Mattresses, microenvironments, and multivariate analyses
BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7371.981 (Published 02 November 2002) Cite this as: BMJ 2002;325:981
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Millions of babies, including my own, have been placed to sleep prone
and all but the first born have usually been placed to sleep used
mattresses. Despite this the overwhelming majority must have grown up to
be healthy and intelligent adults. I find it difficult, therefore, to
believe that either the prone position or used mattresses might be an
important cause of SIDS.
In adults Gattinoni et al have shown that oxygenation is improved
in patients with the acute respiratory distress syndrome if nursed prone
but that the improvement in oxygenation is not accompanied by an
improvement in outcome (1). In discussing the benefits of nursing these
patients prone Gattinoni makes the point that “the aetiology of acute
respiratory distress syndrome may markedly affect the response to prone
positioning”(2). I suspect the same applies to neonates and that nursing
babies prone or on an old mattress is only of pathophysiolgic significance
in SIDS in those babies who had another reasons for developing an
impairment of tissue oxygenation in their cots.
In adults an inadequacy of tissue oxygenation, identified from the
presence of a gastric intramucosal acidosis, would appear to be the
primary determinant of outcome in the acutely ill (3,4). Supplementary
efforts to improve the adequacy of tissue oxygenation triggered by the
presence of a gastric intramucosal acidosis may improve outcome (5). The
gastric intramucosal pH appears to reflect the balance between energy
release by ATP hydrolysis and ATP re-synthesis by mitochondrial oxidative
phosphorylation (6,7). There are many causes for an impairment of
mitochondrial oxidative phosphorylation including hypoxaemia,
hypovolaemia, cytokine release, the carbon monoxide present in cigarette
smoke, mutant mitochondrial DNA, medications, recreational drugs,
insecticides, herbicides, molluscicides, chemicals present in industrial
waste and elevated levels of homocysteine caused by a deficiency in B
vitamins (8,9,10). Any one of these could be present in neonates.
I submit that the probability is that SIDS is caused by the occult
presence of an impairment of mitochondrial oxidative phosphorylation
either inherited from the mother or acquired in utero, during parturition
and/or after birth. In which case its presence should be detectable with
measurements of gastric intramucosal pH made with tonometers placed in the
stomach of neonates either in utero or immediately after birth. I suspect
that any adverse effect that placing infants prone on used mattresses
might have is no more than last straws that might break the camel’s back.
If the presence of an impairment of mitochondrial oxidative
phosphorylation were identified on the day of birth more effective steps
might be taken to prevent SIDS.
1. Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D,
Labarta V, Malacrida R, Di Giulio P, Fumagalli R, Pelosi P, Brazzi L,
Latini R. Effect of prone positioning on the survival of patients with
acute respiratory failure.
N Engl J Med. 2001 Aug 23;345(8):568-73.
2. Pelosi P, Brazzi L, Gattinoni L. Prone position in acute respiratory
distress syndrome.
Eur Respir J. 2002 Oct;20(4):1017-28.
3. Doglio GR, Pusajo JF, Egurrola MA, Bonfigli GC, Parra C, Vetere L,
Hernandez MS, Fernandez S, Palizas F, Gutierrez G. Gastric mucosal pH as a
prognostic index of mortality in critically ill patients.
Crit Care Med. 1991 Aug;19(8):1037-40.
4. Maynard N, Bihari D, Beale R, Smithies M, Baldock G, Mason R, McColl I.
Assessment of splanchnic oxygenation by gastric tonometry in patients with
acute circulatory failure.
JAMA. 1993 Sep 8;270(10):1203-10.
5. Gutierrez G, Palizas F, Doglio G, Wainsztein N, Gallesio A, Pacin J,
Dubin A, Schiavi E, Jorge M, Pusajo J, et al. Gastric intramucosal pH as a
therapeutic index of tissue oxygenation in critically ill patients.
Lancet. 1992 Jan 25;339(8787):195-9.
6. Fiddian-Green RG. Gastric intramucosal pH, tissue oxygenation and acid-
base balance.
