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Current Pediatric Reviews
ISSN: 1573-3963
Current Pediatric Reviws
Volume 1, Number 3, November 2005
Contents
Twin-to-Twin Transfusion Syndrome: From Placental
Anastomoses to Long-Term Neurodevelopmental Outcome Pp.191
Enrico Lopriore, Johanna M. Middeldorp, Marieke Sueters,
Frank P. Vandenbussche and Frans J. Walther
[Abstract]
Varicella-Zoster Virus Infections During Pregnancy:
Epidemiology, Clinical Symptoms, Diagnosis, Prevention and
Therapy Pp.205
Andreas Sauerbrei and Peter Wutzler
[Abstract]
White Matter Neuroprotection in Preterm Infants Pp.217
Pierre Gressens and Vincent Lelièvre
[Abstract]
Molecular Defects in the Hypothalamic-Pituitary-Thyroid
Axis Leading to Congenital Hypothyroidism Pp.225
Amalia Sertedaki, Antony Voutetakis and Catherine Dacou-Voutetakis
[Abstract]
Non Pharmacological Analgesia for Newborns Pp.235
Carlo V. Bellieni and Giuseppe Buonocore
[Abstract]
Current Outcomes and Considerations in Hypoplastic
Left Heart Syndrome Pp.243
Alexander A. Kon
[Abstract]
The Influence of Traumatic Lumbar Puncture (TLP) on
Outcome of Paediatric Patients Pp. 249
Angela Rech and Algemir L. Brunetto
[Abstract]
What Does a Pediatrician Need to Know About Chronic
Diarrhea? Pp.253
Mukadder A. Selimog and Vildan Ertekin
[Abstract]
Current Options for Treatment of End-Stage Liver Disease
in Children Pp.261
Roberto Gugig and Philip Rosenthal
[Abstract]
Hypersensitivity Pneumonitis Pp.265
James Temprano, Alan P. Knutsen and Raymond G. Slavin
[Abstract]
Defining the Cough Spectrum and Reviewing the Evidence
for Treating Non- Specific Cough in Children Pp.283
Anne B. Chang
[Abstract]
Abstracts
[Back to top]
Twin-to-Twin Transfusion Syndrome: From Placental
Anastomoses to Long-Term Neurodevelopmental Outcome
Enrico Lopriorea, Johanna M. Middeldorpb, Marieke Suetersb,
Frank P. Vandenbusscheb and Frans J. Walthera
Twin-to-twin transfusion syndrome (TTTS) is a complication
of monochorionic twin pregnancies associated with high perinatal
mortality and morbidity. Placental vascular anastomoses, almost
invariably present in monochorionic placentas, are the essential
anatomical substrate for the development of TTTS. According
to recent studies, different pathophysiological mechanisms
may play a role. Diagnosis of TTTS is no longer based on neonatal
criteria such as birth weight discordance and hemoglobin difference,
but on strict prenatal ultrasound criteria. A significant
evolution in prenatal care strategies and management options
for patients with TTTS has occurred during the last decade.
Endoscopical laser ablation of communicating placental vessels
is a new treatment modality that has led to an increase in
survival rates. In perinatology, a decrease in mortality rates
may be associated with an increase in morbidity rates. Follow-up
studies in infants with TTTS are shedding more light on the
wide range of morbidity associated with TTTS, such as neurological,
cardiac and renal sequelae. This review analyzes the possible
pathophysiological mechanisms involved, discusses the latest
findings in diagnosis, therapy and prognosis, and focuses
on neonatal and pediatric morbidity associated with TTTS.
[Back to top]
Varicella-Zoster Virus Infections During Pregnancy:
Epidemiology, Clinical Symptoms, Diagnosis, Prevention and
Therapy
Andreas Sauerbrei and Peter Wutzler
Varicella belongs to serious infections during pregnancy.
After introduction of prevention by vaccination in several
countries, there is a particular interest to learn more about
the consequences of maternal varicella for the infant. Pregnant
women who contract varicella are at risk of severe pneumonia
and death. At any stage during pregnancy, chickenpox may cause
intrauterine infection by placental transmission of the virus.
The consequences for the infant depend on the time of maternal
disease. During the first two trimesters, maternal varicella
may cause the congenital varicella syndrome which has been
reported in about 2%. Maternal infection near term is associated
with a substantial risk of neonatal varicella. Serious disseminated
infections with visceral involvement may occur in the infant.
