Abstract: Aims: To estimate the incidence and clinical characteristics in hospital admissions due to dehydration or undernutrition and their laboratory evaluation and treatment outcome in exclusively breastfed infants. Methods: All hospital admissions during the first 3 months of life assessed by the Dutch Paediatric Surveillance Unit (DPSU) between mid 2003 and mid 2005. Results: Nationwide 158 cases reported, correspond to an incidence of 58/y/100 000 breastfed infants; it is lower for severe dehydration at risk for hypernatraemia; 20/y/100 000. Sixty-five per cent of cases were <2 weeks old, their median weight loss was 9.3% and median age at admission 5 days; Serum sodium value was measured in only 12% of all cases. Insufficient volume intake and inadequate growth were most frequently reported (61% and 41%). Lethargy, jaundice or clinical dehydration was scored in 11-25%, seizures or shock in 3%. A breast pump at home was used in only 31%. In the hospital breast pumps were available (82%) as lactation consultants (73%). For treatment 65% was offered formula, in 30% by nasogastric drip. Most admissions lasted up to 3 days, all recovered fully and 33% were breastfed exclusively at discharge. Conclusion: The incidence of severe dehydration in the Netherlands is relatively low. With extended use of breast pumps at home it could be lower. To prevent complications, we recommend applying a reference weight chart, a full clinical examination and more extensive screening of serum sodium and glucose.
Abstract: AIM: The aim of this study was to gain insight into contraception practised and related to breastfeeding duration. METHODS: Mothers with infants up to 6 months received a questionnaire on infant feeding (breast or formula feeding) and contraception (hormonal or non-hormonal methods). Estimates of the time interval between resuming contraception and cessation of lactation was calculated by Chained Equations Multiple Imputation. RESULTS: Of all women (n = 2710), 30% choose condoms, 22% the combined oral contraceptive pill (OCP) and few other methods. Breastfeeding was started by 80%, and 18% continued up to 6 months. Of the breastfeeding mothers, 5% used hormonal contraception; 7% of women who used hormonal contraception practised breastfeeding. After adjustment for background variables, the use of OCP is strongly associated with formula feeding: after delivery to the third month postpartum, the crude OR being 17.5 (95% CI: 11.3-27.0), the adjusted OR 14.5 (9.3-22.5); between the third and sixth month postpartum, respectively, 13.1 (95% CI: 8.6-19.9) and 11.7 (7.6-17.9). Of all breastfeeding women, 20-27% resumed OCP at 25 weeks postpartum and 80% introduced formula feeding. The time lag between these events is 6 weeks. Hormonal contraception was resumed after formula introduction. CONCLUSION: Mothers avoid hormonal contraception during lactation; they change to formula feeding 6 weeks before they resume the OCP. To effectively promote longer duration of breastfeeding, the BFHI needs to address contraception as practised.
Abstract: OBJECTIVE: To determine the prevalence, neonatal characteristics, and first-year mortality in Down syndrome (DS) among children in The Netherlands. STUDY DESIGN: The number of DS births registered by the Dutch Paediatric Surveillance Unit (DPSU) in 2003 was compared with total live births (reference population) and perinatal registrations. RESULTS: The prevalence of DS was 16 per 10,000 live births. Compared with the reference population, the 182 children with trisomy 21 had a gestational age of 38 weeks versus 39.1 weeks (P < .001), a birth weight of 3119 g versus 3525 g in males (P < .001) and 2901 g versus 3389 g in females (P < .001), and mothers with a parity of > or = 4.17% versus 5% (P < .001) and a mean age of 33.6 years versus 31 years (P < .001) and 33% (n = 54) > or = 36 years). The mean age of DS diagnosis was 10.2 days in nonhospital deliveries and 1.8 days in hospital deliveries (P < .001). Children with DS were less often breast-fed (P < .05), and 86% (n = 156) were hospitalized after birth. Neonatal and infant mortality were higher in DS, 1.65% versus 0.36% (P < .02) and 4% versus 0.48% (P < 0.001), respectively. CONCLUSIONS: The prevalence of DS in The Netherlands exceeds previously reported levels and is influenced by the mother's age. Neonatal and infant DS mortality have declined, but still exceed those in the reference population.
