Preconception Counseling
Medical and Pregnancy History
- Comprehensive Review: Assess previous pregnancy outcomes, chronic medical conditions, surgical history, and family history of genetic disorders.
Smoking and Substance Use Cessation
Smoking Cessation
- Consider nicotine replacement therapy (NRT) if counseling alone is unsuccessful.
Alcohol Cessation
- Abstinence from alcohol is recommended due to risks of:
- Facial abnormalities (e.g., short palpebral fissures, hypertelorism, small eyes, thin upper lip)
- Low birthweight (LBW)
- Small stature
- Low intelligence
- Psychological hyperactivity
- Cardiac lesions, including atrial and ventricular septal defects
Recreational Drug Cessation
- Cease all recreational drug use.
Caffeine Reduction
- Reduce caffeine intake as it may impact conception and increase the risks of miscarriage and low birthweight (LBW).
Supplements
- Folate:
- Recommended dose: 400-500 mcg/day at least 1 month before conception and through the first 12 weeks of pregnancy.
- Reduces the risk of neural tube defects.
- higher dose of folic acid (5 mg daily) is recommended before conception and during pregnancy to reduce the risk of neural tube defects and other complications.
- The indications for 5 mg folic acid include:
- Personal history of neural tube defect or previous child with NTD
- Family history of NTD (first- or second-degree relative)
- Pre-existing diabetes mellitus (type 1 or 2)
- Epilepsy treated with anti-epileptic drugs (especially valproate, carbamazepine, phenytoin, phenobarbital)
- BMI ≥30 kg/m²
- Malabsorption syndromes (e.g., coeliac disease, inflammatory bowel disease, bariatric surgery)
- Haemolytic anaemia
- Women on folate-antagonist medications, e.g.:
- Methotrexate
- Trimethoprim
- Sulfasalazine
- Special Circumstances (consider 5 mg)
- Aboriginal and Torres Strait Islander background (based on increased background risk)
- Smoking during pregnancy (reduced folate levels)
- Multiple pregnancy (e.g., twins or more)
- Iodine:
- Recommended dose: 150 mcg/day during pregnancy and breastfeeding.
- Supports fetal brain development and maternal thyroid function.
Nutrition and BMI Optimization
- Optimize BMI:
- Aim for a BMI within the normal range (18.5-24.9).
- Set a realistic goal to lose 5-10% of body weight prior to conception if overweight or obese.
- Referral: Refer to a dietitian for personalized nutritional guidance.
- Limit fish containing high levels of mercury:
- Shark/flake, marlin, broadbill/swordfish: No more than one serve (100g cooked) per fortnight, with no other fish consumed that fortnight.
- Orange roughy (deep sea perch) or catfish: One serve (100g cooked) per week, with no other fish consumed that week.
Immunizations and Screenings
- Rubella Immunity:
- Check immunity status.
- Administer booster if necessary, advising against pregnancy within 28 days post-vaccination.
- other vaccines:
- Diphtheria, Tetanus, Pertussis (DTP)
- Varicella
- Influenza
- STI Screening:
- Screen for common STIs (chlamydia, gonorrhoea, syphilis, HIV).
- Thyroid Function:
- Check TSH levels, especially if there is a history of thyroid disease or symptoms.
- Vitamin D:
- Assess levels and supplement if deficient.
- Thalassemia Screening:
- Perform if there is an abnormal FBC or the patient belongs to a high-risk group (e.g., Mediterranean, Asian, Middle Eastern descent).
Physical Examinations
- Oral Health: Conduct a dental check-up to identify and treat any potential issues.
- Breast Examination: Perform a clinical breast exam.
- Thyroid Examination: Check for thyroid enlargement or nodules.
- Cardiovascular Examination: assess for murmurs and other cardiovascular anomalies.
- Cervical Screening: Ensure cervical screening is up to date according to Australian guidelines.
