Abstracts de Abril 2008
Abstract 1 of 21 
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Serum Cytokine and Chemokine Profiles in Neonates With Meconium
Aspiration Syndrome
a Divisions of Neonatology, Tokyo Metropolitan Hachioji Children's
Hospital, Tokyo, Japan
b Gunma Prefectural Institute of Public Health and Environmental
Sciences, Gunma, Japan
c Department of Virology III
d Infectious Diseases Surveillance Center, National Institute of
Infectious Diseases, Tokyo, Japan
OBJECTIVES. Various inflammatory cytokines and chemokines are thought
to be associated with the pathophysiology of meconium aspiration
syndrome. To clarify any such association, we compared various serum
cytokine and chemokine profiles in patients with and without
meconium aspiration syndrome.
PATIENTS AND METHODS. Using a highly sensitive fluorescence microsphere
method, 17 types of cytokines and chemokines in sera were measured
in 11 neonatal patients with meconium aspiration syndrome, 16
neonatal patients without meconium aspiration syndrome, and 9
healthy children.
RESULTS. The concentrations of 8 types of proinflammatory cytokines
and chemokines were significantly higher in the meconium aspiration syndrome
group than in healthy controls: interleukin-1β, interleukin-6, interleukin-8, granulocyte-macrophage
colony-stimulating factor, granulocyte colony-stimulating factor,
interferon-
, macrophage inflammatory protein-1β, and tumor necrosis factor-
. Six types of proinflammatory cytokines and chemokines were
significantly higher in the meconium aspiration syndrome group than
in the nonmeconium aspiration syndrome group: interleukin-6, interleukin-8,
granulocyte-macrophage colony-stimulating factor, granulocyte
colony-stimulating factor, interferon-, and tumor necrosis factor-. Serum concentrations of interleukin-10 (anti-inflammatory cytokine)
in the meconium aspiration syndrome group were higher than those in
both the nonmeconium aspiration syndrome group and healthy children
group (P = .007 and 0.001, respectively).
CONCLUSIONS. Most types of proinflammatory cytokines and chemokines
in sera of neonates with meconium aspiration syndrome were higher than
those without meconium aspiration syndrome, giving support to the
suggestion that elevated levels are associated with the pathogenesis
of meconium aspiration syndrome.
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Use of Nasal Continuous Positive Airway Pressure During Retrieval of
Neonates With Acute Respiratory Distress
Newborn Emergency Transport Service, Royal Women's Hospital, Carlton,
Victoria, Australia
OBJECTIVE. Although nasal continuous positive airway pressure is
widely used in neonatal units, its use in neonatal transport is not
yet established. Previous reports have been limited to small numbers
of primary road transports and larger numbers of return transports
while its use in air transportation has not been reported. The aim
of this study was to assess the safety and effectiveness of
transporting neonates and infants by road or air while treated with
nasal continuous positive airway pressure.
METHODS. We conducted a retrospective review of the records of
all infants transported between January 1, 2004, and November 1,
2005.
RESULTS. A total of 220 infants were treated with nasal continuous positive
airway pressure; of these, 13 infants (6%) were intubated before
transport, leaving 207 infants transported on a median nasal
continuous positive airway pressure of 
32 weeks' gestational age and <72 hours old at transport. Fraction
of inspired oxygen was significantly lower at the end of transport
(0.45 vs 0.34).
CONCLUSIONS. Nasal continuous positive airway pressure is effective
and has an acceptable safety margin for the road-based transportation
of infants with acute respiratory distress. Air transport is feasible
but larger studies are required to assess safety.
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Outcome and Growth of Infants Fetally Exposed to Heart Block-Associated
Maternal Anti-Ro52/SSA Autoantibodies
a Rheumatology Unit, Department of Medicine
b Pediatric Cardiology Unit
c Obstetrics and Gynecology, Department of Women and Child Health,
Karolinska Institutet, Stockholm, Sweden
OBJECTIVE. The purpose of this work was to analyze outcome with focus
on growth in infants fetally exposed to heart block-associated maternal
anti-Ro52/SSA autoantibodies and identify maternal factors other
than the autoantibodies increasing the risk of fetal heart block.
PATIENTS AND METHODS. Thirty-two pregnancies in 30 anti-Ro52-positive
mothers were included. Seven fetuses developed second-degree or
third-degree atrioventricular block, 8 developed first-degree atrioventricular
block, and 17 had normal atrioventricular conduction, as diagnosed
by using Doppler echocardiography. Three of 6 surviving fetuses with
second-degree or third-degree atrioventricular block received
treatment with fluorinated steroids. Two fetuses with second-degree
atrioventricular block converted to first-degree atrioventricular
block without any signs of progression during the study period. Maternal
and longitudinal infant data were collected from planned neonatal
follow-up and childhood health records from birth to 12 months of age
in 31 survivors.
RESULTS. Women giving birth to infants with prenatal second-degree or
third-degree atrioventricular block were older and with higher parity
than those with first-degree atrioventricular block or normal
atrioventricular conduction. Second-degree or third-degree atrioventricular
block pregnancies were <40 completed weeks, whereas pregnancies
with first-degree atrioventricular block or normal atrioventricular
conduction had a normal duration. Fetuses with second-degree or
third-degree atrioventricular block were retarded by –0.98 ± 0.77 SD
in weight at birth and did not show any catch-up during infancy. In
contrast, fetuses with first-degree atrioventricular block or normal
atrioventricular conduction had a weight reduction of –0.51 ± 1.01
SD with a catch-up during the first months after birth.
