Diabetes in Pregnancy

There is a separate article on Gestational Diabetes.

• Diabetes is the most common pre-existing medical disorder complicating pregnancy in the UK.
• Type 1, 2 and gestational diabetes affect 2-5% of pregnancies in England and Wales.¹
• The number of people with type 1 diabetes and the prevalence of type 2 diabetes amongst women of child-bearing age is increasing.
• Pregnancies of women with diabetes are regarded as high-risk for both the woman and the baby.²
• Approximately 87.5% of pregnancies complicated by diabetes are due to gestational diabetes, 7.5% are due to type 1 diabetes and 5% are due to type 2 diabetes.¹

An National enquiry was published in February 2007 by the Confidential Enquiry into Maternal and Child Health (CEMACH). (This was separate to the triennial report on maternal deaths.) It looked specifically at diabetes in pregnancy and whether we are providing the best care. It examined the outcomes of 3808 pregnancies in women with type 1 and type 2 diabetes between March 2002 and February 2003.

The Saint Vincent Declaration (1989) aims were that 'in five years, the outcome of diabetic pregnancy should approximate that of a non-diabetic pregnancy'.⁴ Unfortunately, the National enquiry found that this has not yet been achieved. It found that there was suboptimal pre-conception and pregnancy care including pre-conception counselling, glycaemic control before and during pregnancy, appropriate screening and management of diabetes complications, and fetal surveillance during pregnancy. Various clinical skills and training issues for medical staff were found to be a cause of this, as well as social and lifestyle issues for the woman. Maternal social deprivation was found to be associated with poor pregnancy outcome. Half of the women in the enquiry also had suboptimal postnatal diabetes care.

The findings support the argument that preparation for pregnancy, glycaemic control and the standard of preconception and pregnancy care need to be improved if better pregnancy outcomes are to be achieved for women with diabetes.

Diabetes causes a rise in blood glucose above normal physiological levels. Pregnancy causes a physiological reduction in insulin action. This means that women with diabetes have an increased requirement for insulin during pregnancy. There are various complications that the pregnancy may face. Preconception care and good glucose control before and during pregnancy can reduce these risks.^2,5,6,7

Increased risk of complications of diabetes

• Ketoacidosis may occur during the pregnancy.
• Hypoglycaemia: almost half of the women in the Confidential Enquiry had recurrent hypoglycaemia during pregnancy, although there was no evidence that this was associated with a poor pregnancy outcome for the baby.³
• Progression of microvascular complications including retinopathy and nephropathy: poor glycaemic control in the first trimester and pregnancy-induced or chronic hypertension are independently associated with the progression of retinopathy.⁸ Worsening nephropathy can affect maternal blood pressure and nephropathy with superimposed pre-eclampsia is the most common cause of pre-term delivery in women with diabetes.²

Increased risk of obstetric complications

• Pregnancy-induced hypertension: women with type 2 diabetes are at increased risk of hypertension during pregnancy.⁹
• Thromboembolism rates are higher.
• Premature labour: babies are 5 times more likely to be delivered before 37 weeks.
• Spontaneous abortion rates are higher in women with pre-gestational diabetes.⁶
• Obstructed labour: in the Confidential Enquiry twice as many singleton babies were macrosomic (had a birth weight of ≥ 4000g) compared to the general maternity population. 8% of babies had shoulder dystocia (compared to 3%).³
• Polyhydramnios is more common in pregnancies where the women has pre-existing diabetes.
• Maternal infection is more likely to occur.
• Caesarean section: the Confidential Enquiry found a 67% caesarean section rate compared to 22% in the general maternity population.³

Increased risk of fetal and neonatal complications

• Late intrauterine death/stillbirth: the Confidential Enquiry showed a fivefold increased risk of stillbirth.³
• Fetal distress can occur during labour.
• Congenital malformation: neurological and cardiac abnormalities are particularly common. A twofold increased risk of congenital anomaly was found in the Confidential Enquiry.³
• Fetal macrosomia and its associated complications can occur.
• Hypoglycaemia and postnatal adaptation complications are more common in babies born to mothers with pre-existing diabetes.¹
• Respiratory distress syndrome is more likely.
• Jaundice is more common.
• Birth injury: babies of women with diabetes were 10 times more likely to have Erb's palsy in the Confidential Enquiry (risk increased in a macrosomic baby who may go through a difficult delivery).³
• Increased perinatal mortality: the enquiry showed a threefold increased risk of perinatal mortality (i.e. death within the first month of life).³

The focus should be on information, advice and support to help reduce the risks of adverse pregnancy outcomes for the mother and the baby. A review of the woman's diabetes should be conducted before pregnancy to include glycaemic targets, glucose monitoring, medication and screening for complications. Women planning to become pregnant should be offered a structured education programme if they have not previously attended one. These include 'Dose adjustment for normal eating (DAFNE)' for type 1 diabetes, 'Diabetes education and self management for ongoing and newly diagnosed type 2 diabetes (DESMOND)' and X-PERT for type 2 diabetes (see Internet and Further Reading section).