Aside from epidemiology and clinical consequences, the present
paper reviews the current possibilities of diagnosis, prevention
and therapy of varicella-zoster virus infections during pregnancy.
[Back to top]
White Matter Neuroprotection in Preterm Infants
Pierre Gressens and Vincent Lelièvre
Human preterm infants are at risk to develop cerebral palsy,
cognitive or behavioural impairments. The most recognized
underlying brain lesion in preterms is periventricular white
matter damage (WMD) which can be focal, multifocal or diffuse.
Periventricular leukomalacia is the best described type of
periventricular WMD. Clinical, epidemiological and experimental
studies have allowed demonstrating the multifactorial origin
of these WMD in preterms, generating more than one potential
target for neuroprotection. These studies have permitted to
unravel some key factors such as inflammation and excess production
of cytokines, oxidative stress, hypoxic-ischemic insults,
excess release of glutamate and the excitotoxic cascade. Animal
models have also revealed that pre-oligodendrocytes, macrophages-microglia
and sub-plate neurons are key cells in the pathophysiology
of periventricular WMD. One key safety issue for potential
neuroprotective strategies in premature newborns is the demonstration
of the lack of interference with normal brain development.
Several neuroprotective approaches are currently tested in
animal models of WMD, including drugs targeting glutamate
receptors, drugs targeting inflammation, cytokines or macrophage
activation, anti-oxidant molecules, and strategies such as
growth factors and cell replacement aiming at improving post-lesional
plasticity and tissue repair. Finally, some clinical trials
using magnesium sulfate in preterms have been completed or
are in progress.
[Back to top]
Molecular Defects in the Hypothalamic-Pituitary-Thyroid
Axis Leading to Congenital Hypothyroidism
Amalia Sertedaki, Antony Voutetakis and Catherine Dacou-Voutetakis
In recent years, the application of molecular techniques
in the evaluation of patients with CH has made it possible
to define the molecular basis in a number of cases. A prerequisite
for molecular studies is the distinction between primary and
secondary or central CH. In primary CH (disordered organogenesis
of the thyroid gland or defective thyroxine synthesis), the
genetic defects, thus far identified, include those of genes
encoding the transcription factors TTF1, TTF2 and PAX8 or
the TSHR, NIS, TG and TPO. In some of these molecular abnormalities
(TTF2), CH may be associated with various morphogenetic defects.
In central CH, the defect lies in the hypothalamic-pituitary
axis: TRH synthesis, TRH receptor, synthesis of the TSH β
subunit. The biochemical localization of the defect in such
cases can be accomplished by a TRH test. Genetic defects in
transcription factors involved in pituitary ontogenesis (HESX1,
LHX3, Prop1, Pit1) can also result in CH. In such cases, low
TSH occurs in association with other pituitary hormone deficiencies.
It must be underlined that, in patients with CH, as in other
genetically determined disorders, the localization of the
molecular defect is very important for genetic counseling,
antenatal diagnosis and delineation of prognosis.
[Back to top]
Non Pharmacological Analgesia for Newborns
Carlo Valerio Bellieni and Giuseppe Buonocore
In the last few years much attention has been devoted to
neonatal analgesia, and in particular non-pharmacological
analgesia. We know the effectiveness of oral sucrose administration
and non-nutritional sucking and some papers exist on these
topics. However, there has not been any review of applications
of non-pharmacological analgesia. Here we examine the above
two methods and other strategies described in the literature,
among which: oral glucose, fructose milk or sweeteners; breastfeeding;
cuddling; music; vestibular stimulation; kangaroo care, Newborn
Individualized Developmental Care and Assessment Program (NIDCAP);
sensorial saturation, springloaded lances, supine position,
swaddling and facilitated tucking. Seventy-seven studies assessing
the efficacy of non-pharmacologic procedures for relieving
pain in neonates were identified. It emerges from this review
that certain strategies can be combined with oral sucrose
and non-nutritional sucking to provide effective and almost
complete analgesia for acute pain in neonates.
