Preconception care 

1. Smoking cessation
   1. Consider nicotine replacement therapy (NRT) if smoking cessation counseling is not successful
2. Abstinence from alcohol
   1.  facial abnormality – short palpebral fissures and nose, hypertelorism, small eyes, thin top lip
   2. low birthweight
   3. small stature
   4. low intelligence
   5. psychological over-activity
   6. cardiac lesions include atrial and ventricular septal defects
3. Recreational drug cessation
4. Reduce caffeine intake
   1. may make it more difficult to conceive
   2. inc risk of miscarriage
   3. inc risk of LBW
5. Folic acid: from 1/12 prior to conception to 12/40
   1. reduces the risk of having a baby with a neural tube defect
   2. 0.5mg daily for low risk
   3. 5mg daily for high risk
      1. on Antieplieptic medications/take folate antagonists (eg, methotrexate, sulfonamides)
      2. DM
      3. Have a child or fhx of NTD
      4. BMI >30
      5. at risk of malabsorption syndrome eg. Coeliac
      6. Fhx of congenital heart disease
      7. multiple pregnancy
6. Iodine supplement 150microgram daily
7. Nutrition & weight assessment
8. Review of:
   1. immunization status: MMR, DTP, varicella, influenza
   2. medications
      1. Teratogenic meds
         1. ACE (angiotensin converting enzyme) inhibitors such as enalapril etc..
         2. Acne medication isotretinoin (Accutane, RetinA).
         3. Alcohol 
         4. Antibiotics tetracycline and doxycycline.
         5. warfarin
         6. Anticonvulsants (phenytoin, valproic acid, carbamazepine)
         7. lithium
         8. thiouracil/propylthiouracil and carbimazole/methimazole.
         9. Thalidomide
   3. oral health
   4. chronic medical conditions
      1. DM
      2. Hypothyroidism
      3. Epilepsy
      4. thrombophilia
   5. psychosocial health
9. Pregnancy history
   1. previous infant death/ fetal loss/ birth defects/ LBW/ gestational DM/ pre-term birth
10. Interpregnancy interval
    1. Perinatal outcomes are worse with interpregnancy intervals <18/12 or > 5yrs
    2. Outcomes affected: preterm birth, LBW, small size for gestational age
11. Genetic/ family history
    1. congenital abnormalities
    2. consanguity
    3. thalassemia
12. medication review
    1. (chronic meds, OTC)
13. Breast exam & cervical screening test
14. Ax BMI, BP & dentition
15. Discuss environment at home & work
16. Social circumstances and support network
    1. psychological review
    2. domestic violence
17. ADVISE OVERSEAS PLANE TRAVEL NOT RECOMMENDED AFTER K28
18. Models of care available

Avoiding TORCH

1. Toxoplasmosis
2. Other [syphilis, varicella, mumps, parvovirus, HIV, listeriosis]
3. Rubella – congenital rubella syndrome – deafness, cataracts, cardiac defects
4. Cytomegalovirus
5. Herpes simplex

1. avoid TORCH  – vertically transmitted, during delivery through birth canal, through breast milk) = complications include preterm birth, delayed development, malformations, loss of pregnancy 

2. Toxoplasmosis:
   1. avoid cat litter
   2. garden soil
   3. raw/undercooked meat & unpasteurized milk products
   4. Wash all fruit & vegetables

3. Cytomegalovirus

4. Parvovirus B19
   1. discuss importance of frequent handwashing. Wear gloves when changing nappies if working in health care/ childcare 
   2. Clinical features: Erythema infectiosum (‘slapped cheek’ appearance or  fifth disease), 30 – 40 % of infection is sub-clinical, Rubella-like rash, Like rubella, can cause arthralgia or arthritis, particularly in adults
   3. Route of transmission: Person to person through direct contact with respiratory secretions and hand-mouth contact, mother to fetus
   4. can lead to spontaneous miscarriage and stillbirth. 
   5. The spontaneous loss rate of fetuses before 20 weeks’ gestation is 13% and after 20 weeks’ gestation is 0.5%
   6. associated with hydrops fetalis, Thrombocytopaenia

