MARZO
2008
Abstract 1 of 21 
Black/White
Differences in Very Low Birth Weight Neonatal Mortality Rates Among New York
City Hospitals
a Departments of Health Policy
b Obstetrics, Gynecology, and Reproductive Science
c Pediatrics, Mount Sinai School of Medicine, New York, New York
OBJECTIVE. We sought to determine whether differences in the hospitals
at which black and white infants are born contribute to black/white
disparities in very low birth weight neonatal mortality rates in New
York City.
METHODS. We performed a population-based cohort study using New
York City vital statistics records on all live births and deaths of
infants weighing 500 to
RESULTS. Risk-adjusted neonatal mortality rates for very low birth
weight infants in New York City hospitals ranged from 9.6 to 27.2
deaths per 1000 births. White very low birth weight infants were
more likely to be born in the lowest mortality tertile of hospitals
(49%), compared with black very low birth weight infants (29%). We
estimated that, if black women delivered in the same hospitals as
white women, then black very low birth weight mortality rates would
be reduced by 6.7 deaths per 1000 very low birth weight births,
removing 34.5% of the black/white disparity in very low birth weight
neonatal mortality rates in New York City. Volume of very low birth
weight deliveries was modestly associated with very low birth weight
mortality rates but explained little of the racial disparity.
CONCLUSION. Black very low birth weight infants more likely to
be born in New York City hospitals with higher risk-adjusted neonatal
mortality rates than were very low birth weight infants, contributing
substantially to black-white disparities.
Key Words: infant mortality • racial disparities • quality of care •
very low birth weight
Abbreviations: VLBW—very low birth weight
Accepted Jul 24, 2007.
[Full Text of Howell et al.] [Reprint (PDF) Version of
Howell et al.]
Routine
Measurement of Head Circumference as a Tool for Detecting Intracranial
Expansion in Infants: What Is the Gain? A Nationwide Survey
a Department of Surgery, Voss Hospital, Voss, Norway
b Section for Neurosurgery, Department of Surgical Sciences,
University of Bergen, Bergen, Norway
c Department of Neurosurgery, Haukeland University Hospital, Bergen,
Norway
OBJECTIVE. The aim of the present study was to investigate the importance
of routine head circumference measurements in the detection of
intracranial expansive conditions, because only fragmented evidence
exists in favor of this routine.
METHODS. The study was a nationwide study based on the medical records
of all Norwegian departments of pediatrics and neurosurgery. The
study included all Norwegian children <5 years of age who were
hospitalized because of intracranial expansion during a 4-year
period (1999–2002). Information about diagnostic codes, symptoms,
and ages at symptom onset and at admission was collected from the
medical records.
RESULTS. The study included 298 patients. For 173 (58%), hydrocephalus
was the primary diagnosis; 57 (19%) had intracranial tumors and
68 (23%) had other primary diagnoses. For 46% of the children, increased
head circumference was the first and main symptom leading to
diagnosis. Increased head circumference was much more common as the
symptom that led to diagnosis for patients with hydrocephalus (72%),
compared with patients with cysts (31%) or tumors (5%). Increasing
head circumference seems important mainly in detecting hydrocephalus
and cysts, especially during the first 10 months of life.
CONCLUSIONS. Routine measurements of head circumference during the
first year of life mainly detect infants with hydrocephalus or
cysts; other expansive conditions yield other symptoms. Most children
with increased head circumference as a symptom of intracranial expansion
are identified during the first 10 months of life.
Key Words: child health services • clinical practice • head
circumference • hydrocephalus • tumors
Abbreviations: HC—head circumference
Accepted Jul 23, 2007.
[Full Text of Zahl and Wester] [Reprint (PDF) Version of Zahl and Wester]
Effects
of Prolonged and Exclusive Breastfeeding on Child Behavior and Maternal
Adjustment: Evidence From a Large, Randomized Trial
a Departments of Pediatrics
b Epidemiology and Biostatistics
c Psychiatry, McGill University Faculty of Medicine, Montreal,
Quebec, Canada
d National Research and Applied Medicine Mother and Child Centre,
Minsk, Belarus
e Groupe de recherche sur l'inadaptation psychosociale chez
l'enfant, Université de Montréal, Montreal, Quebec, Canada
f Department of Epidemiology and Community Health, Queen's
University, Kingston, Ontario, Canada
OBJECTIVE. The objective of this study was to assess the long-term effects
of breastfeeding on child behavior and maternal adjustment.
METHODS. We followed up children who were in the Promotion of Breastfeeding
Intervention Trial, a cluster-randomized trial of a breastfeeding
promotion intervention based on the World Health Organization/United
Nations Children's Fund Baby-Friendly Hospital Initiative. A total
of 17046 healthy, breastfeeding mother–infant pairs were enrolled
from 31 Belarussian maternity hospitals and affiliated polyclinics;
13889 (81.5%) were followed up at 6.5 years. Mothers and teachers
completed the Strengths and Difficulties Questionnaire and
supplemental questions bearing on internalizing and externalizing
behavioral problems. Mothers also responded to questions concerning
their relationships to their partner and child and their
breastfeeding of subsequently born children.
RESULTS. The experimental intervention led to a large increase in
exclusive breastfeeding at 3 months (43.3% vs 6.4%) and a significantly
higher prevalence of any breastfeeding at all ages up to and
including 12 months. No significant treatment effects were observed
on either the mother or the teacher Strengths and Difficulties
Questionnaire ratings of total difficulties, emotional symptoms,
conduct problems, hyperactivity, peer problems, or prosocial
behavior or on the supplemental behavioral questions. We found no
evidence of treatment effects on the parent's marriage or on the
mother's satisfaction with her relationships with her partner or
child, but the experimental intervention significantly increased the
duration of any breastfeeding, and mothers in the experimental group
were nearly twice as likely to breastfeed exclusively the next-born
child for at least 3 months.
CONCLUSIONS. On the basis of the largest randomized trial ever conducted
in the area of human lactation, we found no evidence of risks or
benefits of prolonged and exclusive breastfeeding for child and
maternal behavior. Breastfeeding promotion does, however, favorably
affect breastfeeding of the subsequent child.