CONCLUSIONS. This report documents that newborns with
autoantibody-mediated second-degree or third-degree atrioventricular
block are retarded in growth, with no catch-up during infancy,
whereas fetuses with first-degree atrioventricular block or normal
atrioventricular conduction have a normal growth soon after birth. Increased
maternal age and/or parity seem to carry an increased risk for fetal
heart block.
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Maternal Smoking and Congenital Heart Defects
a Department of Pediatrics, College of Medicine, University of Arkansas
for Medical Sciences, Little Rock, Arkansas
b National Center on Birth Defects and Developmental Disabilities,
Centers for Disease Control and Prevention, Atlanta, Georgia
c Department of Epidemiology, University of Iowa, Iowa City, Iowa
d Department of Human Genetics, University of Utah School of
Medicine, Salt Lake City, Utah
OBJECTIVES. In a population-based case-control study, we investigated
the association between congenital heart defects and maternal smoking.
METHODS. The National Birth Defects Prevention Study enrolled 3067
infants with nonsyndromic congenital heart defects and their parents
and 3947 infants without birth defects and their parents. Affected
infants had 
1 of the following defects: conotruncal, septal, anomalous
pulmonary venous return, atrioventricular septal defects, and
left-sided or right-sided obstructive heart defects. Mothers of case
and control infants were asked if they smoked during the
periconceptional period, defined as 1 month before pregnancy through
the first trimester. Maternal home and workplace exposure to tobacco
smoke during the same period was also determined. Logistic
regression was used to compute odds ratios and 95% confidence
intervals while controlling for potential confounders.
RESULTS. Case infants were more likely to be premature and have lower
birth weight than control infants. Women who smoked anytime during
the month before pregnancy to the end of the first trimester were
more likely to have infants with septal heart defects than women who
did not smoke during this time period. This association was stronger
for mothers who reported heavier smoking during this period. This
relation was independent of potential confounding factors, including
prenatal vitamin use, alcohol intake, maternal age, and race or
ethnicity. Women who smoked 25 cigarettes per day were more likely than nonsmoking
mothers to have infants with right-sided obstructive defects. There
was no increased risk of congenital heart defects with maternal
exposure to environmental tobacco smoke.
CONCLUSIONS. Maternal smoking during pregnancy was associated with
septal and right-sided obstructive defects. Additional investigation
into the timing of tobacco exposure and genetic susceptibilities
that could modify this risk will provide a more precise evidence
base on which to build clinical and public health primary prevention
strategies.
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Elevated Morphine Concentrations in Neonates Treated With Morphine and
Prolonged Hypothermia for Hypoxic Ischemic Encephalopathy
a First Department of Paediatrics, Semmelweis University, Budapest,
Hungary
b Research Group of Paediatrics and Nephrology, Hungarian Academy of
Sciences, Budapest, Hungary
c Division of Clinical Sciences, Hammersmith Campus, Imperial
College London, United Kingdom
OBJECTIVES. Asphyxia and hypothermia may modify drug pharmacokinetics.
We investigated whether analgesia with morphine in neonates with
hypoxic ischemic encephalopathy undergoing prolonged moderate systemic
hypothermia resulted in elevated serum morphine concentrations compared
with normothermic infants.
PATIENTS AND METHODS. Infants from 1 center participating in a
multicenter randomized study of moderate whole-body hypothermia after
perinatal asphyxia (the Total Body Hypothermia Study) were randomly
selected for treatment with hypothermia (n = 10) or for
standard care on normothermia (n = 6). Hypothermia (
RESULTS. Serum morphine concentrations at 24 to 72 hours after birth
were (median [range]) 292 ng/mL (137–767 ng/mL) in the
hypothermia-treated infants and 206 ng/mL (88–327 ng/mL) in the infants
on normothermia, despite similar morphine infusion rates and
cumulative doses. Morphine concentrations correlated with morphine
infusion rate, cumulative dose, and treatment with hypothermia. Serum
morphine concentrations reached a steady state after 24 hours in the
normothermic infants but continued to increase throughout the
assessment period in the hypothermia group. Morphine clearance was
low in both groups: (median [range]) morphine clearance estimated
from area under the curve was 0.69 mL/min per kg (0.58–1.21 mL/min
per kg) in hypothermic group and 0.89 mL/min per kg (0.65–1.33 mL/min
per kg) in infants on normothermia. Serum morphine concentrations >300
nL/mL occurred more often in the hypothermia group and when the
morphine infusion rate was >10 µg/kg per h.
CONCLUSIONS. Infants with hypoxic ischemic encephalopathy have reduced
morphine clearance and elevated serum morphine concentrations when
morphine infusion rates are based on clinical state. Potentially toxic
serum concentrations of morphine may occur with moderate hypothermia
and infusion rates >10 µg/kg per h.
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Prevention of Vitamin K Deficiency Bleeding in Breastfed Infants:
Lessons From the Dutch and Danish Biliary Atresia Registries
a Department of Pediatrics, Wilhelmina Children's Hospital
e Laboratory for Metabolic Diseases, University Medical Center
Utrecht, Utrecht, Netherlands
b Departments of Pediatric Surgery
d Pediatrics, University Hospital of Copenhagen, Copenhagen, Denmark
c Department of Pediatrics, University Medical Center Groningen,
Groningen, Netherlands
OBJECTIVE. Newborns routinely receive vitamin K to prevent vitamin K
deficiency bleeding. The efficacy of oral vitamin K administration may
be compromised in infants with unrecognized cholestasis. We aimed to
compare the risk of vitamin K deficiency bleeding under different
propylactic regimens in infants with biliary atresia.
