PEDIATRICS
FEBRERO 2008
Abstract 1 of 18 
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Mercury Level in Newborns and Infants After Receipt of
Thimerosal-Containing Vaccines
a Department of
Microbiology/Immunology, Pediatrics, and Medicine, University of Rochester,
Rochester, New York
b Department of Epidemiology, R. Gutierrez Children's Hospital,
Buenos Aires, Argentina
c Department of Environmental Medicine, University of Rochester,
Rochester, New York
d Center of Toxicology Research, Buenos Aires, Argentina
e EMMES Corp, Rockville, Maryland
OBJECTIVES. Thimerosal is a mercurial
preservative that was widely used in multidose vaccine vials in the
United States and Europe until 2001 and continues to be used in many
countries throughout the world. We conducted a pharmacokinetic study
to assess blood levels and elimination of ethyl mercury after
vaccination of infants with thimerosal-containing vaccines.
METHODS. Blood, stool, and urine samples were
obtained before vaccination and 12 hours to 30 days after
vaccination from 216 healthy children: 72 newborns (group 1), 72
infants aged 2 months (group 2), and 72 infants aged 6 months (group
3). Total mercury levels were measured by atomic absorption. Blood
mercury pharmacokinetics were calculated by pooling the data on the
group and were based on a 1-compartment first-order pharmacokinetics
model.
RESULTS. For groups 1, 2, and 3, respectively,
(1) mean ± SD weights were 3.4 ± 0.4, 5.1 ± 0.6, and 7.7 ±
CONCLUSIONS. The blood half-life of
intramuscular ethyl mercury from thimerosal in vaccines in infants
is substantially shorter than that of oral methyl mercury in adults.
Increased mercury levels were detected in stools after vaccination,
suggesting that the gastrointestinal tract is involved in ethyl
mercury elimination. Because of the differing pharmacokinetics of
ethyl and methyl mercury, exposure guidelines based on oral methyl
mercury in adults may not be accurate for risk assessments in children
who receive thimerosal-containing vaccines.
Key Words: thimerosal • vaccine • neurotoxicity • ethyl mercury
Abbreviations: Hib—Haemophilus influenzae type b • HBV—hepatitis B virus •
CI—confidence interval • DTwP—diphtheria–tetanus–whole-cell pertussis •
CVAFS—cold-vapor atomic fluorescence spectrophotometry • GGT—
-glutamyl transpeptidase
Accepted Jul 16, 2007.
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Fathers’ Experiences
in the Neonatal Intensive Care Unit: A Search for Control
a Departments of
Pediatrics
b Occupational Science and Occupational Therapy, University of
British Columbia, Vancouver, British Columbia, Canada
c Centre for Community Child Health Research, Child and Family
Research Institute, Vancouver, British Columbia, Canada
d B.C. Children's and Women's Hospitals, Vancouver, British
Columbia, Canada
OBJECTIVE. This qualitative study aimed at
understanding the experiences of fathers of very ill neonates in the
NICU.
METHODS. Sixteen fathers of very ill and/or
very preterm infants who had been in the NICU for >30 days were
interviewed by a male physician. Fathers were asked about their
level of comfort with or concerns about staff communication
regarding their infant, about accessing information, and about more
general perceptions of their experience in the neonatal intensive
care unit. Interviews were audiotaped and transcribed for analysis.
Coding used content analysis with construction of themes by 3
researchers.
RESULTS. The overarching theme for fathers was
a sense of lack of control. Their world view, as a "backdrop"
theme, provided context for all of the themes. Four other
interrelated subthemes were identified, including information;
communication, particularly with the health care team; fathers’
various roles; and external activities. Fathers reported that relationships
with friends/family/health care team, receiving information
consistently, and receiving short written materials on common
conditions were ways of giving them support. The fathers said that
speaking to a male physician was a positive and useful experience.
CONCLUSIONS. Fathers experience a sense of lack
of control when they have an extremely ill infant in the NICU. Specific
activities help fathers regain a sense of control and help them
fulfill their various roles of protectors, fathers, partners, and
breadwinners. Understanding these experiences helps the health care
team offer targeted supports for fathers in the NICU.
Key Words: preterm infant • fathers • stress • NICU
Accepted Jun 20, 2007.
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Effect of Late-Preterm
Birth and Maternal Medical Conditions on Newborn Morbidity Risk
a Division of
Reproductive Health, National Center for Chronic Disease Prevention and Health
Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
b Department of Maternal and Child Health, Boston University School
of Public Health, Boston, Massachusetts
c Massachusetts Department of Public Health, Bureau of Family and
Community Health, and Northeastern University, Boston, Massachusetts
OBJECTIVES. Late-preterm infants (34–36 weeks’
gestation) account for nearly three quarters of all preterm births
in the United States, yet little is known about their morbidity
risk. We compared late-preterm and term (37–41 weeks’ gestation)
infants with and without selected maternal medical conditions and
assessed the independent and joint effects of these exposures on
newborn morbidity risk.
METHODS. We used 1998–2003, population-based,
Massachusetts birth and death certificates data linked to infant and
maternal hospital discharge records from the Massachusetts Pregnancy
to Early Life Longitudinal data system. Newborn morbidity risks that
were associated with gestational age and selected maternal medical
conditions, both independently and as joint exposures, were
estimated by calculating adjusted risk ratios. A new measure of
newborn morbidity that was based on hospital discharge diagnostic codes,
hospitalization duration, and transfer status was created to define
newborns with and without life-threatening conditions. Eight
selected maternal medical conditions were assessed (hypertensive disorders
of pregnancy, diabetes, antepartum hemorrhage, lung disease,
infection, cardiac disease, renal disease, and genital herpes) in
relation to newborn morbidity.
