The landmark research by Yoshinaga-Itano et al of the USA in 1998[1]
provided by far the greatest impetus for the current global drive for the
detection of newborns with permanent congenital and early-onset hearing
loss (PCEHL) before 3 months and intervention by 6 months of age. However,
there have since been reservations about the generalisability of the 6
months threshold for optimal outcome...
The landmark research by Yoshinaga-Itano et al of the USA in 1998[1]
provided by far the greatest impetus for the current global drive for the
detection of newborns with permanent congenital and early-onset hearing
loss (PCEHL) before 3 months and intervention by 6 months of age. However,
there have since been reservations about the generalisability of the 6
months threshold for optimal outcomes in cognitive, speech and language
development across populations.[2,3] The recent review by Kennedy and
McCann[4] has highlighted significant differences between this earlier US
study and current findings from Australia and UK on optimal threshold for
efficacious intervention..
It is difficult to predict ways in which the emerging evidence will
affect public health policy on universal newborn hearing screening (UNHS).
It may well be that there will never be a uniform age when intervention
can be considered late within and across populations But there is little
doubt that this information is quite important for the beneficiaries of
UNHS as well as the service providers. For instance, it could abate the
sense of hopelessness that is often inadvertently conveyed to parents who
may prefer more time beyond the hospital stay to confront and overcome the
anxiety about possible screening outcomes. Similarly, it offers service
providers wider time-span for detecting some children with progressive and
late-onset hearing loss that would have been otherwise missed by current
UNHS programmes.
It could be rightly argued that there is no effective alternative to
screening of all newborns before hospital discharge if we must detect the
highest number of children with PCEHL as early as possible. Getting
parents to return to hospital solely for newborn hearing screening is less
likely to be as effective, but in busy neonatal units where babies are
discharged in less than 48 hours we may well avoid an Olympic sprint race
to screen by all means because of the hope that the new evidence on early
intervention offers. Perhaps we should place more emphasis on the need to
see parents as much enthusiastic as the service providers about newborn
hearing screening. The chances are that screening will still hardly be
delayed beyond the most propitious period for intervention even in
communities where significant number of births occurs outside hospitals.
References
(1). Yoshinaga-Itano C, Sedey AL, Coulter DK, et al. Language of early- and
later-identified children with hearing loss. Pediatrics 1998;102:1116-71
(3). Olusanya BO, Luxon LM, Wirz SL. Benefits and challenges of newborn
hearing screening for developing countries. Int J Pediatr Otorhinolaryngol
2004;68:287-305
(4). Kennedy C, McCann D. Universal neonatal hearing screening moving from
evidence to practice. Arch Dis Child Fetal Neonatal Ed 2004;89:F378-F383
We read with interest the article on neonatal long lines[1] and the accompanying editorial[2] published in Archives recently. One of the important conclusions reached was that 76% of cases of pericardial effusion/cardiac tamponade occurred in units who aimed to position the tip in the vena cavae. So simply following the Department of Health guidelines to avoid the cardiac chambers may not be sufficient to avo...
We read with interest the article on neonatal long lines[1] and the accompanying editorial[2] published in Archives recently. One of the important conclusions reached was that 76% of cases of pericardial effusion/cardiac tamponade occurred in units who aimed to position the tip in the vena cavae. So simply following the Department of Health guidelines to avoid the cardiac chambers may not be sufficient to avoid this complication, although accurate positioning of long lines clearly remains important.
We undertook an audit to look at the position of the long lines
inserted in our unit (Hammersmith Hospital, London) over a 7 months period
from January to July 2002. All the 66 long lines in 61 neonates,
(Epicutaneo-Cava-Katheter - Vygon, UK) placed during the study period were
reviewed on the Picture Archiving and Communication System (PACS) using
the magic glass (sharpen and invert) tools as surrogate contrasts. All the
films with a long line were looked at to identify malposition and/or
migration. 41 of the 66 long lines were outside the heart in the initial Xray and remained outside henceforth. 15 lines were inside the heart on
the initial Xray but were re-positioned and remained outside thereafter.
10 lines were inside the heart for varying periods. 7 of these 10 lines
were inside the heart from the time of insertion for between 2 to 10 days
before being withdrawn or removed. The remaining 3 lines were in an
acceptable position on the initial Xray but subsequently migrated
remaining inside the heart for 7, 7 and 14 days respectively before being
withdrawn or removed. No instances of pericardial effusion or cardiac
tamponade were observed during the audit period.
Despite attempting to place all long lines outside the heart 10/66
(15%) were inside the heart for times ranging from 2 to 14 days. Long line
position should be carefully checked on insertion and reviewed regularly
as a small but significant number of lines migrate prior to removal.
References
(1) G. Menon. Neonatal Long lines. Arch Dis Child Fetal Neonatal Ed 2003;88:F260–F262.
(2) Beardsall K, White DK, Pinto EM, et al. Pericardial effusion and cardiac tamponade as complications of neonatal long lines: are they really a problem? Arch Dis Child Fetal Neonatal Ed 2003;88:292–5.
We are glad to respond to the comments of Dr. George Morley
[1] on our paper entitled “Multiorgan Dysfunction in Infants with Post-
asphyxial Hypoxic Ischaemic Encephalopathy”.[2] Dr. Morley raised the
possibility that the cause of the HIE in our patients was hypovolaemia due
to deprivation of the placental transfusion (with or without tight nuchal
cord) rather than intrapartum asphyxia. We will att...
We are glad to respond to the comments of Dr. George Morley
[1] on our paper entitled “Multiorgan Dysfunction in Infants with Post-
asphyxial Hypoxic Ischaemic Encephalopathy”.[2] Dr. Morley raised the
possibility that the cause of the HIE in our patients was hypovolaemia due
to deprivation of the placental transfusion (with or without tight nuchal
cord) rather than intrapartum asphyxia. We will attempt to respond to most
of the items in Dr. Morley’s two letters.
