Sleep disturbances in hospitalized children: a wake-up call.

Although sleep is essential for (recovery of) health, it is adversely affected by hospitalization, due to disease discomfort, environmental noise, and care routines, causing reduced sleep and increased disturbances. This study evaluates factors affecting sleep quality and quantity in hospitalized children and compares inpatient sleep with sleep at home. Using an observational, prospective study design, we assessed sleep in hospitalized children aged 1-12 years, admitted to a tertiary center, and compared this with home 6-8 weeks after discharge. We measured total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency, awakenings, and subjective sleep quality, using actigraphy, sleep diaries, and PROMIS questionnaires. We explored an array of sleep-disturbing factors. Regression analyses identified key determinants affecting sleep patterns, while mixed linear models compared sleep in hospital to sleep at home. Out of 621 eligible patients, 467 were invited, and 272 (58%) consented to participate. Key determinants of sleep included pain, number of previous admissions, (underlying) chronic illness, and environment-, staff-, and disease-related factors. Parents reported lower perceived sleep quality in the hospital compared to at home, 97-min (SE 9) lower TST, 100-min (5) longer WASO, more difficulties with falling asleep, lower sleep satisfaction, and more awakenings. Actigraphy outcomes revealed shorter TST (20 min (6)), but better sleep efficiency and fewer awakenings in the hospital. Conclusion: Sleep in hospital was compromised in comparison to sleep at home, primarily due to disturbances related to treatment, environment, and staff. These findings underscore the necessity and potential of relative simple interventions to improve sleep quality and minimize sleep disturbances in hospitalized children.

A preconception lifestyle intervention in women with obesity and cardiovascular health in their children.

BACKGROUND: Maternal obesity during pregnancy is associated with poorer cardiovascular health (CVH) in children. A strategy to improve CVH in children could be to address preconception maternal obesity by means of a lifestyle intervention. We determined if a preconception lifestyle intervention in women with obesity improved offspring's CVH, assessed by magnetic resonance imaging (MRI). METHODS: We invited children born to women who participated in a randomised controlled trial assessing the effect of a preconception lifestyle intervention in women with obesity. We assessed cardiac structure, function and geometric shape, pulse wave velocity and abdominal fat tissue by MRI. RESULTS: We included 49 of 243 (20.2%) eligible children, 24 girls (49%) girls, mean age 7.1 (0.8) years. Left ventricular ejection fraction was higher in children in the intervention group as compared to children in the control group (63.0% SD 6.18 vs. 58.8% SD 5.77, p = 0.02). Shape analysis showed that intervention was associated with less regional thickening of the interventricular septum and less sphericity. There were no differences in the other outcomes of interest. CONCLUSION: A preconception lifestyle intervention in women with obesity led to a higher ejection fraction and an altered cardiac shape in their offspring, which might suggest a better CVH. IMPACT: A preconception lifestyle intervention in women with obesity results in a higher ejection fraction and an altered cardiac shape that may signify better cardiovascular health (CVH) in their children. This is the first experimental human evidence suggesting an effect of a preconception lifestyle intervention in women with obesity on MRI-derived indicators of CVH in their children. Improving maternal preconception health might prevent some of the detrimental consequences of maternal obesity on CVH in their children.

Preconception lifestyle intervention in women with obesity and echocardiographic indices of cardiovascular health in their children.

BACKGROUND: Improving maternal lifestyle before conception may prevent the adverse effects of maternal obesity on their children's future cardiovascular disease (CVD) risk. In the current study, we examined whether a preconception lifestyle intervention in women with obesity could alter echocardiographic indices of cardiovascular health in their children. METHODS: Six years after a randomized controlled trial comparing the effects of a 6-month preconception lifestyle intervention in women with obesity and infertility prior to fertility care to prompt fertility care, 315 of the 341 children conceived within 24 months after randomization were eligible for this study. The intervention was aimed at weight loss (≥5% or until BMI < 29 kg/m2). Children underwent echocardiographic assessment of cardiac structure and function, conducted by a single pediatric cardiologist, blinded to group allocation. Results were adjusted for multiple variables including body surface area, age, and sex in linear regression analyses. RESULTS: Sixty children (32 girls, 53%) were included, mean age 6.5 years (SD 1.09). Twenty-four children (40%) were born to mothers in the intervention group. Children of mothers from the intervention group had a lower end-diastolic interventricular septum thickness (-0.88 Z-score, 95%CI -1.18 to -0.58), a lower left ventricle mass index (-8.56 g/m2, 95%CI -13.09 to -4.03), and higher peak systolic and early diastolic annular velocity of the left ventricle (1.43 cm/s 95%CI 0.65 to 2.20 and 2.39 cm/s 95%CI 0.68 to 4.11, respectively) compared to children of mothers from the control group. CONCLUSIONS: Children of women with obesity, who underwent a preconception lifestyle intervention, had improved cardiac structure and function; a thinner interventricular septum, lower left ventricle mass, and improved systolic and diastolic tissue Doppler velocities. Despite its high attrition rates, our study provides the first experimental human evidence suggesting that preconception lifestyle interventions may present a method of reducing CVD risk in the next generation. CLINICAL TRIAL REGISTRATION: LIFEstyle study: Netherlands Trial Register: NTR1530 ( https://www.trialregister.nl/trial/1461 ). This follow-up study was approved by the medical ethics committee of the University Medical Centre Groningen (METC code: 2008/284).

Concordance between creatinine- and cystatin C-based eGFR in clinical practice.

