Search

Much remains to be understood about the socioeconomic inequalities in hypertension that continue to exist. We investigated the association of socioeconomic status with blood pressure and prehypertension in childhood. In a prospective cohort, 3024 five- to six-year-old children had blood pressure measurements and available information on potential explanatory factors, namely birth weight, gestational age, smoking during pregnancy, pregnancy-induced hypertension, familial hypertension, maternal body mass index, breastfeeding duration, domestic tobacco exposure, and body mass index. The systolic and diastolic blood pressures of children from mid-educated women were 1.0-mm Hg higher (95% CI, 0.4-1.7) and 0.9-mm Hg higher (95% CI, 0.3-1.4), and the blood pressures of children with low-educated women were 2.2-mm Hg higher (95% CI, 1.4-3.0) and 1.7-mm Hg higher (95% CI, 1.1-2.4) compared with children with high-educated women. Children with mid- (odds ratio, 1.50; 95% CI, 1.18-1.92) or low-educated mothers (odds ratio, 1.80; 95% CI, 1.35-2.42) were more likely to have prehypertension compared with children with high-educated mothers. Using path analyses, birth weight, breastfeeding duration, and body mass index were determined as having a role in the association of maternal education with offspring blood pressure and prehypertension. The socioeconomic gradient in hypertension appears to emerge from childhood as the results show a higher blood pressure and more prehypertension in children from lower socioeconomic status families. Socioeconomic disparities could be reduced by improving 3 factors in particular, namely birth weight, breastfeeding duration, and body mass index, but other factors might also play a role. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study is to report on the feasibility, reliability, validity, and the norm-references of the Dutch version of the PedsQL™ Multidimensional Fatigue Scale.Methods: The study participants are four hundred and ninety-seven parents of children aged 2-18 years and 366 children aged 5-18 years from various day care facilities, elementary schools, and a high school who completed the Dutch version of the PedsQL™ Multidimensional Fatigue Scale.Results: The number of missing items was minimal. All scales showed satisfactory internal consistency reliability, with Cronbach's coefficient alpha exceeding 0.70. Test-retest reliability was good to excellent (ICCs 0.68-0.84) and inter-observer reliability varied from moderate to excellent (ICCs 0.56-0.93) for total scores. Parent/child concordance for total scores was poor to good (ICCs 0.25-0.68). The PedsQL™ Multidimensional Fatigue Scale was able to distinguish between healthy children and children with an impaired health condition.Conclusions: The Dutch version of the PedsQL™ Multidimensional Fatigue Scale demonstrates an adequate feasibility, reliability, and validity in another sociocultural context. With the obtained norm-references, it can be utilized as a tool in the evaluation of fatigue in healthy and chronically ill children aged 2-18 years. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the association between (self-reported) maternal pre-pregnancy body mass index (pBMI), and child's weight, height and BMI at age 14 months. DESIGN: Prospective multi-ethnic community-based cohort study. SETTING: Amsterdam, The Netherlands. PARTICIPANTS: 8266 pregnant women from the Amsterdam Born Children and their Development study, filled out a questionnaire covering socio-demographic data, obstetric history, lifestyle, dietary habits and psychosocial factors, 2 weeks after their first antenatal visit. 7730 gave birth to a viable term singleton infant with information on birth weight, gender and pregnancy duration. Growth data were available for 3171 of these children. MAIN OUTCOME MEASURES: Weight (g), height (cm) and BMI (kg/m(2)) of the child at age 14 months. RESULTS: pBMI was linearly associated with weight and BMI of the child at age 14 months. One unit increase in pBMI resulted in an increment of 29 g (95% CI 19 to 39) in weight and 0.041 kg/m(2) (95% CI 0.030 to 0.053) in BMI. The effect size decreased after adjustment for birth weight (weight: beta coefficient 19 g, 95% CI 10 to 28; BMI: beta coefficient 0.034 kg/m(2), 95% CI 0.023 to 0.046) and hardly changed after adjustment for all other variables (weight: beta coefficient 21 g, 95% CI 11 to 30; BMI: beta coefficient 0.031 kg/m(2), 95% CI 0.019 to 0.043). pBMI was not related to height. CONCLUSIONS: pBMI is an independent determinant of weight and BMI of the child at age 14 months. At least one third of this effect is mediated through birth weight. [ABSTRACT FROM AUTHOR]

Objective: To test the effects of monitoring and discussing of health-related quality of life (HRQoL) in adolescents with type 1 diabetes in a multicenter randomized controlled trial.Research Design and Methods: Four centers were randomly assigned to the HRQoL intervention (46 adolescents) or control (45 adolescents) group, with three regular visits scheduled within 12 months in both groups. In the HRQoL intervention group, HRQoL of adolescents was assessed using the Pediatric Quality of Life Inventory, and outcomes were discussed face-to-face during the consultation. The control group received care as usual. Mean differences between the groups at 12 months in physical and psychosocial well-being (Child Health Questionnaire [CHQ]-CF87/PF50, Diabetes-Specific Family Conflict Scale, and Center for Epidemiological Studies Scale for Depression), satisfaction with care (Patients' Evaluation of the Quality of Diabetes Care), and A1C were determined, controlling for baseline scores.Results: Mean scores on the CHQ subscales of psychosocial health (P < 0.001), behavior (P < 0.001), mental health (P < 0.001), and family activities (P < 0.001) improved in the HRQoL intervention group, except for adolescents with the highest A1C values. Adolescents in the HRQoL intervention group reported higher self-esteem (CHQ) at follow-up (P = 0.016), regardless of A1C, and were more satisfied with care (P = 0.009) than control subjects. No significant differences between the two groups over time were observed in A1C levels.Conclusions: Periodic monitoring and discussion of HRQoL in adolescents with diabetes is appreciated and has positive effects on their psychosocial well-being, except for those in poorest control. [ABSTRACT FROM AUTHOR]

The link between cystatin C and mortality independent of glomerular filtration rate (GFR) in adults has prompted the "Shrunken Pore Syndrome" (SPS) hypothesis, where high serum cystatin C with normal creatinine is explained by smaller glomerular pores, through which creatinine can pass freely, while the larger cystatin C, beta-trace protein (BTP) and pro-inflammatory molecules are retained. This study set out to apply the definition of SPS to children. In 294 children who underwent inulin clearance (Cin) test, serum creatinine, cystatin C and BTP were measured. For all three markers eGFR x was calculated using the full age spectrum equations. The ratio eGFR cys /eGFR crea was plotted against the error of eGFR BTP (%) (i.e. eGFR BTP -Cin)/Cin*100%). Patients with and without SPS according to different cut-off points of eGFRcys/eGFRcrea and eGFR cys /Cin (i.e. ≤0.6,0.7,0.8) were compared in terms of eGFR x , Cin, error of eGFRx(%) and eGFR BTP /eGFR crea -ratio. The ratio eGFR cys /eGFR crea and error of eGFR BTP (%) were positively correlated. The prevalence of SPS by eGFR cys /eGFR crea with a cut-off of 0.6 was 4.8%. Patients with SPS had a more negative error of eGFR cys (%) and eGFR BTP (%) and higher Cin regardless of the definition. Overestimation of eGFR crea in patients with SPS was only present when using the eGFR cys /eGFR crea rather than the eGFR cys /Cin definition. Cystatin C and BTP are related independent of creatinine, suggesting glomerular pore size as a common denominator. The prevalence of SPS in children is comparable to adults. For research in SPS, a definition based on eGFR cys /exogenous clearance study may be useful to study the effect of SPS on creatinine metabolism.

