[Show abstract][Hide abstract] ABSTRACT: Background:
Cardiac involvement in HIV infected children has been frequently reported, but whether this is due to HIV infection itself or to antiretroviral treatment (ART) is unknown.
This cross sectional study involved 114 vertically-acquired HIV-infected (56 ART-naive, 58 ART-exposed) and 51 healthy children in Jakarta, Indonesia. Echocardiography was performed to measure dimensions of the left ventricle (LV) and systolic functions. We applied general linear modeling to evaluate the associations between HIV infection/treatment status and cardiac parameters with further adjustment for potential confounders or explanatory variables. Findings are presented as (adjusted) mean differences between each of the two HIV groups and healthy children, with 95% confidence intervals and p values.
Compared to healthy children, ART-naïve HIV-infected children did not show significant differences in age-and-height adjusted cardiac dimensions apart from larger LV internal diameter (difference 2.0 mm, 95%CI 0.2 to 3.7), whereas ART exposed HIV infection showed thicker LV posterior walls (difference = 1.1 mm, 95%CI 0.5 to 1.6), larger LV internal diameter (difference = 1.7 mm, 95%CI 0.2 to 3.2) and higher LV mass (difference = 14.0 g, 7.4 to 20.5). With respect to systolic function, reduced LV ejection fraction was seen in both ART-naïve HIV infected (adjusted difference = -6.7%, -11.4 to -2.0) and, to a lesser extent, in ART-exposed HIV infected children (difference = -4.5%, -8.5 to -0.4). Inflammation level seemed to be involved in most associations in ART-exposed HIV-infected, but few, if any, for decreased function in the ART-naive ones, whereas lower hemoglobin appeared to partially mediate chamber dilation in both groups and reduced function, mainly in ART-exposed children.
ART-naive HIV infected children have a substantial decrease in cardiac systolic function, whereas the ART-exposed have thicker ventricular walls with larger internal diameter and higher mass, but less functional impairment.
[Show abstract][Hide abstract] ABSTRACT: Aims:
Human immunodeficiency virus (HIV) infection may alter childhood vascular properties and influence future cardiovascular risk. Whether vascular changes are associated with HIV infection per se or antiretroviral therapy (ART) is unknown. We investigated the effects of ART-naive or ART-exposed HIV infection in children on childhood vascular characteristics.
Methods and results:
We performed vascular ultrasound to measure carotid intima media thickness (cIMT), distensibility, and elastic modulus on 114 children with vertically acquired HIV infection (56 ART-naive, 58 ART treated) and 51 healthy children in Jakarta, Indonesia. Children also underwent clinical and blood examinations. We used general linear modelling to estimate associations between HIV infection/treatment status and vascular characteristics with adjustment for confounders or possible mediators. Vascular measurements were successful in 42 ART-naive HIV-infected [median age 4.0 years (min 0.4-max 11.5)]; 53 ART-treated HIV infected [5.7 years (0.6-12.2), median ART duration 2.4 years (0.1-9.9)]; and 48 healthy children, 6.5 years (2.4-14.0). The ART-naive HIV infected had thicker cIMT (difference 70.4 µm, 95% CI 32.1-108.7, P < 0.001), adjusted for age, sex, socioeconomic status, parental smoking, body mass index, systolic and diastolic blood pressure, LDL cholesterol, and HbA1c. Addition of high-sensitivity C-reactive protein (hs-CRP) level to the model did not affect the results (71.6 µm, 31.9-111.2, P = 0.001). The ART-exposed children had similar cIMT dimensions to healthy children. Distensibility was not significantly different between HIV infected, either ART-naive or -exposed, and healthy children, but adjusted analysis including only ART-exposed children with controlled HIV (CD4+ ≥200/mm(3) or CD4+ ≥15%) showed that the ART-exposed had an increased elastic modulus (difference 37.9 kPa, 95% CI 6.5-69.3, P = 0.02), and following adjustment for hs-CRP (35.5 kPa, 95% CI 4.2-66.8, P = 0.03).
ART-naive HIV infection in children is associated with increased cIMT. Children with ART-controlled HIV may have increased arterial stiffness, although further confirmation is required.
No preview · Article · Jan 2016 · European Heart Journal
[Show abstract][Hide abstract] ABSTRACT: Background In 2006, the Dutch guideline for active treatment of extremely preterm neonates advised to lower the gestational age threshold for active intervention from 26 0/7 to 25 0/7 weeks gestation.
