The authors are to be thanked for looking into outcomes of fetuses
identified with Critical Congenital Heart Disease (CCHD) based on the
location of birth. Bennett et al (1) came to the same conclusion: that
birth hospital had little impact on survival. As the authors point out,
75% of CCHD may be missed during prenatal evaluations. This means that the
physicians at the non-specialty hospitals have to be able to recognize...
The authors are to be thanked for looking into outcomes of fetuses
identified with Critical Congenital Heart Disease (CCHD) based on the
location of birth. Bennett et al (1) came to the same conclusion: that
birth hospital had little impact on survival. As the authors point out,
75% of CCHD may be missed during prenatal evaluations. This means that the
physicians at the non-specialty hospitals have to be able to recognize and
stabilize these critically ill babies. Based on the data from Anagnostou
et al and Bennett, I argue that it is better to deliver these babies
wherever the mother wants and provide local support as necessary. These
episodes of planned care will help the local staff remain competent to
care for the majority of patients with CCHD who will arrive unexpectedly.
(1) Influence of Birth Hospital on Outcomes of Ductal-Dependent
Cardiac Lesions Tellen D. Bennett, Matthew B. Klein, Mathew D. Sorensen,
Anneclaire J. De Roos
and Frederick P. Rivara DOI: 10.1542/peds.2009-2829
; originally published online November 22, 2010; 2010;126;1156 Pediatrics
We read with interest the thought provoking paper written by Dr.
Bodeau-Livinecr and colleagues on behalf of the EPIPAGE. They concluded
that compared with very preterm singletons, twins had higher mortality, no
difference in severe deficiencies, but slightly lower Mental Processing
Composite scores at 5 years. 1
The Authors suggest that although all the infants studied who were
born preterm had been exposed...
We read with interest the thought provoking paper written by Dr.
Bodeau-Livinecr and colleagues on behalf of the EPIPAGE. They concluded
that compared with very preterm singletons, twins had higher mortality, no
difference in severe deficiencies, but slightly lower Mental Processing
Composite scores at 5 years. 1
The Authors suggest that although all the infants studied who were
born preterm had been exposed to a pregnancy complication that had led to
their early birth, these may not be the same (i.e. in utero death of the
co-twin, being born second, monochorionic placenta, and birthweight
discordance) and may not have the same neurodevelopmental consequences in
singletons and twins. 1
Accumulating evidence indicates that the prenatal environment plays a
significant role in shaping children's neurodevelopment. Some authors
hypothesize that prenatal psychological distress on the part of the mother
is a risk factor for children's neurocognitive development. 2 We have been
assessing subjective states in singleton and twin pregnant women using
L?scher's 8-color test. 3 According to test results, singleton and twin
pregnant women share feelings denoting a particular emotional state,
idealizing their status, although perceiving it as stressful. Twin
pregnant women are afraid of building a relationship with their infants
and those women who became pregnant with twins following assisted
reproduction technologies perceive their pregnancy as exhausting,
characterized by a deep-seated anxious state and by the wish to give
birth soon. This is a particularly complex situation in which mothers are
at risk for anxiety, depression, and unsatisfactory postnatal bonding.
Studies specifically including maternal psychological distress in
their design will be able to assess the relative and/or synergistic impact
of these prenatal experiences on developmental trajectories. Once again,
we would like to thank the Authors for bringing these considerations to
the forefront and hope to read other articles on this timely subject.
References
1. Bodeau-Livinec F, Zeitlin J, et al. Do very preterm twins and
singletons differ in their neurodevelopment at 5 years of age? Arch Dis
Child Fetal Neonatal Ed. 2013 Jul 17.
I enjoyed reading this paper, but I have some comments about the
statistics, which I think should have been picked up in the peer review
process.
In the paper it is stated that the Bland Altman plot showed good
correlation. Correlation should produce a coefficient and a p-value.
The paper does not report the value for the mean difference between
the two methods. From the graph it looks about -0.01 mmol/L. The limits of
agreement look to be about 0.49 mmol/L to -0.49 mmol/L.
