A. I suppose somewhere in the region of ten years ago, there was then doubt expressed as to whether secondary CMV did, in fact, cause exacerbations of the foetus and since that time it has been accepted that it can do so."
180 Dr Kendall was not cross examined about the Alabama study. I accept that Mr Cranitch did not have access to the study at the time Dr Kendall was in the witness box. Although opportunity was given for Dr Kendall's recall after the introduction of the evidence of the study, Dr Kendall was not recalled.
181 Dr Grigor did not express a view as to whether the CMV was primary or the result of a reactivated virus when he was first called. However like Prof Isaacs, he was recalled after considering the Alabama study. That study did not cause Dr Grigor to alter his diagnosis but when asked specifically (T312) whether he categorised the nature of the infection that was passed on to the child as being primary or reactivated, Dr Grigor said he did not have a view about that "one way or the other." I take that response as indicating that Dr Grigor was undecided on this issue. Because of the obvious importance of the question, I would infer that Dr Grigor would have been asked to consider this issue before he was called, and to express an opinion if he was able to do so. Whether this be so or not, Dr Grigor's evidence does not assist the plaintiffs on this critical issue.
182 Prof Rawlinson, in his report of 3 September 1998, said (para 6):
"Jacob Hughes suffers from severe disability, which never results from the rare instances of reactivation infection or reinfection during pregnancy."
183 Given the finding I have made of CMV infection, that opinion would tend to support the plaintiffs' contention that this CMV was primary in the sense being considered.
184 However, when alerted to the Alabama study, Prof Rawlinson regarded that study as revealing that the incidence of infection of babies from the reactivated process was much higher than previously appreciated, and after considering the study, he said that the sentence set out above from his report required correction and should read:
"Jacob Hughes suffers from severe disability which can result from reactivation infection or reinfection during pregnancy."
185 In cross examination, Prof Rawlinson was asked this question and gave this answer (T362):
"Q. It is still the position, is it not, that if it was, contrary to your views, congenital CMV, then on the very strong probabilities it was a primary infection?
A. No, on the basis of the publication evidence from last year, the possibility - looking at a child who is severely affected rather than looking from the other direction, taking a child and saying what is the likelihood of this child having acquired congenital CMV on the basis of primary or reactivation infection, it's approximately one in two. There were a significant number of - there was forty-seven babies in the Boppana studies I understand, about half of those, I think twenty-two, had CMV, which it was uncertain whether it was primary or reactivation. The authors felt that a significant number of those were reactivation, but they did not know."
186 If Prof Rawlinson was intending by the above answer to indicate that the Alabama study established that severe abnormality occurs just as frequently following reactivation as following primary infection, it does not seem to me that the Alabama study resulted in any such conclusion. In fairness to the witness, I doubt that this was what was intended to be conveyed by his answer, particularly having regard to his later cross examination to which I shall refer presently.
187 I return to the Alabama study itself (Exhibit 4). It seems that the study was conducted between 1991 and 1997 and the study subjects included 246 children with congenital CMV infection. Forty-seven of these children had clinical abnormalities following birth and of those infants, eight were born to mothers with confirmed reactivated infection. Another eight cases were cases of abnormalities following primary maternal infection. The study findings were that the range of severity of clinical abnormalities during the newborn period did not differ in the cases determined to be primary infection cases and those that were not. It is stated in the paper following the Alabama study:
"A previous study from this laboratory has thoroughly investigated the association between maternal antibody status and outcome in 197 children with congenital CMV infection born between 1972 and 1990. None of the 64 congenitally infected children who were born to women with recurrent CMV infection and were included in the study had clinical abnormalities at birth, and all 24 infants with symptomatic infection were born after a primary maternal infection. An earlier publication from this laboratory by Stagno et al also reported that none of the congenitally infected children born to women with preexisting immunity had symptomatic infection. Based on these findings, it has been believed widely that symptomatic congenital CMV infection almost always occurs after a primary maternal infection. However, the results of the present study clearly document that symptomatic congenital CMV infection after a recurrent maternal infection occurs more frequently than has been thought previously…"
188 The concluding paragraph of the report contained the following expression of reservation:
"A major limitation of the present study is our inability to categorize the type of maternal infection in more than half of the children with symptomatic congenital CMV infection born during the study period. It is possible, and perhaps likely, that the vast majority of symptomatic infections occur after a primary CMV infection during pregnancy. It is also possible that categorization of most maternal infections will lead to identification of an increased proportion of children who were born to mothers with preexisting immunity among infants with symptomatic congenital CMV infection…"
189 I do not read the authors of the report as conveying in the above passage that they regarded it as unlikely that the vast majority of symptomatic infections occur after a primary CMV infection during pregnancy. Indeed they say this is "perhaps likely", and this in the expression of medical as opposed to legal opinion . Before this most recent Alabama study, the same laboratory had made the finding that 100% of infants symptomatically infected with CMV were born to mothers whose infection was primary, and then there was the earlier study by Stagno leading to the same conclusion. Having considered the Alabama study, (and allowing for the major limitation to which the report refers (para 186 above)), the earlier studies to which Exhibit 4 refers and the evidence of Prof Isaacs to which I have referred (at paras 172-173), it seems to me to be more probable than not that the majority of symptomatic infections in infancy occur after primary CMV infection in the mother during pregnancy.
