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1.  A new growth chart for preterm babies: Babson and Benda's chart updated with recent data and a new format 
BMC Pediatrics  2003;3:13.
The Babson and Benda 1976 "fetal-infant growth graph" for preterm infants is commonly used in neonatal intensive care. Its limits include the small sample size which provides low confidence in the extremes of the data, the 26 weeks start and the 500 gram graph increments. The purpose of this study was to develop an updated growth chart beginning at 22 weeks based on a meta-analysis of published reference studies.
The literature was searched from 1980 to 2002 for more recent data to complete the pre and post term sections of the chart. Data were selected from population studies with large sample sizes. Comparisons were made between the new chart and the Babson and Benda graph. To validate the growth chart the growth results from the National Institute of Child Health and Human Development Neonatal Research Network (NICHD) were superimposed on the new chart.
The new data produced curves that generally followed patterns similar to the old growth graph. Mean differences between the curves of the two charts reached statistical significance after term. Babson's 10th percentiles fell between the new data percentiles: the 5th to 17th for weight, the 5th and 15th for head circumference, and the 6th and 16th for length. The growth patterns of the NICHD infants deviated away from the curves of the chart in the first weeks after birth. When the infants reached an average weight of 2 kilograms, those with a birthweight in the range of 700 to 1000 grams had achieved greater than the 10th percentile on average for head growth, but remained below the 3rd percentile for weight and length.
The updated growth chart allows a comparison of an infant's growth first with the fetus as early as 22 weeks and then with the term infant to 10 weeks. Comparison of the size of the NICHD infants at a weight of 2 kilograms provides evidence that on average preterm infants are growth retarded with respect to weight and length while their head size has caught up to birth percentiles. As with all meta-analyses, the validity of this growth chart is limited by the heterogeneity of the data sources. Further validation is needed to illustrate the growth patterns of preterm infants to older ages.
PMCID: PMC324406  PMID: 14678563
2.  X-linked Hyper IgM (HIGM1) in an African kindred: the first report from South Africa 
BMC Pediatrics  2003;3:12.
The objective of this study was to describe the clinical and molecular features of the first South African family with X-linked hyper-IgM syndrome (HIGM1).
Diagnoses were based on immunoglobulin results and the absence of CD40 ligand (CD40L) expression on activated T-cells. Complete molecular characterisation involved CD40L cDNA sequencing, and genomic DNA analysis by polymerase chain reaction amplification, restriction enzyme digestion and sequencing. A PCR-based diagnostic assay was established for carrier detection and prenatal diagnosis in this family.
There were originally six children, three males and three females. The eldest boy died after being diagnosed with hypogammaglobulinaemia, before HIGM1 was considered. This disorder was diagnosed in the second eldest boy at the age of 5 years, after failing to detect CD40L expression on his activated T-cells. A deficiency of CD40L was also confirmed in the youngest male at the age of 5 years. Both younger brothers have since died of infections relating to HIGM1. Molecular investigation showed that exon 3 was deleted from the CD40L mRNA of the affected males. Genomic DNA analysis identified a 1.5 kilobase deletion, spanning exon 3 and including extended flanking intronic sequence. Carrier status in the mother was confirmed by RT-PCR of her CD40L mRNA. Genetic analysis of the three female children was deferred because they were below the legal consenting age of 18 years. A PCR-based assay for genomic DNA was established for easy identification of female carriers and affected males in the future.
This study confirmed the diagnosis of HIGM1 in the first South African family to be investigated and identified a novel mutation in the CD40L gene.
PMCID: PMC317313  PMID: 14641931
3.  Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar ataxia 
BMC Pediatrics  2003;3:11.
Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells. We investigated the sera of children with infections and post-varicella ataxia and related conditions for reactivity to five recombinant centrosome proteins: γγ-enolase, pericentrin, ninein, PCM-1, and Mob1.
Sera from 12 patients with acute post-varicella ataxia, 1 with post-Epstein Barr virus (EBV) ataxia, 5 with uncomplicated varicella infections, and other conditions were tested for reactivity to cryopreserved cerebellum tissue and recombinant centrosome proteins. The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF) using rabbit antibodies to the recombinant protein. Antibodies to phospholipids (APL) were detected by ELISA.
Eleven of 12 children with post-varicella ataxia, 4/5 children with uncomplicated varicella infections, 1/1 with post-EBV ataxia, 2/2 with ADEM, 1/2 with neuroblastoma and ataxia, and 2/2 with cerebellitis had antibodies directed against 1 or more recombinant centrosome antigens. Antibodies to pericentrin were seen in 5/12 children with post-varicella ataxia but not in any of the other sera tested. IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells. APL were detected in 75% of the sera from children with post-varicella ataxia and 50% of children with varicella without ataxia and in none of the controls.
This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella. Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin.
PMCID: PMC222907  PMID: 14503922
4.  Failure of erythromycin to eliminate airway colonization with ureaplasma urealyticum in very low birth weight infants 
BMC Pediatrics  2003;3:10.
Airway colonization of mechanically ventilated very low birth weight infants (birth weight < 1500 grams) by Ureaplasma urealyticum (Uu) is associated with an increased risk of bronchopulmonary dysplasia (BPD). While Uu is sensitive to erythromycin in vitro, the efficacy of intravenous (IV) erythromycin to eliminate Uu from the airways has not been studied.
17 very low birth weight infants with Uu positive tracheal aspirate (TA) cultures were randomized to either 5 (8 infants) or 10 days (9 infants) of IV erythromycin lactobionate (40 mg/kg/day in 3 divided doses). Tracheal aspirate cultures for Uu were performed on days 0, 5, 10 and 15.
Intravenous erythromycin failed to eliminate airway colonization in a large proportion of infants regardless of whether they received 5 or 10 days of treatment. Ureaplasma urealyticum was isolated from 4/15 (27%) of TAs obtained at 5 days, 5/12 TAs (42%) obtained at 10 days and 6/11(55%) TAs obtained at 15 days (combined group data).
Erythromycin administered IV does not eliminate Uu from the airways in a large proportion of infants. Failure of erythromycin to eliminate Uu from the airways may contribute to the lack of efficacy of this drug in reducing the incidence of BPD in very low birth weight infants.
PMCID: PMC212466  PMID: 12956892
5.  Is fever suppression involved in the etiology of autism and neurodevelopmental disorders? 
BMC Pediatrics  2003;3:9.
There appears to be a significant increase in the prevalence rate of autism. Reasons for the increase are unknown, however, there is a substantial body of evidence that suggests the etiology involves infections of the pregnant mother or of a young child. Most infections result in fever that is routinely controlled with antipyretics such as acetaminophen. The blocking of fever inhibits processes that evolved over millions of years to protect against microbial attack. Immune mechanisms in the central nervous system are part of this protective process.
The blockage of fever with antipyretics interferes with normal immunological development in the brain leading to neurodevelopmental disorders such as autism in certain genetically and immunologically disposed individuals.
Testing the hypothesis
Epidemiological studies to determine associations between the use of antipyretics and neurodevelopmental disorders should be undertaken. Biochemical tests will involve the examination of fluids/serum by mass spectrometry and the determination of cytokine/chemokine levels in serum and cell culture fluids after stimulation with fever-inducing molecules from bacteria, viruses and yeast. Postmortem brain can be examined by immunohistochemistry or other methods such as fluorescent in situ hybridization (FISH) to determine altered expression levels of chemokines/cytokines and other molecules.
Implications of the hypothesis
1) The use of antipyretics during pregnancy or in young children may be reserved for more severe fevers. 2) The perplexing genetic findings in autism may be better understood by categorizing genes along functional pathways. 3) New treatments based on immune, cell, pharmacological or even heat therapies may be developed.
PMCID: PMC194752  PMID: 12952554
6.  Interleukin-4 and 13 concentrations in infants at risk to develop Bronchopulmonary Dysplasia 
BMC Pediatrics  2003;3:8.
An exaggerated inflammatory response occurs in the first few days of life in infants who subsequently develop bronchopulmonary dysplasia (BPD). The increase of inflammatory cytokines in many disease processes is generally balanced by a rise in anti-inflammatory cytokines. Interleukin-4 (IL-4) and interleukin-13 (IL-13) have been shown to inhibit production of several inflammatory cytokines important in the development of BPD.
We sought to determine if a correlation exists between the presence or absence of IL-4 and IL-13 in tracheal aspirates (TA) during the first 3 weeks of life and the development of BPD in premature infants. Serial TAs were prospectively obtained from 36 very low birth weight infants and IL-4 and IL-13 concentrations were determined by ELISA.
Infants who developed BPD (n = 19) were less mature (25.3 ± 0.02 wks vs. 27.8 ± 0.05 wks; p < 0.001), and had lower birth weights (739 ± 27 g vs.1052 ± 41 g; p < 0.001). IL-4 and IL-13 were detectable in only 27 of 132 and 9 of 132 samples assayed respectively. Furthermore, the levels detected for IL-4 and IL-13 were very low and did not correlate with the development of BPD.
TA concentrations of IL-4 and IL-13 do not increase significantly during acute lung injury in premature infants.
PMCID: PMC194674  PMID: 12925236
7.  Self-hypnosis for anxiety associated with severe asthma: a case report 
BMC Pediatrics  2003;3:7.
Management of asthma can be complicated by both medical and psychiatric conditions, such as gastroesophageal reflux, chronic sinusitis, and anxiety. When symptoms of asthma are interpreted without regard to such conditions treatment may yield a suboptimal outcome. For example, anxiety-associated dyspnea, tachypnea, and chest tightness can be mistakenly interpreted as resulting from an exacerbation of asthma. Medical treatment directed only for asthma may thus lead to overuse of asthma medications and increased hospitalizations.
Case Presentation
The described case illustrates how a systemic steroid-dependent patient with asthma benefited from receiving care from a pediatric pulmonologist who also was well versed in the diagnosis and treatment of anxiety. By using self-hypnosis, the patient was able to reduce her dependence on bronchodilators. Following modification of her medical therapy under supervision of the pulmonologist, and regular use of hypnosis, the patient ultimately was weaned off her systemic steroid therapy.
This report emphasizes that anxiety must be considered as a comorbid condition in the treatment of asthma. Self-hypnosis can be a useful skill in the treatment of a patient with anxiety and asthma.
PMCID: PMC169186  PMID: 12875663
anxiety; asthma; dyspnea; hypnosis; vocal cord dysfunction
8.  A nearly continuous measure of birth weight for gestational age using a United States national reference 
BMC Pediatrics  2003;3:6.
Fully understanding the determinants and sequelae of fetal growth requires a continuous measure of birth weight adjusted for gestational age. Published United States reference data, however, provide estimates only of the median and lowest and highest 5th and 10th percentiles for birth weight at each gestational age. The purpose of our analysis was to create more continuous reference measures of birth weight for gestational age for use in epidemiologic analyses.
We used data from the most recent nationwide United States Natality datasets to generate multiple reference percentiles of birth weight at each completed week of gestation from 22 through 44 weeks. Gestational age was determined from last menstrual period. We analyzed data from 6,690,717 singleton infants with recorded birth weight and sex born to United States resident mothers in 1999 and 2000.
Birth weight rose with greater gestational age, with increasing slopes during the third trimester and a leveling off beyond 40 weeks. Boys had higher birth weights than girls, later born children higher weights than firstborns, and infants born to non-Hispanic white mothers higher birth weights than those born to non-Hispanic black mothers. These results correspond well with previously published estimates reporting limited percentiles.
Our method provides comprehensive reference values of birth weight at 22 through 44 completed weeks of gestation, derived from broadly based nationwide data. Other approaches require assumptions of normality or of a functional relationship between gestational age and birth weight, which may not be appropriate. These data should prove useful for researchers investigating the predictors and outcomes of altered fetal growth.
PMCID: PMC169185  PMID: 12848901
MeSH Headings: Birth weight; fetal weight; gestational age; premature birth; ultrasonography
9.  Breastfeeding intentions, patterns, and determinants in infants visiting hospitals in La Paz, Bolivia 
BMC Pediatrics  2003;3:5.
Recent ecological research from Latin America has shown that infant health could be promoted through exclusive breastfeeding in infants aged 0–3 months and partial breastfeeding throughout the remainder of infancy.
In a cross-sectional study in 1995, the author interviewed 518 mothers with infants ≤ 1 year in La Paz, Bolivia, to describe the breastfeeding pattern and its determinants including socio-economic, religious and ethnic background.
The rate of any breastfeeding remained above 85% during the first year. Exclusive breastfeeding rates fell from 89% at one week of age to 45% as early as one month of age, and then gradually declined to 20–25% in 6-month-old infants. The overall exclusive breastfeeding rate in infants < 4 months was 46% (n = 246). The use of prelacteal feeds (p < 0.0001, n = 436), not feeding the infant colostrum (p = 0.0008, n = 436), and Latin ethnicity (p = 0.0091, n = 436) were associated with a shorter duration of exclusive breastfeeding. Rural mothers were four times more likely to discard the colostrum than urban mothers (p = 0.0110, n = 501). Actual exclusive breastfeeding duration was shorter than what the mothers reported to be the ideal duration of exclusive breastfeeding for the infant.
The rate of exclusive breastfeeding in Bolivian infants fell rapidly during the first months of life. Avoidance of prelacteal feeding and use of colostrum were associated with improved breastfeeding patterns.
PMCID: PMC198277  PMID: 12818005
10.  Breastfeeding in Bolivia – information and attitudes 
BMC Pediatrics  2003;3:4.
The main objective of the present study was to investigate the relationship between the attitudes of the mother and her family towards breastfeeding and the actual feeding pattern in a Bolivian population. A second objective was to study the relationship between breastfeeding information, specified according to source and timing, and feeding pattern.
Cross-sectional interviews with 420–502 Bolivian mothers with an infant less than or equal to 1 year of age. Duration of exclusive breastfeeding, use of prelacteal food and/or colostrum were the main outcome measures.
The attitudes of the mother, her partner (the infant's father) and the infant's grandmother towards breastfeeding did not influence the infant feeding pattern. Women who had received breastfeeding information from health care personnel before birth or on the maternity ward breastfed exclusively for a longer duration (adjusted p = 0.0233) and avoided prelacteal food to a greater extent (adjusted odds ratio (AOR) = 0.42; 95% confidence interval for adjusted odds ratio (95% CI AOR) = 0.23–0.72). Information from a doctor before birth or on the maternity ward was associated with less use of prelacteal food (AOR = 0.53; 95% CI AOR = 0.31–0.93), an increased use of colostrum (AOR = 3.30; 95% CI AOR = 1.16–9.37), but was not linked to the duration of exclusive breastfeeding (p = 0.1767).
The current study indicates that breastfeeding information delivered by health care personnel in a non-trial setting may affect the infant feeding pattern including the use of prelacteal foods and colostrum. There was no evidence that the attitudes of the mother, or the infant's father or grandmother influenced actual feeding behavior. The lack of a "negative or neutral attitude" towards breastfeeding in the participants of the current study does, however, diminish the chances to link attitude to feeding behavior.
PMCID: PMC161813  PMID: 12769829
11.  The relation of menarcheal age to obesity in childhood and adulthood: the Bogalusa heart study 
BMC Pediatrics  2003;3:3.
Several studies have shown that girls who undergo menarche at a relatively young age tend to be more obese as adults. However, because childhood (pre-menarcheal) levels of weight and height are associated with an earlier menarche, the increased prevalence of adult obesity among early maturers may largely reflect the persistence of childhood obesity into adulthood.
We examined these interrelationships among 1179 girls (65% white, 35% black) who were examined as children (mean age, 9 y), adolescents, and adults (mean age, 26 y) in the Bogalusa Heart Study.
Both white and black women who reported that they underwent menarche before age 12 y had, on average, higher adult levels of weight (+10 kg), body mass index (BMI, +4 kg/m2) and skinfold thicknesses (+6 mm) than did women who underwent menarche after age 13.5 y. However, relatively fat children tended to undergo menarche earlier than did thinner children, with each standard deviation increase in pre-menarcheal BMI increasing the odds of early menarche (<12 y) by approximately 2-fold. Stratified and regression analyses indicated that (1) adult obesity was more strongly associated with childhood obesity than with menarcheal age, and (2) about 60% to 75% of the apparent effect of menarcheal age was due to the influence of childhood obesity on both menarcheal age and adult obesity.
Although additional longitudinal studies are needed, it is likely that the importance of early menarche in adult obesity has been overestimated. Most of apparent influence of menarcheal age on adult obesity is attributable to the association of childhood obesity with both menarcheal age and adult obesity.
PMCID: PMC156622  PMID: 12723990
females; menarche; puberty; childhood; adult; longitudinal; obesity
12.  Treatment of hemangiomas in children using a Nd:YAG laser in conjunction with ice cooling of the epidermis: techniques and results 
BMC Pediatrics  2003;3:2.
Hemangiomas are the most common type of congenital anomaly in childhood. Although many resolve spontaneously, intervention is required when their growth could damage vital adjacent structures. Various therapeutic approaches to childhood hemangiomas with different types of laser have been described previously. The objective of this study was to determine whether the cooling of the epidermis during irradiation of hemangiomas with a Nd:YAG laser prevents thermal damage and decreases the number of sessions required to treat these lesions.
Between 1993 and 2001, 110 patients aged 3 months to 4 years, with cutaneous hemangiomas were treated with a Nd:YAG laser. The lesion was cooled with ice prior to, during, and after the irradiation. During each session the laser beam passed through the pieces of ice. The laser power was between 35–45 W with a pulse length of 2–10 seconds.
After 6 months of follow-up, from the first session of laser treatment, total resolution was obtained in 72 (65.5%) patients. A second or third session followed in 30 out of 38 patients in which, the initial results were good, moderate, or poor. The parents of the remaining eight children refused this second session and these patients excluded from the study Complications were seen in nine (8.8%) patients. One patient had postoperative bleeding which stopped spontaneously, while atrophic scars occurred in six (5.8%) patients, and hypertrophic scars in two (1.9%) patients.
Nd:YAG laser irradiation in conjunction with ice protection of the epidermis produces good cosmetic results for the treatment of cutaneous hemangiomas in children, and decreases the number of sessions for treatment of these lesions.
PMCID: PMC155650  PMID: 12697072
Children; Hemangioma; Nd:YAG Laser
13.  Randomized controlled trials in pediatric complementary and alternative medicine: Where can they be found? 
BMC Pediatrics  2003;3:1.
The safety and effectiveness of CAM interventions are of great relevance to pediatric health care providers. The objective of this study is to identify sources of reported randomized controlled trials (RCTs) in the field of pediatric complementary and alternative medicine (CAM).
Reports of RCTs were identified by searching Medline and 12 additional bibliographic databases and by reviewing the reference lists of previously identified pediatric CAM systematic reviews.
We identified 908 reports of RCTs that included children under 18 and investigated a CAM therapy. Since 1965, there has been a steady growth in the number of these trials that are being published. The four journals that published the most reported RCTs are The American Journal of Clinical Nutrition, Pediatrics, Journal of Pediatrics, and Lancet. Medline, CAB Health, and Embase were the best database sources for identifying these studies; they indexed 93.2%, 58.4% and 42.2 % respectively of the journals publishing reports of pediatric CAM RCTs.
Those working or interested in the field of pediatric CAM should routinely search Medline, CAB Health and Embase for literature in the field. The four core journals identified above should be included in their collection.
PMCID: PMC151673  PMID: 12589711
alternative medicine; bibliometrics; information services; medical informatics applications; pediatrics, evidence-based medicine

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