RESULTS. Our final study population included
26170 infants born late preterm and 377638 born at term. Late-preterm
infants were 7 times more likely to have newborn morbidity than term
infants (22% vs 3%). The newborn morbidity rate doubled in infants
for each gestational week earlier than 38 weeks. Late-preterm infants
who were born to mothers with any of the maternal conditions assessed
were at higher risk for newborn morbidity compared with similarly
exposed term infants. Late-preterm infants who were exposed to
antepartum hemorrhage and hypertensive disorders of pregnancy were
especially vulnerable.
CONCLUSIONS. Late-preterm birth and, to a
lesser extent, maternal medical conditions are each independent risk
factors for newborn morbidity. Combined, these 2 factors greatly
increased the risk for newborn morbidity compared with term infants
who were born without exposure to these risks.
Key Words: preterm birth • near-term infant • late-preterm infant • morbidity •
maternal health
Abbreviations: HDP—hypertensive disorders of pregnancy • PELL—Pregnancy to Early Life
Longitudinal • ICD-9-CM—International Classification of Diseases, Ninth
Revision, Clinical Modification • GED—general equivalency diploma •
cRR—crude risk ratio • aRR—adjusted risk ratio • CI—confidence interval
Accepted Jun 19, 2007.
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Prevention and
18-Month Outcomes of Serious Pulmonary Hemorrhage in Extremely Low Birth Weight
Infants: Results From the Trial of Indomethacin Prophylaxis in Preterms
a Departments of
Pediatrics
c Clinical Epidemiology and Biostatistics, McMaster University,
Hamilton, Ontario, Canada
b Department of Pediatrics, University of British Columbia,
Vancouver, British Columbia, Canada
d Department of Pediatrics, University of Toronto, Toronto, Ontario,
Canada
OBJECTIVES. A patent ductus arteriosus is a
risk factor for pulmonary hemorrhage; however, despite halving the
incidence of patent ductus arteriosus, indomethacin prophylaxis did
not reduce the rate of pulmonary hemorrhage in the Trial of
Indomethacin Prophylaxis in Preterms. Inclusion of mild bleeds after
trauma to the upper airways may have masked a beneficial drug
effect. Using the Trial of Indomethacin Prophylaxis in Preterms
database, we studied the effect of prophylactic indomethacin on the
prevention of serious hemorrhages in extremely low birth weight
infants. We also compared the 18-month outcomes of infants with and
without a serious pulmonary bleed.
METHODS. Pulmonary hemorrhage was classified as
serious when it was treated with increased ventilator support, a
higher concentration of oxygen, or transfusion of blood products. The
cumulative risk for serious pulmonary hemorrhage was estimated for
the first week of life and for the entire NICU stay. Poor outcome
at a corrected age of 18 months was death or survival with cerebral palsy,
cognitive delay, blindness, and/or deafness.
RESULTS. A total of 123 (10.2%) of 1202 infants
developed a serious pulmonary hemorrhage. During week 1,
prophylactic indomethacin reduced the risk for serious pulmonary
hemorrhage by 35%; however, during the entire NICU stay, the risk
for such hemorrhages was decreased by only 23%. A reduced risk for
patent ductus arteriosus explained 80% of the beneficial effect of
prophylactic indomethacin on serious pulmonary bleeds. The risks for
death or for survival with neurosensory impairment were doubled
after a serious pulmonary hemorrhage.
CONCLUSIONS. Extremely low birth weight infants
with serious pulmonary hemorrhage have an increased risk for poor
long-term outcome. Prophylactic indomethacin reduces the rate of
early serious pulmonary hemorrhage, mainly through its action on
patent ductus arteriosus. Prophylactic indomethacin is less
effective in preventing serious pulmonary hemorrhages that occur
after the first week of life.
Key Words: extremely low birth weight • pulmonary hemorrhage • indomethacin
prophylaxis
Abbreviations: PDA—patent ductus arteriosus • TIPP—Trial of Indomethacin Prophylaxis
in Preterms • ELBW—extremely low birth weight
Accepted Jul 19, 2007.
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Effects of Basic
Developmental Care on Neonatal Morbidity, Neuromotor Development, and Growth at
Term Age of Infants Who Were Born at <32 Weeks
a Subdivision of
Neonatology, Department of Pediatrics
c Department of Medical Statistics, Leiden University Medical
Center, Leiden, Netherlands
b Subdivision of Neonatology, Department of Pediatrics, Haga
Hospital, Juliana Children's Hospital, The Hague, Netherlands
OBJECTIVE. The goal of this study was to
investigate the effect of basic elements of developmental care
(incubator covers and positioning aids) on days of respiratory
support and intensive care, growth, and neuromotor development at
term age in infants who were born at <32 weeks’ gestation.
METHODS. Infants were randomly assigned within
48 hours of birth to the developmental care group or the standard
care control group (no covers or nests). The intervention continued
until the infant either was transferred to a regional hospital or
was discharged from the hospital. Length, weight, and head circumference
were measured (bi)weekly and at term age. Neuromotor development was
defined as definitely abnormal (presence of a neonatal neurologic syndrome,
such as apathy or hyperexcitability, hypotonia or hypertonia,
hyporeflexia or hyperreflexia, hypokinesia or hyperkinesia, or a
hemisyndrome), mildly abnormal (presence of only part of such a
syndrome), or normal.
RESULTS. A total of 192 infants were included
(developmental care: 98; control: 94). Thirteen infants
(developmental care: 7; control: 6) were excluded according to
protocol (admitted for less than or died within the first 5 days: n
= 12; taken out at parents’ request: n = 1), which left a
total of 179 infants who met inclusion criteria. In-hospital
mortality was 12 (13.2%) of
CONCLUSIONS. Providing basic developmental care
in the NICU had no effect on short-term physical and neurologic
outcomes in infants who were born at <32 weeks’ gestation.