Br J Anaesth. 1995 May;74(5):591-606. Review
7. Fiddian-Green RG. Monitoring of tissue pH: the critical measurement.
Chest. 1999 Dec;116(6):1839-41
8. Fiddian-Green RG. Headaches and cerebral tissue oxygenation
http://bmj.com/cgi/eletters/325/7369/881#26368, 18 Oct 2002
9. Fiddian-Green RG. Iatrogenic diseases with a common cause?
http://bmj.com/cgi/eletters/325/7370/913#26512, 25 Oct 2002
10. Fiddian-Green RG. Homocysteine causes mitochondrial dysfunction
http://bmj.com/cgi/eletters/325/7374/1202#27538, 2 Dec 2002
Competing interests:
None declared
Competing interests: No competing interests
Quote from the authors of the Scottish paper: "We regret that few
other research groups have collected data on used infant mattresses and
none have published their data as peer reviewed articles. We hope that
this position will change, for the sake of parents seeking clarity in this
area." 1
I was aware year ago that data suggesting higher risk of cot death
with used mattresses rather than new ones was held by the research group
in Scotland, but it was clear that nothing would be published until an
appropriate peer review had been completed for dissemination by a
respected biomedical journal.
The results that were published eventually matched what I had been
led to believe was being held in Scotland as might be confirmed from
emails between myself and national media outlets.
The question I tried to get answered was whether the results were
important enough for the prevention of death in small babies that they
should be made available on preliminary basis without prejudicing ultimate
peer reviewed publication, This is possible I understand under
international guidance on biomedical publication.
On the other hand the implications of confirmation of a much higher
risk associated with used mattresses are quite serious - and publication
of a false claim could lead to alarm.
What would be helpful now that the data have been released is whether
the appropriate authorities would say whether, all other things being
equal, and all other safeguards being applied - regarding smoking and
sleeping posture for example - whether parents should or should not get
rid of used cot mattresses and use only new ones?
As a bit of an aside, but perhaps related - readers might know of the
experience in New Zealand where a very controversial campaign promoting an
impermeable washable mattress covering to a certain specification has
claimed (anecdotally) 100% success in preventing cot death. The degree of
controversy surrounding this subject there would suggest that if coroners
did come across a case where a baby had died on such a mattress this would
have been publicised.
What is not known for certain from NZ is the take up of mattress
covering. Mattress covers to this specification are now being marketed by
mail from within the UK, from Wales as it happens but there is no
connection with this correspondent. New Zealand cot death rates in the
white or Pakeha population were previously very much higher than the UK's.
For the latest period where figures are available they were lower than the
UK's - and recently of course UK figures were criticised as understating
the true incidence of cot death. There are differences in procedures
leading to verification of cot death status between NZ and UK - sources
suggest there is a much more intensive attention to post mortem detail in
NZ where the population is much smaller of course, figures take at least a
year longer to be officially released. It is suggested that cot death
figures there may be relied on to a greater degree than in the UK as
excluding an ascertainable cause of death.
So, to return to the quote from Tappin et al at the head of this
response - why has there been such historical reluctance on the part of
researchers south of the Scottish border to investigate links between cot
mattress age and the incidence of cot death? Will new attention to what
seems to be conceded is still only a potential link, south of the border,
produce a definitive answer and when?
1. Tappin, DM, Brooke H, Ecob R, Gibson A. Used infant mattresses and
sudden infant death syndrome in Scotland: case-control study. BMJ 2002;
325: 1007-9.
Competing interests:
It is possible that I might prepare something for the media about cot mattresses and cot death for which I will, as a journalist, be paid.
Competing interests: No competing interests
Dear Sirs
We wish to respond to the questions raised by the editorial (1) commenting
on our publication “Used infant mattresses and sudden infant death
syndrome in Scotland” (2).
1. Adjustment for socio-economic status
The authors of the editorial question the use of Deprivation Category as a
measurement of socio-economic status. The full results table, available
on the BMJ website, shows that Deprivation Category was only one of eight
variables describing socio-economic status. We therefore reject the
implication in the editorial that Deprivation Category was our only
measurement.
2. Response rate of controls
We attempted to arrange interviews with parents of 156 cases notified to
us in time for an interview within 28 days of death and actually achieved
interviews within this period with 131 (84%). 312 controls were
identified, two for each case, and we achieved interviews with parents of
278 which is 90%, not 71% as suggested in the editorial.
3. Adjustment for parity
In our data, the association between used infant mattress and SIDS is not
removed when parity is added to the multivariate model. However, the
apparent effect of parity is reduced to non-significance only by the
addition of used infant mattress. The evidence from our data is that the
parity effect is an artefact due to confounding by used infant mattress.
4. Age of infants at death
As with the CESDI study, the infants in our study who died on a used
mattress were older on average than those on a new mattress (98 cf. 89
days). Blackwell et al (3) have suggested that infant vulnerability to
bacterial infection is at a peak at 3 months, partly due to the fall in
maternally-derived immunoglobulin within the baby and this may explain the
older age of the infants on a used mattress.
