8.1 Introduction

An optimal outcome may be obtained in diabetic pregnancy if excellent glycaemic control is achieved before and during pregnancy. However, type 1 diabetes is a high risk state for both the woman and her fetus. There are increased complications of diabetes, such as ketoacidosis, severe hypoglycaemia, and progression of microvascular complications. There are also increased risks of obstetric complications, such as pre-eclampsia, premature labour, spontaneous abortion, obstructed labour, polyhydramnios, and maternal infection. Fetal and neonatal complications include late intrauterine death, fetal distress, congenital malformation, hypoglycaemia, respiratory distress syndrome and jaundice. Rates of fetal and neonatal loss and major congenital malformation are increased by at least two to threefold. Type 2 diabetes is less common than type 1 diabetes during the reproductive years, but management prior to and during pregnancy should follow the same intensive programme of metabolic, obstetric and neonatal supervision.

An audit of implementation of the pilot SIGN guideline on management of diabetes in pregnancy indicated that adverse pregancy outcomes remain higher in women with diabetes than in the non-diabetic population.³⁶¹

An experienced multidisciplinary team led by a named obstetrician and physician should provide comprehensive maternity care.

Effective communication between all members of the team is essential, recognising that the key member is the woman with diabetes.

8.2 Contraception

Contraception should be discussed on an individual basis with all women of childbearing age with diabetes. There is little evidence on choice of contraceptive method specifically in women with diabetes. In general, the contraceptive advice for a woman with diabetes should follow that in the general population but the combined oestrogen-progesterone pill should be avoided in women with complications or risk factors for vascular disease. Progesterone-only prepartations may be suitable in these women, but the increased failure rate must be noted:^{362, 363}

The levonorgestrel-releasing intrauterine system (Mirena coil) is a safe method of contraception which may be particularly suitable for use in women with diabetes as it is as effective as sterilisation and produces low circulating hormone levels.³⁶⁴ Evidence level 4

Pregnancy should be planned and good contraceptive advice and pre-pregnancy counselling are essential.

8.3 Pre-pregnancy care

Infants whose mothers with diabetes received dedicated multidisciplinary pre-pregnancy care show significantly fewer major congenital malformations (approximating to the rate in non-diabetic women) compared to infants of non-attending mothers. Attendance at a pre-pregnancy clinic is associated with a reduction in the rate of spontaneous abortion and in complications of pregnancy. Infants of mothers attending pre-pregnancy clinics have fewer problems and are kept in special care for shorter periods than infants of non-attending mothers.^{365, 366} Evidence level 2+

The essential components of a pre-pregnancy care programme include review and consideration of the medical (including drug treatment), obstetric and gynaecological history; advice on glycaemic control to optimise HbA1c; and screening for complications.

Pre-pregnancy care provided by a multidisciplinary team is strongly recommended for women with diabetes.

All healthcare professionals in contact with women with diabetes of child-bearing age should be aware of the importance of pre-pregnancy care and local arrangements for its delivery, and should share this information with the woman.

8.4 Nutritional management

It is good clinical practice to provide dietary advice to women before, during and after pregnancy.³⁶⁷ Evidence level 4

Dietetic advice should be available in all diabetic antenatal clinics, and should encourage diets with high levels of complex carbohydrates, soluble fibre and vitamins, and reduced levels of saturated fats.

Neural tube defects in high risk pregnancies are associated with lower levels of folate.³⁶⁸ A large study in non-diabetic women has shown that prescription of 4 mg folate supplementation pre- and peri-conceptually has been shown to confer protection against neural tube defects, particularly in women at high risk.³⁶⁹ Evidence level 1++, 2++

All women with diabetes should be prescribed pre-pregnancy folate supplementation (c. 4 mg), continuing up to 12 weeks gestation.

Folic acid 5 mg tablets are readily available, suitable, and should be provided wherever pre-pregnancy care is delivered.

8.5 Optimisation of glycaemic control

Optimal glucose control before and during pregnancy reduces congenital malformations, stillbirth, neonatal hypoglycaemia, and respiratory distress syndrome. Women should aim to maintain blood glucose as near to the non-diabetic range as possible without excessive risk of hypoglycaemia.³⁷⁰ This usually means targeting levels between 4 and 7 mmol/l. Diabetes specialist nurses and midwives have an important role in educating women on the need for home blood glucose monitoring (4-6 times a day) and intensive insulin regimens. Intensive basal bolus regimens are commonly used and insulin analogues are increasingly used, although published research on their role and safety in pregnancy is limited. Evidence level 4

Before and during pregnancy, women with diabetes should aim to have blood glucose between 4 and 7 mmol/l.