Background: Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate host defence against infection, which remain a cause of morbidity and death. Suppression commonly occurs in the first days after cessation of glucocorticoid therapy, but the exact duration is unclear. This review is the second update of a previously published Cochrane review., Objectives: To examine the occurrence and duration of HPA axis suppression after (each cycle of) glucocorticoid therapy for childhood ALL., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11), MEDLINE/PubMed (from 1945 to December 2016), and Embase/Ovid (from 1980 to December 2016). In addition, we searched reference lists of relevant articles, conference proceedings (the International Society for Paediatric Oncology and the American Society of Clinical Oncology from 2005 up to and including 2016, and the American Society of Pediatric Hematology/Oncology from 2014 up to and including 2016), and ongoing trial databases (the International Standard Registered Clinical/Social Study Number (ISRCTN) register via http://www.controlled-trials.com, the National Institutes of Health (NIH) register via www.clinicaltrials.gov, and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (WHO) via apps.who.int/trialsearch) on 27 December 2016., Selection Criteria: All study designs, except case reports and patient series with fewer than 10 children, examining effects of glucocorticoid therapy for childhood ALL on HPA axis function., Data Collection and Analysis: Two review authors independently performed study selection. One review author extracted data and assessed 'Risk of bias'; another review author checked this information., Main Results: We identified 10 studies (total of 298 children; we identified two studies for this update) including two randomised controlled trials (RCTs) that assessed adrenal function. None of the included studies assessed the HPA axis at the level of the hypothalamus, the pituitary, or both. Owing to substantial differences between studies, we could not pool results. All studies had risk of bias issues. Included studies demonstrated that adrenal insufficiency occurs in nearly all children during the first days after cessation of glucocorticoid treatment for childhood ALL. Most children recovered within a few weeks, but a small number of children had ongoing adrenal insufficiency lasting up to 34 weeks.Included studies evaluated several risk factors for (prolonged) adrenal insufficiency. First, three studies including two RCTs investigated the difference between prednisone and dexamethasone in terms of occurrence and duration of adrenal insufficiency. The RCTs found no differences between prednisone and dexamethasone arms. In the other (observational) study, children who received prednisone recovered earlier than children who received dexamethasone. Second, treatment with fluconazole appeared to prolong the duration of adrenal insufficiency, which was evaluated in two studies. One of these studies reported that the effect was present only when children received fluconazole at a dose higher than 10 mg/kg/d. Finally, two studies evaluated the presence of infection, stress episodes, or both, as a risk factor for adrenal insufficiency. In one of these studies (an RCT), trial authors found no relationship between the presence of infection/stress and adrenal insufficiency. The other study found that increased infection was associated with prolonged duration of adrenal insufficiency., Authors' Conclusions: We concluded that adrenal insufficiency commonly occurs in the first days after cessation of glucocorticoid therapy for childhood ALL, but the exact duration is unclear. No data were available on the levels of the hypothalamus and the pituitary; therefore, we could draw no conclusions regarding these outcomes. Clinicians may consider prescribing glucocorticoid replacement therapy during periods of serious stress in the first weeks after cessation of glucocorticoid therapy for childhood ALL to reduce the risk of life-threatening complications. However, additional high-quality research is needed to inform evidence-based guidelines for glucocorticoid replacement therapy.Special attention should be paid to patients receiving fluconazole therapy, and perhaps similar antifungal drugs, as these treatments may prolong the duration of adrenal insufficiency, especially when administered at a dose higher than 10 mg/kg/d.Finally, it would be relevant to investigate further the relationship between present infection/stress and adrenal insufficiency in a larger, separate study specially designed for this purpose.

The onset of behavioral problems starts in early life. This study examined whether excessive infant crying (maternal ratings) is a determinant of emotional and behavioral problems at age 5-6 years. In the Amsterdam Born Children and their Development (ABCD) study, a large prospective, observational, population-based multiethnic birth cohort, excessive infant crying (crying for three or more hours per 24 h day over the past week) during the 13th week after birth (range 11-25 weeks, SD 2 weeks), maternal burden of infant care and maternal aggressive behavior (either angry speaking, or physical aggression) was assessed using a questionnaire. Children's behavioral and emotional problems at the age of 5-6 were assessed by Goodman's Strengths and Difficulties Questionnaire (SDQ), by the subscale of generalized anxiety of the preschool anxiety scale (PAS), and by the Short Mood and Feelings Questionnaire (SMFQ). Inclusion criterion was singleton birth. Exclusion criteria were preterm born babies or congenital disorders. Among 3389 children, excessive infant crying (n = 102) was associated with a twofold increased risk of the overall problem behavior, conduct problems, hyperactivity, and mood problems at the age of 5-6 [ORs between 1.75 (95 % CI 1.09-2.81) and 2.12 (95 % CI 1.30-3.46)]. This association was mediated by maternal burden of infant care (change in odds' ratio 1-17 %) and maternal aggressive behavior (change in odds' ratio 4-10 %). There was no effect modification by the child's gender or maternal parity. Excessive infant crying was not associated with general anxiety problems. Excessive infant crying doubles the risk of behavioral, hyperactivity, and mood problems at the age of 5-6, as reported by their mother. Maternal burden of infant care partially mediates the association between excessive crying and behavioral and mood problems. Special care for mothers with a high burden of care for their excessive crying infant, notwithstanding their own good health, can be a feasible strategy for possible prevention of mood and behavioral problems in their children later in life.

Background: Suboptimal prenatal and early postnatal growths are associated with obesity in later life, but the underlying mechanisms are unknown. The aim of this study was to systematically review the literature that reports on the longitudinal association of (i) birth size or (ii) infant growth with later (i) energy intake, (ii) eating behaviors, (iii) physical activity or (iv) sedentary behavior in humans., Methods: A comprehensive search of MEDLINE, EMBASE, PsycINFO and The Cochrane Library was conducted to identify relevant publications. We appraised the methodological quality of the studies and synthesized the extracted data through a best-evidence synthesis., Results: Data from 41 publications were included. The quality of the studies was high in three papers, moderate in 11 and low in the large majority (n = 27) of papers appraised. Our best-evidence synthesis indicates that there is no evidence for an association of birth weight with later energy intake, eating behavior, physical activity or sedentary behavior. We found moderate evidence for an association of extreme birth weights (at both ends of the spectrum) with lower physical activity levels at a later age. Evidence for the association of infant growth with energy balance-related behavior was generally insufficient., Conclusions: We conclude that current evidence does not support an association of early-life growth with energy balance-related behaviors in later life, except for an association of extreme birth weights with later physical activity., Competing Interests: The authors have declared that no competing interests exist.