First, we wish to define “asphyxia”. Asphyxia is defined in
the literature on either a pathophysiological or syndromal basis. The
former consists of hypoxia, hypercapnia and metabolic acidaemia. The
latter is defined in various consensus statements of national obstetrical
and other professional societies, and in the so-called International
Consensus Statement. [3] It is our strong impression that noone today
accepts depression at birth or, for example a low 5-minute Apgar score as
a definition of asphyxia. We wish to point out that Dr. Morley’s statement
regarding the 5-minute Apgar score is not relevant to our study, as a
score of <_5 was="was" not="not" an="an" essential="essential" inclusion="inclusion" criterion="criterion" it="it" one="one" of="of" three="three" sub-criteria.="sub-criteria." in="in" our="our" response="response" to="to" dr.="dr." morley="morley" the="the" unqualified="unqualified" term="term" asphyxia="asphyxia" indicates="indicates" either="either" pathophysiological="pathophysiological" or="or" syndromal="syndromal" severe="severe" means="means" both="both" and="and" mild="mild" moderate="moderate" implies="implies" only.="only." p="p"/> In his letter, Dr. Morley questions the plausibility of the
diving reflex as a response to asphyxia. Knowledge of the fetal and
neonatal diving reflex is based mainly on experiments in animals, and on
clinical observations in the human newborn infant (we compare the two in
more detail below). For animal data on the diving reflex in severe
asphyxia, the interested reader is referred to the paper of Behrman et
al3, and a detailed recent review by Jensen et al on fetal circulatory
responses to hypoxia and asphyxia induced by various means.4 A
considerable body of evidence suggests that in the human with hypoxia and
asphyxia, the circulation is centralized to brain, heart and adrenal gland
(the so-called “vital organs”).[2,4] Dr. Morley reiterated some of our
criteria for organ involvement and pointed to some differences; owing to
limitations of time we will not deal with our relatively minor differences
of opinion. Dr. Morley points out that the diving reflex “does not last
very long”. At some point in the progression of severe asphyxia in
animals, the reflex breaks down. [4] When the diving reflex breaks down,
the non-vital organs are likely to be more acidotic than the vital organs,
so the latter have a relative advantage. It is reasonable to think that
during the period that the reflex is active and for some period after,
this compensatory mechanism provides relative protection to the vital
organs.
Dr. Morley relates to repeated cord compression, the diving
reflex and organ damage/ dysfunction. Before addressing this issue, we
wish to point out that in contrast to “dysfunction”, organs other than
brain and heart rarely sustain irreversible damage in severe asphyxia. We
therefore prefer to use the term “dysfunction” to “damage”.
In animal models, repeated hypoxic episodes with intervening
episodes of recovery or partial recovery (the prolonged partial asphyxial
model of Myers[5]) was more strongly associated with multi-organ
dysfunction than continued severe asphyxia with prolonged bradycardia (the
“total” asphyxia animal model of Windle[6]).[4] Analogies have been drawn
to human conditions,[7,8] but to our knowledge, no empirical evidence has
been published that compares the multi-organ dysfunction after acute near-
total vs. prolonged partial insults. To clarify this issue, we reviewed
and analyzed our data. Since all of our patients with post-asphyxial
hypoxic ischemic encephalopathy (HIE) had multiorgan dysfunction (MOD),
the subgroups defined by the above time-courses of asphyxial insult were
identical regarding the presence of MOD. We also determined from our data
the proportion of infants with two or more dysfunctional organs in the two
groups. Of infants in the acute near-total group, 70 percent had two or
more dysfunctional organs, whereas 80 percent of infants in the prolonged
partial asphyxia group had two or more dysfunctional organs. This
difference was not statistically significant, nor do we consider it
clinically significant.
Dr. Morley points to hypovolaemia as a pathophysiological
mechanism that may supplement the adverse effects of co-existing asphyxia.
He refers to two causes of hypovolaemia: cord compression as a cause of
acute fetal blood loss into the placenta, and early clamping of the
umbilical cord by depriving the newborn infant of the placental
transfusion. We are glad that Dr. Morley draws attention to these
phenomena; it is our impression that both are under-recognized as
potential contributing causes of brain injury, especially when co-existing
with asphyxia.
Nuchal cord, especially if tight, results in blood loss due
to compression of the umbilical vein but not the arteries, as well as
asphyxia due to failure of placental gas exchange, either or both varying
from none to severe.[4,5] Haemorrhagic shock representing a threat to the
brain occurs only in extreme cases. [6] In our study, we excluded infants
with haemorrhagic shock. Infants thought to have “pure” haemorrhagic
shock, which presents with relatively mild depression at birth and a
progressive postnatal depression until blood volume is replenished, were
excluded. Babies with tight nuchal cord and haemoglobin concentrations
within normal limits were considered to have suffered “pure” asphyxia and
were included in the study. The mean haemoglobin and haematocrits of our
patients (including those with tight nuchal cord) were 161 g/l and 0.47,
higher than the mean values for infants with tight nuchal cord studied by
Cashore and Usher [4] (haematocrit 0.39), and similar to the values
observed by Shepherd et al5 (mean haematocrit 0.48 and haemoglobin 164
g/L), and Linderkamp et al7 (haematocrit 0.46). It is notable that the
infants studied by Cashore and Usher [4] (with an average blood loss of 20
percent of blood volume) showed only pallor and mild hypotension in the
hours after birth; post-asphyxial HIE was not reported. Of the 27 cases of
Shepherd et al5 with tight nuchal cord eligible for their study, [5] had
haemoglobin values less than 132 g/L (which we consider to be well below
the lower limit of normal) and [3] received emergency blood transfusion
for pallor, tachycardia and hypotension. These authors also did not report
HIE in their subjects. In our experience term infants can tolerate acute
blood losses of up to 40 percent of blood volume and even more without
developing obvious haemorrhagic shock, provided that they are free of
preceding or concurrent asphyxia.
Early clamping of the umbilical cord with deprivation of the
placental transfusion is also a well established cause of peri-partum
hypovolaemia. Many published studies have compared early with delayed
timing of cord clamping of apparently healthy infants born after
uncomplicated pregnancy and parturition or Caesarean section. A number of
studies of preterm infants have also been performed. In many studies,
early clamping was accomplished within seconds of birth. Delayed clamping
was defined in most studies as three minutes after birth or by cessation
of cord pulsation. The effects of “delayed” and “early” cord clamping have
been compared for a great variety of end-points including haematological,
respiratory, cardiovascular, rheological and renal function measurements.
