Significant impact of recurrent respiratory tract infections in children with Down syndrome.

OBJECTIVE: Parents and health professionals believe that recurrent respiratory tract infections (RRTI) have a large impact on children with Down syndrome (DS). We studied the relation between parent-reported RRTI and development, behaviour and health-related quality of life (HRQoL) in 8-year-old children with DS. METHOD: During a 3-year period, 325 children with DS were recruited for inclusion in this observational study. Parents were asked to fill in the Child Behavior Checklist and TNO-AZL Children's Quality of Life Parent Form. A psychological assistant administrated the McCarthy Scales of Children's Abilities. The children were divided into a group with presence of RRTI (RRTI (+) ) and a group without RRTI (RRTI (-) ), on the basis of parental report. Linear regression analyses were performed to assess the effect of RRTI, while correcting for the influence of confounders. RESULTS: Compared with RRTI (-) children (n = 176), RRTI (+) children (n = 149, 46%) showed decreased mental and motor development (mean developmental age 3.67 vs. 4.08 years), more behavioural problems and lower scores on most HRQoL scales (P < 0.05). Moreover, school enrolment is less favourable in RRTI (+) children. CONCLUSION: In 8-year-olds with DS, the children with parent-reported RRTI show more delayed development, more behavioural problems and lower HRQoL compared with the children without RRTI. Although this association does not prove a causal relationship, further studies should focus on this, because RRTI are potentially preventable.

[Smoking during pregnancy: trends between 2001 and 2010]. / Roken tijdens de zwangerschap: trends in de periode 2001-2010.

OBJECTIVE: To establish trends in the prevalence of smoking during pregnancy between 2001 and 2010 and to relate these to differences in educational gradient in the Netherlands. DESIGN: National surveys. METHOD: In 2001, 2002, 2003, 2005, 2007 and 2010, 28,720 questionnaires were handed out to mothers with infants aged up to 6 months at periodic check-ups at well baby clinics. A total of 16,358 (57%) mothers completed this questionnaire. RESULTS: Between 2001 and 2010, the number of women who smoked daily during their pregnancy dropped by half. In 2010 6.3% (95% CI: 5.0-7.6) smoked. The prevalence of smoking was highest among mothers with a low level of education (13.8% in 2010; 95% CI 9.3-18.4%) and lowest among mothers with a high level of education (2.4% in 2010; 95% CI 1.2-3.6). Four percent of pregnant smokers stopped smoking during pregnancy. Women limited the median number of ten cigarettes per day during the six months prior to pregnancy to five per day during pregnancy. The difference in prevalence of smoking in pregnancy between women with a low level of education and those with a high level of education was 18.9% in 2001 and 11.4% in 2010. The difference in smoking prevalence between mothers with an average level of education and mothers with a higher level education was 6.5% in 2001 and 5.4% in 2010. CONCLUSION: Between 2001 and 2010, the percentage of women who smoked throughout pregnancy dropped by half. In 2010, 6.3% of Dutch pregnant women were still smoking. The prevalence of smoking differed strongly between different levels of education and this difference did not change during the study.

Unchanged prevalence of Down syndrome in the Netherlands: results from an 11-year nationwide birth cohort.

OBJECTIVE: This study aims to evaluate trends in prevalence of Down syndrome (DS) births in the Netherlands over an 11-year period and how they have been affected by maternal age and introduction of prenatal screening. METHOD: Nationwide data of an 11-year birth cohort (1997-2007) from the Netherlands Perinatal Registry were analyzed. First-trimester combined screening was introduced in 2002, free of charge only for women 36 years of age or older and only on patients' request. Changes in maternal age, prevalence of DS births, and rates of births at <24 weeks (legal limit for termination of pregnancy in the Netherlands) during the study period were evaluated using logistic and linear regression analyses. RESULTS: In total, 1,972,058 births were registered (91% of the births in 1997-2007). Mean prevalence of DS was 14.57 per 10,000 births (95% confidence interval 14.43; 14.73); 85% of DS were live births. No significant trend in overall prevalence of DS births was observed (p = 0.385), in spite of a significant increase of mean maternal age during the same period (p < 0.001). The increased prevalence of DS births at ≥ 24 weeks among women ≥ 36 years of age (p = 0.011) was offset by a significant increase in the proportion of DS births at <24 weeks among women aged <36 years (p = 0.013). CONCLUSION: The proportion of DS births in the Netherlands has not changed during the period 1997-2007.

