Diabetes in pregnancy

This article deals with pregnancy in patients with pre-existing diabetes. See also the separate Gestational Diabetes article.

There are also articles on Management of Type 1 Diabetes, Type 2 Diabetes Treatment and Management, and Self-monitoring in Diabetes Mellitus.

How common is diabetes in pregnancy? (Epidemiology)

• Diabetes is the most common pre-existing medical disorder complicating pregnancy in the UK.

• Up to 5% of women giving birth in England and Wales have either pre-existing diabetes or gestational diabetes.¹

• The number of people with type 1 diabetes and the prevalence of type 2 diabetes amongst women of child-bearing age are increasing.

• Pregnancies of women with diabetes are regarded as high-risk for both the woman and the baby.²

• Of women who have diabetes during pregnancy, it is estimated that approximately 87.5% have gestational diabetes, 7.5% have type 1 diabetes and the remaining 5% have type 2 diabetes.¹

Possible complications^{3 4}

Diabetes in pregnancy is associated with risks to the woman and to the developing fetus.¹

• Miscarriage, pre-eclampsia and preterm labour are more common in women with pre-existing diabetes. Diabetic retinopathy can worsen rapidly during pregnancy.

• Stillbirth, congenital malformations, macrosomia, birth injury, perinatal mortality and postnatal adaptation problems (eg, hypoglycaemia) are more common in babies born to women with pre-existing diabetes.

Pre-conception care and good glucose control before and during pregnancy can reduce these risks.

Increased risk of complications of diabetes

• Ketoacidosis may occur during the pregnancy.

• Hypoglycaemia.⁵

• 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. Worsening nephropathy can affect maternal blood pressure, and nephropathy with superimposed pre-eclampsia is the most common cause of preterm delivery in women with diabetes.

Increased risk of obstetric complications

• Pregnancy-induced hypertension: women with type 2 diabetes are at increased risk of hypertension during pregnancy.⁶

• Thromboembolism rates are higher.

• Premature labour: babies are five times more likely to be delivered before 37 weeks.

• Spontaneous abortion rates are higher in women with pre-gestational diabetes.

• Obstructed labour: associated with increased risk of macrosomia and shoulder dystocia.^{7 8}

• Polyhydramnios is more common in pregnancies where the woman has pre-existing diabetes.

• Maternal infection is more likely to occur.

• Caesarean section.⁹

Increased risk of fetal and neonatal complications

• Late intrauterine death/stillbirth.

• Fetal distress can occur during labour.

• Congenital malformation: neurological and cardiac abnormalities are particularly common.

• 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.

• Respiratory distress syndrome is more likely.

• Jaundice is more common.

• Birth injury eg, Erb's palsy (risk increased in a macrosomic baby who may go through a difficult delivery).

• Increased perinatal mortality.

Pre-conception care¹⁰

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.

The National Institute for Health and Care Excellence (NICE) advises the following:¹

• Give advice about the avoidance of unplanned pregnancies. This should be given regularly from adolescence.

• Contraception: women with diabetes can use oral contraceptives if there are no standard contra-indications to their use.

• Give advice about good glycaemic control before conception and during pregnancy, to reduce the risks of stillbirth, miscarriage, congenital malformation and neonatal death:
  

  • Agree individualised targets for self-monitoring of blood glucose with women who have diabetes and are planning to become pregnant, taking into account the risk of hypoglycaemia. Advise women with diabetes who are planning to become pregnant to aim for the same capillary plasma glucose target ranges as recommended for all people with type 1 diabetes.

  • Offer up to monthly measurement of HbA1c levels for women with diabetes who are planning a pregnancy.

  • Advise women with diabetes who are planning to become pregnant to aim to keep their HbA1c level below 48 mmol/mol (6.5%), if this is achievable without causing problematic hypoglycaemia. Any reduction in HbA1c level towards the target of 48 mmol/mol (6.5%) is likely to reduce the risk of congenital malformations in the baby.

  • Advise women with diabetes whose HbA1c level is above 86 mmol/mol (10%) not to get pregnant because of the associated risks.

• 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 who 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 impaired awareness 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 previous six 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 μmol/L, 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.

• Discuss that the risks associated with pregnancy increase with the duration of the diabetes.

• Women should be advised that they will need frequent contact with health professionals during their pregnancy.