5. Listeriosis: 
   1. Listeria monocytogenes –  facultative, intracellular, gram-positive rod with ability to replicate at refrigerator temperatures. can be found in refrigerated, ready-to-eat foods (meat, poultry, seafood, and dairy – unpasteurized milk and milk products)
   2. Utilization of PPI or other stomach acid suppression modalities makes it easier for L. monocytogenes to pass through the stomach and invade enterocytes
   3. cause : miscarriage, premature labor, the delivery of a low-birth-weight infant, or infant death, intellectual disability, paralysis, seizures, blindness. 
   4. Hispanic women may have a higher incidence
   5. Listeria is destroyed in normal cooking, so freshly cooked hot food is safe if eaten straight away.
      • is safe to eat foods that are listed as a higher risk provided it is heated above 74 °c for over two minutes
   6. Avoid
      • pate, soft cheese, pre-packaged salads, cold deli meats, chilled/ smoked seafood
      • Wash all fruit & vegetables before eating
      • Avoid eating food if it has been made more than 24 hours ago. If you choose to eat food prepared the day before, it should always be reheated to steaming hot.
6. Fish:
   • limit fish containing high levels of mercury 
   • If consuming shark/flake, marlin or broadbill/swordfish, have no more than one serve (100g cooked) per fortnight and no other fish that fortnight.
   • If consuming orange roughy (deep sea perch) or catfish, have one serve (100 g cooked) per week and no other fish that week

Genetic Testing

1. Cystic fibrosis
   1. Tests: CF mutation
   2. Parents: Test for carrier status 
   3. Fetal: Test in T1
2. Down syndrome
   1. Tests: 1^st trimester screen, NIPT
3. Fragile X syndrome
   1. Tests: karyotype
   2. Fetal: any age for diagnosis
   3. Parents: prior to pregnancy for carrier status
4. Haemoglobinopathies & thalassemias
   1. Tests: MCV, MCH, Ferritin, Hb electrophoresis
   2. Test couple for carrier status 

genetic carrier screening

• Who?
  • Carrier screening is relevant to everyone
  • Most carriers of recessive conditions have no family history of the condition
  • therefore, carrier screening should be offered regardless of presence or absence of family history.
  • If there is a family history of a particular genetic condition, need to inform testing laboratory to reduce the chance of a false negative result.
  • one partner is tested first, and the second is only tested if the first is a carrier of an autosomal recessive condition.
    • In general, the woman is tested first, as it is the woman’s result that is important for X-linked conditions such as FXS.
  • In couple screening, both members of the couple are tested simultaneously. 
  • They are given one of two results:
    • an increased risk of having a child with a genetic condition if both are carriers of the same autosomal recessive condition or the woman is a carrier of an X-linked condition, or 
    • low risk if the couple are not carriers of the same autosomal recessive condition and the woman is not a carrier of an X-linked condition.
  • Sequential screening is generally cheaper for the couple if they are paying, since the majority of couples will only require one person to be tested if the person tested is not found to be a carrier of any of the conditions for which screening is done. 
  • Sequential screening also enables carrier testing of close relatives (cascade testing) who are at increased risk of being a carrier of a genetic condition because of a family member being identified as a carrier of a genetic condition.
  • The advantages of couple screening are twofold.
    • First, far fewer people require genetic counselling, as most couples do not carry the same condition, and therefore they receive a combined ‘low risk’ result. 
    • Second, a definitive result is available in a shorter time frame, which is advantageous when screening is done once the woman is already pregnant. 
    • The lost opportunity for cascade family carrier testing is negated if couple screening is offered widely in a community.
  • Misconception
    • “screening is not necessary if a couple have no known family history of a genetic disorder”
    • Almost 90% of carriers of CF, SMA and FXS have no known family history of the condition.
    • conditions less common than these, it is even less likely that a family history will identify at-risk couples.
  • It is critical that screening is offered as an option rather than as a ‘routine test’ done before or early in pregnancy, and that every effort is made to facilitate an informed choice by couples about whether or not to be screened. 
  • Individuals and couples contemplating screening should be made aware that having screening can lead to difficult decisions about current and future reproductive options. 
  • Couples who choose not to have screening and who have a child with an autosomal recessive or X-linked recessive condition must be fully supported.