NICE advises the following:

1. Give advice about the avoidance of unplanned pregnancies. This should be given regularly from adolescence.
2. Give advice about good glycaemic control before conception and during pregnancy to reduce the risks of stillbirth, miscarriage, congenital malformation and neonatal death (note they are not totally eliminated by good glycaemic control).
   • The aim is to maintain HbA1c below 6.1% if that can be safely achieved. Any reduction towards 6.1% is likely to reduce the risk of congenital malformations.
   • Women with HbA1c above 10% should be strongly advised to avoid pregnancy.
   • As well as self-monitoring of blood glucose, HbA1c testing should be offered monthly.
3. Discuss how diabetes affects pregnancy and how pregnancy affects diabetes, including:
   • The role of diet, weight and exercise: women with diabetes who are planning to become pregnant and have a Body Mass Index > 27 kg/m² should be offered advice on how to lose weight (in accordance with the NICE obesity guidelines).¹¹
   • Risks of hypoglycaemia and its unawareness during pregnancy.
   • Effects of nausea and vomiting on glycaemic control.
   • Increased risk of having a large for gestational age baby and the possible complications of this (birth trauma, induction of labour, caesarean section).
   • Diabetic retinopathy and the importance of assessment for this before pregnancy. Retinal assessment should be offered at the first pre-conception appointment (if it has not taken place within the last 6 months). It should then be offered every year if no retinopathy is found.
   • Diabetic nephropathy and the importance of assessment for this before and during pregnancy. This should include a measure of microalbuminuria and serum creatinine/eGFR. If serum creatinine is ≥ 120 micromol/litre, or the eGFR is < 45 ml/minute/1.73 m², a referral should be made to a nephrologist before contraception is discontinued.
   • Why it is important to achieve good glycaemic control for the mother during labour and birth and the importance of early feeding of the baby to reduce the risk of neonatal hypoglycaemia.
   • The possibility of admission to the neonatal unit for the baby during the neonatal period due to transient morbidity.
   • The risk of the baby developing obesity and/or diabetes in later life.
4. Discuss that the risks associated with pregnancy increase with the duration of the diabetes.
5. Women should be advised that they will need frequent contact with health professionals during their pregnancy.
6. Women with diabetes who are planning to become pregnant should take 5 mg folic acid daily until 12 weeks gestation to reduce the risk of neural tube defects.
7. Ketone testing strips should be offered to women and they should be advised to test for ketonuria or ketonaemia if they become hypoglycaemic or unwell.

In addition, it may be good practice to also discuss:

• Smoking cessation advice and support should be given as appropriate.
• Advice on reducing or cutting down alcohol should be given as appropriate.
• Documentation of the care and counselling given should be carried out.
• Consider referral of the woman to a preconception diabetes clinic if available, or to their local diabetes care team. Contraception should be continued until the woman is seen.
• Methyldopa could be consider if antihypertensives are still needed. Labetolol and nifedipine can also be used.² Diuretics and beta-blockers are not advised in pregnancy and should be discontinued/changed.
• Explanation of the benefits of breastfeeding (improved blood glucose control, easier weight loss) should be discussed.

• Metformin should be used as an adjunct or alternative to insulin in the pre-conception period and during pregnancy, when the likely benefits from improved glycaemic control outweigh the potential for harm.
• All other hypoglycaemic agents should be discontinued before pregnancy and insulin substituted.
• The rapid-acting insulin analogues (aspart and lispro) do not seem to adversely affect pregnancy or the health of the fetus or newborn baby.
• There is insufficient evidence about the long-acting insulin analogues during pregnancy. Isophane insulin (NPH insulin) is the first choice.
• Angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists should be stopped before conception or as soon as pregnancy is confirmed. They should be substituted for alternative antihypertensives that are known to be safe in pregnancy.
• Statins should be stopped before pregnancy or as soon as pregnancy is confirmed.

Women with diabetes who are pregnant should be offered immediate contact with a joint diabetes and antenatal clinic. They should be seen every 1-2 weeks during pregnancy by the diabetes care team.
They should receive routine antenatal care as per NICE guidelines.¹² In addition to this, there is some additional monitoring and care for women with pre-existing diabetes.

Glycaemic control and monitoring

• If this can be safely done, the aim is:
  • To keep fasting glucose between 3.5 and 5.9 mmol/litre
  • To keep 1-hour postprandial blood glucose below 7.8 mmol/litre
• HbA1c should not be used routinely to assess glycaemic control in the 2nd and 3rd trimesters.
• Advise women to test fasting blood glucose and 1-hour postprandial levels after every meal during pregnancy.
• Women on insulin should also test their blood glucose before going to bed.
• Women with type 1 diabetes should be offered ketone testing strips and they should be advised to test for ketonuria or ketonaemia if they become hypoglycaemic or unwell.

