Obstetrical ultrasound is performed in a complicated atmosphere, partly tense and anxious, partly joyous and affirming.  The expectant parents are usually happy and excited by the prospect of viewing their baby on the screen, but some may be concerned, aware that a problem could be found. This may be either because they are carrying a baby already known to be at risk for problems, or because they know that "bad things happen to good people" as the saying goes, and that problems in pregnancy are not infrequent.  The sonographer (usually a trained allied health professional from an appropriate background - a radiographer, nuclear medicine technologist or midwife) is hoping to reassure the parents of the life, normal anatomy and growth of the fetus, but is aware that there are many limitations to the scan, and that many fetuses indeed are not perfect.  Some commentators have considered the ultrasound examination to be an excellent tool for creating anxiety in the expectant parents. This may also affect the person performing the scan! When one considers that many genetic, metabolic and physical congenital abnormalities cannot be visualised by ultrasound, and that there is a distressingly wide range of appearances of normal development and developmental variants which overlap the pathological, it becomes evident that making discrimination of the normal from the abnormal fetus is fraught with caveats. Many sonographers have confessed, during conversations with the author, that they have decided not to perform obstetrical ultrasound as they feel unduly stressed by the responsibility involved as well as being threatened by the legal implications of not finding or recognising a problem appearance. Also, new equipment is continually pushing the frontiers of what can be imaged.  One sonologist (a medical practitioner trained in interpreting as well as performing ultrasound scans) has said: 

 

Rapid technological advance means that each machine update shows the observer features never recognised before, necessitating a reappraisal of the range of normal at each stage of pregnancy, and adding to an extensive repertoire of artifacts and red herrings. (Furness^82, † )

 

1.2           The Paradigm of Cyst Criteria

In the seminal definition given by Thomas Kuhn, author of The Structure of Scientific Revolutions¹¹⁵, a paradigm is a set of established opinions or “shared values” which temper the way the world is viewed by scientists.  It acts as a filter to consciousness, allowing the acceptance of only those observations which fit the prevaling paradigm, as the contemplation of ideas which confute it are, by definition, not related to it.  For example the prevailing astronomical paradigm before Copernicus was that the earth was the centre of the universe.  All remarks on astronomy were based on this premise and therefore, to Kuhn’s analysis, twisted or falsely intrepreted in such a way to reinforce this particular explanation of celestial mechanics.  It took several centuries before Copernicus’s iconoclastic interpretation, (in fact a return to ancient Greek theories) that the earth and the planets revolve around the sun became accepted.  When later refined by Kepler, who further broke the paradigm of circular planetary motion, it allowed the complicated system of refining the cycles of the celestial spheres (ellipsoids!) to be abandoned.  Since then a new astronomical paradigm has been in place. 

 

The ultrasound appearance of cystic spaces within the otherwise homogenous and bright echoes of the choroid plexus of the lateral ventricles in the fetal brain was first described by Chudleigh⁴⁹ in 1984, although they had been reported in the ultrasound study of the brains of normal infants⁷⁴ and in autopsy and embryological studies on many occasions previously.  For the last ten years in the ultrasound literature there has been heated scientific discussion on the significance of this finding.  Early investigators initially considered fetal choroid plexus cysts (CPC) to be a “red herring”, a normal variant which required no further investigation, while others wondered if an underlying structural brain malformation may be present.  Nicolaides¹³¹ was the first, in 1986, to note an association with chromosomal abnormalities, particularly trisomy 18 (T18, Edward’s syndrome) and later on other authors found an association with trisomy 21 (T21, Down syndrome).  No such association had ever been made in the autopsy studies of CPC or in the radiology and anatomy literature in the past. 

 

Once these associations had been made, CPC could not be ignored.  However, when a screening program produces a positive indicator of a relatively uncommon finding such as T18, some have felt that inappropriate actions and unnecessary anxiety are the usual result¹⁹⁹. It is the nature of screening programs to find a balance between the detection of truly abnormal findings with falsely abnormal (normal variants, "red herrings", etc...) as well as the missed abnormalities with those found. This balance is usually displayed as a statistical finding. But it sometimes requires a little bit of rethinking to place the published results of screening test, such as obstetric ultrasound, into a usable context. The interpreting of statistics is not necessarily easy or straight forward as "statistical significance" does not always equate to "clinical or medical significance." When a study attempts to correlate a common appearance with a rare problem, one must be careful of the management implications of acting merely upon a mathematical justification, particularly as one is dealing with the most delicate and fundamental human situation - the propagation of the species.

