Early-life residential green spaces and traffic exposure in association with young adult body composition: a longitudinal birth cohort study of twins.

BACKGROUND: Globally, the rapid increase of obesity is reaching alarming proportions. A new approach to reduce obesity and its comorbidities involves tackling the built environment. Environmental influences seem to play an important role, but the environmental influences in early life on adult body composition have not been thoroughly investigated. This study seeks to fill the research gap by examining early-life exposure to residential green spaces and traffic exposure in association with body composition among a population of young adult twins. METHODS: As part of the East Flanders Prospective Twin Survey (EFPTS) cohort, this study included 332 twins. Residential addresses of the mothers at time of birth of the twins were geocoded to determine residential green spaces and traffic exposure. To capture body composition, body mass index, waist-to-hip ratio (WHR), waist circumference, skinfold thickness, leptin levels, and fat percentage were measured at adult age. Linear mixed modelling analyses were conducted to investigate early-life environmental exposures in association with body composition, while accounting for potential confounders. In addition, moderator effects of zygosity/chorionicity, sex and socio-economic status were tested. RESULTS: Each interquartile range (IQR) increase in distance to highway was found associated with an increase of 1.2% in WHR (95%CI 0.2-2.2%). For landcover of green spaces, each IQR increase was associated with 0.8% increase in WHR (95%CI 0.4-1.3%), 1.4% increase in waist circumference (95%CI 0.5-2.2%), and 2.3% increase in body fat (95%CI 0.2-4.4%). Stratified analyses by zygosity/chorionicity type indicated that in monozygotic monochorionic twins, each IQR increase in land cover of green spaces was associated with 1.3% increase in WHR (95%CI 0.5-2.1%). In monozygotic dichorionic twins, each IQR increase in land cover of green spaces was associated with 1.4% increase in waist-circumference (95%CI 0.6-2.2%). CONCLUSIONS: The built environment in which mothers reside during pregnancy might play a role on body composition among young adult twins. Our study revealed that based on zygosity/chorionicity type differential effects of prenatal exposure to green spaces on body composition at adult age might exist.

Properties of non-coding mutation hotspots as urinary biomarkers for bladder cancer detection.

Mutations at specific hotspots in non-coding regions of ADGRG6, PLEKHS1, WDR74, TBC1D12 and LEPROTL1 frequently occur in bladder cancer (BC). These mutations could function as biomarkers for the non-invasive detection of BC but this remains largely unexplored. Massively-parallel sequencing of non-coding hotspots was applied to 884 urine cell pellet DNAs: 591 from haematuria clinic patients (165 BCs, 426 non-BCs) and 293 from non-muscle invasive BC surveillance patients (29 with recurrence). Urine samples from 142 non-BC haematuria clinic patients were used to optimise variant calling. Non-coding mutations are readily detectable in the urine of BC patients and undetectable, or present at much lower frequencies, in the absence of BC. The mutations can be used to detect incident BC with 66% sensitivity (95% CI 58-75) at 92% specificity (95% CI 88-95) and recurrent disease with 55% sensitivity (95% CI 36-74) at 85% specificity (95% CI 80-89%) using a 2% variant allele frequency threshold. In the NMIBC surveillance setting, the detection of non-coding mutations in urine in the absence of clinically detectable disease was associated with an increased relative risk of future recurrence (RR = 4.62 (95% CI 3.75-5.48)). As urinary biomarkers, non-coding hotspot mutations behave similarly to driver mutations in BC-associated genes and could be included in biomarker panels for BC detection.

India's National Action Plan on Antimicrobial Resistance: a critical perspective.