Key Words: breastfeeding • child behavior • conduct disorder • ADHD •
peer relations • randomized trial
Abbreviations: PROBIT—Promotion of Breastfeeding Intervention Trial •
SDQ—Strengths and Difficulties Questionnaire • CI—confidence interval • OR—odds
ratio • ICC—intraclass correlation coefficient
Accepted Jul 20, 2007.
[Full Text of Kramer et al.] [Reprint (PDF) Version of
Kramer et al.]
Breastfeeding
Helps Explain Racial and Socioeconomic Status Disparities in Adolescent
Adiposity
a Department of Pediatrics,
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, and University
of Cincinnati College of Medicine, Cincinnati, Ohio
b Department of Pediatrics, Floating Hospital for Children at
Tufts-New England Medical Center, Boston, Massachusetts, and Tufts University
School of Medicine, Boston, Massachusetts
OBJECTIVES. Studies suggest that breastfeeding is protective for
later obesity; however, this association has not held among all
racial and socioeconomic status groups. Racial and socioeconomic status
differences in breastfeeding behavior have also been noted. In this
study, we formally test whether breastfeeding mediates the
relationship between race and socioeconomic status with adolescent
adiposity.
METHODS. Data were analyzed from 739 black and white 10- to 19-year-old
adolescents who participated in a large, school-based study. Parents
provided information on parental education, used to measure
socioeconomic status, and whether the child was breastfed as an
infant. BMI was used to measure adolescent adiposity and was
analyzed as a continuous measure (BMI z score) using linear regression
and categorically (BMI 
85th and 95th percentile) using logistic regression.
RESULTS. Black adolescents and those without a college-educated parent
were less likely to have been breastfed for >4 months. Race and
parental education were each independent predictors of BMI z
score and of having BMI 85th percentile or BMI 95th percentile. When added to the model, being breastfed for
>4 months was also independently associated with lower BMI z
score and lower odds of having BMI 85th percentile or BMI 95th percentile. Inclusion of being breastfed for >4
months resulted in a 25% decrease in racial and parental education
differences in adolescent BMI z score, supporting partial
mediation.
CONCLUSIONS. Having been breastfed for >4 months was associated with
lower adolescent BMI z score and lower odds of having a BMI 85th percentile or BMI 95th percentile, independent of race or parental education. Furthermore,
these analyses suggest that being breastfed for >4 months
partially explains the relationship between social disadvantage and
increased adiposity. Increasing breastfeeding duration could result
in lower adolescent adiposity for all racial and socioeconomic
status groups and potentially minimize socioeconomic disparities in
adiposity.
Key Words: adolescent obesity • breastfeeding • epidemiology • racial
differences • socioeconomic status
Abbreviations: SES—socioeconomic status • PSD—Princeton School District
• aOR—adjusted odds ratio • CI—confidence interval
Accepted Jul 21, 2007.
[Full Text of Woo et al.] [Reprint (PDF) Version of
Woo et al.]
Role
of Complement and CD14 in Meconium-Induced Cytokine Formation
a Institute of Immunology
b Department of Pediatric Research, University of Oslo and
Rikshospitalet University Hospital, Oslo, Norway
c Tanox Inc, Houston, Texas
OBJECTIVE. Meconium aspiration syndrome has a complex, poorly defined
pathophysiology. Meconium is a potent activator of complement in
vitro and in vivo; the latter is associated with a systemic inflammatory
response. The complement system and Toll-like receptors are 2
important upstream components of the innate immune system that act
partly independently in the inflammatory network. The aim of this
study was to investigate the relative role of complement and CD14 in
meconium-induced cytokine production.
METHODS. Human adult (n = 6) and cord whole blood (n = 6)
anticoagulated with lepirudin was collected and distributed into
tubes that contained inhibitory antibodies (anti-CD14, anti-C2,
anti–factor D, or combinations thereof). The tubes were preincubated
for 5 minutes before addition of meconium or buffer and then
incubated for 4 hours at
RESULTS. Fourteen of the 27 mediators measured were induced by
meconium both in cord and adult blood. In cord blood, 2 additional chemokines
were induced and the inflammatory response was, in general, more
potent. Blocking of complement or CD14 differentially reduced the
formation of most mediators, anti-CD14 being more effective. Notably,
the combined inhibition of complement and CD14 almost completely
abolished meconium-induced formation of the cytokines and the
chemokines and markedly reduced the formation of growth factors. The
endogenous lipopolysaccharide content of meconium could not explain
the CD14-mediated response.
CONCLUSIONS. Meconium-induced triggering of the cytokine network is
differentially mediated by complement and CD14. A combined inhibition
of these effector mechanisms may be an alternative approach to
reduce the inflammatory reaction in meconium aspiration syndrome.
Key Words: meconium • complement system • lipopolysaccharide • CD14 •
Toll-like receptor • cord blood
Abbreviations: MAS—meconium aspiration syndrome • TNF-
—tumor necrosis factor • IL—interleukin • TLR—Toll-like receptor • PBS—phosphate-buffered
saline • IgG1—immunoglobulin G1 • TCC—terminal sC5b-9 complement complex •
ELISA—enzyme-linked immunosorbent assay • AU—arbitrary units • IFN-
—interferon • MIP—macrophage inflammatory protein • G-CSF—granulocyte colony-stimulating
factor • GM-CSF—granulocyte macrophage colony-stimulating factor •
FGF—fibroblast growth factor • VEGF—vascular endothelial growth factor •
IP-10—interferon-inducible protein
Accepted Jul 19, 2007.
[Full Text of Salvesen et al.] [Reprint (PDF) Version of
Salvesen et al.]