Key Words: preterm infants • developmental care • NIDCAP • growth • respiratory
support • intensive care • neurodevelopment
Abbreviations: DC—developmental care • NIDCAP—Newborn Individualized Developmental
Care and Assessment Program • RCT—randomized, controlled trial •
CPAP—continuous positive airway pressure • IVH—intraventricular hemorrhage
Accepted Jun 18, 2007.
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Pepsin, a Marker of
Gastric Contents, Is Increased in Tracheal Aspirates From Preterm Infants Who
Develop Bronchopulmonary Dysplasia
a Division of
Gastroenterology and Nutrition and Nemours Biomedical Research, Alfred I. duPont
Hospital for Children, Wilmington, Delaware
b Departments of Pediatrics/Neonatology
c Pathology, Cooper University Hospital-UMDNJ-Robert Wood Johnson
Medical School, Camden, New Jersey
d Division of Gastroenterology and Nutrition, Nemours Children's Clinic,
Orlando, Florida
OBJECTIVE. The objective of this study was to
study the association between pepsin in tracheal aspirate samples
and the development of bronchopulmonary dysplasia in preterm
infants.
METHODS. Serial tracheal aspirate samples were
collected during the first 28 days from mechanically ventilated
preterm neonates. Bronchopulmonary dysplasia was defined as the need
for supplemental oxygen at 36 weeks’ postmenstrual age. An enzymatic
assay with a fluorescent substrate was used to detect pepsin. Total
protein was measured by the Bradford assay to correct for the dilution
during lavage. Immunohistochemistry using antibody against human
pepsinogen was performed in 10 lung tissue samples from preterm
infants.
RESULTS. A total of 256 tracheal aspirate
samples were collected from 59 preterm neonates. Pepsin was detected
in 234 (91.4%) of 256 of the tracheal aspirate samples. Twelve
infants had no bronchopulmonary dysplasia, 31 infants developed bronchopulmonary
dysplasia, and 16 infants died before 36 weeks’ postmenstrual age.
The mean pepsin concentration was significantly lower in infants
with no bronchopulmonary dysplasia compared with those who developed
bronchopulmonary dysplasia or developed bronchopulmonary dysplasia/died
before 36 weeks’ postmenstrual age. Moreover, the mean pepsin level
was significantly higher in infants with severe bronchopulmonary
dysplasia compared with moderate bronchopulmonary dysplasia. The
mean pepsin level in tracheal aspirate samples from the first 7 days
was also lower in infants with no bronchopulmonary dysplasia
compared with those who developed bronchopulmonary dysplasia or
developed bronchopulmonary dysplasia/died before 36 weeks’
postmenstrual age. Pepsinogen was not localized in the lung tissues
by immunohistochemistry.
CONCLUSION. The concentration of pepsin was
increased in the tracheal aspirate of preterm infants who developed
bronchopulmonary dysplasia or died before 36 weeks’ postmenstrual
age. Recovery of pepsin in tracheal aspirate samples is secondary
to gastric aspiration, not by hematogenous spread or local synthesis
in the lungs. Chronic aspiration of gastric contents may contribute in
the pathogenesis of bronchopulmonary dysplasia.
Key Words: gastric aspiration • gastroesophageal reflux • pepsin • preterm infants
• bronchopulmonary dysplasia
Abbreviations: BPD—bronchopulmonary dysplasia • GER—gastroesophageal reflux •
TA—tracheal aspirate • PMA—postmenstrual age • GA—gestational age • BSA—bovine serum
albumin
Accepted Jul 6, 2007.
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Baby Care Products:
Possible Sources of Infant Phthalate Exposure
a Departments of
Occupational and Environmental Health Sciences
b Pediatrics
c Biostatistics, University of Washington, Seattle, Washington
d Centers for Disease Control and Prevention, Atlanta, Georgia
e Department of Obstetrics and Gynecology, University of Rochester
School of Medicine and Dentistry, Rochester, New York
OBJECTIVES. Phthalates are man-made chemicals
found in personal care and other products. Recent studies suggest
that some phthalates can alter human male reproductive development,
but sources of infant exposure have not been well characterized. We
investigated the relationship between phthalate metabolite
concentrations in infant urine and maternal reported use of dermally
applied infant care products.
METHODS. We measured 9 phthalate metabolites in
163 infants who were born in 2000–2005. An infant was considered to
have been exposed to any infant care product that the mother reported
using on her infant within 24 hours of urine collection. Results of
multiple linear regression analyses are reported as the ratio of
metabolite concentrations (with 95% confidence intervals) in exposed
and unexposed infants. We standardized concentrations by forming z
scores and examined combined exposure to multiple metabolites.
RESULTS. In most (81%) infants, 
7 phthalate metabolites were above the limit of detection. Exposure
to lotion was predictive of monoethyl phthalate and monomethyl
phthalate concentrations, powder of monoisobutyl phthalate, and
shampoo of monomethyl phthalate. Z scores increased with
number of products used. Most associations were stronger in younger
infants.
CONCLUSIONS. Phthalate exposure is widespread
and variable in infants. Infant exposure to lotion, powder, and
shampoo were significantly associated with increased urinary
concentrations of monoethyl phthalate, monomethyl phthalate, and
monoisobutyl phthalate, and associations increased with the number
of products used. This association was strongest in young infants,
who may be more vulnerable to developmental and reproductive
toxicity of phthalates given their immature metabolic system
capability and increased dosage per unit body surface area.
