This document discusses the importance and applications of genetic counseling in modern obstetrics. It outlines several key points: 1. Genetic counseling should be provided to all pregnant women to help them understand risks of various genetic disorders and recurrence rates to help make informed decisions. 2. Common indications for genetic counseling include advanced maternal age, abnormal screening tests, family history of genetic disorders, and previous children with genetic conditions. 3. Genetic counseling helps evaluate risks of conditions like chromosomal abnormalities, birth defects, genetic diseases based on family history and test results. It allows discussing options like prenatal diagnosis. 4. Emerging tools like non-invasive prenatal testing are improving detection rates of conditions like Down

1. Genetic Counseling in
Modern Obstetrics
Dr. Sharda Jain
Director :-
Sec General : Delhi Gynae Forum

3. Teacher

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 child swap case
 Identification profiling - theft & rape
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 Property dispute Cases
 Immigration /Visa purpose
 Genetic Test - Anccesity Services

6. Genetic Predisposing Test
 25 chronic disease
 7 types caners
 Diabetes type 1 & 2
 Migraine
 Obesity

7. Background
 Genetics: Role in virtual congenital malformation disorders
 - Causation
- Recurrence Rate
- Carrier State
- Management
Each of us carry at least 20 harmful
genes !!!
Future counseling will be routine

12. H/O poly hyd.
In 2 preg.
Club foot
Myotonia

13. Myopathic facias Myopathic facias

16. Still birth with talipes + Meningo

17. Obstetric load
 3-4% all births associated with major congenital
malformation
 1 in 13 conceptus has chromosomal abnormality
 50% 1st
trimester abortions have chromosomal
abnormality
 0.2% babies born with balanced chromosomal
rearrangements
 5.6 & 11.5% still births & neonatal deaths associated
with chromosomal defects

18. No scientific field has greater
impact of Genetics on clinical
practice than Obstetrics !!!

19. Basic knowledge of Genetics
essential in modern Obstetrics

20. Some Common Disorders / RR
Case Histories
Disorder Mode of
Inheritance
Recurrence
risk
Method of prenatal diagnosis
ß – thalassemia Autosomal
recessive
25% Mutation detection
Sickle cell
disease
Autosomal
recessive
25% Direct detection of mutation
Spinal
muscular
Atrophy
Autosomal
recessive
25% Mutation detection
Cystic Fibrosis Autosomal
Recessive
25% Mutation detection

21. Disorder Mode of
Inheritance
Recurrence
risk
Method of prenatal
diagnosis
Duchenne
Muscular
Dystrophy
X- linked
recessive
25% of all children
or
50% of male
children
Mutation detection
Achondroplasia Autosomal
dominant
50% if one parent
affected
Mutation detection
Neural Tube
defect
Unknown 3-5% after one
10% after two
Ultrasound / a FP

22. Objectives of good counseling
Need of GC extended to all pregnant women
 Help family comprehend medical facts about disease
 Emphasize role of heredity in occurrence & risk of
recurrence
 Elaborate options for dealing with RR
 Help choose appropriate course of action in view of
family goals
 Help family members to accept disorder or its RR
 PGD

23. Indications of GC in Obstetrics
 Advanced maternal age
 Abnormal maternal serum screening test result
 Abnormal USG evaluation during pregnancy
(fetus/ amniotic fluid)
 Previous fetus / child with genetic disorder /
CMF/ MR
 Family history of genetic disorder
 Maternal disorders associated with increased
risk of fetal CMF or exposure to teratogens
 Consanguinity
 Bad obstetric history (RSA, Unexplained IUD or
still birth & NND)

24. Common areas for Genetic
Counseling in obstetric practice

25. Pre-conception counseling
 Ideal time for GC in Obstetrics
 Opportunity to screen & discuss
conditions that can affect pregnancy
outcome

26. Screening for Common genetic
disorders in community
 USA: Tay Sachs ds, Sickle cell anm & Thalassemia
 India: Thalassemia
 Couples counseled about reproductive alternatives
- prenatal diagnosis
- artificial insemination
- deferral of childbearing
1st Problem
3 case studies