Objective To evaluate the association between the guideline modification and early neonatal outcome.
Design National cohort study, using prospectively collected data from The Netherlands Perinatal Registry.
Patients The study population consisted of 9713 infants with a gestational age between 24 0/7 and 29 6/7 weeks, born between 2000 and 2011. Three gestational age subgroups were analysed: 24 0/7 to 24 6/7 weeks (n=269), 25 0/7 to 25 6/7 weeks (n=852) and 26 0/7 to 29 6/7 weeks (n=8592).
Main outcome measures Neonatal intensive care unit (NICU) admission, live births, neonatal in-hospital mortality, morbidity and favourable outcome (no mortality or morbidity) before (2000–2005; period 1) and after (2007–2011; period 2) introduction of the modified guideline, using χ2 tests and univariable and multivariable logistic regression analyses.
Results In the second period, the proportion of live births and NICU admissions increased and the proportion of neonatal and in-hospital mortality decreased significantly in all subgroups. Morbidity in surviving infants of 25 weeks increased significantly, although the association between guideline modification and morbidity became non-significant after case-mix adjustment. Overall, favourable outcome did not change significantly after guideline modification in all subgroups when adjusted for variation in case-mix.
Conclusions Overall, the trend in mortality gradually declined at all gestational ages, starting before 2006. This suggests that the guideline modification was a formalisation of already existing daily practice.
Preview · Article · Jan 2016 · Archives of Disease in Childhood - Fetal and Neonatal Edition
[Show abstract][Hide abstract] ABSTRACT: Background:
Atherosclerosis begins in childhood with the occurrence of inflammatory vascular wall alterations that are detectable with B-mode ultrasound. Chemokines appear to be involved in the development of these alterations given that they occur early in the atherosclerotic pathway as mediators of vascular inflammation. However, this has not extensively been investigated. Therefore, we studied in healthy young children whether chemokines monocyte chemotactic protein 1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES), and vascular and intercellular adhesion molecules (VCAM and ICAM) related to vascular characteristics of the carotid artery.
Methods and results:
We obtained demography, anthropometry, and overnight fasting plasma of 139 eight-year-old children of the Wheezing Illnesses Study Leidsche Rijn birth cohort. Carotid intima-media thickness (CIMT), distensibility, and Young's Elastic Modulus (YEM) of the common carotid artery were measured sonographically. Chemokine plasma levels were assessed using a multiplex assay. We studied the relation between the chemokines and vascular characteristics using multivariable linear regression analyses with adjustments for sex, systolic blood pressure, homeostasis model assessment of insulin resistance, triglycerides, low-density lipoprotein- and high-density lipoprotein-cholesterol. Of the studied chemokines, RANTES related to common carotid distensibility and YEM. One standard deviation increase in RANTES level related to a 5.45-MPA(-1) (95% confidence interval [CI], -9.43, -1.39; P=0.01) decrease in distensibility and to a 5.55-kPa increase in YEM (95% CI, 0.40, 10.85; P=0.03). RANTES did not relate to CIMT. MCP-1, VCAM, and ICAM did not relate to any of the studied vascular characteristics.
RANTES appears to be involved in the development of preatherosclerotic inflammatory vascular alterations already in healthy, young children. This may provide further insight into the early-life origins of atherosclerosis.
Full-text · Article · Dec 2015 · Journal of the American Heart Association
[Show abstract][Hide abstract] ABSTRACT: Using data on weight and height at 6 and 11 months of age and primary care electronic health records data from 1960 children participating in the WHISTLER birth cohort study, we found that BMIat 6 and 11 months of age was not associated with otitis media occurrenceduring the first 4 years of life.
No preview · Article · Sep 2015 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Probiotics are used by women in the perinatal period and may improve balance of microbiota, with possible health benefits for both mother and baby. Characteristics and (health) behaviour patterns of mothers using probiotics during pregnancy, and health effects on their offspring, were investigated. Differences between mothers using probiotics during pregnancy and those who did not, were assessed. In total, 341 out of 2491 (13.7 %) mothers reported use of probiotics during pregnancy. There were no significant differences in maternal features (gestation, age, ethnicity, education) between users and non-users. Logistic regression analyses showed that consumption of probiotics was significantly associated with use of homeopathic products [odds ratio (OR) 1.65, 95 % confidence interval (CI) 1.17-2.33, p = 0.005], maternal history of smoking (OR 1.72, 95 % CI 1.25-2.37, p = 0.001) and paternal history of smoking (OR 1.39, 95 % CI 1.01-1.89, p = 0.05). Common disease symptoms during the first year of life in the offspring did not differ between both groups.