Early clamping undoubtedly leaves some infants “with an uncomfortably
small blood volume”.8 On the other hand, late clamping is associated with
more jaundice [9] and hyperviscosity. [10] To our knowledge, a
comprehensive health outcome has not been studied in relation to placental
transfusion.
Studies of the effects of timing of cord clamping in
severely asphyxiated infants and experimental animals have provided mixed
results. According to Smith [11] “perinatal asphyxia may speed and
increase the process of placental transfusion, even unto a prenatal
transfusion.”[11] Hey [8] stated that “fatally asphyxiated babies usually
have a relatively high haematocrit and circulating blood volume at birth.”
The studies of Ackerman and colleagues [12,13] showed that infants with
low Apgar scores and low umbilical arterial pH at birth tended to have
small residual placental blood volumes, suggesting that a shift of blood
volume from placenta to foetus had preceded cord clamping. These
observations accord with those of Behrman et al in the experimental fetal
primate. [14]
By contrast, acute intrapartum asphyxia defined as a 1-
minute Apgar score of 5 or less was found to be associated with a reduced
haematocrit of 0.49 (cord clamped at 15 seconds) as compared with 0.54 in
infants with scores of 6 or greater (both were delivered vaginally). [7]
This was considered to be caused by a shift of blood from fetus to
placenta. In view of the early cord clamping at 15 seconds, another
interpretation of this finding is possible. The infants with low 1-minute
Apgar scores may represent the infants to which Dr. Morley refers. The
depressed 1-minute Apgar scores and lower haematocrits may be attributable
to early clamping of the cord and deprivation of a relatively large
portion of the placental transfusion in some infants. As with the
instances cited above from the literature, no mention is made of HIE in
the 17 term infants studied. In addition, the definition of “acute
intrapartum asphyxia” would not be acceptable on either pathophysiological
or syndromal grounds.
The appropriate time to clamp the cord of babies with severe
asphyxia has, to our knowledge, not been the subject of clinical trial. In
a review of placental transfusion, Yao and Lind [15] stated: “In the
presence of foetal distress or birth asphyxia, even during a vaginal
delivery, it is also advisable not to delay clamping of the cord to avoid
hypovolaemia except when there is obvious evidence of fetoplacental
bleeding before and during birth and the infant appears pale and in shock.
In such circumstances, cord clamping should be delayed if resuscitation
can be given simultaneously. Otherwise, early separation of the infant
from the cord will facilitate the resuscitation.”
Non-response to initial resuscitation measures suggests the
possibility of hypovolaemia and the need for blood volume expansion.
During placement of the umbilical venous catheter, central venous pressure
can be measured; a low pressure is an additional indication for emergency
blood volume expansion. Blood volume expansion is initially provided by
colloid or crystalloid, soon followed by blood if indicated. [16] Group O
rhesus negative whole blood should be given with great urgency if there is
historical or physical evidence of a large acute blood loss (e.g.,
velamentous insertion of the cord with a tear in a large blood vessel;
incision of the placenta prior to the delivery of the infant during the
Caesarean section) and if the infant has signs of haemorrhagic shock
(extreme pallor, weak peripheral pulses, hypotension, etc.).
The appropriate time to clamp the cord in an intermediate
group of infants born after complicated deliveries with relatively mild
depression has also not been the subject of clinical trial. We have seen
babies born with mild to moderate asphyxia associated with tight nuchal
cord, whose condition deteriorated after birth until the hypovolaemia was
corrected, and who proved to be moderately severely anaemic. The severity
of the anaemia caused by deprivation of blood volume in some cases of
tight nuchal cord is far greater than the physiological placental
transfusion would have been. A similar effect can be caused by gravity
(holding the newly born infant well above the level of the placenta before
clamping the cord).[17] Another potential cause of neonatal blood loss is
the removal of cord blood for banking for possible future autologous cord
blood transplantation (blood volumes as large as 110 ml, or about one-
third of a 4 kg birth weight infant, have been banked). Hypovolaemia
associated with mild to moderate intrapartum asphyxia, if not speedily
recognised and treated by blood volume expansion, may cause neonatal
morbidity.
We did not find the statement attributed by Dr. Morley to
Peltonen18 that “In the compromised neonate, immediate cord clamping may
result in fatality” was not found on review of the cited article. Peltonen
[18] did allude to the “highly unphysiological” effects of early clamping
on the neonatal heart during the first three or four cardiac cycles after
cord clamping and before the first breath. He also referred to the animal
study of Born et al [19] in which clamping of the cord before the onset of
pulmonary respiration caused “profound asphyxia”. Despite these
observations, Peltonen [18] concluded his review of early cord clamping
with the citation that “It appears that umbilical cord clamping should be
done at the discretion of the obstetrician.”
To our knowledge no studies have been conducted that
compared measures of neonatal well being including morbidity and mortality
in early-clamped with late-clamped term infants born after uncomplicated
deliveries. This is not surprising in light of the large sample size that
would be required for such a trial, and ethical hesitations about
depriving some infants of large blood volumes, and causing polycythemia in
others. In light of the observed adverse associations with very early and
with delayed clamping, avoiding these extremes would appear to be
sensible. Likewise, delay in resuscitation of a severely asphyxiated
infant to await a placental transfusion that is unlikely to occur owing to
constricted umbilical arteries is likely to cause more harm than benefit.
One circumstance that may justify an attempt to resuscitate
the term infant with an intact foetal circulation may be after delivery
complicated by tight nuchal cord in which it proved possible to deliver
the infant without ligating and cutting the cord. Even in this situation,
one can speculate that delay in clamping the cord may be harmful. For
example, re-establishing the umbilical-foetal placental circulation after
a period of stasis may cause placental thromboembolism and consequent harm
such as neonatal stroke.
Randomized controlled trials comparing different timings of
placental transfusion may be justified for some populations. One example
referred to above is mild to moderate asphyxia where it is likely that the
infant is in primary rather than secondary apnoea. Another is the newly
born small for gestational age infants (presumably the “intra-uterine
asphyxia” or placental insufficiency group of Linderkamp [7]). On the
other hand, in our opinion it would be far more difficult to persuade a
research ethics committee today to approve a comparative trial of delayed
clamping (with attendant suboptimal conditions for resuscitation) versus
immediate clamping (to optimize the resuscitation conditions) in severely
asphyxiated infants who are most likely in secondary apnoea. Likewise, it
would be difficult to justify a comparison of measures of neonatal well
being, morbidity and mortality in very early-clamped with very late-
clamped apparently healthy term infants, especially as so much is known
about the effects of deprivation or maximization of placental transfusion
in these infants. Whatever happens to the depressed infant at birth with
regard to cord-clamping, the team progressing through the steps of
resuscitation should not overlook the possibility that blood volume
expansion may urgently be indicated.