[Back to top]
Current Outcomes and Considerations in Hypoplastic
Left Heart Syndrome
Alexander A. Kon
Hypoplastic Left Heart Syndrome (HLHS) is a devastating
congenital cardiac defect affecting approximately one thousand
newborns annually in the United States. Without surgery, this
condition is universally fatal. Currently, there are three
management options for children born with HLHS: the Norwood
palliative surgical procedure, neonatal cardiac transplantation,
and comfort care without surgery. In the following review,
I will first briefly describe the anatomy and embryology of
HLHS. I will then describe the three management options, including
published survival statistics, neurodevelopmental outcomes,
and other considerations for infants receiving each of the
treatment options. I will also describe new developments that
may improve outcomes in the near future. Published data of
parental choices in the care of infants born with HLHS, as
well as published data on physician attitudes towards the
three treatment options will be presented. Finally, I will
offer guidelines for physician-parent discussions drawing
from the informed consent literature and case law.
[Back to top]
The Influence of Traumatic Lumbar Puncture (TLP) on
Outcome of Pediatric Patients
Angela Rech and Algemir L. Brunetto
Although lumbar puncture is generally safe, bleeding into
the cerebrospinal fluid (CSF), may occur as a result of trauma
during the procedure. As a consequence bacteria (in patients
with sepsis) or leukemic cells (in patients with leukemia)
circulating in blood may be introduced into the CSF as a result
of TLP. Therefore paediatric preventive measures must be taken
when performing diagnostic LP procedures in pediatric patients
suspected of having leukaemia or bacteremia, including the
use of deep sedation or general anaesthesia, collection of
the initial diagnostic CSF by a very skilled practitioner,
and platelets transfusion for ALL patients with thrombocytopenia
and circulating leukaemic cells.
[Back to top]
What Does a Pediatrician Need to Know About Chronic
Diarrhea?
Mukadder A. Selimog and Vildan Ertekin
A wide spectrum of disorders may cause chronic diarrhea
in children and most of the times, it is not very easy to
establish a specific diagnosis by pediatricians. In this review,
some simple clues regarding history, physical examination,
and laboratory tests are given to pediatricians in order to
help their approach to the infant/child/adolescent with chronic
diarrhea. Among the causes, post-enteritis syndrome, a still
common but under-recognized entity especially in under-developed
or developing countries, is also discussed.
[Back to top]
Current Options for Treatment of End-Stage Liver Disease
in Children
Roberto Gugig and Philip Rosenthal
Liver transplantation has become the accepted method of
treatment for children with end-stage liver disease. Combining
new methods of immunosuppression, modifications in surgical
technique, improved anesthetic management, organ availability,
and identification and treatment of postoperative complications,
survival rates have reached 80% to 90% in many centers performing
pediatric liver transplants.
With the improvement in survival rates, indications for liver
transplantation in children have broadened; however, the availability
of organs suitable for children is still extremely limited.
Although pediatric cases only represent approximately 10%
of the total patients on the waiting list, the number of deaths
on the waiting list increased from 196 in 1988 to 1753 in
1999.
The recent development of surgical procedures that enable
the use of cut down “reduced” livers, split liver
grafts (splitting a cadaveric liver for 2 different recipients),
and living related donors, are creating new options for the
long list of children waiting for hepatic transplants.
In light of the increasing incidence of liver disease and
continuing shortage of donor organs, cell-based therapies
are getting attention as promising treatments for liver failure.
These include: isolated cell transplantation, tissue engineering
of implantable constructs, transgenic xenotransplantation,
and extracorporeal bioartificial liver devices.
Hepatocyte transplantation aims to correct inborn errors
or acquired liver function defects by supplying metabolically
active cells to the diseased liver. Experimentally, hepatocytes
can be successfully isolated by collagenase digestion of the
liver. Cells can then be transplanted in the spleen or the
liver via the portal vein or hepatic artery. In both
sites, cells engraft and become metabolically active, can
synthesize albumin, or correct inborn errors of metabolism.
They have been shown to prolong survival in models of fulminant
liver failure, and so far have been shown to bring partial
metabolic control in Crigler-Najjar disease type I and Refsum
disease. Extracorporeal support for patients with liver failure
has been attempted for over 40 years. Various nonbiological
approaches have met with limited success, presumably because
of the role of synthetic and metabolic functions of the liver
that are inadequately replaced in these systems. Bioartificial
devices typically incorporate isolated cells into bioreactors
to simultaneously promote cell survival and function as well
as provide for the level of transport seen in vivo.