27. Carrier state can be diagnosed
in Delhi
 Thalassemia
 Sickle cell dis
 Cystic Fibroids
 Spinal Muscular Atrophy (SMA)
 Duchene muscular dystrophy
 Haemophilia
 Achondroplasia

28. Advanced parental age
 Maternal age: increased risk of chromosomal
abnormality (Trisomy 13, 18, 21, 47XXY, 47XXX)
 Paternal age: increased risk of Autosomal dominant, X-
linked recessive Ds
2nd
Problem

29. Screening for Major Fetal malformation
 All pregnant women: 3-4% risk of CMF in fetus
 Routine screening by USG at 16-18 weeks: Detection
rate 50-75%
 Sensitivity 53-75% in low risk women
 Component of routine antenatal care
3rd
Problem

30. Soft markers for Fetal aneuploidy
4th
Problem
NT
NB
Echogenic Bowel
Echogenic heart focus
Short humerus
Short femur
Choroid Plxus Cyst
Pyelectasis

31. 4th
Problem
Down syndrome
Patau Syndrome
Edward Syndrome

32. Screening for Chromosomal
aneuploidy
 Each pregnancy: 0.6% risk;
 Commonest Trisomy 21
 Dual test / Triple test offered to all pregnant
women
 Risk of trisomy calculated by computer program
 Screen +ve (risk above specified cut-off):
Offered prenatal diagnosis
 Detection rate: 75-89%
5th
Problem

33. “FASTER” TRIAL
NEJM 2005
First- and Second-Trimester Evaluation
of Risk Research Consortium trial
 First trimester - 85 - 87 % detection rate
 Quadruple test – 81 % detection rate
 Triple test – 69% detection rate
 Sequential test – 95 -96 % DR
Earlier is clearly better

34. Policy to sort out which baby
affected
 Fish test
 Culture for karyotyping
< 1 : 50
> 1: 1500
50 : 1500

35. What laboratory test
Q1.Only FISH ?
FISH and culture ?
case study
---------------------------------------------------------------
Q2.---Does a chromosomal analysis suffice
for all genetic disorders ?
 Molecular analysis for single gene disorders
 Enzyme testing for biochemical disorders
 Amniotic fluid analyte testing like CAH, urea cycle
disorders

36. Case History
Positive triple test
AFP – 0.59 MoM
uE3 – 1.10 MoM
HGG –3.57 MoM
Triple risk for DS – 1 :130
USG at 15 wks:
NFT – 1.2mm,
DV flow - normal
27 yrs
17 weeks gestation
FISH analysis - normal

37.  Unbalanced
chromosomes in the
fetus
 Not compatible with
normal phenotype
 46,XX,der(5)t(5;8)
(p13;q22)
 Missed if karyotype not
performed
Culture remains GOLD Standard
FISH + culture performed together

38. Non – Invasive prenatal
genetic testing for fetal
Down Syndrome- the
NIFTY test

40. Comparison of prenatal screening any
diagnosis tests for fetal Down Syndrome
Method Detection
Rate
Missed
Diagnosis
False
Positive
Rates
Limitations
Amniocentesis 100% 0% 0% 0.5% abortion risk
Done after 19 weeks
Chorionicc Villus
sampling (CVS)
100% 0% 0% 0.5% abortion risk
Done in 11-13 week
First Trimester
Combined screening
(OSCCAR)
90% 10% 5-7% Must be done in
11-13 week
Mid- Trimester
maternal serum
65% 35% 5-7% Must be done in
14-20 week
NIFTY >99% <1% <1% Can be done any time
after 12 week

41. Previous child with Down’s syndrome
 F/H +ve: Increased risk upto 3rd
degree relative
 R/R depends on Karyotype of affected child
- Trisomy: R/R 1% above maternal age specific risk
- Translocation: Mother carrier- 15% (100% if t 21;21)
Father carrier - 5%
De novo - 2-3%
 Amniocentesis offered to all at 16-18 weeks
5th
(B) Problem

42. Previous child with aneuploidy
 R/R usually < 1%
 Karyotyping of parents only if structural abnormality of
chromosomes like translocation or duplication or deletion
in child
 Exact counseling depending on type of abnormality
detected
 Prenatal diagnosis available
 Extended family counseling if a parent found to be a
carrier of a balanced structural rearrangement
5th
(A) Problem