With regard to sampling of blood gases Dr. Morley refers to the “later
withdrawn” ACOG Practice Bulletin 138 which suggested that obstetricians
clamp the cord quickly in order to send samples for blood gases. In the
process they “amputate a functioning placenta”. He advises “the prudent
obstetrician” to “approach the pulsating cord with due caution”. We agree
with this advice with emphasis on “a pulsating cord”. Parenthetically,
repeated research has indicated that delayed cord clamping is advantageous
for the adaptation of the preterm infant to extra-uterine life.[20,21] The
reason often given in the past for early clamping of preterm infants was
the perceived threat of the increased levels of jaundice associated with
late clamping in the pre-phototherapy era. This is of much less concern
today than it was when phototherapy was unavailable and before it was
found to be efficacious and safe. Late clamping of preterm infants is
probably safer than early clamping.
We agree that for the infants who are more likely than not
to benefit from delayed cord clamping, the technical difficulty that may
be caused by the delay in sampling from the cord artery may be relatively
unimportant, and the potential enhancement of the circulating blood volume
is the greater priority. To complete the diagnosis (pathophysiological or
syndromal) of asphyxia, and if necessary its treatment, a sample can be
taken from the infant rather than the cord. This has the advantage of
avoiding errors such as sampling from the umbilical vein instead of an
artery. Moreover, even umbilical arterial samples after severe cord
compression are occasionally unrepresentative of the infant’s condition at
birth, and capillary sampling is likely to reflect the infant’s current
condition more accurately.
Dr. Morley also addressed the issue of hypoxic versus
ischemic aetiopathogenesis of brain lesions. Considerable ambiguity exists
between the terms “hypoxia” and “ischaemia”. From the aetiological
standpoint (aetiology meaning “root cause”) we interpret Dr. Morley’s
statements to differentiate between the hypoxia of asphyxia, and the
ischaemia of hypovolaemia (in the context of his letter, hypovolaemia is
caused by acute blood loss due to deprivation of the placental
transfusion, associated or not with early cord clamping or tight nuchal
cord). From the aetiological standpoint, we prefer the term “haemorrhagic
shock” to describe the latter condition. Haemorrhagic shock causes tissue
hypoxia, the end-results of which on brain and other organs are very
similar to those of severe asphyxia (incidentally, one intermediate result
that asphyxia and hypovolaemic shock have in common is the centralization
of the blood circulation).
On the other hand, severe asphyxia is often associated with
hypotension, the pathogenesis (mechanism as opposed to aetiology) of which
is vasodilatation. Whatever the pathogenesis of ischaemia in severely
asphyxiated infants (eg, cerebral vasoconstriction due to break-down in
the protective diving reflex, cardiogenic shock, or hypovolaemic shock of
the various causes considered above), it is considered to be the more
important pathogenetic mechanism of brain injury than the hypoxia that is
an essential part of the definition of asphyxia (with mild to moderate
asphyxia, the fetus is unlikely to develop ischaemia and to sustain brain
injury).
The complexity of these overlapping conditions is nicely illustrated by
the example of extreme cases of tight nuchal cord in which severe asphyxia
and haemorrhagic shock coexist. To our knowledge brain MRI cannot
differentiate between the end-results of severe asphyxia with secondary
brain ischaemia, and haemorrhagic shock.
As indicated above, we wish to compare the primate fetus with severe
asphyxia studied mainly between the 1960s and the 1970s as a model for
brain injuries associated with severe fetal asphyxia in the human. Dr.
Morley’s statement that “the degree of asphyxia in the human HIE neonate
is minor compared to that required to damage a monkey’s brain” is
surprising. The relative immaturity of the term human fetus and the larger
stores of glycogen compared with the monkey fetus would be expected to
provide the human with greater tolerance to severe asphyxia. This appears
to be supported by empirical data. Perusal of recently published case
series that report durations of sustained bradycardia and outcomes in a
variety of near-total asphyxia scenarios shows that the human fetus with
sustained bradycardia seems to have greater staying power than the
experimental fetal term monkey with total asphyxia and sustained
bradycardia. For example, in a report of the short-term outcomes of the
babies of 97 women with uterine rupture (82 of whom had a trial of
labour); it was observed that “significant neonatal morbidity” occurred
only in those cases in which “18 or more minutes elapsed between the onset
of the prolonged deceleration and delivery”. This was the case even in
cases that had prior severe late or variable decelerations. Of the 13
babies with sustained decelerations for 18 or more minutes without prior
severe late or variable decelerations, only one (with 32 minutes of
deceleration) had a severe neonatal outcome, viz, HIE (the long-term
outcome was not reported). [22]
Review of published case series of severe total or near-total asphyxia
provides a similar perspective. For example, Cases 3 and 4 of Pasternak
and Gorey [23] had uterine rupture and known durations of bradycardia (18
and 15 minutes); their outcomes were relatively moderate (respectively,
mild spasticity and dystonia with normal cognition and head circumference
at 3.5 years of age, and mild transient hypotonia and normal cognition and
head circumference at 4 years of age). Of particular interest is Case 9
with umbilical cord rupture (an acute total asphyxia; blood loss was not
mentioned); sustained bradycardia was present for 31 minutes; this infant
had mild transient hypotonia with normal cognition and head circumference
at 18 months. [23] These durations of bradycardia are beyond the duration
of bradycardia seen in experimental total asphyxia that proved lethal in
term rhesus monkeys.
We summarize by stating where we agree and disagree with Dr.
Morley. We disagree that “Most, if not all neonates in this study had the
placenta amputated at the moment of birth together with a large volume of
blood.” In our opinion, it is likely that the umbilical cord had lost its
function in the great majority of our cases by the time the cord was
clamped; these were cases of severe asphyxia. In our opinion, maintaining
the umbilical cord connection was unlikely to provide a placental
transfusion. “Amputation” of a non-functioning placenta with poor
potential for recovery of function is appropriate. Based on the
eligibility and exclusion criteria of our study, and on the haemoglobin
and haematocrit values reported here, we are confident that immediate cord
clamping did not cause significant blood losses in the great majority of
our cases.
