[show abstract][hide abstract] ABSTRACT: In a previous study we devised a diagnostic decision rule to improve management of children with meningeal signs, suspected of having bacterial meningitis. The decision rule aimed to guide decisions on (1) whether a lumbar puncture is necessary in children with meningeal signs, and (2) which children need hospitalisation and empirical antibiotic treatment for bacterial meningitis. In this study we assessed the validity of this rule in an external population of four (paediatric) hospitals in The Netherlands. The decision rule included two scoring algorithms using symptoms, signs and quickly available blood and cerebrospinal fluid (CSF) laboratory tests. To evaluate the discriminative value of both algorithms, the absolute numbers of correctly diagnosed patients and the area under the receiver operator characteristic curve were estimated, and compared with the results from the original population (n = 360). In a 18 month period, we included 226 children, median age 2.2 years, who visited the emergency department with meningeal signs. Bacterial meningitis was present in 25 (11%). Using the scoring algorithms patients could be categorised in groups of increasing risk of bacterial meningitis. The discriminative values of the clinical and CSF algorithm in this new population were similar to those in the original population. In the total population of 586 children with meningeal signs, the rule selected 205 children (35%) who did not need a lumbar puncture and 366 children who did not need empirical treatment (62%). In conclusion, this diagnostic rule performed well in a new population of children with meningeal signs. This diagnostic decision rule is a valuable tool for the clinician when deciding to treat these children for bacterial meningitis and thus improving their management.
European Journal of Epidemiology 08/2013; · 5.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: At the same time that H. pylori prevalence is declining in Western countries, immigrants from developing countries with high H. pylori prevalence have settled in Western urban areas. Actual epidemiologic data on H. pylori in a migrant community may help in realizing a more selective approach to assess H. pylori-related diseases. We aimed to define H. pylori prevalence as well as risk groups for H. pylori in a cohort of young women living in a multi-ethnic European city.
We measured IgG anti-H. pylori and CagA-antibodies in serum of pregnant women included in a population-based prospective cohort study. Information on demographics, and socio-economic status was collected by questionnaires. Chi-square and logistic regression were used.
In total, 3146 (46%) of the 6837 tested women (mean age 29.7 ± 5.3) were H. pylori-positive and 1110 (35%) of them were CagA-positive. The H. pylori prevalence in Dutch women was 24%, which was significantly lower than in non-Dutch women (64%; p<0.001). In particular, H. pylori positivity was found in 92% of Moroccan (OR 19.2; 95% CI 11.8-32.0), 80% of Cape Verdean (7.6; 5.0-11.5), 81% of Turkish (9.0; 6.7-12.1), 60% of Dutch Antillean (3.3; 2.3-4.7), and 58% of Surinamese women (3.0; 2.3-3.8). Among H. pylori-positive Dutch subjects, 19% were CagA-positive compared with 40% of the non-Dutch subjects (p<0.001).
Despite a general trend of declining prevalence in Western countries, H. pylori remains highly prevalent in migrant communities, which may constitute target groups for screening and eradication to prevent H. pylori-related diseases.
Journal of Gastroenterology and Hepatology 06/2013; · 3.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess the associations of folate, homocysteine and vitamin B12 levels of children at birth and their methylenetetrahydrofolate reductase (MTHFR) variants with asthma and eczema in childhood.
This study was embedded in a population-based prospective cohort study (n = 2,001). Neonatal cord blood folate, homocysteine and vitamin B12 levels were measured, and MTHFR C677T and A1298C genotyped. Wheezing and physician-diagnosed eczema were annually obtained by questionnaire until 4 years. At 6 years, we collected information on physician-diagnosed asthma ever and self-reported eczema ever, measured fractional exhaled nitric oxide (FeNO), and interrupter resistance (Rint). Data were analysed with generalized estimating equations or logistic regression: continuous outcomes with linear regression models.
Folate, homocysteine and vitamin B12 levels of children at birth were not associated with wheezing or eczema until 4 years, asthma and eczema ever, or FeNO or Rint at 6 years. In children carrying C677T mutations in MTHFR, higher folate levels were associated with an increased risk of eczema (repeated eczema until 4 years: OR 1.40 (95% CI 1.09-1.80) (SD change) P-interaction = 0.003, eczema ever at 6 years: OR 1.41 (0.97-2.03) P-interaction = 0.011). No interactions between MTHFR and child folate and homocysteine levels were observed for wheezing and asthma.
Folate, homocysteine and vitamin B12 levels of children at birth did not affect asthma- and eczema-related outcomes up to the age of 6 years. Further studies are warranted to establish the role of MTHFR variants in these associations.