I estimate the standard deviation of the differences to be around
0.25 mmol/L, making the standard error of the mean about 0.02 mmol/L. Thus
there is no systematic difference between the two methods as the 95%
confidence intervals for the mean difference are approximately 0.03 mmol/L
to -0.05 mmol/L, crossing zero.
If you want to replace one measure with another you must demonstrate
that there is no a systematic difference. While it is implicit in the
figures and text it is not stated.
More importantly 95% of the differences are within 0.5 mmol/L.
However, once the glucose value in the baby is only 2 to 2.5 this has
massive clinical importance.
I think there are 2 ways of addressing this issue. First whatever your
unit's lower limit of glucose acceptability is you must add the limits of
agreements to that (0.5 mmol/L in this case). However, would it be better,
given the consequences of prolonged hypoglycaemia, to calculate the 99%
confidence interval, or even higher and add that to your usual lower
limit. If enough samples were collected it is possible to calculate a
minimum acceptable value for the new test.
There is another method to address the accuracy of the new
instrument, although seemingly constant, but possibly significantly
clinically less reliable at lower glucose readings. We note that the
spread of difference is reasonably constant over the range of
measurements, as suggested in the graph. However, at 8 mmol/L the limits
of agreement of 0.5 mmol/L represent a margin of error of around 6%, but
at 2 mmol/L it is 25%. I have seen studies re-plot the Bland Altman graph
with the differences as a percentage of the mean value. In this case it
would emphasise how at clinically important low values, an in house
guideline must be in place to ensure that hypoglycaemia is not
undiagnosed.
It is my firm belief that these issues should have been picked up in
the peer review. The authors could have then have shown the data I have
estimated and concluded that their validation is useful for their unit,
but your unit would need to do its own testing before adopting this new
method of measuring glucose in preterm arterial samples.
I read with great interest the commentary by John D. Lantos on the
SUPPORT study controversy. Dr. Lantos makes a compelling argument that the
OHRP was misguided in its criticism of SUPPORT, primarily because both
arms of the trial were within standard of care.1-2
Eligible infants whose parents refused to participate in SUPPORT
received the same medical care, but instead of randomization via protocol,
they were su...
I read with great interest the commentary by John D. Lantos on the
SUPPORT study controversy. Dr. Lantos makes a compelling argument that the
OHRP was misguided in its criticism of SUPPORT, primarily because both
arms of the trial were within standard of care.1-2
Eligible infants whose parents refused to participate in SUPPORT
received the same medical care, but instead of randomization via protocol,
they were subject to "idiosyncratic clinical judgments in the absence of
good evidence."1 That is a frightening concept. How can it be easier for a
physician to change clinical practice on a whim than it is for her to
study those very same differences in practice using the scientific method?
I agree that the informed consent process needs to change, but I
propose that we change the entire system. If both intervention arms of a
clinical trial are within standard practice, the IRB should not require
written informed consent at all. "In such situations," according to Dr.
Lantos, "there may be no incremental risk to being in a study. There may
even be some benefit." 1 Of course, these studies would continue to
require verbal assent from parents and prior approval from the IRB, but
shifting to an opt-out rather than an opt-in regime would significantly
benefit the progress of medicine. Indeed, some institutions outside of the
United States have already adopted this policy.3
No one wants to get rid of oversight for clinical research entirely,
but too much oversight has had a measurable and significant chilling
effect on scientific advancement.4 In my opinion, there is no doubt that
the obstacles to initiating and conducting clinical research would be more
navigable without the burden of universal written informed consent.
REFERENCES 1. Landtos JD. Learning the right lessons from the SUPPORT
study controversy. Arch Dis Child Fetal Neonatal Ed. 2013;epub ahead of
print. 2. SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal
Research Network. Target ranges of oxygen saturation in extremey preterm
infants. N Engl J Med. 2010;362:1959-1969. 3. Reignier J, Mercier E, Le
Gouge A, et al. Effect of not monitoring residual gastric volume on risk
of ventilator-associated pneumonia in adults receiving mechanical
ventilation and early enteral feeding: a randomized controlled trial.