Medication Review
Teratogenic Medications to Avoid/Review:
- ACE inhibitors (e.g., enalapril)
- Acne medications (e.g., isotretinoin)
- Alcohol-containing products
- Antibiotics (e.g., tetracycline, doxycycline)
- Warfarin
- Anticonvulsants (e.g., phenytoin, valproic acid, carbamazepine)
- Lithium
- Thyroid medications (e.g., propylthiouracil, carbimazole)
- Thalidomide
Optimizing Health Before Conception
- Chronic Disease Management: Ensure optimal control of chronic conditions such as diabetes, hypertension, and epilepsy.
- Diabetes Mellitus (DM)
- Hypothyroidism
- Epilepsy
- Thrombophilia
- TORCH Infections: Assess risk for
- Toxoplasmosis
- Other (syphilis, varicella-zoster, parvovirus B19)
- Rubella
- Cytomegalovirus (CMV)
- Herpes simplex virus
Specific Infections and Preventive Measures
Toxoplasmosis
- Avoidance Strategies:
- Cat litter: Avoid handling; if necessary, use gloves and wash hands thoroughly afterward.
- Garden soil: Use gloves and wash hands after gardening.
- Raw/undercooked meat and unpasteurized milk products: Ensure thorough cooking and avoid unpasteurized dairy.
- Fruits and vegetables: Wash thoroughly before consumption.
Cytomegalovirus (CMV)
- Prevention:
- Frequent handwashing, particularly after handling diapers or coming into contact with bodily fluids.
- Use gloves when changing nappies, especially for individuals working in healthcare or childcare settings.
Parvovirus B19 (Erythema Infectiosum / “Slapped Cheek Syndrome”)
- Clinical Features:
- Erythema infectiosum: “Slapped cheek” rash, rubella-like rash, arthralgia or arthritis (more common in adults).
- 30-40% of infections are subclinical.
- Transmission:
- Person-to-person contact through respiratory secretions or hand-to-mouth contact.
- Vertical transmission from mother to fetus.
- Complications:
- Risk of spontaneous miscarriage and stillbirth (13% before 20 weeks’ gestation; 0.5% after 20 weeks).
- Associated with fetal hydrops, thrombocytopenia.
Listeriosis
- Pathogen: Listeria monocytogenes (a gram-positive rod capable of replicating at refrigerator temperatures).
- High-Risk Foods:
- Refrigerated, ready-to-eat foods such as deli meats, soft cheeses, pre-packaged salads, and chilled/smoked seafood.
- Unpasteurized milk and dairy products.
- Prevention:
- Avoid foods unless thoroughly cooked or heated to at least 74°C for over two minutes.
- Wash all fruits and vegetables thoroughly.
- Avoid consuming food prepared more than 24 hours ago unless reheated to steaming hot.
- Increased caution for Hispanic women, as they may have a higher incidence of infection.
- Complications:
- Miscarriage, preterm labor, low-birth-weight infants, or infant death.
- Long-term complications: intellectual disability, paralysis, seizures, blindness.
Rubella
- Complications:
- Congenital rubella syndrome, including deafness, cataracts, and cardiac defects.
Psychosocial Assessment:
- Assess psychological well-being, including screening for domestic violence.
- Review social circumstances and available support networks.
Counseling and Education
- Exercise: Recommend at least 150 minutes of moderate-intensity exercise per week.
- Healthy BMI – recommended weight gain 11-16kg
- Antenatal Care: Discuss the importance of early and regular antenatal care to monitor the health of the mother and baby.
Interpregnancy Intervals
- Optimal Timing:
- Educate about the risks associated with interpregnancy intervals of less than 18 months or more than 59 months.
- Emphasize that 2-5 years is the optimal interval to reduce the risk of pre-term birth, low birth weight, and small size for gestational age.
Pre-conception Testing
- Oral Glucose Tolerance Test (OGTT): Recommended for high-risk groups, including women with PCOS.
Reproductive Genetic Carrier Screening
Screen healthy adults pre-conception or in early pregnancy to identify carrier status for serious recessive or X-linked disorders.
Provides couples with quantitative risk (e.g., 1 in 4 for recessive conditions) and informs reproductive choices.
Who to Offer
- All individuals/couples planning pregnancy or ≤ 12 weeks gestation, regardless of family history.