On the other hand we emphasize that we agree with Dr. Morley
that early clamping of the pulsating cord of an infant may cause harmful
blood losses and postnatal haemorrhagic shock, particularly in infants who
were mildly to moderately asphyxiated at birth with a shift of blood
volume from fetus to placenta. Similarly, placement of an infant above the
level of the placenta without clamping the still-functioning cord, or
“transplanting” cord blood in large volume may cause harmful blood losses.
Dr. Morley has drawn attention to aspects of neonatal care that are
sometimes overlooked in contemporary practice. We hope that this
correspondence will stimulate clinicians to review the older literature on
placental transfusion, cord clamping, and haemorrhagic shock. Where
questions still remain to be answered, there is a place for new clinical
and even animal studies to elucidate the role of sequestration of blood in
the placenta in the aetiopathogenesis of maladaptation at birth, and of
neonatal brain illness and injury.
References
(1). Morley GM. Hypovolemia:The Cause of Multiorgan Dysfunction. 2004. BMJ
Publishing Group. http://fn.bmjjournals.com/cgi/eletters/89/2/F152#407
(2). Shah P, Riphagen S, Beyene J, Perlman M. Multiorgan
dysfunction in infants with post-asphyxial hypoxic-ischaemic
encephalopathy. Arch Dis Child Fetal Neonatal Ed 2004;89:F152-F155.
(3). MacLennan A. A template for defining a causal relation
between acute intrapartum events and cerebral palsy: international
consensus statement. BMJ 1999;319:1054-9.
(4). Cashore WJ, Usher RH. Hypovolemia resulting from tight
nuchal cord at birth. Pediatr Res 1973;7:339.
(5). Shepherd AJ, Richardson J, Brown JP. Nuchal cord as a
cause of neonatal anemia. Am J Dis Child 1985;139:71-3.
(6). Vanhaesebrouck P, Vanneste K, De Praeter C, Van Trappen
Y, Thery M. Tight nuchal cord and hypovolaemic shock. Arch Dis Child
1987;62:62-3.
(7). Linderkamp O, Versmold HT, Messow-Zahn K, Muller-Holve
W, Riegel KP, Betke K. The effect of intra-partum and intra-uterine
asphyxia on placental transfusion in premature and full-term infants. Eur
J Pediatr 1978;127:91-9.
(8). Hey E. Resuscitation at birth. Br J Anaesth 1977;49:25-
33.
(9). Saigal S, O'Neill A, Surainder Y, Chua LB, Usher R.
Placental transfusion and hyperbilirubinemia in the premature. Pediatrics
1972;49:406-19.
(10). Linderkamp O, Nelle M, Kraus M, Zilow EP. The effect
of early and late cord-clamping on blood viscosity and other
hemorheological parameters in full-term neonates. Acta Paediatr
1992;81:745-50.
(11). Smith CA, Nelson NM. The physiology of newborn infant.
In: Thomas CC, 4th ed. 1976:157-77.
We thank Dr Theo Fenton and Professor Murat Yurdakok for their responses.[1,2]
We agree with Dr T Fenton that there is the practical question of how
much information can we give. However we think a policy of “don’t ask,
don’t tell” may be unwise.
Professor M Yurdakok discusses the issue with regards to Islam. We
are grateful to him for providing religious guidance, which may help
fa...
We thank Dr Theo Fenton and Professor Murat Yurdakok for their responses.[1,2]
We agree with Dr T Fenton that there is the practical question of how
much information can we give. However we think a policy of “don’t ask,
don’t tell” may be unwise.
Professor M Yurdakok discusses the issue with regards to Islam. We
are grateful to him for providing religious guidance, which may help
families to be optimally informed.
Clinicians know that the source of these two surfactants is from minced
pig and cow lung. Most people know that Muslims and Jews avoid pork while
Hindus avoid beef for religious reasons. We also know that there is no
important clinical difference in efficacy between these products. While
there is a choice of products, should we allow parents to choose on
religious grounds? The Scottish executive has recently advised
paediatricians to inform parents of the source of these products.
Part of the reason for our letter was to report that where fully
explained the issues, some families had a clear view. We think most
parents will accept these products, but favour open discussion of the
issues. We would favour similar candour with Jehovah’s witnesses.
We have read with interest Forsyth et al’s article in your journal
[1]. They have concluded that “angiotensin converting enyzme (ACE) is
increasingly identified as a risk factor for cardiovascular disease, and
serum activity in infancy may contribute to the link between low birth
weight and later cardiovascular events.”
We think, in this manner that it is inappropriate to come to a...
We have read with interest Forsyth et al’s article in your journal
[1]. They have concluded that “angiotensin converting enyzme (ACE) is
increasingly identified as a risk factor for cardiovascular disease, and
serum activity in infancy may contribute to the link between low birth
weight and later cardiovascular events.”
We think, in this manner that it is inappropriate to come to a conclusion
by means of Forsyth et al’s study methods since none of the cardiologic
parameters of any healthy term infants were assessed in the study. Though
emphasizing the ACE being important in regulation of peripheral blood
pressure, arterial pressure measurements on infants were done neither at
birth, nor 1st and 3rd months. Nevertheless, some influent questions
mentioned below remained unanswered:
1.How many infants of high ACE level
had any cardiologic problems?
2.How many infants were assessed
echocardiographically?
3.Are all of the infants of lower ACE levels
healthy cardiologically?
The authors stressed on their conclusion that especially “later”
cardiovascular events had a relation with ACE level. However “later”
cardiovascular events could not be foreseen by following up the infants
for 3 months.
Overall, mentioning the relation would be impossible. There is a need for
controlled studies having longitudinal extended case numbers and well-
monitorized cardiologic parameters.
Reference
(1). Forsyth JS, Reilly J, Fraser CG, Struthers AD. Angiotensin converting
enyzme activity in infancy is related to birth weight. Arch Dis Child
Fetal Neonatal Ed 2004;89:F442-F444.