One-third of the new paediatric patients with sickle cell disease in The Netherlands are immigrants and do not benefit from neonatal screening.

OBJECTIVES: To estimate the prevalence of children with sickle cell disease (SCD) in The Netherlands. To estimate the annual number of children newly diagnosed as having SCD and the proportion with diagnoses through neonatal screening To estimate the proportion of children with SCD receiving paediatric care in a comprehensive care setting. DESIGN: Data from two sources, a survey of paediatric practices (n=107) and a laboratory database (n=20), were analysed by the capture-recapture method. PARTICIPANTS: Children with SCD aged <18 years, either born before 2003 or newly diagnosed as having SCD between 2003 and 2007. MAIN OUTCOME MEASURES: Prevalence, annual number of children newly diagnosed as having SCD, proportion of children with diagnoses through neonatal screening, proportion of children receiving paediatric care. RESULTS: The prevalence of SCD in children living in The Netherlands on 1 January 2003 was 1:5152 (95% CI 1:4513 to 1:6015). In the next 4 years, the annual incidence was 1:2011 (95% CI 1:1743 to 1:2376). Nearly one-third (27%) of the children newly diagnosed as having SCD immigrated to The Netherlands after birth and would, therefore, be missed by the neonatal screening programme. Approximately 60% of all children with SCD were not reported by paediatricians. CONCLUSION: The number of children with SCD in The Netherlands is much higher than previously estimated, and the majority of these children seem not to be reviewed regularly by a paediatrician. Children born abroad (27% of new cases) do not benefit from neonatal screening and are at high risk of life-threatening complications before SCD is diagnosed. As this introduces disparities in healthcare, the initiation of adequate measures should be considered.

[Slight decrease in the prevalence of smoking around pregnancy]. / Licht dalende prevalentie van roken rondom de zwangerschap.

OBJECTIVE: To establish smoking prevalence of fertile-aged women; before and during pregnancy, and 6 months after delivery. DESIGN: Cross-sectional. METHOD: Yearly surveys by questionnaires handed out during 2001-2003 to mothers visiting a Well Baby Clinic with infants aged 0-6 months. RESULTS: Out ofa total of 14,540 questionnaires, 9133 (63%) were completed and returned. Before pregnancy 25% of all the women concerned smoked, 6% stopped 6 months before getting pregnant; this percentage rose between 2001 (5%) and 2003 (7%). During pregnancy, 14% of the women smoked. This percentage was significantly lower in 2002 and 2003 (13%) compared to 16% in 2001. 11% smoked while pregnant (average 5 cigarettes daily), and 3% stopped some time during pregnancy. Of the mothers who quitted smoking before or during pregnancy, two thirds did so permanently. Nevertheless 15% of all women smoked during the first half year after delivery. This percentage was lowest in 2003 (14%) and highest in 2001 (17%). 28% of all mothers with infants aged 0-6 months had partners who smoked (daily 10 cigarettes average), these women were more likely to start smoking again (RR: 2). CONCLUSION: Minor positive changes were observed within the study period. A smoking partner contributed to smoking relapse after delivery.

Ethnic differences in the timely diagnosis of children with Type 1 diabetes mellitus in the Netherlands: clinical presentation at onset.