PATIENTS AND METHODS. From Dutch and Danish national biliary atresia
registries, we retrieved infants who were either breastfed and
received 1 mg of oral vitamin K at birth followed by 25 µg of daily
oral vitamin K prophylaxis (Netherlands, 1991–2003), 2 mg of oral
vitamin K at birth followed by 1 mg of weekly oral prophylaxis
(Denmark, 1994 to May 2000), or 2 mg of intramuscular prophylaxis at
birth (Denmark, June 2000–2005) or were fed by formula. We
determined the absolute and relative risk of severe vitamin K
deficiency and vitamin K deficiency bleeding on diagnosis in
breastfed infants on each prophylactic regimen and in formula-fed
infants.
RESULTS. Vitamin K deficiency bleeding was noted in 25 of 30 of
breastfed infants on 25 µg of daily oral prophylaxis, in 1 of 13 on
1 mg of weekly oral prophylaxis, in 1 of 10 receiving 2 mg of
intramuscular prophylaxis at birth, and in 1 of 98 formula-fed infants
(P < .001). The relative risk of a bleeding in breastfed compared
with formula-fed infants was 77.5 for 25 µg of daily oral
prophylaxis, 7.2 for 1 mg of weekly oral prophylaxis, and 9.3 for 2
mg of intramuscular prophylaxis at birth.
CONCLUSIONS. A daily dose of 25 µg of vitamin K fails to prevent
bleedings in apparently healthy infants with unrecognized cholestasis
because of biliary atresia. One milligram of weekly oral prophylaxis
offers significantly higher protection to these infants and is of
similar efficacy as 2 mg of intramuscular prophylaxis at birth. Our
data underline the fact that event analysis in specific populations
at risk can help to evaluate and improve nationwide prophylactic
regimens.
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Readmission for Neonatal Jaundice in California, 1991–2000: Trends and
Implications
a Departments of Pediatrics
b Health Research and Policy, Stanford University, Stanford,
California
c Veterans’ Administration Hospital, Palo Alto, California
OBJECTIVE. We sought to describe population-based trends, potential
risk factors, and hospital costs of readmission for jaundice for
term and late preterm infants.
METHODS. Birth-cohort data were obtained from the California Office
of Statewide Health Planning and Development and contained infant
vital statistics data linked to infant and maternal hospital discharge
summaries. The study population was limited to healthy, routinely
discharged infants through the use of multiple exclusion criteria. All
linked readmissions occurred within 14 days of birth. International
Classification of Diseases, Ninth Revision, codes were used to
further limit the sample to readmission for jaundice. Hospital
discharge records were the source of diagnoses, hospital charges,
and length-of-stay information. Hospital costs were estimated using
hospital-specific ratios of costs to charges and adjusted to 1991.
RESULTS. Readmission rates for jaundice generally rose after 1994
and peaked in 1998 at 11.34 per 1000. The readmission rate for late
preterm infants (as a share of all infants) over the study period
remained at <2 per 1000. Factors associated with increased
likelihood of hospital readmission for jaundice included gestational
age 34 to 39 weeks, birth weight of <
CONCLUSIONS. Risk-adjusted readmission rates for jaundice rose following
the 1994 hyperbilirubinemia guidelines and declined after postpartum
length-of-stay legislation in
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Neonatal Dexamethasone Treatment for Chronic Lung Disease of Prematurity
Alters the Hypothalamus-Pituitary-Adrenal Axis and Immune System Activity at
School Age
a Department of Neonatology
b Laboratory of Psychoneuroimmunology
f Department of Obstetrics and Gynaecology, University Medical
Center Utrecht, Utrecht, Netherlands
c Department of Neonatology, Isala Clinics Zwolle, Zwolle,
Netherlands
d Department of Neonatology, University Medical Center Leiden,
Leiden, Netherlands
e Department of Neonatology, VU University Medical Center,
Amsterdam, Netherlands
OBJECTIVE. To compare long-term effects of neonatal treatment with
dexamethasone or hydrocortisone for chronic lung disease of
prematurity on the hypothalamus-pituitary-adrenal axis and the
immune response in children at school age.
PATIENTS AND METHODS. A total of 156 prematurely born children were
included in this retrospective matched cohort study. Children treated
with dexamethasone (n = 52) or hydrocortisone (n = 52) were
matched for gestational age, birth weight, grade of infant respiratory
distress syndrome, grade of periventricular or intraventricular hemorrhage,
gender, and year of birth. A reference group of 52 children not
treated with corticosteroids was included for comparison. Plasma
adrenocorticotropic hormone and cortisol in response to a social
stress task were determined. Cytokine production was analyzed after
in vitro stimulation of whole-blood cultures.
RESULTS. The Trier Social Stress Test adapted for children induced an
adrenocorticotropic hormone and cortisol response in all of the
groups. The adrenocorticotropic hormone response was blunted in the
dexamethasone group. The overall cortisol level was lower in the
dexamethasone than in the hydrocortisone and reference group. Cortisol
and adrenocorticotropic hormone in the hydrocortisone and reference
groups were similar. The ratio of T-cell mitogen-induced interferon-/interleukin-4 secretion was significantly higher in the
dexamethasone group than in the hydrocortisone group. Interferon- production and the ratios of interferon-/interleukin-4 and interferon-/ interleukin-10 were significantly higher in the
dexamethasone group than the reference group. However, production of
these cytokines did not differ between the hydrocortisone and the
reference groups.
CONCLUSION. Neonatal treatment of prematurely born children with
dexamethasone but not with hydrocortisone resulted in long-lasting programming
effects on hypothalamus-pituitary-adrenal axis and on the T-helper
1/T-helper 2 cytokine balance. Follow-up of these children is
required to investigate long-term clinical consequences. We
recommend that authors of previously performed randomized,
controlled trials on neonatal glucocorticoid treatment include
immune and neuroendocrine analyses in prolonged follow-up of these
children.