Clinical
Outcomes After an Unstructured Treatment Interruption in Children and
Adolescents With Perinatally Acquired HIV Infection
a Division of Infectious Diseases, Department of Pediatrics
c Division of Biostatistics and Bioinformatics, Department of Family
and Preventive Medicine, University of California San Diego,
b Division of Infectious Disease, Department of Pediatrics, Columbia
University, New York, New York
d Division of Infectious Diseases, Department of Pediatrics,
University of South Florida College of Medicine, Tampa, Florida
e Division of Infectious diseases, Department of Pediatrics, School
of Medicine, University of California, Los Angeles, California
OBJECTIVE. An unstructured treatment interruption in children with
perinatally acquired HIV infection is an issue with unresolved significance.
The objective of this study was to investigate the actual prevalence
and clinical outcomes of a treatment interruption in children and
adolescents with perinatally acquired HIV-1 infection.
METHODS. Clinical data were analyzed for 72 children and adolescents
who had HIV-1 infection and stopped their medications at 4 academic centers
in the United States between January 2000 and September 2004.
RESULTS. Among 405 patients with perinatal HIV-1 infection, 72
(17.8%) experienced a treatment interruption during the observation period.
The mean age of patients at the time of the treatment interruption
was 12.8 years, and the mean length of the treatment interruption
was 14 months. Medication fatigue was the most common reason for a
treatment interruption. The CD4+ T-cell percentage nadir
before the treatment interruption did not predict CD4+
T-cell percentage declines during the treatment interruption; however,
the CD4+ T-cell percentage gain from nadir to the time of
the treatment interruption predicted CD4+ T-cell percentage declines
during the treatment interruption. During the median follow-up of 19
months (range: 6–48 months), 48 (67%) patients resumed
antiretroviral medications. As expected, there was a continuous CD4+
T-cell percentage decrease and plasma HIV-1 RNA increase during the
observation period. Overall, 7 (10%) patients were admitted to the
hospital; 2 (3%) patients experienced an AIDS-defining illness.
CONCLUSIONS. An unstructured treatment interruption seems to be
a major issue for youth with perinatally acquired HIV-1 infection. Patients
who experienced the greatest rise in CD4+ T-cell percentage on
treatment had the largest CD4+ T-cell percentage decline after
the treatment interruption. Close monitoring is required when a
treatment interruption occurs in children and adolescents with HIV
infection.
Key Words: treatment interruption • HIV-1 • children • adolescent •
nadir CD4+ T-cell percentage • medication fatigue
Abbreviations: HAART—highly active antiretroviral therapy • TI—treatment
interruption • CD4%—CD4+ T-cell percentage • NRTI—nucleoside reverse
transcriptase inhibitor • NNRTI—non–nucleoside reverse transcriptase inhibitor
• PI—protease inhibitor • PCP—Pneumocystis jiroveci pneumonia •
CI—confidence interval
Accepted Jul 19, 2007.
[Full Text of Saitoh et al.] [Reprint (PDF) Version of
Saitoh et al.]
High-Concentration
Nitrous Oxide for Procedural Sedation in Children: Adverse Events and Depth of
Sedation
Emergency Department, Royal Children's Hospital, Murdoch Children's
Research Institute and University of Melbourne, Melbourne, Australia
OBJECTIVE. Nitrous oxide is an attractive agent for procedural sedation
and analgesia in the emergency department; however, there are
limited safety data for high-concentration continuous-flow nitrous
oxide (50%–70%) and its use in young children. We set out to
characterize the depth of sedation and incidence of adverse events
associated with various concentrations of nitrous oxide used in a
pediatric emergency department.
METHODS. This was a prospective observational study of nitrous oxide
use for procedural sedation and analgesia in a tertiary children's
hospital emergency department. Nitrous oxide concentration, adverse
events, and sedation depth were recorded. Adverse events were
categorized as mild or serious. Sedation depth was recorded on a
sedation scale from 0 to 6.
RESULTS. A total of 762 patients who were aged 1 to 17 years received
nitrous oxide during the 2-year study period. A total of 548 (72%)
received nitrous oxide 70%, and 101 (13%) received nitrous oxide
50%. Moderate or deep sedation with scores of 
2 occurred in 3% of patients who had received nitrous oxide 70%
and no patients who had received nitrous oxide 50%. Mean sedation
scores were 4.4 at nitrous oxide 70% and 4.6 at nitrous oxide 50%. Sixty-three
(8.3%) patients sustained 70 mild and self-resolving adverse events,
most of which were vomiting (5.7%); 2 (0.2%) patients had serious
adverse events. There was no significant difference in adverse
events rates between nitrous oxide 70% (8.4%) and nitrous oxide 50%
(9.9%). There was no significant difference in the percentage of
deep sedation when children who were 3 years of age (2.9%) were compared with older children (2.8%).
CONCLUSIONS. In this largest prospective emergency department series,
high-concentration continuous-flow nitrous oxide (70%) was found to
be a safe agent for procedural sedation and analgesia when embedded
in a comprehensive sedation program. Nitrous oxide also seems safe
in children aged 1 to 3 years.
Key Words: nitrous oxide • procedural sedation and analgesia • adverse
events • emergency department
Abbreviations: N2O—nitrous oxide • ED—emergency department •
PSA—procedural sedation and analgesia • O2—oxygen •
IQR—interquartile range • CI—confidence interval
Accepted Jul 19, 2007.
[Full Text of Babl et al.] [Reprint (PDF) Version of
Babl et al.]
Cyst(e)ine
Requirements in Enterally Fed Very Low Birth Weight Preterm Infants
a Division of Neonatology, Department of Pediatrics, University Medical
Center
b Mass Spectrometry Laboratory, Division of Neonatology, Department
of Pediatrics, Erasmus Medical Center–Sophia Children's Hospital, Rotterdam,
Netherlands
c Department of Pediatrics, Amphia Hospital, Breda, Netherlands
d Department of Pediatrics, Medical Center Rijnmond-Zuid, Rotterdam,
Netherlands
e Department of Pediatrics, Albert Schweitzer Hospital, Dordrecht,
Netherlands
OBJECTIVE. Optimal nutrition is of utmost importance for the preterm
infant's later health and developmental outcome. Amino acid
requirements for preterm infants differ from those for term and
older infants, because growth rates differ. Some nonessential amino
acids, however, cannot be sufficiently synthesized endogenously. Cyst(e)ine
is supposed to be such a conditionally essential amino acid in
preterm infants. The objective of this study was to determine, at 32
and 35 weeks’ postmenstrual age, cyst(e)ine requirements in fully
enterally fed very low birth weight preterm infants with gestational
ages of <29 weeks.