Objective: Small birth size and rapid postnatal growth have been associated with higher future blood pressure. The timing of these effects, the relative importance of weight gain and linear growth and the role of infant feeding need to be clarified., Methods: We assessed how blood pressure relates to birth weight, infant and childhood growth and infant feeding (duration of exclusive breastfeeding and timing of introduction of complementary feeding) in 2227 children aged 5 years from a prospective cohort study (Amsterdam Born Children and their Development). Postnatal growth was represented by statistically independent measures of relative weight gain (weight gain independent of height) and linear growth in four age periods during infancy (0-1 month; 1-3 months; 3-6 months; 6-12 months) and from 12 months to 5 years., Results: Lower birth weight was associated with higher childhood diastolic blood pressure (-0.38 mm Hg.SD-1; P = 0.007). Faster relative weight gain and linear growth after 1 month were positively associated with systolic and diastolic blood pressure. Associations of linear growth with systolic blood pressure ranged from 0.47 to 1.49 mm Hg.SD-1; P<0.01 for all. Coefficients were similar for different periods of infancy and also for relative weight gain and linear growth. Compared to breastfeeding <1 month, breastfeeding >1 month was associated with lower blood pressure (e.g. >6 months -1.56 mm Hg systolic blood pressure; P<0.001). Compared to >6 months, introduction of complementary feeding <6 months was associated with higher blood pressure (e.g. 4-6 months 0.91 mm Hg systolic blood pressure; P = 0.004)., Conclusions: After the age of one month faster growth in either weight or height is associated with higher childhood blood pressure. It is unknown whether faster weight gain and linear growth carry the same risk for adult hypertension and cardiovascular morbidity. Longer breastfeeding and delayed introduction of complementary feeding may be associated with lower adult blood pressure., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Previous research showed that children with cancer are at risk for developing behavioral adjustment problems after successful treatment; however, the course of adjustment remains unclear. This study focuses on adjustment trajectories of children during treatment for acute lymphoblastic leukemia (ALL) and aims to distinguish subgroups of patients showing different trajectories during active treatment, and to identify sociodemographic, medical, and psychosocial predictors of the distinct adjustment trajectories., Methods: In a multicenter longitudinal study, 108 parents of a child (response rate 80 %) diagnosed with ALL were assessed during induction treatment (T0), after induction/consolidation treatment (T1), and after end of treatment (T2). Trajectories of child behavioral adjustment (Child Behavior Checklist; CBCL) were tested with latent class growth modeling (LCGM) analyses., Results: For internalizing behavior, a three-trajectory model was found: a group that experienced no problems (60 %), a group that experienced only initial problems (30 %), and a group that experienced chronic problems (10 %). For externalizing behavior, a three-trajectory model was also found: a group that experienced no problems (83 %), a group that experienced chronic problems (12 %), and a group that experienced increasing problems (5 %). Only parenting stress and baseline QoL (cancer related) were found to contribute uniquely to adjustment trajectories., Conclusions: The majority of the children (77 %) showed no or transient behavioral problems during the entire treatment as reported by parents. A substantial group (23 %) shows maladaptive trajectories of internalizing behavioral problems and/or externalizing behavioral problems. Screening for risk factors for developing problems might be helpful in early identification of these children., Competing Interests: Compliance with ethical standards The study was approved by each of the medical ethical review boards of the participating institutions. Informed consent was obtained from all participants in this study. Conflict of interest This study was supported by the Dutch Childhood Oncology Group (SKION). The authors have had full access to all data in the study and had full responsibility for the design of the study, collection, analysis, and interpretation of data, and the writing of the report.

Background: The purpose of this study was to examine the association of birth weight and infant growth with childhood autonomic nervous system (ANS) activity and to assess whether ANS activity mediates the associations of birth weight and infant growth with energy-balance-related behaviours, including energy intake, satiety response, physical activity and screen time., Methods: In 2089 children, we prospectively collected birth weight, infant growth defined as conditional weight and height gain between birth and 12 months and-at 5 years-indices of cardiac ANS activity and parent-reported energy-balance-related behaviours. A mediation analysis was conducted, based on MacKinnon's multivariate extension of the product-of-coefficients strategy., Results: Birth weight and infant height gain were inversely associated with sympathetic, but not parasympathetic, activity at age 5. Infant weight gain was not associated with childhood ANS activity. Infant weight gain was predictive of increased childhood screen time and infant height gain of diminished childhood energy intake, but sympathetic activity did not mediate these associations., Conclusions: Low-birth-weight children have higher sympathetic activity, which is considered a risk factor for cardiovascular disease. Height gain in infancy seems to be beneficial for childhood sympathetic activity. However, sympathetic activity was no mediator of the associations of infant growth with childhood energy-balance-related behaviours. As individual differences in ANS activity predict increased risk of cardiovascular disease, these differences may offer insight into the early-life origins of chronic diseases and provide further basis for public health strategies to optimize birth weight and infant growth., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Low and high birth weight and accelerated postnatal weight gain are associated with an increased risk of obesity. Perinatal effects on energy intake and eating behavior have been proposed as underlying mechanisms. This study aimed to examine the independent associations of birth weight and postnatal weight and height gain with childhood energy intake and satiety response., Methods: In a birth cohort study, we used data from 2227 children (52% male), mean age 5.6 (±0.4) years. Mean daily energy intake and satiety response were parent-reported through validated questionnaires. Exposures were birth weight z-score and conditional weight and height gain between 0-1, 1-3, 3-6, 6-12 months and 12 months to 5 years. Conditional weight and height are residuals of current weight and height regressed on prior growth data, to represent deviations from expected growth. Analyses were adjusted for a set of potential confounding variables., Results: Conditional weight gain between 1-3, 3-6 months and 12 months to 5 years was significantly associated with energy intake, with 29.7 (95%-CI: 4.6; 54.8), 24.0 (1.8; 46.1) and 79.5 (29.4; 129.7) kcal/day more intake for each Z-score conditional weight gain between 1-3, 3-6 months and 12 months to 5 years, respectively. Conditional height gain between 0-1, 1-3 months and 12 months to 5 years was negatively associated with energy intake (β: -42.0 [66.6; -17.4] for 0-1 months, -35.1 [-58.4; -11.8] for 1-3 months and -37.4 [-72.4; -2.3] for 12 months to 5 years). Conditional weight gain in all periods was negatively associated with satiety response, with effect sizes from - 0.03 (-0.06; -0.002) in early infancy to -0.12 (-0.19; -0.06) in childhood. Birth weight was not associated with energy intake or satiety response., Conclusions: Our findings suggest that accelerated infant and childhood weight gain are associated with increased energy intake and diminished satiety response at 5 years. Accelerated height gain seems to be beneficial for childhood energy intake. This perinatal 'programming' of energy intake and eating behavior provide a potential mechanism linking early life influences with later obesity and cardiovascular disease.

Background: Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate host defence against infections, which remains a cause of morbidity and death. Suppression commonly occurs in the first days after cessation of glucocorticoid therapy, but the exact duration is unclear. This review is an update of a previously published Cochrane review., Objectives: To examine the occurrence and duration of HPA axis suppression after (each cycle of) glucocorticoid therapy for childhood ALL., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 6, 2014), MEDLINE/PubMed (from 1945 to June 2014), and EMBASE/Ovid (from 1980 to June 2014). In addition, we searched reference lists of relevant articles, conference proceedings (the International Society for Paediatric Oncology and the American Society of Clinical Oncology from 2005 to 2013), and ongoing trial databases (the ISRCTN register and the NIH register via http://www.controlled-trials.com in June 2014)., Selection Criteria: All study designs, except case reports and patient series with fewer than 10 children, examining the effect of glucocorticoid therapy for childhood ALL on the HPA axis function., Data Collection and Analysis: Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessment, which another review author checked., Main Results: We identified eight studies (total of 218 children), including two randomised controlled trials (RCTs), that assessed the adrenal function. None of the studies assessed the HPA axis at the level of the hypothalamus, pituitary, or both. Due to substantial differences between studies, we could not pool results. All of the studies had some methodological limitations. The included studies demonstrated that adrenal insufficiency occurs in nearly all children in the first days after cessation of glucocorticoid treatment for childhood ALL. The majority of children recovered within a few weeks, but a small number of children had ongoing adrenal insufficiency lasting up to 34 weeks. In the RCTs, the occurrence and duration of adrenal insufficiency did not differ between the prednisone and dexamethasone arms. In one study, it appeared that treatment with fluconazole prolonged the duration of adrenal insufficiency. Furthermore, one of the studies evaluated the presence of infections or stress episodes, or both as a risk factor for adrenal insufficiency. The authors found no relationship between the presence of infection/stress and adrenal insufficiency., Authors' Conclusions: We concluded that adrenal insufficiency commonly occurs in the first days after cessation of glucocorticoid therapy for childhood ALL, but the exact duration is unclear. Since no data on the level of the hypothalamus and the pituitary were available, we cannot make any conclusions regarding those outcomes. Clinicians should consider prescribing glucocorticoid replacement therapy during periods of serious stress in the first weeks after cessation of glucocorticoid therapy for childhood ALL to reduce the risk of life-threatening complications. However, more high-quality research is needed for evidence-based guidelines for glucocorticoid replacement therapy.Special attention should be paid to patients receiving fluconazole therapy, and perhaps similar antifungal drugs, as this may prolong the duration of adrenal insufficiency.Finally, it would be relevant to further investigate the relationship between present infection/stress and adrenal insufficiency in a larger, separate study specially designed for this purpose.