The use of probiotics or other health-related products without doctor's prescription during pregnancy might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not seem to induce positive health effects in the offspring in an unselected population. What is Known: • Aberrant microbiota compositions have been detected during critical periods when early programming occurs including pregnancy and early neonatal life. • Probiotics modulate intestinal microbiota composition and are associated with positive health effects. What is New: • The use of probiotics or other health-related products without doctor's prescription during pregnancy is associated with and might point to compensation for types of less favourable behaviour. • Probiotic use during pregnancy does not induce positive health effects in the offspring in this unselected population.
Full-text · Article · Aug 2015 · European Journal of Pediatrics
[Show abstract][Hide abstract] ABSTRACT: Background:
Most estimates of the incidence of acute otitis media (AOM) are based on general practitioner (GP) or pediatrician diagnoses. It is likely that these figures underestimate the community incidence of AOM since parents do not visit their doctor every time their child suffers from acute ear symptoms. The impact of these symptom episodes may be substantial since they affect the child's quality of life and parents' productivity.
To determine AOM symptoms in the community, we measured parent-reported AOM symptoms daily for 12 consecutive months in 1,260 children participating in a prospective birth cohort in the Netherlands. The mean age of these children was at study enrollment 0.9 months (standard deviation 0.6). A parent-reported AOM symptom episode was defined as fever (temperature 38˚C or above) plus at least one of the following symptoms: ear pain and ear discharge. These febrile AOM symptom episodes were linked to GP-consultations and diagnoses in the GP electronic health records.
With an estimated 624 parent-reported symptom episodes per 1,000 child-years (95% CI: 577 to 674) incidence of febrile AOM symptoms during the child's first year is high. The GP was consulted in half of these symptom episodes and AOM was diagnosed in 49% of these consultations.
Conclusions and relevance:
The incidence of febrile AOM symptoms in the first year of life is high in Dutch children and leads to a GP-consultation in only half of the cases. This suggests that AOM symptomatology in the community is underestimated when focusing on GP-diagnosed AOM episodes alone, since a considerable proportion of febrile AOM symptom episodes are treated symptomatically by parents at home and do not come to the attention of the GP. Having data on community AOM symptomatology available for each country is important when the potential impact of preventive and therapeutic interventions for AOM are studied.
[Show abstract][Hide abstract] ABSTRACT: Introduction
Asthma control is considered the major goal of asthma management, while many determinants of control are difficult to modify. We studied the association between respiratory infection episodes (RTIs) of various types and asthma control.
Cross-sectional data were used from children aged 4-18 years with physician-diagnosed asthma who participated in a web-based electronic portal for children with asthma, allergies or infections. Asthma control was measured using the Childhood Asthma Control Test (C-ACT) or the Asthma Control Test (ACT). Linear regression was used to analyse the association between categories of numbers of various types of RTIs sustained in the preceding 12 months (categorized) and asthma control, adjusted for potential confounders.
Asthma control was assessed in 654 children, and 68.5% were clinically well controlled (ACT≥20). Higher total numbers of RTIs in the last 12 months were strongly associated with a lower level of asthma control (ptrend<0.001). Similarly strong statistically significant associations were found for subtypes of RTI: ≥4 vs. 0 otitis episodes: coefficient -1.7 (95% CI -3.3 to -0.2); ≥5 vs.0 colds: coefficient -2.3 (95% CI -3.0 to -1.6); ≥3 vs. 0 bronchitis episodes: coefficient -3.1 (95% CI -4.0 to -2.3), each with ptrend <0.05.
Higher numbers of reported respiratory tract infections are associated with lower level of asthma control. The different type of respiratory tract infections contribute equally to less controlled asthma.
No preview · Article · Oct 2014 · Respiratory Medicine
[Show abstract][Hide abstract] ABSTRACT: Background
Atherosclerosis is a process that begins in childhood, develops over decades and underlies the majority of cardiovascular events in adulthood. Previously, we demonstrated in adults with cardiovascular disease that levels of extracellular vesicle (EV) proteins CD14, Serpin F2 and cystatin C predict vascular outcome. Here, we study for the first time whether these EV proteins are related to vascular characteristics in healthy, young children.