METHODS. Infants were randomly assigned to 1 of the 5 graded cystine
test diets that contained generous amounts of methionine. Cyst(e)ine
requirement was determined with the indicator amino acid oxidation
technique ([1-13C]phenylalanine) after 24-hour adaptation.
RESULTS. Fractional [1-13C]phenylalanine oxidation was
established in 47 very low birth weight preterm infants (mean
gestational age: 28 weeks ± 1 week SD; birth weight:
CONCLUSIONS. These data do not support the hypothesis that endogenous
cyst(e)ine synthesis is limited in very low birth weight preterm infants
with gestational ages of <29 weeks, both at 32 and 35 weeks
postmenstrual age. It is safe to conclude that cyst(e)ine requirement
is <18 mg/kg per day in enterally fed very low birth weight preterm
infants who are older than 32 weeks’ postmenstrual age and whose
methionine intake is adequate. Therefore, cyst(e)ine is probably not
a conditionally essential amino acid in these infants.
Key Words: requirements • amino acids • indicator amino acid oxidation •
nutrition
Abbreviations: VLBW—very low birth weight • IAAO—indicator amino acid
oxidation • PMA—postmenstrual age • GA—gestational age • APE—atom percentage
excess
Accepted Aug 1, 2007.
[Full Text of Riedijk et al.] [Reprint (PDF) Version of
Riedijk et al.]
Luteinizing
Hormone and Follicle-Stimulating Hormone Levels in Extreme Prematurity:
Development of Reference Intervals
a Departments of Complex Biochemistry
b Neonatal Medicine
c Core Laboratory
d Endocrinology and Diabetes, Royal Children's Hospital, Victoria,
Australia
OBJECTIVES. Establishing pediatric reference intervals has always been
challenging, with most ranges used in pediatric laboratories developed
over many years. The clinical interpretation of gonadotropins is
important in the context of ambiguous genitalia. The aim of this
study was to develop reference intervals for luteinizing hormone and
follicle-stimulating hormone in infants born between 24 and 29
weeks’ gestation.
METHODS. Samples were collected at 0 to 43 days after birth from
82 premature infants born <30 weeks’ gestation for analysis of
luteinizing hormone and follicle-stimulating hormone by automated
immunochemiluminometric immunoassays.
RESULTS. The 43 male infants demonstrated a range of luteinizing hormone
levels from 0.1 to 13.4 IU/L and of follicle-stimulating hormone
levels from 0.3 to 4.6 IU/L. The 39 female infants demonstrated a
range of luteinizing hormone levels from 0.2 to 54.4 IU/L and of
follicle-stimulating hormone levels from 1.2 to 167.0 IU/L. The
ratio of luteinizing hormone/follicle-stimulating hormone levels
differed with males, ranging from 0.3 to 9.4, and females, at
<0.5.
CONCLUSION. These data provide guidance for the interpretation of
luteinizing hormone and follicle-stimulating hormone levels for the
first 6 weeks of life in extremely premature infants born between 24
and 29 weeks’ gestation. The availability of age-appropriate
reference intervals is essential for correct and timely interpretation
of biochemical results to the clinician.
Key Words: extremely premature infants • follicle-stimulating hormone •
luteinizing hormone • reference range
Abbreviations: LH—luteinizing hormone • FSH—follicle-stimulating hormone
• hCG—human chorionic gonadotropin • CV—coefficient of variation
Accepted Aug 13, 2007.
[Full Text of Greaves et al.] [Reprint (PDF) Version of
Greaves et al.]
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Motivations
of Mothers to Enroll Their Newborn Infants in General Clinical Research on
Well-Infant Care and Development
a Department of Neonatology, Edmond
and Lili Safra Children's Hospital, Sheba Medical Center, and Sackler Faculty
of Medicine, Tel Aviv University, Tel Aviv, Israel
b Psychology Department, Bar-Ilan University, Ramat-Gan, Israel
OBJECTIVE. The purpose of this work was to identify possible motivations
for mothers to consent to having their newborn infants participate
in medical research on well-infant care and to compare between
mothers of term infants and mothers of stable preterm infants.
METHODS. Two-hundred mothers answered a questionnaire regarding their
consent to have their newborns participate in 5 simulated studies at
different risk levels and their willingness to provide a telephone
number for future contact. Demographic data, attitudes about
medicine, medical research, and evaluation of research conditions
served as predictors of the degree of consent.
RESULTS. Degree of consent was affected mainly by perceived risk,
because the research did not offer a direct personal benefit; that
is, 80% consented to a psychological study as opposed to 25% who
consented to a vaccine study. The strength of the predicting variables
differentiated according to the suggested study. No significant
difference was found between the mothers of term infants (n =
127) and the mothers of preterm infants (n = 73), either in
the degree of consent to the 5 suggested studies or in the
predicting variables, except for the measure of actual behavior (ie,
revealing a telephone number). Only 23% of the mothers of term
infants in comparison with 48% of the mothers of preterm infants
were willing to reveal their telephone numbers.
CONCLUSIONS. There is some willingness to consent when the infant is
healthy and the research is not directed at solving a specific problem
of the infant. The degree of consent decreases in accordance with
the increase in risk. The altruistic motive is the main predictor
for research that is perceived as very risky. The benefit of
learning about their infant's development served as a motivating
force for less risky studies. We deduce that pointing out personal
benefits to balance the usual conveyed information on risks or
burdens of the research can increase the willingness to consent.
Key Words: clinical research • altruism • ethics • parents • newborn •
attitudes
Abbreviations: MANOVA—multivariate analysis of variance • df—degrees
of freedom • Fwilks—Wilks lambda approximation F statistic
Accepted Jul 31, 2007.
[Full Text of Maayan-Metzger et al.] [Reprint (PDF) Version of
Maayan-Metzger et al.]
