Screening for familial hyper-beta-lipoproteinaemia in children in hospital.

1510 plasma cholesterol estimations were made in 1391 children admitted to hospital as part of a biochemical profile. Babies under 1 year and children known to have familial hyperlipoproteinaemia were excluded. The mean concentration was 4-28 mmol/l +/- 1-04 (1 SD) (165-3 mg/100 ml +/- 38-6), and levels exceeded 5-93 mmol/l (229 mg/100 ml) in 68 children. Repeat estimations on 55 of these children showed 34 still to have values greater than 5-93 mmol/l and family studies were performed in 19 of these. In 8 children hypercholesterolaemia was secondary and no familial lipoprotein disorder was present. Familial hyper-beta-lipoproteinaemia (FH) was diagnosed in 3 children and in 2 of the families there was a history of early ischaemic heart disease. In 2 children the diagnosis was in doubt. In the remaining 6 children FH and secondary hyperlipoproteinaemia were excluded so the hypercholesterolaemia was presumably environmentally induced, possibly in association with polygenic inheritance. In the present state of knowledge screening of the childhood population for FH by means of plasma cholesterol determinations cannot be recommended. Studies of lipoproteins should, however, be made in children from families known to have FH or early coronary heart disease.     

Developmental trajectories of positive and negative affect in children at high and low familial risk for depressive disorder

Background: Although low positive affect (PA) and high negative affect (NA) have been posited to predispose to depressive disorders, little is known about the developmental trajectories of these affects in children at familial risk for mood disorders. Methods: We examined 202 offspring of mothers who had a history of juvenile‐onset unipolar depressive disorder (n = 60) or no history of major psychopathology (n = 80). Offspring participated in up to seven annual, structured laboratory tasks that were designed to elicit PA and NA. Results: Growth curve analyses revealed that PA increased linearly and similarly for all children from late infancy through age 9. However, there also were individual differences in early PA. Relative to control peers, offspring of mothers with lifetime unipolar depression had consistently lower levels of PA, and this association remained significant even when controlling for current maternal depression and maternal affect displays. Growth curve analyses also revealed a significant linear decrease in NA in children across time; however, there was no significant inter‐individual variation either in early NA or rate of change in NA. Conclusion: Attenuated PA (rather than excessive NA) may be an early vulnerability factor for eventual unipolar depressive disorder in at‐risk children and may represent one pathway through which depression is transmitted.     

The apolipoprotein epsilon4 allele confers additional risk in children with familial hypercholesterolemia

Children with familial hypercholesterolemia (FH) exhibit substantial variance of LDL cholesterol. In previous studies, family members of children with FH were included, which may have influenced results. To avoid such bias, we studied phenotype in 450 unrelated children with FH and in 154 affected sib-pairs. In known families with classical FH, diagnosis was based on plasma LDL cholesterol above the age- and gender-specific 95th percentile. Girls had 0.47 +/- 0.15 mmol/L higher LDL cholesterol, compared with boys (p = 0.002). Also in girls, HDL cholesterol increased by 0.07 +/- 0.03 mmol/L per 5 y (pfor trend = 0.005); this age effect was not observed in boys. The distribution of apolipoprotein (apo) E genotypes was not significantly different between probands, their paired affected siblings, or a Dutch control population. Carriers with or without one epsilon4 allele had similar LDL and HDL cholesterol levels. Within the affected sib-pairs, the epsilon4 allele explained 72.4% of the variance of HDL cholesterol levels (-0.15 mmol/L, 95% confidence interval -0.24 to -0.05, p = 0.003). The effect of apoE4 on HDL cholesterol differed with an analysis based on probands or on affected sib-pairs. The affected sib-pair model used adjustment for shared environment, type of LDL receptor gene mutation, and a proportion of additional genetic factors and may, therefore, be more accurate in estimating effects of risk factors on complex traits. We conclude that the epsilon4 allele was associated with lower HDL cholesterol levels in an affected sib-pair analysis, which strongly suggests that apoE4 influences HDL cholesterol levels in FH children. Moreover, the strong association suggests that apoE4 carries an additional disadvantage for FH children.     

