Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis.

BACKGROUND: Accumulating evidence suggests that breastfeeding benefits children's intelligence, possibly due to long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk. Under a nutritional adequacy hypothesis, an interaction between breastfeeding and genetic variants associated with endogenous LC-PUFAs synthesis might be expected. However, the literature on this topic is controversial. METHODS: We investigated this gene × environment interaction through a collaborative effort. The primary analysis involved >12 000 individuals and used ever breastfeeding, FADS2 polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores. RESULTS: There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e. difference between genetic groups of the difference in IQ Z scores comparing ever with never breastfed individuals) of 0.12[(95% confidence interval (CI): -0.19; 0.43] and 0.06 (95% CI: -0.16; 0.27) for the rs174575 and rs1535 variants, respectively. Secondary analyses corroborated these results. In studies with ≥5.85 and <5.85 months of breastfeeding duration, pooled estimates for the rs174575 variant were 0.50 (95% CI: -0.06; 1.06) and 0.14 (95% CI: -0.10; 0.38), respectively, and 0.27 (95% CI: -0.28; 0.82) and -0.01 (95% CI: -0.19; 0.16) for the rs1535 variant. CONCLUSIONS: Our findings did not support an interaction between ever breastfeeding and FADS2 polymorphisms. However, subgroup analysis suggested that breastfeeding may supply LC-PUFAs requirements for cognitive development if breastfeeding lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and further improve our understanding on the breastfeeding × FADS2 interaction.

The child's perspective on discomfort during medical research procedures: a descriptive study.

OBJECTIVE: The evaluation of discomfort in paediatric research is scarcely evidence-based. In this study, we make a start in describing children's self-reported discomfort during common medical research procedures and compare this with discomfort during dental check-ups which can be considered as a reference level of a 'minimal discomfort' medical procedure. We exploratory study whether there are associations between age, anxiety-proneness, gender, medical condition, previous experiences and discomfort. We also describe children's suggestions for reducing discomfort. DESIGN: Cross-sectional descriptive study. SETTING: Paediatric research at three academic hospitals. PATIENTS: 357 children with and without illnesses (8-18 years, mean=10.6 years) were enrolled: 307 from paediatric research studies and 50 from dental care. MAIN OUTCOME MEASURES: We measured various generic forms of discomfort (nervousness, annoyance, pain, fright, boredom, tiredness) due to six common research procedures: buccal swabs, MRI scans, pulmonary function tests, skin prick tests, ultrasound imaging and venepunctures. RESULTS: Most children reported limited discomfort during the research procedures (means: 1-2.6 on a scale from 1 to 5). Compared with dental check-ups, buccal swab tests, skin prick tests and ultrasound imaging were less discomforting, while MRI scans, venepunctures and pulmonary function tests caused a similar degree of discomfort. 60.3% of the children suggested providing distraction by showing movies to reduce discomfort. The exploratory analyses suggested a positive association between anxiety-proneness and discomfort. CONCLUSIONS: The findings of this study support the acceptability of participation of children in the studied research procedures, which stimulates evidence-based research practice. Furthermore, the present study can be considered as a first step in providing benchmarks for discomfort of procedures in paediatric research.

Anxiety and the Risk of Stroke: The Rotterdam Study.

BACKGROUND AND PURPOSE: It is unclear whether anxiety is a risk factor for stroke. We assessed the association between anxiety and the risk of incident stroke. METHODS: This population-based cohort study was based on 2 rounds of the Rotterdam Study. Each round was taken separately as baseline. In 1993 to 1995, anxiety symptoms were measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A). In 2002 to 2004, anxiety disorders were assessed using the Munich version of the Composite International Diagnostic Interview. Participants were followed up for incident stroke until January 2012. RESULTS: In the sample undergoing HADS-A (N=2625; mean age at baseline, 68.4 years), 332 strokes occurred during 32 720 years of follow-up. HADS-A score was not associated with the risk of stroke during complete follow-up (adjusted hazard ratio, 1.02; 95% confidence interval, 0.74-1.43; for HADS-A≥8 compared with HADS-A <8), although we did find an increased risk after a shorter follow-up of 3 years (adjusted hazard ratio, 2.68; 95% confidence interval, 1.33-5.41). In the sample undergoing the Munich version of the Composite International Diagnostic Interview (N=8662; mean age at baseline, 66.1 years), 340 strokes occurred during 48 703 years of follow-up. Participants with any anxiety disorder had no higher risk of stroke than participants without anxiety disorder (adjusted hazard ratio, 0.95; 95% confidence interval, 0.64-1.43). We also did not observe an increased risk of stroke for the different subtypes of anxiety. CONCLUSIONS: Anxiety disorders were not associated with stroke in our general population study. Anxiety symptoms were only related to stroke in the short term, which needs further exploration.