The original article from Cambridge by Beardsall et al.[1] reminds us of
the problems of neonatal long lines and also presented the outcome of
managing cardiac tamponade in 82 cases.
In my unit in a busy district
general hospital with 3 NICU cots with an average of 3300 deliveries per
year and with 10% of this admitted to the neonatal unit, we have had a
share of this rare problem. In the l...
The original article from Cambridge by Beardsall et al.[1] reminds us of
the problems of neonatal long lines and also presented the outcome of
managing cardiac tamponade in 82 cases.
In my unit in a busy district
general hospital with 3 NICU cots with an average of 3300 deliveries per
year and with 10% of this admitted to the neonatal unit, we have had a
share of this rare problem. In the last 10 years we have regularly
inserted neonatal catheters for parenteral feeding and also inserted
umbilical catheters for fluid resuscitation when venous access is
difficult. On average, 20-50 catheter insertions occur every year. Over
this period we have experienced the unfortunate death of a term newborn
who had a portex catheter inserted for the infusion of hypertonic dextrose
solution for managing persisting hypoglycaemia. An unexpected collapse did
occur which made us suspect cardiac tamponade. Active resuscitation was
carried out but was regrettably unsuccessful.
The DOH inquiry[2] into the cases in greater Manchester has highlighted the
need for vigilance and the ensuing debates has created more questions
which calls for appropriate research to establish the right answers.
Although this is a rare complication, (1 case in 10 years from my unit),
it can result in fatality. Cardiac tamponade remains a serious
complication that must be considered always and should leave no room for
complacency.
We have since strengthened our good practice guideline for the use of
neonatal catheters especially after the DOH reviews. We run through the
following points each time a central line insertion is contemplated: (a) Decide if catheter use was the best mode for venous access for the neonate. (b) The person inserting must be experienced or adequately supported by an accomplished colleague. (c) When a decision to insert a catheter is taken an informed consent is obtained from parents. The need for the insertion is discussed and complications detailed. (d) After placement, contrast is used to locate position and this is adequately documented. (e) Neonates with indwelling catheter have detailed review of line care and splinting of limb is encouraged to minimise migration. Any sudden deterioration in clinical state is flagged as possible cardiac tamponade (vigilance).
(f) The length of stay for catheters is constantly reviewed and removed as soon as alternative means for nutrition is established. (g) Consultant must be involved in the decision to insert neonatal catheter.
There is need to determine the best position for indwelling catheters, the
type of catheter material, and best way to prevent migrations. The DOH
report has highlighted this issue and made suggestions based on limited
evidence. In this review, Beardsall et al showed that 50 out of 60
patients survived after management of this complication. Therefore
vigilance and prompt action to treat is essential and units performing
this procedure must be able to provide emergency treatment for cardiac
tamponade.
References
(1) Beardsall K, White D, Pinto EM et al. Pericardial Effusion and cardiac
Tamponade as complications of neonatal long lines; Are they really a problem? Arch Dis Child Fetal Neonatal Ed. 2003;88;F292-295.
(2) Department of health Review of deaths of 4 babies due to cardiac Tamponade associated with the presence of central venous catheter. London:HSMO, 2001.
The primary immunisation schedule in the UK is about to change for
the seventh time since the accelerated schedule was introduced in 1990.
The latest change, to a combined DTPaHibIPV vaccine (Pediacel), provoked a
flurry of lay concern.
Given the rapid advancement of vaccine technology that has prompted
such frequent changes to our primary immunisation policy it is inevitable
that we would...
The primary immunisation schedule in the UK is about to change for
the seventh time since the accelerated schedule was introduced in 1990.
The latest change, to a combined DTPaHibIPV vaccine (Pediacel), provoked a
flurry of lay concern.
Given the rapid advancement of vaccine technology that has prompted
such frequent changes to our primary immunisation policy it is inevitable
that we would have lessons to learn along the way. Amongst the important
ones are that not all populations respond to vaccines alike, (preterm
populations are different from those born at term [1], and ethnicity
matters [2]), interactions occur if vaccines are combined [3], and ‘minor’
changes may have ‘major’ consequences (DTPaHib combinations result in far
poorer Hib protection than DTPwHib combinations [4]).
It is sometimes impossible to determine precisely which immunisations
have been given to a study population, and how they were administered –
for example whether as separate or combined immunisations. Whilst we read
with great interest further data from Clarke and Robinson [5] on the
effect of steroid treatment on preterm infants’ immunisation responses
several important points are illustrated. The twelve infants reported
share identical demographic characteristics with (and are presumably the
same infants as) 12 infants previously reported in this journal after a
fourth dose of conjugate Haemophilus influenzae type b (Hib) vaccine (PRP-
T), where the implication was that a booster dose of PRP-T in such infants
would not increase Hib protection [6]. In the original paper no mention is
made of the fact that the extra PRP-T dose was actually administered with
DTPw, a fact only deducible with care 18 months later, yet one which may
alter the interpretation of the original paper. Likewise, the historical
data from both Ramsay [7] and Booy [8] predate the introduction of Hib and
Men C into the schedule. Comparison of the post primary immunisation GMTs
presented by Clarke [5] (immunised with the Trivax AD DTP vaccine) with
those of a more contemporaneous group of preterm steroid treated infants
(immunised with the Pasteur Meriuex DTPHib vaccine [9]) shows that only
the 95% confidence intervals for FIM and FHA overlap:
Vaccine Study
GMT
(95% CI)
Trivax AD(9)
ActHibDTP(5)
Diphtheria
0.424 (0.29-0.6)
2.08 (1.39-3.10)
Tetanus Pertussis
0.62 (0.42-0.91)
3.15 (1.67-5.93)
FIM
5085 (3360-7697)
15922 (6869-36908)
PT
264
(185-375)
1567 (613-4005)
FHA
1382 (1025-1863)
3011 (1806-5022)
As the schedule changes yet again may we suggest that future
publications ensure clear and explicit identification by name,
manufacturer and method of administration of all vaccines administered to
study subjects, whether or not the antibody response to a particular
component is the major focus of the paper. Such information would clearly
aid interpretation of the data.
References
(1). Slack MH, Schapira D, Thwaites RJ, Burrage M, Southern J, Andrews
N, et al. Immune response of premature infants to meningococcal serogroup
C and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus
influenzae type b conjugate vaccines. Journal of Infectious Diseases
2001;184(12):1617-20.