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Impaired
Autoregulation in Preterm Infants Identified by Using Spatially Resolved
Spectroscopy
a Ritchie Centre for Baby Health Research, Monash University, Melbourne,
Victoria, Australia
Departments of b Paediatrics and Child Health
c Medical Physics and Bioengineering, University College London,
London, United Kingdom
OBJECTIVE. The absence of cerebral autoregulation in preterm infants
has been associated with adverse outcome, but its bedside assessment
in the immature brain is problematic. We used spatially resolved
spectroscopy to continuously measure cerebral oxygen saturation
(expressed as a tissue-oxygenation index) and used the correlation
of tissue-oxygenation index with spontaneous fluctuations in mean
arterial blood pressure to assess cerebral autoregulation.
PATIENTS AND METHODS. The tissue-oxygenation index and mean arterial
blood pressure were continuously measured in very premature infants
(n = 24) of mean (±SD) gestational age of 26 (±2.3) weeks at
a mean postnatal age of 28 (±22) hours. The correlation between mean
arterial blood pressure and tissue-oxygenation index in the
frequency domain was assessed by using cross-spectral analysis
techniques (coherence and transfer-function gain). Values of
coherence reflect the strength of linear correlation, whereas
transfer-function gain reflects the amplitude of tissue-oxygenation index
changes relative to mean arterial blood pressure changes.
RESULTS. High coherence (coherence 0.5) values were found in 9 infants who were of lower
gestational age, lower birth weight, and lower mean arterial blood
pressure than infants with coherence of <0.5; high-coherence
infants also had higher median Clinical Risk Index for Babies scores
and a higher rate of neonatal deaths. Coherence of 0.5 predicted mortality with a positive predictive value of
67% and negative predictive value of 100%. In multifactorial analysis,
coherence alone was the best predictor of mortality and Clinical
Risk Index for Babies score alone was the best predictor of
coherence.
CONCLUSIONS. High coherence between mean arterial blood pressure and
tissue-oxygenation index indicates impaired cerebral autoregulation in
clinically sick preterm infants and is strongly associated with
subsequent mortality. Cross-spectral analysis of mean arterial blood
pressure and tissue-oxygenation index has the potential to provide
continuous bedside assessment of cerebral autoregulation and to
guide therapeutic interventions.
Key Words: cerebrovascular autoregulation • cerebral oxygenation •
near-infrared spectroscopy • premature infants • spectral coherence
Abbreviations: CBF—cerebral blood flow • MAP—mean arterial blood
pressure • NIRS—near-infrared spectroscopy • SRS—spatially resolved
spectroscopy • TOI—tissue-oxygenation index • CRIB—Clinical Risk Index for
Babies • PSD—power spectral density • Coh—coherence function • G—transfer-function
gain • ULF—ultralow frequency • VLF—very low frequency • LF—low frequency •
IVH—intraventricular hemorrhage • CI—confidence interval • HbD—intravascular
oxygenation • CBFV—cerebral blood flow velocity
Accepted Aug 2, 2007.
[Full Text of Wong et al.] [Reprint (PDF) Version of
Wong et al.]
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Incremental
Diagnostic Yield of Pediatric Cardiac Assessment After Fetal Echocardiography
in the Offspring of Women With Congenital Heart Disease: A Prospective Study
University of Toronto Pregnancy and Heart Disease Research Program,
Mount Sinai Hospital, Toronto General Hospital, Hospital for Sick Children,
University of Toronto, Toronto, Ontario, Canada
OBJECTIVE. We sought to determine the incremental diagnostic utility
of pediatric cardiac assessment in the offspring of women with
congenital heart disease who have had previous fetal echocardiography.
PATIENTS AND METHODS. We prospectively followed pregnant women with
congenital heart disease who were receiving care at 2 obstetric and
cardiac centers and identified 276 infants who underwent both fetal
echocardiography and pediatric cardiac assessment. All of the
infants with abnormal fetal echocardiography findings or abnormal
pediatric cardiac assessments underwent subsequent confirmatory
pediatric echocardiography.
RESULTS. In this cohort, congenital heart disease was detected in
22 (8%) of 276 offspring born to women with congenital heart disease.
There was concordance between the results of fetal echocardiography
and pediatric cardiac assessment in 235 (85%) of 276 offspring (231,
both normal; 4, both abnormal) and discordance between the results
of fetal echocardiography and pediatric cardiac assessment in 41
(15%) of 276 infants. In the 41 subjects with discordant results,
there were normal fetal echocardiography findings but abnormal
pediatric cardiac assessments in 35 of 41 (pediatric
echocardiography revealed congenital heart disease in 18 of 35 and
normal anatomy in 17 of 35) and abnormal fetal echocardiography
findings but normal pediatric cardiac assessments in 6 of 41
(pediatric echocardiography findings normal in all 6 of the
infants). Fetal echocardiography detected all of the major forms of
congenital heart disease. Lesions missed by fetal echocardiography
but detected on pediatric cardiac assessment included shunt lesions
and minor valvular abnormalities.
CONCLUSIONS. Although fetal echocardiography can reliably exclude major
forms of congenital heart disease, minor congenital heart disease
lesions can be missed on fetal echocardiography; however, these can
be diagnosed with careful pediatric cardiac assessment. Postnatal
pediatric cardiac assessment has incremental diagnostic utility for
the detection of congenital heart disease in the offspring of women
with congenital heart disease and previous fetal echocardiography.
Key Words: fetal • pediatrics • diagnosis • congenital heart defects •
echocardiography • pregnancy
Abbreviations: CHD—congenital heart disease • FE—fetal echocardiography
• CA—pediatric cardiac assessment • PE—pediatric echocardiography • PDA—patent
ductus arteriosus • VSD—ventricular septal defect
Accepted Aug 20, 2007.
[Full Text of Thangaroopan et al.] [Reprint (PDF) Version of
Thangaroopan et al.]
