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.

Secular trends in gestational age and birthweight in twins.

BACKGROUND: In recent decades, the overall rate of preterm births has increased. The aim of the present study was to examine whether this trend is also seen for multiple gestations. More specifically, we examined if there has been a decrease in gestational age for live born monozygotic (MZ) and dizygotic (DZ) twins and if there has been a simultaneous change in birthweight. The contributions of fertility treatments and Caesarean sections were taken into consideration. All analyses were carried out in two large European twin cohorts. METHODS: Cross-sectional study of 6310 live born twin pairs, born between 1964-2007, from the Belgian East Flanders Prospective Twin Survey and 14,712 twin pairs, born between 1990-2006, from the Netherlands Twin Register. Multiple regression analyses were performed with gestational age as outcome variable, and multilevel analysis with birthweight as outcome variable. All analyses were performed with and without adjustment for zygosity, parity, maternal age, mode of conception and delivery and, for the analyses of birthweight, gestational age. RESULTS: Gestational age decreased in a linear fashion from 1964 to 2007 with a decrease of 0.25 days per year in a similar way for MZ and DZ twins. Changes in birthweight depended on gestational age: up to 32 weeks, birthweight decreased and after 32 weeks birthweight increased. The frequency of infertility treatment and Caesarean sections, primiparity and advanced maternal age increased over the years, but none of these factors influenced the secular trends in gestational age and birthweight. CONCLUSIONS: The decrease in gestational age and change in birthweight in twins are sources of concern, especially for very preterm twins, for whom birthweight decreased. For twins born after 32 weeks, an increase in birthweight was observed and this is very likely the explanation for the decrease in gestational age.

Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials.

Calcium plays a role in blood pressure (BP) regulation, but the importance of supplemental calcium intake for the prevention of hypertension is still debated. We conducted a meta-analysis of randomized controlled trials to determine the effect of calcium supplementation on BP. A systematic search for randomized trials of calcium supplementation and BP in non-pregnant subjects was performed in Medline from 1966 to June 2003. Seventy-one trials were identified, 40 of which met the criteria for meta-analysis (total of 2492 subjects). Two persons independently extracted data from original publications on changes in calcium intake and BP. In addition, data were collected on subjects' characteristics, that is, age, gender, initial BP and initial calcium intake. A random effects model was used to obtain the effect of calcium supplementation on BP, overall and in predefined population subgroups. Calcium supplementation (mean daily dose: 1200 mg) reduced systolic BP by -1.86 mm Hg (95% confidence interval: -2.91 to -0.81) and diastolic BP by -0.99 mm Hg (-1.61 to -0.37). In people with a relatively low calcium intake (< or =800 mg per day) somewhat larger BP estimates were obtained, that is, -2.63 (-4.03 to -1.24) for systolic BP and -1.30 (-2.13 to -0.47) for diastolic BP. Our study suggests that an adequate intake of calcium should be recommended for the prevention of hypertension. More research on BP in people with calcium-deficient diets is warranted.

The influence of occupational exposure to pesticides, polycyclic aromatic hydrocarbons, diesel exhaust, metal dust, metal fumes, and mineral oil on prostate cancer: a prospective cohort study.

AIMS: To investigate the relation between exposure to pesticides, polycyclic aromatic hydrocarbons (PAHs), diesel exhaust, metal dust, metal fumes, and mineral oil in relation to prostate cancer incidence in a large prospective study. METHODS: This cohort study was conducted among 58,279 men in the Netherlands. In September 1986, cohort members (55-69 years) completed a self-administered questionnaire on potential cancer risk factors, including job history. Follow up for prostate cancer incidence was established by linkage to cancer registries until December 1995 (9.3 years of follow up). The analyses included 1386 cases of prostate cancer and 2335 subcohort members. A blinded case-by-case expert exposure assessment was carried out to assign cases and subcohort members a cumulative probability of exposure for each potential carcinogenic exposure. RESULTS: In multivariate analyses there was a significant negative association for pesticides (RR 0.60; 95% CI 0.37 to 0.95) when comparing the highest tertile of exposure to pesticides with no exposure. No association was found for occupational exposure to PAHs (RR 0.75; 95% CI 0.42 to 1.31), diesel exhaust (RR 0.81; 95% CI 0.62 to 1.06), metal dust (RR 1.01; 95% CI 0.72 to 1.40), metal fumes (RR 1.11; 95% CI 0.80 to 1.54), or mineral oil (RR 0.99; 95% CI 0.66 to 1.48) when comparing the highest tertile of exposure with no exposure. In subgroup analysis, with respect to tumour invasiveness and morphology, null results were found for occupational exposure to pesticides, PAH, diesel exhaust, metal dust, metal fumes, and mineral oil. CONCLUSIONS: These results suggest a negative association between occupational exposure to pesticides and prostate cancer. For other carcinogenic exposures results suggest no association between occupational exposure to PAHs, diesel exhaust, metal dust, metal fumes, or mineral oil and prostate cancer.