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Pulmonary Hypertension in Patients With Congenital Portosystemic Venous
Shunt: A Previously Unrecognized Association
a Department of Pediatrics, Graduate School of Medical Sciences, Kyushu
University, Fukuoka, Japan
b Department of Pediatrics, Kyushu Kouseinenkin Hospital, Fukuoka,
Japan
c Japanese Research Institute of Pulmonary Vasculature, Miyagi,
Japan
BACKGROUND. Pulmonary arterial hypertension has been reported to
be observed in association with acquired portal hypertension. However,
the contribution of congenital anomalies occurring in the portal
system to the development of pulmonary arterial hypertension remains
to be elucidated.
METHODS. Nine patients with congenital portosystemic venous shunt
were studied from January 1990 through September 2005.
RESULTS. Patent ductus venosus was detected in 5 patients, including
3 patients with an absence of the portal vein. The presence of
either a gastrorenal or splenorenal shunt was evident in another 4
patients. Six patients had a history of hypergalactosemia with
normal enzyme activities, as seen during neonatal screening. Six
(66.7%) of the 9 patients were identified to have clinically significant
pulmonary arterial hypertension (mean pulmonary artery pressure:
34–79 mm Hg; pulmonary vascular resistances: 5.12–38.07 U). The
median age at the onset of pulmonary arterial hypertension was 12
years and 3 months. Histologic studies of lung specimens, which were
available in 4 of the 9 patients with congenital portosystemic
venous shunt, showed small arterial microthrombotic lesions in 3
patients. This characteristic finding was recognized even in the
congenital portosystemic venous shunt patients without PAH.
CONCLUSIONS. This study demonstrated thromboembolic pulmonary arterial
hypertension to be a crucial complication in congenital portosystemic
venous shunt, and this pathologic state may be latently present in
patients with pulmonary arterial hypertension of unknown etiology.
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Differences in Rates and Short-term Outcome of Live Births Before 32
Weeks of Gestation in Europe in 2003: Results From the MOSAIC Cohort
a Department of Obstetrics and Gynecology, INSERM, UMR S149,
Epidemiological Research Unit on Perinatal and Women's Health, and Université
Pierre et Marie Curie-Paris6, Paris, France
b Department of Health Sciences, University of Leicester, Leicester,
United Kingdom
c Department of Obstetrics and Gynecology, University Children's
Hospital, University Medical Center Nijmegen, Nijmegen, Netherlands
d Department of Obstetrics and Gynecology, Royal Victoria Infirmary,
Newcastle upon Tyne, United Kingdom
e Department of Paediatrics, Hvidovre University Hospital, Hvidovre,
Denmark
f Department for Mother's and Infant's Health, Hospital S. Giovanni
Calibita–Fatebenefratelli, Rome, Italy
g Department of Obstetrics and Gynecology, Pediatric University
Hospital, University of Saarland, Homburg, Germany
h Department of Neonatology, Antwerp University Hospital, University
of Antwerp, and Study Centre for Perinatal Epidemiology, Flanders, Belgium
i Department of Obstetrics and Gynecology, Service de Réanimation
Néonatale, Hopital Antoine Béclere, Clamart, France
j Department of Neonatology, University of Medical Sciences, Poznan,
Poland
k Department of Obstetrics and Gynecology, Université Paris V Réné
Descartes et Maternité de Port-Royal, Assistance-Publique Hôpitaux de Paris,
Paris, France
OBJECTIVES. Advances in perinatal medicine increased survival after
very preterm birth in all countries, but comparative population-based data
on these births are not readily available. This analysis contrasts
the rates and short-term outcome of live births before 32 weeks of
gestation in 10 European regions.
METHODS. The Models of Organizing Access to Intensive Care for Very
Preterm Births (MOSAIC) study collected prospective data on all very
preterm births in 10 European regions covering 494463 total live
births in 2003. The analysis sample was live births between 24 and
31 weeks of gestation without lethal congenital anomalies (N
= 4908). Outcomes were rates of preterm birth, in-hospital
mortality, intraventricular hemorrhage grades III and IV or cystic
periventricular leukomalacia and bronchopulmonary dysplasia. Mortality
and morbidity rates were standardized for gestational age and
gender.
RESULTS. Live births between 24 and 31 weeks of gestation were 9.9
per 1000 total live births with a range from 7.6 to 28 weeks of gestation as well as 28 to 31 weeks of gestation.
Morbidity among survivors also varied (intraventricular
hemorrhage/periventricular leukomalacia ranged from 2.6% to 10% and bronchopulmonary dysplasia from 10.5% to 21.5%) but
differed from mortality rankings. A total of 85.2 very preterm
infants per 10000 total live births were discharged from the
hospital alive with a range from 64.1 to 117.1; the range was 10 to
31 per 10000 live births for infants discharged with a diagnosis of
neurologic or respiratory morbidity.
CONCLUSIONS. Very preterm mortality and morbidity differed between European
regions, raising questions about variability in treatment provided
to these infants. Comparative follow-up studies are necessary to
evaluate the impact of these differences on rates of cerebral palsy
and other disabilities associated with preterm birth.
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Changing Patterns in Neonatal Escherichia coli Sepsis and
Ampicillin Resistance in the Era of Intrapartum Antibiotic Prophylaxis
Divisions of a
Perinatal Medicine
e Infectious Diseases, Department of Pediatrics
b Department of Internal Medicine
c Department of Epidemiology and Public Health, Yale University
School of Medicine, New Haven, Connecticut
d Department of Quality Improvement Support Services, Yale-New Haven
Hospital, New Haven, Connecticut
OBJECTIVE. The goal was to determine current trends in Escherichia
coli-related early- and late-onset sepsis and patterns of ampicillin
resistance in relation to institutional changes in the use of intrapartum
antibiotic prophylaxis.
