Pre-existing diabetes in pregnancy

Definition

• This denotes diabetes mellitus type 1 or type 2 present before pregnancy; it is the commonest cause of diabetic embryopathy.
• Diabetic embryopathy is the collective term for congenital malformations and secondary complications caused by maternal diabetes; poorly controlled gestational diabetes can also contribute if hyperglycaemia is present early in pregnancy.

Occurrence & epidemiology

Epidemiology

• The malformation rate is markedly higher than in the general population; in large meta-analyses it did not differ between type 1 and type 2 diabetes and was about 5–6% in each.

Aetiopathogenesis

Risks and pathophysiology

• Diabetic embryopathy develops during organogenesis (up to 8th week) and includes malformations such as neural tube defects, heart defects and caudal regression syndrome.
• In type 1 diabetes, there is an additional risk of ketoacidosis, which can occur even with moderately high glucose levels.

Aetiology and risk factors

• Maternal hyperglycaemia is teratogenic, especially during organogenesis up to about 10 weeks; proposed mechanisms include oxidative and hypoxic stress in the embryo.
• Higher glucose or HbA1c levels are associated with a higher risk of malformation.
• Genetic predisposition, obesity, hypertension and dyslipidaemia can compound the teratogenic effect.

Clinical features

Clinical features and complications

• Typical malformations are neural tube defects, heart defects (particularly outflow tract anomalies), craniofacial anomalies, limb deficiencies and caudal regression syndrome; poor control during organogenesis also raises the risk of miscarriage.
• Poor control later in pregnancy increases the risk of macrosomia, pre-eclampsia, shoulder dystocia and stillbirth; neonates are at risk of respiratory distress, hypoglycaemia, hypocalcaemia, hyperbilirubinaemia and polycythaemia.

Diagnosis

• Prenatally, first-trimester ultrasound and fetal echocardiography allow early detection of malformations.
• Caudal regression syndrome with agenesis of the lower spine is regarded as particularly characteristic of maternal diabetes.

Keep learning in the app

Further reading (selection)

1. StatPearls: Diabetic Embryopathy (NCBI Bookshelf)
2. Ups J Med Sci 2016: The status of diabetic embryopathy (PMC, open access)
3. MSD Manual Professional Edition: Diabetes Mellitus in Pregnancy
4. DocCheck Flexikon, Diabetes mellitus

Cross-references