JAMA. 2013;309:249-56 4. O'Herrin JK, Kudsk K, Frost N. Health insurance
portability Accountability Act (HIPAA) regulations: effect on medical
record research. Ann Surg. 2004;239:772-776.
Enrico Bertino (1), Silvano Milani (2), Elena Spada (2)
(1). Department of Public and Pediatric Health Sciences - Neonatal
Unit, Universita' degli Studi di Torino
(2). Department of Clinical Sciences and Community Health - Unit of
Medical Statistics & Biometry, Universita' degli Studi di Milano
Sir, we have read with great interest the paper by Cole et al. (1) on
the longitudinal growth in infants bo...
Enrico Bertino (1), Silvano Milani (2), Elena Spada (2)
(1). Department of Public and Pediatric Health Sciences - Neonatal
Unit, Universita' degli Studi di Torino
(2). Department of Clinical Sciences and Community Health - Unit of
Medical Statistics & Biometry, Universita' degli Studi di Milano
Sir, we have read with great interest the paper by Cole et al. (1) on
the longitudinal growth in infants born below 32 weeks of gestation. It
raises a current and essential problem that neonatologists and
paediatricians take on daily: how to evaluate somatic growth in preterm-
born infants and children.
Cole et al. describe postnatal weight growth of preterm neonates,
analysing a very large number infants. They observe that the weight gain
of the mean growth curve peaks at about 16 g/kg/d at 32 weeks and falls to
about 8 g/kg/d at 42 weeks, i.e. about 4 and 14 weeks after birth, mean
gestational age at birth being 28.14 weeks (as can be derived from table 1
in their paper). We reported analogous results in a paper which described
the growth of 262 very low birth weight infants between birth and two
years of age (2). In particular, we also noticed that growth rate
presents an early peak (17.9 g/kg/d) at 3 weeks after birth, and falls to
10 g/kg/d at 14 weeks. These findings were based on a much lower number
of neonates (262, instead of 5009) selected according to a different
criterion of inclusion (birth weight below 1,500 g, instead of gestational
age below 32 weeks), and on a quite different approach to model individual
growth shape and trace median growth curve. This seems to confirm that
the peak in growth rate, observed in both studies a few weeks after birth
in preterm babies, is a fact, not an artifact due to the methods used to
analyze data.
We are grateful to Cole et al. for their important contribution which
clearly shows the pattern of postnatal growth in preterm neonates. We
hope that further studies may shed light on the biological mechanisms that
control postnatal weight gain in preterm and term babies.
1. Cole TJ, Statnikov Y, Santhakumaran S, Pan H, Modi N; on behalf of
the Neonatal Data Analysis Unit and the Preterm Growth Investigator Group.
Birth weight and longitudinal growth in infants born below 32 weeks'
gestation: a UK population study. Arch Dis Child Fetal Neonatal Ed. 2013,
Epub ahead of print.
2. Bertino E, Coscia A, Mombro' M, Boni L, Rossetti G, Fabris C, Spada E,
Milani S. Postnatal weight increase and growth velocity of very low
birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2006, 91:F349-56
At the end of this helpful review the Guideline is unclear, and
potentially harmful, regarding Vitamin D supplementation.
The phrase: "If no increase in phosphate levels and ALP continues to rise,
consider" suggests that otherwise Vitamin D supplements should not be
considered. The AAP guidance quoted, as well as clear guidance now in the
UK from the Chief Medical Officers, the RCPCH and the British Paediatric
and Adolesc...
At the end of this helpful review the Guideline is unclear, and
potentially harmful, regarding Vitamin D supplementation.