METHODS. A retrospective review of data for all infants with E
coli sepsis at Yale-New Haven Hospital from 1979 to 2006 was performed.
Study periods were based on predominant intrapartum antibiotic
prophylaxis practices at Yale-New Haven Hospital, that is, (1) 1979
to 1992 (no formal intrapartum antibiotic prophylaxis), (2) 1993 to
1996 (risk factor-based), and (3) 1997 to 2006 (screening-based). Sepsis
rates and patterns of ampicillin resistance were compared.
RESULTS. Fifty-three cases of E coli early-onset sepsis and 129
cases of E coli late-onset sepsis were identified over 3 eras.
In very low birth weight (<
CONCLUSIONS. Studies to provide a better understanding of potential
consequences of intrapartum antibiotic exposure and its contribution
to evolving trends in neonatal sepsis are urgently needed.
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Neonatal Antibiotic Treatment Is a Risk Factor for Early Wheezing
a Department of Pediatrics, Göteborg University, Göteborg, Sweden
b Pediatric Outpatient Clinic, Skene, Sweden
c Central Infant Welfare Bureau, Uddevalla Hospital, Uddevalla,
Sweden
d Department of Pediatrics, Skaraborg Hospital, Skövde, Sweden
OBJECTIVE. The use of antibiotics in infancy and subsequent changes
in the intestinal bacterial flora have been discussed as risk
factors for the development of asthma. However, it has been
difficult to exclude the possibility that antibiotics have been
given in early episodes of wheezing. As a result, there has been a
risk of reverse causation. To minimize the risk of reverse
causation, we have focused on the effect of antibiotics that are
already administered on the neonatal ward.
METHODS. In a cohort study of infants born in western Sweden in
2003, we studied the development of wheezing. The families of the
infants were randomly selected and sent a questionnaire at child
ages 6 and 12 months. The response rate was 68.5% to the 6-month questionnaire
and 68.9% to the 12-month questionnaire.
RESULTS. At 12 months, 20.2% of infants had had 1 or more episodes of
wheezing, and 5.3% had had 3 or more episodes. Inhaled corticosteroids had
been taken by 4.1% of the infants. Independent risk factors for
wheezing disorder treated with inhaled corticosteroids were neonatal
antibiotic treatment, male gender, gestational age of <37 weeks,
having a mother with asthma, having a sibling with asthma or eczema,
and breastfeeding for <5 months.
CONCLUSIONS. Treatment with antibiotics in the neonatal period was
an independent risk factor for wheezing that was treated with
inhaled corticosteroids at 12 months of age. These results indirectly
support the hypothesis that an alteration in the intestinal flora can
increase the risk of subsequent wheezing.
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Fluconazole Prophylaxis in Extremely Low Birth Weight Neonates Reduces
Invasive Candidiasis Mortality Rates Without Emergence of Fluconazole-Resistant
Candida Species
Departments of a
Pediatrics
c Molecular Virology and Microbiology, Baylor College of Medicine,
Houston, Texas
b Woman's Hospital of Texas, Houston, Texas
OBJECTIVE. We evaluated the impact of fluconazole prophylaxis for
extremely low birth weight infants on invasive candidiasis incidence,
invasive candidiasis-related mortality rates, and fluconazole
susceptibility of Candida isolates.
METHODS. Extremely low birth weight infants <5 days of age, except
those with liver dysfunction, were eligible for fluconazole prophylaxis.
NICU infants (all birth weights) with invasive candidiasis between
April 2002 and March 2006 were compared with those with invasive
candidiasis before fluconazole prophylaxis (2000–2001).
RESULTS. Twenty-two infants had invasive candidiasis (all candidemia)
during fluconazole prophylaxis; before fluconazole prophylaxis, there
were 19 cases (candidemia: 17 cases; meningitis: 2 cases). Invasive
candidiasis incidence in NICU infants decreased from 0.6% (19 of
3012 infants) before fluconazole prophylaxis to 0.3% (22 of 6393
infants) in 2002–2006 and that in extremely low birth weight infants
decreased 3.6-fold. No Candida-attributable deaths occurred
during 2002–2006 fluconazole prophylaxis, compared with 4 (21%)
before fluconazole prophylaxis. The onset of invasive candidiasis
was later during 2002–2006 (23.5 vs 12 days), but risk factors were
similar. The invasive candidiasis species distribution remained
stable. Of 409 infants who received fluconazole prophylaxis, 119
(29%) received 42 days. Shorter fluconazole prophylaxis duration was
related to intravenous access no longer being necessary in 242 cases
(59%), noninvasive candidiasis-related death in 29 (7%), hospital
transfer in 8 (2%), invasive candidiasis diagnosis in 8 (2%), and
transient increase in serum transaminase levels in 4 (1%). One
hundred twenty-seven infants (31%) who received fluconazole
prophylaxis developed cholestasis during hospitalization, two thirds
of whom had other predisposing conditions. On multivariate logistic
regression necrotizing enterocolitis and increasing days of total
parenteral nutrition, but not increasing number of doses on days of
fluconazole, were significantly associated with the development of
cholestasis.
CONCLUSION. During 4 years of fluconazole prophylaxis, the incidence
of invasive candidiasis and invasive candidiasis-associated mortality
rates in extremely low birth weight infants were reduced significantly,
without the emergence of fluconazole-resistant Candida
species.
