Pre-pregnancy counselling

Question 1

What should be covered at the prepregancy consultation?

Answer 1

• Medical and surgical history - to optimise medical conditions prior to pregnancy
• Medication history - optimise medications and check for teratogenicity
• Immunisation history - Check DTP, MMR, chicken pox Hx. If not vaccinated/suboptimal seroconversion for rubella, Hep B, varicella zoster - recommend vaccination prior to pregnancy. Will need flu vaccine if winter and DTP any time from 16 weeks, usually 28-32 weeks pregnancy.
• Document allergies
• Family history and screening for possible heritable diseases / chromosomal abnormalities - to guide couples regarding prepregnancy carrier screening, PIGD, antenatal screening tests
• check smoking and illicit drug use - refer to relevant drugs/alcohol services and provide nicotine replacement to aid cessation
• Physical examination and at minimum height, weight, BMI, pulse and blood pressure for baseline readings
• Address high BMI >30 - dietary advice, minimising weight gain, moderate exercise, bariatric surgery if appropriate
• Dietary advice to minimise exposure to food-borne pathogens, not least high risk food groups for listeriosis, toxoplasmosis and salmonella
• Advise no safe level of alcohol consumption known for pregnancy
• Minimise exposure to toxins/chemicals at home and work
• Travel guidance - avoiding areas with high risk of infection, particularly Zika endemic countries
• Advice re. different options for antenatal care and frequency of visits

Question 2

What medications should be started?

Answer 2

Folic acid 0.4-0.8mg daily from at least 4 weeks prior to conception till 12 weeks. If high risk for NTDs should take 5mg daily (on anti epileptic medication, diabetes prior to pregnancy, family Hx of NTDs).

Iodine 150mcg daily from prepregnancy, till a minimum of 12 weeks gestation.

Consider risk factors for preeclampsia and SGA - good time to counsel re. starting LDA 100-150mg and calcium 1.5g daily from 12 weeks till 36 weeks in pregnancy.

Question 3

What is the benefit of prepregnancy carrier screening?

Answer 3

To test for recessive and X-linked mutations to prevent inheritance by offspring.
1 in 400 couples have a pregnancy with a preventable genetic abnormality, despite being asymptotic themselves.
This is due to 2 carriers of the same mutation being themselves asymptomatic, but producing a homozygous offspring. Though each condition is often rare, there are many hundreds of recessive or x-linked conditions that can be inherited.
Prepregnancy awareness of potential genetic conditions allows discussion of possible reproductive options ideally from prior to conception.

Question 4

What conditions are screened for at prepregancy carrier screening?

Answer 4

Most common autosomal recessive and X-linked disorders:

• cystic fibrosis
• Thalassemia
• Spinal Muscular atrophy
• Fragile X syndrome

An expanded panel can be offered which can screen up to hundreds of different conditions.

Question 5

If both parents test positive for a recessive allele, or the woman has an X-linked condition, what reproductive options are available to them?

Answer 5

• Not having children
• Adoption
• IVF with PIGD
• IVF with donor egg or sperm
• Natural conception with antenatal testing - amniocentesis or CVS
• Natural conception with testing after birth

Question 6

What additional conditions might ashkenazi jews require to be screened at prepregancy carrier screening?

Answer 6

• Tay Sachs disease - lysosomal storage disorder leading to build up of glycosides in lysosomes of neurones
• Niemann Pick disease type A - lysosomal storage disorder
• mucolipidosis type IV - lysosomal storage disorder
• Fanconi anaemia group C - AR or X-linked, inherited bone marrow failure, increased risk cancers incl. AML
• familial dysautonomia - progressive degeneration of the autonomic nervous system and sensory nerves
• Bloom syndrome - small stature, genomic instability and predisposition to cancer
• Canavan disease - progressive neurological disease, demyelination in infancy

Question 7

Who is eligible for funded genetic carrier screening?

Answer 7

• Family hx genetic disorder
• One partner known carrier (e.g. thalasemia trait)
• High risk ethnicities (e.g. ashkenazi jewish descent)

Majority of people are not eligible and will have to self fund.

Question 8

What is the prevalence of carrier status for cystic fibrosis, SMA and fragile X in the general population?

Answer 8

CF = 1 in 35
SMA = 1 in 50
Fragile X = 1 in 332

An Australian study found 1 in 20 self-funded people under going carrier testing were carriers for one of the above conditions.

Question 9

What is expanded genetic carrier screening? What are its benefits and drawbacks?

Answer 9

• It looks at up to 1000 different known mutations
• It can either be by searching specific mutations, or decoding the nucleotide sequences of all 23,000 genes in the human genome.
• This will detect the highest number of possible genetic carriers, BUT also detects variants of uncertain significance and may cause unnecessary anxiety.

Question 10

What are the options/approaches for carrier screening?

Answer 10

• Standard carrier screening vs Expanded carrier screening

- Partner screening vs sequential screening

Question 11

How is thalassemia screened for?

Answer 11

All women should have FBC on booking bloods to check for microcytic anaemia.

Screening with specific assays for haemoglobinopathies (such as HPLC or EPG and haemoglobinopathy DNA testing) should be considered in high probability ethnic or population groups (Mediterranean, middle east, indian subcontinent, African).

Question 12

Compare couple screening to sequential screening? What are the benefits and drawbacks?

Answer 12

Couple screening = both partners are tested simultaneously. If both partners demonstrate carrier status for same condition they are deemed”high risk”. If not they are “low risk”. The individuals will not find out their individual carrier status.

Sequential screening= the woman is screened first for autosomal recessive and X-linked carrier status. If any mutations are detected they are informed so the partner can then be tested. Allows “cascade testing” - where other family members may then come forward for carrier testing knowing they are at higher risk for carrying the tested condition.

Benefits couple screening over sequential =

• Results faster
• Avoids anxiety caused by woman being told has mutation and then waiting for second result
• Fewer couples are identified with an adherent result and thus fewer require genetic counselling

Benefits sequential over couple screening =

• Cheaper as often only 1 partner needs to be tested
• Allows for “cascade testing”
• As individual knows their carrier status, they can then use this information in future relationships

Question 13

What should couples be counselled about carrier screening?

Answer 13

• It may demonstrate a partner has a condition (i.e. homozygous for a specific mutation)
• Not all mutations causing a condition are tested, therefore there is still possibility of any offspring having a condition that has been tested for
• If couple testing it is only valid for the specific couple - it will not apply if they meet a new reproductive partner in the future
• The cost if not eligible for publicly funded in the realm of $400