Update on Less invasive prenatal testing


Non-invasive tests have become cheaper and are more available to women in rural areas.

The basic Harmony test (trisomy 13, 18 & 21)  now costs $425. A Medicare rebate is not available for this test.

Another local lab offers a basic Generation test costing $395 and an extended test for $695

I have refined what I offer in the last last few year,

  1. Will offer a dating scan to confirm dates
  2. NIPT after 10 weeks if you can afford it
  3. First trimester ultrasound and screening bloods  if you have had a NIPT, or risk assessment if no NIPT. This is done between 11 to 13+6 weeks.



31 March 2018


The most recent ANZJOG  has two papers and an editorial about non-invasive prenatal testing for certain fetal genetic disorders.

This should really be called less invasive as unlike some DNA testing it does require a blood specimen. But it is certainly less invasive than an amniocentesis or chorionic villus sampling (CVS) with the attendant risk of miscarriage.

Although operator dependent, the risk of miscarriage with CVS is between 1:100 to 1:200; whilst there is less risk from an amniocentesis; 1:200  to 1:300. CVS can however be performed earlier in the pregnancy.

The risk of miscarriage and stillbirth may be increased by factors such maternal age and weight, previous miscarriage, or stillbirth, low PAPP-A, high  high fetal nuchal translucency, pre-existing diabetes, ovulation induction. chronic hypertension and smokers.

Obviously it would not be acceptable to do these tests on all pregnancies. Not every woman want to know her child’s genetics. To many the option ending a pregnancywith Down Syndrome is unacceptable.

In South Australia, screening  done by SAMSAS at the Women’s & Children’s Hospital.

Screening requires

  1. blood at 9 to 13 weeks
  2. nuchal translucency at 11 to 13+6 weeks

For practical purposes I usually organise testing at 11 to 12 weeks with the ultrasound first to confirm dates then the blood drawn if dates are accurate.

The detection rates for Down Syndrome with this test are

  • Serum biochemistry alone 70.1%
  • Ultrasound alone 72.7%
  • Serum biochemistry + Ultrasound 88.3%

I offer screening to all pregnant women as a way to better define the risk of having a baby with Down Syndrome than age alone. For an estimate of age related risk I use SAMSAS update 15.

I use the risk of greater than 1:250 to recommend an invasive test. If the test then identifies an abnormality, the woman may be offered a termination of the pregnancy. I usually offer my personal view that if I would never terminate a pregnancy then I wouldn’t undertake the screening test.

Some women still want to know more about their risk but baulk at the risk of the CVS or amniocentesis. For them the non-invasive test is attractive.

For women who fall into the more than high risk screening group the non-invasive test is also attractive.

For a paper on the science of the test you may read The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis by Wright C, Burton in Human Reproduction Update, Vol.15, No.1 pp. 139–151, 2009)

Currently in Australia, non-invasive tests have some limitations.

There is no consensus on it utility.

There is no Medicare funding; nor is it covered by private insurance companies. The test cost will $900 to $1250.

The blood test has to be done in a major capital city on a specific day. So there is the cost of the journey to consider. The blood is then flown to the US for testing. Interestingly, Tasmanian women can have it done at the Royal Hobart but pay a $100 premium over those in Melbourne.

There is a wait for 7 to 10 days.

Accuracy is dependent upon fetal DNA yield.

The tests may be performed from 9 weeks which is prior to the nuchal translucency ultrasound and would necessitate a dating scan if dates are uncertain.

Some companies offer a second free test is the first is inconclusive.

Current tests in Australia

QML/Laverty/Western/Abbott offer Generation
SNP/ClinPath offer Harmony
VCGS offer percept
IVF Australia group offer Panaroma

And honestly, I’m note sure which is the best.


Where does this technology fit into my practice?

Hui and Hyett have discuss how this new technology should fit into Australian screening. Hui, L and Hyett J. Noninvasive prenatal testing for trisomy 21: Challenges for implementation in Australia Australian and New Zealand Journal of Obstetrics and Gynaecology 2013; 53: 416–424

How would I decide who to offer the test to?

  • following a high risk screen
  • maternal age
  • family or personal history
  • genetic condition
  • everyone who can afford it?

