1. Risk of fetal malformation
Maternal illness
Risk of fetal malformation

2. Maternal illness Key areas
Does the condition itself produce risk?
Does illness presenting during pregnancy produce risk?
Risks of treatment v risk of disease

3. Pre-existing disease and risk of malformation
Diabetes
Respiratory disease
Renal disease
Neurological disease
Hypertensive disease
Connective tissue disease
Endocrine disease
Haematological disease

4. Diabetes Rate of major malformations 41.8 per 1000 (CEMACH 2005)
Excess of neural tube defects
Excess of congenital heart defects
Disproportionately high rate of conotruncal abnormalities
Type 1 and Type 2 diabetes

5. Diabetes
Clear relationship between degree of periconception control and malformation rate
Near linear relation between HbA1c and risk malformation
Mechanism of production of malformation not simple
Both hyper and hypoglycaemia may be involved

6. Endocrine disease
Undiagnosed hypothyroidism in the first trimester and microcephaly
Is it real?
Fetal thyrotoxicosis
Rare but preventable cause of hydrops
Fetal goitre
Differential diagnosis of neck mass

7. Fetal goitre

8. Respiratory disease Asthma Cystic fibrosis Pneumonia
No known link between disease and malformation
Cystic fibrosis
Other than risk CF, no obvious additional risk from respiratory problems of disease itself
Pneumonia
Exclude VZV, HIV

9. Renal disease
No data that links renal disease itself with increased risk of congenital malformation
Specific causes of renal disease may increase risk fetal malformation
Adult polycystic disease
Familial renal dysplasia
Chronic pyelonephritis/reflux and family history
Apert’s disease and other rare genetic causes
Always make sure you know aetiology of renal disease

10. Neurological disorders
Epilepsy
Unless genetic or syndromal cause, epilepsy itself does not increase risk
Watch for rare causes such as Neurofibromatosis, tuberosclerosis

11. Neurological disorders
Multiple sclerosis
Muscular dystrophies
Neurodegenerative disease
Other than genetic recurrence risks no known association

12. Haematological disease
Haemoglobinopathies
Allo-immune disease
Cancer

13. Haemoglobinopathy
Differential diagnosis of hydrops/ascites

14. Allo-immune disease
Differential
Hydrops
Brain malformation

15. Connective tissue disease
Rheumatoid arthritis
SLE
Behcet’s disease
Sjogren’s syndrome

16. Anti-RNA antibodies Ro and La
Antibodies most likely where SLE or Sjogren’s syndrome or where unspecified disease
Risk of congenital heart block
2% of anti-Ro, 3% if both
Up to 40% mortality in first year
Small risk structural disease

17. New maternal illness during pregnancy
Syphilis
Viral infection
Various congenital syndromes
Conditions causing hypoxia
Risk of acquired cerebral malformation
Risk of ischaemic lesions (gut, renal)

18. Therapeutic drugs and malformation
What data is available from animal studies and how applicable is this?
Are there theoretical reasons why the drug might be harmful even if no data?
What are the human data and how was it collected?
Are there alternatives that might be safer?
What are the risks to mother and fetus of stopping/changing?

19. Examples of bad science
Steroids and cleft
Animal work, wrong steroid, placental barrier
Metformin
Never proven risk, blanket ban may have actually increased risk in type 2 diabetes
Anticonvulsants
Reassuring animal work not translated to human studies

20. Consequences of stopping
ACE inhibitors and diabetic nephropathy
Antithyroid medication
Anti-cytokine agents in SLE or asthma
Immunosuppressants and transplant

21. Maternal disease and malformation
Rarely directly implicated
Ensure know aetiology of individual disease
Interaction with therapy