Antimicrobial resistance (AMR) is widely recognised as a global health threat, which is projected to account for more deaths than cancer by 2050. The Government of India has formulated a National Action Plan to tackle AMR (NAP-AMR), largely modelled on the World Health Organization's Global Action Plan on AMR. While the NAP-AMR successfully mirrors the Global Action Plan and lays out ambitious goals, we find that the lack of financial allocation across states, poor enforcement and inadequate multisectoral co-ordination have hampered progress. A broader focus on improving infrastructure for water and sanitation, linking the issue of AMR to existing vertical health programmes for human immunodeficiency virus (HIV) and tuberculosis (TB), prioritising infection prevention and control, strengthening the frontline healthcare workforce in rural and peri-urban settings to reduce reliance on antibiotics, leveraging point-of-care testing and mobile app-based health interventions for diagnosis and surveillance, and adopting a socioecological approach to health and development would help to create an enabling environment for concrete action on AMR in India.

The PERFORM-P (Principles of Evidence-based Reporting in FORensic Medicine-Pathology version).

INTRODUCTION: Most findings of forensic pathology examinations are presented as written reports. There are currently no internationally accepted recommendations for writing forensic pathology reports. Existing recommendations are also varied and reflect the differences in the scope and role of forensic medical services and local settings in which they are to be implemented. The legal fact-finder thus faces wide variation in the quality of forensic pathology reports, which poses a threat to the reliability of legal decision-making. To address this issue, the development of the "PERFORM-P (Principles of Evidence-based Reporting in FORensic Medicine-Pathology version)" was undertaken. The goal of the PERFORM-P is to provide common practice recommendations adaptable to local requirements to promote evidence-based practice (EBP) in forensic pathology. METHODS: An international consensus study was conducted in three phases by (1) developing a long-list of items to be considered in the reporting recommendations, (2) conducting a Delphi process (an iterative survey method to transform individual opinions into group consensus) with international forensic pathologists, and (3) designing the PERFORM-P prototype and its accompanying manual. RESULTS: With assistance from 106 forensic pathologists/forensic medical practitioners from 41 countries, the PERFORM-P was developed. The PERFORM-P consists of a list of 61 items to be included in a forensic pathology report, which is accompanied by its Explanation and Elaboration (E&E) document. DISCUSSION: To prepare forensic pathology (postmortem) reports that incorporate principles of evidence-based practice, internationally accepted recommendations might be helpful. The PERFORM-P identifies recommendations for necessary elements to include in a forensic pathology report. PERFORM-P can be applied to a wide range of matters requiring forensic pathological analysis, acceptable to forensic pathologists from a representative selection of jurisdictions and medico-legal systems.

Effect of one year krill oil supplementation on depressive symptoms and self-esteem of Dutch adolescents: A randomized controlled trial.

INTRODUCTION: Observational studies have shown a relationship between omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) and depression in adolescents. However, n-3 LCPUFA supplementation studies investigating the potential improvement in depressive feelings in adolescents from the general population are missing. METHODS: A one-year double-blind, randomized, placebo controlled krill oil supplementation trial was conducted in two cohorts. Cohort I started with 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or placebo, after three months this increased to 800 mg EPA and DHA per day, whilst cohort II started with this higher dose. Omega-3 Index (O3I) was monitored via finger-prick blood measurements. At baseline, six and 12 months participants completed the Centre for Epidemiologic Studies Depression Scale (CES-D) and the Rosenberg Self Esteem questionnaire (RSE). Adjusted mixed models were run with treatment allocation/O3I as predictor of CES-D and RSE scores. RESULTS: Both intention-to-treat and assessing the change in O3I analyses did not show significant effects on CES-D or RSE scores. CONCLUSION: There is no evidence for less depressive feelings, or higher self-esteem after one year of krill oil supplementation. However, due to a lack of adherence and drop-out issues, these results should be interpreted with caution.

Fluid intake and clinicopathological characteristics of bladder cancer: the West Midlands Bladder Cancer Prognosis Programme.