The American College of Obstetricians and Gynecologists Committee on Genetics issued a  position statement on non-invasive prenatal testing for fetal aneuploidy in December 2012:  

“Noninvasive prenatal testing that uses cell free fetal DNA from the plasma of pregnant  women offers tremendous potential as a screening tool for fetal aneuploidy. Cell free fetal  DNA testing should be an informed patient choice after pretest counseling and should not be  part of routine prenatal laboratory assessment. Cell free fetal DNA testing should not be  offered to low-risk women or women with multiple gestations because it has not been  sufficiently evaluated in these groups. A negative cell free fetal DNA test result does not  ensure an unaffected pregnancy. A patient with a positive test result should be referred for  genetic counseling and should be offered invasive prenatal diagnosis for confirmation of test  results.”

I believe that RANZCOG and RCOG are still considering how this test fits into their guidelines for prenatal testing.

For the time being, given I do not do CVS or amniocentesis my plan is to continue to offer all my pregnant patient the SAMSAS screen and if they can afford the test to discuss it with the obstetrician in the tertiary centre prior to undergoing an invasive test.  I know some women would struggle with the cost but the test may well avoid having a CVS or amniocentesis with its attendant risks.

Help Me Doc ….. I’m tired all the time

“Help Me Doc ….. I’m tired all the time”

Its Friday 4:30, the end of the day, you skipped lunch to cut off a BCC, spent the first hour of the day organising retrieval of a patient you admitted late yesterday with chest pain who had a troponin leak overnight.

And you’ve almost caught with your schedule having benefiting from a couple of “just script” patients. The 35 year old farmhand booked a 15 minute appointment and you’ve never met him before.  In fact, a quick glance of his history shows he was last seen 10 years ago to have a laceration repaired. In all certainty his wife sent him in because she was tired of his complaining or falling asleep on the couch after dinner in front of the TV.

How do you start?

  1. Take a big breath, listen briefly, ask a few questions then order a dozen blood and urine test?
  2. Listen to the tale, nodding with chin rubbing, reassure, recommend Centrum and ask them to return in 6 months if there is no improvement
  3. Check blood pressure and refer to a colleague skilled in work cover, chronic pain, fibromyalgia and especially heart sinkers
  4. Listen to the account of the symptoms, acknowledge it is real, do a system screen to exclude serious causes; then explain that a longer consultation is vital to explore the cause, to do an examination and consider investigations.

Okay so there is a big fat chocolate frog for those who picked 4 as the best answer. Ever been tempted to do otherwise??

Back to my patient.

First I like to make sure we are talking about the same thing. With the benefit of a medical school education (and UpToDate) fatigue can describe as difficulty initiating activity, perception of weakness, reduced capacity to maintain activity, difficulty with concentration, memory, or emotional stability. Can I distinguished fatigue from somnolence, dyspnea, and muscle weakness. Fatigue is common with 5 to 20% of GP patients having it. Fatigue is a symptom and the patient is hoping for a diagnosis. And, unfortunately maybe only 10% will get one. Recalling the patient is a bloke sent in by his wife, a few opened ended questions maybe useful. And if you listen to experts on Mens’ Health maybe a few comments about the footy on the weekend?

I need to learn about his tiredness.

  • Onset – abrupt or gradual, related to event or illness?
  • Course – stable, improving or worsening?
  • Duration is it recent, prolonged (>1/12) or chronic (>6/12)
  • Daily pattern, is it worse in the morning, does having a weekend off effect it?
  • Factors that alleviate or exacerbate symptoms?
  • Impact on daily life – ability to work, socialize, participate in activities?
  • Accommodations made to adjust to fatigue symptoms?
  • Can it be quantified?

And a question to get the elephant out of the room …….

What do you think is causing this tiredness?

Dunno Doc…. it’s cancer/ I drink too much/I hate my life/I think I am depressed!!