Background: Low birth weight and accelerated infant growth are independently associated with childhood obesity. We hypothesized that birth weight and infant growth are associated with physical fitness in childhood, and thereby could act as a link in the developmental origins of obesity. In addition, we assessed whether these associations were mediated by fat-free mass (FFM), moderate-to-vigorous physical activity (MVPA) or sedentary behavior (SB)., Methods: We assessed physical fitness in 194 children of Dutch ethnicity aged 8.6 (±0.35) years from the ABCD cohort. Aerobic fitness was assessed using the 20-meter multistage shuttle run test (20-m MSRT), and neuromuscular fitness using the standing broad jump (SBJ) test and hand grip strength test. MVPA and SB were measured by accelerometry, and FFM by bioelectrical impedance analysis. Low birth weight was defined as below the 10th percentile and accelerated infant growth as an s.d. score weight gain of >0.67 between birth and 12 months., Results: Children with low birth weight and subsequent accelerated infant growth attained a lower 20-m MSRT score than the remainder of the cohort, adjusted for multiple confounders (P<0.01). Birth weight and infant growth were both independently positively associated with hand grip strength, but not after adjusting for current height and body mass index. There was no association of birth weight or infant growth with SBJ. FFM mediated >75% of the association of birth weight and infant growth with hand grip strength, but FFM, MVPA and SB did not mediate the associations with 20-m MSRT., Conclusions: Our results indicate that low birth weight and accelerated infant growth might negatively affect childhood aerobic and neuromuscular fitness. Differences in FFM largely explain the developmental origins of neuromuscular fitness. Consequently impaired fitness may constitute a link between low birth weight, accelerated infant growth and obesity. Hence, optimization of fitness in these children may affect their obesity and cardiovascular disease risk.

Background: Growth and feeding during infancy have been associated with later life body mass index. However, the associations of infant feeding, linear growth and weight gain relative to linear growth with separate components of body composition remain unclear., Methods: Of 5551 children with collected growth and infant-feeding data in a prospective cohort study (Amsterdam Born Children and their Development), body composition measured using bioelectrical impedance analysis at the age of 5-6 years was available for 2227 children. We assessed how feeding (duration of full breastfeeding and timing of introduction of complementary feeding) and conditional variables representing linear growth and relative weight gain were associated with childhood fat-free mass (FFM) and fat mass (FM)., Results: Birth weight was positively associated with both FFM and FM in childhood, and more strongly with FFM than FM. Faster linear growth and faster relative weight gain at all ages in infancy were positively associated with childhood FFM and FM. The associations with FM were stronger for relative weight gain than for linear growth (FM z score: β coefficient 0.23 (95% con 0.19 to 0.26), P<0.001 and 0.14 (0.11 to 0.17), P<0.001 per s.d. change in relative weight gain and linear growth between 1 and 3 months, respectively). Compared with full breastfeeding <1 month, full breastfeeding >6 months was associated with lower FM (FM z score: -0.17 (-0.28 to -0.05), P=0.005) and lower FFM (FFM z score: -0.13 (-0.23 to -0.03), P=0.015), as was the introduction of complementary feeding >6 months (FM z score: -0.22 (-0.38 to -0.07), P=0.004), compared with <4 months., Conclusions: Faster infant weight gain is associated with a healthier childhood body composition when it is caused by faster linear growth. Full breastfeeding >6 months and introduction of complementary feeding >6 months are associated with lower childhood FM.

Purpose: Improvement in survival of pediatric acute lymphoblastic leukemia (ALL) has increased the attention to quality of life (QoL) . QoL is impaired during maintenance treatment, but little is known about QoL during induction therapy. Identification of patients with poor QoL during induction will provide opportunities for early interventions, and may subsequently improve future QoL. This national multi-center study aimed to assess QoL and its determinants during ALL induction treatment., Methods: Proxy reports of the Child Health Questionnaire (CHQ) and the PedsQL cancer version were collected. Child, treatment, and parental characteristics were analyzed as potential determinants in a multiple regression model., Results: One hundred thirty parents of children participated (response rate 82 %), median child age was 5.7 years and 48 % were female. QoL, as measured with the CHQ, was significantly lower than the norm, the effect sizes were large, and the differences were clinically relevant. Physical QoL was more often affected than psychosocial QoL. Regression models could be constructed for 4/ 10 CHQ scales and 6/ 8 PedsQL cancer scales, accounting for 7 to 36 % of the variance in scores. Impaired QoL was most often associated with older children, girls, and time since diagnosis. Also, father respondents seem to have a lower QoL perception compared to mother respondents although this needs to be confirmed in future research., Conclusions: Specific counseling for subsets of patients with a higher risk of low QoL during the early phases of therapy is warranted.

Objectives: To analyse which dysmorphic features are most recognised in newborns with Down syndrome (DS). Furthermore to evaluate the communication techniques used by clinicians to inform parents about the postnatal diagnosis and compare these to current best practice guidelines., Study Design: Prospective study of a birth cohort of newborns with DS born between 1 January 2003 and 31 December 2006 registered by the Dutch Paediatric Surveillance Unit (DPSU)., Results: A total of 586 children with trisomy 21 were analysed. Most recognised dysmorphic features in DS newborns were 'upslanted palpebral fissures' (74.1%; n = 426), 'hypotonia' (73.7%; n = 424) and 'epicanthic folds' (68.5%; n = 394). The majority of parents were informed about the suspected diagnosis on the day of birth (76.5%; n = 390). Hospital deliveries had a significantly earlier suspected diagnosis (mean age 3-4 days) compared with home deliveries (mean age 7 days) (P < 0.05). In 10% (n = 44), paediatricians described dissatisfaction with the first conversation with parents. In 88.9% (n = 499) parents were both present when the diagnosis was told, however the child was not present during the conversation in 51.3% (n = 288). In 10.8% (n = 61) parents were not informed about local parent support groups or community resources., Conclusion: DS is still often diagnosed after birth, usually on the first day of postnatal life. Most identified clinical features were upslanted palpebral fissures, epicanthic folds and hypotonia. Special attention for recognition of all present clinical features is needed for early diagnosis. Appropriate communication with the parents of the message that their child has DS can be difficult. Guidelines can help to make counselling easier and more effective, which in turn may increase parental satisfaction. Not all recommendations for the first conversation with parents were fully implemented in Dutch clinical practice., (© 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Highly prevalent maternal psychosocial complaints are accompanied by increases in glucocorticoid stress hormones, which may predispose the offspring for type 2 diabetes and cardiovascular disease later in adulthood. The aim of the current research is to study whether prenatal maternal psychosocial stress is associated with parameters of blood glucose metabolism in their children aged 5-6 years. The study design was a prospective birth cohort (the Amsterdam Born Children and their Development study, the Netherlands). Depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain were recorded by questionnaire (gestational week 16). A cumulative score was also calculated. Possible sex differences in the associations were considered. The subjects were 1952 mother-child pairs. Outcome measures were fasting glucose (n=1952), C-peptide and insulin resistance (HOMA2-IR) (n=1478) in the children at the age of 5-6 years. The stress scales, single and cumulative, were not associated with glucose/C-peptide/insulin resistance (all P>0.05). We did not find evidence for sex differences. In conclusion, we did not find evidence for an association between psychosocial stress during early pregnancy and parameters of glucose metabolism in offspring at the age of 5-6 years. Differences emerging later in life or in response to a metabolic challenge should not be ruled out.