43. Previous child with NTD
 Commonest congenital malformation (1/1000 live births),
incidence higher in North India
 R/R: - 3-5% after 1 affected child
- 10% after 2 affected children
- 25% after 3 affected children
 Correct diagnosis important for proper counseling (R/o
monogenic syndromes, chromosomal ds &
environmental factors)
 MSAFP & USG at 16-18 weeks for diagnosis
5th
(c) Problem

45. Previous child with mental retardation
 Prevalence of MR in general population: 2-3%
 R/R varies from 0-50% depending on cause of MR
(identified in 40-60% cases)
 Associated malformations suggest a genetic etiology
 No cause known: give empiric figures (5-7%)
 R/R modified according to associated features
 Both parents normal, one has affected sibling: 2.5%
 Both parents normal but one affected child: 12.5%
5th
(D) Problem

46. Recurrent abortions
 Incidence: 0.8% -1% couples
 Recombinations & abnormal segregation produce gametes
with partial trisomy / monosomy
 Karyotype of couple advised after ruling out non-genetic
cause
 Risk of RSA in translocation carriers: 20-30%
 Risk of RSA in carriers of pericentric inversion: 40-50%
 Risk more if previous baby with CMF & chromosomal
abnormality
 Risk more if mother is a carrier
7th
Problem

47. Counseling in carriers of
chromosomal rearrangements
 Explain risk of abortion, liveborn with chromosomal
imbalance & normal liveborn
 Need for CVS / amniocentesis
 USG for fetal malformations
 Siblings of carriers offered karyotyping before
pregnancy

48. Karyotyping products of conception
How important it is ??
(Chrosomes 13,18,21,X& y)
 Only indicated in RSA, may give idea of possible
chromosomal rearrangement in parents
 Karotyping in couple more informative
 Absence of structural chromosomal abnormality
does not rule out possibility of chromosomal
rearrangement in parents

49. Still birth
 Incidence of chromosomal abnormality 10 times (5.6%)
compared to live births (0.6%)
 Fetal autopsy ,chromosomal analysis, radiography &
clinical photography must be done in all
 Important for providing more definitive cause of loss
and R/R for future pregnancy
8th
Problem

50. Polyhydramnios & oligohydramnios
 Polyhydramnios associated with structural abnormality in
10-20% cases
 Incidence of chromosomal abnormality: 3.2%
 Karyotype recommended if polyhydramnios associated
with structural abnormality
 Oligohydramnios associated with aneuploidy & fetal
malformations (renal agenesis, renal dysplasia, post
uretheral valve)
9th
A. Specific Condition

51. Early onset IUGR
 High risk pregnancy: 5% SGA have chromosomal
abnormality
 Indication for chromosomal studies
 25-35% fetus with chromosomal abnormality have no
structural anomaly on USG except IUGR
9th
B. Specific Condition

52. USG detected malformation
 Targeted scan for associated malformations, Fetal
ECHO, Fetal karyotyping essential
 Prognosis depends on type & severity of abnormality,
associated malformation & chromosomal abnormality
(1/3rd
cases)
 Dilemma about continuation of pregnancy: Careful
counseling about diagnosis, prognosis & future
implications
 Fetal autopsy after termination
10th
Problem

53. Prenatal diagnosis
 Choice should be personal based on non-directive
counseling
 Couple informed about all options
 Counsel about risk associated with PND procedures
 Discuss limitations & implications of test results
 Discuss reproductive options before offering tests
 PND only after written informed consent
 Precise mutation/ defect should be demonstrated in
proband before attempting PND

54. Take home message…
Gynaecologist have to know basics in GC
 All pregnancy need GC
 Increased public knowledge & expectations
with introduction of triple marker screening,
TIFFA & access to prenatal diagnosis
 Failure to prevent birth of abnormal baby: Medico-legal
consequences
 Future of genetics in obstetrics:
Genetic testing will become commonplace & will replace
current diagnostic tests
 GC in Infertility Male & Female

55. Torch Infection
Through Case Studies
Harmonse Drugs
X-Ray/CT/MRI
Other Viral Infection
eg Chicken Pox
Case Study
Specific Medical
disorder
Safety / Risk
Eg HIV,TB, epilepsy

56. Thank You