[show abstract][hide abstract] ABSTRACT: Background/objectives:Many parents do not follow recommendations for the timing of introduction of complementary feeding. The aim of this study was to identify determinants associated with the timing of introduction of complementary feeding in a multiethnic birth cohort.Subjects/methods:Subjects were 3561 mothers and infants participating in a prospective cohort study. The timing of introduction of complementary feeding and maternal and infant characteristics were obtained by parent-derived questionnaires. Regression analyses were performed to identify determinants for the timing of introduction of complementary feeding (<3, 3-6 and 6 months).Results:In total, 62% of infants were introduced to complementary feeding before the age of 6 months. Determinants for very early (<3 months) introduction were being a single parent and infant day care attendance. Determinants for early (3-6 months) introduction were young maternal age, multiple parities, no infant family history of asthma, atopy and no infant history of allergy to cow's milk. Determinants for both very early and early introduction were low educational level and not fully breastfeeding for 4 months. Maternal educational level was only significantly associated with the timing of introduction in mothers of Western origin.Conclusions:This study confirmed determinants for the timing of introduction of complementary feeding that have been identified by previous studies, which may be appropriate targets for education and guidance. Moreover, mothers whose infants attend day care and have a family history of asthma, atopy or allergy to cow's milk may need guidance to follow infant feeding recommendations.European Journal of Clinical Nutrition advance online publication, 6 March 2013; doi:10.1038/ejcn.2013.50.
European journal of clinical nutrition 03/2013; · 3.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background/Objectives:Maternal fish consumption during pregnancy might influence the fetal immune system through anti-inflammatory effects of omega-3 fatty acids, and might affect the risks of childhood asthma and atopy. In Generation R, a prospective cohort study in the Netherlands, we examined the associations of first trimester fish consumption with childhood wheezing and eczema in the first 4 years of life.Methods:In total, 2976 mothers completed a 293-item semiquantitative food frequency questionnaire covering dietary intake in the first trimester. The occurrence of wheezing and eczema was yearly assessed by questionnaires.Results:Median weekly fish consumption was 83 (95% range 0-316) grams per week. We observed no consistent associations of maternal total-, lean- or fatty-fish consumption during pregnancy with the risks of childhood wheezing. Maternal shellfish consumption of 1-13 g per week was associated with overall increased risks of childhood wheezing and eczema (OR 1.20 (1.04, 1.40) and OR 1.18 (1.01, 1.37), respectively). Maternal fatty fish consumption of 35-69 g per week was associated with increased overall risks of childhood eczema (OR 1.17 (1.00, 1.38)), but maternal total- or lean-fish consumption was not.Conclusions:During pregnancy, shellfish consumption was associated with increased risks of wheezing and eczema, while fatty fish consumption was associated with a higher risk of eczema only. Maternal total fish or lean fish consumption were not associated with wheezing or eczema. Further studies are needed to replicate these findings and to explore underlying mechanisms.European Journal of Clinical Nutrition advance online publication, 27 February 2013; doi:10.1038/ejcn.2013.36.
European journal of clinical nutrition 02/2013; · 3.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Achtergrond: De evaluatie van het jonge kind (1 tot 36 maanden oud) met koorts zonder focus (lichaamstemperatuur =38,0 °C, zonder duidelijk
focus op basis van anamnese en/of lichamelijk onderzoek) is vaak een diagnostisch en therapeutisch dilemma, ondanks gepubliceerde
richtlijnen. Van het handelen bij kinderen met koorts zonder focus in de dagelijkse praktijk door kinderartsen in Nederland
zijn geen gegevens.
Doel: Het beleid bij jonge kinderen met koorts zonder focus in de acute kindergeneeskundige praktijk inventariseren en vergelijken
met de gepubliceerde Nederlandse en Amerikaanse beleidsadviezen.
Methode: In een enquête werden vier casussen beschreven van niet-toxisch zieke kinderen (2, 10, 10 en 20 maanden oud) met koorts
zonder focus. Kinderartsen werd gevraagd aan te geven welke diagnostische en behandelstrategie zij per casus zouden volgen.
De resultaten werden vergeleken met gepubliceerde Nederlandse en Amerikaanse adviezen.
Resultaten: De respons was 81%. De variabiliteit in zowel de diagnostische strategieën als de behandelopties was groot. De variatie
in het aantal respondenten dat volgens de richtlijnen diagnostiek uitvoerde en behandelde (ongeacht de laboratoriumbevindingen),
was respectievelijk 16% tot 74% en 36% tot 69%. Er werd vaker dan aanbevolen gekozen voor ziekenhuisopname bij de casus van
het jonge en het zieker ogend kind met normale laboratoriumbevindingen.
Conclusie: Er is een grote variabiliteit in het beleid bij jonge kinderen met koorts zonder focus in de acute kindergeneeskunde. De
compliantie met richtlijnen varieert sterk, afhankelijk van de leeftijd en het risicoprofiel van de casus. Aandacht voor implementatie
van richtlijnen zal de compliantie vergroten.
Background: The evaluation of a young child (1-36 months of age) with fever without apparent source (fws: body temperature =38,0 °C and no apparent source found after history taking and physical examination) is often a diagnostic
and therapeutic dilemma, despite published guidelines. Data on management of children with fws in daily Dutch pediatric practice are not available.
Aim: To characterize the management of children with fws in paediatric practice and to compare this with published Dutch and American practice guidelines.
Methods: In a self-administered questionnaire four case scenarios of non-toxic-appearing children (2, 10, 10 and 20 months of age)
with fws were described. For each case, paediatricians were asked to select which diagnostic and therapeutic strategy they would perform.