Background: Evidence on the association between different screen behaviours and cardiometabolic biomarkers in children is limited. We examined the independent relationship of TV time and PC time with cardiometabolic biomarkers in Dutch 5-6 year old children., Methods: Cross-sectional analyses were conducted December 2012-March 2013 using data from a multi-ethnic cohort (the ABCD study, n = 1,961). TV and PC time and physical activity were assessed by parent-report. Body weight, height, waist circumference and blood pressure were measured using a standard protocol. Fasting capillary blood samples were collected. A cardiometabolic function score was computed as the mean of the inverted standardised values of waist circumference, mean of systolic and diastolic blood pressure, glucose, HDLC (not inverted), and triglycerides., Results: Mean TV time was 1.2 (± 0.8) hr/day and mean PC time was 0.2 (± 0.4) hr/day. After adjustment for birth weight, height, maternal education, PC time, and physical activity, excessive TV time (>2 hrs/day) was adversely associated with waist circumference (b = 0.39, 95% CI: 0.004;0.78) while PC time was beneficially associated with HDLC levels (b = 0.04, 95% CI: 0.001;0.08). We found no additional significant associations of TV time, or PC time with any of the cardiometabolic biomarkers., Conclusions: We found no convincing evidence for an association between TV or PC time and cardiometabolic function in apparently healthy 5-6 yr olds.

Objective: To investigate whether (1) maternal psychosocial stress (depression/anxiety) during pregnancy is associated with offspring vascular function and (2) whether any association differs depending on the gestational timing of exposure to stress. We also investigated whether any association is likely to be due to intrauterine mechanisms by (3) comparing with the association of paternal stress with offspring vascular function and (4) examining whether any prenatal association is explained by maternal postnatal stress., Methods and Results: Associations were examined in a UK birth cohort, with offspring outcomes (systolic and diastolic blood pressure, SBP and DBP, endothelial function assessed by brachial artery flow-mediated dilatation (FMD); arterial stiffness assessed by carotid to radial pulse wave velocity (PWV), brachial artery distensibility (DC), and brachial artery diameter (BD) assessed at age 10-11 years (n = 4,318). Maternal depressive symptoms and anxiety were assessed at 18 and 32 weeks gestation and 8 months postnatally. Paternal symptoms were assessed at week 19. With the exception of DBP and BD, there were no associations of maternal depressive symptoms with any of the vascular outcomes. Maternal depressive and anxiety symptoms were associated with lower offspring DBP and wider BD, though the latter attenuated to the null with adjustment for confounding factors. Paternal symptoms were not associated with offspring outcomes. Maternal postnatal depressive symptoms were associated with lower offspring SBP., Conclusions: We found no evidence to support the hypothesis that maternal stress during pregnancy adversely affects offspring vascular function at age 10-12 years via intrauterine mechanisms., (© Authors 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Children with Down syndrome (DS) have an increased susceptibility to infections, due to altered humoral and/or cellular immunity. The aim of the study was to determine the cytokine production in whole blood of children with DS upon stimulation with heat-killed Streptococcus pneumoniae and lipopolysaccharide (LPS), in comparison with their healthy siblings., Methods: Whole blood of 61 children with DS and 57 of their healthy siblings was stimulated with 200 ng/ml LPS and 4 × 10(7) colony-forming units/ml S. pneumoniae during 6, 24, and 48 h. Concentrations of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-12p70, and IL-10 were determined at all time points., Results: Children with DS show an increased IL-10 production upon stimulation with S. pneumoniae compared to their healthy siblings. At most time points, no significant differences were seen in cytokine production upon stimulation with LPS., Conclusion: Children with DS may be prone to a severe course of pneumococcal pneumonia, because of an increased anti-inflammatory response.

Background: Measuring utilities and health-related quality of life (HRQL) in children is challenging due to their cognitive abilities and changing developmental stages., Purpose: . To identify methodological issues on utility measurements in children, we performed a systematic review on utilities measured with a single instrument, the Health Utilities Index (HUI), in pediatric acute lymphoblastic leukemia (ALL). The secondary goal was to facilitate future cost-utility analyses without the need for time-consuming assessments. Data Sources. PubMed, Embase, Cochrane Library, CINAHL, and PsycINFO were searched from inception to June 2012. Studies had to report on utility scores in pediatric ALL, either on or after treatment, to be included., Results: . Fifteen studies were included. Most studies had methodological shortcomings, which mainly concerned, Study Design: and definition and representativeness of the study group. Utility scores were dependent on treatment variables, and there generally was an improvement in HRQL as treatment or survivorship advanced. In general, proxy-respondents were less reliable for subjective phenomena than for observable conditions. HUI2 and HUI3 scores were not interchangeable. Limitations. Studies may have been missed because no validated search method for utility studies exists, due to language bias or the exclusion of non-peer-reviewed papers., Conclusions: . Most studies in this review were methodologically suboptimal. Future developments should focus on including developmentally appropriate items for the whole pediatric age group. Adding disease-specific domains may enhance the sensitivity and responsiveness of instruments. Efforts should be undertaken to elicit valuation of health states from older children and teenagers as much as possible. For now, it remains difficult to make valid and informed decisions on the financing of interventions until health state valuation in children has become more methodologically robust.

Survivors of childhood ALL have been demonstrated to have increased morning cortisol levels compared to healthy controls. Information regarding the response of the HPA axis and the sympathetic nervous system to stress in childhood ALL survivors is not available. The present study aimed at assessing the endocrine and cardiovascular stress response in childhood ALL survivors and healthy controls by evaluating perceived stress on visual analog scales, by determining saliva cortisol, blood pressure and heart rate in response to the Trier Social Stress Test for Children (TSST-C). Fifty survivors who had completed their treatment for childhood ALL 57 (IQR 47.0-72.3) months before and 50 healthy age and sex matched controls were included. Exposure to the TSST-C induced a significant response of perceived stress, saliva cortisol and cardiovascular outcome variables in the total study group. These responses did not significantly differ between survivors of childhood ALL and healthy controls. We conclude that the endocrine and cardiovascular response to social stress are intact in survivors of childhood ALL., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aim: In 2004, a model identifying children at risk of academic or behavioural limitations after bacterial meningitis (BM) was presented. Risk factors were male gender, low birthweight, lower educational level of the father, Streptococcus pneumoniae, lower cerebrospinal fluid (CSF) leucocyte count, delay between admission and start of antibiotics, dexamethasone <2 days, seizures and prolonged fever. The aim of this study was to validate that prediction model in an independent cohort., Methods: Academic or behavioural limitations were determined in 93 Dutch school-age BM survivors. Risk factors for limitations were obtained from medical files. Validation was performed by applying the model in the cohort, then assessing discrimination and goodness of fit. Multiple imputation techniques were used to deal with missing values., Results: Although fit of the model appeared good when it came to similarity of expected and observed cases (p-value of the Hosmer-Lemeshow test 0.24-0.57), discrimination was poor. Area under the curve (AUC) of the receiver operated characteristics (ROC) curve of the model was 0.83 (95% CI: 0.77-0.89) in the development cohort and 0.53 (95% CI: 0.41-0.65) in the validation cohort., Conclusion: External validation of the model was unsuccessful. It is not suitable for implementation in practice., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Low birth weight and accelerated infant growth have been identified as independent risk factors for childhood and adult obesity and cardiovascular disease. This led to the 'Developmental Origins of Health and Disease' (DOHaD) hypothesis, stating that environmental factors during pregnancy and early postnatal life affect disease risk in later life. There is growing evidence that perinatal factors may influence adult health through the programming of energy balance regulation, including sedentary behavior and physical activity. The present study focuses on the influence of birth weight and infant growth on physical fitness, physical activity and sedentary behavior in 8-9 year old children, as this might partly explain the higher obesity and cardiovascular risk associated with low birth weight and accelerated infant growth. In addition, this study provides the opportunity for a validation study of a linguistic and cross-cultural translated physical activity questionnaire compared to accelerometer data. This article describes the study protocol for this study., Methods/design: This is a study embedded in the Amsterdam Born Children and their Development (ABCD) birth cohort. In 200 children of Dutch ethnicity, physical fitness, physical activity and sedentary behavior were assessed at age 8-9. We measured aerobic fitness using the 20 meter multistage shuttle run test, and neuromuscular fitness using the standing broad jump and handgrip strength test. Sedentary behavior and physical activity levels were measured using accelerometry. All children also completed a translated physical activity questionnaire, the scores of which will be compared to accelerometry data to assess the construct validity of the questionnaire in Dutch school-aged children., Discussion: This study will be the first population-based prospective cohort study to address the association of both prenatal and postnatal growth with physical fitness and objectively-assessed physical activity and sedentary behavior. This will contribute to a better understanding of the way perinatal growth relate to lifestyle and obesity in later life. The results may guide both future studies in the field of DOHaD, and public health strategies in the prevention of childhood obesity.