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Cord
Blood and Breast Milk Iron Status in Maternal Anemia
a Division of Neonatology, Department of Pediatrics
b Department of Biochemistry, Institute of Medical Sciences
c Department of Botany, Faculty of Science, Banaras Hindu
University, Varanasi, India
OBJECTIVES. The purpose of this work was to assess the effect of
severe maternal iron-deficiency anemia and nutritional status on
cord blood and breast milk iron status.
METHODS. We conducted a prospective observational study over a
6-month period in a teaching hospital in central India. The study
population consisted of 55 anemic (hemoglobin: <110 g/L) and 20
healthy nonanemic (hemoglobin: 110 g/L) pregnant women who delivered singleton live births
at term gestation. We measured hemoglobin, iron, and ferritin levels
in paired maternal and cord blood and iron levels in early (day 3 ±
1) and late (day 15 ± 3) transitional milk. Maternal anthropometry,
including weight, height, midarm circumference, triceps skinfold
thickness, and placental weight, were recorded. The main outcome
measure of the study was to find out the relationship of maternal
hemoglobin, iron, ferritin, and anthropometry with hemoglobin, iron,
and ferritin in cord blood and iron levels in breast milk.
RESULTS. Concentrations of hemoglobin, iron, and ferritin were significantly
lower in the cord blood of anemic mothers and showed linear
relationships with maternal hemoglobin and ferritin levels. Breast
milk iron content was significantly reduced in severely anemic
mothers but not in those with mild-to-moderate anemia. Breast milk
iron level correlated with maternal hemoglobin and iron levels but
not with ferritin levels. Maternal anthropometry had significant
correlations with indices of iron nutriture in maternal and cord
blood but showed no relationship with breast milk iron content. Placental
weight was comparable between anemic and nonanemic mothers.
CONCLUSIONS. Maternal anemia, particularly the severe type, adversely
affects cord blood and breast milk iron status. Maternal nutritional
status exerts a significant influence on fetal iron status but has
little influence on breast milk iron content.
Key Words: breast milk • cord blood • iron status • maternal anemia •
newborn
Accepted Aug 22, 2007.
[Full Text of Kumar et al.] [Reprint (PDF) Version of
Kumar et al.]
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Risk
Factors for Developing Apnea After Immunization in the Neonatal Intensive Care
Unit
a Vaccine Studies Center
b Division of Research
c Systems Research Initiative
d Perinatal Research Unit, Kaiser Permanente, Oakland, California
e Division of Pediatric Infectious Diseases, Stanford University
School of Medicine, Stanford, California
f Department of Inpatient Pediatrics, Kaiser Permanente Medical
Center, Walnut Creek, California
OBJECTIVES. Among hospitalized NICU infants, preimmunization apnea
is a well-recognized predictor of postimmunization apnea. However,
predictors for postimmunization apnea among NICU infants without
preimmunization apnea have not been investigated.
METHODS. Using a large NICU database in the Northern California Kaiser
Permanente Medical Care Program, we abstracted NICU charts of
infants who were hospitalized for 53 days and who were also immunized, capturing
preimmunization (24 hours before immunization) and postimmunization
(48 hours after immunization) events. We assessed factors associated
with postimmunization apnea by using multivariate logistic
regression.
RESULTS. Of 16 146 infants admitted to the NICU, 557 received 1 vaccine and 497 met the criteria for study entry. All infants with
preimmunization apnea (n = 27) and all except 3 infants with
postimmunization apnea (n = 65) had gestational ages of <31
weeks. Multivariate analyses revealed preimmunization apnea as the
most important predictor of postimmunization apnea, although higher
12-hour Score for Neonatal Acute Physiology II and age of <67
days (mean cohort age) were also associated. Multivariate analysis
exclusively among infants without preimmunization apnea similarly
found elevated Score for Neonatal Acute Physiology II, age of <67
days, and weight of <1 apnea predictor were discharged within 48 hours after
immunization; 2 were subsequently readmitted because of apnea.
CONCLUSIONS. For infants in the NICU without apnea during the 24
hours immediately before immunization, younger age, smaller size,
and more severe illness at birth are important predictors of postimmunization
apnea.
Key Words: vaccines • apnea • premature infants
Abbreviations: DTP—diphtheria/tetanus/whole-cell pertussis •
DTaP—diphtheria/tetanus/acellular pertussis • IPV—inactivated polio vaccine •
Hib—Haemophilus influenzae type b • SNAP-II—Score for Neonatal Acute
Physiology II • HBV—hepatitis B virus • AOR—adjusted odds ratio • CI—confidence
interval • KPMCP—Kaiser Permanente Medical Care Program
Accepted Aug 9, 2007.
[Full Text of Klein et al.] [Reprint (PDF) Version of
Klein et al.]
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Neurodevelopmental
Outcomes After Staged Palliation for Hypoplastic Left Heart Syndrome
Department of
Pediatrics, Divisions of a Cardiology
d General Pediatrics
e Psychology
f Genetics
g Neurology
b Department of Anesthesia and Critical Care Medicine
h Department of Surgery, Division of Cardiothoracic Surgery,
Children's Hospital of Philadelphia and University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania
c Department of Medicine, Division of Medical Genetics, University
of Washington, Seattle, Washington
OBJECTIVE. The goal was to determine the relative effects of underlying
genetic factors and current management strategies on
neurodevelopmental disabilities among one-year old survivors of
palliation for hypoplastic left heart syndrome.
METHODS. Children who underwent staged reconstruction for hypoplastic
left heart syndrome and variants were assessed at 1 year of age
by using a neuromuscular examination and the Bayley Scales of Infant
Development II, which provide the Mental Development Index and the
Psychomotor Development Index. The effects of perioperative,
operative, and genetic variables on developmental scores were
evaluated.
RESULTS. The median birth weight was
CONCLUSIONS. At 1 year of age, there was a significant incidence of
neurodevelopmental disabilities in children with hypoplastic left
heart syndrome and variants; motor scores were particularly concerning.
Many children had suspected or confirmed genetic syndromes, which
negatively affected neurodevelopmental outcomes. Surgical
variables did not affect neurologic outcomes.
