The study of Platt and Pharaoh, confirms the increased risk of SIDS
in twins compared to singletons.[1] They point out that a major component of
that higher accrued risk is that twins tend to be of low birthweight.
Their finding that like-sex twins are at no greater risk than unlike-sex
twins adds to the substantial evidence concerning the very limited role of
genetic susceptibility for SIDS, and the rari...
The study of Platt and Pharaoh, confirms the increased risk of SIDS
in twins compared to singletons.[1] They point out that a major component of
that higher accrued risk is that twins tend to be of low birthweight.
Their finding that like-sex twins are at no greater risk than unlike-sex
twins adds to the substantial evidence concerning the very limited role of
genetic susceptibility for SIDS, and the rarity of recurrence in siblings
of victims.[2]
The authors illustrate the gratifying fall in the number of SIDS
during the six years of their 1990's study. As the number of infants
categorised each year as SIDS in England and Wales comes nearer to that of
200, so it becomes more important for those involved in epidemiological
studies to be sure that the categorisation (i.e. the diagnosis) is
correct.
I refer to infants who a few years after they have been categorised
as SIDS have been re-assessed, usually because of a subsequent child being
abused or killed, and, in the course of court proceedings, findings are
made that the previous infant/s were killed by the parent, rather than
dying of natural causes. Currently, there does not seem to be a mechanism
for correcting the national childhood mortality statistics when later,
correct diagnoses are made. For instance, in the 1990s, I am aware of at
least 20 infants who were initially categorised as SIDS, but who in later
years, after extensive child protection investigations, were deemed to
have been killed, usually by smothering. Colleagues will know of other
cases: the true number will be higher. It is unfortunate that, even in
cases where the finding has been made "beyond all reasonable doubt" in a
criminal court, the official statistics do not seem to be altered, and
remain a misleading figure for any research worker. I should add that,
since none of the cases of parental killing of which I am aware involve
twins, the conclusions of Platt and Pharoah are more likely to have been
strengthened rather than weakened by such false diagnosis. However, as
the number of SIDS continues to fall, it will become ever more difficult
for research workers to compare small sub-groups of SIDS within national
mortality statistics unless the statistics are revised retrospectively in
response to later correct diagnosis.
It is appropriate to warn of an additional hazard for research
workers in this field. In the same issue of The Archives there was an
interesting letter from epidemiologists in Paris concerning the
possibility of vagal over-activity as a cause of sudden infant death.[3]
They referred to a "positive family history of SIDS". A particular hazard
there is that, unless details of that family history are verified in
considerable detail, mistakes may be made. In recent years I have been
involved with families in which parents who have repetitively smothered or
killed children have provided to paediatricians, genetic counselling
services, and to SIDS research workers, a false family history of SIDS -
for instance, mother saying that two of her own siblings "died of SIDS".
Such statements invariably are taken at face value and become part of the
medical history: they are included in family trees in the hospital notes,
and they have been quoted and displayed in published research concerning
SIDS, yet subsequent questioning of the relevant grandparent has revealed
that no such infant deaths occurred. Presumably, the mother responsible
for smothering or killing her child has invented the family history,
either to gain more medical attention for herself, or as a cover to
distract from her actions. A second reason for verifying the alleged
previous infant deaths in more detail is that, even if a death has
occurred, it is necessary to explore the extent of the contemporary
investigation and pathological examination. In one of Professor Emery's
studies of infants initially categorised as SIDS, detailed re-assessment
pointed to either a definite natural cause, or abuse, in two thirds of
cases.[4]
References
(1) Platt MJ. Pharaoh PO.
The epidemiology of sudden infant death syndrome. Arch Dis Child 2003;
88: 27-29.
(2) Hunt CE.
Sudden Infant Death Syndrome and other causes of infant mortality.
American Journal of Respiratory and Critical Care Medicine 2001; 164: 346-
357.
(3) Shojaei-Brosseau T, Bonaiti-Pellie C, Lyonnet S et al. Vagal
overactivity: a risk factor of sudden infant death syndrome? Arch Dis
Child 2003; 88: 88.
(4) Wolkind S, Taylor EM, Waite AJ et al.
Recurrence of unexpected infant death. Acta Paediatr 1993; 82: 873-876.
Although, many studies have shown that breast-feeding reduces the
incidence of allergic diseases and multiple allergic diseases developing
in the same child,[1] there are many controversies to this. Some studies
have shown that children with asthmatic mothers were more likely to
develop asthma later if they were exclusively breast fed [2] whereas some
studies have shown the exact opposite.[3] The breast...