Methods and results
In 141 eight-year old children of the Wheezing-Illnesses-Studie-LEidsche-Rijn birth cohort, anthropometrics and blood pressure were measured. In addition, common carotid intima-media thickness, carotid distensibility and carotid Young's elastic modulus were obtained non-invasively using ultrasound imaging. A fasting lipid spectrum was obtained and EVs were isolated from plasma. Levels of EV proteins CD14, Serpin F2 and cystatin C were measured using a multiplex assay. In a multivariable linear regression model we assessed the relation between these EV proteins and the selected vascular characteristics. Of the studied EV proteins, CD14 levels were positively related to common carotid intima-media thickness (log transformed, beta = 7.31 ln(mm)/(ng/mg) (1.24, 13.38), p = 0.02). EV proteins Serpin F2 and cystatin C were not related to common carotid intima-media thickness. In addition, we found no relation between all three EV proteins and carotid distensibility or carotid Young's elastic modulus.
In healthy eight-year old children, extracellular vesicle protein CD14 levels seem positively related to common carotid intima-media thickness. This would point towards inflammatory vascular alterations inflicted by extracellular vesicle protein CD14 already in early life and warrants further investigation.
[Show abstract][Hide abstract] ABSTRACT: Many Muslim women worldwide are pregnant during Ramadan and adhere to Ramadan fasting during pregnancy. In the present study, we determined whether maternal adherence to Ramadan fasting during pregnancy has an impact on the birth weight of the newborn, and whether the effects differed according to trimester in which Ramadan fasting took place. A prospective cohort study was conducted in 130 pregnant Muslim women who attended antenatal care in Amsterdam and Zaanstad, The Netherlands. Data on adherence to Ramadan fasting during pregnancy and demographics were self-reported by pregnant women, and the outcome of the newborn was retrieved from medical records after delivery. The results showed that half of all the women adhered to Ramadan fasting. With strict adherence to Ramadan fasting in pregnancy, the birth weight of newborns tended to be lower than that of newborns of non-fasting mothers, although this was not statistically significant ( - 198 g, 95 % CI - 447, 51, P= 0·12). Children of mothers who fasted in the first trimester of pregnancy were lighter at birth than those whose mothers had not fasted ( - 272 g, 95 % CI - 547, 3, P= 0·05). There were no differences in birth weight between children whose mothers had or had not fasted if Ramadan fasting had taken place later in pregnancy. Ramadan fasting during early pregnancy may lead to lower birth weight of newborns. These findings call for further confirmation in larger studies that should also investigate potential implications for perinatal and long-term morbidity and mortality.
No preview · Article · Sep 2014 · British Journal Of Nutrition
[Show abstract][Hide abstract] ABSTRACT: Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee and tea consumption were assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found no significant association between overall gastric cancer risk and consumption of total coffee (HR 1.09, 95%-confidence intervals [CI]: 0.84-1.43; quartile 4 vs. non/quartile 1), caffeinated coffee (HR 1.14, 95%-CI: 0.82-1.59; quartile 4 vs. non/quartile 1), decaffeinated coffee (HR 1.07, 95%-CI: 0.75-1.53; tertile 3 vs. non/tertile 1) and tea (HR 0.81, 95%-CI: 0.59-1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100 mL/day (HR 1.06, 95%-CI: 1.03-1.11). Similarly, a significant positive association was observed between gastric cardia cancer risk and caffeinated coffee consumption (HR 1.98, 95%-CI: 1.16-3.36, p-trend=0.06; quartile 3 vs. non/quartile 1) and per increment of 100 mL/day (HR 1.09, 95%-CI: 1.04-1.14). In conclusion, consumption of total, caffeinated and decaffeinated coffee and tea is not associated with overall gastric cancer risk. However, total and caffeinated coffee consumption may be associated with an increased risk of gastric cardia cancer. Further prospective studies are needed to rule out chance or confounding.
What's New? Can drinking coffee or tea lead to cancer? Can they protect against cancer? These popular drinks certainly contain antioxidants, but despite many investigations into the question, we still have no clear answer. A new study has plied the data from the European Prospective Investigation into Cancer and Nutrition (EPIC) in search of a link. Participants self-reported their coffee and tea consumption by questionnaire. The authors found no link between drinking tea or coffee - with or without caffeine - and overall risk of gastric cancer; they did discern a slight increase in gastric cardia cancer with consumption of caffeinated coffee.