While the safety of bioartificial liver devices has been established,
there are no uniform standards of efficacy that may vary with
the etiology of the liver failure. Consensus is needed in
clinical trial design, including choice of the end points,
use of controls, and indications for enrollment. Also, a better
understanding of the interplay between liver regeneration
and bioartificial liver support therapy will be critical to
optimizing the implementation of this modality.
Pediatric liver transplantation is a challenging and rewarding
field with continued improvement in patient and graft survival.
A multidisciplinary team approach coupled with improvement
in organ availability, immunosuppression, and peri-operative
management has had a dramatic impact on survival. The increasing
incidence of liver disease and continuing shortage of donor
organs has led to the development of new therapies using cell-based
therapies as an alternative to transplantation. The procedure
is less radical, less invasive, potentially less expensive,
and fully reversible. It may, to a certain extent, alleviate
the problem of organ shortage.
Despite these advances, transplantation remains a costly
procedure and patients still require lifelong immunosuppressive
therapy subjecting them to potential side effects and infections.
In some children with liver disease, transplantation is the
only alternative, whereas in others the risks and benefits
must be considered relative to other treatment options.
[Back to top]
Hypersensitivity Pneumonitis
James Temprano Alan P. Knutsen and Raymond G. Slavin
Hypersensitivity pneumonitis (extrinsic allergic alveolitis)
is an immunological mediated hypersensitivity reaction to
a variety of inhaled allergens that may cause an acute and
subacute interstitial pneumonitis and may lead to a chronic
end-stage lung disease. Though more common in adults, hypersensitivity
pneumonitis needs to be considered in the differential diagnosis
of interstitial pneumonitis in children. In children, the
most common antigens are from residential exposure to birds,
humidifiers and indoor molds. Clinical features are dependent
upon stage of disease, and can include fevers, chills, cough,
dyspnea, fatigue and weight loss. Physical examination often
reveals rales, and dyspnea and hypoxemia are usually present.
Routine laboratory testing demonstrates a moderately elevated
erythrocyte sedimentation rate, leukocyte count, total IgG
level and a positive rheumatoid factor. Though serum IgG antibodies
are elevated to the inhaled antigen(s) in hypersensitivity
pneumonitis, they may be present in asymptomatic exposed individuals.
The immunopathogenesis involves cellular immunity to inhaled
allergens, especially CD8+ cytotoxic T cells, multinucleated
giant cells, and ultimately granulomas. The role of antigen-specific
IgG antibodies is unclear, but may be involved in antibody-dependent-cellular-cytotoxicity
(ADCC) and/or interaction with FcRγ
on dendritic cells and monocytes that enhance a Th1 response.
Pulmonary function studies demonstrate a restrictive pattern
with a diffusion defect resulting in hypoxemia. Radiographic
changes vary according to the stage of the disease and are
best evaluated by high resolution computerized tomography.
Bronchoalveolar lavage demonstrates a lymphocytosis with characteristic
increase of CD8+ T cells and NK cells. However, recent literature
suggests that the CD4+/CD8+ ratio may not be decreased in
children as found in adults. Treatment of hypersensitivity
pneumonitis is antigen avoidance and systemic corticosteroids,
and prognosis depends on early recognition of the disease.
[Back to top]
Defining the Cough Spectrum and Reviewing the Evidence
for Treating Non-Specific Cough in Children
Anne B. Chang
Cough is the most common presenting symptom to medical practitioners
to the USA and Australia. Worldwide, the desire to reduce
the impact of the symptom of cough is reflected in the billions
of dollars spent on over the counter cough medications. Easy
to apply and clinically relevant definitions of cough are
necessary for effective communication and to progress clinical
research. Based on current data, pediatric cough definitions
have been formulated on timeframe (acute and chronic), clinical
cough characteristics (dry vs wet/productive and
classical recognizable cough sounds) and suggestive broad
underlying etiology categories (expected cough, specific cough,
non-specific cough and protracted bronchitis). These definitions
are distinct from adult definitions, as many of adult-type
aspects of cough cannot be applied to young children. With
the lack of pediatric data, adult data is often inappropriately
extrapolated to children.
In the second part of this paper, the evidence for and against
the use of the various pharmaceuticals (such as OTC medications,
antimicrobials, treatment for gastroesophageal reflux and
asthma) for cough in children are reviewed. The utility of
‘time to response’ is important in the management
of cough in children to minimize possible associated morbidity
of the therapies for non-specific cough.
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