Management of diabetes

• Rapid acting insulin analogues have advantages over soluble human insulin in pregnancy and their use should be considered.
• Women on insulin should be given concentrated glucose solution to treat hypoglycaemia. Women with type 1 diabetes should also be given glucagon. Partners and families should also be advised on how to treat hypoglycaemia.
• Continuous subcutaneous insulin infusion should be considered if glycaemic control is not adequate.

Screening for diabetes complications

Retinal assessment:

• This should be offered to women with pre-existing diabetes at their first antenatal clinic appointment if it has not been performed in the last 12 months.
• If any diabetic retinopathy is present, an additional retinal assessment should be offered at 16-20 weeks.
• Assessment should be offered again at 28 weeks if the first assessment was normal.

Renal assessment:

• This should be arranged at the first contact in pregnancy if it has not been carried out in the preceding 12 months.
• If serum creatinine is ≥ 120 micromol/litre or if total protein excretion is > 2 g/day, consider referral to a nephrologist.
• eGFR should not be used during pregnancy.
• Thromboprophylaxis should be considered in women with proteinuria > 5 g/day.

Screening and monitoring of the fetus

• A scan should be offered at 7-9 weeks to confirm viability and gestational age.
• Women with diabetes should be offered antenatal examination of the four-chamber view of the fetal heart and outflow tracts at 18-20 weeks.
• Ultrasound monitoring of fetal growth and amniotic fluid volume should be performed every 4 weeks from 28 to 36 weeks.
• At 38 weeks, regular (weekly) tests of fetal well-being should be offered to women with diabetes who are awaiting spontaneous labour. (These may include CTGs or biophysical profiles).

• Preterm labour:
  • If steroids are given for fetal lung maturation, additional insulin may be needed by the mother and they should be closely monitored.
  • Betamimetic drugs should not be used for tocolysis in women with diabetes.
• Women should be advised to give birth in hospitals where advanced neonatal resuscitation facilities are continuously available.
• At 38 completed weeks, women with a normally grown fetus should be offered elective birth through induction of labour or elective caesarean section if indicated.
• If the fetus is macrosomic, the woman should be informed of the risks and benefits of vaginal birth, induction of labour and caesarean section.
• Blood glucose should be monitored hourly through labour and birth and should be kept between 4 and 7 mmol/litre.
• If blood glucose cannot be kept between 4 and 7 mmol/litre, an intravenous infusion of insulin and dextrose is recommended.
• If a women has type 1 diabetes, consider an intravenous infusion of insulin and dextrose from the onset of established labour.

• The baby should only be admitted to a neonatal intensive care unit if there is a specific complication (e.g. hypoglycaemia, respiratory distress, signs of cardiac decompensation, neonatal encephalopathy).
• Babies should feed as soon as possible after birth (within 30 minutes) and then every 2-3 hours until pre-feed glucose levels are at least 2 mmol/litre.
• Blood glucose testing should be carried out routinely in babies of women with diabetes at 2-4 hours after birth.
• Test blood glucose in babies who show signs of hypoglycaemia (abnormal muscle tone, level of consciousness, fits or apnoea) and treat with intravenous dextrose as soon as possible.
• Babies should have an echocardiogram if they should clinical signs associated with congenital heart disease or cardiomyopathy.
• Babies should not be discharged from hospital care until they are at least 24 hours old, they are maintaining blood glucose levels and are feeding well.

• If a woman is treated with insulin, their insulin should be reduced immediately after birth and blood glucose levels monitored to find the appropriate dose. They are at an increased risk of hypoglycaemia and should be warned about this and how to treat it. (When the placenta has been delivered, maternal insulin sensitivity improves. The insulin infusion rate is likely to need reducing by up to 50% and blood glucose levels should be monitored closely. Pre-pregnancy insulin doses are likely to be required except if the women is breastfeeding, when the insulin requirements will be up to 30% less.^9,13)
• Breastfeeding affects glycaemic control.
• Women with type 2 diabetes who are breastfeeding can resume or continue to take metformin and glibenclamide immediately after birth. Other oral hypoglycaemics should not be used.
• Any drugs for the treatment of complications of diabetes that were discontinued because of safety reasons during pre-conception/pregnancy should continue to be avoided.
• Usual routine diabetes care arrangements should be recommenced.
• Women should be reminded of the importance of contraception and the need for pre-conception care when planning future pregnancies.

A recent commentary in the BMJ¹⁴ has mentioned the following points concerning the NICE guidelines for women with pre-existing diabetes who are pregnant or planning to become pregnant:

• That maintaining HbA1c below 6.1% during the pre-conception period is an optimistic recommendation given that two-thirds of women in the Confidential Enquiry report had HbA1c greater than 7%.^3,14 The author suggests that this may have resource implications because significant structured education programmes and possible subcutaneous insulin infusion pumps may be needed.
• The author also comments on the recommendation to offer delivery at 38 weeks to all women with diabetes. They state that there is limited evidence to support this and that this is likely to be a significant change in practice for many.