Tumor risk in Beckwith-Wiedemann syndrome: A review and meta-analysis.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with macroglossia, abdominal wall defects, ear anomalies, and an increased risk for embryonic tumors. Reported tumor risk estimates vary between 4% and 21%. It has been hypothesized that tumor predisposition in BWS is related to the imprinting status of the H19 and LIT1 genes on chromosome 11p15. A loss of imprinting (LOI) of H19 implies a higher tumor risk. However, a systematic analysis of available data is lacking. Therefore, we performed a review and meta-analysis of reported associations between the imprinting status of the LIT1 and H19 genes and the risk for tumor development in BWS. Five publications suitable for meta-analysis were identified by electronic database searches. Sufficient data were available for 402 out of 520 patients. Patients were divided into four groups based on the imprinting status of H19 and LIT1: group I with LOI of LIT1 (45%); group II with LOI of H19 (9%); group III with LOI of LIT1 and LOI of H19 (21%); and group IV with normal imprinting patterns (26%). Differences in tumor risk between groups were studied with random effects meta-analysis. Tumors occurred in 55 patients. The odds of tumor development was significantly lower in group I when compared to group II (OR=0.06; 95% CI: 0.02-0.21) and group III (OR=0.12; 95% CI: 0.04-0.37). Tumor risk did not differ significantly between groups II and III (OR=1.40; 95% CI: 0.56-3.50). Compared to group IV, tumor risk was significantly lower in group I (OR=0.33; 95% CI: 0.12-0.87) and higher in groups II (OR=4.0; 95% CI: 1.5-10.4) and III (OR=2.6; 95% CI: 1.2-5.7). Tumor incidence rate for group IV was 10.6% (95% CI: 3.6-17.7). Calculated absolute risks were 3% for group I, 43% for group II, and 28% for group III, respectively. No Wilms tumor was seen in group I. In total, other tumors were seen with comparable frequencies in groups I-III. The results show a strong association between a LOI of H19 and especially Wilms tumor development in BWS.

Should nortriptyline be used as a first-line aid to help smokers quit? Results from a systematic review and meta-analysis.

OBJECTIVES: The objective of this paper is to evaluate the efficacy of nortriptyline for smoking cessation compared to placebo and bupropion sustained release. DATA SOURCES: Randomized trials were identified by (1) checking electronic and (2) online publicly accessible registers of clinical trials; (3) searching references of identified studies and screening abstract books of conferences and symposia, and (4) personal communication with the first authors of identified papers. REVIEW METHODS: We included randomized trials in which nortriptyline was compared to placebo or bupropion hydrochloride SR. The main clinical outcome measure was (at least) 6-month prolonged abstinence, confirmed with a biochemical test. To investigate the efficacy of nortriptyline in time, we calculated the percentage of smokers who relapsed in time. RESULTS: We identified five randomized trials, including 861 smokers. Compared to placebo medication, nortriptyline resulted in significantly higher prolonged abstinence rates after at least 6 months [relative risk (RR) = 2.4, 95% CI 1.7-3.6; RD = 0.11, 95% CI 0.07-0.15]. The difference in efficacy between nortriptyline and placebo was highest in the first months after the target quit date. However, the number of people who remained abstinent decreased substantially and significantly faster over time in the nortriptyline group. Although bupropion resulted in higher abstinence rates compared with nortriptyline, the difference was not statistically significant (RR = 1.7, 95% CI 0.7-4.1). CONCLUSION: This systematic review and meta-analysis shows that the use of nortriptyline for smoking cessation resulted in higher prolonged abstinence rates after at least 6 months compared to placebo treatment. Furthermore, the use of nortriptyline for smoking cessation is well tolerated and safe. As a result, we believe health care professionals should be recommended to prescribe nortriptyline as a first-line therapy for smoking cessation, also because of the much lower cost of nortriptyline compared to bupropion SR.