Abstract: This prospective study of 4438 infants (0-4 months) examined differences in infant-feeding patterns in relation to the ethnic origin of their mothers, based on the mother's native language: Dutch (87%), Turkish (4%), Moroccan (3%), other European languages (3%), and various other languages (4%). Breastfeeding at birth varied between 75% and 94%. Dutch and Moroccan mothers breastfed for a shorter period (32% and 37% at 4 months, respectively) than did Turkish mothers and mothers with a native European language other than Dutch (47% and 51% at 4 months, respectively; P < .001). Of all mothers, 71% started exclusive breastfeeding at birth, and 21% continued exclusive breastfeeding for at least 4 months. The reasons why mothers discontinued breastfeeding (both exclusive breastfeeding and breastfeeding) were generally infant related. The average weight gain between birth and day 133 was 3.45, 3.87, and 3.69 kg for Dutch, Turkish, and Moroccan infants, respectively. Weight gain was influenced by ethnicity of the mothers and exclusive breastfeeding.
Abstract: BACKGROUND: Within the context of the obesity epidemic identifying young adults at risk for type 2 diabetes and cardiovascular disease is important. A practical approach is based on the identification of metabolic syndrome (MetS). Our objective was to develop a simple and efficient stepwise strategy to identify MetS in young adults. METHODS: Subjects were part of a birth cohort (n = 2599) in Terneuzen, The Netherlands, born in 1977-86. In 2004-05: 642 of these young adults participated in a physical examination and blood tests. Tree regression was used to determine the optimal decision strategy to identify MetS. RESULTS: Overall prevalence of MetS, defined according to the NCEP ATPIII, was 7.5%. The tree regression yielded an optimal stepwise strategy that eliminated the need for blood tests for the diagnosis of MetS in 50-90% of the cases, depending on the accepted level of error. A large group (52% of the total) with BMI <35 had a normal waist circumference (WC) and normal blood pressure (BP). None of them had MetS. Subjects with BMI > or =35 all had MetS. If BMI <30, 38% had an increased WC or increased BP with a risk of MetS of only 6%. So for them the omission of blood tests could also be considered. CONCLUSION: In most young adults MetS can be identified or excluded without blood tests by a simple and stepwise strategy, based on the measurement of BMI, WC and BP. This makes it possible to develop simple prevention strategies for young adults at risk for type 2 diabetes and cardiovascular disease.
Abstract: OBJECTIVE: The validity of the rule of thumb that infants may have a weight loss of 10% in the first days after birth is unknown. We assessed the validity of this and other rules to detect breast-fed infants with hypernatraemic dehydration. DESIGN: A reference chart for relative weight change was constructed by the LMS method. The reference group was obtained by a retrospective cohort study. PARTICIPANTS: 1544 healthy, exclusively breast-fed infants with 3075 weight measurements born in the Netherlands and 83 cases of breast-fed infants with hypernatraemic dehydration obtained from literature. RESULTS: The rule of thumb had a sensitivity of 90.4%, a specificity of 98.3% and a positive predictive value of 3.7%. Referring infants if their weight change is below -2.5 SDS (0.6th centile) in the reference chart in the first week of life and using the rule of thumb in the second week had a sensitivity of 85.5%, a specificity of 99.4% and a positive predictive value of 9.2%. CONCLUSIONS: The rule of thumb is likely to produce too many false positive results, assuming that for screening purposes the specificity needs to be high. A chart for relative weight change can be helpful to detect infants with hypernatraemic dehydration.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: AIM: To examine the association of excessive infant crying with maternal smoking during and after pregnancy, paternal smoking, and smoking by other people in the living environment of the infant. METHODS: We collected data on infant crying and smoking in a Dutch national sample of 5845 infants aged 0-3 mo (response 62.8%). We defined excessive crying as crying over 3 h a day on more than 3 d of the preceding week. RESULTS: The prevalence rate of excessive crying was 4.0% (95% CI 3.5 to 4.5%). Excessive crying occurred more frequently among infants of fathers smoking 15 + cigarettes/d (odds ratio (OR) 1.99, 95% CI 1.38 to 2.86) and of mothers smoking 10 + cigarettes/d during pregnancy (OR 1.86, 95% CI 1.02 to 3.42). Infants whose parents were heavy current smokers or whose mothers had been so during pregnancy had a 69% higher prevalence of excessive crying than infants of non-smoking parents (rates: 6.3% and 3.7%, respectively; odds ratio 1.80; 95% CI 1.26 to 2.57). CONCLUSION: Parents stopping smoking may prevent excessive infant crying.