Background: Although there is convincing evidence for the association between small for gestational age (SGA) and socioeconomic status (SES), it is not known to what extent explanatory factors contribute to this association., Aim: To examine to what extent risk factors could explain educational inequalities in SGA., Study Design: In this study fully completed data were available for 3793 pregnant women of Dutch origin from a population-based cohort (ABCD study). Path-analysis was conducted to examine the role of explanatory factors in the relation of maternal education to SGA., Results: Low-educated pregnant women had a higher risk of SGA offspring compared to the high-educated women (OR 1.98, 95% CI 1.35-2.89). In path-analysis, maternal cigarette smoking and maternal height explained this association. Maternal age, hypertension, chronic disease, late entry into antenatal care, neighborhood income, underweight, environmental cigarette smoking, drug abuse, alcohol use, caffeine intake, fish intake, folic acid intake, anxiety, and depressive symptoms did not play a role in the association between maternal education and SGA birth., Conclusion: Among a large array of potential factors, the elevated risk of SGA birth among low-educated women appeared largely attributable to maternal smoking and to a lesser extent to maternal height. To reduce educational inequalities more effort is required to include low-educated women especially in prenatal intervention programs such as smoking cessation programs instead of effort into reducing other SGA-risk factors, though these factors might still be relevant at the individual level., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Body mass index (BMI) does not make a distinction between fat mass and lean mass. In children, high fat mass appears to be associated with low maternal education, as well as low lean mass because maternal education is associated with physical activity. Therefore, BMI might underestimate true obesity in children of low-educated mothers., Objective: To investigate the associations of maternal education with fat mass index (FMI), lean mass index (LMI) and BMI., Methods: In total, 1965 Dutch children from a prospective cohort, aged 5.7 years (standard deviation 0.5), had available data on body composition based on bioelectrical impedance analysis., Results: Maternal education was not associated with BMI after adjustment for confounders. In contrast, children of low-educated mothers had a higher FMI (β 0.28 95% confidence interval [CI] 0.07; 0.49) and a lower LMI (β -0.18 95% CI -0.33; -0.03) compared with children of high-educated mothers., Conclusions: This suggests that BMI underestimates the educational gradient of childhood obesity., (© 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.)

Background: Prevalence rates of psychosocial stress during pregnancy are substantial. Evidence for associations between psychosocial stress and birth outcomes is inconsistent. This study aims to identify and characterize different clusters of pregnant women, each with a distinct pattern of psychosocial stress, and investigate whether birth outcomes differ between these clusters., Methods: Latent class analysis was performed on data of 7740 pregnant women (Amsterdam Born Children and their Development study). Included constructs were depressive symptoms, state anxiety, job strain, pregnancy-related anxiety and parenting stress., Results: Five clusters of women with distinct patterns of psychosocial stress were objectively identified. Babies born from women in the cluster characterized as 'high depression and high anxiety, moderate job strain' (12%) had a lower birth weight, and those in the 'high depression and high anxiety, not employed' cluster (15%) had an increased risk of pre-term birth., Conclusions: Babies from pregnant women reporting both high levels of anxiety and depressive symptoms are at highest risk for adverse birth outcomes.

The autonomic nervous system (ANS) controls mainly automatic bodily functions that are engaged in homeostasis, like heart rate, digestion, respiratory rate, salivation, perspiration and renal function. The ANS has two main branches: the sympathetic nervous system, preparing the human body for action in times of danger and stress, and the parasympathetic nervous system, which regulates the resting state of the body. ANS activity can be measured invasively, for instance by radiotracer techniques or microelectrode recording from superficial nerves, or it can be measured non-invasively by using changes in an organ's response as a proxy for changes in ANS activity, for instance of the sweat glands or the heart. Invasive measurements have the highest validity but are very poorly feasible in large scale samples where non-invasive measures are the preferred approach. Autonomic effects on the heart can be reliably quantified by the recording of the electrocardiogram (ECG) in combination with the impedance cardiogram (ICG), which reflects the changes in thorax impedance in response to respiration and the ejection of blood from the ventricle into the aorta. From the respiration and ECG signals, respiratory sinus arrhythmia can be extracted as a measure of cardiac parasympathetic control. From the ECG and the left ventricular ejection signals, the preejection period can be extracted as a measure of cardiac sympathetic control. ECG and ICG recording is mostly done in laboratory settings. However, having the subjects report to a laboratory greatly reduces ecological validity, is not always doable in large scale epidemiological studies, and can be intimidating for young children. An ambulatory device for ECG and ICG simultaneously resolves these three problems. Here, we present a study design for a minimally invasive and rapid assessment of cardiac autonomic control in children, using a validated ambulatory device (1-5), the VU University Ambulatory Monitoring System (VU-AMS, Amsterdam, the Netherlands, www.vu-ams.nl).

Purpose: Increase of survival in pediatric acute lymphoblastic leukemia (ALL) has made outcomes such as health-related quality of life (HRQL) and economic burden more important. To make informed decisions on the use of healthcare resources, costs as well as utilities need to be taken into account. Among the preference-based HRQL instruments, the Health Utilities Index (HUI) is the most employed in pediatric cancer. Information on utility scores during ALL treatment and in long-term survivors is available, but utility scores in short-term survivors are lacking. This study assesses utility scores, health state, and HRQL in short-term (6 months to 4 years) ALL survivors., Methods: Cross-sectional single-center cohort study of short-term ALL survivors using HUI3 proxy assessments., Results: Thirty-three survivors (median 1.5 years off treatment) reported 14 unique health states. The majority of survivors (61 %) enjoyed a perfect health, but 21 % had three affected attributes. Overall, HRQL was nonsignificantly lower compared to the norm, although the difference was large and may be clinically relevant. Cognition was significantly impaired (p = 0.03)., Conclusion: Although 61 % of short-term survivors of ALL report no impairment, the health status of the other patients lead to a clinically important impaired HRQL compared to norms. Prospective studies assessing utility scores associated with pediatric ALL should be performed, enabling valid and reliable cost-utility analyses for policy makers to make informed decisions.

