery in hospital is advised.

The caesarean section rate for diabetic mothers is 65%.^1,3,4 Diabetes is not a contraindication to vaginal birth after caesarean section.^1,3

The baby will be observed to ensure there is no hypoglycaemia or respiratory distress. Women are advised to feed their baby within 30 minutes of birth and then every two to three hours to maintain neonatal blood glucose levels.

Postnatally, women with GDM can stop their hypoglycaemics. Women with type 2 diabetes can continue metformin or glibenclamide while breastfeeding. Those with insulin-dependent type 1 diabetes can revert to their pre-pregnancy insulin regimen.^4,6

Section 4: Prognosis

Pre-existing type 1 diabetes-related nephropathy, renal impairment, retinopathy, autonomic neuropathy and hypertension are likely to worsen during pregnancy. Renal impairment usually reverses after delivery.

Women who developed GDM should undergo repeat glucose tolerance testing six weeks postnatally and annually thereafter. These patients have a 40-60% chance of developing type 2 diabetes in the next 10 years. Modification of diet and lifestyle, especially avoiding obesity, can help to prevent this. Without significant weight loss, GDM usually recurs in subsequent pregnancies.

Diabetes during pregnancy is a factor in later metabolic disturbance in the offspring. Obesity and type 2 diabetes are more prevalent in patients when diabetes was present during their fetal development.⁶

Section 5: Case study

Bianca, a 37-year-old nulliparous woman, attends the GP surgery because she and her partner have been trying for a baby for six months with no success. Bianca has type 1 diabetes, which was diagnosed at the age of 11. She takes insulin glargine 10IU at night and has no allergies.

Her GP calculates her BMI at 32 and discovers she is smoking four to five cigarettes a day. He advises her about smoking cessation and weight loss by diet and exercise, and commences her on 5mg folic acid. Her HbA1c is 7.2%. He advises her to return as soon as she has a positive pregnancy test.

Three months later, Bianca attends again. She has managed to lose 9kg and stop smoking, and is delighted to have a positive pregnancy test.

The GP checks her urine (NAD) and BP (100/60mmHg) and confirms her pregnancy with urinalysis.

By her last menstrual period, she is approximately seven weeks pregnant. Her GP refers her for an early pregnancy ultrasound to confirm viability and makes a referral to the local antenatal clinic. He checks her eyes and tests U&Es to ensure her renal function is normal, and HbA1c, which returns a result of 6.3%.

Bianca has first trimester screening, which shows she is low risk for trisomy. Attending the antenatal clinic, she is counselled by the obstetrician and midwives regarding the risks of pregnancy in diabetes. She sees the dietitian. She decides to have amniocentesis, which shows a normal male fetus, 46 XY. At 18 weeks, Bianca has an anomaly ultrasound, which is normal, then a fetal cardiac echo, also normal. She is booked for a growth scan at 30 weeks and appointments with the diabetic team.

Her HbA1c at 30 weeks is 8.4%. She says she can't avoid 'eating for two'. This is reflected in the size of her baby on ultrasound. With an abdominal circumference >95th centile, excessive amniotic fluid index and estimated fetal weight of 4.5kg at 36 weeks, Bianca is counselled to undergo elective caesarean section.

Her insulin regimen is adjusted to ensure her sugars fall between 3.5-5.9mmol/L fasting and <7.8mmol/L postprandial. The caesarean section takes place at 38 weeks after sliding scale the night before. Delivery is uneventful and her son is born at 4.8kg.

Section 6  Evidence base

Clinical trials

• Crowther CA, Hiller JE, Moss JR et al. Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial 

Group: effect of treatment of gestational diabetes mellitus on pregnancy outcomes.N Engl J Med 2005: 352: 2477.

This is an interesting trial by ACHOIS, the Australian Carbohydrate Intolerance Study. A lot of current thinking about glucose control and its effects on pregnancy outcomes are founded on this trial.  

Guidelines

• NICE. Diabetes in pregnancy: management of diabetes and its complications from pre-conception to the postnatal period. CG63. London, NICE, March 2008. www.nice.org.uk/CG063   

NICE has published a report on the management of diabetes in pregnancy. The website includes a quick reference guide, with checklists for preconception counselling.

HbA1c conversion chart

• A chart to convert HbA1c percentages to the newer International Federation of Clinical Chemistry (IFCC) standardised mmol/mol concentration is available to download at: www.wales.nhs.uk/sitesplus/documents/866/HbA1c%20converter.pdf

References

1. NICE. Diabetes in pregnancy: management of diabetes and its complications from pre-conception to the postnatal period. CG63. 
London, NICE, March 2008. 
www.nice.org.uk/CG063   

2. Crowther CA, Hiller JE, Moss JR et al. Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group: effect of treatment of gestational diabetes mellitus on pregnancy outcomes. 
N Engl J Med 2005; 352: 2477.

3. Nelson-Piercy C. Diabetes 
mellitus. In: Handbook of Obstetric Medicine (fourth edition). London, Informa Healthcare, 2010. 

4. Confidential Enquiry into Maternal and Child Health. Pregnancy in women with type 1 and 2 diabetes 2002-2003. England, Wales and Northern Ireland. London, CEMACH, 2005.

5. Ballas J, Moore TR, Ramos GA. Management of diabetes in 
pregnancy. Curr Diab Rep 2012; 12(1): 33-42.

6. McElduff A, Cheung NW, McIntyre HD. Australasian Diabetes in Pregnancy society consensus guidelines for the management of type 1 and 2 diabetes in relation to pregnancy. Med J Aust 2005; 183(7): 373-7.

Click here to take a test on this article and claim a certificate on MIMS Learning

• Contributed by Dr Polly Weston, consultant obstetrician and gynaecologist at Joondalup Health Campus, Perth, Western Australia.