About this time you glance at the computer and see the clock has ticked past 20 minutes, your stomach is rumbling, the back door has opened and closed half a dozen times as everyone else has gone home  and despite your best efforts there comes a stifled yawn.  It is time for the tactful, let’s get back for a long appointment.  Hopefully you have been able to engage him and given him a glimmer of hope that you may be able to find a cure. The final thought as he leaves – should I bulk bill to make sure he comes back? No, sorry the final thought is, have I missed something that may kill him before I see him again. Before he does leave the building I get a few blood tubes and some urine in a jar.

I generally don’t think in acronyms as I can never remembering what the bloody letters stand for but obviously someone has come up with one for fatigue.


  • Sleep problems
  • Fat and Food
  • Anaemia
  • Tumour
  • Infection
  • General joint or liver disease
  • Uraemia
  • Endocrine
  • Depression & Drugs & alcohol

Although this leaves out cardiac, respiratory and neurological causes.

Now you might note that I have to examine my patient, which may be a heresy in Medicine but sometime practically I think it can wait. Oh and I’ll probably get a hard time about doing investigations prior to examination. A practical list might be

  • Full blood count
  • Erythrocyte sedimentation rate or C reactive protein
  • Liver function tests
  • Urea and electrolytes
  • Thyroid function tests
  • Creatine kinase
  • Celiac serology
  • Glucose
  • Ferritin (for children and young adults)
  • Urine test for protein, blood and glucose

The utility of investigations has been tested and unfortunately they are often unhelpful.

Gialamas et al, AFP 2003; 32: 663-6 looked at records of 342 patients who had pathology ordered to investigate tiredness by their GP. Only 12 patients or 4% had a significant diagnosis made because of these tests. Of 1046 tests done, 880 were returned normal. The most likely diagnosis made were anaemia, hypothyroidism and diabetes mellitus. A study by Lane et al AJMS, 1990;299(5):313-8 of 100 patients who had suffered from fatigue for at least 1 month showed similar results. Only 5% of patients having a diagnosis made on the basis of tests.

Seems if the history has not been helpful then rushing off a pathology form is pretty low yield.

Now getting back to my heresy.  UptoDate suggests I should note

  • General appearance: level of alertness, psychomotor agitation or retardation, grooming
  • Presence of lymphadenopathy
  • Evidence of thyroid disease: goitre, thyroid nodule, ophthalmologic changes
  • Cardiopulmonary examination: signs of congestive heart failure and chronic lung disease
  • Neurologic examination: muscle bulk, tone, and strength; deep tendon reflexes; sensory and cranial nerve evaluation

Lane’s study suggested that a clinical examination yielded a diagnosis in just 2% of the patients studied. That means that for the 100 patients, up to 93 went away without a diagnosis! They also followed their patients for 10 months and found that no new organic cause was identified for their patient’s fatigue.

Remember that this does not automatically put those patients into the chronic fatigue pigeon hole. Specific criteria have been determined for this by CDC and NICE 

  • Consider a diagnosis of CFS if these three criteria are met:
    • The individual has severe chronic fatigue for 6 or more consecutive months that is not due to ongoing exertion or other medical conditions associated with fatigue (these other conditions need to be ruled out by a doctor after diagnostic tests have been conducted)
    • The fatigue significantly interferes with daily activities and work
    • The individual concurrently has 4 or more of the following 8 symptoms:
      • post-exertion malaise lasting more than 24 hours
      • unrefreshing sleep
      • significant impairment of short-term memory or concentration
      • muscle pain
      • multi-joint pain without swelling or redness
      • headaches of a new type, pattern, or severity
      • tender cervical or axillary lymph nodes
      • a sore throat that is frequent or recurring

Come Monday, following a further chat, filling gaps in the history, reviewing my brief pathology and doing a thorough examination, I am left without a diagnosis. This man’s body and mind are not diseased and I can’t really tell him why he is feeling tired all the time. A few thoughts come to mind. 15 years on the land, working from 6 am to 6 pm every day of the week and not having had a decent break for 5 years; still eating and drinking like a 20 year old and providing for four teenagers may well have something to do with it. In the end he needs a priest or social worker as much as her needs me.

Some useful strategies to prevent fatigue becoming chronic include

  • Identifying and dispel unhelpful beliefs
  • Managing and structure activity and avoid over activity
  • Explore depression and anxiety with CBT & maybe medication
  • Manage occupational, relationship and other social stressors