Body shape index in comparison with other anthropometric measures in prediction of total and cause-specific mortality.

BACKGROUND: The association of body mass index (BMI) with mortality remains controversial among the middle-aged and elderly. Moreover, the contribution of other anthropometric measures to predict mortality is unclear. METHODS: We assessed the association of BMI, waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR) and a body shape index (ABSI=WC/(BMI(2/3)×height(1/2))) with total, cardiovascular and cancer mortality by using Cox proportion hazard models among 2626 men and 3740 women from the prospective population-based Rotterdam Study. Predictive performance was assessed through informativeness, c-statistic, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). RESULTS: During 22 years of follow-up, 3675 deaths from all-causes, 1195 from cardiovascular disease, and 873 from cancer occurred. In the multivariable model, ABSI showed a stronger association with mortality compared with BMI, WC, WHtR and WHR. HRs and CIs (95% CIs) for total mortality per 1 SD increase in ABSI were 1.15 (1.09 to 1.21) for men and 1.09 (1.04 to 1.14) for women. For cardiovascular and cancer mortality, these HRs (95% CI) were 1.18 (1.08 to 1.29) and 1.10 (0.99 to 1.22) for men, 1.04 (0.96 to 1.12) and 1.18 (1.07 to 1.30) for women, respectively. The models including ABSI did not increase the c-statistics. Among men, in prediction of total mortality the model including ABSI was more informative (χ(2)=26.4) and provided improvement in risk stratification (IDI 0.003, 95% CI 0.001 to 0.005; cNRI 0.13, 95% CI 0.06 to 0.21). CONCLUSIONS: In our population-based study, among different anthropometric measures, ABSI showed a stronger association with total, cardiovascular and cancer mortality. However, the added predictive value of ABSI in prediction of mortality was limited.

The Rotterdam Study: 2016 objectives and design update.

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over 1200 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy ). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.

Risk factors for complicated grief in older adults.

BACKGROUND: Older adults grieving the death of a spouse have been found to have a higher risk of complicated grief compared with younger adults. OBJECTIVE: The study objective was to find out whether personal characteristics of the patient and the bereaved partner, or characteristics of the patient's illness, end-of-life care, and the nature of death are risk factors for complicated grief in older adults. METHODS: We performed a nested case-control study within the Rotterdam Study. We selected 100 couples of which one person had deceased and the other person experienced "complicated grief," and 100 control couples of which one person had deceased and the other person experienced "normal grief." Complicated grief was assessed with a 17-item Inventory of Complicated Grief (ICG). Determinants were assessed using several sources of information that were available for all participants of the Rotterdam Study. Additionally, medical files of the deceased were manually screened. Logistic regression analysis was performed. RESULTS: Only depression at baseline was significantly associated with complicated grief. Bereaved partners with depression at baseline had a higher risk of complicated grief compared to bereaved partners without depression (OR=3.48; 95% CI=1.40-8.68). CONCLUSIONS: Our results suggest that complicated grief in older adults is not clearly related to the circumstances of dying of the deceased partner. Preexisting conditions such as depression seem to be more important in explaining the occurrence of complicated grief.

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

Perceived sleep quality is worse than objective parameters of sleep in pregnant women with a mental disorder.

OBJECTIVE: Disturbed sleep during pregnancy is associated with adverse obstetric outcomes and less mental well-being. In pregnant women with a mental disorder, who frequently suffer from sleep problems, it is unknown whether predominantly objective or subjective sleep quality is more affected. To clarify this, we compared objective and subjective parameters of sleep quality between patients and healthy controls during pregnancy. METHODS: This observational study was embedded in an ongoing study among pregnant women with a mental disorder at the department of Psychiatry of Erasmus University Medical Center Rotterdam, the Netherlands. We compared 21 pregnant women with a confirmed mental disorder with 33 healthy controls (gestational age, 23-29 weeks). To measure objective parameters of sleep quality, all participants continuously wore a wrist actigraph for 7 days and nights. Subjective sleep quality was retrospectively assessed using the Pittsburgh Sleep Quality Index (PSQI) and on a daily basis with the Subjective Sleep Quality-scale (SSQ). Differences in parameters of sleep between patients and controls were tested using a multivariate linear regression analysis adjusted for parity, gestational age, educational level, and employment status. RESULTS: Objective parameters of sleep quality and subjective sleep quality as assessed by the PSQI did not differ significantly between patients and controls. Daily sleep reports showed that, relative to controls, patients had a significantly worse average SSQ-score (5.2 vs. 7.6, adjusted ß = 0.12, 95%CI = 0.03-0.53, p < 0.01). CONCLUSIONS: Our exploratory study suggests that perceived sleep quality reported on a daily basis by pregnant women with a mental disorder is worse than the sleep quality as measured by wrist actigraphy.