8.6 Complications during pregnancy

8.6.1 OBSTETRIC COMPLICATIONS

There is no specific evidence on management of obstetric complications, including pregnancy-induced hypertension and increased risk of thromboembolism, in women with diabetes. These risks should be managed as for other pregnant women.

8.6.2 METABOLIC COMPLICATIONS

During pregnancy, hypoglycaemic unawareness and severe hypoglycaemia are common and diabetic ketoacidosis can develop more rapidly. Women and their partners need education on the management of hypoglycaemia, including the use of glucagon, and on the recognition and prevention of ketoacidosis, which may result in fetal death. Local emergency contact arrangements must be explicit.

8.6.3 MICROVASCULAR COMPLICATIONS

Diabetic retinal and renal disease can deteriorate during pregnancy.³⁷¹ The presence of retinopathy alone is not associated with a poorer pregnancy outcome for the fetus unless concurrent nephropathy is evident.³⁷² Evidence level 2+ ,3

Retinopathy

In one study, 77.5% of women with baseline retinopathy showed progression during pregnancy, with 22.5% requiring panretinal photocoagulation.³⁷³ Poor glycaemic control in the first trimester and pregnancy-induced or chronic hypertension are independently associated with the progression of retinopathy.³⁷¹ Evidence level 2+

Fundal examination prior to conception and during each trimester is advised. More frequent assessment may be required in those with poor glycaemic control or hypertension.

Early referral of pregnant women with moderate retinopathy to an ophthalmologist is recommended due to the potential for rapid development of neovascularisation.

Parous women with type 1 diabetes have significantly lower levels of all retinopathy compared with nulliparous.³⁷⁴ The associated significant difference in HbA1c suggests that improved glycaemic control associated with pregnancy may be sustained over time, with beneficial effects on long term complications. Evidence level 2+

Women should be reassured that tight glycaemic control during and immediately after pregnancy can effectively reduce the long term risk of retinopathy in future.

Nephropathy

There is an association between pre-existing nephropathy (microalbuminuria or albuminuria) and a poorer pregnancy outcome, though this is not due to any increase in congenital malformations. Proteinuria increases transiently during pregnancy, returning to a pre-pregnancy level within three months of delivery. The incidence of worsening chronic hypertension or pregnancy-induced hypertension/pre-eclampsia is high (varying from 40% to 73% across series) in women with both incipient and overt nephropathy. Worsening nephropathy and superimposed pre-eclampsia are the most common causes of pre-term delivery in women with diabetes.

The management of pregnant women with diabetic nephropathy should follow the recommendations in section 5 (target blood pressure <140/80 mm Hg). However, ACE inhibitors should be avoided as they may adversely affect the fetus. Appropriate antihypertensive agents which may be used during pregnancy include methyl dopa, labetalol and nifedipine.

8.7 Fetal monitoring

Diabetic pregnancies are at high risk, thus regular monitoring is appropriate. The risk is greater in women with complications of diabetes (e.g. vascular or renal disease) or of pregnancy (e.g. pre-eclampsia).³⁷⁵ Evidence level 3

The clinical judgement of an obstetrician experienced in diabetic pregnancy is essential and ultrasound scanning must be available for assessing gestational age, examining for congenital abnormalities and monitoring fetal growth. No evidence has been identified on the effectiveness of any single technique, and the most reliable method for fetal monitoring may involve the use of more than one technique. A suggested minimum monitoring provision in the third trimester involves weekly clinical assessment and regular cardiotocography. Women should be encouraged to report a perceived reduction in fetal movement during pregnancy.

The use of Doppler ultrasound in high risk pregnancies appears to improve a number of obstetric care outcomes and appears promising in helping to reducing perinatal deaths.³⁷⁶ Evidence level 1++

8.8 Delivery

National audit data in Scotland indicate that delivery in women with diabetes is generally expedited within 40 weeks gestation.³⁶¹ No clear evidence was identified to inform the optimal timing for delivery. The timing of delivery should be determined on an individual basis. Evidence level 3

Women with diabetes in pregnancy who are at risk of pre-term delivery should receive antenatal corticosteroids in line with local protocols.³⁷⁷ If steroids are clinically indicated for pre-term labour, inpatient supervision by an experienced team is essential to regulate diabetic control. Evidence level 1++

Women with diabetes have a high rate of caesarean section even after controlling for confounding factors.³⁷⁸ Estimated fetal weight >4.5 kg is generally regarded as an indication for delivery by elective caeserean section.³⁷⁹ Evidence level 2+, 4

Women with insulin-requiring diabetes in pregnancies which are otherwise progressing normally should be assessed at 38 weeks gestation to ensure delivery by 40 weeks. Women with diabetes should be delivered in consultant-led maternity units which have a senior physican, obstetrician, and neonatologist available. The progress of labour should be monitored as for other high risk women, including continuous electronic fetal monitoring. Intravenous insulin and dextrose should be administered as necessary to maintain blood glucose levels between 4 and 7 mmol/l.