190 What the study indicates is that the effects of the reactivation of the virus can be just as severe as the effects from a primary infection. This feature of the study appears to have influenced Prof Rawlinson to change his mind in the respects indicated, but Prof Isaacs had considered before he saw the report that severe congenital infection could follow reactivated maternal infection (indeed he indicated this in his report of 27 June 1999), and the Alabama study has not altered his opinion.
191 I find on the evidence that the incidence of reactivation of CMV in the mother causing severe abnormality in the infant is very much less than the incidence of primary infection in the mother resulting in severe abnormality in the infant.
192 I am assisted in making this finding by the evidence of Prof Rawlinson concerning a paper which he wrote "a couple of years ago" (T393). This paper was entitled "Diagnosis of human CMV infection and disease". The professor wrote that congenital infection occurred mainly in the babies of women who had primary infection during pregnancy, and in cross examination (T394) the professor agreed this remained the position notwithstanding the Alabama study. Prof Rawlinson was asked the following questions about the paper (T394):
"Q. Then you go on to say:
'Primary maternal infection is much more likely to result in intrauterine transmission than maternal reactivation of CMV.'
A. Yes.
Q. That is still your position isn't it?
A. Yes, it is.
Q. Then you say that:
'The maternofoetal transmission rate in primary infection is approximately 50 per cent'
and that is still your understanding?
A. Yes.
……………….
Q. Then you say that for those people who have had it before, there is a 0.5 to 1.5 percentage possibility that they will have a foetal infection during what you call a reactivation infection?
A. Yes.
Q. And leading to clinically apparent disease in 0 to 0.5 per cent of cases?
A. Yes, these are ranges based - they are consensus figures to convey the general impression of the transmission rate.
Q. Then in the other column you deal with women who start off their pregnancy with no immunity?
A. Seronegative.
Q. And of those you say 50 per cent - what are the 50 percent and 10 per cent figures referred to there? First of all you have 50 per cent higher SES, what does that mean?
A. That is 50 percent are immune and 50 percent are non-immune, and for lower socioeconomic status, 90 percent are immune and 10 percent are non-immune to CMV. That is 50 percent of higher SES are seronegative to CMV and 10 percent of lower SES are seronegative to CMV.
Q. Then in the maternal infection box, which is the next one, you have got 1 to 5 percent?
A. Yes.
Q. What are you saying about that?
A. That something like the average of that, 3 percent of women are infected during pregnancy from both of those groups.
Q. Women who have not had CMV before?
A. Yes, that is developed primary infection during pregnancy.
Q. And then the next box is obvious, that of those who do get it in pregnancy, 50 percent of them or thereabouts suffer some primary infection?
A. 50 percent of those mothers will pass the virus to their unborn child, across the placenta.
Q. Leading to clinically apparent disease in 10 to 15 per cent of cases?
A. Yes.
Q. So that the net result is that on percentage basis, women who had some immunity have extraordinarily small prospect of passing on clinically apparent disease to the foetus, than those who have not?