Exploring the relation of harsh parental discipline with child emotional and behavioral problems by using multiple informants. The generation R study.

Parental harsh disciplining, like corporal punishment, has consistently been associated with adverse mental health outcomes in children. It remains a challenge to accurately assess the consequences of harsh discipline, as researchers and clinicians generally rely on parent report of young children's problem behaviors. If parents rate their parenting styles and their child's behavior this may bias results. The use of child self-report on problem behaviors is not common but may provide extra information about the relation of harsh parental discipline and problem behavior. We examined the independent contribution of young children's self-report above parental report of emotional and behavioral problems in a study of maternal and paternal harsh discipline in a birth cohort. Maternal and paternal harsh discipline predicted both parent reported behavioral and parent reported emotional problems, but only child reported behavioral problems. Associations were not explained by pre-existing behavioral problems at age 3. Importantly, the association with child reported outcomes was independent from parent reported problem behavior. These results suggest that young children's self-reports of behavioral problems provide unique information on the effects of harsh parental discipline. Inclusion of child self-reports can therefore help estimate the effects of harsh parental discipline more accurately.

The Rotterdam Study: 2014 objectives and design update.

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy ). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.

Postnatal parental smoking: an important risk factor for SIDS.

BACKGROUND: Sudden infant death syndrome (SIDS) is the unexpected death of an infant that remains unexplained after a thorough investigation of the circumstances, family history, paediatric investigation and complete autopsy. In Western society, it is the leading cause of post-neonatal death below 1 year of age. In the Netherlands, the SIDS incidence is very low, which offers opportunities to assess the importance of old and new environmental risk factors. For this purpose, cases were collected through pathology departments and the working group on SIDS of the Dutch Paediatrician Foundation. A total of 142 cases were included; these occurred after the parental education on sleeping position (1987), restricted to the international age criteria and had no histological explanation. Age-matched healthy controls (N = 2,841) came from a survey of the Netherlands Paediatric Surveillance Unit, completed between November 2002 and April 2003. A multivariate analysis was performed to determine the risk factors for SIDS, including sleeping position, antenatal maternal smoking, postnatal parental smoking, premature birth, gender, lack of breastfeeding and socio-economic status. Postnatal smoking was identified as an important environmental risk factor for SIDS (OR one parent = 2.5 [1.2, 5.0]; both parents = 5.77 [2.2, 15.5]; maternal = 2.7 [1.0, 6.4]; paternal = 2.4 [1.3, 4.5] ) as was prone sleeping (OR put prone to sleep = 21.5 [10.6, 43.5]; turned prone during sleep = 100 [46, 219]). Premature birth was also significantly associated with SIDS (OR = 2.4 [1.2, 4.8]). CONCLUSION: Postnatal parental smoking is currently a major environmental risk factor for SIDS in the Netherlands together with the long-established risk of prone sleeping.

Individual accumulation of heterogeneous risks explains perinatal inequalities within deprived neighbourhoods.

Dutch' figures on perinatal mortality and morbidity are poor compared to EU-standards. Considerable within-country differences have been reported too, with decreased perinatal health in deprived urban areas. We investigated associations between perinatal risk factors and adverse perinatal outcomes in 7,359 pregnant women participating in population-based prospective cohort study, to establish the independent role, if any, for living within a deprived urban neighbourhood. Main outcome measures included perinatal death, intrauterine growth restriction (IUGR), prematurity, congenital malformations, Apgar at 5 min < 7, and pre-eclampsia. Information regarding individual risk factors was obtained from questionnaires, physical examinations, ultrasounds, biological samples, and medical records. The dichotomous Dutch deprivation indicator was additionally used to test for unexplained deprived urban area effects. Pregnancies from a deprived neighbourhood had an increased risk for perinatal death (RR 1.8, 95% CI [1.1; 3.1]). IUGR, prematurity, Apgar at 5 min < 7, and pre-eclampsia also showed higher prevalences (P < 0.05). Residing within a deprived neighbourhood was associated with increased prevalence of all measured risk factors. Regression analysis showed that the observed neighbourhood related differences in perinatal outcomes could be attributed to the increased risk factor prevalence only, without a separated role for living within a deprived neighbourhood. Women from a deprived neighbourhood had significantly more 'possibly avoidable' risk factors. To conclude, women from a socioeconomically deprived neighbourhood are at an increased risk for adverse pregnancy outcomes. Differences regarding possibly avoidable risk factors imply that preventive strategies may prove effective.