Full-text · Article · Sep 2014 · International Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Aim:
It was recently suggested that early postoperative seizure relapse implicates a failure to define and resect the epileptogenic zone, that late recurrences reflect the persistence or re-emergence of epileptogenic pathology, and that early recurrences are associated with poor treatment response. Timing of antiepileptic drugs withdrawal policies, however, have never been taken into account when investigating time to relapse following epilepsy surgery.
Of the European paediatric epilepsy surgery cohort from the "TimeToStop" study, all 95 children with postoperative seizure recurrence following antiepileptic drug (AED) withdrawal were selected. We investigated how time intervals from surgery to AED withdrawal, as well as other previously suggested determinants of (timing of) seizure recurrence, related to time to relapse and to relapse treatability. Uni- and multivariable linear and logistic regression models were used.
Based on multivariable analysis, a shorter interval to AED reduction was the only independent predictor of a shorter time to relapse. Based on univariable analysis, incomplete resection of the epileptogenic zone related to a shorter time to recurrence. Timing of recurrence was not related to the chance of regaining seizure freedom after reinstallation of medical treatment.
For children in whom AED reduction is initiated following epilepsy surgery, the time to relapse is largely influenced by the timing of AED withdrawal, rather than by disease or surgery-specific factors. We could not confirm a relationship between time to recurrence and treatment response. Timing of AED withdrawal should be taken into account when studying time to relapse following epilepsy surgery, as early withdrawal reveals more rapidly whether surgery had the intended curative effect, independently of the other factors involved.
Full-text · Article · Sep 2014 · Epileptic disorders: international epilepsy journal with videotape
[Show abstract][Hide abstract] ABSTRACT: Increases in human population size, dengue vector-density and human mobility cause rapid spread of dengue virus in Indonesia. We investigated the changes in dengue haemorrhagic fever (DHF) incidence in Indonesia over a 45-year period and determined age-specific trends in annual DHF incidence.
Using an on-going nationwide dengue surveillance program starting in 1968, we evaluated all DHF cases and related deaths longitudinally up to 2013. Population demographics were used to calculate annual incidence and case fatality ratios (CFRs). Age-specific data on DHF available from 1993 onwards were used to assess trends in DHF age-distribution. Time-dependency of DHF incidence and CFRs was assessed using the Cochrane-Armitage trend test.
The annual DHF incidence increased from 0.05/100,000 in 1968 to ~ 35-40/100,000 in 2013, with superimposed epidemics demonstrating a similar increasing trend with the highest epidemic occurring in 2010 (85.70/100,000; p < 0.01). The CFR declined from 41% in 1968 to 0.73% in 2013 (p < 0.01). Mean age of DHF cases increased during the observation period. Highest incidence of DHF was observed among children aged 5 to 14 years up to 1998, but declined thereafter (p < 0.01). In those aged 15 years or over, DHF incidence increased (p < 0.01) and surpassed that of 5 to 14 year olds from 1999 onwards.
Incidence of DHF over the past 45 years in Indonesia increased rapidly with peak incidence shifting from young children to older age groups. The shifting age pattern should have consequences for targeted surveillance and prevention.
[Show abstract][Hide abstract] ABSTRACT: It is unknown why respiratory syncytial virus (RSV) causes mild disease in some children and severe disease, requiring hospitalisation, in others. We aimed to assess whether diminished premorbid lung function in healthy term infants predisposes to hospitalisation during RSV bronchiolitis, and to post-RSV wheeze. In a prospective birth cohort study of unselected term healthy children, neonatal lung function was measured before the age of 2 months (n = 2133). From birth through the first year of life, respiratory symptoms were recorded in a diary, and general practitioner consultations and hospitalisations were documented. In a subgroup (n = 417) repeated nose and throat swabs were collected for PCR to detect RSV infections. Median neonatal respiratory system compliance (Crs) was significantly lower (41.2 versus 47.4 mL·kPa(-1), p = 0.03) and resistance (Rrs) was higher (8.2 versus 6.3 kPa·s·L(-1), p = 0.10) in hospitalised RSV patients (n = 18) compared with nonhospitalised RSV-positive infants (n = 84). Every 10 mL·kPa(-1) increase in Crs was associated with 55% less post-RSV wheeze (OR 0.56, 95% CI 0.35-0.90), and each kPa·s·L(-1) increase in Rrs was associated with 42% more post-RSV wheeze, which was only marginally explained by pre-RSV wheeze or severity of the RSV disease. This unselected birth cohort study shows for the first time that decreased lung function at birth predisposes to severe RSV disease, and to post-RSV wheeze.
No preview · Article · Jul 2014 · European Respiratory Journal