(2). Ward J, Brenneman G, Letson G, Heyward W, and the Alaskan
Haemophilus influenzae group. Limited efficacy of a Haemophilus influenzae
type b conjugate vaccine in Alaskan native infants. New England Journal of
Medicine 1990;323:1393-1401.
(3). Bell F, Martin A, Blondeau C, Thornton C, Chaplais J and Finn A.
(1996) Combined diphtheria, tetanus, pertussis, and Haemophilus influenzae
type b vaccines for primary immunisation. Archives of Disease in
Childhood;75(4):298-303.
(4). Eskola J, Olander RM, Hovi T, Litmanen L, Peltola S, Kayhty H.
Randomised trial of the effect of co-administration with acellular
pertussis DTP vaccine on immunogenicity of Haemophilus influenzae type b
conjugate vaccine. Lancet 1996;348(9043):1688-92.
(5). Clarke P, Robinson M. DTP immunisation of steroid treated preterm
infants. Archives of Disease in Childhood Fetal & Neonatal Edition
2004;89:F468-470.
(6). Clarke P, Powell P, Goldblatt D, Robinson M. Effect of a fourth
Haemophilus influenzae type b immunisation in preterm infants who received
dexamethasone for chronic lung disease. Archives of Disease in Childhood
2003;88(S1):58-61.
(7). Ramsay ME, Miller E, Ashworth LA, Coleman TJ, Rush M, Waight PA.
Adverse events and antibody response to accelerated immunisation in term
and preterm infants. Archives of Disease in Childhood 1995;72(3):230-2.
(8). Booy R, Aitken SJ, Taylor S, Tudor-Williams G, Macfarlane JA,
Moxon ER, et al. Immunogenicity of combined diphtheria, tetanus, and
pertussis vaccine given at 2, 3, and 4 months versus 3, 5, and 9 months of
age. Lancet 1992;339(8792):507-10.
(9). Robinson M, Heal C, Gardener E, Powell P, Sims D. Antibody
response to diphtheria-tetanus-pertussis immunisation in preterm infants
who receive dexamethasone for chronic lung disease. Pediatrics
2004;113(4):733-737.
In this interesting and very important study where each newborn with fever was compared to an afebrile neonate matched for gestational age and
date of birth, the authors used a logistic model to test for risk factors
associated with fever. Unfortunately, their results may not be valid as in
matched case control studies, a conditional logistic model should have
been used instead. The reviewers of the manusc...
In this interesting and very important study where each newborn with fever was compared to an afebrile neonate matched for gestational age and
date of birth, the authors used a logistic model to test for risk factors
associated with fever. Unfortunately, their results may not be valid as in
matched case control studies, a conditional logistic model should have
been used instead. The reviewers of the manuscript, with the help of a
statistical adviser, should have advised the authors to use the
appropriate method prior to publication, if the validity and credibility
of the results of this very important study are to be ensured. In the age
of evidence-based medicine when most readers are not necessarily familiar
with advanced statistics, the role and responsibilities of reviewers and
statistical advisers become even more crucial.
We are grateful to colleagues for their comments on our annotation.[1]
We would stress that we merely abstracted the views of others so any
criticisms (apart from our brevity) will be of the lawyers, doctors,
nurses, physiotherapists and parents who contributed to the Royal
Commission Report. We found it to be systematic, rational and objective.
We strongly refute any suggestion that any of t...
We are grateful to colleagues for their comments on our annotation.[1]
We would stress that we merely abstracted the views of others so any
criticisms (apart from our brevity) will be of the lawyers, doctors,
nurses, physiotherapists and parents who contributed to the Royal
Commission Report. We found it to be systematic, rational and objective.
We strongly refute any suggestion that any of the New Zealand
professionals should be criticised let alone made scapegoats (witness our
final paragraph). We are puzzled that Drs Rosenbloom and Ryan discount
the quoted witness statements of the parents and involved clinicians. The
lawyers and doctors are clear that the physiotherapy and nursing practices
did occur and that the levels of head shaking were not monitored.
We are concerned with infant brain injuries not lung disease and
consider this to be topical. We share colleagues’ concern at the need to
base opinions on speculative presumption extrapolated from animal or
accident research and are aware of the limited evidence that identifies
the minimal forces needed to cause shaken brain damage in neonates or
older infants. We found the reported experiences to be a helpful insight.
We are delighted that Dr Rushton (eLetter) has taken this opportunity
to state he thought vigorous chest physiotherapy without supporting the
head was responsible for the porencephalic lesions and to
inform of his pivotal involvement in advising New Zealand colleagues. We
understand there were earlier concerns that publishing the speculation
about physiotherapy would open liability to litigation. Lawyers might
consider the inference that fear of litigation led to suppression of
information that might have prevented the New Zealand deaths and the
dilemma facing clinicians who reported the cerebral implications of
vigorous physiotherapy. Dr Knight reports (eLetter) their unit has been
‘subject to a long official public inquiry, law suits and had twenty
medical, nursing and physiotherapy staff investigated by registration
authorities, lasting 8 years.’
We do not accept criticisms of inaccurate references. The Cochrane
review we both cited was last updated in 1997. There has been an updated
review this year (dealing with lung not brain disease), which was
unavailable to the editors or us at the time of submission. Dr Knight
(eLetter) states there was no change in the vigour of chest physiotherapy
from 1985 until the end of 1994 but he co-authored the paper [2] we cited
that states that there was no policy to support the head during chest
physiotherapy and no data on the extent the head moved during
physiotherapy whether given by nurses or physiotherapists. The Royal
Commission Report found no record of the vigour of chest percussion and
understood there was considerable variation with no standardisation of
training.
We recommend interested colleagues to read this Report and the
publications of Knight and Harding et al before dismissing the possibility
that vigorous chest physiotherapy without supporting the head may cause
brain injuries in certain circumstances.
References
(1) Williams AN, Sunderland R, Neonatal shaken baby syndrome: an
aetiological view from Down Under. Arch Dis Child 2002;87:F29-30
(2) Knight DB, Bevan CJ, Harding JE, et al. Chest physiotherapy and
porencephalic lesions in very preterm infants. J Paediatr Child Health
2001;37:554–8.