What is screened

Currently offering carrier screening for:

• haemoglobinopathies
  • Maternal genotypes that may affect the woman and the fetus (depending upon partner study results)
  • MCV, MCH, Ferritin, Hb electrophoresis
    • Alpha thalassaemia:
      • αα/α- ,  αα/–  ,   α-/α- (carrier or minor trait)
      • α-/–   (haemoglobin H disease)
      • –/– (Barts hydrops generally resulting in death in utero)
      • Southeast Asia, India, Middle East, Africa and Mediterranean
    • Beta thalassaemia:
      • β/β0,      β/β+   (carrier or minor trait)
      • β+/β+,   β0/β+ (Beta thalassemia intermedia)
      • β0/β0                (Beta thalassemia major)
      • Southeast Asia, Indian subcontinent, Middle East, Africa and Mediterranean
    • Haemoglobin S:
      • AS (sickle cell trait)
        SS, SC, S/β thal., SD, S/O-Arab (sickle cell disease)
      • Africa including North Africans, African American, African Caribbean, British African or any other African ethnicity
• cystic fibrosis
• fragile X syndrome
• spinal muscular atrophy
• Expanded carrier screening panels offering screening for a large number of conditions are also available.

• if carrier
  • partner testing
  • prenatal testing
  • IVF and testing the embryo before implantation. 
  • Need genetic counsellor (Sonic Genetics offers free genetic counselling)

fragile X syndrome – X-linked dominant pattern

• 2^nd most common heritable cause of mental retardation after Down’s syndrome. 
• caused by a dominant X-linked gene with a penetrance of only 50% in females.
  • fragile X syndrome is caused by a mutation in DNA segment –   CGG triplet repeat within the FMR1 gene
  • Normally, this FMR1 gene CGG triplet is repeated from 5 to about 40 times.
  • In fragile X syndrome – CGG segment is repeated more than >200 times
  • In FMR1 gene premutation
    • CGG segment is repeated 55 to 200 repeats
    • Most people with this premutation are intellectually normal, mild versions of the physical features seen in fragile X syndrome (such as prominent ears) and may experience emotional problems such as anxiety or depression
    • Some children may have learning disabilities or autistic-like behaviour
    • female carriers with a pre-mutation develop premature ovarian failure (before the age of 40) and developing a tremor disorder later in life

• Of the patients carrying the full mutation:
  • 80% of males are mentally retarded
  • 20% of males are normal and are termed “transmitting males”
  • males experience more severe symptoms of the disorder than females 
  • 30% of females are mildly mentally retarded (except if the gene is inherited from a transmitting male, in which case the daughter is unaffected but is an obligate carrier)

Symptoms/Signs

• Pre-pubertal features:
  • normal growth but large head – greater than 50th percentile
  • delayed attainment of developmental milestones
    • Fragile X should be considered for all children with developmental delay of unknown cause.
  • tantrums, hyperactivity and autism
• Post-pubertal
  • low IQ (20-70)
  • long face, prominent forehead, large ears, large jaw
  • macroorchidism
• Other features
  • ophthalmologic – strabismus
  • orthopaedic – pes planus & joint hyperextension
  • dermatologic – soft, smooth skin
  • cardiac – mitral valve prolapse

Cystic Fibrosis 

• Inheritance: autosomal recessive pattern – each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
• Mutations in the CFTR gene 
• disrupt the function of the chloride channels, preventing them from regulating the flow of chloride ions and water across cell membranes. 
• as a result, cells that line the passageways of the lungs, pancreas, and other organs produce mucus that is unusually thick and sticky. 
• This mucus clogs the airways and various ducts, causing the characteristic signs and symptoms of cystic fibrosis.
• occurs in 1 in 2,500 to 3,500 white newborns, less common in other ethnic groups – 1 in 17,000 Africans 1 in 31,000 Asians

Spinal muscular atrophy

• Cause: Mutations in the SMN1 gene 
• Inheritance: autosomal recessive pattern
  • one in four chance (25%) in every pregnancy that they will each pass the faulty SMA gene to their child, who will then have SMA at birth or later
• Results in
  • weakness and wasting/atrophy in skeletal muscles
  • muscle weakness usually worsens with age. 
  • There are many types of spinal muscular atrophy that are caused by changes in the same genes. 
• The types differ in age of onset and severity of muscle weakness; however, there is overlap between the types. 
• Other forms of spinal muscular atrophy and related motor neuron diseases are caused by mutations in other genes.
  • spinal muscular atrophy with progressive myoclonic epilepsy
  • spinal muscular atrophy with lower extremity predominance
  • spinal muscular atrophy with respiratory distress type 1
  • X-lnked infantile spinal muscular atrophy