• Women with diabetes who are planning to become pregnant should take 5 mg folic acid daily until 12 weeks of gestation, to reduce the risk of neural tube defects.

• Ketone testing strips should be offered to women, who should be advised to test for ketonuria or ketonaemia if they become hyperglycaemic or unwell.

In addition, it may be good practice also to 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 pre-conception diabetes clinic if available, or to their local diabetes care team. Contraception should be continued until the woman is seen.

• Methyldopa could be considered if antihypertensives are still needed. Labetalol and nifedipine can also be used. 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.

Medication for diabetes and diabetic complications before and during pregnancy¹

• 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 affect pregnancy or the health of the fetus or newborn baby adversely.

• Use isophane insulin (NPH insulin) as the first choice for long-acting insulin during pregnancy. Consider continuing treatment with long-acting insulin analogues (insulin detemir or insulin glargine) in women with diabetes who have established good blood glucose control before pregnancy.

• 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 by alternative antihypertensives that are known to be safe in pregnancy.

• Statins should be stopped before pregnancy or as soon as pregnancy is confirmed.

Antenatal care¹

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

Advise pregnant women with type 1 diabetes to test their fasting pre-meal and one hour post-meal, and to test bedtime blood glucose levels daily during pregnancy.

Offer real-time continuous glucose monitoring (rtCGM) to all pregnant women with type 1 diabetes to help them meet their pregnancy blood glucose targets and improve neonatal outcomes.

Offer intermittently scanned continuous glucose monitoring (isCGM or 'flash') to pregnant women with type 1 diabetes who are unable to use rtCGM or express a clear preference for isCGM.

Consider rtCGM for pregnant women who are on insulin therapy but do not have type 1 diabetes, if:

• They have problematic severe hypoglycaemia (with or without impaired awareness of hypoglycaemia), or

• They have unstable blood glucose levels that are causing concern despite efforts to optimise glycaemic control.

Advise pregnant women with type 2 diabetes who are on a multiple daily insulin injection regimen to test their fasting pre-meal and one hour post-meal, and to test bedtime blood glucose levels daily during pregnancy.

Advise pregnant women with type 2 diabetes to test their fasting and one hour post-meal blood glucose levels daily during pregnancy if they are on diet and exercise therapy, or taking oral therapy (with or without diet and exercise therapy) or single-dose intermediate-acting or long-acting insulin.

Target blood glucose levels
Agree individualised targets for self-monitoring of blood glucose with women with diabetes in pregnancy, taking into account the risk of hypoglycaemia.

Advise pregnant women with any form of diabetes to maintain their capillary plasma glucose below the following target levels, if these are achievable without causing problematic hypoglycaemia: fasting glucose 5.3 mmol/L and glucose levels 7.8 mmol/L one hour after meals, or 6.4 mmol/L two hours after meals.

Advise pregnant women with diabetes who are taking insulin to maintain their capillary plasma glucose level above 4 mmol/L.

Monitoring HbA1c
Measure HbA1c levels in all pregnant women with pre-existing diabetes at the booking appointment to determine the level of risk for the pregnancy.

Consider measuring HbA1c levels in the second and third trimesters of pregnancy for women with pre-existing diabetes, to assess the level of risk for the pregnancy. The level of risk for the pregnancy for women with pre-existing diabetes increases with an HbA1c level above 48 mmol/mol (6.5%).

Do not use HbA1c levels routinely to assess a woman's blood glucose control in the second and third trimesters of pregnancy.

Insulin treatment and risks of hypoglycaemia
Rapid-acting insulin analogues (aspart and lispro) have advantages over soluble human insulin during pregnancy.

Advise women with insulin-treated diabetes of the risks of hypoglycaemia and impaired awareness of hypoglycaemia in pregnancy, particularly in the first trimester. Advise pregnant women with insulin-treated diabetes always to have available a fast-acting form of glucose (eg, dextrose tablets or glucose-containing drinks). Provide glucagon to pregnant women with type 1 diabetes for use if needed.

Offer women with insulin-treated diabetes continuous subcutaneous insulin infusion (CSII) during pregnancy if adequate blood glucose control is not obtained by multiple daily injections of insulin without significant disabling hypoglycaemia.