AIMS: Little is known about ethnic differences in the timely diagnosis of Type 1 diabetes mellitus (Type 1 DM). This study aimed to assess ethnic inequalities in the timely diagnosis of Type 1 DM, as indicated by a more adverse clinical condition at onset. In addition, we assessed whether these differences could be explained by differences in socio-economic status. METHODS: From a national register, we selected 3128 children aged < 15 years with newly diagnosed Type 1 DM. Ethnic differences in serum glucose, blood pH, bicarbonate, presence of ketonuria, level of consciousness, hydration status,and diabetic ketoacidosis were assessed by logistic regression. A measure of socioeconomic status based on postal codes was used as an explanatory variable. RESULTS: The risk of adverse clinical presentation was 1.5-2 times higher in non-Western immigrants than Dutch children, while Western immigrant children did not differ from Dutch children. Blood pH, bicarbonate level, and level of consciousness were lower in Turkish and Antillean children in particular. The adverse socio-economic position of immigrant children contributed very little to these differences in clinical presentation. CONCLUSIONS: Non-Western children were likely to be sicker at first presentation of Type 1 DM, and thus diagnosis may have been delayed. These disparities were not accounted for by differences in socio-economic status. Possible explanations may be difficulties in recognition of symptoms, failure of GPs to take symptom reporting seriously and lack of awareness of the fact that Type 1 DM occurs more often in certain ethnic groups.

[Weight loss, serum sodium concentration and residual symptoms in patients with hypernatremic dehydration caused by insufficient breastfeeding]. / Gewichtsverlies, serumnatriumconcentratie en restverschijnselen bij patiëntjes met hypertone dehydratie door onvoldoende borstvoeding.

OBJECTIVE: To determine the relationship between serum sodium concentration and weight loss as well as residual symptoms in newborns with hypernatremic dehydration caused by insufficient breastfeeding; and to determine the sensitivity of the following rule of thumb 'if weight loss is less than 10%, the baby does not have hypernatremic dehydration caused by insufficient breastfeeding'. DESIGN: Systematic literature search. METHOD: Medline was searched using the terms 'dehydration AND breastfeeding' for case reports on patients with 'hypernatremic dehydration caused by insufficient breastfeeding'. Reference lists from the articles retrieved were also searched. Articles published in 1970-2004 in Dutch, English, French, and German were included. All cases that the author diagnosed as 'hypernatremic dehydration caused by insufficient breastfeeding' were included. RESULTS: A total of 47 articles were found, containing 128 relevant cases. Of these, 9 had less than 10% weight loss. Therefore, the sensitivity of the 10% rule was 93%. We found a linear relationship between the degree of weight loss and serum sodium concentration (Pearson's correlation coefficient = 0.71; p < 0.001). For every 10% increase in weight loss, the serum sodium concentration increased by 16 mmol/l (95% CI: 13-19). As the serum sodium concentration increased, the prevalence of residual symptoms increased. No residual symptoms were reported in patients with less than 10% weight loss. CONCLUSION: A relatively strong linear relationship was found between weight loss and serum sodium concentration. If the weight loss was more than 10%, the serum sodium concentration was beyond the range of normal values. The rule of thumb had a high sensitivity; however, the specificity should be determined before the rule of thumb is implemented.

Cost-effectiveness of different treatment strategies with intrapartum antibiotic prophylaxis to prevent early-onset group B streptococcal disease.

OBJECTIVE: To estimate the costs and effects of different treatment strategies with intrapartum antibiotic prophylaxis to prevent early-onset group B streptococcal (GBS) disease in the Netherlands. The treatment strategies include a risk-based strategy, a screening-based strategy, a combined screening/risk-based strategy and the current Dutch guideline. DESIGN: Cost-effectiveness analysis based on decision model. SETTING: Obstetric care system in the Netherlands. POPULATION/SAMPLE: Hypothetical cohort of 200,000 neonates. METHODS: A decision analysis model was used to compare the costs and effects of different treatment strategies with no treatment. Baseline estimates were derived from literature and a survey among parents of children affected by GBS disease. The analysis was performed from a societal perspective, and costs and effects were discounted at a percentage of 3%. Main outcome measures Cost per quality adjusted of life-year (QALY). RESULT: The risk-based strategy will prevent 352 cases of early-onset GBS for 5.0 million Euros, indicating a cost-effectiveness ratio of 7600 Euros per QALY gained. The combined screening risk-based strategy has comparable results. The current Dutch guideline resulted in lower effects for higher costs. The screening-based strategy shows the highest reduction in cases of early-onset GBS, however, at a cost-effectiveness ratio of 59,300 Euros per QALY gained. Introducing the polymerase chain reaction (PCR) test may lead to a more favourable cost-effectiveness ratio. CONCLUSION: In the Dutch system, the combined screening/risk-based strategy and the risk-based strategy have reasonable cost-effectiveness ratios. If it becomes feasible to add the PCR test, the cost-effectiveness of the combined screening/risk-based strategy may even be more favourable.