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Characteristics Associated With Older Adolescents Who Have a Television
in Their Bedrooms
Division of Epidemiology and Community Health, School of Public Health,
University of Minnesota, Minneapolis, Minnesota
OBJECTIVES. The goals were to examine the prevalence of adolescents
having a television in their bedroom and to describe associated personal,
social, and behavioral characteristics.
METHODS. Participants included 781 adolescents (mean age: 17.2 years)
who completed a mailed Project Eating Among Teens II questionnaire. The
relationships between adolescents having a television in their
bedroom and sociodemographic, behavioral, and personal
characteristics were examined.
RESULTS. Nearly two thirds (62%) of participants had a bedroom television.
Gender, race/ethnicity, socioeconomic status, and age were
associated with the presence of a bedroom television. Compared with
girls without a bedroom television, girls with a bedroom television
reported less time spent in vigorous activity (1.8 vs 2.5
hours/week), more time spent watching television (20.7 vs 15.2
hours/week), lower vegetable intake (1.7 vs 2.0 servings per day),
greater sweetened beverage consumption (1.2 vs 1.0 servings per
day), and fewer family meals (2.9 vs 3.7 meals per week). Compared
with boys without a bedroom television, boys with a bedroom
television reported more time spent watching television (22.2 vs
18.2 hours/week), lower fruit intake (1.7 vs 2.2 servings per day),
fewer family meals (2.9 vs 3.6 meals per week), and lower grade
point average (2.6 vs 2.9). Twice as many youths with a television
in their bedroom were heavy television users (watched >5
hours/day), compared with youths without a television in their
bedroom (16% vs 8%).
CONCLUSIONS. Adolescents with a bedroom television reported more
television viewing time, less physical activity, poorer dietary
habits, fewer family meals, and poorer school performance. Refraining
from placing a television in teenagers’ rooms may be a first step in
helping to decrease screen time and subsequent poor behaviors
associated with increased television watching.
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Just, in Time: Ethical Implications of Serial Predictions of Death and
Morbidity for Ventilated Premature Infants
a Department of Pediatrics
b MacLean Center for Clinical Medical Ethics, University of Chicago,
Chicago, Illinois
OBJECTIVES. For a cohort of extremely premature, ventilated, newborn
infants, we determined the power of either serial caretaker intuitions
of "die before discharge" or serial illness severity scores
to predict the outcomes of death in the NICU or neurologic performance
at corrected age of 2 years.
METHODS. We identified 268 premature infants who were admitted to
our NICU in 1999–2004 and required mechanical ventilation. For each infant
on each day of mechanical ventilation, we asked nurses, residents,
fellows, and attending physicians the following question: "Do
you think this child is going to live to go home or die before
hospital discharge?" In addition, we calculated illness severity
scores until either death or extubation.
RESULTS. A total of 17066 intuition profiles were obtained on 5609
days of mechanical ventilation in the NICU. One hundred (37%) of 268
profiled infants had 1 intuition of die before discharge. Only 33 infants (33%)
with an intuition of die actually died in the NICU. Of 48 infants
with even 1 day of corroborated intuition of die in the NICU, only 7
(14%) were alive with both Mental Developmental Index and
Psychomotor Developmental Index scores of >69, and only 2 (4%)
were alive with both Mental Developmental Index and Psychomotor
Developmental Index Scores of >79 at corrected age of 2 years. On
day of life 1, the Score for Neonatal Acute Physiology II value for
nonsurvivors (38.2 ± 18.1) was significantly higher than that for
survivors (26.3 ± 12.7). However, this difference decreased steadily
over time as scores improved for both groups.
CONCLUSIONS. Illness severity scores become progressively less helpful
over time in distinguishing infants who will either die in the NICU
or survive with low Mental Developmental Index/Psychomotor Developmental
Index scores. Serial caretaker intuitions of die before discharge
also fail to identify prospective nonsurviving infants. However,
corroborated intuitions of die before discharge identify a subset of
infants whose likelihood of surviving to 2 years with both MDI and
PDI >80 is approximately 4%.
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Volumetric MRI Study of Brain in Children With Intrauterine Exposure to
Cocaine, Alcohol, Tobacco, and Marijuana
Departments of a
Neurology
b Radiology
c Psychiatry, Children's Hospital and Harvard Medical School,
Boston, Massachusetts
d Department of Biostatistics, Boston University School of Public
Health, Boston, Massachusetts
e Department of Pediatrics, Boston University School of Medicine,
Boston, Massachusetts
OBJECTIVE. The objective of this study was to use volumetric MRI
to study brain volumes in 10- to 14-year-old children with and
without intrauterine exposure to cocaine, alcohol, cigarettes, or
marijuana.
METHODS. Volumetric MRI was performed on 35 children (mean age: 12.3
years; 14 with intrauterine exposure to cocaine, 21 with no
intrauterine exposure to cocaine) to determine the effect of
prenatal drug exposure on volumes of cortical gray matter; white
matter; subcortical gray matter; cerebrospinal fluid; and total
parenchymal volume. Head circumference was also obtained. Analyses
of each individual substance were adjusted for demographic characteristics
and the remaining 3 prenatal substance exposures.
RESULTS. Regression analyses adjusted for demographic characteristics
showed that children with intrauterine exposure to cocaine had lower
mean cortical gray matter and total parenchymal volumes and smaller
mean head circumference than comparison children. After adjustment
for other prenatal exposures, these volumes remained smaller but
lost statistical significance. Similar analyses conducted for
prenatal ethanol exposure adjusted for demographics showed
significant reduction in mean cortical gray matter; total
parenchymal volumes; and head circumference, which remained smaller
but lost statistical significance after adjustment for the remaining
3 exposures. Notably, prenatal cigarette exposure was associated
with significant reductions in cortical gray matter and total
parenchymal volumes and head circumference after adjustment for
demographics that retained marginal significance after adjustment
for the other 3 exposures. Finally, as the number of exposures to
prenatal substances grew, cortical gray matter and total parenchymal
volumes and head circumference declined significantly with smallest
measures found among children exposed to all 4.