Key Words: phthalate • infant • environmental exposure • baby care product
Abbreviations: DEHP—di-2-ethylhexyl phthalate • DBP—dibutyl phthalate • MEP—monoethyl
phthalate • MBP—mono-n-butyl phthalate • MBzP—monobenzyl phthalate •
MiBP—monoisobutyl phthalate • DiNP—di-isononyl phthalate • SFFI—Study for
Future Families, Phase I • SFFII—Study for Future Families, Phase II •
MMP—monomethyl phthalate • MCPP—mono-3-carboxypropyl phthalate •
DnOP—di-n-octyl phthalate • MEHP—mono-2-ethylhexyl phthalate •
MEHHP—mono-2-ethyl-5-hydroxyhexyl phthalate • MEOHP—mono-2-ethyl-5-oxohexyl
phthalate • LOD—limit of detection • LPMC—log phthalate metabolite
concentration • CI—confidence interval • NHANES—National Health and Nutrition
Examination Survey • DEP—diethyl phthalate • BBzP—butylbenzyl phthalate
Accepted Jul 16, 2007.
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Population-Based
Assessments of Ophthalmologic and Audiologic Follow-up in Children With Very
Low Birth Weight Enrolled in Medicaid: A Quality-of-Care Study
a Departments of
Pediatrics and Maternal and Child Health, Boston Medical Center and Boston
University Schools of Medicine and Public Health, Boston, Massachusetts
b Rand Health, Santa Monica, California
c Division of General Internal Medicine, Department of Medicine
d Department of Pediatrics, Mattel Children's Hospital, David Geffen
School of Medicine
e Department of Health Services, School of Public Health, University
of California, Los Angeles, California
OBJECTIVE. The purpose of our work was to
determine whether children with very low birth weight (<
PATIENTS AND METHODS. We conducted a
retrospective analysis of 2182 children born in South Carolina from
1996 to 1998 with birth weights of 401 to 24 weeks, and survival of 90 days of life. Receipt of services for Medicaid-enrolled children
was assessed by using a linked data set that included files from
vital records, death certificates, Medicaid, Chronic Rehabilitative
Services, and the Early Intervention Program. We assessed the
receipt of hearing rehabilitation by 6 months of age for children
with nonconductive hearing loss and routine ophthalmologic
examination between ages of 1 and 2 years for all children with very
low birth weight. Multivariate logistic regression was restricted to
ophthalmologic examinations because of sample size.
RESULTS. Among children with very low birth
weight with nonconductive hearing loss, 20% received hearing
rehabilitation by 6 months of age. Twenty-three percent of children
with very low birth weight received an ophthalmologic examination
between the ages of 1 and 2 years. Limiting our analysis to children
<7, and black maternal race. Among children born at <
CONCLUSIONS. There is a shortfall in the
provision of critical services for children with very low birth
weight. These findings reinforce the Institute of Medicine's
concerns regarding inadequate outcome data and health care services
for preterm infants and support the importance of enrollment in the
Early Intervention Program for children with very low birth weight.
Key Words: low birth weight • quality of care • early intervention
Abbreviations: VLBW—very low birth weight • ELBW—extremely low birth weight •
ROP—retinopathy of prematurity • EIP—Early Intervention Program • CRS—chronic
rehabilitative services • ICD-9—International Classification of Diseases,
Ninth Revision • OR—odds ratio
Accepted Jul 16, 2007.
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Chlamydia trachomatis as a Cause of Neonatal
Conjunctivitis in Dutch Infants
a Department of
Pediatrics, Sophia Children's Hospital
c Department of Medical Microbiology and Infectious Diseases,
Erasmus MC University Medical Center, Rotterdam, Netherlands
b Department of Pediatrics, Division of Infectious Diseases, State
University of New York Downstate Medical Center, Brooklyn, New York
d Department of Ophthalmology, Rotterdam Eye Hospital, Rotterdam,
Netherlands
BACKGROUND. Chlamydia trachomatis is the
most common sexually transmitted pathogen in adults, which at
delivery may be transmitted from mother to child and cause
conjunctivitis and pneumonia. In the Netherlands, prenatal
chlamydial screening and treatment of pregnant women is not routine
practice. The contribution of C trachomatis to neonatal
ophthalmic disease has not been studied in the Netherlands and
remains unclear.
METHODS. At the Sophia Children's Hospital and
Rotterdam Eye Hospital, 2 cohorts of infants <3 months of age
presenting with conjunctivitis were studied, 1 retrospectively (July
1996 to July 2001) and 1 prospectively (September 2001 to September
2002). Laboratory diagnosis was based on bacterial culture and polymerase
chain reaction for C trachomatis.
RESULTS. C trachomatis was detected in
27 (64%) of 42 retrospectively studied infants and 14 (61%) of 23
prospectively studied infants. Mucopurulent discharge was present in
35 (95%) of 37, swelling of the eyes in 27 (73%) of 37, conjunctival
erythema in 24 (65%) of 37, respiratory symptoms in 14 (38%) of 37,
and feeding problems in 5 (14%) of 37 infants respectively. Before
microbiological diagnosis, general practitioners prescribed
antichlamydial antibiotics locally to 5 (12%) of 41 and systemically
to 4 (10%) of 41 infants who tested positive for chlamydia, and
ophthalmologists prescribed to 21 (51%) of 41 and 7 (17%) of 41,
respectively.
CONCLUSIONS. C trachomatis was the major
cause of bacterial conjunctivitis in this population. Clinically,
differentiation from other pathogens was not possible. Many infants
who tested positive for chlamydia did not receive appropriate
antibiotic treatment.
Key Words: Chlamydia trachomatis • neonatal conjunctivitis
Abbreviations: REH—Rotterdam Eye Hospital • SCH—Sophia Children's Hospital •
GP—general practitioner • PCR—polymerase chain reaction
Accepted Jun 25, 2007.