The phrase: "If no increase in phosphate levels and ALP continues to rise,
consider" suggests that otherwise Vitamin D supplements should not be
considered. The AAP guidance quoted, as well as clear guidance now in the
UK from the Chief Medical Officers, the RCPCH and the British Paediatric
and Adolescent Bone Group is that babies with many other risk factors
should have Vitamin D supplements (eg babies born to Vitamin D deficient
mothers).
More importantly the suggestion that "ergocalciferol or alphacalcidol" be
considered is wrong. Ergocalciferol (vitamin D2) or cholecalciferol
(Vitamin D3) are similar and should be considered. Alphacalcidol is a
potent activated form of Vitamin D and should only be used with caution
and by metabolic bone physicians or endocrinologists. Vitamin D dose
recommendations vary between experts and national policies because little
pharmacological data is available yet. In a neonatal unit these doses can
be increased as long as the recommended monitoring suggested in this paper
is followed (weekly blood bone profile). If hypercalcaemia develops
Vitamin D supplements should be stopped until the blood Vitamin D and
Parathyroid hormone levels are known.
Sir, we thank Professor Bertino and his colleagues for their interest
in our paper. We too were struck by the existence of a peak in relative
weight velocity (g/kg/d) at 30-35 weeks postmenstrual age. It is striking
that the timing of the peak is broadly the same irrespective of gestation
- neonates born at 23 weeks take 10 weeks or so to reach peak velocity,
whereas those born at 31 weeks reach their peak in only 2-3 wee...
Sir, we thank Professor Bertino and his colleagues for their interest
in our paper. We too were struck by the existence of a peak in relative
weight velocity (g/kg/d) at 30-35 weeks postmenstrual age. It is striking
that the timing of the peak is broadly the same irrespective of gestation
- neonates born at 23 weeks take 10 weeks or so to reach peak velocity,
whereas those born at 31 weeks reach their peak in only 2-3 weeks. Of
course these are average figures, and individuals vary considerably in
their age at peak velocity, and this may be a risk factor for later
adverse outcomes over and above their gestational age.
T J Cole and H Pan
Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of
Child Health, London, UK
Y Statnikov, S Santhakumaran and N Modi
Imperial College London, Section of Neonatal Medicine, London, UK
Randomised controlled trial of early frenotomy in breastfed infants
with mild-moderate tongue-tie. Edmond et al (2014)
Dear Editor,
I read this report on frenotomy to support breastfeeding with great
interest as currently there is limited evidence to support this procedure.
The outcomes contrast considerably with my own experience and audit data,
particularly with regard to persistence of breastfeeding for more...
Randomised controlled trial of early frenotomy in breastfed infants
with mild-moderate tongue-tie. Edmond et al (2014)
Dear Editor,
I read this report on frenotomy to support breastfeeding with great
interest as currently there is limited evidence to support this procedure.
The outcomes contrast considerably with my own experience and audit data,
particularly with regard to persistence of breastfeeding for more than 5
days with painful breast and objective improvement in breastfeeding at 5
days. Of course, it is not uncommon for mothers and babies to attend for
frenotomy after 5 days as time is needed to learn the art and skill of
breastfeeding before intervention, but that was not the scope of this
report. That mothers report improved self-efficacy after frenotomy
certainly fits with my experience and data, but I find that most continue
to breastfeed as their babies can latch, and both enjoy breastfeeding post
-frenotomy.
I have run frenulotomy clinics for the north west region of England for
six years, using validated assessment tools for frenulotomy , latch, self-
efficacy and pain. The women's experience of feeding is assessed pre-
operatively and immediately post-frenulotomy, and then by telephone at 24-
48 hours and again at 3 months. Of 2048 babies that were in need of
frenuotomy (November 2008 to January 2014), 62.7% of had 100% tongue-tie
(to the tip of the tongue), 12.2% had 75% tongue-tie, and 15.7% had a
posterior tongue-tie. All were referred for assessment and division by a
person skilled in infant feeding and following support with positioning
and attachment to improve breastfeeding. If the baby was formula milk-fed
by bottle, the referring practitioner had provided support with the
technique. Assessment carried out by two International Board Certified
Lactation Consultants indicated that the babies referred with notable
feeding challenges had limitations when extending, lifting and
lateralising their tongues.