The results were compared to the published Dutch and American guidelines.
Results: The response rate was 81%. The variability in both the diagnostic and therapeutic strategies was large. The compliance with
the guidelines varied for diagnostics from 16% to 74% and for therapy (irrespective of laboratory test results) from 36% to
69%. In the case scenarios of the younger child and the more ill-appearing child with normal laboratory findings, the respondents
more often selected the option to hospitalize the patient then suggested in the guidelines.
Conclusion: There is a large variability in the management of children with FWS in the paediatric emergency medicine. The compliance
with guidelines varies strongly, depending on the age and the risk profile of the case scenario. Attention for implementation
of guidelines will enlarge the compliance.
Tijdschrift voor kindergeneeskunde 04/2012; 75(2):64-69.
[show abstract][hide abstract] ABSTRACT: Achtergrond: De implementatie van een elektronisch patiëntendossier (epd) lijkt grote voordelen te bieden boven het gebruik van een papieren dossier, onder meer door betere leesbaarheid, beschikbaarheid
en datakwaliteit. In een epd biedt het gebruik van gestructureerde gegevensinvoer extra voordelen: controle op documentatie en juistheid van belangrijke
gegevens, betere toegankelijkheid van gegevens voor naslag en mogelijkheden voor wetenschappelijk onderzoek en beslissingsondersteuning.
Een generieke applicatie voor gestructureerde gegevensinvoer (Opensde) werd ontwikkeld en toegesneden op de algemene kindergeneeskunde.
Doelstelling: Het evalueren van het gebruik van Opensde met betrekking tot compleetheid van het dossier, de uniformiteit in documentatie en de bruikbaarheid in de algemene kindergeneeskunde.
Methoden: Vier artsen documenteerden de gegevens van acht nieuwe patiënten op de polikliniek in het gangbare papieren dossier en meteen
daarna in Opensde (epd). Elk van de 32 papieren dossiers fungeerde vervolgens als databron voor gegevensinvoer in Opensde door de andere drie artsen. De gegevens uit elk papieren dossier werden ook door twee ervaren gebruikers ingevoerd in Opensde en dienden als ‘referentiedossier’. De benodigde tijd voor invoer van de gegevens werd bijgehouden en een vragenlijst werd
gebruikt voor gebruikerservaringen.
Resultaten: Van de beschikbare patiënteninformatie werd 44% identiek gedocumenteerd in het papieren dossier en het epd. Vijfentwintig procent werd alleen gedocumenteerd in het papieren dossier en 31% alleen in het epd. Er waren verschillen in de documentatie van anamnese en lichamelijk onderzoek (lo) in het epd: in de anamnese ontbrak meer informatie (39%) dan in het lo (15%). In het epd bevatte het lo bovendien meer extra informatie (39%) dan de anamnese (21%), ten opzichte van het papieren dossier. De interobserverovereenkomst
in documentatie van dezelfde patiëntgegevens door verschillende artsen in Opensde was matig met ?=0,39 voor de anamnese en ?=0,40 voor lo. De benodigde tijd voor invoer van patiëntgegevens in Opensde nam af van 25 minuten tot minder dan 15 minuten, hetgeen duidt op een leereffect. De gebruikers waren erg positief over het
gebruik van Opensde voor verslaglegging van anamnese en lo in het epd.
Conclusie: Opensde lijkt een veelbelovende applicatie voor de ondersteuning van de documentatie van patiëntgegevens in de algemene kindergeneeskunde.
Background: Implementation of electronic medical record systems promises significant advances in patient care, because such systems
enhance readability, availability, and data quality. Structured data entry (sde) applications can prompt for completeness, provide greater accuracy and better ordering for searching and retrieval, and
permit validity checks for data quality monitoring, research, and especially decision support. A generic sde application (Opensde) to support documentation of patient history and physical examination findings was developed and tailored for the domain
of general pediatrics.
Objective: To evaluate Opensde for its completeness, uniformity of reporting, and usability in general pediatrics.
Methods: Four (trainee) pediatricians documented data for eight first-visit patients in the traditional, paper-based, medical record
and immediately thereafter in Opensde (electronic record). The 32 paper records obtained served as the common data source for data entry in Opensde by the other three physicians (transcribed record). Data entered by two experienced users, with all patient information present
in the paper record, served as the control record. Data entry times were recorded, and a questionnaire was used to assess
users’ experiences with Opensde.
Results: Clinicians documented 44% of all available patient information identically in the paper and electronic records. Twenty-five
percent of all patient information was documented only in the paper record, and 31% was present only in the electronic record.
Differences were found in patient history and physical examination documentation in the electronic record; more information
was missing for patient history (38%) than for physical examination (15%). Furthermore, physical examination contained more
additional information (39%) than did patient history (21%). The interobserver agreement of documentation of patient information
from the same data source was fair to moderate, with ?=0.39 for patient history and ?=0.40 for physical examination. Data
entry times in Opensde decreased from 25 minutes to <15 minutes, indicating a learning effect. The questionnaire revealed a positive attitude toward
the use of Opensde in daily practice.