Screening for auditory dysfunction in high risk neonates

Brainstem auditory evoked responses were recorded in 117 pre-term and 71 full-term infants from the general population of infants born at a referral obstetric unit. The threshold intensity required to evoke a reliable BAER was determined at different post-menstrual ages (PMAs) and in many cases at follow-up clinics. The BAER thresholds for 12 infants born and tested at less than 31 wk PMA were all greater than or equal to 50 dBHL. Sixty-two low-gestational-age infants who were tested between 31 and 36 wk PMA had BAER thresholds between less than or equal to 30 dBHL and greater than or equal to 80 dBHL. The majority of pre-term and term infants tested at term equivalent age had BAER thresholds less than or equal to 30 dBHL. Longitudinal studies also indicated that BAER thresholds can decline rapidly during the pre-term period. Follow-up studies showed that those pre-term and term infants with BAER thresholds less than or equal to 30 dBHL had normal auditory thresholds as determined using conventional behavioural testing at 4 or more months of age. Of those infants with BAER thresholds greater than or equal to 40 dBHL at the time of discharge or at term equivalent age, 67% (n = 16) were confirmed later as having a moderate to profound hearing deficit. The remaining 8 infants in this group had had BAER thresholds at term of 40 or 50 dBHL and had normal BAER and behavioural thresholds at follow-up. The cross-sectional and longitudinal data indicate that the majority of low-gestational-age infants who are at risk of hearing deficit achieve BAER thresholds less than or equal to 30 dBHL by term equivalent age. We recommend that auditory screening of infants in this group is best performed at the time of discharge from hospital or at term equivalent age, whichever is the later. Those infants with thresholds greater than or equal to 40 dBHL at that time should be encouraged to attend follow-up testing and, if high thresholds persist, they should then be referred on for behavioural testing and assessment for habilitative support.     

Associations between familial affluence and obesity risk behaviours among children

BACKGROUND

Results of studies examining associations between socioeconomic status and obesity among children are mixed.

OBJECTIVE

To examine whether physical activity, television viewing, computer use, and fruit, vegetable, soft drink and sweet consumption differed according to familial affluence of children attending schools in disadvantaged communities.

METHOD

A total of 218 children (seven to 11 years of age) recruited from three Calgary (Alberta) schools located in two adjacent socioeconomically disadvantaged neighbourhoods completed online surveys during the spring of 2005/2006. The number of days per week participating in vigorous physical activity for more than 20 min, and weekly frequency of fruit, vegetable, sweet and soft drink consumption were collected. Time spent watching television and using a computer during a normal school day was also captured. A family affluence scale was used to assess socioeconomic status (number of family holidays in the past year, ownership of motor vehicles and computers, and bedroom sharing). Associations between familial affluence and obesity risk behaviours were estimated using Pearson’s correlation and demographic-adjusted logistic regression ORs.

RESULTS

Higher family affluence scale scores were significantly associated with weekly fruit consumption (r=0.14). Children with lower affluence were less likely to participate in vigorous physical activity five days/week or more (OR=0.39), and to use a computer for more than 2 h/day (OR=0.41) than children with higher affluence. Linear trends between familial affluence and the likelihood of participating in physical activity and using a computer were also found. However, no other behaviours were related to affluence.

CONCLUSIONS

Increasing opportunities for physical activity and accessibility to healthy food may be important for reducing obesity risk among less affluent children.     

Treatment with probucol of children with familial hypercholesterolaemia

Nine children with familial hypercholesterolaemia, age range 2 to 12 years, were treated with a low cholesterol diet and probucol (10 mg/kg/day). The year before, the children received, as only treatment, a low fat-cholesterol diet. During this period their mean plasma total cholesterol level fell from 8.2 +/- 1.45 mmol/l to 7.17 +/- 0.84 mmol/l (12.6%). This level was further reduced to 5.92 +/- 0.63 mmol/l (17.1%) after the addition of probucol. Plasma high density lipoprotein cholesterol levels were lowered in absolute terms but not in relation to total cholesterol. No apparent side effects were observed. However, the use of probucol should be restricted for the moment to severe cases of hypercholesterolaemia as the long-term excretion of the drug in children is not yet known.     

Screening for fungal endophthalmitis in children at risk.

To evaluate the efficacy of screening ophthalmologic examinations in high-risk children, we reviewed the medical records for all patients hospitalized from 1985 through 1989 at The Hospital for Sick Children, Toronto, Ontario, who underwent ophthalmological consultation to rule out endogenous fungal endophthalmitis (n = 176). The patients were divided into groups: Group 1 (n = 47), those with deep-tissue fungal infection, and Group 2 (n = 129), those at risk for invasive fungal disease. Group 2 was subdivided further into two subgroups: Group 2a (n = 48), those with evidence of superficial fungal colonization (positive fungal culture) but no deep-tissue involvement, and Group 2b (n = 81), those with no evidence of fungal colonization (negative fungal culture). Of these 176 patients, 7 were diagnosed with endogenous fungal endophthalmitis: 6 from Group 1, 1 from Group 2a, and 0 from Group 2b. We found a significant association between the development of endogenous fungal endophthalmitis and the status of the fungal culture result (P less than .005). The odds ratio indicated the risk of endogenous fungal endophthalmitis in Group 1 patients with deep-tissue infection was at least 19 times that of Group 2 at-risk patients. The risk of endogenous fungal endophthalmitis in Group 1 patients was at least 7 times that of Group 2a colonized patients and 12 times that of Group 2b patients with no positive fungal culture. Our study confirms the necessity of careful dilated ophthalmoscopic examination in patients with invasive fungal disease and suggests screening for those at-risk patients with superficial fungal colonization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence of bacteremias and invasive mycoses in children with high risk neuroblastoma