The mean of GFR-estimates based on serum creatinine (eGFRcrea) and cystatin C (eGFRcys) has superior accuracy than each estimate alone. Recent studies have shown that agreement between eGFRcrea and eGFRcys is an indicator for the accuracy of the mean of the two estimates. As long as the difference between the two (|ΔeGFR|) is below 40%, a high P30 accuracy rate of more than 90% was documented in research settings using gold-standard GFR measurements. This was the case in approximately 80% of the measurements. The study was set out to explore |ΔeGFR| in a broader pediatric nephrological population and identify factors influencing the discrepancy between eGFRcrea and eGFRcys. We retrospectively analyzed 1596 simultaneous cystatin C and creatinine measurements in 649 unique patients at the pediatric nephrology outpatient clinic of VU university medical center. The FASage equation was used to calculate eGFRcrea, FAScys for eGFRcys. |ΔeGFR| was calculated as 100x(|eGFRcrea-eGFRcys|)/(0.5x(eGFRcrea+eGFRcys). ΔeGFR below 40% was considered high agreement. Patient characteristics like age, diagnosis, glucocorticosteroid use, eGFR, BMI and sex were analyzed for their effect on ΔeGFR below or above 40% using non-parametric tests and a potential explanation for measurements with low agreement was sought. Eighty-seven percent of the population had a |ΔeGFR| lower than 40%. Measurements with |ΔeGFR| above 40% were significantly more frequent from patients with neural tube defects. In 102 out of 208 measurements with low agreement, a potential explanation was found. In a broad pediatric nephrological population, |ΔeGFR| is below 40% in the vast majority of measurements. In this group, the mean of eGFRcrea and eGFRcys can be used as an accurate estimate of GFR.

Natural History of Vanishing White Matter.

OBJECTIVE: To comprehensively describe the natural history of vanishing white matter (VWM), aiming at improving counseling of patients/families and providing natural history data for future therapeutic trials. METHODS: We performed a longitudinal multicenter study among 296 genetically confirmed VWM patients. Clinical information was obtained via disease-specific clinical questionnaire, Health Utilities Index and Guy's Neurological Disability Scale assessments, and chart review. RESULTS: First disease signs occurred at a median age of 3 years (mode = 2 years, range = before birth to 54 years); 60% of patients were symptomatic before the age of 4 years. The nature of the first signs varied for different ages of onset. Overall, motor problems were the most common presenting sign, especially in children. Adolescent and adult onset patients were more likely to exhibit cognitive problems early after disease onset. One hundred two patients were deceased. Multivariate Cox regression analysis revealed a positive relation between age at onset and both preservation of ambulation and survival. Absence of stress-provoked episodes and absence of seizures predicted more favorable outcome. In patients with onset before 4 years, earlier onset was associated with more severe disability and higher mortality. For onset from 4 years on, disease course was generally milder, with a wide variation in severity. There were no significant differences for sex or for the 5 eIF2B gene groups. The results confirm the presence of a genotype-phenotype correlation. INTERPRETATION: The VWM disease spectrum consists of a continuum with extremely wide variability. Age at onset is a strong predictor for disease course. Ann Neurol 2018;84:274-288.

Endogenous markers for kidney function in children: a review.

Although glomerular filtration rate (GFR) in children can be measured using a gold-standard technique following injection of an exogenous marker, this invasive and cumbersome technique is not widely available and GFR is commonly estimated using serum levels of endogenous markers. Creatinine, urea, cystatin C, beta-trace protein, and beta-2 microglobulin are well-established endogenous markers of kidney function. These markers differ in site of production and effects of diet and medication, as well as renal-tubular handling and extra-renal elimination. For each marker, different methods are available for measurement. Importantly, the measurements of creatinine and cystatin C have recently been standardized with the introduction of international reference standards. In order to allow estimation of GFR from serum marker concentrations, different equations for estimated GFR (eGFR) have been developed in children, using simple or more complex regression strategies with gold standard GFR measurements as a dependent variable. As a rule, estimation strategies relying on more than one marker - either by calculating the average of single parameter equations or by using more complex equations incorporating several parameters - outperform eGFR estimations using only a single marker. This in-depth review will discuss the physiology, measurement and clinical use of creatinine, urea, cystatin C, beta-trace protein, and beta-2 microglobulin in children. It will also address the generation of eGFR equations in children and provide an overview of currently available eGFR equations for the pediatric age group.

Excessive infant crying doubles the risk of mood and behavioral problems at age 5: evidence for mediation by maternal characteristics.

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.

The association of birth weight and postnatal growth with energy intake and eating behavior at 5 years of age - a birth cohort study.

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 (ß: -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.

Predicting trajectories of behavioral adjustment in children diagnosed with acute lymphoblastic leukemia.

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.

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia.

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.

Increased production of interleukin-10 in children with Down syndrome upon ex vivo stimulation with Streptococcus pneumoniae.

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)-1ß, 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.

Determinants of quality of life during induction therapy in pediatric acute lymphoblastic leukemia.

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.

Screen time and cardiometabolic function in Dutch 5-6 year olds: cross-sectional analysis of the ABCD-study.

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.

Infant nutrition in relation to eating behaviour and fruit and vegetable intake at age 5 years.

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 (ß -0·09; 95 % CI -0·16, -0·02). Introducing solid foods after 6 months was associated with less enjoyment of food (ß -0·07; 95 % CI -0·12, -0·01) and food responsiveness (ß -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.

Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

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.

Suboptimal maternal vitamin D status and low education level as determinants of small-for-gestational-age birth weight.

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.

Health-related quality of life and utility scores in short-term survivors of pediatric acute lymphoblastic leukemia.

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.

The association between interpregnancy interval and birth weight: what is the role of maternal polyunsaturated fatty acid status?

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.

Psychosocial stress during pregnancy is related to adverse birth outcomes: results from a large multi-ethnic community-based birth cohort.

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.

Study protocol: the relation of birth weight and infant growth trajectories with physical fitness, physical activity and sedentary behavior at 8-9 years of age - the ABCD study.

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.