[The incidence and initial symptoms of diabetes mellitus type 1 in 0-14-year-olds in the Netherlands, 1996-1999]. / De incidentie en de eerste symptomen van diabetes mellitus type 1 bij 0-14-jarigen in Nederland, 1996-1999.

OBJECTIVE: To determine the incidence and characteristics of type-1 diabetes mellitus (DM) in children aged 0-14 years during the period 1996-1999 and to compare this with previous measurements of the incidence. DESIGN: Descriptive. METHOD: Data were collected via reports from all practicing paediatricians to the Dutch Paediatric Surveillance Unit and a questionnaire among members of the Dutch Diabetes Association. The incidence was calculated by the capture-recapture method, and the characteristics and symptoms of the children were determined from the questionnaires. RESULTS: The incidence of DM type 1 among 0-14-year-olds increased to 18.6/100,000/year (95% CI: 17.7-19.4) compared to 11.1/100,000/year (10.5-11.7) in 1978-1980. The increase was highest in the youngest age group, 0-4 years. DM type 1 was diagnosed at an average age of 7.6 years (7.4-7.9) and in 1988-1990 at 9.2 years (9.0-9.5). The boy-girl ratio also increased. Children with a mother from Surinam, Turkey or The Netherlands Antilles had lower risk of DM type 1 while a higher risk was calculated for children from Moroccan and Somali mothers. In comparison with 1993-1994, there were less frequent lethargy or dehydration; lower average serum-glucose values, a better blood pH and less frequent ketonuria at the time of diagnosis. Treatment on an outpatient basis had increased. However, over the time span 1993-1999, Moroccan children (n = 108) showed dehydration, ketonuria and low blood-pH values more frequently than children of Dutch parents (n = 1825) and their hospital admission lasted longer. CONCLUSION: The incidence of DM type 1 had increased and the disease manifested itself at a younger age. The clinical condition at time of diagnosis, however, was better. The incidence and clinical characteristics differed between children of different ethnic origin.

Sudden infant death syndrome in child care settings in the Netherlands.

BACKGROUND: In the Netherlands, there is a very low incidence of sudden infant death syndrome (SIDS) due to effective preventive campaigns. METHODS: During the period September 1996 to August 2002, nationwide 161 deaths from SIDS (about 85% of all cases of SIDS during that time) were investigated by the Cot Death Committee of the Dutch Paediatric Association. RESULTS AND DISCUSSION: Over 10% of cases of SIDS took place during some type of child care. From a national survey carried out in 2000/01 information was available on the child care attendance of 2000 Dutch infants aged 3-6 months. Based on the hours usually spent in child care by these infants, the number of similarly aged infants that died from SIDS while attending child care was 4.2 times higher than expected. Remarkably, the prevalence of known risk factors for SIDS, such as sleeping position and parental smoking, was favourable in the SIDS cases in child care settings. The adherence of child care facilities to the safe sleeping recommendations is high in the Netherlands, and no explanation as to why child care settings may be associated with an increased risk of SIDS is apparent. The possibility of other explanations, such as stress and change in routine care, is hypothesised.

[Optimal medical care for children with Down syndrome and their parents]. / Optimale zorg voor kinderen met het Down-syndroom en voor hun ouders.