- Higher-risk groups (known family history, specific ethnic backgrounds) should be referred to genetics services for tailored panels
3. Timing
- Ideal: Pre-conception – maximises options (e.g., IVF + PGT-M).
- Acceptable: Early pregnancy (fewer options once results available)
4. Test Types
| Panel | Conditions Included | Typical Indications |
|---|---|---|
| 3-gene (CF, SMA, FXS) | Most common severe childhood disorders; ~1 in 20 Australians carrier of at least one | First-line, now Medicare-funded |
| Ethnic-specific | e.g., Tay–Sachs, thalassaemias | Couples of shared high-risk ancestry |
| Expanded ( > ~200 genes ) | Broad severe early-onset disorders | When comprehensive risk information desired; not Medicare-funded |
- Cystic Fibrosis (CF) Screening – CFTR gene
- autosomal recessive, Mutations in the CFTR gene causing cystic fibrosis.
- Spinal Muscular Atrophy (SMA) Screening -SMN1 gene
- autosomal recessive, Mutations in the SMN1 gene causing spinal muscular atrophy.
- Fragile X Syndrome Screening -FMR1 gene
- X-linked, Expansions in the FMR1 gene causing fragile X syndrome.
5. Pathways
- Sequential: Test woman → if carrier, test partner (adds X-linked coverage).
- Couple (simultaneous): Tests both partners together; preferred for expanded panels.
MBS funding — sequential vs couple (simultaneous) carrier screening
| Pathway | Which partner is rebated? | Relevant MBS item(s) | Genes covered by the rebate | Key conditions | Fine print |
|---|---|---|---|---|---|
| Sequential 1. Test female partner first 2. If she is carrier of CFTR or SMN1, test male partner | Both partners can be rebated, but only if step 1 is positive | 73451 – female (once per lifetime) 73452 – male partner (once per condition per lifetime) | CFTR (CF) SMN1 (SMA) FMR1 (FXS) – female only | Cystic fibrosis, spinal muscular atrophy, fragile X syndrome | • Item 73452 does not apply to FMR1 (FXS) because paternal carrier status does not alter fetal risk. • Male test must be ordered after female result is known. |
| Couple / Simultaneous (both partners tested at the same time) | Only the female partner qualifies for a rebate; male test is private fee | 73451 – female No MBS item for the male when testing is simultaneous | Same three-gene panel | – | Most labs charge an out-of-pocket fee (~A$350–500) for the male test if done concurrently. |
| Expanded (>200-gene) panels | Neither partner is rebated under current MBS | – | Varies by laboratory | Many severe recessive/X-linked childhood disorders | Entirely self-funded (often A$ |
6. Sample & Accuracy
- Blood or saliva sample; high analytic sensitivity, but not 100 % – residual risk and conditions outside the panel remain.
7. Result Interpretation
| Result | Reproductive Risk | Next Steps |
|---|---|---|
| No variants detected | Residual risk remains | Routine care; document result |
| Single carrier (recessive) | Low unless partner also carrier | Offer partner testing |
| Both carriers (same gene) | 25 % affected / 50 % carrier / 25 % unaffected each pregnancy | Refer for genetics counselling; discuss options below |
| Female carrier (X-linked) | Male fetus 50 % affected | Prenatal diagnosis / PGT-M |
8. Reproductive Options for High-Risk Couples
- Natural conception + prenatal diagnosis (CVS / amnio).
- IVF + PGT-M to transfer unaffected embryos.
- Use of donor gametes or adoption.
- Decide to conceive naturally without testing or not have children.
9. Medicare Funding (Australia)
- MBS item 73451 – CF/SMA/FXS carrier testing for the pregnant/planning patient.
- MBS item 73452 – Follow-up CF/SMA testing for the reproductive partner if patient positive.
- Available from 1 Nov 2023; no family-history criteria; pathology lab must be accredited.
10. Counselling & Ethical Considerations
refer to : https://www.virtusgenetics.com.au/individuals/genetic-carrier-screening/
- Informed consent mandatory – optional test; discuss potential emotional impact.
- Genetic counselling recommended for positive or inconclusive findings.
- Family implications: encourage cascade information to relatives.