Conclusion: Opensde seems to be a promising application for the support of physician data entry in general pediatrics.
Tijdschrift voor kindergeneeskunde 04/2012; 75(2):54-59.
[show abstract][hide abstract] ABSTRACT: Triage op de spoedeisende hulp is een belangrijk instrument om zieke kinderen te prioriteren. Tevens wordt triage gebruikt
om patiënten te identificeren die geen urgente zorg nodig hebben en eventueel door een andere zorgverlener zoals de huisarts
gezien kunnen worden. Het Manchester Triage Systeem, de Emergency Severity Index en de Canadian Triage and Acuity Scale zijn
veel gebruikte triagesystemen en hebben onderdelen die specifiek zijn voor kinderen. In Nederland wordt het Manchester Triage
Systeem op grote schaal toegepast. Evaluatie van een triagesysteem omvat de reproduceerbaarheid (interrater agreement en intrarater
agreement) en validiteit (vergelijking met een gouden standaard). Het Manchester Triage Systeem lijkt een redelijk veilig
triagesysteem voor kinderen. Echter, overtriage is een probleem. Met specifieke aanpassingen is het systeem te verbeteren.
Voor een optimale uitvoering van het triageproces is een geautomatiseerde applicatie noodzakelijk, die beschikbaar is op de
Triage on the emergency department is an important tool to prioritize seriously ill children. Besides that triage is used
to identify patients who do not need urgent care and can be seen by another caregiver such as a general practitioner. The
Manchester Triage System, the Emergency Severity Index and the Canadian Triage and Acuity Scale are common used triage systems
and contain specific parts for children. The Manchester Triage System is widely used in the Netherlands. Evaluation of a triage
system has to include reproducibility and validity. The Manchester Triage System seems to be a relatively safe triage system
for children but suffers from overtriage. The system can be improved with specific modifications. To optimize the triage process,
a computerized version that is available at the workplace, is needed.
Tijdschrift voor kindergeneeskunde 04/2012; 76(6):270-276.
[show abstract][hide abstract] ABSTRACT: In dit artikel wordt het Generation R Onderzoek gepresenteerd. Dit onderzoek bestudeert de groei, ontwikkeling en gezondheid
vanaf het vroege foetale leven tot de jongvolwassenheid. Het onderzoek richt zich op vier primaire onderzoeksgebieden: (1)
groei en fysieke ontwikkeling, (2) gedragsmatige en cognitieve ontwikkeling, (3) ziekten op de kinderleeftijd, en (4) gezondheid
en gezondheidszorg voor zwangeren en hun kinderen. De algemene doelstellingen van het onderzoek zijn:
het beschrijven van de normale en abnormale groei, ontwikkeling en gezondheid vanaf het vroege foetale leven tot de jongvolwassenheid
in een multi-etnische populatie;
het identificeren van biologische, sociale en omgevingsgerelateerde determinanten van deze normale en abnormale groei, ontwikkeling
het bestuderen van de effectiviteit van de huidige strategieën voor preventie en vroege identificatie van risicogroepen.
Uiteindelijk moet dit onderzoek een bijdrage leveren aan het ontwikkelen van strategieën voor het optimaliseren van de gezondheid
en gezondheidszorg voor zwangeren en hun kinderen. Het Generation R Onderzoek is een prospectief populatie-gebaseerd cohortonderzoek
in Rotterdam. In deze stedelijke omgeving zullen 10.000 individuen vanaf het vroege foetale leven tot de jongvolwassenheid
worden gevolgd. Gegevens worden verkregen door middel van lichamelijk onderzoek, vragenlijsten, interviews, echografisch onderzoek
en onderzoek in lichaamsmaterialen. De volledige inclusie en gegevensverzameling zijn begonnen in 2002.
In this paper the Generation R Study is presented. This study examines growth, development and health in urban children from
fetal life until young adulthood. This study focuses on four primary areas of research: (1) growth and physical development,
(2) behavioural and cognitive development, (3) diseases in childhood, and (4) health and healthcare for pregnant women and
children. The general aims of the study are:
to describe normal and abnormal growth, development and health from fetal life until young adulthood in a multi-ethnic population-based
to identify biological, social and environmental determinants of normal and abnormal growth, development and health;
to examine the effectiveness of current strategies for prevention and early identification of groups at risk.
Eventually, this study has to contribute to the development of strategies for optimising health and healthcare for pregnant
women and children. The Generation R Study is a prospective population-based cohort study in Rotterdam, the Netherlands. In
this urban setting, 10,000 subjects will be examined from early fetal life until young adulthood. Data are collected by physical
examinations, questionnaires, interviews, ultrasounds and biological samples. Full participant recruitment and data collection
started in 2002.
Tijdschrift voor kindergeneeskunde 04/2012; 73(2):181-186.