OBJECTIVE: Between 10 and 20% of bladder cancer patients who are diagnosed with nonmuscle-invasive bladder cancer will progress to muscle-invasive disease. Risk of progression depends on several factors at diagnosis including age, tumour stage, grade, size and number, and the presence or absence of carcinoma in situ. Fluid intake may be related to these factors. METHODS: Data of 1123 participants from the West Midlands Bladder Cancer Prognosis Programme were used. Data collection was via a semistructured questionnaire, and case report forms were used to collect clinicopathological data. Fluid intake was measured for six main categories: alcoholic fluids, hot fluids, fruit fluids, milk, fizzy drinks, and water, and converted into quintile variables. Multilevel mixed-effects linear regression was performed for every beverage category per clinicopathological variable and corrected for age, gender, and smoking status. RESULTS: Age at diagnosis was distributed differently amongst those in different total fluid intake quintiles (predicted means 71.5, 70.9, 71.5, 69.9, and 67.4, respectively) and showed a significant inverse linear trend in alcohol (P < 0.01), hot fluids (P < 0.01), and total fluids intake (P < 0.01), in nonmuscle-invasive bladder cancer patients. CONCLUSION: Our results suggest an inverse association for alcohol intake and total fluid intake with age at diagnosis. These results should be confirmed by future studies, alongside a possible (biological) mechanism that could influence tumour growth, and the effect of micturition frequency.

Correction to: Exploring the association between whole blood Omega-3 Index, DHA, EPA, DPA, AA and n-6 DPA, and depression and self-esteem in adolescents of lower general secondary education.

The original version of this article unfortunately contained a mistake. Title was incorrect.

The association of maternal polyunsaturated fatty acids during pregnancy with social competence and problem behaviours at 7 years of age: The MEFAB cohort.

BACKGROUND: The prenatal exposure to maternal n-6 and n-3 polyunsaturated fatty acids (PUFAs) might influence the development of social competence and internalizing and externalizing behaviours of the child, because of the numerous functions of PUFAs within the nervous system. METHODS: To analyse the association of selected maternal PUFAs (i.e., AA, EPA, DHA, total n-6, total n-3, and the n-6:n-3 ratio) measured during gestation with childhood social competence and problem behaviours, we examined 311 mother-child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort. For each woman, PUFA-specific changes in relative concentrations were calculated by identifying the best-fitting curve of PUFA concentration by linear splines of gestational age. The associations of changes in maternal PUFAs in early and late pregnancy with childhood social competence, total problems, internalizing and externalizing behaviours, measured with the Child Behaviour Checklist 4/18 at age 7, were investigated with linear regression analyses adjusted for maternal and children's socio-demographic characteristics. RESULTS: In late gestation (i.e., from gestational week 30), an increase in AA was associated with higher social competence, while a decrease in total n-6 was associated with lower externalizing behaviours. No other significant associations were found. DISCUSSION: In this prospective study, increasing maternal AA and decreasing total n-6 were associated with improved social competence and externalizing behaviours, respectively, in 7-year old children. Nonetheless, the clinical significance of the identified associations is modest and further investigations are warranted to clarify the relationship between maternal AA and total n-6 during pregnancy and childhood social and behavioural development.

Selective citation in scientific literature on the human health effects of bisphenol A.

INTRODUCTION: Bisphenol A is highly debated and studied in relation to a variety of health outcomes. This large variation in the literature makes BPA a topic that is prone to selective use of literature, in order to underpin one's own findings and opinion. Over time, selective use of literature, by means of citations, can lead to a skewed knowledge development and a biased scientific consensus. In this study, we assess which factors drive citation and whether this results in the overrepresentation of harmful health effects of BPA. METHODS: A citation network analysis was performed to test various determinants of citation. A systematic search identified all relevant publications on the human health effect of BPA. Data were extracted on potential determinants of selective citation, such as study outcome, study design, sample size, journal impact factor, authority of the author, self-citation, and funding source. We applied random effect logistic regression to assess whether these determinants influence the likelihood of citation. RESULTS: One hundred sixty-nine publications on BPA were identified, with 12,432 potential citation pathways of which 808 citations occurred. The network consisted of 63 cross-sectional studies, 34 cohort studies, 29 case-control studies, 35 narrative reviews, and 8 systematic reviews. Positive studies have a 1.5 times greater chance of being cited compared to negative studies. Additionally, the authority of the author and self-citation are consistently found to be positively associated with the likelihood of being cited. Overall, the network seems to be highly influenced by two highly cited publications, whereas 60 out of 169 publications received no citations. CONCLUSION: In the literature on BPA, citation is mostly driven by positive study outcome and author-related factors, such as high authority within the network. Interpreting the impact of these factors and the big influence of a few highly cited publications, it can be questioned to which extent the knowledge development in human literature on BPA is actually evidence-based.