Following frenotomy, 96% of mothers reported an immediate difference with
feeding. For example, breastfeeding mothers reported reduction in pain,
improved latch was noted, and later improved contentment and in some cases
weight gain. Bottle-feeding mothers suggested improvements such as baby
not chomping on the teat, no spurting of milk from the sides of the baby's
mouth, and more controlled and faster feeding.
At 48 hours, 71% of mothers who responded continued to experience improved
feeding, 29% of the sample either did not answer the phone, or were
already managing problems such as fungal infections, sore nipples or low
milk supply that would take time to resolve. At 3 months the sample size
was poor: only 21% of mothers answered the call. Yet 43% of this group
were continuing with exclusive breastfeeding and suggested that without
frenulotomy they would not have achieved this.
A study to provide stronger evidence of these outcomes is being submitted
for funding, and a comparison of results will be interesting. The reasons
for differences in outcomes will be important in enhancing frenulotomy
and breast-feeding support services.
Dr Val Finigan MBE
Consultant Midwife infant feeding
Pennine Acute NHS Hospitals Trust
Rochdale Road
Oldham
OL1 2JH
I am writing to express my concern regarding the discordance between the results and conclusions of this paper. The paper compares a point of
care glucose measurement with a laboratory "gold standard". The results
are presented in a number of forms (and with no consistency regarding
units of measurement). The error-grid analysis is unhelpful as high
levels will be high and low levels will be low for both methods and the
scale...
I am writing to express my concern regarding the discordance between the results and conclusions of this paper. The paper compares a point of
care glucose measurement with a laboratory "gold standard". The results
are presented in a number of forms (and with no consistency regarding
units of measurement). The error-grid analysis is unhelpful as high
levels will be high and low levels will be low for both methods and the
scale of the graph is too large to see what the real differences are. The
"accurate estimate zone" includes potential values 4mmol/l above and below
zero in the lower glucose range.
Whilst the authors are to be applauded for inserting a Bland Altman plot,
this plot demonstrates "limits of agreement" which are around 0.5mmol/l
above and below the line of zero. 6 points lie outside the limits of
agreement with the extremes being 0.7mmol/l above and below zero.
Therefore the plot demonstrates that in an unpredictable manner the
glucometer may be over reading or under reading by a value as great as
0.7mmol/l. This is not of clinical significance in the normoglycaemic or
hyperglycaemic range, but acquires clinical significance when blood
glucose levels are low. For example if a glucometer reading is 2.0mmol/,
the accurate level (at the extreme) could be 1.3-2.7mmol/l which will
result in over diagnosis and treatment or under diagnosis and treatment.
The authors state in the results section that the plot shows "good
correlation", but the plot does not represent correlation, and the
agreement between the values is not good.
The conclusion that there is good "correlation" between the glucometer and
the laboratory measurement draws on the wrong statistical method.
Correlation does not provide accuracy data. Under "what this study adds"
it is stated that the glucometer provides accurate results and is suitable
for measuring glucose levels in premature infants. I suggest that the
results as plotted on Bland Altman plot are directly counter to this
conclusion.
We read Val Finigan's letter with interest, and agree with her
experience that most mothers do report an improvement in the comfort and
efficacy of breastfeeding after their baby has had a frenotomy. The
difficulty is in showing objective improvement in breastfeeding after
division of less severe degrees of tongue tie.
In the Bristol Tongue Tie Trial, the median age of the babies at...
We read Val Finigan's letter with interest, and agree with her
experience that most mothers do report an improvement in the comfort and
efficacy of breastfeeding after their baby has had a frenotomy. The
difficulty is in showing objective improvement in breastfeeding after
division of less severe degrees of tongue tie.