[show abstract][hide abstract] ABSTRACT: Doel van deze studie was het verkrijgen van inzicht in de reden van komst van kinderen op een polikliniek algemene kindergeneeskunde
en in de mogelijke verschillen met betrekking tot de etnische achtergrond. Van patiënten die in de periode 1988−1998 de polikliniek
algemene kindergeneeskunde bezochten werden de volgende gegevens verzameld: achtergrondkenmerken, reden van komst (probleemgeoriënteerd
patiëntenclassificatiesysteem), verrichte diagnostiek, follow-up en definitieve diagnose (icd−9-codering). Etniciteit werd met behulp van de achternaam geclassificeerd. In totaal bezochten 11.998 kinderen de polikliniek,
van wie 38% afkomstig uit de stad Rotterdam. Van deze 3913 patiënten was 45% van allochtone afkomst (15% Turks, 9% Marokkaans
en 9% Surinaams). Turkse kinderen bezochten de polikliniek vaker met gastro-intestinale klachten (odds-ratio [or] 1,57, 95%-betrouwbaarheidsinterval [95%bi] 1,14−2,16) en op de leeftijd van 5−15 jaar ook met klachten van de urinewegen (or 2,0, 95%bi 1,13−3,54). Obstipatie en enuresis waren de meest voorkomende oorzaken. Marokkaanse kinderen presenteerden zich vaker met
urinewegklachten (or 2,39, 95%bi 1,34−4,25) en luchtwegklachten (or 2,31, 95%bi 1,37−3,87). Bij hen werd de diagnose astma significant vaker gesteld (or 2,31, 95%bi 1,37−3,87) dan bij Nederlandse kinderen. Bij Surinaamse kinderen werd in beide leeftijdsgroepen de diagnose astma vaker gesteld
(or 2,30, 95%bi 1,22−4,33, respectievelijk 1,92, 95%bi 1,09−3,37). Er bestaan duidelijke verschillen in reden van komst samenhangend met de etniciteit van de kinderen op een polikliniek
algemene kindergeneeskunde. In de toekomst moeten we ons richten op de problemen die vaker bij allochtone kinderen voorkomen
(gastro-intestinale problemen en enuresisklachten bij Turkse kinderen, luchtwegklachten, astma en enuresisklachten bij Marokkaanse
kinderen en luchtwegklachten en astma bij Surinaamse kinderen), teneinde de zorg voor deze groepen te optimaliseren.
Aim of this study was to evaluate whether there are differences in health problems between Dutch and ethnic-minority children
at a paediatric outpatient department. Data were collected from children visiting the paediatric outpatient department of
the Sophia Children's Hospital Rotterdam in the period 1988−1998: background characteristics, reason for encounter (problem-oriented
patient classification system), diagnostic workup, follow-up and final diagnosis. Ethnicity was determined by the patient's
family name. The outpatient department was visited by in total 11.998 patients, of whom 38% lived in the city of Rotterdam.
From these 3913 patients, 15% were Turkish, 9% Moroccan and 9% Surinamese. Turkish children presented more often with gastro-intestinal
symptoms (odds ratio [or] 1,57, 95% confidence interval [ci] 1,14−2,16) and between the ages of 5 and 15 years with urinary-tract symptoms (or 2,00, 95%ci 1,13−3,54), compared to Dutch children. Constipation and enuresis mainly caused these symptoms. Moroccan children of 5−15
years had more often urinary tract symptoms (or 2,39, 95%ci 1,34−4,25) and symptoms of the airways (or 2,31, 95%ci 1,37−3,87). Asthma was more often diagnosed in these children compared to Dutch children (or 2,31, 95%ci 1,37−3,87). In Surinamese children, asthma was more often diagnosed in both age groups (or 2,30, 95%ci 1,22−4,33 and 1,92, 95%ci 1,09−3,37, respectively). There are differences in health problems presented at a paediatric outpatient department in relation
to ethnicity. In future, one should focus on health problems that occur more often in ethnic minorities (gastro-intestinal
symptoms and enuresis symptoms in Turkish, enuresis and asthma in Moroccan, and asthma in Surinamese children) in order to
optimise cure and care in these children.
Tijdschrift voor kindergeneeskunde 04/2012; 69(5):39-45.
[show abstract][hide abstract] ABSTRACT: Gene variants on chromosome 17q12-21 are associated with an increased risk of childhood-onset asthma, a risk known to be modified by environmental tobacco smoke (ETS).
To assess whether the association of rs2305480 on chromosome 17q12 in the GSDML gene with asthma-like symptoms in the first 4 years of life is modified by smoke exposure during fetal and early postnatal life.
We used data from two independent prospective cohort studies from fetal life onwards in the Netherlands. We genotyped rs2305480 and assessed maternal smoking during pregnancy and ETS exposure at the age of 2. Asthma-like symptoms, defined as any reported wheezing, shortness of breath or dry nocturnal cough, were reported by parents when the children were 1, 2, 3, and 4 years. Analyses were based on a total group of 4461 Caucasian children.
The G risk-allele of rs2305480 was associated with asthma-like symptoms [overall odds ratio 1.17 (1.11, 1.24), 2.66E-9]. The effect of rs2305480 on asthma-like symptoms was stronger among children who were exposed to smoke during fetal life (P-interaction = 0.04). Smoke exposure in early postnatal life was also associated with an increased effect of the 17q12 single nucleotide polymorphism (SNP) on asthma-like symptoms (P-interaction = 5.06E-4). These associations were consistent in both cohorts.