CONCLUSIONS. These data suggest that intrauterine exposures to
cocaine, alcohol, and cigarettes are individually related to reduced
head circumference; cortical gray matter; and total parenchymal
volumes as measured by MRI at school age. Adjustment for other
substance exposures precludes determination of statistically significant
individual substance effect on brain volume in this small sample;
however, these substances may act cumulatively during gestation to
exert lasting effects on brain size and volume.
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Epidemiologic Features of the Presentation of Critical Congenital Heart
Disease: Implications for Screening
Departments of a
Pediatrics
c Biostatistics and Epidemiology
d Medicine
b Center for Clinical Epidemiology and Biostatistics, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania
e Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
OBJECTIVE. Critical congenital heart disease has been proposed as
a target of newborn screening. This study aimed to define the
incidence and timing of significant physiologic compromise attributable
to critical congenital heart disease as well as the distribution of
vulnerable lesions. These descriptive parameters must be defined to
evaluate the impact and feasibility of any proposed screening
strategy.
METHODS. A retrospective cohort study of neonates who had critical congenital
heart disease and were admitted to a single institution was
conducted. Critical congenital heart disease was defined as
congenital heart disease that required invasive intervention or
resulted in death in the first 30 days of life. Significant physiologic
compromise was defined by severe metabolic acidosis, seizure,
cardiac arrest, or laboratory evidence of renal or hepatic injury
before invasive intervention. Significant physiologic compromise was
classified as potentially preventable when it occurred as a result
of undiagnosed congenital heart disease after 12 hours of life.
RESULTS. Significant physiologic compromise occurred in 76 (15.5%) of
490 patients, and potentially preventable significant physiologic compromise
occurred in 33 (6.7%) of 490 patients. Most (83%) significant
physiologic compromise as a result of unrecognized congenital heart
disease occurred after 12 hours of age. A total of 90.9% of cases of
potentially preventable significant physiologic compromise had
aortic arch obstruction. The incidence of potentially preventable
significant physiologic compromise as a result of congenital heart
disease in the general population is estimated to be 1 per 15000 to
1 per 26000 live births.
CONCLUSIONS. The incidence and timing of significant physiologic compromise
as a result of critical congenital heart disease seems amenable to
postnatal screening. Any viable screening strategy must be sensitive
for lesions with aortic arch obstruction.
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Positive Screening for Autism in Ex-preterm Infants: Prevalence and Risk
Factors
a Department of Neurology and Neurosurgery, School of Physical and
Occupational Therapy, and Department of Pediatrics, McGill University,
Montreal, Quebec, Canada
b Fetal-Neonatal Neurology Research Program, Department of Neurology
c Developmental Medicine Center
d Department of Radiology, Children's Hospital Boston and Harvard
Medical School, Boston, Massachusetts
e Department of Neonatology, Brigham and Women's Hospital and
Harvard Medical School, Boston, Massachusetts
OBJECTIVE. The survival of very low birth weight infants has increased
markedly in recent years. Unfortunately, the prevalence of
significant and lifelong motor, cognitive, and behavioral dysfunction
has remained a major problem confronting these children. The
objective of this study was to perform screening tests for early
autistic features in children with a history of very low birth
weight and to identify risk factors associated with a positive
screening result.
METHODS. We studied 91 ex-preterm infants 1500 g at birth. Infants underwent conventional MRI studies
at preterm and/or term-adjusted age. We collected pertinent
demographic, prenatal, intrapartum, acute postnatal, and short-term
outcome data for all infants. Follow-up assessments were performed
at a mean age of 21.9 ± 4.7 months, using the Modified Checklist
for Autism in Toddlers, the Vineland Adaptive Behavior Scale, and
the Child Behavior Checklist.
RESULTS. Twenty-six percent of ex-preterm infants had a positive result
on the autism screening tool. Abnormal scores correlated highly with
internalizing behavioral problems on the Child Behavior Checklist
and socialization and communication deficits on the Vineland Scales.
Lower birth weight, gestational age, male gender, chorioamnionitis,
acute intrapartum hemorrhage, illness severity on admission, and
abnormal MRI studies were significantly associated with an abnormal
autism screening score.
CONCLUSIONS. Early autistic behaviors seem to be an underrecognized
feature of very low birth weight infants. The results from this study
suggest that early screening for signs of autism may be warranted in
this high-risk population followed by definitive autism testing in
those with positive screening results.
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Growth and Nutrient Intakes of Human Milk–Fed Preterm Infants Provided
With Extra Energy and Nutrients After Hospital Discharge
a Physiology and Experimental Medicine Program
b Department of Clinical Dietetics
j Department of Neonatology, Hospital for Sick Children, Toronto,
Ontario, Canada
Departments of c Nutritional Sciences
d Pediatrics
i Ophthalmology and Vision Sciences, University of Toronto, Toronto,
Ontario, Canada
e Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario,
Canada
f Department of Pediatrics, St Michael's Hospital, Toronto, Ontario,
Canada
g Department of Newborn and Developmental Pediatrics, Sunnybrook
Hospital, Toronto, Ontario, Canada
h Department of Paediatrics, St Joseph's Health Centre, Toronto,
Ontario, Canada
OBJECTIVES. The purpose of this pilot study was to determine whether
mixing a multinutrient fortifier to approximately one half of the
human milk fed each day for a finite period after discharge improves
the nutrient intake and growth of predominantly human milk–fed low
birth weight infants. We also assessed the impact of this intervention
on the exclusivity of human milk feeding.