However, a Cochrane review looking at CSII versus multiple daily injections of insulin for pregnant women with diabetes found that there is currently no evidence to support the use of one particular form of insulin administration over another for pregnant women with diabetes.¹³

Ketone testing and diabetic ketoacidosis
Offer pregnant women with type 1 diabetes blood ketone testing strips and a meter; advise them to test for ketonaemia and to seek urgent medical advice if they become hyperglycaemic or unwell.

Advise pregnant women with type 2 diabetes or gestational diabetes to seek urgent medical advice if they become hyperglycaemic or unwell.

Test urgently for ketonaemia if a pregnant woman with any form of diabetes presents with hyperglycaemia or is unwell, to exclude diabetic ketoacidosis.

Retinal assessment during pregnancy
Offer pregnant women with pre-existing diabetes retinal assessment by digital imaging with mydriasis using tropicamide following their first antenatal clinic appointment (unless they have had a retinal assessment in the previous three months), and again at 28 weeks. If any diabetic retinopathy is present at booking, perform an additional retinal assessment at 16-20 weeks.

Diabetic retinopathy should not be considered a contra-indication to rapid optimisation of blood glucose control in women who present with a high HbA1c in early pregnancy.

Ensure that women who have preproliferative diabetic retinopathy or any form of referable retinopathy diagnosed during pregnancy, have ophthalmological follow-up for at least six months after the birth of the baby.

Diabetic retinopathy should not be considered a contra-indication to vaginal birth.

Renal assessment during pregnancy
If renal assessment has not been undertaken in the preceding three months in women with pre-existing diabetes, arrange it at the first contact in pregnancy. If the serum creatinine is abnormal (120 micromol/L or more), the urinary albumin:creatinine ratio is greater than 30 mg/mmol or total protein excretion exceeds 2 g/day, referral to a nephrologist should be considered (eGFR should not be used during pregnancy). Thromboprophylaxis should be considered for women with proteinuria above 5 g/day (macroalbuminuria).

Preventing pre-eclampsia
NICE advises women at high risk of pre-eclampsia (which includes women with type 1 or type 2 diabetes) to take 75 mg of aspirin daily from 12 weeks until the birth of the baby.¹⁴

Detecting congenital malformations
Offer women with diabetes an ultrasound scan for detecting fetal structural abnormalities, including examination of the fetal heart, at 20 weeks.

Monitoring fetal growth and well-being
Offer pregnant women with diabetes ultrasound monitoring of fetal growth and amniotic fluid volume every four weeks from 28-36 weeks.

Intrapartum care¹

Preterm labour
Diabetes should not be considered a contra-indication to antenatal steroids for fetal lung maturation or to tocolysis.¹⁵ Do not use betamimetic medicines for tocolysis in women with diabetes.

Timing and mode of birth
Advise pregnant women with type 1 or type 2 diabetes and no other complications to have an elective birth by induction of labour, or by elective caesarean section if indicated, between 37+0 weeks and 38+6 weeks of pregnancy. Consider elective birth before 37+0 weeks for women with type 1 or type 2 diabetes if there are metabolic or any other maternal or fetal complications.

Diabetes should not in itself be considered a contra-indication to attempting vaginal birth after a previous caesarean section.

Explain to pregnant women with diabetes who have an ultrasound-diagnosed macrosomic fetus about the risks and benefits of vaginal birth, induction of labour and caesarean section.

Care for the baby once delivered¹

• The baby should only be admitted to a neonatal intensive care unit if there is a specific complication (eg, 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/L.

• 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 IV dextrose as soon as possible.

• Babies should have an echocardiogram if they show 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, are maintaining blood glucose levels and are feeding well.

Postnatal care¹

Women with insulin-treated pre-existing diabetes should reduce their insulin immediately after birth and monitor their blood glucose levels carefully to establish the appropriate dose.

Women with insulin-treated pre-existing diabetes are at increased risk of hypoglycaemia in the postnatal period, especially when breastfeeding. Provide advice to have a meal or snack available before or during feeds.

Women with pre-existing type 2 diabetes who are breastfeeding can resume or continue to take metformin immediately after birth, but should avoid other oral blood glucose-lowering agents while breastfeeding.

Women with diabetes who are breastfeeding should continue to avoid any medicines for the treatment of diabetes complications that were discontinued for safety reasons in the pre-conception period.

Refer women with pre-existing diabetes back to their routine diabetes care arrangements.