Exploring the association between whole blood Omega-3 Index, DHA, EPA, DHA, AA and n-6 DPA, and depression and self-esteem in adolescents of lower general secondary education.

PURPOSE: Depression is common in adolescents and long-chain polyunsaturated fatty acids (LCPUFA) are suggested to be associated with depression. However, research in adolescents is limited. Furthermore, self-esteem has never been studied in relation to LCPUFA. The objective here was to determine associations of depression and self-esteem with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), Omega-3 Index (O3I), n-6 docosapentaenoic acid (n-6 DPA, also called Osbond acid, ObA), n-3 docosapentaenoic acid (DPA), and arachidonic acid (AA) concentrations in blood of adolescents attending lower general secondary education (LGSE). METHODS: Baseline cross-sectional data from a krill oil supplementation trial in adolescents attending LGSE with an O3I ≤ 5% were analysed using regression models built with the BayesFactor package in R. Fatty acids and O3I were determined in blood. Participants filled out the Centre for Epidemiologic Studies Depression (CES-D) scale and the Rosenberg Self-Esteem scale (RSE). RESULTS: Scores indicative of depression (CES-D ≥ 16) were found in 29.4% of the respondents. Of all fatty acids, we found extreme evidence [Bayes factor (BF) > 100] for a weak negative association between ObA and depression score [- 0.16; 95% credible interval (CI) - 0.28 to - 0.04; BF10 = 245], and substantial evidence for a weak positive association between ObA and self-esteem score (0.09; 95% CI, - 0.03 to 0.20; BF10 = 4). When all fatty acids were put in one model as predictors of CES-D or RSE, all of the 95% CI contained 0, i.e., no significant association. CONCLUSION: No evidence was found for associations of DHA, EPA and O3I with depression or self-esteem scores in LGSE adolescents with O3I ≤ 5%. The associations of higher ObA status with lower depression and higher self-esteem scores warrant more research.

Estimation of the postmortem interval based on the human decomposition process.

Postmortem interval (PMI) estimations which are used as evidence in Dutch court are sometimes solely based on the experience of the forensic physician without a scientific background. The aim of this study was to investigate the degree of agreement between forensic physicians and their PMI estimations. Fifteen cases were selected from 1534 external postmortem investigations. Photographs of the human remains were presented to 89 forensic physicians in the Netherlands with the instruction to estimate the PMI based on their experience, knowing the remains were found indoors and in which season. Data analysis was conducted by using an interclass correlation (ICC) and Spearman's rank correlation coefficient. This study shows a poor correlation (ICC = 0.254) between the PMI estimations of the 89 forensic physicians. It is therefore not advised that PMI estimations based on experience be used as evidence in court.

Polyunsaturated fatty acid levels at birth and child-to-adult growth: Results from the MEFAB cohort.