BACKGROUND: Information on the incidence of infectious complications during for treatment for high risk neuroblastoma (HR-NB) is limited. Bacteremias and invasive mycoses may be considered surrogate markers of the infection burden. PATIENTS AND METHODS: Data on bacteremias and invasive mycoses occurring during 3 consecutive protocols for front line (NB-89; NB-92; NB-97) or salvage therapy (TVD) for HR-NB were reviewed. The cumulative risk of developing a first episode and the rate of infections during the entire length of each protocol were evaluated. RESULTS: Front line protocols were given to 80 patients for a total of 22,070 days at risk; salvage treatment was given to 24 children for 2,909 days at risk. During front line therapy 41 infectious episodes were diagnosed in 29 (36%) patients, for a 45% cumulative risk and an infection rate (IR) of 0.19/100 patient-days-at risk. Salvage therapy determined five infectious episodes in four (17%) patients, with a 39% cumulative risk, and an IR of 0.17. The IR during the phase of high dose chemotherapy with hematopoietic stem cell rescue (megatherapy) included in the three front line protocols decreased over time (1.54 in NB-89; 0.52 in NB-92 and 0.0 in NB 97; P = 0.001), possibly because of the use of less aggressive conditioning regimens, without radiotherapy. CONCLUSIONS: The IRs of protocols for HR-NB did not change over time. The megatherapy-related phases are those at highest risk.     

营养支持对高营养风险患儿临床结局的影响

目的探讨营养支持对有高营养风险患儿临床结局的影响。方法应用改良的儿科营养不良筛查评分法(STAMP),对连续入院的1 296例患儿进行营养风险筛查评分,并分析营养支持对临床结局的影响。结果 1 296例住院患儿中,379例STAMP评分≥4分,高营养风险检出率为29.24%。304例患儿纳入进一步分析,其中85例(27.96%)有营养支持。营养支持患儿中,37例肠外营养支持(PN),23例肠内营养支持(EN),25例PN和EN联合应用;EN、PN、PN和EN联合应用比较,人均和日均营养支持费用的差异有统计学意义(P均0.001);EN的人均和日均费用均为最低。与无营养支持患儿比较,营养支持患儿感染发生率有所降低,但差异无统计学意义(P=0.095);无营养支持患儿抗感染治疗费用高于有营养支持患儿,抗生素治疗费用也明显高于有营养支持患儿,差异均有统计学意义(P均0.001)。无营养支持、EN、PN、PN+EN四组间住院费用差异有统计学意义(P=0.003),而四组间住院时间差异无统计学意义(P=0.213)。结论改良的STAMP评分作为儿科患者营养风险筛查工具简单实用;不同的营养支持方式费用存在差异;营养支持可有效改善临床结局,特别是减少感染和降低抗感染治疗费用。     

Amyloidosis in children with familial Mediterranean fever

In this survey 113 children with secondary amyloidosis due to familial Mediterranean fever are reviewed in regard to their respective histories, and physical and laboratory findings. The beneficial effects of colchicine in the treatment of this condition are evaluated. The number of children presented with amyloidosis secondary to familial Mediterranean fever was considerable. The male-female ratio was 4/3. It was observed that the number of patients with amyloidosis increased through the adolescent period, and that most of the cases demonstrated phenotype I (74.33%). Another important finding was the increase of partial thromboplastin time in 96 out of 113 cases (84.95%). All the symptoms of the periodic attacks were relieved by colchicine. A significant difference was found between the serum total protein and albumin values before and after colchicine therapy.     

Amyloidosis in children with familial Mediterranean fever

The clinical and laboratory findings of 35 children with familial Mediterranean fever who developed amyloidosis are described. The types, frequency, and severity of attacks of familial Mediterranean fever in these children were no different from patients with this disease without amyloidosis. Although amyloid was widely deposited in all tissues, the major clinical manifestations of the amyloidosis were proteinuria, the nephrotic syndrome, and progressive renal failure. Only 20% of the patients were alive 5 years after the first appearance of proteinuria.     

Normal children with large heads--benign familial megalencephaly.

Fifteen normal children with large heads (circumference greater than 0.5 cm above the 98th centile) were studied. CAT scans were pefrormed to exclude hydrocephalus, and ventricular size was compared with that of hydrocephalic children. In 11 of the 13 families in which the parents' heads were measured, one parent (10 fathers and one mother) was found to have a large head, as had 6 of 17 siblings. Head circumference at birth was large in 7 of 10 babies and rate of head growth was excessive in 8 of 13. Skull x-ray showed suture diastasis in 7 infants. These families have a benign familial megalencephaly. It is important to recognise this so as to avoid unnecessary investigation and anxiety about normal children with large heads.