In the Bristol Tongue Tie Trial, the median age of the babies at
recruitment was 5 days, and the median age at follow-up for the primary
outcome was 11 days. We are now planning a larger trial of frenotomy,
involving all degrees of tongue tie, with a primary outcome 2 weeks after
recruitment, using a more detailed tool to assess breastfeeding.
For more information on the proposed trial design, please contact
alan.emond@bristol.ac.uk
Yours sincerely,
Alan Emond
Jenny Ingram
Centre for Child and Adolescent Health, University of Bristol
The authors are to be thanked for looking into outcomes of fetuses identified with Critical Congenital Heart Disease (CCHD) based on the location of birth. Bennett et al (1) came to the same conclusion: that birth hospital had little impact on survival. As the authors point out, 75% of CCHD may be missed during prenatal evaluations. This means that the physicians at the non-specialty hospitals have to be able to recognize...
We read with interest the thought provoking paper written by Dr. Bodeau-Livinecr and colleagues on behalf of the EPIPAGE. They concluded that compared with very preterm singletons, twins had higher mortality, no difference in severe deficiencies, but slightly lower Mental Processing Composite scores at 5 years. 1
The Authors suggest that although all the infants studied who were born preterm had been exposed...
Dear Editor,
I enjoyed reading this paper, but I have some comments about the statistics, which I think should have been picked up in the peer review process.
In the paper it is stated that the Bland Altman plot showed good correlation. Correlation should produce a coefficient and a p-value.
The paper does not report the value for the mean difference between the two methods. From the graph it...
I read with great interest the commentary by John D. Lantos on the SUPPORT study controversy. Dr. Lantos makes a compelling argument that the OHRP was misguided in its criticism of SUPPORT, primarily because both arms of the trial were within standard of care.1-2
Eligible infants whose parents refused to participate in SUPPORT received the same medical care, but instead of randomization via protocol, they were su...
Enrico Bertino (1), Silvano Milani (2), Elena Spada (2)
(1). Department of Public and Pediatric Health Sciences - Neonatal Unit, Universita' degli Studi di Torino (2). Department of Clinical Sciences and Community Health - Unit of Medical Statistics & Biometry, Universita' degli Studi di Milano
Sir, we have read with great interest the paper by Cole et al. (1) on the longitudinal growth in infants bo...
At the end of this helpful review the Guideline is unclear, and potentially harmful, regarding Vitamin D supplementation. The phrase: "If no increase in phosphate levels and ALP continues to rise, consider" suggests that otherwise Vitamin D supplements should not be considered. The AAP guidance quoted, as well as clear guidance now in the UK from the Chief Medical Officers, the RCPCH and the British Paediatric and Adolesc...
Sir, we thank Professor Bertino and his colleagues for their interest in our paper. We too were struck by the existence of a peak in relative weight velocity (g/kg/d) at 30-35 weeks postmenstrual age. It is striking that the timing of the peak is broadly the same irrespective of gestation - neonates born at 23 weeks take 10 weeks or so to reach peak velocity, whereas those born at 31 weeks reach their peak in only 2-3 wee...
Randomised controlled trial of early frenotomy in breastfed infants with mild-moderate tongue-tie. Edmond et al (2014)
Dear Editor, I read this report on frenotomy to support breastfeeding with great interest as currently there is limited evidence to support this procedure. The outcomes contrast considerably with my own experience and audit data, particularly with regard to persistence of breastfeeding for more...
I am writing to express my concern regarding the discordance between the results and conclusions of this paper. The paper compares a point of care glucose measurement with a laboratory "gold standard". The results are presented in a number of forms (and with no consistency regarding units of measurement). The error-grid analysis is unhelpful as high levels will be high and low levels will be low for both methods and the scale...
Dear Editors:
We read Val Finigan's letter with interest, and agree with her experience that most mothers do report an improvement in the comfort and efficacy of breastfeeding after their baby has had a frenotomy. The difficulty is in showing objective improvement in breastfeeding after division of less severe degrees of tongue tie.
In the Bristol Tongue Tie Trial, the median age of the babies at...
Pages