A 17q12 variant, rs2305480, was associated with asthma-like symptoms in preschool children, and this association was modified by smoke exposure already during fetal life, and in infancy. Further investigation regarding SNPs in linkage disequilibrium with rs2305480 in relation to pathophysiological pathways is needed.
[show abstract][hide abstract] ABSTRACT: Although the vast majority of children with acute infections are managed at home, this is one of the most common problems encountered in children attending emergency departments (EDs) and primary care. Distinguishing children with serious infection from those with minor or self-limiting infection is difficult. This can result in misdiagnosis of children with serious infections, which results in a poorer health outcome, or a tendency to refer or admit children as a precaution; thus, inappropriately utilising secondary-care resources.
We systematically identified clinical features and laboratory tests which identify serious infection in children attending the ED and primary care. We also identified clinical prediction rules and validated those using existing data sets.
We searched MEDLINE, Medion, EMBASE, Cumulative Index to Nursing and Allied Health Literature and Database of Abstracts of Reviews of Effects in October 2008, with an update in June 2009, using search terms that included terms related to five components: serious infections, children, clinical history and examination, laboratory tests and ambulatory care settings. We also searched references of included studies, clinical content experts, and relevant National Institute for Health and Clinical Excellence guidelines to identify relevant studies. There were no language restrictions. Studies were eligible for inclusion if they were based in ambulatory settings in economically developed countries.
Literature searching, selection and data extraction were carried out by two reviewers. We assessed quality using the quality assessment of diagnostic accuracy studies (QUADAS) instrument, and used spectrum bias and validity of the reference standard as exclusion criteria. We calculated the positive likelihood ratio (LR+) and negative likelihood ratio (LR-) of each feature along with the pre- and post-test probabilities of the outcome. Meta-analysis was performed using the bivariate method when appropriate. We externally validated clinical prediction rules identified from the systematic review using existing data from children attending ED or primary care.
We identified 1939 articles, of which 35 were selected for inclusion in the review. There was only a single study from primary care; all others were performed in the ED. The quality of the included studies was modest. We also identified seven data sets (11,045 children) to use for external validation. The most useful clinical features for ruling in serious infection was parental or clinician overall concern that the illness was different from previous illnesses or that something was wrong. In low- or intermediate-prevalence settings, the presence of fever had some diagnostic value. Additional red flag features included cyanosis, poor peripheral circulation, rapid breathing, crackles on auscultation, diminished breath sounds, meningeal irritation, petechial rash, decreased consciousness and seizures. Procalcitonin (LR+ 1.75-2.96, LR- 0.08-0.35) and C-reactive protein (LR+ 2.53-3.79, LR- 0.25-0.61) were superior to white cell counts. The best performing clinical prediction rule was a five-stage decision tree rule, consisting of the physician's gut feeling, dyspnoea, temperature ≥ 40 °C, diarrhoea and age. It was able to decrease the likelihood of serious infections substantially, but on validation it provided good ruling out value only in low-to-intermediate-prevalence settings (LR- 0.11-0.28). We also identified and validated the Yale Observation Scale and prediction rules for pneumonia, meningitis and gastroenteritis.
Only a single study was identified from primary-care settings, therefore results may lack generalisability.
Several clinical features are useful to increase or decrease the probability that a child has a serious infection. None is sufficient on its own to substantially raise or lower the risk of serious infection. Some are highly specific ('red flags'), so when present should prompt a more thorough or repeated assessment. C-reactive protein and procalcitonin demonstrate similar diagnostic characteristics and are both superior to white cell counts. However, even in children with a serious infection, red flags will occur infrequently, and their absence does not lower the risk. The diagnostic gap is currently filled by using clinical 'gut feeling' and diagnostic safety-netting, which are still not well defined. Although two prediction rules for serious infection and one for meningitis provided some diagnostic value, we do not recommend widespread implementation at this time. Future research is needed to identify predictors of serious infection in children in primary-care settings, to validate prediction rules more widely, and determine the added value of blood tests in primary-care settings.
The National Institute for Health Research Health Technology Assessment programme.
[show abstract][hide abstract] ABSTRACT: This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life until young adulthood. This study focused on the relationship between Deciduous Molar Hypomineralization (DMH) and Molar Incisor Hypomineralization (MIH). First permanent molars develop during a period similar to that of second primary molars, with possible comparable risk factors for hypomineralization. Children with DMH have a greater risk of developing MIH. Clinical photographs of clean, moist teeth were taken with an intra-oral camera in 6,161 children (49.8% girls; mean age 74.3 mos, SD ± 5.8). First permanent molars and second primary molars were scored with respect to DMH or MIH. The prevalence of DMH and MIH was 9.0% and 8.7% at child level, and 4.0% and 5.4% at tooth level. The Odds Ratio for MIH based on DMH was 4.4 (95% CI, 3.1-6.4). The relationship between the occurrence of DMH and MIH suggests a shared cause and indicates that, clinically, DMH can be used as a predictor for MIH.