Abstract: AIM: The aim of the study was to describe infant feeding practices and associated factors, and to explore mothers' main reasons for starting and stopping breastfeeding. METHODS: We performed a national inquiry into milk feeding practices among 9133 Dutch infants aged < 7 mo by means of a questionnaire. RESULTS: 78% of mothers initiated breastfeeding. At 1 and 4 mo, respectively, 51 and 25% of infants were fed primarily on human milk; after 6 mo, only 15% of mothers still provided human milk as the only source of milk feeding. During the whole 6-mo period, another 11 to 18% was fed on both breast and formula milk. Women initiating breastfeeding were more likely to be higher educated, have a higher-educated partner, be non-smokers, have a full-time job, and be primiparous. In addition, breastfeeding initiation rate was higher for women born outside the Netherlands. Longer duration of breastfeeding was mostly found amongst higher-educated, non-smoking women. The odds for continuation of breastfeeding after 4 mo increased when mothers' working hours did not exceed 16 h/wk. Infant delivery at home was associated with a higher initiation rate as well as longer duration of breastfeeding compared to hospital delivery. Infants born after 38 wk of gestation, with a birthweight of 3500 g had higher odds to be breastfed for a longer period. CONCLUSION: Only a minority of Dutch infants is breastfed for 6 mo. Maternal and infant characteristics are important predictors of breastfeeding initiation and duration.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: Total Serum Zinc (TSZn) and albumin were determined, and low molecular weight serum Zn measured by radiochemical UltraFiltration (UFSZn) in healthy Dutch infants and children, and in samples obtained from those with diseases that are expected to alter TSZn. Our control TSZn values, 10.2 +/- 3.5 mumol/L, were low compared to those reported in the literature. Variation in serum albumin could not explain this: No correlation of TSZn with serum albumin was found (p > 0.5). Likely explanations are the nonfasting state and the stress owing to hospital surroundings at the time of sampling. A range of other influences not registered may be active and are discussed. No significant age-dependence was found (p < 0.8). Boys over 9 yr of age showed higher TSZn compared with girls of the same age (p < 0.08). In a separate experiment a 17% decrease in TSZn was demonstrated by food intake (eggs). These results support the opinion that TSZn is of little value to measure Zn status. There was no discrimination in TSZn between healthy subjects and patients. Our UFSZn values, 0.28 +/- 0.13 mumol/L in the controls as well as in the patients, were correlated with TSZn and therefore not a suitable alternative for the measurement of TSZn as parameter to determine the Zn status. The UFSZn was not correlated with serum albumin (p < 0.7). UFSZn values were higher in infants (p < 0.01), no sex dependence was found. We conclude that TSZn as well as UFSZn are of limited clinical relevance.
Abstract: 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.
Abstract: In 20 Dutch children with acute lymphoblastic leukemia (ALL), Cu and Zn levels in cerebrospinal fluid (CSF) were studied during standard treatment (Protocol ALL-BFM-86/SNWLK-ALL-VII). CSF-Cu in 10 controls was 0.04 +/- 0.02 mumol/L, lower compared to values in adults. At the moment of diagnosis, CSF-Cu values were higher, 0.06 +/- 0.03 mumol/L, and during maintenance therapy lower, 0.01 +/- 0.01 mumol/L. Children with central nervous system (CNS) involvement ALL as judged by CAT Scan and EEG--in addition to cytology--showed lower CSF-Cu values compared to children without. CSF-Zn values were also measured. CSF-Zn was 0.05 mumol/L and did not vary. Cu/Zn molar ratios were increased at the onset of treatment, and decreased during maintenance therapy. The changes in CSF-Cu may follow the natural course of the disease or may relate to the success of treatment, reflecting a decrease of leukemia activity. Another explanation concerns a risk of CNS damage by low CSF-Cu causing neuron dysfunction. Conditions necessary for the interpretation of these results into a clinical strategy for followup study are outlined.