METHODS. Human milk–fed (80% feeding per day) low birth weight (750–1800 g) infants (n
= 39) were randomly assigned at hospital discharge to either a
control or an intervention group. Infants in the control group were
discharged from the hospital on unfortified human milk. Nutrient
enrichment of human milk in the intervention group was achieved by
mixing approximately one half of the human milk provided each day
with a powdered multinutrient human milk fortifier for 12 weeks
after discharge. Milk with added nutrients was estimated to contain 
80 kcal (336 kJ) and
RESULTS. Infants in the intervention group were longer during the
study period, and those born 1250 g had larger head circumferences than infants in the
control group. There was a trend toward infants in the intervention
group to be heavier at the end of the intervention compared with
those in the control group. Mean protein, zinc, calcium, phosphorus,
and vitamins A and D intakes were higher in the intervention group.
CONCLUSIONS. Results from this study suggest that adding a multinutrient
fortifier to approximately one half of the milk provided to predominantly
human milk–fed infants for 12 weeks after hospital discharge may be
an effective strategy in addressing early discharge nutrient
deficits and poor growth without unduly influencing human milk
feeding when intensive lactation support is provided.
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Annual Summary of Vital Statistics: 2006
a Division of Vital Statistics,
National Center for Health Statistics, Centers for Disease Control and
Prevention, Hyattsville, Maryland
b Department of Population and Family Health Sciences, Johns Hopkins
Bloomberg School of Public Health, Baltimore, Maryland
c Division of Biostatistics, Public Health Statistics and
Information Services, South Carolina Department of Health and Environmental
Control, Columbia, South Carolina
US births increased 3% between 2005 and 2006 to 4265996, the largest
number since 1961. The crude birth rate rose 1%, to 14.2 per 1000
population, and the general fertility rate increased 3%, to 68.5 per
1000 women 15 to 44 years. Births and birth rates increased among
all race and Hispanic-origin groups. Teen childbearing rose 3% in
2006, to 41.9 per 1000 females aged 15 to 19 years, the first
increase after 14 years of steady decline. Birth rates rose 2% to 4%
for women aged 20 to 44; rates for the youngest (10–14 years) and
oldest (45–49) women were unchanged. Childbearing by unmarried women
increased steeply in 2006 and set new historic highs. The
cesarean-delivery rate rose by 3% in 2006 to 31.1% of all births;
this figure has been up 50% over the last decade. Preterm and low
birth weight rates also increased for 2006 to 12.8% and 8.3%,
respectively. The 2005 infant mortality rate was 6.89 infant deaths
per 1000 live births, not statistically higher than the 2004 level. Non-Hispanic
black newborns continued to be more than twice as likely as non-Hispanic
white and Hispanic infants to die in the first year of life in 2004.
For all gender and race groups combined, expectation of life at
birth reached a record high of 77.9 years in 2005. Age-adjusted
death rates in the United States continue to decline. The crude
death rate for children aged 1 to 19 years decreased significantly
between 2000 and 2005. Of the 10 leading causes of death for
children in 2005, only the death rate for cerebrovascular disease
was up slightly from 2000, whereas accident and chronic lower
respiratory disease death rates decreased. A large proportion of
childhood deaths, however, continue to occur as a result of
preventable injuries.
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Prevention of Influenza: Recommendations for Influenza Immunization of
Children, 2007–2008
The American Academy of Pediatrics recommends annual influenza immunization
for all children with high-risk conditions who are 6 months of age
and older, for all healthy children ages 6 through 59 months, for
all household contacts and out-of-home caregivers of children with
high-risk conditions and of healthy children younger than 5 years,
and for all health care professionals.
To more fully protect against the morbidity and mortality of influenza,
increased efforts are needed to identify and immunize all children
at high risk and all healthy children ages 6 through 59 months and
to inform their parents when annual immunizations are due. Previously
unimmunized children who are at least 6 months of age but younger
than 9 years should receive 2 doses of influenza vaccine, given 1
month apart, beginning as soon as possible on the basis of local
availability during the influenza season. If children in this cohort
received only 1 dose for the first time in the previous season, it
is recommended that 2 doses be administered in the current season. This
recommendation applies only to the influenza season that follows the
first year that a child younger than 9 years receives influenza
vaccine. A child who then also fails to receive 2 doses the next
year should be given only 1 dose per year from that point on. Influenza
vaccine should also continue to be offered throughout the influenza season,
even after influenza activity has been documented in a community.
On the basis of global surveillance of circulating virus strains, the
influenza vaccine may change from year to year; indeed, 1 of the 3
strains in the 2007–2008 vaccine is different from the previous
year's vaccine. All health care professionals, influenza campaign
organizers, and public health agencies should develop plans for
expanding outreach and infrastructure to immunize all children for
whom influenza vaccine is recommended. Appropriate prioritization of
administering influenza vaccine will also be necessary when vaccine
supplies are delayed or limited. Because the influenza season often
extends into March, immunization against influenza is recommended to
continue through late winter and early spring. Lastly, it is
recommended that for the 2007–2008 season, and likely beyond, health
care professionals do not prescribe amantadine or rimantadine for
influenza treatment or chemoprophylaxis, because widespread
resistance to these antiviral medications now exists among influenza
A viral strains. However, oseltamivir and zanamivir can be
prescribed for treatment or chemoprophylaxis, because influenza A
and B strains remain susceptible.