Key Words: developmental outcomes • hypoplastic left heart syndrome
Abbreviations: HLHS—hypoplastic left heart syndrome • DHCA—deep
hypothermic circulatory arrest • CPB—cardiopulmonary bypass • MDI—Mental
Development Index • PDI—Psychomotor Development Index • ECMO—extracorporeal
membrane oxygenation • LOS—length of stay • S1R—stage 1 reconstruction •
PVL—periventricular leukomalacia • mBTS—modified Blalock-Taussig shunt
Accepted Aug 10, 2007.
[Full Text of Tabbutt et al.] [Reprint (PDF) Version of
Tabbutt et al.]
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Effect
of Skin Barrier Therapy on Neonatal Mortality Rates in Preterm Infants in
Bangladesh: A Randomized, Controlled, Clinical Trial
a Departments of International Health
d Population and Family Health Sciences, Bloomberg School of Public
Health, Johns Hopkins University, Baltimore, Maryland
b Departments of Microbiology
e Neonatology, Bangladesh Institute of Child Health, Dhaka Shishu
Hospital, Dhaka, Bangladesh
c Department of Pediatrics, Kumudini Women's Medical College,
Mirzapur, Tangail, Bangladesh
f Department of Medical Informatics, Kennedy Krieger Institute,
Johns Hopkins Medical Institutions, Baltimore, Maryland
OBJECTIVE. Skin barrier therapy during the neonatal period, when
the skin barrier is most highly compromised and the risk of death is
greatest, has been shown to have a number of potential benefits,
including reduced risk of nosocomial sepsis. Topical application of
emollients that augment skin barrier function was evaluated as a
strategy for improving survival rates among hospitalized preterm
infants in Bangladesh.
METHODS. A prospective, randomized, controlled, clinical trial was
conducted in the special care nursery at Dhaka Shishu (Children) Hospital,
the largest tertiary care children's hospital in Bangladesh. Preterm
infants (gestational age: 33 weeks; N = 497) received daily topical applications
of sunflower seed oil or Aquaphor ointment. Neonatal mortality rates
were compared in an intent-to-treat analysis with a control group
that did not receive emollient therapy.
RESULTS. Treatment with sunflower seed oil resulted in a statistically
significant 26% reduction in mortality rates, compared with infants
not receiving topical emollient therapy. Aquaphor therapy also
significantly reduced mortality rates, by 32%.
CONCLUSIONS. Topical therapy with skin barrier-enhancing emollients
improved survival rates among preterm hospitalized infants in Bangladesh.
This study provides strong evidence for the implementation of
topical therapy for high-risk preterm neonates in developing countries.
Key Words: developing country • emollient • low birth weight • mortality
• preterm
Abbreviations: SSO—sunflower seed oil • CI—confidence interval
Accepted Aug 20, 2007.
[Full Text of Darmstadt et al.] [Reprint (PDF) Version of
Darmstadt et al.]
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Prevalence
of Cerebral Palsy in 8-Year-Old Children in Three Areas of the United States in
2002: A Multisite Collaboration
a National Center on Birth Defects and Developmental Disabilities,
Centers for Disease Control and Prevention, Atlanta, Georgia
b Department of Kinesiology
d Waisman Center
e Department of Population Health Sciences, University of
Wisconsin-Madison, Madison, Wisconsin
c Department of Maternal and Child Health, School of Public Health,
University of Alabama at Birmingham, Birmingham, Alabama
OBJECTIVE. The goal was to estimate the prevalence of cerebral palsy
and cerebral palsy subtypes among children in 3 areas of the United
States by using a population-based surveillance system.
METHODS. Using methods developed by the Centers for Disease Control
and Prevention Metropolitan Atlanta Developmental Disabilities Surveillance
Program, investigators from the Autism and Developmental Disabilities
Monitoring Network conducted surveillance of cerebral palsy among
8-year-old children living in northern Alabama, metropolitan
Atlanta, and southeastern Wisconsin in 2002 (N = 114897). Cross-sectional
data were collected through retrospective record review from
multiple sources. Cases were linked to birth certificate and census
files to obtain additional information. Period prevalence estimates
were calculated per 1000 children 8 years of age.
RESULTS. The average prevalence of cerebral palsy across the 3
sites was 3.6 cases per 1000, with notably similar site-specific prevalence
estimates (3.3 cases per
CONCLUSION. These findings contribute new knowledge to the epidemiology
of cerebral palsy in the United States. The similarities in prevalence
rates and patterns of cerebral palsy reported for 8-year-old
children at 3 geographically distinct sites provide evidence of the
reliability of the surveillance methods used by the Autism and
Developmental Disabilities Monitoring Network.
Key Words: prevalence • cerebral palsy • developmental disabilities •
population-based surveillance
Abbreviations: ADDM—Autism and Developmental Disabilities Monitoring •
CP—cerebral palsy • SES—socioeconomic status • CI—confidence interval
Accepted Aug 15, 2007.
[Full Text of Yeargin-Allsopp et al.] [Reprint (PDF) Version of
Yeargin-Allsopp et al.]
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Plasma
Biomarkers of Oxidative Stress: Relationship to Lung Disease and Inhaled Nitric
Oxide Therapy in Premature Infants
a Department of Pediatrics, University of California, San Francisco,
California
b Department of Pediatrics, Children's Mercy Hospitals and
Clinics/University of Missouri-Kansas City School of Medicine, Kansas City,
Missouri
c Department of Pediatrics and Biostatistics, Children's Hospital of
Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania
d Department of Pediatrics, New York Medical College/Maria Fareri
Children's Hospital at Westchester Medical Center, Valhalla, New York
e Department of Pharmacology and Toxicology, Rutgers University, New
Brunswick, New Jersey
OBJECTIVES. Inhaled nitric oxide treatment for ventilated premature
infants improves survival without bronchopulmonary dysplasia. However,
there has been no information regarding possible effects of this
therapy on oxidative stress. We hypothesized that inhaled nitric
oxide therapy would not influence concentrations of plasma biomarkers
of oxidative stress.