- Testing once per lifetime – can screen again if new partner and Woman previously screened and is a carrier of CF or SMA
11. Limitations / Caveats
- Does not detect all pathogenic variants or dominant de-novo conditions.
- False reassurance possible; normal result ≠ healthy baby guarantee.
- Expanded panels: increased detection but more variants of uncertain significance and cost.
12. Follow-Up Documentation
- Record panel type, genes covered, result, residual risk, counselling provided, and patient decision in the medical record.
- If high-risk, document referral to genetics/obstetrics and chosen reproductive plan.
- Expanded Carrier Screening Panels
- Haemoglobinopathies & ancestry-based tests
- FBC (MCV/MCH) ± Hb-electrophoresis if the partner’s ethnicity carries a risk (Mediterranean, Asian, African, Middle-Eastern).
- Expanded (self-funded) panels
- Couples who want wider reassurance can choose commercial NGS panels covering hundreds of recessive genes.
- Results are independent of Medicare history.
- Counselling & documentation
- must understand possible outcomes
- privacy issues
- life-insurance implications (moratorium ≤ $500 k until 2027).
- Haemoglobinopathies & ancestry-based tests
Later pregnancies with a new partner – what changes?
| Scenario | Does anyone need another Medicare-funded test? | Practical steps |
|---|---|---|
| Woman previously screened under 73451 and is not a carrier for CF, SMA or FXS | No. 73451 is “once per lifetime”. A new partner is not eligible for 73452 because that item is only available when the woman is a carrier of CFTR or SMN1. The couple’s overall risk for those three conditions remains very low. | • Offer the new partner private (self-funded) carrier testing if they still want it. • Ensure routine tests that depend on the partner’s ancestry (e.g. full blood count ± Hb‐electrophoresis for thalassaemia) are repeated. |
| Woman previously screened and is a carrier of CF or SMA | Yes – the new partner may now claim 73452. 73452 is billed per person, once per condition, and can be used for each reproductive partner who has never had the test before. | • Order 73452 for the new partner before 12 weeks if pregnant. • If he is also a carrier of the same condition, refer the couple for genetic counselling to discuss CVS/amnio, IVF-PGT, donor gametes, etc. |
| Woman is a carrier of FMR1 (fragile X) | Partner testing does not attract an MBS rebate because the male’s status does not alter the inheritance risk (X-linked). | • Explain that the recurrence risk (≈50 % for a male fetus) is unchanged no matter who the partner is. • Offer counselling and targeted prenatal diagnosis if desired. |
| Woman was never screened (missed last time) | She can still claim 73451 once in her lifetime (planning or ≤12 wks pregnant). | • Order 73451 for her first. • If positive for CF/SMA, proceed to 73452 for the partner. |
Fragile X syndrome
Prevalence
- Fragile X syndrome is the second most common heritable cause of intellectual disability after Down syndrome.
Inheritance Pattern
- X-linked dominant inheritance with sex-modified, with incomplete penetrance in females.
Genetic Cause
- Fragile X syndrome results from a CGG triplet repeat expansion in the FMR1 gene.
| CGG Repeats | Allele Class | Clinical Significance |
|---|---|---|
| 5 – 40 | Normal | Stable; no disease |
| 45 – 54 | Intermediate (“grey”) | Usually asymptomatic; low risk of change |
| 55 – 200 | Premutation | Carrier state; risk of expansion in maternal meiosis |
| > 200 | Full mutation | FMR1 promoter methylation → ↓FMRP → Fragile X syndrome |
Key Features
- Most individuals with the premutation remain intellectually normal, though they may exhibit mild physical traits such as prominent ears and may experience emotional issues such as anxiety or depression.
- Female carriers of the premutation may develop premature ovarian failure (before age 40) and are at risk of a tremor/ataxia syndrome later in life.