Journal of dental research 02/2012; 91(6):551-5. · 3.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: Overall diet in early childhood may affect the development of respiratory symptoms. This study examined whether childhood dietary patterns are associated with respiratory symptoms in Dutch pre-school children, and whether this association could be explained by energy intake. A prospective cohort study was performed in 2,173 children aged ≤ 4 yrs. Data on asthma-related symptoms were obtained by questions from the age-adapted version of the "International Study of Asthma and Allergies in Childhood" questionnaires. Data on respiratory tract infections, defined as episodes of physician attended fever with respiratory symptoms, was obtained by questionnaire. Principal components analysis was used to develop dietary patterns at 14 months of age. Compared with low adherence, high adherence to the "Western" dietary pattern was significantly associated with frequent wheeze at 3 yrs of age (relative risk (RR) 1.39, 95% CI 1.02-1.89) and frequent shortness of breath (RR 1.44, 95% CI 1.03-2.01) and respiratory tract infections (RR 1.54, 95% CI 1.08-2.19) at 4 yrs of age. However, this association was partially explained by energy intake. A "Western" diet may increase the risk of frequent respiratory symptoms at 3 and 4 yrs of age. In some measure, this association was explained by energy intake.
European Respiratory Journal 02/2012; 40(3):681-9. · 6.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Breastfeeding has a protective effect on childhood obesity, but the influences on body composition in early childhood are not known. The objective of this study is to assess whether the duration and exclusiveness of breastfeeding, and the timing of introduction of solid foods are associated with the subcutaneous fat mass in early childhood.
This study was embedded in a population-based prospective cohort study among 779 children. Peripheral (biceps, triceps) and central (suprailiacal and subscapular) subcutaneous fat mass was measured as skinfold thickness at the ages of 1.5, 6 and 24 months.
Breastfeeding duration was not associated with subcutaneous fat mass at the age of 1.5 months. Shorter breastfeeding was associated with higher peripheral and total subcutaneous fat mass at the age of 6 months (P-value for trend <0.05), but not at the age of 24 months. As compared to children who were exclusively breast fed for 4 months, those who were non-exclusively breast fed had a higher central fat mass at the age of 24 months (P-value for trend <0.01). Timing of introduction of solid foods was not associated with subcutaneous fat mass.
Our results suggest that a shorter duration and non-exclusive breastfeeding affect early body composition during the first 2 years of life. Follow-up studies at older ages are needed to explore the long-term consequences.
European journal of clinical nutrition 02/2012; 66(2):253-60. · 3.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: To develop reference values and centile charts for respiratory rate based on age and body temperature, and to determine how well these reference values can predict the presence of lower respiratory tract infections (LRTI) in children with fever.
Prospective observational study. PARTICIPANTS : Febrile children aged at least 1 month to just under 16 years (derivation population, n = 1555; validation population, n = 671) selected from patients attending paediatric emergency departments or assessment units in hospitals.
One hospital in the Netherlands in 2006 and 2008 (derivation population); one hospital in the Netherlands in 2003-05 and one hospital in the United Kingdom in 2005-06 (validation population).
We used the derivation population to produce respiratory rate centile charts, and calculated 50th, 75th, 90th, and 97th centiles of respiratory rate at a specific body temperature. Multivariable regression analysis explored associations between respiratory rate, age, and temperature; results were validated in the validation population by calculating diagnostic performance measures, z scores, and corresponding centiles of children with diagnoses of pneumonic LRTI (as confirmed by chest radiograph), non-pneumonic LRTI, and non-LRTI.
Age, respiratory rate (breaths/min) and body temperature (°C), presence of LRTI.
Respiratory rate increased overall by 2.2 breaths/min per 1°C rise (standard error 0.2) after accounting for age and temperature in the model. We observed no interactions between age, temperature, and respiratory rates. Age and temperature dependent cut-off values at the 97th centile were more useful for ruling in LRTI (specificity 0.94 (95% confidence interval 0.92 to 0.96), positive likelihood ratio 3.66 (2.34 to 5.73)) than existing respiratory rate thresholds such as Advanced Pediatrics Life Support values (0.53 (0.48 to 0.57), 1.59 (1.41 to 1.80)). However, centile cut-offs could not discriminate between pneumonic LRTI and non-pneumonic LRTI.
Age specific and temperature dependent centile charts describe new reference values for respiratory rate in children with fever. Cut-off values at the 97th centile were more useful in detecting the presence of LRTI than existing respiratory rate thresholds.
[show abstract][hide abstract] ABSTRACT: We assessed whether exhaled nitric oxide fraction (F(eNO)), a marker of eosinophilic airway inflammation, at 6 months was associated with the risk of wheezing during the first 2 yrs of life. In the Generation R birth cohort, pre- and post-natal risk factors for respiratory morbidity and respiratory symptoms were assessed by questionnaires at 6 and 24 months. In 428 infants, off-line mixed oral/nasal F(eNO) was successfully measured during tidal breathing at 6 months. Complete data on F(eNO) and respiratory symptoms within the first 6 months of life were available for 294 infants. F(eNO) was higher in males, was positively associated with age and was negatively associated with upper and lower respiratory symptoms within the first 6 months. Logistic regression analysis showed that for every ppb increase of F(eNO) measured at 6 months, infants had a 1.06 (95% confidence interval 1.01-1.11)-fold increased risk of wheezing in the second year of life. High F(eNO) (>17.5 ppb) showed a limited added value in predicting wheezing in the second year. We conclude that F(eNO) at 6 months is positively associated with the risk of wheezing, but has limited added value in predicting wheezing in the second year of life in individual children.