Background: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. This cross-sectional study examined sleep and fatigue in relation to depression and quality of life (QoL) after treatment for childhood ALL., Procedure: Sleep, fatigue, depression, and QoL were evaluated by parent proxy and/or child self-reports of the Children's Sleep Habits Questionnaire, the PedsQL™ multidimensional fatigue scale, the Children's Depression Inventory and the Child Health Questionnaire. All total scores were compared to Dutch norm references., Results: Sixty-two children were included, being 36 (interquartile range 22-62) months after finishing treatment. Parents rated the ALL survivors as having more disturbed sleep, more fatigue and poorer physical QoL compared to the Dutch norm. ALL survivors themselves reported less sleep problems, less depressive symptoms, and better psychosocial QoL than the Dutch norm. More sleep disturbances and fatigue correlated with more symptoms of depression and a worse QoL., Conclusions: Differences in parental and self-reports, including worse parental ratings, might be explained by worried parents and/or the adaptive style of the children. Impaired sleep and fatigue correlated with more depressive symptoms and a worse QoL., (Copyright © 2012 Wiley Periodicals, Inc.)

Infant nutrition may influence eating behaviour and food preferences in later life. The present study explores whether exclusive breast-feeding duration and age at introduction of solid foods are associated with children's eating behaviour and fruit and vegetable intake at age 5 years. Data were derived from the Amsterdam Born Children and their Development study, a prospective birth cohort in the Netherlands, and included 3624 children. During infancy, data on infant nutrition were collected. Child eating behaviour (satiety responsiveness, enjoyment of food, slowness in eating and food responsiveness) was assessed with the Children's Eating Behaviour Questionnaire; and fruit and vegetable intake was calculated from a validated child FFQ. Both questionnaires were filled in by the mothers after their child turned 5 years. Exclusive breast-feeding duration was not associated with later eating behaviour, although longer exclusive breast-feeding was significantly associated with a higher vegetable intake at age 5 years. Compared with the introduction of solid foods at age 6 months, introduction before the age of 4 months was associated with less satiety responsiveness at age 5 years (β -0·09; 95 % CI -0·16, -0·02). Introducing solid foods after 6 months was associated with less enjoyment of food (β -0·07; 95 % CI -0·12, -0·01) and food responsiveness (β -0·04; 95 % CI -0·07, -0·01). Introducing solid foods before the age of 4 months was associated with a higher fruit intake compared with introduction at 6 months. These findings suggest that prolonged breast-feeding and introduction of solid foods between 4 and 6 months may lead to healthier eating behaviour and food preferences at age 5 years.

Purpose: This study aimed firstly to investigate the contribution of maternal 25(OH) vitamin D to the association of maternal education and small-for-gestational-age birth weight (SGA) and secondly to examine whether the contribution of 25(OH) vitamin D differs by overweight, season, and maternal smoking., Methods: Logistic regression analysis was carried out in this study, using data of 2,274 pregnant women of Dutch ethnicity from the ABCD study, a population-based cohort study in the Netherlands. Maternal 25(OH) vitamin D was measured in early pregnancy. Stratified analyses were conducted for overweight, season of blood sampling, and smoking., Results: Low-educated women had lower 25(OH) vitamin D levels compared to high-educated women, and women in the lowest 25(OH) vitamin D quartile had a higher risk of SGA offspring. In addition, low-educated women had a higher risk of SGA offspring (OR 1.95 [95% CI: 1.20-3.14]). This association decreased with 7% after adjustment for 25(OH) vitamin D (OR 1.88 [95% CI 1.16-3.04]). In stratified analyses, adjustment for 25(OH) vitamin D resulted in a decrease in OR of about 17% in overweight women and about 15% in women who conceived in wintertime., Conclusions: 25(OH) vitamin D appears to be a modifiable contributor to the association between low maternal education and SGA offspring, particularly in overweight women and women who conceived in the winter period. In those women, increasing the intake of vitamin D, either through dietary adaptation or through supplementation in order to achieve the recommendation, could be beneficial.

Background: The objective of this study was to evaluate the mediating role of maternal early pregnancy plasma levels of long chain polyunsaturated fatty acids (LCPUFAs) in the association of interpregnancy interval (IPI) with birth weight and smallness for gestational age (SGA) at birth., Methods: We analysed a subsample of the Amsterdam Born Children and their Development (ABCD) cohort, comprising 1,659 parous pregnant women recruited between January 2003 and March 2004. We used linear and logistic regression to evaluate the associations between fatty acid status, interpregnancy interval and pregnancy outcome., Results: Low plasma phospholipids concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-gamma-linolenic acid (DGLA), and high concentrations of arachidonic acid (AA) during early pregnancy were associated with reduced birth weight and/or an increased risk of SGA. Short IPIs (< 6 months, with 18-23 months as a reference) were associated with a mean decrease of 207.6 g (SE: ± 73.1) in birth weight (p = 0.005) and a twofold increased risk of SGA (OR: 2.05; CI: 0.93-4.51; p = 0.074). Adjustment for maternal fatty acid concentrations did not affect these results to any meaningful extent., Conclusions: Despite the observed association of maternal early pregnancy LCPUFA status with birth weight and SGA, our study provides no evidence for the existence of an important role of maternal EPA, DHA, DGLA or AA in the association of short interpregnancy intervals with birth weight and SGA.

Objective: This study aimed external validation of a formerly developed prediction model identifying children at risk for hearing loss after bacterial meningitis (BM). Independent risk factors included in the model are: duration of symptoms prior to admission, petechiae, cerebral spinal fluid (CSF) glucose level, Streptococcus pneumoniae and ataxia. Validation helps to evaluate whether the model has potential in clinical practice., Study Design: 116 Dutch school-age BM survivors were included in the validation cohort and screened for sensorineural hearing loss (>25 dB). Risk factors were obtained from medical records. The model was applied to the validation cohort and its performance was compared with the development cohort. Validation was performed by application of the model on the validation cohort and by assessment of discrimination and goodness of fit. Calibration was evaluated by testing deviations in intercept and slope. Multiple imputation techniques were used to deal with missing values., Results: Risk factors were distributed equally between both cohorts. Discriminative ability (Area Under the Curve, AUC) of the model was 0.84 in the development and 0.78 in the validation cohort. Hosmer-Lemeshow test for goodness of fit was not significant in the validation cohort, implying good fit concerning the similarity of expected and observed cases. There were no significant differences in calibration slope and intercept. Sensitivity and negative predicted value were high, while specificity and positive predicted value were low which is comparable with findings in the development cohort., Conclusions: Performance of the model remained good in the validation cohort. This prediction model might be used as a screening tool and can help to identify those children that need special attention and a long follow-up period or more frequent auditory testing.

Objective: To assess associations between body size and blood pressure in children (5-6 years) from different ethnic origins., Method: Five ethnic groups of the ABCD cohort were examined: Dutch (n=1 923), Turkish (n=99), Moroccan (n=187), Black-African (n=67) and Black-Caribbean (n=121). Data on body-mass-index (BMI), waist-to-height ratio (WHtR), fat-mass-index (FMI), and systolic blood pressure (SBP) and diastolic blood pressure (DBP), were collected. Linear regression analysis with restricted cubic splines was used to examine non-linear associations between body size and blood pressure, adjusted for age, sex, height and birth weight., Results: Ethnic differences were found in associations of BMI with SBP and DBP (SBP: p=0.001 and DBP: p=0.01) and FMI with SBP (p=0.03). BMI and FMI had a relatively large positive association with SBP in Turkish children (BMI: β=2.46mmHg; 95%CI:1.20-3.72; FMI: β=2.41mmHg; 95%CI:1.09-3.73) compared to Dutch (BMI: β=1.31mmHg; 95%CI:0.71-1.92; FMI: β=0.84mmHg; 95%CI:0.23-1.45). Black-Caribbean and Moroccan children showed high blood pressure with low BMI and FMI. Moroccan children showed higher SBP with high BMI and FMI. WHtR was positively associated with SBP and DBP, similar in all ethnic groups. Generally, strongest associations with blood pressure were found for BMI in all ethnic groups., Conclusion: Ethnic-specific associations between BMI, and FMI and blood pressure are present at young age, with Turkish children showing the highest increase in blood pressure with increasing body size. The higher blood pressure in the Black-Caribbean and Moroccan children with low BMI needs further research. WHtR or FMI do not seem to be associated more strongly to blood pressure than BMI in any ethnic group.