 

When a scan shows a CPC, what is the right thing to tell the patient, and what, if any, follow-up procedures should be recommended?

Investigators began to wonder if the association with T18 was strong enough to warrant amniocentesis for assessing the fetal chromosomes for those women who were otherwise at low-risk, unless there were other fetal abnormalities.  Some investigators considered that those isolated (i.e. no other problems seen) CPC which were:

 

1.    large, 

2.    bilateral, and 

3.    present after 24 weeks of gestation 

should also undergo amniocentesis.  Several articles proposing this protocol or close variants (single versus multiple, for example) were published in the radiology and obstetrics literature during the mid to late eighties.  Due to the early promulgation of this protocol, theirs became the established paradigm.  Gradually, antithetic articles were published in which the data and research failed to find the claimed significant statistical association with these criteria, but still the discussion always seemed to revolve around these criteria.  But measuring and counting CPC (the most basic and easiest ultrasound assessment) sonographers were reinforcing these characteristics as important by incorporating them in their scan routines, reinforcing these criteria indeed as paradigmatic.

 

But the debate continued through the pages of these journals.  When should karyotyping be recommended?  The result was confusion for those sonographers, radiologists and obstetricians trying to deal sensibly with what is one of the most common ultrasound abnormalities when a relatively uncommon chromosomal aberration was implicated. Sonographers who had not seen a case of T18 for years, were finding CPC at the rate of several per week.

 

1.3           Purpose of this study

At the Geelong Hospital (Ryrie St, Geelong, Victoria, Australia) we found a malformed fetus subsequently diagnosed, after post-termination autopsy, as having T18. Our unstated policy at that time was not to report CPC in order to avoid undue concern. However the malformations in this fetus included CPC. In order to determine what our policy should be, we decided to perform an observational study. We intended to review the ultrasound findings and birth data prospectively all fetuses with CPC seen in the ultrasound section of the Medical Imaging Department of the Geelong Hospital for as long a period as possible, until we obtained about 50 further cases of CPC.  As this was initialy an informal observational study, monitoring our current practices, no informed consent was offered to the patients. We were as confused as any others about what to advise our clients, the medical practitioner referrers and the patients.  We wondered if the prevailing paradigm actually could be verified.  We understood that it would be unlikely for a small single hospital study to determine the answer due to the relatively rare occurrence (prevalence) of T18 in low-risk patients.  However many of the published articles were of a similar size to our anticipated study, and this did not prevent their authors making statements and judgments based on what might appear as similarly tenuous statistical results. In order to obtain a more significant base for statistical judgment, an extended study of the literature (meta-analysis) was performed to try and verify if the published data confirmed the appropriateness of the paradigm espoused by many of the authors for a patient population such as ours. A discussion of the ethics and economics of routine ultrasound scanning and of amniocentesis protocols was developed from issues raised in the literature search.  A new form was developed for our sonographers to use when a fetus was considered to be at risk for chromosomal abnormality.

 

Was the paradigm likely to survive close scrutiny?  Could obstetric ultrasound itself stand such scrutiny?

This thesis will attempt to provide clarification of the topic:

1.    by describing the growth of the choroid plexus in the fetus and the cause of the presence of cysts within it;

2.    by reviewing our own experience from a prospective study carried out from September 1990 to December 1993; 

3.    by an extensive literature survey of articles dealing with CPC and chromosomal abnormalities; 

4.    by analysing the arguments proposed in the paradigm for using cyst characteristics to improve the sensitivity for detection of chromosomal abnormalities, using information gathered from the above literature search; 

5.    by examining other “soft” signs for T18;

6.    by describing the production of our own protocol and pro-forma which may assist other sonographers confronted with a fetus with CPC  or other “soft” ultrasound signs of chromosomal abnormality;

7.    by discussing the use of routine ultrasound and the role of amniocentesis; and 

8.    by comparing the effects of different protocols for CPC on the live-birth rate of T18 and the loss rate of fetuses without T18 attributable to amniocentesis.

 

 

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