European Respiratory Journal 09/2011; 39(3):567-72. · 6.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of our study was to examine the associations of breastfeeding duration and exclusiveness with the risks of asthma-related symptoms in preschool children, and to explore whether these associations are explained by atopic or infectious mechanisms. This study was embedded in a population-based prospective cohort study of 5,368 children. Information on breastfeeding duration, exclusiveness and asthma-related symptoms, including wheezing, shortness of breath, dry cough and persistent phlegm, was obtained by questionnaires. Compared with children who were breastfed for 6 months, those who were never breastfed had overall increased risks of wheezing, shortness of breath, dry cough and persistent phlegm during the first 4 yrs (OR 1.44 (95% CI 1.24-1.66), 1.26 (1.07-1.48), 1.25 (1.08-1.44) and 1.57 (1.29-1.91), respectively). Similar associations were observed for exclusive breastfeeding. The strongest associations per symptom per year were observed for wheezing at 1 and 2 yrs. Additionally adjusted analyses showed that the associations of breastfeeding with asthma-related symptoms were not explained by eczema but partly by lower respiratory tract infections. Shorter duration and nonexclusivity of breastfeeding were associated with increased risks of asthma-related symptoms in preschool children. These associations seemed, at least partly, to be explained by infectious, but not by atopic, mechanisms.
European Respiratory Journal 07/2011; 39(1):81-9. · 6.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Manchester Triage System (MTS) determines an inappropriately low level of urgency (undertriage) to a minority of children. The aim of the study was to assess the clinical severity of undertriaged patients in the MTS and to define the determinants of undertriage.
Patients who had attended the emergency department (ED) were triaged according to the MTS. Undertriage was defined as a 'low urgent' classification (levels 3, 4 and 5) under the MTS; as a 'high urgent' classification (levels 1 and 2) under an independent reference standard based on abnormal vital signs (level 1), potentially life-threatening conditions (level 2), and a combination of resource use, hospitalisation, and follow-up for the three lowest urgency levels. In an expert meeting, three experienced paediatricians used a standardised format to determine the clinical severity. The clinical severity had been expressed by possible consequences of treatment delay caused by undertriage, such as the use of more interventions and diagnostics, longer hospitalisation, complications, morbidity, and mortality. In a prospective observational study we used logistic regression analysis to assess predictors for undertriage.
In total, 0.9% (119/13,408) of the patients were undertriaged. In 53% (63/119) of these patients, experts considered undertriage as clinically severe. In 89% (56/63) of these patients the high reference urgency was determined on the basis of abnormal vital signs. The prospective observational study showed undertriage was more likely in infants (especially those younger than three months), and in children assigned to the MTS 'unwell child' flowchart (adjusted OR<3 months 4.2, 95% CI 2.3 to 7.7 and adjusted ORunwell child 11.1, 95% CI 5.5 to 22.3).
Undertriage is infrequent, but can have serious clinical consequences. To reduce significant undertriage, the authors recommend a systematic assessment of vital signs in all children.
Archives of Disease in Childhood 04/2011; 96(7):653-7. · 3.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: To unravel the mechanisms underlying the previously demonstrated associations between low birthweight and cardiovascular disease in adulthood, we examined whether maternal smoking during pregnancy leads to fetal arterial resistance adaptations, and subsequently to fetal growth retardation and changes in postnatal blood pressure and cardiac development. Design: Prospective cohort study from early fetal life onwards.
Analyses were based on 1120 children aged 2 years.
Maternal smoking during pregnancy [non-smoking, first trimester smoking, continued smoking (< 5 and ≥ 5 cigarettes/day)] was assessed by questionnaire.
Third trimester placental and fetal arterial resistance indices and fetal growth were assessed by ultrasound and Doppler measurements. Postnatal blood pressure and cardiac structures (aortic root diameter, left atrial diameter, left ventricular mass) were measured at 2 years of age.
First trimester smoking was not associated with third trimester placental and fetal blood flow adaptations. Continued smoking of ≥ 5 cigarettes/day was associated with an increased resistance in uterine, umbilical and middle cerebral arteries, and with a decreased flow and diameter of the ascending aorta. Among mothers who continued to smoke, the third trimester estimated fetal weights and birthweights were most affected in children with the highest umbilical artery resistance. Fetal arterial resistance indices were also associated with aortic root diameter and left atrial diameter.
Fetal arterial resistance adaptations may be involved in the pathways leading from maternal smoking during pregnancy to low birthweight and cardiovascular developmental changes in childhood in the offspring.
BJOG An International Journal of Obstetrics & Gynaecology 03/2011; 118(6):755-62. · 3.76 Impact Factor