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Analgesic Properties
of Oral Sucrose During Routine Immunizations at 2 and 4 Months of Age
a Pennsylvania State
University School of Nursing, College of Health and Human Development,
University Park, Pennsylvania
b Division of General Pediatrics, Pennsylvania State University
College of Medicine
c Division of Biostatistics, Public Health Sciences, Penn State
Milton S. Hershey Medical Center, Hershey, Pennsylvania
d Biobehavioral Research Center, University of Pennsylvania School
of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania
OBJECTIVE. The purpose of this work was to
evaluate the analgesic properties of oral sucrose during routine
immunizations in infants at 2 and 4 months of age.
PATIENTS AND METHODS. A prospective,
randomized, placebo-controlled clinical trial was conducted at a
pediatric ambulatory care clinic. One-hundred healthy term infants
scheduled to receive routine immunizations were recruited, randomly
stratified into 2- or 4-month study groups, and further randomly
assigned to receive 24% oral sucrose and pacifier or the sterile
water control solution. The study preparations were administered 2
minutes before the combined diphtheria-tetanus-acellular pertussis,
inactivated polio vaccine, and hepatitis B vaccine. Haemophilus influenzae
type b vaccine was administered 3 minutes after the combined
injection, followed by the pneumococcal conjugate vaccine, 2 minutes
after the H influenzae type b injection. The University of
Wisconsin Children's Hospital Pain Scale measured serial acute pain
responses for the treatment and control groups at baseline and 2, 5,
7, and 9 minutes after solution administration. Repeated-measures
analysis of variance examined between-group differences and
within-subject variability of treatment effect on overall pain
scores.
RESULTS. Two- and 4-month-old infants receiving
oral sucrose (n = 38) displayed reductions in pain scores 2
minutes after solution administration compared with 2- and
4-month-old infants in the placebo group (n = 45). Between-group
comparisons for the oral sucrose and placebo groups showed lower
pain responses at 5, 7, and 9 minutes after solution administration.
The oral sucrose and placebo groups demonstrated their highest mean
pain score at 7 minutes, with a mean pain score of 3.8 and 4.8,
respectively. At 9 minutes, the placebo group had a mean pain score
of 2.91 whereas the mean pain score for the oral sucrose group
returned to near baseline, reflecting a 78.5% difference in mean
pain score (oral sucrose – placebo) relative to the placebo mean.
CONCLUSIONS. Oral sucrose is an effective,
easy-to-administer, short-acting analgesic for use during routine
immunizations.
Key Words: immunizations • infant • pain • sucrose
Abbreviations: RCT—randomized, controlled trial • NNS—nonnutritive sucking •
UWCH—University of Wisconsin Children's Hospital • CI—confidence interval •
NNT—number needed to treat
Accepted Jul 19, 2007.
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Evaluating Loss to
Follow-up in Newborn Hearing Screening in Massachusetts
Center for Community Health, Massachusetts
Department of Public Health, Boston, Massachusetts
OBJECTIVE. The purpose of this work was to
examine loss to follow-up on the use of diagnostic or intervention
services for Massachusetts infants and children screened or
diagnosed with hearing loss and risk factors for becoming lost to
follow-up.
METHODS. We used data from the Massachusetts
Childhood Hearing Data System and Early Intervention Information
System. We calculated the percent use of audiologic evaluation for
Massachusetts infants born in 2002–2003 who did not pass hearing
screening and Early Intervention services for those with hearing
loss. We generated crude and adjusted relative risks, as well as
confidence intervals, to estimate associations of maternal and
infant factors with the use of audiologic evaluation and early
intervention services. Factors evaluated included child's birth
weight and hearing screening or diagnostic results and maternal age,
race or ethnicity, marital status, smoking status during pregnancy,
educational attainment, health insurance, and residence region.
RESULTS. In 2002–2003, 11% of Massachusetts
children who did not pass hearing screening became lost to follow-up
on the audiologic evaluation, and 25% of those with hearing loss did
not receive early intervention services. Children were at higher risk
of becoming lost to follow-up on audiologic evaluation if their
mothers were nonwhite, covered by public insurance, smokers during
pregnancy, or residing in western, northeastern, or southeastern
Massachusetts compared with those in the Boston region. Of children
with hearing loss, those with a unilateral or mild or moderate
degree of hearing loss, normal birth weight, or living in the
southeastern or Boston region were more likely to go without early
intervention services.
CONCLUSIONS. Massachusetts has excellent
follow-up rates overall. Our analyses allow the program to
prioritize limited resources to subgroups of infants who are at high
risk of becoming lost to follow-up.
Key Words: early hearing detection and intervention • lost to follow-up • early
intervention
Abbreviations: MDPH—Massachusetts Department of Public Health • ADC—audiologic
diagnostic center • EI—Early Intervention • IFSP—Individualized Family Service
Plan • UNHSP—Universal Newborn Hearing Screening Program • EHDI—Early Hearing
Detection and Intervention • CHDS—Childhood Hearing Data System • EIIS—Early
Intervention Information System • EBC—electronic birth certificate •
AE—audiologic evaluation report • FIR—family intake record • ABR—auditory
brainstem response • OAE—otoacoustic emission • aRR—adjusted relative risk •
CI—confidence interval
Accepted Jul 5, 2007.
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Effect of a Short
Course of Prednisolone in Infants With Oxygen-Dependent Bronchopulmonary
Dysplasia
a Division of Pediatric
Pulmonology, Connecticut Children's Medical Center, Hartford, Connecticut
b Division of Neonatology, Department of Pediatrics, University of
Connecticut School of Medicine, Farmington, Connecticut
OBJECTIVE. The purpose of this work was to
determine whether oral prednisolone is effective in weaning infants
with bronchopulmonary dysplasia, after 36 weeks' postmenstrual age,
off supplemental oxygen and to identify factors associated with
successful weaning.