PATIENTS AND METHODS. As part of the Nitric Oxide Chronic Lung Disease
Trial, we collected blood samples at specified intervals from a
subpopulation of 100 infants of <
RESULTS. The demographic characteristics and primary outcome for
the infants were representative of the entire group of infants who
were in the Nitric Oxide Chronic Lung Disease Trial. For all infants
at baseline, before receiving study gas, the concentration of total
protein was inversely correlated with the respiratory severity
score, and plasma carbonyl was positively correlated with severity
score, supporting an association between oxidative stress and
severity of lung disease. Infants who survived without bronchopulmonary
dysplasia had 30% lower protein carbonylation concentrations at
study entry than those who had an adverse outcome. At each of 3 time
points (1–10 days) during exposure to study gas, there were no
significant differences between control and treated infants for
concentrations of plasma protein, 3-nitrotyrosine, and
carbonylation.
CONCLUSIONS. Inhaled nitric oxide treatment for premature infants who
are at risk for bronchopulmonary dysplasia does not alter plasma
biomarkers of oxidative stress, which supports the safety of this
therapy.
Key Words: nitric oxide • premature infant • 3-nitrotyrosine • carbonyl
• bronchopulmonary dysplasia
Abbreviations: NO—nitric oxide • iNO—inhaled nitric oxide •
BPD—bronchopulmonary dysplasia • NO-CLD—Nitric Oxide Chronic Lung Disease •
RSS—respiratory severity score • PMA—postmenstrual age • FIO2—fraction of inspired oxygen
Accepted Oct 9, 2007.
[Full Text of Ballard et al.] [Reprint (PDF) Version of
Ballard et al.]
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Intrauterine
Risk Factors for Precocious Atherosclerosis
Human Nutrition Research Centre, Université Claude Bernard, Lyon, France
Evidence from noninvasive ultrasound studies of the neonatal aorta
and fetal and early childhood postmortem studies indicates that
impaired fetal growth, in utero exposure to maternal hypercholesterolemia,
and diabetic macrosomia may all be important risk factors for vascular
changes consistent with the earliest physical signs of
atherosclerosis. Although the exact mechanisms that underlie these
associations remain unclear, animal models have suggested that the
use of antioxidant, lipid-lowering, and other innovative therapies
may counteract the impact of these intrauterine risk factors for
cardiovascular disease. This review summarizes the current evidence
for intrauterine factors that have a direct impact on
atherosclerosis and provides potential treatment and prevention
strategies.
Key Words: cardiovascular disease • fetal growth restriction • lipids
Abbreviations: LDL—low-density lipoprotein • IUGR—intrauterine
growth-restricted
Accepted Aug 13, 2007.
[Full Text of Skilton] [Reprint (PDF) Version of Skilton]
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Postdischarge
Follow-up of Infants With Congenital Diaphragmatic Hernia
Infants with congenital diaphragmatic hernia often require intensive
treatment after birth, have prolonged hospitalizations, and have
other congenital anomalies. After discharge from the hospital, they
may have long-term sequelae such as respiratory insufficiency, gastroesophageal
reflux, poor growth, neurodevelopmental delay, behavior problems,
hearing loss, hernia recurrence, and orthopedic deformities. Structured
follow-up for these patients facilitates early recognition and
treatment of these complications. In this report, follow-up of
infants with congenital diaphragmatic hernia is outlined.
Key Words: congenital diaphragmatic hernia • gastroesophageal reflux •
pulmonary hypoplasia • follow-up
Abbreviations: CDH—congenital diaphragmatic
hernia • ECMO—extracorporeal membrane oxygenation
[Full Text of Section on Surgery and the Committee on Fetus and
Newborn] [Reprint (PDF) Version of Section on Surgery and the Committee on Fetus
and Newborn]
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STATE-OF-THE-ART REVIEW ARTICLE
Ethical,
Legal, and Social Concerns About Expanded Newborn Screening: Fragile X Syndrome
as a Prototype for Emerging Issues
a RTI International, Research Triangle Park, North Carolina
b FPG Child Development Institute
c Department of Social Medicine
d Department of Pediatrics, University of North Carolina, Chapel
Hill, North Carolina
ABSTRACT
Technology will make it possible to screen for fragile X syndrome and
other conditions that do not meet current guidelines for routine
newborn screening. This possibility evokes at least 8 broad ethical,
legal, and social concerns: (1) early identification of fragile X
syndrome, an "untreatable" condition, could lead to
heightened anxiety about parenting, oversensitivity to development, alterations
in parenting, or disrupted bonding; (2) because fragile X syndrome
screening should be voluntary, informed consent could overwhelm
parents with information, significantly burden hospitals, and reduce
participation in the core screening program; (3) screening will
identify some children who are or appear to be phenotypically
normal; (4) screening might identify children with other conditions
not originally targeted for screening; (5) screening could overwhelm
an already limited capacity for genetic counseling and comprehensive
care; (6) screening for fragile X syndrome, especially if carrier
status is disclosed, increases the likelihood of negative
self-concept, societal stigmatization, and insurance or employment
discrimination; (7) screening will suggest risk in extended family
members, raising ethical and legal issues (because they never
consented to screening) and creating a communication burden for
parents or expanding the scope of physician responsibility; and (8)
screening for fragile X syndrome could heighten discrepancies in
how men and women experience genetic risk or decide about testing. To
address these concerns we recommend a national newborn screening
research network; the development of models for informed decision-making;
materials and approaches for helping families understand genetic information
and communicating it to others; a national forum to address carrier
testing and the disclosure of secondary or incidental findings; and
public engagement of scientists, policy makers, ethicists,
practitioners, and other citizens to discuss the desired aims of
newborn screening and the characteristics of a system needed to
achieve those aims.
Key Words: newborn screening
Abbreviations: ACMG—American College of Medical Genetics • NBS—newborn
screening • FXS—fragile X syndrome • FMRP—fragile X mental retardation protein
• CF—cystic fibrosis • IDM—informed decision-making
Accepted Jul 16, 2007.
[Full Text of Bailey et al.] [Reprint (PDF) Version of
Bailey et al.]