We regret that few other research groups have collected data on used
infant mattresses and none have published their data as peer reviewed
articles. We hope that this position will change, for the sake of parents
seeking clarity in this area.
1. Fleming PJ, Blair PS, Mitchell EA. Mattresses, microenvironments,
and multivariate analyses. BMJ 2002; 325: 981-2.
2. Tappin, DM, Brooke H, Ecob R, Gibson A. Used infant mattresses and
sudden infant death syndrome in Scotland: case-control study. BMJ 2002;
325: 1007-9.
3. Blackwell CC, Gordon AE, James VS et al. The role of bacterial toxins
in Sudden Infant Death Syndrome (SIDS). Int J Med Microbiol 2002; 291: 561
-570.
Competing interests:
None declared
Competing interests: No competing interests
Used Infant Mattresses, Parity and Sudden Infant Death Syndrome
Sir,
Does parity confound the association between used infant mattress and
Sudden Infant Death Syndrome (SIDS) in Scotland (1)? That is to say, is
the observed association (2,3) in fact a result of the confounding effect
of parity and not due to used infant mattress at all. Clarification of
this issue is important as 33% of babies in Scotland sleep on a used
infant mattress as do many infants in New Zealand (4). We explore this
issue using case-control data from two studies in Scotland from January
1992 to May 2000 (2,3).
Questionnaires were completed on 278/317 (88%) cases notified in time
for an interview within 28 days of death and 554/634 (87%) controls.
Parity was determined by asking How many live births has mother had,
including this one? Exposure to a used infant mattress was assessed by
asking parents about routine sleeping place for both cases and controls
and ascertaining the mattress status (new for this baby or not). Routine
bed sharers were excluded (35 cases and 33 controls). Multivariate
analysis, to control for possible confounding factors including parity,
confirmed a valid statistical association between used infant mattresses
and SIDS, OR 2.51 (95%CI 1.39, 4.52) (2) and OR 3.07 (1.51, 6.22) (3).
However further criticism advised: ‘A careful analysis of mattress re-use,
stratified by families of different sizes to clarify the possible
importance of parity, which is obscured by the multivariate model used’
(1). Table 1 shows the stratified analysis of the pooled data. The
observed association between used infant mattress and SIDS remains, OR
2.26 (1.40, 3.63).
Of more interest is the alternative hypothesis that the observed
association between parity and SIDS is in fact due to the confounding
effect of used infant mattress and not due to parity at all. The
multivariate fixed effects analysis (3) inferred this conclusion as parity
became insignificant only when used infant mattress was added to the
model. Using stratified analysis we confirm that the increase in the risk
of SIDS associated with each one unit increase in parity, OR 1.49 (1.28,
1.73), almost disappears, OR 1.20 (0.95, 1.50), when controlled for used
infant mattress and the matched nature of the data.
In summary, parity does not confound the association between used
infant mattress and SIDS; on the contrary, used infant mattress is in fact
the probable reason for the observed association between parity and SIDS
in Scotland.
References
1. Fleming PJ, Blair PS, Mitchell EA. Mattresses, microenvironments, and
multivariate analyses. BMJ 2002; 325: 981-982.
2. Brooke H, Gibson A, Tappin D, Brown H. Case-control study of Sudden
Infant Death Syndrome in Scotland 1992-5. BMJ 1997; 314: 1516-20.
3. Tappin D, Brooke H, Ecob R, Gibson A. Used Infant Mattresses and Sudden
Infant Death Syndrome (SIDS) in Scotland. A Case-control study. BMJ 2002;
325:1007-9.
4. Gregory G. Expert rebuffs cot death study. New Zealand Herald; Section
1, page 3, 4th November 2002.
Competing interests:
None declared
Competing interests: Table 1: Stratified unmatched analysis of the effect ofUsed Infant Mattress on Sudden Infant Death Syndromecontrolling for ParityUsed infant mattressParity New Used OR(95%CI) MHOR(95%CI)3+ SIDS 8 28 3.75(1.14,12.69) 2.26(1.40, 3.63)controls 15 14 1.00 3 SIDS 17 37 2.46(1.13,15.41) controls 43 38 1.00 2 SIDS 24 50 1.88(1.02,3.46) controls 83 92 1.00 1 SIDS 51 28 3.92(2.06,7.48) controls207 29 1.00 Total SIDS 100 143 2.88(2.08, 3.99) controls348 173 1.00 MHOR is the Mantel Haenszel Odds Ratio showingthe association between used infant mattressand SIDS after controlling for parity and thematched nature of the data.