Of all malignancies in children, acute lymphoblastic leukemia (ALL) is the most common type. Since survival significantly improves over time, treatment-related side effects become increasingly important. Glucocorticoids play an important role in the treatment of ALL, but they may suppress the hypothalamic-pituitary-adrenal (HPA) axis. The duration of HPA axis suppression is not yet well defined. The present study aimed at assessing the function of the HPA axis by determining the cortisol awakening response (CAR) and the dexamethasone (DEX) suppression test in children that were treated for childhood ALL, compared to a healthy age and sex matched reference group. In addition, questionnaires regarding sleep, fatigue, depression and quality of life were completed by the children and their parents. Fourty-three survivors who finished their treatment for childhood ALL 37 (interquartile range 22-75) months before and 57 healthy controls were included. No differences in CAR were observed between ALL survivors and the reference group, but survivors of ALL had higher morning cortisol levels and an increased cortisol suppression in response to oral dexamethasone. Higher cortisol levels in childhood ALL survivors were associated with more fatigue and poorer quality of life. We conclude that the experience of a stressful life event in the past may have caused a long-term dysregulation of the HPA axis in childhood ALL survivors, as reflected in an increased cortisol production and an enhanced negative feedback mechanism., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Socioeconomic inequalities in cardiovascular disease are pervasive, yet much remains to be understood about how they originate. The objective of this study was to explore the relations of socioeconomic status to lipid and glucose metabolism as indicators of cardiovascular health in 5-6 year olds. Additionally to explore the explanatory role of maternal factors, birth outcome, and child factors., Methods: In 1308 5-6 year old ethnic Dutch children from the ABCD cohort study, lipids (cholesterol, LDL, HDL, triglycerides), glucose and C-peptide were measured after an overnight-fast., Results: There were no differences in cholesterol, HDL, LDL, and triglycerides between socioeconomic groups, as indicated by maternal education and income adequacy. However, children of low educated mothers had on average a higher glucose (β = 0.15; 95% confidence interval (CI) 0.03 - 0.27), logC-peptide (β = 0.07; 95% CI 0.04 - 0.09), and calculated insulin resistance (HOMA-IR) (β = 0.15; 95% CI 0.08 - 0.22) compared to children of high educated mothers. Only childhood BMI partly explained these differences (models controlled for age, height, and sex)., Conclusions: The socioeconomic gradient in cardiovascular risk factors seems to emerge in early childhood. In absence of underlying mechanisms these empirical findings are relevant for public health care and further explanatory research.

Aim: Children with Down syndrome (DS) experience respiratory tract infections (RTIs) more frequently than healthy children. We investigated whether this is related to different immunological characteristics associated with DS., Methods: The study group consisted of 22 children with DS and 22 of their healthy, age-range matched siblings. Data were collected on infections and hospitalizations because of lower RTIs. Immunoglobulin and IgG subclass levels in blood, as well as lymphocyte and T cell (subset) counts, were determined., Results: The children with DS had a significantly higher frequency of lower RTIs and related hospitalization than their siblings. We also found significantly reduced IgG2 levels as well as significantly lower counts of total lymphocytes, CD4(+) T lymphocytes, CD4(+) invariant natural killer (iNKT) cells and regulatory T cells in the DS group., Conclusion: In children with DS, reduced levels of IgG2, total lymphocytes, T lymphocytes, iNKT cells and regulatory T cells might contribute to their higher susceptibility to lower RTIs., (© 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.)

Background: Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate host defence against infections, which remains a cause of morbidity and death. The exact occurrence and duration of HPA axis suppression after glucocorticoid therapy for childhood ALL are unclear., Objectives: To examine the occurrence and duration of HPA axis suppression after (each cycle of) glucocorticoid therapy for childhood ALL., Search Methods: We searched the Cochrane Central Register of Controlled Trials (in The Cochrane Library, issue 3, 2010), MEDLINE/PubMed (from 1945 to July 2010) and EMBASE/Ovid (from 1980 to July 2010). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trial databases., Selection Criteria: All study designs, except case reports and patient series with fewer than 10 patients, examining the effect of glucocorticoid therapy for childhood ALL on the HPA axis function., Data Collection and Analysis: Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessment, which was checked by another review author., Main Results: We identified seven studies (total number of participants = 189), including one randomised controlled trial (RCT), which assessed the adrenal function. None of the studies assessed the HPA axis at the level of the hypothalamus, pituitary, or both. Due to substantial differences between studies, results could not be pooled. All studies had some methodological limitations. The included studies demonstrated that adrenal insufficiency occurs in nearly all patients in the first days after cessation of glucocorticoid treatment for childhood ALL. The majority of patients recovered within a few weeks, but a small amount of patients had ongoing adrenal insufficiency lasting up to 34 weeks. In the RCT, the occurrence and duration of adrenal insufficiency did not differ between the prednisolone and dexamethasone arms. In one study included in the review it appeared that treatment with fluconazole prolonged the duration of adrenal insufficiency., Authors' Conclusions: Based on the available evidence, we conclude that adrenal insufficiency commonly occurs in the first days after cessation of glucocorticoid therapy for childhood ALL, but the exact duration is unclear. Since no data on the level of the hypothalamus and the pituitary were available we cannot make any conclusions regarding those outcomes. Clinicians should consider prescribing glucocorticoid replacement therapy during periods of serious stress in the first weeks after cessation of glucocorticoid therapy for childhood ALL, to reduce the risk of life-threatening complications. However, more high-quality research is needed for evidence-based guidelines for glucocorticoid replacement therapy.Special attention should be paid to patients receiving fluconazole therapy, and perhaps similar antifungal drugs, as this may prolong the duration of adrenal insufficiency.

This longitudinal prospective study examined the relation between maternal anxiety during pregnancy and specific aspects of children's cognitive functioning at age five. Antenatal maternal state-anxiety was measured around the 16th week of pregnancy. Children's neurocognitive functioning was examined using a simple reaction time (RT) task, and a choice RT task. Multiple regression analyses in the total sample (N = 922) showed that antenatal anxiety was positively related to children's intra-individual variability in RT in the simple task. In a subsample (n = 100) of women with state-anxiety scores above the 90th percentile, antenatal anxiety was positively associated with mean RT and intra-individual variability in RT in the incompatible trials of the choice RT task. In addition, in this subsample of highly anxious mothers we found a significant positive association in boys but not in girls, between prenatal maternal anxiety and intra-individual variability in RT in the simple task., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: Children with down syndrome (DS) have an increased susceptibility to infections, due to altered humoral and/or cellular immunity. The aim of this study was to determine the cytokine production in whole blood of children with DS upon stimulation with live influenza A virus., Methods: Whole blood of 61 children with DS and 57 of their healthy siblings was stimulated with 2.5 × 10(4) TCID50/ml influenza A virus during 6, 24, and 48 h. TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IFN-α, IFN-γ concentrations, and viral load were measured at all time points., Results: At most of the time points, TNF-α, IL-1β, IL-6, and IL-8 concentrations were significantly higher in children with DS following stimulation with live influenza A virus. IFN-α and IFN-γ levels were also significantly higher in the DS group. Viral clearance, however, was equal in both groups., Conclusions: Children with DS have an altered immune response to influenza A virus. The production of higher levels of pro-inflammatory cytokines may be responsible for a more severe clinical course of viral disease in these children.