Children with Down's syndrome have an increased risk of congenital anomalies and additional medical problems. These can be treated but are often seen as part of the syndrome and not as the cause of developmental retardation. Based on the current level of knowledge, specific medical tests and evaluations are recommended. The reasons for these guidelines, composed by the Down's syndrome Work Group of the Paediatric Association of the Netherlands, are illustrated by the case reports of five patients: in a 4-year-old boy, retardation improved after celiac disease had been diagnosed. In a 5-year-old boy, slow speech development was reversed after hearing loss was diagnosed. In a 2-year-old girl, development improved after a mitral valve stenosis had been corrected. In a 6-month-old boy, drinking problems were reversed when torticollis was diagnosed and a self-deflating drinking bottle was introduced. An adult man suffering from epilepsy and from self-mutilative rubbing and hitting of his eyes, regained his sight after cataract, myopia and atrophy bulbi were diagnosed. A well-balanced disclosure of the diagnosis, repeated medical screening, early motor training and social interventions combined with active parental participation, warrant optimal development. In cooperation with the Down's syndrome Parent Association, multidisciplinary medical teams have been established to offer and promote this care.

[Unobserved death of an infant: cot death?]. / Een onverwacht overleden zuigeling: wiegendood?

Three children, two girls aged 8 and 12 months and one boy aged 7 weeks, were found dead unexpectedly. Autopsy revealed pneumonia in two children, following which the diagnosis of 'natural, explained death' was made; one child showed no abnormalities and the diagnosis read 'natural, unexplained death' (cot death). Autopsy may currently only be performed with parental permission or, in case of doubt about unnatural cause of death, by order of the public prosecutor. The authors propose routine performance of a protocolled autopsy by GP, pediatrician, pathologist and medical examiner in order to avoid subsequent and possibly incorrect doubt about the cause of death.

Growth characteristics in laboratory animals fed zinc-deficient, copper-deficient, of histidine-supplemented diets.

The effects of growth in male Wistar rats and female Swiss Random mice were studied during dietary zinc (Zn) deficiency, copper (Cu) deficiency, and during the feeding of a histidine (His) supplement Growth was analyzed by comparing the characteristics of the decreasing exponential growth curve plotted for the experimental period. When the animals were pair-fed the experimental diets, the growth pattern in the animals remained unaltered. The growth rate decreased during Zn deficiency by a factor of 0.64 over a period of 10 d (male young adult rats) and by a factor of 0.76 over a period of 28 d (female weaning mice). On the other hand, a supplement of His increased the growth rate by a factor of 1.11 (in the mice). The effect of Cu deficiency on the growth rate was not statistically significant (in the rats). However, Cu deficiency causes effects in the Zn status that may over-compensate minor growth retardation during Cu deficiency. The effect of the His supplement is explained by its having an effect on the Zn-absorption (His enhancing Zn transport over the gut) and by a stimulating effect of this amino acid on the thickness of the growth plate in bone.

Familial thrombocytosis in infancy presenting with a leukaemoid reaction.

Familial thrombocytosis (FT) is a hereditary disorder probably involving the regulation of megakaryopoiesis. This report is the first documented case of FT in infancy. The clinical course was complicated by a leukaemoid reaction which lasted for several months, in combination with failure to thrive and hepatosplenomegaly. At the age of 5 years the patient, with the exception of thrombocytosis, is healthy and without medication.

Clinical and laboratory assessment of zinc deficiency in Dutch children. A review.

The clinical spectrum of acrodermatitis enteropathica (n = 226) is compared with symptoms reported in other Zn deficiencies: total parenteral nutrition without Zn (n = 21), protein energy malnutrition (n = 24), gastrointestinal disease (n = 79), geophagia (n = 227), and dietary low intake (n = 23). Common features of deficiency are diarrhea, recurrent infection, and growth retardation. Dermatitis is less common in other types of deficiency than in acrodermatitis enteropathica (9 vs 88% of cases). Anorexia and/or hypogeusia is reported more frequently in the other types of deficiency (30 vs 16%). The main symptoms in acrodermatitis enteropathica vary with age. These differences in the clinical picture of Zn deficiency are discussed in relation to the degree of the deficiency (acute, subacute, or chronic; severe, mild, or subclinical). The results of the conventional laboratory tests to diagnose Zn deficiency (Zn levels in serum, urine, or hair) are reviewed. In healthy Dutch infants and children, the mean values of these levels vary by a factor of 1.6-3.0. Also, the clinical interpretation of their results is prone to errors. Therefore, we advocate the erythrocytic 65Zn uptake test. Its mean varies by 1.3. However, its reference values for different age intervals need to be established. From the comparison of the results of three conventional tests of samples taken concurrently (serum, urine, and hair) in groups of Dutch children with symptoms common in Zn deficiency (diarrhea, recurrent infection, or growth retardation), it is estimated that +/- 1% of Dutch children with minor complaints suffer from either acute or subacute Zn deficiency. Other deficiencies occur occasionally. In order to detect the individual patient with deficiency, the erythrocytic 65Zn uptake test is promising and needs to be evaluated. Therefore, we review a set of reference laboratory tests with results that alter during sequential stages of overload and deficiency. Such a scheme is advocated as a guidance for future clinical research on deficiency, and solves the problem of differentiating those conditions that identify the individual patients who need treatment by supplementation.