Abstract: In adult rats, the influence of vitamin E deficiency on zinc metabolism in general and specifically in 15 tissues was studied. After 50 days, we found evidence of vitamin E deficiency and at this time point we injected a tracer amount of 65Zn. During the next 18 days the zinc status was unaffected. The zinc metabolism, however, was altered: the apparent retention increased and the biological half life was prolonged. On day 68, the changes in various tissues varied. Some tissues were affected in zinc concentration (higher in plasma and spleen; lower in cerebrum, fur and tail), others in specific activity (higher in pancreas; lower in cerebellum). The different effects may reflect differences in tissue response on impairement, caused by vitamin E deficiency.
Abstract: A young girl with recurrent upper respiratory tract infection showed minor skin lesions and was found to suffer from acrodermatitis enteropathica. She responded dramatically to treatment with zinc sulphate. We review the signs and symptoms and their reported frequencies in 196 reported patients. The classical triad, dermatitis, alopecia and intractable diarrhoea is present in only 20% of the cases. Their intermittent occurrence and the vast range of other, also misleading symptoms, may cause a diagnostic problem. Treatment is effective, safe and simple: 3 to 30 mumol zinc per kg per day. Attention should be paid to sorbitol, added to the standard Dutch zinc sulphate prescription. It may induce diarrhoea.
Abstract: In 47 children with malignancy, zinc status, growth, and performance during standard treatment were compared with those in controls. At diagnosis, growth was retarded and hair zinc values were high, 2.4 +/- 0.7 mumol/g, as in chronic deficiency. During induction therapy, serum declined to 10.4 +/- 2.3 mumol/L and urinary excretion increased to 5.3 +/- 2.8 mumol/mol creatinine, as in acute exacerbation of deficiency. Control CSF values in children in remission, 0.04 +/- 0.01 mumol/L, were lower than reference values in adults. No difference in mean CSF zinc was observed during therapy, or in those with acute lymphoblastic leukemia (1) at high risk, (2) with central nervous system involvement, (3) with low performance, or (4) resistant to therapy. In six children unexplained values, up to 0.28 mumol/L during induction, were measured. No correlations between the various zinc parameters were found.
Abstract: Male weaning rats were pair-fed a low-zinc diet or a control diet. After 10 d, the animals fed the low-zinc diet showed physiologic signs of deficiency; however, they showed no clinical symptoms. Their estimated whole body zinc was 25 mumol versus 39 mumol for the controls. The 65Zn absorption increased 2-fold and the tissue distribution altered: muscle and erythrocytes contained more, small intestine and liver less activity at 0.5 h postdose. In vitro, the erythrocyte 65Zn uptake rate increased also. The 65Zn uptake experiments required small quantities of erythrocytes. The difference observed between the deficient and control cells was significant and showed little overlap. The increase of the 65Zn uptake from a medium was not affected when the animals underwent endotoxin exposure 24 h before, as was reported to occur in whole blood 65Zn uptake. Therefore, we suggest the in vitro erythrocyte 65Zn uptake, performed in a standardized, near physiologic medium, to detect early, subclinical zinc deficiency.
Abstract: In fetus with a mean gestational age of 18 weeks (range 15-25, n = 14), zinc and copper concentrations in liver, femur, rib, and skeletal muscle were measured. Zinc and copper concentrations are highest in liver. A trend of decreasing liver zinc concentrations during gestational age is suggested. Zinc concentrations are significantly correlated with copper concentrations in liver and in femur, suggesting steady growth in both organs. Femur zinc values rank ca. 30% of those in liver, femur copper, ca. 2%. Zinc or copper concentrations in rib are of the same levels as in skeletal muscle. Their concentration for zinc ranks ca. 20%, for copper, ca. 5% of the values in liver. All zinc and copper values are lower than reported in third trimester fetal organs. Calculated zinc/copper molar ratios are distinctive for the various organs: in liver, 6 +/- 1, in femur, 73 +/- 8, and in soft tissues, 26 +/- 3. Calculated ratios from published values obtained from the third trimester of pregnancy show that the ratios in liver and skeletal muscle maintain these levels. The zinc/copper molar ratio can serve as an internal reference in zinc and/or copper measurements.