METHODS. Data were abstracted from a
standardized prospectively collected database at the John Dempsey
Hospital NICU. Logistic regression and receiver operating curve
analyses were used.
RESULTS. Of 385 infants, 131 (34%) received
oral prednisolone and 254 (66%) did not. There was no significant
difference in race, gender, birth weight, or gestational age between
the groups receiving and not receiving oral prednisolone. Infants in
the oral prednisolone group were more likely to have received
previous dexamethasone therapy, had longer duration of mechanical
ventilation, had longer length of hospital stay, and were more
likely to be discharged from the hospital on oxygen. Of those in the
oral prednisolone group, 63% responded to treatment. Pulmonary
acuity score and PCO2 were the only parameters that
remained significant on multiple logistic regression analyses. The
oral prednisolone-responsive group had a lower pulmonary acuity
score compared with the oral prednisolone-nonresponsive group. A
pulmonary acuity score value of 
0.5 had a sensitivity of 20% and specificity of 97.4%, with positive
and negative predictive values of 94.1% and 42.1%, respectively. Capillary
PCO2 values were significantly lower
in the oral prednisolone-responsive group compared with the oral
prednisolone-nonresponsive group. In predicting a successful response
to oral prednisolone, a capillary PCO2 value of <48.5 mmHg
had a sensitivity of 50% and specificity of 89.7%, with positive and
negative predictive values of 89.1% and 51.8%, respectively.
CONCLUSIONS. Oral prednisolone therapy is
effective in weaning off supplemental oxygen in a postterm infant
with oxygen-dependent bronchopulmonary dysplasia who has a pulmonary
acuity score of <0.5 and PCO2 of <48.5 mmHg. In addition, if a
single course of prednisolone fails, there is no clear benefit of
using multiple courses.
Key Words: BPD • prednisolone • oxygen therapy • outcome
Abbreviations: BPD—bronchopulmonary dysplasia • PMA—postmenstrual age • OP—oral prednisolone
• No-OP—subjects who did not receive oral prednisolone • OP-R—subjects who
responded to oral prednisolone therapy • OP-NR—subjects who did not respond to
oral prednisolone therapy • PAS—pulmonary acuity score • FIO2—fraction of inspired oxygen • ROC—receiver operating curve •
CI—confidence interval
Accepted Jul 5, 2007.
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Neurodevelopmental
Outcomes of Extremely Low Birth Weight Infants Exposed Prenatally to
Dexamethasone Versus Betamethasone
a Division of
Neonatal-Perinatal Medicine, Emory University School of Medicine, Atlanta,
Georgia
b MidAtlantic Neonatology Associates, Morristown, New Jersey
c Research Triangle Institute, Research Triangle Park, North
Carolina
d National Institute of Child Health and Human Development,
Washington, DC
OBJECTIVE. We compared the development of
adverse neurodevelopmental outcomes at corrected ages of 18 to 22
months for extremely low birth weight infants exposed prenatally to
dexamethasone, betamethasone, or no steroid.
METHODS. Study infants were extremely low birth
weight (401–1000 g) infants who were in the care of National
Institute of Child Health and Human Development Neonatal Research
Network centers between January 1, 2002, and April 30, 2003; they
were assessed neurodevelopmentally at corrected ages of 18 to 22
months. Outcomes were defined as Bayley Scales of Infant
Development-II Mental Development Index of <70, Bayley Scales of
Infant Development-II Psychomotor Development Index of <70,
bilateral blindness, bilateral hearing aid use, cerebral palsy, and
neurodevelopmental impairment. Neurodevelopmental impairment was
defined as 1 of the aforementioned outcomes.
RESULTS. A total of 1124 infants met entry
criteria. There were no statistically significant associations
between prenatal dexamethasone exposure and any follow-up outcome,
compared with no prenatal steroid exposure. Prenatal betamethasone
exposure was associated with reduced risks of hearing impairment and
neurodevelopmental impairment and with increased likelihood of
unimpaired status, compared with no prenatal steroid exposure. Compared
with betamethasone, dexamethasone was associated with a trend for
increased risk of Psychomotor Development Index of <70, increased
risk of hearing impairment, and decreased likelihood of unimpaired
status.
CONCLUSIONS. Prenatal betamethasone exposure
was associated with increased likelihood of unimpaired
neurodevelopmental status and reduced risk of hearing impairment at
corrected ages of 18 to 22 months among extremely low birth weight
infants, compared with prenatal dexamethasone exposure or no
prenatal steroid exposure. Pending a randomized, clinical trial, it
may be in the best interests of infants to receive betamethasone,
rather than dexamethasone, when possible.
Key Words: prenatal glucocorticoid treatment • dexamethasone • betamethasone •
extremely low birth weight • neurodevelopmental outcome
Abbreviations: BSID-II—Bayley Scales of Infant Development-II • CP—cerebral palsy •
ELBW—extremely low birth weight • MDI—Mental Development Index • NICHD—National
Institute of Child Health and Human Development • NDI—neurodevelopmental
impairment • PDI—Psychomotor Development Index • PVL—periventricular
leukomalacia • PDA—patent ductus arteriosus • CLD—chronic lung disease •
ROP—retinopathy of prematurity • OR—odds ratio • CI—confidence interval •
EGA—estimated gestational age • IVH—intraventricular hemorrhage
Accepted Jul 23, 2007.
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Prematurely Born
Children Demonstrate White Matter Microstructural Differences at 12 Years of
Age, Relative to Term Control Subjects: An Investigation of Group and Gender
Effects
a Departments of
Diagnostic Imaging
b Pediatrics
c Neurology
f Epidemiology and Public Health, Yale University School of
Medicine, New Haven, Connecticut
d Department of Pediatrics, Brown Medical School, Providence, Rhode
Island
e Department of Psychiatry, Stanford University School of Medicine,
Palo Alto, California
OBJECTIVE. The goal was to use diffusion tensor
imaging to test the hypothesis that prematurely born children
demonstrate long-term, white matter, microstructural differences,
relative to term control subjects.