Although, many studies have shown that breast-feeding reduces the
incidence of allergic diseases and multiple allergic diseases developing
in the same child,[1] there are many controversies to this. Some studies
have shown that children with asthmatic mothers were more likely to
develop asthma later if they were exclusively breast fed [2] whereas some
studies have shown the exact opposite.[3] The breast milk of atopic
mothers was found to have cytokines that promote allergy (IL-4, IL-5 and
IL-13).[4] Moreover, concentrations of IL-8 and RANTES, which are
chemoattractants, involved in recruitment and activation of cells involved
with allergic reactions was higher among atopic mothers.[5] This may
explain the controversial finding regarding exclusive breast-feeding and
the subsequent development of allergy in infants.
Allergic diseases such as atopic dermatitis may occur even while
breast-feeding. It has been shown that the protective effect of breast
milk is enhanced if atopic mothers avoid common dietary allergens during
pregnancy and lactation[6] and allergic diseases such as atopic eczema id
reduced if mothers consume probiotics during both pregnancy and lactation.[7]
Therefore, the effects of exclusive breast-feeding in the prevention
of allergic diseases may be enhanced if the lactating mothers are educated
about avoidance of common dietary allergens and consuming food with
probiotics.
References
(1) Kull I, Wickman M, Lilja G, Nordvall SL, Pershagen G. Breast
feeding and allergic diseases in infants-a prospective birth cohort study.
Arch Dis Child 2002 Dec;87(6):478-81
(2) Wright AL, Holberg CJ, Taussig LM, Martinez FD. Factors influencing
the relation of infant feeding to asthma and recurrent wheeze in
childhood. Thorax 2001 Mar;56(3):192-7
(3) Oddy WH, Peat JK, de Klerk NH. Maternal asthma, infant feeding, and
the risk of asthma in childhood. J Allergy Clin Immunol 2002 Jul;110(1):65
-7
(4) Bottcher MF, Jenmalm MC, Garofalo RP, Bjorksten B. Cytokines in
breast milk from allergic and nonallergic mothers. Pediatr Res 2000
Jan;47(1):157-62
(5) Bottcher MF, Jenmalm MC, Bjorksten B, Garofalo RP. Chemoattractant
factors in breast milk from allergic and nonallergic mothers. Pediatr Res
2000 May;47(5):592-7
(6) Chandra RK, Puri S, Suraiya C, Cheema PS. Influence of maternal
food antigen avoidance during pregnancy and lactation on incidence of
atopic eczema in infants. Clin Allergy 1986 Nov;16(6):563-9
(7) Rautava S, Kalliomaki M, Isolauri E. Probiotics during pregnancy
and breast-feeding might confer immunomodulatory protection against atopic
disease in the infant. J Allergy Clin Immunol 2002 Jan;109(1):119-21
I have been disappointed by the lack of response to the paper by Todd et al. [1] and to my accompanying editorial,[2] and I am indebted to Pearce
and Mabin for opening what I hope will be an interesting discussion,
although I must take issue with much of what they say.
Their opening comment to the effect that clinical studies rather than a
questionnaire-based survey should form the basis for advice...
I have been disappointed by the lack of response to the paper by Todd et al. [1] and to my accompanying editorial,[2] and I am indebted to Pearce
and Mabin for opening what I hope will be an interesting discussion,
although I must take issue with much of what they say.
Their opening comment to the effect that clinical studies rather than a
questionnaire-based survey should form the basis for advice on drug
selection does not bear close examination. Had we relied upon clinical
studies, we would still be using Opren?, or for that matter thalidomide.
Surveys, yellow cards and the like are vital in providing early warning of
unforeseen side-effects. As Pearce and Mabin say, many clinical studies
have shown no increased risk of hypothalamic pituitary axis suppression
with fluticasone propionate when compared with other inhaled steroids. On
the basis of such studies, the apparent toxicity of fluticasone at high
doses was indeed unforeseen, and was only likely to have been detected by
the previously published reports and by surveys such as that of Todd et al. As Pearce and Mabin also emphasise, individuals have differing
sensitivities to inhaled corticosteroids. It is because of this that
clinical studies, involving the relatively small numbers of patients
dictated by economics and patient co-operation, are inadequate to identify
the occasional hypersensitive individual, or to determine risk in the
population at large.
It is not in dispute that adrenal suppression is a dose-related class
effect, and has been reported with all inhaled corticosteroids, but this
does not explain the extraordinarily high proportion of reported cases
associated with the use of fluticasone. The results of the questionnaire
survey indicating that fluticasone is favoured by British paediatric
respirologists for high-dose therapy might go some way towards explaining
this proportion, but does not explain why acute adrenal failure was so
rare when the only drugs available for high-dose therapy were Becloforte?
or standard strength budesonide.
