Search

Background: Exposures during the prenatal period may have lasting effects on maternal and child health outcomes. To better understand the effects of the in utero environment on children's short- and long-term health, large representative pregnancy cohorts with comprehensive information on a broad range of environmental influences (including biological and behavioral) and the ability to link to prenatal, child and maternal health outcomes are needed. The Research Program on Genes, Environment and Health (RPGEH) pregnancy cohort at Kaiser Permanente Northern California (KPNC) was established to create a resource for conducting research to better understand factors influencing women's and children's health. Recruitment is integrated into routine clinical prenatal care at KPNC, an integrated health care delivery system. We detail the study design, data collection, and methodologies for establishing this cohort. We also describe the baseline characteristics and the cohort's representativeness of the underlying pregnant population in KPNC. Methods: While recruitment is ongoing, as of October 2014, the RPGEH pregnancy cohort included 16,977 pregnancies (53 % from racial and ethnic minorities). RPGEH pregnancy cohort participants consented to have blood samples obtained in the first trimester (mean gestational age 9.1 weeks ± 4.2 SD) and second trimester (mean gestational age 18.1 weeks ± 5.5 SD) to be stored for future use. Women were invited to complete a questionnaire on health history and lifestyle. Information on women's clinical and health assessments before, during and after pregnancy and women and children's health outcomes are available in the health system's electronic health records, which also allows long-term follow-up. Discussion: This large, racially- and ethnically-diverse cohort of pregnancies with prenatal biospecimens and clinical data is a valuable resource for future studies on in utero environmental exposures and maternal and child perinatal and long term health outcomes. The baseline characteristics of RPGEH Pregnancy Cohort demonstrate that it is highly representative of the underlying population living in the broader community in Northern California. [ABSTRACT FROM AUTHOR]

In 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine animal models of Parkinson's disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A ( ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 ( CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association. Parkinson's Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Two ADORA2A polymorphisms were inversely associated with PD risk - rs71651683, a 5′ variant (adjusted allelic OR = 0.51, 95% CI 0.33-0.80, permutation-adjusted P = 0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wild-type genotype were 0.76 (95% CI 0.57-1.02) and 0.37 (95% CI 0.13-1.01), respectively (permutation-adjusted P for trend = 0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 ( P = 0.05) or rs2470890 ( P = 0.04). In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms. Click to view the accompanying paper in this issue. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine whether patients with multiple sclerosis (MS) are more likely to have other autoimmune disorders particularly prior to the diagnosis of MS. We conducted a population-based case-control study of patients enrolled in the Northern California Kaiser Permanente Medical Care Program. Electronic clinical records through 2005 were used to ascertain incident and prevalent MS cases and identify the presence and timing of 44 other diagnoses. Controls were matched 5 : 1 for gender, age, and Kaiser membership characteristics. We identified 5296 MS cases (including 924 diagnosed between 2001 and 2004) and 26,478 matched controls. Prior to MS diagnosis, cases were more likely than controls to have uveitis (OR=3.2, 95%; CI 1.7-5.7), inflammatory bowel disease (IBD, OR=1.7, 95%; CI 1.2-2.5), and Bell's palsy (OR=3.2, 95%; CI 1.2-8.3). Cases were also more likely to develop Guillain-Barr syndrome (GBS, OR=5.0, 95%; CI 1.6-15.4) and bullous pemphigoid (OR=6.7, 95%; CI 1.5-29.9). Cases were not more likely than controls to have or to develop rheumatoid arthritis, lupus or thyroiditis. MS may share environmental triggers, genetic susceptibilities and/or alterations in immune homeostasis with IBD and uveitis, but not with other autoimmune disorders. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 31, 424–431 Background Quality of life among women with irritable bowel syndrome may be affected by pelvic floor disorders. Aim To assess the association of self-reported irritable bowel syndrome with urinary incontinence, pelvic organ prolapse, sexual function and quality of life. Methods We analysed data from the Reproductive Risks for Incontinence Study at Kaiser Permanente, a random population-based study of 2109 racially diverse women (mean age = 56). Multivariate analyses assessed the association of irritable bowel syndrome with pelvic floor disorders and quality of life. Results The prevalence of irritable bowel syndrome was 9.7% ( n = 204). Women with irritable bowel had higher adjusted odds of reporting symptomatic pelvic organ prolapse (OR 2.4; 95% CI, 1.4–4.1) and urinary urgency (OR 1.4; 95% CI, 1.0–1.9); greater bother from pelvic organ prolapse (OR 4.3; 95% CI, 1.5–11.9) and faecal incontinence (OR 2.0; 95% CI, 1.3–3.2); greater lifestyle impact from urinary incontinence (OR 2.2; 95% CI, 1.3–3.8); and worse quality of life ( P < 0.01). Women with irritable bowel reported more inability to relax and enjoy sexual activity (OR 1.8; 95% CI, 1.3–2.6) and lower ratings for sexual satisfaction (OR 1.8; 95% CI, 1.3–2.5), but no difference in sexual frequency, interest or ability to have an orgasm. Conclusions Women with irritable bowel are more likely to report symptomatic pelvic organ prolapse and sexual dysfunction, and report lower quality of life. [ABSTRACT FROM AUTHOR]

An exploratory case-control study to detect risk factors for pancreatic cancer was conducted within a large cohort of people who had received multiphasic health checkups in the San Francisco Bay Area. Four hundred and fifty who later developed pancreatic cancer were compared with 2687 who did not with respect to 779 characteristics recorded at the checkups. There was strong confirmation that cigarette smoking and diabetes mellitus were associated with risk of subsequent pancreatic cancer. Higher levels of serum iron, iron saturation and body weight were also predictive. Less striking associations of interest were with the leukocyte count, pulse rate and certain questionnaire items suggesting non-specific health impairment. Past concerns about alcohol and coffee consumption were not confirmed. [ABSTRACT FROM AUTHOR]

A response by R. A. Popat and colleagues to a letter to the editor about his article "An attempt to replicate interaction between coffee and CYP1A2 gene in connection to Parkinson's disease" in the 2011 issue is presented.