Wright and Lee's article [1] provides an excellent overview of the
options to consider when parents decline the offer of conventional autopsy
following perinatal death.
Although a less invasive autopsy (LIA), such as one based on MRI, may
be more acceptable to many parents, the provision of such a service could
have significant implications, not just with regard to the availability of
a scar...
Wright and Lee's article [1] provides an excellent overview of the
options to consider when parents decline the offer of conventional autopsy
following perinatal death.
Although a less invasive autopsy (LIA), such as one based on MRI, may
be more acceptable to many parents, the provision of such a service could
have significant implications, not just with regard to the availability of
a scarce resource, in terms of availability of MRI services but also with
regard to how such a service should be provided.
Just as perinatal autopsy has largely become a regional specialist
service, it could be argued that MRI LIA (if offered) should also be a
regional specialist service, as smaller centres are unlikely to acquire
the expertise with smaller local numbers of perinatal deaths. In addition,
as experience is being acquired, conventional post-mortem should be
performed on referrals for MRI autopsy, and therefore probably restricted
to research studies, with appropriate informed consent.
If LIA was indeed more acceptable to parents, this would have
significant implications for audit and counselling. As Wright and Lee
highlight, current evidence suggests that MRI autopsy may not detect
clinically significant anomalies in different organ systems including the
gastrointestinal tract and the heart. Other abnormalities such as
anomalous lung lobation may also go undetected, and the quality of
counselling by obstetricians and neonatologists could be reduced. Genetic
syndromes may not be recognised, or be misdiagnosed, with false-negative
findings.
The loss of the 'gold-standard' autopsy would also have implications
for audit within fetal medicine and obstetric ultrasound services.
Although published work on post-mortem MRI of the fetal CNS is
encouraging [2], with regard to its specificity and sensitivity, we need
more data with which to counsel parents who are seeking a less-invasive
autopsy, but also potentially to explain its limitations in the apparent
absence of abnormality on MRI (even after one was suspected on antenatal
ultrasound, for example). Absence of evidence of abnormality (normal MRI
autopsy) cannot be at present equated with evidence of absence of
abnormality (normal conventional autopsy), and parents must be aware of
this when making choices at this difficult time. Consent for a
conventional or less-invasive autopsy, must therefore be sought by a
skilled clinician aware of these difficulties, as well as insight into
organ and tissue retention issues.
The proposed DoH-funded Less Invasive Autopsy studies [3] will make a
welcome contribution to our understanding of this area.
References
(1). Wright, C and Lee, REJ. Investigating perinatal death: a review of
the options when autopsy consent is refused
Arch. Dis. Child. Fetal Neonatal Ed. 2004; 89: F285-F288
(2). Griffiths, P.D., et al., Postmortem MR imaging of the fetal and
stillborn central nervous system. AJNR Am J Neuroradiol, 2003. 24(1): p.
22-7.
Dear Editor,
The landmark research by Yoshinaga-Itano et al of the USA in 1998[1] provided by far the greatest impetus for the current global drive for the detection of newborns with permanent congenital and early-onset hearing loss (PCEHL) before 3 months and intervention by 6 months of age. However, there have since been reservations about the generalisability of the 6 months threshold for optimal outcome...
Dear Editor
We read with interest the article on neonatal long lines[1] and the accompanying editorial[2] published in Archives recently. One of the important conclusions reached was that 76% of cases of pericardial effusion/cardiac tamponade occurred in units who aimed to position the tip in the vena cavae. So simply following the Department of Health guidelines to avoid the cardiac chambers may not be sufficient to avo...
Dear Editor,
We are glad to respond to the comments of Dr. George Morley [1] on our paper entitled “Multiorgan Dysfunction in Infants with Post- asphyxial Hypoxic Ischaemic Encephalopathy”.[2] Dr. Morley raised the possibility that the cause of the HIE in our patients was hypovolaemia due to deprivation of the placental transfusion (with or without tight nuchal cord) rather than intrapartum asphyxia. We will att...
Dear Editor
We thank Dr Theo Fenton and Professor Murat Yurdakok for their responses.[1,2]
We agree with Dr T Fenton that there is the practical question of how much information can we give. However we think a policy of “don’t ask, don’t tell” may be unwise.
Professor M Yurdakok discusses the issue with regards to Islam. We are grateful to him for providing religious guidance, which may help fa...
Dear Editor,
We have read with interest Forsyth et al’s article in your journal [1]. They have concluded that “angiotensin converting enyzme (ACE) is increasingly identified as a risk factor for cardiovascular disease, and serum activity in infancy may contribute to the link between low birth weight and later cardiovascular events.”
We think, in this manner that it is inappropriate to come to a...
Dear Editor
The original article from Cambridge by Beardsall et al.[1] reminds us of the problems of neonatal long lines and also presented the outcome of managing cardiac tamponade in 82 cases.
In my unit in a busy district general hospital with 3 NICU cots with an average of 3300 deliveries per year and with 10% of this admitted to the neonatal unit, we have had a share of this rare problem. In the l...
Dear Editor,
The primary immunisation schedule in the UK is about to change for the seventh time since the accelerated schedule was introduced in 1990. The latest change, to a combined DTPaHibIPV vaccine (Pediacel), provoked a flurry of lay concern.
Given the rapid advancement of vaccine technology that has prompted such frequent changes to our primary immunisation policy it is inevitable that we would...
Dear Editor
In this interesting and very important study where each newborn with fever was compared to an afebrile neonate matched for gestational age and date of birth, the authors used a logistic model to test for risk factors associated with fever. Unfortunately, their results may not be valid as in matched case control studies, a conditional logistic model should have been used instead. The reviewers of the manusc...
Dear Editor
We are grateful to colleagues for their comments on our annotation.[1] We would stress that we merely abstracted the views of others so any criticisms (apart from our brevity) will be of the lawyers, doctors, nurses, physiotherapists and parents who contributed to the Royal Commission Report. We found it to be systematic, rational and objective.
We strongly refute any suggestion that any of t...
Dear Editor,
Wright and Lee's article [1] provides an excellent overview of the options to consider when parents decline the offer of conventional autopsy following perinatal death.
Although a less invasive autopsy (LIA), such as one based on MRI, may be more acceptable to many parents, the provision of such a service could have significant implications, not just with regard to the availability of a scar...
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