Oral essential fatty acid supplementation in atopic dermatitis-a meta-analysis of placebo-controlled trials.

BACKGROUND: Essential fatty acids are components of cell membranes and precursors of immunomodulating factors that may play a role in the inflammatory and immunological pathogenesis of atopic dermatitis. Trials of supplementation with essential fatty acids (EFA) to alleviate atopic dermatitis (AD) have given inconsistent results. OBJECTIVES: To summarize and quantify the results of placebo-controlled trials with EFA for AD. DESIGN: Publications of clinical trials were searched in a systematic way and the study characteristics assessed independently by three assessors. Trials were selected for inclusion in the meta-analysis when they had included a placebo group and when the outcome measure included the severity of AD. The pooled effect sizes of improvement of the overall severity of AD were calculated by random effects meta-analysis. The dependence of the results on study characteristics was studied using meta-regression analysis. RESULTS: We identified 34 publications of controlled trials in AD up to April 2002. Nineteen trials of gamma-linolenic acid (GLA) and five trials of fish oil matched our inclusion criterion of placebo-controlled trial. The effect size of GLA supplementation on the improvement of the overall severity of AD could be calculated from 11 of these trials. The pooled effect size was 0.15 [95% confidence limits (CL) - 0.02, 0.32]. The effect size of fish oil supplementation, calculated from three trials was - 0.01 (95% CL - 0.37, 0.30). For component subscales such as itch, scaling and lichenification, EFA supplementation showed no benefit. The study characteristics showed no detectable influence on the overall result. CONCLUSIONS: Supplementation with EFA has no clinically relevant effect on the severity of AD.

Gly972Arg variant in the insulin receptor substrate-1 gene and association with Type 2 diabetes: a meta-analysis of 27 studies.

AIMS/HYPOTHESIS: Several case-control studies have examined the association between the Gly972Arg variant in the IRS-1 gene and Type 2 diabetes, but most had limited power and results could therefore be conflicting. METHODS: We systematically reviewed the literature by means of a meta-analysis and investigated sources of heterogeneity in results of different studies. RESULTS: The summary risk ratio, based on 3408 cases and 5419 control cases from 27 studies, was 1.25 (95% CI 1.05-1.48). The results, however, differed according to the type of study, method of verifying non-diabetic status of the control subjects, and age of the case subjects. Population-based studies reported lower odds ratios than hospital-based studies (OR 0.98, 95% CI 0.74-1.30 vs OR 1.43, 95% CI 1.17-1.74). Also, the diagnostic test to exclude diabetes amongst control subjects interacted with the association between the IRS-1 Gly972Arg variant and Type 2 diabetes (p=0.03). Finally, the odds ratio reduced with increasing age ( p=0.03). CONCLUSION/INTERPRETATION: Overall, carriers of the 972Arg variant of the IRS-1 gene are at a 25% increased risk of having Type 2 diabetes compared with non-carriers. The odds ratios are generally higher in hospital-based studies, including relatively young, symptomatic, cases.

Genetic counseling for prostate cancer risk.

Major risk factors for developing prostate cancer, including positive family history and African-American ethnicity, can be quantified for genetic counseling. Factors increasing familial risk for prostate cancer are closer degree of kinship, number of affected relatives, and early age of onset (< 50 years) among the affected relatives. Genetic testing may be useful for modification of risk, but currently should be performed only within the context of a well-designed research study that will determine penetrance and genotype-phenotype correlation of specific mutations. Even in the absence of genetic testing, African-American men and men with a strong family history of prostate cancer may opt to initiate screening by prostate specific antigen (PSA) and digital rectal exam (DRE) screening at age 40.