1. A Simple Question

2. Mrs. M, aged 32 years, Pre pregnancy counseling My first baby boy was healthy at birth, was told to have heart disease and died on 14 th day of life….I am scared of my next baby having the same problem “ ” And she asks you

3. Mrs. M, aged 32 years, Pre pregnancy counseling Will this recur again? “ ” What would your response be?

4. Recurrence risk – determination ASK few relevant questions – What kind of CHD was the baby having? She doesn’t know – Does she or her partner have CHD? Mother had a VSD, repaired, asymptomatic now – Do they have any family history of CHD? No other family member – Are they a consanguinous couple? No Why should you ask these

5. What kind of CHD was the baby having? Does she or her partner have CHD? Do they have any family history of CHD? Are they a consanguinous couple? Recurrence risk depends on the type

6. Recurrence Risk - Based on type of defect Unaffected parentsAffected parents 1 child affected >2 child affected MotherFather VSD 3 %10 %9 -10 %2-3 % ASD 2-3 %8 %6 %1-2 % TOF 2 %8 %2-5 %1-2 % CoA 2 %6 %4 %2-3 % AS 2 %6 %12 -20 %5 % PS 2 %6 %6-7 %2 % HLHS 3 %10 %NR AVSD 3-4 %NR10-14%1 % PA 1 %3 %NR TA 1 %3 %NR TGA 1-2 %5 %NR L-TGA 5-6 %NR Ebsteins 1 %3 %6 %NR Heteroplexy 5-6 %NR OVERALL1-6 %2-10 %2- 20%1-5 %

7. CHD Recurrence Risk MotherFather One Siblings More than one sibling Risk No Yesno1-6 % No Yes 10 % YesNo 5-10 % NoYesNo 1-5 %

8. If Many Family Members have CHD Familial recurrence is high Many CHD in family - recurrence – Concordance (same type of CHD) – 37% – Any CHD – 47%

9. Recurrence risk – determination ASK few relevant questions – Was the baby normal looking ? Photograph ? Yes – Did the baby have any other abnormalities? No – Are you having diabetes? No she doesnt – Are you having epilepsy, and taking medications? No – Were you taking any medications? No Why should you ask these

10. Of all CHD 8 – 10 % Chromosomal Down – most common (40-50%) Velocardiofacial syndrome (80%) Edwards syndrome

11. Other genetic defects CNV - Copy number variations Mendelian syndromes – Alagille syndrome – Holt Oram syndrome – Noonan syndrome

12. Non syndromal single gene disorders 30 genes detected Autosomal dominant Detection by – Linkage analysis – Candidate gene approach Most common – NKX2 -5 – GATA4

13. Environmental factors Diabetes mellitus – 5 times risk – Before 7 weeks – Why – gene expression, oxidative stress – Defective primary cardiogenesis Heterotaxy ASD VSD Outflow tract abnormalities

14. Any Drugs Antiepileptics Warfarin Thalidomide Antidepressants

15. Recommendations to decrease risk Folic acid supplements Rubella vaccination preconception Control of diabetes / phenylketonuria Antiepileptics – Monotherapy – Least dosage Avoiding medication use – in early pregnancy – Taking only if it’s a must

16. The Last Line in Counseling The risk of adverse outcome is NEVER ever more than the chances having of a good outcome And this principle of life is the basis of any adverse outcome counseling

17. While there is life…there is hope