Clinical Spectrum
| Group | Cognitive / Behaviour | Dysmorphic & Systemic Features |
|---|---|---|
| Premutation carriers | Typically normal IQ anxiety mood disorders possible | • M: risk of FXTAS (Fragile X-Associated Tremor/Ataxia Syndrome) • F: 20 % risk of FXPOI (Fragile X-Associated Primary Ovarian Insufficiency) |
| Full-mutation males | 80 % moderate–severe ID 20 % “transmitting males” cognitively normal | • Long narrow face • large protruding ears • prominent jaw • macroorchidism (post-puberty) • joint hyperlaxity • pes planus • soft skin • strabismus • mitral-valve prolapse |
| Full-mutation females | ~30 % mild ID others with learning or emotional difficulties depending on X-inactivation | Same facial gestalt (often subtler) macroorchidism absent |
Developmental red flags
- Large head circumference early in life
- Global developmental delay, speech–language lag
- Behavioural triad: hyperactivity, tantrums, autism-spectrum traits
Inheritance Counselling Pearls
| Carrier / Affected Parent | Risk to Sons | Risk to Daughters |
|---|---|---|
| Mother – premutation | 50 % chance of inheriting allele; may expand to full mutation | 50 % chance; may expand |
| Mother – full mutation | 50 % affected sons | 50 % carrier/affected daughters |
| Father – premutation | None (Y inherited) | 100 % premutation carriers (no expansion) |
| Father – full mutation | None | 100 % full-mutation daughters (variable phenotype) |
note:
• A premutation never expands in spermatogenesis → sons get the Y, daughters get the unchanged premutation (carriers, not affected).
• A full-mutation male would indeed give a full-mutation X to all daughters, but such men are exceptionally rare (severe ID, sub-fertility) and are usually clinically evident rather than “silent” carriers.
• If a man is clinically suspected of having Fragile X (e.g. ID, macro-orchidism) or mosaicism, his clinician can order diagnostic molecular testing under other genetic items (e.g. 73345/73346), but not under the reproductive-screening items.
Management & Supports
- Developmental therapies (speech, occupational, behavioural).
- Address comorbid ADHD, anxiety, ASD features with evidence-based pharmacologic / behavioural strategies.
- FXPOI surveillance in premutation females: fertility counselling, bone-health monitoring.
- Neurology review for older male carriers (FXTAS risk).
- Family genetic counselling for cascade testing and reproductive options (pre-implantation or prenatal diagnosis).
Cystic Fibrosis
Inheritance
- Cystic fibrosis (CF) follows an autosomal recessive inheritance pattern, meaning that both parents must carry one copy of the mutated gene. Carriers typically do not exhibit symptoms of the condition.
Genetic Cause
- CF is caused by mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene.
- These mutations disrupt the function of chloride channels, impairing the regulation of chloride and water flow across cell membranes.
Pathophysiology
- Dysfunctional chloride channels lead to the production of thick and sticky mucus in the passageways of various organs, such as the lungs and pancreas.
- This abnormal mucus accumulation clogs airways and ducts, resulting in characteristic symptoms and complications associated with cystic fibrosis.
Prevalence
- CF occurs in approximately 1 in 2,500 to 3,500 white newborns, making it relatively common in this population.
- It is less common among other ethnic groups, with a prevalence of around 1 in 17,000 among people of African descent and 1 in 31,000 in Asian populations.
Spinal Muscular Atrophy (SMA)
Genetic Cause
- SMA is primarily caused by mutations in the SMN1 (Survival Motor Neuron 1) gene.
Inheritance Pattern
- SMA follows an autosomal recessive inheritance pattern.
- When both parents carry a mutated SMN1 gene, there is a 25% chance with each pregnancy that the child will inherit the condition.
Clinical Manifestation
- SMA results in muscle weakness and progressive wasting (atrophy) of skeletal muscles, which often worsens over time.
- The severity and age of onset vary depending on the type of SMA.
Types and Variants
- While different types of SMA are caused by changes in the same genes, they differ in terms of age of onset and severity. There can be overlap in symptoms among the types.
- Other, less common forms of SMA and related motor neuron diseases are caused by mutations in different genes, such as:
- Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy
- Spinal Muscular Atrophy with Lower Extremity Predominance
- Spinal Muscular Atrophy with Respiratory Distress Type 1
- X-Linked Infantile Spinal Muscular Atrophy