METHODS. Twenty-nine preterm subjects (birth
weight: 600–1250 g) without neonatal brain injury and 22 matched,
term, control subjects were evaluated at 12 years of age with MRI
studies, including diffusion tensor imaging and volumetric imaging;
voxel-based morphometric strategies were used to corroborate
regional diffusion tensor imaging results. Subjects also underwent
neurodevelopmental assessments.
RESULTS. Neurodevelopmental assessments showed
significant differences in full-scale, verbal, and performance IQ
and Developmental Test of Visual Motor Integration scores between
the preterm and term control subjects. Diffusion tensor imaging
studies demonstrated widespread decreases in fractional anisotropy
(a measure of fiber tract organization) in the preterm children,
compared with the control subjects. Regions included both
intrahemispheric association fibers subserving language skills,
namely, the right inferior frontooccipital fasciculus and anterior
portions of the uncinate fasciculi bilaterally, and the deep white
matter regions to which they project, as well as the splenium of the
corpus callosum. These changes in fractional anisotropy occurred in
subjects with significant differences in frontal, temporal, parietal,
and deep white matter volumes. Fractional anisotropy values in the
left anterior uncinate correlated with verbal IQ, full-scale IQ, and
Peabody Picture Vocabulary Test-Revised scores for preterm male
subjects. In addition, preterm male subjects were found to have the
lowest values for fractional anisotropy in the right anterior
uncinate fasciculus, and fractional anisotropy values in that region
correlated with both verbal IQ and Peabody Picture Vocabulary
Test-Revised scores for the preterm groups; these findings were
supported by changes identified with voxel-based morphometric
analyses.
CONCLUSIONS. Compared with term control
subjects, prematurely born children with no neonatal ultrasound
evidence of white matter injury manifest changes in neural
connectivity at 12 years of age.
Key Words: diffusion tensor imaging • premature • language
Abbreviations: DTI—diffusion tensor imaging • FA—fractional anisotropy • ROI—region of
interest • VBM—voxel-based morphometry • PPVT-R—Peabody Picture Vocabulary
Test-Revised • VMI—Developmental Test of Visual Motor Integration •
FSIQ—full-scale IQ • VIQ—verbal IQ
Accepted Jul 20, 2007.
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Clinical Utility of
Echocardiography for the Diagnosis and Management of Pulmonary Vascular Disease
in Young Children With Chronic Lung Disease
a Divisions of Critical
Care
c Cardiology
d Pulmonary Medicine, Pediatric Heart-Lung Center, Department of
Pediatrics
b Department of Preventative Medicine and Biometrics, Children's
Hospital and University of Colorado Denver School of Medicine, Denver, Colorado
OBJECTIVE. The goal was to determine the
clinical utility of Doppler echocardiography in predicting the
presence and severity of pulmonary hypertension in patients with
chronic lung disease who subsequently underwent cardiac catheterization.
METHODS. A retrospective review of data for all
patients <2 years of age with a diagnosis of bronchopulmonary
dysplasia, congenital diaphragmatic hernia, or lung hypoplasia who
underwent echocardiography and subsequently underwent cardiac catheterization
for evaluation of pulmonary hypertension was performed. The accuracy
of echocardiography in diagnosing pulmonary hypertension, on the
basis of estimated systolic pulmonary artery pressure, was compared
with the detection of pulmonary hypertension with the standard
method of cardiac catheterization.
RESULTS. Thirty-one linked measurements for 25
children were analyzed. Systolic pulmonary artery pressure could be
estimated in 61% of studies, but there was poor correlation between echocardiography
and cardiac catheterization measures of systolic pulmonary artery pressure
in these infants. Compared with cardiac catheterization measurements,
echocardiographic estimates of systolic pulmonary artery pressure
diagnosed correctly the presence or absence of pulmonary
hypertension in 79% of the studies in which systolic pulmonary
artery pressure was estimated but determined the severity of
pulmonary hypertension (severe pulmonary hypertension was defined as
pulmonary/systemic pressure ratio of 0.67) correctly in only 47% of those studies. Seven (58%) of
12 children without estimated systolic pulmonary artery pressure
demonstrated pulmonary hypertension during subsequent cardiac
catheterization. In the absence of estimated systolic pulmonary
artery pressure, qualitative echocardiographic findings, either
alone or in combination, had worse predictive value for the
diagnosis of pulmonary hypertension.
CONCLUSION. As used in clinical practice,
echocardiography often identifies pulmonary hypertension in young
children with chronic lung disease; however, estimates of systolic
pulmonary artery pressure were not obtained consistently and were
not reliable for determining the severity of pulmonary hypertension.
Key Words: chronic lung disease • bronchopulmonary dysplasia • pulmonary
hypertension • echocardiography • cardiac catheterization
Abbreviations: CLD—chronic lung disease • PH—pulmonary hypertension • sPAP—systolic
pulmonary artery pressure • mPAP—mean pulmonary artery pressure •
TRJV—tricuspid regurgitant jet velocity • BPD—bronchopulmonary dysplasia •
CDH—congenital diaphragmatic hernia • PA—pulmonary artery • sBP—systemic
systolic blood pressure: CI—confidence interval • RAP—right atrial pressure
Accepted Jul 21, 2007.