8.9 Infants of mothers with diabetes

Labour and delivery should only be undertaken in a maternity unit supported by neonatal intensive care facilities. A paediatrician skilled in resuscitation should be present at the delivery of all women with diabetes, but there is no need for routine admission of the infant to the neonatal unit. There is insufficient evidence on the preferred method of cotside blood glucose measurement in neonates; however, whichever method is used, the glucose value should be confirmed by laboratory measurement. Neonatal hypoglycaemia is defined at blood glucose <2.6 mmol/l and is associated with adverse short and long term neurodevelopmental outcomes.³⁸⁰ Evidence level 4

Early feeding is advised to avoid neonatal hypoglycaemia and to stimulate lactation.

Six-week post partum fasting plasma glucose levels of women with type 1 diabetes, who exclusively breast fed, have been found to be significantly lower than those who bottle fed.³⁸¹ There are well-documented health benefits for infants that are breast-fed. Evidence level 2++

Breast feeding is recommended for infants of mothers with diabetes, but mothers should be supported in the feeding method of their choice.

8.10 Postnatal care

Women with type 1 or type 2 diabetes may require adjustment of their treatment regimen postnatally. Women with gestational diabetes should be investigated postnatally to clarify the diagnosis and exclude type 1 or type 2 diabetes. The opportunity should also be taken to provide lifestyle advice to reduce the risk of subsequent type 2 diabetes.

Postnatal follow up should be seen as an opportunity to initiate pre-pregnancy care for any subsequent pregnancy. Appropriate contraception should be provided and the importance of good glycaemic control emphasised.

8.11 Gestational diabetes

There is no consensus on the definition, management or treatment of gestational diabetes (GDM). GDM can be defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy.³ This definition will include women with abnormal glucose tolerance that reverts to normal after delivery, those with undiagnosed type 1 or type 2 diabetes, and rarely women with monogenic diabetes.³⁸² If type 1 or type 2 diabetes is presumed (e.g. due to early presentation or grossly elevated blood glucose), urgent action is required to normalise metabolism. The most appropriate strategies for screening, diagnosing and managing asymptomatic GDM remain controversial.

8.11.1 SCREENING FOR GDM

An important aim of screening in pregnancy is to identify women with undiagosed type 1 or type 2 diabetes. Screening for GDM requires urine to be tested for glycosuria at every antenatal visit. A random venous plasma glucose should be recorded if 2+ glycosuria is detected, and routinely at 28 weeks gestation. The World Health Organisation advise that a 75 g oral glucose tolerance test (OGTT) should be carried out if the blood glucose is >5.5 mmol/l two hours or more after food, or >7 mmol/l within two hours of food.³

8.11.2 DIAGNOSIS OF GDM

The diagnostic label of GDM is associated with an increased likelihood of induction of labour, instrumental delivery and caesarean section. Accurate diagnosis is therefore important, but is hampered by the poor reproducibility of the OGTT during pregnancy.³⁸³ The criteria recommended for diagnosis of GDM are fasting venous plasma glucose >5.5 mmol/l or two hours after OGTT >9 mmol/l.³⁸⁴ Evidence level 2+ , 4

A diagnosis of GDM identifies women at increased risk of developing type 2 diabetes in future.³⁸⁵

8.11.3 MANAGEMENT OF GDM

Impaired glucose tolerance is associated with macrosomia.³⁸⁶ Dietary management, with or without insulin, causes a modest but consistent reduction in birth weight. However, intensive treatment with diet or insulin may compromise babies of mothers with gestational diabetes that are not macrosomic.³⁸⁷ Evidence level 2++

If blood glucose levels are in the range for established diabetes (see section 1.5), intensive specialist management is required.

If, after nutritional advice, pre- and post-prandial glucose levels are normal and there is no evidence of excessive fetal growth, manage as a normal pregnancy.

If, after a trial of dietary intervention, fasting glucose levels exceed 6 mmol/l and 2-hour post-prandial levels exceed 7 mmol/l with evidence of macrosomia on ultrasound (>95th centile), intensive management with diet, blood glucose monitoring and insulin are appropriate.³⁸⁸

Women with gestational diabetes should receive intensive management with diet and/or insulin if macrosomia is suspected or if blood glucose levels are in the range for established diabetes.