BACKGROUND: Prenatal exposure to polyunsaturated fatty acids (PUFAs) may influence childhood growth. However, available evidence mostly derived from short-term studies is inconsistent. OBJECTIVE: To assess whether fetal PUFA exposure is associated with height and body mass index (BMI), a common measure of adiposity, from 6 months to 23 years of age. METHODS: In the MEFAB cohort, we assessed cord blood phospholipid n-3 and n-6 PUFA levels, reflecting fetal exposure in late pregnancy. For 250 (45.2% females) participants, we collected a total of 1770 (n= 802 for females) repeated growth measurements from infancy to young adulthood. We examined sex-specific associations of PUFAs with height and BMI at different developmental ages (infant: 6 months; toddler: 2 years; pre-schooler: 4 years; school-aged child: 7 years; adolescent: 12 years; and young adult: 23 years) using fractional polynomial mixed models adjusted for important covariates. RESULTS: Higher n-3 PUFA levels were associated with higher infant length in males (ß= 0.44cm [95% CI: 0.07, 0.82] per SD increase), whereas, for females, higher n-6 PUFA concentrations were associated with lower length in infancy (ß= -0.69cm [95% CI: -1.08, -0.30] per SD increase). A higher ratio of n-3 to n-6 PUFAs was associated with higher infant length in both sexes (ß= 0.40cm [95% CI: 0.01, 0.78] and 0.42cm [95% CI: 0.05, 0.79] per unit increase for males and females, respectively). These associations were not detectable later in childhood and young adulthood. No associations with BMI were found at any time point examined. CONCLUSIONS: Our findings suggest a small sex-specific influence of PUFA status at birth on length in infancy, but this does not persist in later life up to young adulthood. PUFA status at birth does not seem to affect BMI from infancy till young adulthood.

Associations between maternal long-chain polyunsaturated fatty acid concentrations and child cognition at 7 years of age: The MEFAB birth cohort.

INTRODUCTION: Concentrations of the fish fatty acids EPA and DHA are low among Dutch women of reproductive age. As the human brain incorporates high concentrations of these fatty acids in utero, particularly during third trimester of gestation, these low EPA and DHA concentrations may have adverse consequences for fetal brain development and functioning. METHODS: Analyses were conducted using longitudinal observational data of 292 mother-child pairs participating in the MEFAB cohort. Maternal AA, DHA, and EPA were determined in plasma phospholipids - obtained in three trimesters - by gas-liquid chromatography. Cognitive function was assessed at 7 years of age, using the Kaufman Assessment Battery for Children, resulting in three main outcome parameters: sequential processing (short-term memory), simultaneous processing (problem-solving skills), and the mental processing composite score. Spline regression and linear regression analyses were used to analyse the data, while adjusting for potential relevant covariates. RESULTS: Only 2% of the children performed more than one SD below the mental processing composite norm score. Children with lower test scores (<25%) were more likely to have a younger mother with a higher pre-gestational BMI, less likely to be breastfed, and more likely to be born with a lower birth weight, compared to children with higher test scores (≥25%). Fully-adjusted linear regression models did not show associations of maternal AA, DHA, or EPA status during any of the pregnancy trimesters with childhood sequential and simultaneous processing. CONCLUSION: Maternal fatty acid status during pregnancy was not associated with cognitive performance in Dutch children at age 7.

[Changes in the treatment of Crohn's disease: fewer hospitalizations, less surgery, and reduced glucocorticoid use]. / Veranderingen in de behandeling van ziekte van Crohn.

OBJECTIVE: To study changes in treatment and disease course in patients with Crohn's disease (CD) in the South Limburg region of the Netherlands between 1991 and 2014. DESIGN: Population-based cohort study. METHODS: All 1162 CD patients in the 'IBD South Limburg cohort' were divided across three subcohorts on the basis of year of diagnosis: 1991-1998 (N = 316), 1999-2005 (N = 387) and 2006-2011 (N = 459). We compared the risk of hospitalization, bowel resection and the development of strictures and/or fistulas across the subcohorts. We also compared cumulative corticosteroid use and the relationship between the outcome measures and maintenance medication. RESULTS: In the period 1991-2014 there was an increase in the number of patients treated within 5 years with immunomodulators from 30.6% to 70.8%. For treatment with biologicals there was an increase from 3.1% to 41.2%. In parallel, the risk of hospitalization decreased from 65.9% to 44.2% and the risk of bowel resection decreased from 42.9% to 17.4%. The risk of developing strictures or fistulas remained stable (21.2%). There was no significant association between the outcome measures and the use of immunomodulators or biologicals. Furthermore, corticosteroid use decreased over time; this was linked to use of immunomodulators and biologicals. CONCLUSION: Treatment of Crohn's disease has changed over the past two decades, and the disease course has improved. We found no association between changes in maintenance medication and disease course.