A. Percentage wise, yes.
Q. That is still the position, isn't it?
A. Well the position percentage wise is still that, but the difference now is that the absolute numbers appear to be similar, of a similar order."
193 The above evidence emphasises, statistically, how rare is the chance of reactivated infection leading to clinically apparent disease in the child. It is, Prof Rawlinson, agreed "an extraordinarily small prospect".
194 However, it is to be observed in the answer of Prof Rawlinson last set out above that he referred to the "absolute numbers" appearing to be similar. Prof Rawlinson was then asked to explain what he meant by absolute numbers and his evidence proceeded (T396-397):
"A. As Boppana did, if you take - and in fact as unpublished data have suggested - if you take a group of children with congenital CMV and you carefully look at, retrospectively - so you collect the children as they are affected and you retrospectively and diligently seek out the characteristics of their mothers - then the absolute numbers of congenital CMV cases that are resulting from reactivation appears to be much higher than we previously believed, and that is the thrust of the Boppana article; that even though percentage wise, because primary infection is a relative rare event during pregnancy --
Q. But it is still the position that although there are more cases that have been found and documented, on a percentage basis primary infection is vastly more likely to have caused birth defects, isn't it?
A. Percentage wise. But in a sense what you are looking at is, if I can express it differently, if you look at all symptomatic children, not just severely symptomatic children - and again, I don't think this is in this paper but we have published this - if you look at all children with some type of symptom due to CMV acquired congenitally - and that goes from a relatively mild form with perhaps low platelets, petechiae and evidence at birth of excretion of the virus, who are developmentally normal and not distinguishable from normal children, all the way through to the most severe manifestation of CMV which is cytomegalic inclusion disease which often results in death of the baby - then percentage wise the number of, the percentage of recurrent infections that result in disease is extremely low. But reactivation is an extremely common event during pregnancy, occurring in something like a third to one half of all women and so that is a vast number compared to the number of primary maternal infections during pregnancy.
So even though the percentage is very small, the absolute numbers of any malformation, all the way through from mild to very severe, the absolute numbers due to reactivation infection are very similar to the primary, those due to primary maternal infection, and we have known that for many, many years. The difference with the Boppana article is that it suggests that the severe spectrum, the more severe end of the spectrum of disease, can also result from reactivation infection. So the percentage in a sense has to be seen in the perspective of the number of women who are suffering or who are undergoing this event of reactivation and so the absolute numbers are very - are relatively the same between primary and reactivation infection. That is well established. There is no question about that. And the papers I have referred to all indicate that in Australia as well as elsewhere, although it has been studied better elsewhere.
The difference that the Boppana article is suggesting is that the more severe spectrum can also be due to reactivation because, as you would expect with a disease with spectrum like congenital CMV, there is a lot of children who are born with fairly mild manifestations: A big liver which gets better; petechiae, which are the most common presentation; low platelets which get better as they cope with the infection."
195 I did not overlook what Prof Rawlinson said in the answer last cited when expressing my finding in para 189 above, but it seems to me that the professor's response under immediate consideration does not allow for the qualification expressed in the report of the Alabama studies (para 186 above), because of the inability in that study to determine in more than fifty percent of the cases studies whether the mother had primary or reactivated infection.
196 I have found it to be extremely difficult to reach a conclusion on the evidence I have reviewed as to whether the injury to the second plaintiff was due to primary or reactivated infection in the mother. The severity of Jacob's presentation does not rule out the possibility of reactivated infection as the source of his disabilities, but, subject to the qualification I have expressed, I accept the evidence given by Prof Rawlinson above (paras 192-193) stating his opinion based upon his studies. That evidence inevitably reflects statistical material. Although I have expressed the need for caution in evaluating statistics, since there is no direct evidence as to whether the first plaintiff was seropositive or seronegative immediately before her pregnancy, I am compelled to approach this matter evaluating the statistically based evidence. Statistics may be used in an appropriate case to support a conclusion: see, for example, Papadopoulos v New South Wales Insurance Ministerial Corporation [1999] NSWCA 116, in particular at para 34. The statistics must be weighed with all the evidence in the case, and here in particular, those statistics have to be considered with the medical evidence.
197 I now draw together the following findings: