Age and family history at presentation of pediatric inflammatory bowel disease

OBJECTIVES: Young children are thought to be a unique subset of pediatric patients with inflammatory bowel disease (IBD). The authors' objective was to evaluate the differences in initial clinical presentation of young and older children with IBD and to determine whether a positive family history of IBD is associated with the age of presentation. METHODS: The authors reviewed the records of all patients with new diagnoses of Crohn disease (CD) and ulcerative colitis (UC) who presented between July 1996 and July 1999. Initial evaluation included assessment of growth parameters and laboratory values (hemoglobin concentration, platelet count, erythrocyte sedimentation rate, and serum albumin). Inquiry regarding a family history of IBD was made in every patient. RESULTS: There were 153 patients with new diagnoses (82 with CD and 71 with UC), with a mean age of 11.9 years (range, 16 months-18 years). The children with CD had a higher sedimentation rate and platelet count and a lower mean hemoglobin concentration and serum albumin at presentation than did children with UC. Body mass index (BMI) was significantly lower in patients with newly diagnosed CD than in those with UC. The only significant laboratory differences between patients younger than 11 years and those 11 years or older was a higher mean platelet count in patients with CD who were younger than 11 years. Of the younger patients with CD, 41.7% had a positive family history of IBD, which was significantly greater that that found in the older patients with CD. CONCLUSIONS: Except for higher platelet counts, a lower BMI, and a higher frequency of positive family history in young children with CD, there were no significant differences in the presentation of young children with IBD compared with older children.     

Incidence of high erythrocyte count in infants and young children with iron deficiency anemia: re-evaluation of an old parameter

PURPOSE: To investigate the frequency of high erythrocyte count (red blood cell count >or=5.0 x 106/microL) in infants and young children with iron deficiency anemia and to document the differences in hematologic parameters at diagnosis and during iron therapy in IDA patients with and without a high erythrocyte count. PATIENTS AND METHODS: A total of 140 infants and young children aged 6 to 48 months with nutritional IDA without a history of any bleeding disorder were the subjects of this study. The patients were divided into three groups according to the severity of anemia. Group A1 children had Hb values 8.0 g/dL or less (severe anemia); group A2, 8.1 to 10.0 g/dL (moderate anemia); and group A3, 10.1-11.0 g/dL (mild anemia). All children received oral iron (3-5 mg/kg per day) for 12 weeks. Complete blood counts were done weekly during treatment. RESULTS: A total of 36 of the 140 patients (26%) had a high erythrocyte count. Of the 140 patients, 37 were in group A1, 80 in A2, and 23 in A3. The frequency of high erythrocyte count was 11%, 23%, and 61% in groups A1, A2, and A3, respectively. The patients with a high erythrocyte count had significantly higher Hb and Hct but significantly lower mean corpuscular volume and mean corpuscular hemoglobin (MCH) values than those with a low erythrocyte count (n = 104). A continuous elevation in the erythrocyte count has been observed in patients with a high red cell count, as in those with a low red cell count, after the institution of iron therapy. CONCLUSIONS: A high erythrocyte count is a common feature of iron deficiency anemia in infants and young children, with an increasing frequency from severe to moderate to mild anemia. High erythrocyte count cannot be regarded as a reliable preliminary parameter in differentiating iron deficiency from thalassemias in infants and children aged up to 48 months.     

Iron deficiency anemia and catecholamine metabolism

To assess the effects of iron therapy on platelet monoamine oxidase (MAO) activity and urinary excretion of total metanephrines (MN) in infants and young children with iron deficiency anemia, 24 subjects were tested before and after one month of oral iron treatment. Thirteen healthy children comprised the control group. In the control group, platelet MAO level was 0.21 +/- 0.02 U/mg protein (mean +/- SE), urinary total metanephrine was 2.51 +/- 0.47 micrograms/mg creatinine. In cases with iron deficiency, mean platelet MAO level was 47.6% lower (p less than 0.005) whereas mean urinary metanephrine plus normetanephrine (MN-NMN) was only 20.7% lower (p greater than 0.05) than the control values. After one month, the anemic patients receiving oral iron therapy showed a significant increase in hemoglobin concentration, per cent transferrin saturation and platelet MAO activity (p less than 0.05). However, urinary metanephrine excretion was found to be lower in this group when compared to the metanephrine levels in iron deficiency before the medication (p less than 0.05). Although hemoglobin and transferrin saturation did not return to normal levels, these findings suggested that platelet MAO activity increased and urinary excretion of metanephrines decreased after iron medication.     

Stunting and Nutrient Deficiences in Children on Alternative Diets

Studies in children fed alternative diets showed that anthropometric parameters and the intake of energy and nutrients by macrobiotic children deviated most from current norms. Therefore weaning practice, growth and haematological status were investigated in 3 age-cohorts of macrobiotic fed infants between 4 and 18 months of age and a control group. A mixed longitudinal design was used for this study. Main findings were a growth retardation which was strongest in the second cohort (8–14 months of age) and related to a diet low in energy density, fat and protein. Haematological data revealed very low vitamin B12 concentrations with consequently low values of haematocrit and red blood cell count and higher values of mean corpuscular volume and mean corpuscular haemaglobin mass in the macrobiotic group. High folate concentrations also seemed to be a consequence of Vitamin B12 deficiency. Iron deficiency was found in 15% of the macrobiotic group vs. no infants in the control group. Nutritional recommendations acceptable within the macrobiotic philosophy are discussed.     

Thrombocytosis in childhood: a survey of 94 patients

The introduction of the newer generation of electronic cell counters allows the routine reporting of platelet numbers when the peripheral blood count is requested. In a 12-month period, 100 episodes of marked thrombocytosis (platelet count more than 900 X 10(9)/L) were found among 94 children. These patients were young (median age 9 months). All but one episode of marked thrombocytosis occurred as a phenomenon secondary to a variety of disease states. Infections, especially those involving the central nervous systems were the commonest cause of an elevated platelet count in this series. Malignant diseases alone were rarely associated with thrombocytosis of this magnitude. The elevated platelet count began to decline at a mean of 3 days after diagnosis, and no thrombotic or hemorrhagic complications were encountered. Marked thrombocytosis is a benign, common phenomenon in young children, but specific treatment is not required.     

Faecal calprotectin levels in infants with infantile colic, healthy infants, children with inflammatory bowel disease, children with recurrent abdominal pain and healthy children

This study investigated faecal calprotectin concentration, a measure of intestinal inflammation, in infants and children with abdominal pain. Faecal calprotectin was measured by an enzyme-linked immunosorbent assay kit in spot stool samples in 76 infants with typical infantile colic, 7 infants with transient lactose intolerance and 27 healthy infants. All infants were 2-10 wk of age. In addition, 19 children with recurrent abdominal pain (RAP; mean age 11.5 y), 17 with inflammatory bowel disease (IBD; mean age 11.1 y; 10 had Crohn's disease and 7 ulcerative colitis) and 24 healthy children (mean age 5.3 y) were studied. In infants with infantile colic the mean faecal calprotectin concentration was not different from that in healthy infants (278 +/- 105 vs 277 +/- 109 mg kg(-1), p = 0.97) or in infants with transient lactose intolerance (300.3 +/- 124 mg kg(-1), p = 0.60). The calprotectin level was similar in boys and girls and fell significantly with age (p = 0.04). Children with IBD had faecal calprotectin levels (293 +/- 218 mg kg(-1)) much higher than healthy children (40 +/- 28 mg kg(-1), p < 0.0001) and children with RAP without identified organic disease (18 +/- 24 mg kg(-1), p < 0.0001). Conclusion: Faecal calprotectin may differentiate between functional abdominal pain and IBD in school-aged children. In young infants high faecal calprotectin levels are normal.     

Iron deficiency in infants and children]

A study of the incidence of iron deficiency and its risk factors was carried out in 90 hospitalized or outpatient children and infants, 4 to 48 months old. Iron deficiency (serum iron concentration less than 10 mumol/l) was found in 70% of them and microcytosis (mean corpuscular volume less than 70 fl) in 10%. A good correlation was observed between hemoglobin concentration or mean corpuscular volume, and serum iron or ferritin concentrations. When risk factors were studied, 20% of the children were found to have insufficient meat or vegetable intakes. Only 45% of 6 month-old and 20% of 1 year-old infants received iron fortified milk formulas. However no significant correlation was found between the nutritional factors and the hematological data. Anemia and microcytosis were significantly more frequent in children born from immigrant parents as compared with native children, but there was no difference between these two groups for isolated iron deficiency. These results indicate that there is a need for a better prevention of iron deficiency in French infants and young children; a larger use of iron fortified milk formula until the age of 12 months is to be recommended.     

Red Blood Cell Distribution Width and the Platelet Count in Iron-deficient Children Aged 0.5–3 Years

Early detection of iron deficiency (ID) and iron deficiency anemia (IDA) in young children is important to prevent impaired neurodevelopment. Unfortunately, many biomarkers of ID are influenced by infection, thus limiting their usefulness. The aim of this study was to investigate the value of red blood cell distribution width (RDW) and the platelet count for detecting ID(A) among otherwise healthy children. A multicenter prospective observational study was conducted in the Netherlands to investigate the prevalence of ID(A) in 400 healthy children aged 0.5–3 years. ID was defined as serum ferritin (SF) <12 μg/L in the absence of infection (C-reactive protein [CRP] <5 mg/L) and IDA as hemoglobin <110 g/L combined with ID. RDW (%) and the platelet count were determined in the complete blood cell count. RDW was inversely correlated with SF and not associated with CRP. Calculated cutoff values for RDW to detect ID and IDA gave a relatively low sensitivity (53.1% and 57.1%, respectively) and specificity (64.7% and 69.9%, respectively). Anemic children with a RDW >14.3% had a 2.7 higher odds (95% confidence interval [CI]: 1.2–6.3) to be iron deficient, compared with anemic children with a RDW <14.3%. The platelet count showed a large range in both ID and non-ID children. In conclusion, RDW can be helpful for identifying ID as the cause of anemia in 0.5- to 3-year-old children, but not as primary biomarker of ID(A). RDW values are not influenced by the presence of infection. There appears to be no role for the platelet count in diagnosing ID(A) in this group of children.     

Mean platelet volume in neonatal respiratory distress syndrome

The aim of this study was to investigate the differences in mean platelet volume (MPV) between neonates with and without neonatal respiratory distress syndrome (RDS). Eighty-three premature infants who were admitted to the neonatal intensive care unit were included in the study. Forty-four of these infants were diagnosed as having RDS and the other 39 infants were non-RDS patients. Infants born to mothers with pre-eclampsia, or a drug history that had negative effects on platelet count, perinatal hypoxia, sepsis and necrotizing enterocolitis were excluded. Blood collection was done on the first and third days of life. There were no demographic, gestational or platelet count differences between groups, but MPV was higher in RDS patients and this difference was statistically significant ( P = 0.011). High platelet volumes in RDS patients is probably related to young platelet production and may be a result of increased platelet consumption in pulmonary damage due to RDS.     

Cerebrospinal fluid values in very low birth weight infants with suspected sepsis at different ages.

OBJECTIVES: Lumbar puncture can be an essential part of the septic work-up in premature infants who are at risk for sepsis and meningitis. Cerebrospinal fluid (CSF) values for cell counts, protein concentrations, and glucose concentrations in children and full-term infants are well established. CSF values in premature infants, however, have not been well studied. We sought to determine CSF values in very low birth weight premature infants at different ages (birth, postmenstrual age, and postnatal age). DESIGN: Medical records of all very low birth weight premature infants with suspected sepsis who were admitted to our neonatal intensive care unit between 1991 and 2005 were reviewed. Infants were excluded if they had evidence of intraventricular hemorrhage, sepsis/meningitis, or major congenital abnormalities or had a traumatic lumbar puncture. SETTING: Neonatal intensive care unit. PATIENTS: Patients were 455 infants who underwent lumbar puncture. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of 455 infants who underwent 648 lumbar punctures were reviewed. Of these, 243 infants met our inclusion criteria, and 88 patients underwent lumbar puncture only at birth. Patients' mean gestational age and birth weight were 28.8 +/- 2.6 wks and 1080 +/- 279 g, respectively. There were no correlations between gestational age and CSF white blood cell (WBC) count or between gestational age and CSF protein concentrations at birth. CSF WBC count remained unchanged at different postmenstrual ages. However, CSF protein concentration decreased with advancing postmenstrual age (Spearman's rho correlation coefficient, r = -.29; p < .01), and both CSF WBC count and CSF protein concentration decreased with advancing postnatal age (Spearman's rho correlation coefficient, r = -.319 and r = -.376, respectively; p < .01). A subgroup analysis revealed differences in CSF WBC count and CSF protein concentrations between infants who had a lumbar puncture at birth, at 2 wks, and at 3 wks of life at the same postmenstrual age. CONCLUSIONS: In very low birth weight premature infants, CSF WBC count and CSF protein concentrations vary with advancing postnatal and postmenstrual ages.     

5-Hydroxy-3-indole acetic acid levels in infantile colic: Is serotoninergic tonus responsible for this problem?

Abstract Levels of 5-hydroxy-3-indole acetic acid (5-OHIAA), a metabolite of serotonin, were studied in infants with infantile colic in order to investigate the aetiology of infantile colic pathogenesis. The study included 16 patients with infantile colic and 10 control subjects. Random urinary 5-OH IAA levels of colicky infants were found to be higher than those in the control group. This finding suggested that high serotonin levels may be responsible for infantile colic.     

Prevalence of sleep disorders in early-treated phenylketonuric children and adolescents. Correlation with dopamine and serotonin status

Phenylketonuric (PKU) patients are a population at risk for sleep disorders due to deficits in neurotransmitter synthesis. We aimed to study the prevalence of sleep disorders in early-treated PKU children and adolescents and assessed correlations with dopamine and serotonin status. We compared 32 PKU patients (16 females, 16 males; mean age 12 years), with a healthy control group of 32 subjects (16 females, 16 males; mean age 11.9 years). 19 PKU patients were under dietary treatment and 13 on tetrahydrobiopterin therapy. Concurrent phenylalanine (Phe), index of dietary control and variability in Phe in the last year, tyrosine, tryptophan, prolactin, and ferritin in plasma, platelet serotonin concentration, and melatonin, homovanillic and 5-hydroxyindoleacetic acid excretion in urine were analyzed. Sleep was assessed using Bruni's Sleep Disturbance Scale for Children. Sleep disorders were similar in both groups, 15.6% in control group and 12.5% in PKU group. In PKU patients, no correlations were found with peripheral biomarkers of neurotransmitter synthesis nor different Phe parameters, 43.3% had low melatonin excretion and 43.8% low platelet serotonin concentrations. Despite melatonin and serotonin deficits in early-treated PKU patients, the prevalence of sleep disorders is similar to that of the general population.     

Platelet serotonin in newborns and infants: ontogeny, heritability, and effect of in utero exposure to selective serotonin reuptake inhibitors

Ontogeny of platelet serotonin (5-hydroxytryptamine, 5-HT) during the first year of life was examined in newborns and infants. The effects of in utero exposure to selective serotonin reuptake inhibitors (SSRI, including fluoxetine, sertraline, and citalopram) were examined by comparing cord blood 5-HT levels in exposed and unexposed newborns. Heritability was assessed by correlation of the platelet 5-HT values observed for mother-infant pairs. No age effect was observed in 1-49 wk-old infants (r = 0.13, p = 0.49) and mean platelet 5-HT levels in infants (241 +/- 102 ng/mL, n = 33; 615 +/- 320 ng/10(9) platelets, n = 32) were similar to those reported for older children and adults. However, significantly lower blood 5-HT levels were observed in newborns (81.3 +/- 32.5 ng/mL, n = 16, p < 0.0001; 297 +/- 101 ng/10(9) platelets, n = 11, p = 0.0007) compared with the 1-49 wk-old infants. The mean cord blood 5-HT concentrations in newborns exposed in utero to SSRI (n = 8) were substantially lower than that seen in unexposed (n = 16) newborns (20.6 +/- 14.4 versus. 81.3 +/- 32.5 ng/mL, p = 0.0001; 90.7 +/- 55.4 versus. 297 +/- 101 ng/10(9) platelets, p = 0.0005). Platelet serotonin levels (ng/10(9) platelets) in mother-child pairs (n = 32) were significantly correlated (r = 0.415, p = 0.018). The results indicate that, although platelet 5-HT is low at birth, values quickly increase and stabilize at near-adult levels by 1 mo of age. Gestational exposure to SSRI appears to substantially reduce platelet 5-HT uptake in the fetus, strongly suggesting that such exposure has important physiologic effects. The observed mother-infant correlation agrees with a previous report of high heritability in a large adult population.     

Thrombocytosis and increased circulating platelet aggregates in newborn infants of polydrug users.

Thirty-three prospectively studied neonates born to mothers using methadone plus other drugs developed significant thrombocytosis by the second week of life compared to platelet counts performed during the first week. This increase persisted for over 16 weeks, with a further short-lived significant peak at 10 weeks of age. Platelet counts exceeding 1,000,000/mm3 were found in seven infants. Thrombocytosis was not related to withdrawal symptoms or treatment (phenobarbital or paregoric). No thrombocytosis was found in 36 normal control infants up to eight weeks of life. Twenty-eight of the study group infants were evaluated for circulating platelet aggregates. Thirteen patients had a normal aggregate index and a mean platelet count of 468,000/mm3; 15 patients had increased aggregates and mean platelet count of 754,000/mm3. The risk for increased circulating platelet aggregates correlated directly with an increase in platelet count. Thrombocytosis and increased circulating platelet aggregates may be factors in the pathogenesis of the focal infarcts, and subarachnoid and germinal plate hemorrhages, described at autopsy in infants of addicted mothers.     

Gonadotropins and sex hormones in healthy Chinese infants

This study was conducted to investigate the infantile changing regularity of gonadotropins and sex hormones. Serum samples were obtained from 416 healthy infants (male: 215; females: 201). In male infants, peaks in serum gonadotropins and testosterone concentrations were observed at 2-4 months. In female infants, serum FSH concentrations reached peak at 2-3 months. Before 6 months, serum testosterone and LH concentrations were higher in male, while FSH was on the contrary. Peaks in serum gonadotropins and sex hormones concentrations are reached and sexual dimorphism appears in the early infancy. Defining the range of mean values and the trends for infantile gonadotropins and sex hormones could be helpful for clinical evaluation.     

Relationships between levels of leptin and hematological parameters in healthy term infants

In order to evaluate the role of leptin in neonatal hematological parameters, we studied the serum concentrations of leptin in relation to blood hemoglobin, leukocyte and platelet values in 30 healthy term infants. We also studied the serum concentrations of IGF-I and IGFBP-3 in relation to leptin concentrations. The mean concentrations of leptin, IGF-I and IGFBP-3 were 1.63 +/- 1.09, 24.65 +/- 10.04 and 976.05 +/- 214.50, respectively, at birth. A positive correlation was observed between leptin concentrations and birth weights of the infants. As no relationship could be found between concentrations of leptin and blood hemoglobin, leukocyte and platelet values, we could not determine any involvement of leptin in the regulation of physiologial hemoglobin, leukocyte and platelet concentrations at birth.     

Effects of phototherapy on platelet counts in low-birthweight infants and on platelet production and life span in rabbits.

The effects of conventional phototherapy on platelets in vivo were studied in rabbits and in low-birthweight infants. Rabbits were divided into three groups and individually treated continuously for 96 hours, with blue light, daylight, or no phototherapy. Incorporation of selenomethionine Se75 was used to evaluate platelet production and life span. Platelet turnover was significantly increased in the blue-light phototherapy group, and was also increased in the daylight group but to a lesser degree. Daily platelet counts and hematocrits were performed in infants weighing less than 2,000 gm at birth randomized at 24 +/- 12 hours of life to receive daylight phototherapy continuously for 96 hours (31 infants) or no phototherapy (26 infants). In 12 treated infants (38.7%) platelet counts fell below 150,000/cu mm whereas this occurred in only 3 (11.5%) of the controls. These two lower platelet count subgroups differed significantly in mean gestational age and birthweight with the phototherapy group being the more mature. Pre-phototherapy, the mean platelet count of these 12 infants was lower than the mean of the entire control group, suggesting that these infants had borderline marrow reserve before phototherapy was given. These results suggest that phototherapy increases the rate of platelet turnover. When bone marrow compensation is inadequate, the platelet count may fall.     

Extreme thrombocytosis predicts Kawasaki disease in infants

Infants with Kawasaki disease are at high risk of developing life-threatening coronary complications, yet may elude timely diagnosis because they often lack the full complement of classic clinical features. We retrospectively studied 26,540 children 1 year of age or less who were evaluated at a tertiary care pediatric emergency department in whom a platelet count was performed. Among those infants with fever without a source identified, 8.5% with platelet counts of 800,000 cells/mm(3) or greater had Kawasaki disease compared to 0.4% with platelet counts of less than 800,000 cells/mm(3) (likelihood ratio for Kawasaki disease was 17 [95% confidence interval, 8-34]). Because many infants present atypically, Kawasaki disease should be considered in all children of 1 year or less with prolonged fever, extreme elevation of the platelet count, and no compelling alternative diagnosis.     

INFANTILE AUTISM AND OTHER CHILDHOOD PSYCHOSES IN A SWEDISH URBAN REGION. EPIDEMIOLOGICCAL ASPECTS

A total population screening of children born during 1962-1976 and living in the Gothenburg region at the end of 1980 was carried out in order to obtain prevalence figures for infantile autism and other childhood psychoses. It was found that the prevalence figure for infantile autism was 2.0 per 10,000 and for other childhood psychoses 1.9 per 10,000. Boys were much more often affected by infantile autism than girls. In the case of other psychoses, no such over-representation was seen. A majority of the children were mentally retarded, and only 4% had tested IQs exceeding 100. The results are in good agreement with the three earlier epidemiological studies concerned with childhood psychosis.     

A prospective comparative study of 2540 infants and children with newly diagnosed idiopathic thrombocytopenic purpura (ITP) from the Intercontinental Childhood ITP Study Group

OBJECTIVE: To analyze prospectively the impact of age at diagnosis in childhood idiopathic thrombocytopenic purpura (ITP). STUDY DESIGN: International registry from June 1997 to May 2001, with analysis of data from baseline and 6-month-follow-up questionnaires. RESULTS: Data from 2540 patients were analyzed, including 203 infants (7.6%), 1860 children > or =1 to <10 years of age (69.1%), and 477 children and adolescents between > or =10 and <16 years of age (17.7%). The mean platelet count at diagnosis was similar in all three groups, as was the percentage of patients with initial platelet count <20x10(9)/L. The male/female ratio was highest in infants and decreased with age (P=.009). Immunoglobulin therapy was used more often in infants and corticosteroids in patients > or =10 years of age. Follow-up information at 6 months was available for 1742 children (68.6%). Chronic ITP was seen less frequently in infants (23.1%) than in children >10 years of age (47.3%, P<.0001). Intracranial hemorrhage occurred in 3 of 1742 children during the first 6 months after the diagnosis of ITP. CONCLUSIONS: Pediatric patients with ITP from infancy to adolescence exhibit heterogeneity in clinical, demographic, and treatment factors.