Moreover, there are pharmacological reasons to direct the finger of
suspicion at fluticasone. Based on a literature review, Pedersen and
O?Byrne[3] concluded that on a ?g basis fluticasone had three times the
systemic potency of budesonide, whereas it is generally believed to have
only twice the therapeutic activity. Clark et al.[4] also compared
fluticasone and budesonide on a ?g basis, and found in asthmatic children
that fluticasone produced greater adrenal suppression than budesonide.
Examination of their figures suggests that the difference in favour of
budesonide was apparent when the 800 ?g and even the 1250 ?g doses of
budesonide was compared with 400 ?g fluticasone. Although the literature on
fluticasone is voluminous and capable of several interpretations, there is
a very real possibility that fluticasone has greater bioactivity at higher
doses than the alternative inhaled corticosteroids.
Todd et al. have provided us with numerators but no denominators. I
can see no reason for suggesting that these numerators represent anything
other than an underestimate, as I am sure I am not the only clinician to
have put Dr Todd?s questionnaire aside for completion during the sort of
quiet time that never quite seems to occur in paediatrics. What we need
now is denominators in the form of the numbers of prescriptions issued for
high-dose therapy with each of the three corticosteroids licensed in the
UK for inhaled use. Given the volume of prescribing data collected
routinely by the Ministry of Health, it might be possible to get some
approximation of the comparative risk of adrenal suppression on each of
these drugs when used in high dosage. No more than an approximation will
be possible, because of the marked differences in systemic bioavailability
between metered dose inhalers with and without spacers, and dry powder
inhalers,[5] together with variable pulmonary absorption depending upon
age and the state of the airways. Until then, I for one will remain wary
of prescribing any sort of high dose inhaled corticosteroids to children,
but will be particularly wary of fluticasone.
References
(1) Todd GRG, Acerini CL, Ross-Russell R, Zahra S, Warner JT, McCance
D. Survey of adrenal crisis associated with inhaled corticosteroids in the
United Kingdom. Arch Dis Child 2002; 87: 457-461.
(2) Russell G. Inhaled corticosteroids and adrenal insufficiency Arch Dis
Child 2002; 87:455-456.
(3) Pedersen S, O?Byrne P. A comparison of the efficacy abd safety of
inhaled corticosteroids in asthma. Allergy 1997;52 (Suppl 39):1-34.
(4) Clark DJ, Clark RA, Lipworth BJ. Adrenal suppression with inhaled
budesonide and fluticasone propionate given by large volume spacer to
asthmatic children. Thorax 1996;51:941-3.
(5) Martin RJ, Szefler SJ, Chinchilli VM, et al. Systemic effect
comparisons of six inhaled corticosteroid preparations. Am J Respir Crit
Care Med 2002;1.
Statement of conflict of interest I have received fees for delivering lectures,
hospitality at scientific meetings and/or payments to my discretionary funds
for participation in clinical trials or other asthma-related research from
Astra-Zeneca, Fisons Pharmaceuticals, GSK and MSD.
I thank Dr Edge and other correspondents and am gratified that none
dissents from the view of Dr Inward and myself that the assessment and
fluid management of DKA in childhood needs multispecialty review. Perhaps
this is underway: if not then should our College President - Elect invite
his Newcastle colleague Sir George Alberti to convene and chair it?
Dear Editor
The study of Platt and Pharaoh, confirms the increased risk of SIDS in twins compared to singletons.[1] They point out that a major component of that higher accrued risk is that twins tend to be of low birthweight. Their finding that like-sex twins are at no greater risk than unlike-sex twins adds to the substantial evidence concerning the very limited role of genetic susceptibility for SIDS, and the rari...
Dear Editor
Although, many studies have shown that breast-feeding reduces the incidence of allergic diseases and multiple allergic diseases developing in the same child,[1] there are many controversies to this. Some studies have shown that children with asthmatic mothers were more likely to develop asthma later if they were exclusively breast fed [2] whereas some studies have shown the exact opposite.[3] The breast...
Dear Editor
I have been disappointed by the lack of response to the paper by Todd et al. [1] and to my accompanying editorial,[2] and I am indebted to Pearce and Mabin for opening what I hope will be an interesting discussion, although I must take issue with much of what they say. Their opening comment to the effect that clinical studies rather than a questionnaire-based survey should form the basis for advice...
Dear Editor
I thank Dr Edge and other correspondents and am gratified that none dissents from the view of Dr Inward and myself that the assessment and fluid management of DKA in childhood needs multispecialty review. Perhaps this is underway: if not then should our College President - Elect invite his Newcastle colleague Sir George Alberti to convene and chair it?
TL Chambers
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