Association between prenatal and current exposure to selected LCPUFAs and school performance at age 7.

INTRODUCTION: Long-chain polyunsaturated fatty acids (LCPUFAs) are important for brain functioning and might, thus, influence cognition and school performance. However, research investigating LCPUFAs relationships with school performance is limited. The objective of this study was to determine the association between levels of the LCPUFAs docosahexaenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and n-6 docosapentaenoic acid (Osbond acid, ObA) at study entry, 22 weeks of pregnancy, 32 weeks of pregnancy, at partus, in umbilical cord plasma and child's plasma at age 7 and school performance scores at age 7. METHODS: Data from the Maastricht Essential Fatty Acid Birth cohort (MEFAB) were used for this study. Fatty acid levels of plasma phospholipids were measured in maternal blood plasma at study entry, 22 weeks of pregnancy, 32 weeks of pregnancy and partus. Childs fatty acid levels of plasma phospholipids were measured a in umbilical cord blood plasma, and in blood plasma of the child at age 7. Scores on national standardised tests for spelling, reading and arithmetic at age 7 were obtained via the school (scores were available for 149, 159 and 155 children, respectively). Associations between LCPUFA levels and school performance scores were analysed with categorical regression analyses with correction for covariates (smoking, maternal education, sex, breastfeeding, maternal intelligence, birth weight and BMI at age 7). RESULTS: Significant (p<0.001) associations between DHA level at age 7 and both reading (ß=0.158) and spelling (ß=0.146) were found. Consistent significant negative associations were observed between all maternal DHA plasma levels and arithmetic scores at age 7 (all p<0.001, all ß<-0.019). Additional significant negative associations were observed between maternal LCPUFA plasma levels at study entry and both reading and spelling scores at age 7; these associations were less consistent. CONCLUSION: Plasma DHA levels at age 7 were positively associated with reading and spelling scores at age 7. Consistent significant negative associations between maternal plasma DHA levels and arithmetic scores of the child at age 7 were found. Although this is an observational study, which cannot proof causality, the consistent negative associations observed between maternal plasma DHA levels and the arithmetic scores of the children at age 7 calls upon prudence when considering DHA supplementation during pregnancy.

Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM.

BACKGROUND: Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests. METHODS: We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up. RESULTS: Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, P<0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations. CONCLUSIONS: Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.

Placental telomere length decreases with gestational age and is influenced by parity: a study of third trimester live-born twins.

BACKGROUND: In contrast to the postnatal period, little is known about telomere length (TL) during prenatal life. The decrease in placental TL remains unknown, although intra uterine growth retardation and preeclampsia are associated with shorter placental TL. The aim of this study is to assess the decrease of placental TL during the third trimester of gestation and to explore the role of potential "growth influencing factors". METHODS: The study sample consisted of 329 live-born twins from the East Flanders Prospective Twin Survey. TL was determined using a multiplex quantitative PCR method. Gestational age, sex, birth order, placental characteristics, parity, maternal and paternal age, diabetes, hypertension, smoking, alcohol use, and socio economic status (SES) were considered "growth influencing factors". Bivariable multilevel regression analysis with "growth influencing factors" was performed. RESULTS: Placental TL ranged from 4.3 kbp to 84.4 kbp with a median of 10.8 kbp. Ln(TL) decreased in a linear fashion with an estimated TL decreasing from 13.98 kbp at 28 weeks to 10.56 kbp at 42 weeks. The regression coefficient of gestational age became smaller if considered together with SES (b = -0.017; p = 0.08) or diabetes (b = -0.018; p = 0.07) and bigger if considered together with parity (b = -0.022; p = 0.02), indicating that part of the association between gestational age and telomere length is explained by these three confounding factors. CONCLUSION: Placental TL decreases during the third trimester of gestation of live-born twins with approximately 25% indicating that telomere shortening may play a role in aging of the placenta.