Carnitine deficiency during valproic acid treatment.

Prolonged valproic acid treatment results in secondary carnitine deficiency. In thirteen children paired samples of plasma were drawn at the onset of, and after 9 months of continuous valproic acid treatment. At onset free plasma carnitine values were age dependent; they increased during childhood (r = 0.59, p = 0.016). After 9 months: 1 - mean plasma free carnitine decreased by 40%, from 32.7 mumol/l to 20.9 (p 0.0008 and 3% overlap; 2 - plasma total carnitine decreased by 20%, from 34.9 mumol/l to 27.1 (p 0.016 and no overlap); and 3 - the esterified/free carnitine ratio increased by 40%, from 0.28 to 0.39 (p 0.011 and no overlap). In two out of thirteen patients clinical symptoms were observed, fatigue, besides the biochemical evidence of carnitine deficiency. In four others only biochemical deficiency was found. If the child complains of fatigue during prolonged valproic acid treatment, it is advised to supplement carnitine. A dose of 15 mg/kg body weight is effective to reverse the clinical symptoms of carnitine deficiency within a week. The dose to prevent deficiency is not yet established.

Dietary subacute zinc deficiency and potassium metabolism.

In a controlled animal experiment the effects of dietary subacute Zn deficiency on growth, Zn concentration, and tissue 42-K distribution were studied. Growth retardation caused lower body weight because both skeletal and heart muscle showed a reduction in cell mass. Zn concentrations were reduced in most tissues, however, they remained unaltered in heart muscle. 42-K activity increased in skeletal muscle and pancreas. We hypothesize the latter reflects the organs rate of metabolism, inducing the exocrine pancreas to increase Zn absorption; in skeletal muscle it may induce also alterations in cell potentiation, causing restless behavior. As suggested by the calculated specific K activity (Bq/mol), the K uptake was highest in liver and bone, high in pancreas and skeletal muscle and low in heart muscle. The latter suggests K retention in heart muscle. Specific activity in plasma and jejunum remained unaltered: K status and absorption seem unaffected. Zn deficiency causes different 42-K activities in the various tissues, that respond by alterations in K metabolism without the induction of K deficiency.

The role of the pancreas in the regulation of zinc status.

A low Zn diet resulted in subacute Zn deficiency in young rats. Thirty minutes after the intubation of a trace 65-Zn we determined the total tissue Zn activity in plasma, erythrocytes, liver, pancreas, bone, muscle, and proximal jejunum. Assuming the body behaved like a closed multicompartmental system in steady state, we estimated the initial Zn exchange between plasma, and the erythrocytes or these tissues. In comparison with control animals the exchanges between plasma and erythrocytes or pancreas increased threefold during subacute Zn deficiency. In the pancreas the ratio also reversed from < 1.0 to > 1.0. This confirmed earlier observations that the specific activity (kBq 65-Zn/mol Zn) increased mostly in the pancreas. By increased net Zn uptake during subacute deficiency, the pancreas Zn content remained constant in chronic Zn deficiency. We discussed the regulation of the Zn status by the pancreas. We hypothesize that the exocrine pancreas modulates Zn absorption by an exocrine ligand that enhances absorption in the jejunum during subacute deficiency: Unsaturated with Zn it binds dietary intraluminal Zn and increases the Zn absorption. The literature provides evidence in confirmation. This hypothesis explains also conflicting data on the inherited Zn malabsorption syndrome Acrodermatitis Enteropathica.