Abstract: The effects of histidine on the zinc status are controversial. In mice, we studied the effects of a moderate histidine supplement on the regulation of the zinc status using subcutaneously administered 65Zn. In animals fed a zinc-adequate diet, histidine supplement did not cause changes in the zinc status (zinc concentrations, 65Zn tissue distribution, and tissue specific activities). Neither effects on the regulation of the zinc status (65Zn retention, excretion and biological half-life) could be demonstrated. However, the combination of a low zinc diet and moderate histidine supplementation caused changes in the regulation of the zinc status (lower 65Zn retention, associated with increased fecal excretion and a shorter biological half-life), aggravating the dietary deficiency (lower bone zinc, a shift in the 65Zn tissue distribution). Reviewing the literature, it seems that only a molar histidine/zinc ration of 2,000 or higher will cause zinc deficiency.
Abstract: Exchangeable erythrocytic zinc is measured by 65Zn uptake in and release from erythrocytes under standardized and near, physiological conditions: 7.6 microM zinc and 580 microM albumin in the medium. The intracellular exchangeable erythrocytic zinc pool in healthy volunteers amounts to 5 mumol zinc/L packed cells. The half-time of the exchange is 7 h, its activation energy 84 kJ/mol. The effects of the variation in temperature and the concentrations of albumin, as well as the effects of some zinc carriers, cell transport inhibitors, and stress hormones on the 65Zn uptake are measured.
Abstract: To establish a parameter for zinc status that is independent of the occurrence of infection, we studied the effects of low dietary zinc and endotoxin in weaning rats 21 d after 65Zn intubation. We monitored aspects of zinc status (tissue zinc content, 65Zn distribution, and specific 65Zn activity in tissue) and 65Zn metabolism (absorption, excretion, and biologic half-life), as well as weight gain, feed conversion, and dietary zinc use. The low zinc diet induced classical deficiency with losses of bone zinc, resulting in lower content (7.4 versus 19.6 mumol) and higher spec act (17 versus 8 kBq/mumol). Other tissue-specific and plasma-specific activities were also higher (overall, 20 versus 8 kBq/mumol; plasma, 8 versus 4 kBq/mumol). Endotoxin caused lower total-plasma zinc (0.04 versus 0.05 mumol) but did not affect spec act (4 kBq/mumol); combined endotoxin and low-zinc diet caused low total-plasma zinc (0.01 mumol) and high spec act, as did the low-zinc diet alone (12 kBq/mumol). We conclude that plasma-spec act (or stable isotope enrichment) can serve as an index for nutritional zinc status during recurrent infection.
Abstract: The effect of a high concentration (1%, w/w) of ascorbic acid in a Cu-adequate (150 mumol/kg) purified diet was studied in rats. After 6 wk, ascorbic acid had significantly reduced Cu concentrations in muscle and bone. The estimated whole body content of Cu in rats fed ascorbic acid was reduced by 20%. Within 1 d after oral administration of 64Cu, the recovery of the dose in feces was increased in rats fed ascorbic acid, suggesting that the vitamin depresses intestinal absorption of Cu. After intraperitoneal (ip) administration of 64Cu, the rate of loss of the dose from the body was decreased in rats fed ascorbic acid. This study suggests that the ascorbic acid induces a decreased efficiency of intestinal Cu absorption, which in turn triggers mechanisms to preserve Cu in the body stores. This is supported by the observation that the feeding of a Cu-deficient diet (5 mumol/kg) had similar effects, although more pronounced.
Abstract: The influence of either histidine supplement or nutritional Zn deficiency on growth and the organ and tissue Zn content of mice during a 21-d period was compared with a control group. When the histidine intake was increased from 5 to 9 mumol/g body wt/d we noted increased body weight and higher Zn concentrations in liver, pancreas, spleen, and muscle. As a result, the estimated whole body Zn mass increased. This was explained by enhanced utilization of dietary Zn. These results differed from those seen in Zn deficient animals (fed 5 nmol Zn/g body wt/d instead of 29). Dietary Zn deficiency was characterized by anorexia and growth retardation, lower Zn concentrations in pancreas, muscle, bone, tail, and plasma, plus higher Zn concentrations in spleen and fur. As a result, the estimated total body Zn mass was 20% lower than in the control animals, despite a two-to threefold increase in utilization of dietary Zn. These results are discussed in view of the available literature. It is concluded that in humans and in animals both the absorption and the excretion of Zn may be increased by histidine. Below a certain dose the former will prevail, viz., a situation of increased utilization exists, preventing the development of Zn deficiency.