Effect of maternal n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on adiposity in childhood: a systematic review and meta-analysis of randomized controlled trials.

It is hypothesized that prenatal and early postnatal exposure to n-3 long-chain polyunsaturated fatty acids (LCPUFAs) is negatively associated with adiposity later in life. We conducted a systematic review and meta-analysis to evaluate whether maternal n-3 LCPUFA supplementation in pregnancy and/or lactation exerts a beneficial effect on adiposity status in childhood. We searched six electronic databases till 20 May 2014 for randomized controlled trials (RCTs) of n-3 LCPUFA supplementation to pregnant and/or lactating women that reported data on body mass index (BMI), waist circumference, sum of skinfold thicknesses or body fat mass in children. Adiposity measures were grouped into three age categories: preschool children (<5 years), school-aged children (6-12 years), and adolescents (>13 years). Trial quality was assessed. We conducted fixed-effect and random-effects meta-analyses to combine study-specific estimates of differences between the supplemented and control groups. A total of 6 RCTs (9 publications) involving 2847 participants were included. Summary estimates showed no effect of maternal supplementation on BMI in preschool (standardized mean difference (SMD)=0.07, 95% confidence interval (CI)=-0.22, 0.36, P=0.65) and school-aged children (SMD=0.12, 95% CI=-0.06, 0.30, P=0.20). Because of sparse data, it was not possible to pool study results relating to other adiposity measures. There is currently no evidence to support that n-3 LCPUFA supplementation during pregnancy and/or lactation favourably affects child adiposity. Further high-quality trials are needed.

Heritability and genetic etiology of habitual physical activity: a twin study with objective measures.

Twin studies with objective measurements suggest habitual physical activity (HPA) are modestly to highly heritable, depending on age. We aimed to confirm or refute this finding and identify relevant genetic variants using a candidate gene approach. HPA was measured for 14 days with a validated triaxial accelerometer (Tracmor) in two populations: (1) 28 monozygotic and 24 dizygotic same-sex twin pairs (aged 22 ± 5 years, BMI 21.8 ± 3.4 kg/m(2), 21 male, 31 female pairs); (2) 52 and 65 unrelated men and women (aged 21 ± 2 years, BMI 22.0 ± 2.5 kg/m(2)). Single nucleotide polymorphisms (SNPs) in PPARD, PPARGC1A, NRF1 and MTOR were considered candidates. Association analyses were performed for both groups separately followed by meta-analysis. Structural equation modeling shows significant familiality for HPA, consistent with a role for additive genetic factors (heritability 57 %, 95 % CI 32-74 %, AE model) or common environmental factors (47 %, 95 % CI 23-65 %, CE model). A moderate heritability was observed for the time spent on low- and high-intensity physical activity (P ≤ 0.05), but could not be confirmed for the time spent on moderate-intensity physical activity. For PPARD, each additional effect allele was inversely associated with HPA (P ≤ 0.01; rs2076168 allele C) or tended to be associated with HPA (P ≤ 0.05; rs2267668 allele G). Linkage disequilibrium existed between those two SNPs (alleles A/G and A/C, respectively) and meta-analysis showed that carriers of the AA GC haplotype were less physically active than carriers of the AA AA and AA AC haplotypes combined (P = 0.017). For PPARGC1A, carriers of AA in rs8192678 spent more time on high-intensity physical activity than GG carriers (P = 0.001). No associations were observed with SNPs in NRF1 and MTOR. In conclusion, HPA may be modestly heritable, which is confirmed by an association with variants in PPARD.