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Quality of Life of
Formerly Preterm and Very Low Birth Weight Infants From Preschool Age to
Adulthood: A Systematic Review
a Rehabilitation
Sciences
b Department of Physical Therapy, Faculty of Medicine, University of
British Columbia, Vancouver, British Columbia, Canada
OBJECTIVE. The goal of this systematic review
was to synthesize studies that examined the health-related quality
of life of preschool- and school-aged children, adolescents, and
young adults who were born preterm and/or at very low birth weight.
METHODS. We searched 7 databases up to
September 2006 (Medline, PubMed, Embase, EBM Reviews, Cumulative
Index of Nursing and Allied Health Literature, PsycINFO, and the
Educational Resource Information Center) as well as gray literature
sources. We independently screened studies and included them only if
a quality-of-life outcome measure was used and findings compared
preterm, very low birth weight, or extremely low birth weight
infants with term or normal birth weight peers. We independently
assessed the methodologic quality of each study by using criteria
adapted from the Centre for Reviews and Dissemination.
RESULTS. Fifteen cohort or cross-sectional
studies met the review criteria. In 6 studies of preschool-aged
children, differences were found between study and control groups,
suggesting that many preschool children born preterm or at very low
birth weight perform more poorly than their peers in physical,
emotional, and/or social functioning. Extremely low birth weight
school-aged children had lower health utility scores compared with
their peers, and similar results were found for adolescents. Parents
of preterm and very low birth weight teens noted significantly poorer
performance in their child's global health, behavior, and physical
functioning, whereas the teenagers themselves did not. In young
adulthood, differences in physical functioning remained, but
subjective quality of life was similar to normal birth weight peers.
CONCLUSIONS. The effects of preterm birth/very
low birth weight on health-related quality of life seem to diminish
over time, which possibly reflects issues related to a child's
report versus a parent-proxy report, differing definitions of
health-related quality of life, and adaptation of individuals over
time, versus true change in health-related quality of life.
Key Words: extremely low birth weight • very low birth weight • health-related
quality of life • quality of life • systematic review
Abbreviations: VLBW—very low birth weight • ELBW—extremely low birth weight •
QoL—quality of life • HRQoL—health-related quality of life • NBW—normal birth
weight • ELGA—extremely low gestational age
Accepted Jun 19, 2007.
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and Harris]
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STATE-OF-THE-ART
REVIEW ARTICLE
Etiologic
Classification of Attention-Deficit/Hyperactivity Disorder
Division of Neurology, Children's Memorial
Hospital, Northwestern University Medical School, Chicago, Illinois
ABSTRACT
Attention-deficit/hyperactivity disorder is a
neurobiological syndrome with an estimated prevalence among children
and adolescents of 5%. It is a highly heritable disorder, but
acquired factors in etiology are sometimes uncovered that may be
amenable to preventive measures or specific therapy. Early reports
have described symptoms similar to attention-deficit/hyperactivity
disorder that followed brain trauma or viral encephalitis, and recent
MRI studies have demonstrated brain volumetric changes that may be
involved in the pathophysiology of the syndrome. The American
Psychiatric Association's Diagnostic Statistical Manual,
introduced in 1968, emphasizes symptomatic criteria in diagnosis. Here,
an overview of environmental factors in the etiology of
attention-deficit/hyperactivity disorder is presented to encourage
more emphasis and research on organic causal factors, preventive
intervention, and specific therapies. An organic theory and the
genetic and biochemical basis of attention-deficit/hyperactivity disorder
are briefly reviewed, and an etiologic classification is suggested. Environmental
factors are prenatal, perinatal, and postnatal in origin. Pregnancy-
and birth-related risk factors include maternal smoking and alcohol
ingestion, prematurity, hypoxic-ischemic encephalopathy, and thyroid
deficiency. Childhood illnesses associated with
attention-deficit/hyperactivity disorder include virus infections,
meningitis, encephalitis, head injury, epilepsy, toxins, and drugs. More
controversial factors discussed are diet-related sensitivities and
iron deficiency. Early prenatal recognition, prevention, and
treatment of environmental etiologies of
attention-deficit/hyperactivity disorder may reduce physician reliance
on symptomatic modification with medication, a frequent reason for
parental concern.
Key Words: attention deficit • hyperactivity • etiology • environmental • viral •
nicotine • thyroid
Abbreviations: ADHD—attention-deficit/hyperactivity disorder • GRTH—generalized
resistance to thyroid hormone
Accepted Jul 5, 2007.
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Surfactant-Replacement
Therapy for Respiratory Distress in the Preterm and Term Neonate
Respiratory failure secondary to surfactant
deficiency is a major cause of morbidity and mortality in preterm
infants. Surfactant therapy substantially reduces mortality and
respiratory morbidity for this population. Secondary surfactant
deficiency also contributes to acute respiratory morbidity in
late-preterm and term neonates with meconium aspiration syndrome,
pneumonia/sepsis, and perhaps pulmonary hemorrhage; surfactant
replacement may be beneficial for these infants. This statement
summarizes indications, administration, formulations, and outcomes
for surfactant-replacement therapy. The impact of antenatal steroids
and continuous positive airway pressure on outcomes and surfactant
use in preterm infants is reviewed. Because respiratory
insufficiency may be a component of multiorgan dysfunction, preterm
and term infants receiving surfactant-replacement therapy should be
managed in facilities with technical and clinical expertise to
administer surfactant and provide multisystem support.
Key Words:
surfactant • antenatal steroids • respiratory distress syndrome • meconium
aspiration syndrome • neonatal pneumonia • neonatal sepsis • congenital
diaphragmatic hernia • pulmonary hemorrhage • persistent pulmonary hypertension
• preterm • term
Abbreviations: RR—relative risk • CI—confidence interval • NNT—number needed to treat
[Full Text of Engle and and the
Committee on Fetus and Newborn] [Reprint (PDF) Version of Engle and
and the Committee on Fetus and Newborn]