Abstract: Acrodermatitis enteropathica is an inborn error of metabolism resulting in zinc malabsorption and severe zinc deficiency. From personal experience and a literature review the following conclusions were drawn: 1. Symptoms other than dermatitis, vary with age. Diarrhoea, mood changes, anorexia, and neurological disturbance were reported most frequently in infancy. Growth retardation, alopecia, weight loss and recurrent infections were prevalent in toddlers and schoolchildren. Spontaneous remission may occur at adolescence. 2. The severity of symptoms also varies. Intermittent or mild cases of the disease and those presenting with uncommon features such as ophthalmic, cerebral or hepatic involvement, are easily overlooked. In the severe cases this may result in a fatal outcome. If untreated, the overall mortality rate is 20%, being higher in males. 3. The laboratory diagnosis is hazardous. In patients, mean zinc values in serum, urine and hair were ca. 50% of normal levels. There is a 15% overlap with healthy controls; moreover, low zinc levels in serum, urine or hair are also found in other diseases. A more specific test is required. 4. In cases of doubt, in vitro or in vivo zinc absorption tests using radioisotopes (65Zn or 69mZn) may be performed. These appear not to be influenced by other conditions and show less overlap with controls. If such tests are unavailable, the clinical response to 3-30 mumol zinc/kg per day for 5 days may be awaited. This is recommended in infants or children with one or more symptoms of acrodermatitis enteropathica.
Abstract: In order to gain experience about the detection of adverse effects during a scientific procedure, we carried out a clinical examination of rats with zinc deficiency. In weanling rats fed a zinc-deficient diet (30 mumol zinc/kg) for 10 days, the mean tibial concentration of zinc was reduced by 53% and body weight gain by 73% when compared with rats fed a diet containing an adequate amount of zinc (150 mumol zinc/kg). In a small open field on day 9 of the experiment, the deficient rats more frequently displayed the posture standing upright with elevated heels. On day 10 of the experiment a clinical examination was carried out at random and 'blind' by three independent assessors. Out of 20 variables scored quantitatively on each individual animal, only body size differed between normal and deficient rats. Other classical signs of zinc deficiency, such as alopecia, dermatitis and diarrhoea, were not detected. It is concluded that in this rat model of zinc deficiency, no evidence for extreme discomfort can be demonstrated.
Abstract: Serum, urine and hair zinc levels in 20 patients with recurrent upper respiratory tract infection are compared with those of age- and sex-matched controls. Lower hair zinc (1.44 vs 2.00 mmol/g hair, P = 0.004) and higher urinary zinc levels (2.2 vs 1.6 mmol/mol creatinine, P = 0.05) were found, but no difference in serum zinc. The patients had lower-normal height for age (SD-score 0.2 vs 0.7, P = 0.031), there was no difference in weight for height. No correlation was found between the zinc values and the duration of the complaints.
Abstract: We report on a severely retarded girl with multiple congenital anomalies. Chromosome studies showed a der (8) chromosome with dup(10p) and deficiency for a small distal segment of 8q. Her father proved to be carrier of a de novo balanced translocation between chromosome 8q and 10p. At 1 year the patient was also found to have the Pendred syndrome, an autosomal recessive defect in thyroid organification. The concurrence of chromosome anomalies and single gene disorders might not be too rare, but can be easily overlooked. Yet there are important consequences for genetic counseling. Moreover, recognition of these concurrences may help gene mapping.
Abstract: Zinc concentrations in hair and urine were measured in groups of children varying in one condition - short stature, or after prolonged upper respiratory infection, or during non-infectious diarrhea, or while on chemotherapy for acute lymphatic leukaemia and in healthy controls. As compared with controls, hair zinc was significantly low after respiratory infection (p less than 0.0001) and high in short stature (p less than 0.01). Urinary zinc was increased during initial chemotherapy (p less than 0.001) and diarrhea (p less than 0.02). It is shown that zinc deficiency occurs in one of the common symptoms in paediatric medicine, namely upper respiratory tract infection. The high overlap (34-88%) proves hair and urine zinc to be of no use for reliable individual diagnostic statements.
