Can birth weight discordancy within monozygotic twin pairs be used as an indicator of chorionicity?

Both zygosity and chorionicity provide important information in twin research. The East Flanders Prospective Twin Survey (EFPTS) determines zygosity and chorionicity at birth and therefore provides a gold standard for the testing of diagnostic parameters that can be used to determine chorionicity. The aim of the present study was to investigate whether birthweight discordancy can be used as an indicator of chorionicity. The study sample consisted of 4,060 live-born twin pairs from the EFPTS. We studied MZ twins, using univariate and multivariate logistic regression analyses to calculate odds ratios (OR) and 95% confidence intervals (CI) of being MC in relation to discordancy level. Diagnostic parameters, including sensitivity and specificity, were calculated. A two-fold cross-validation was carried out and a bootstrap distribution with 10,000 samples was created to estimate the standard deviations. For discordancy levels of below 10%, 10-15%, 15-20%, 20-25% and above 25%, the ORs (95% CI) were 1.16 (0.91-1.47), 1.38 (1.05-1.80), 2.13 (1.51-3.01), 2.73 (1.73-4.29) and 2.81 (2.81-4.35) respectively. There were no gender differences. Sensitivity was 42.2% (SD 5.6%), specificity was 72.8% (SD 6.3%), positive predictive value was 72.8% (1.5%) and the negative predictive value was 39.2% (0.7%). In conclusion, although a higher discordancy level resulted in higher ORs of being an MC twin, birthweight discordancy level can only be used to some weak extent as a proxy for chorionicity, highlighting the need to assess and record chorionicity data in obstetrical units

The Contribution of Prenatal Environment and Genetic Factors to the Association between Birth Weight and Adult Grip Strength

Low birth weight has been associated with reduced hand grip strength, which is a marker of future physical function and disease risk. The aim of this study was to apply a twin pair approach, using both ‘individual’ data and ‘within-pair’ differences, to investigate the influence of birth weight on hand grip strength and whether this association may be mediated through fat free mass (FFM). Participants from the East Flanders Prospective Twin Survey were included if born without congenital abnormalities, birth weight >500 g and ≥22 weeks of gestation. Follow up in adulthood (age: 18–34 year), included anthropometric measures and hand grip (n = 783 individuals, n = 326 same-sex twin pairs). Birth weight was positively associated with hand grip strength (β = 2.60 kg, 95% CI 1.52, 3.67, p<0.001) and FFM (β = 4.2, 95% CI 3.16, 5.24, p<0.001), adjusted for gestational age, sex and adult age. Using ‘within-pair’ analyses, the birth weight hand grip association was significant in DZ men only (β = 5.82, 95% CI 0.67, 10.97, p = 0.028), which was attenuated following adjustment for FFM. Within-pair birth weight FFM associations were most pronounced in DZ men (β = 11.20, 95% CI 7.18, 15.22, p<0.001). Our ‘individual’ analyses show that higher birth weight is associated with greater adult hand grip strength, which is mediated through greater adult FFM. The ‘within-pair’ analyses confirm this observation and furthermore show that, particularly in men, genetic factors may in part explain this association, as birth weight differences in DZ men result in greater differences in adult strength and FFM

Estimating the Magnitude of Genetic Factors by Calculating the Genetic Relative Risk of Stroke in First-Ever Lacunar Stroke Patients

BACKGROUND: Positive family history of stroke is an independent risk factor for lacunar stroke. However, the magnitude of familial aggregation of a certain disease is better evaluated by the genetic relative risk. This is calculated by dividing the prevalence of specific disease in family members of patients by the prevalence of this disease in the general population. In a cohort of lacunar stroke patients, who were subtyped clinically and radiologically, we determined the genetic relative risk of stroke. METHODS: By questionnaire and additional interview, we obtained a complete first-degree family history of stroke. The prevalence of stroke in first-degree relatives of these lacunar stroke patients was compared to the self-reported prevalence of stroke in a Dutch community based cohort of elderly volunteers. Secondly, the influence of proband characteristics and family composition on parental and sibling history of stroke were evaluated. PRINCIPAL FINDINGS: We collected data of 1066 first-degree relatives of 195 lacunar stroke patients. Strokes occurred in 13.5% of first-degree relatives. The genetic relative risk was 2.94 (95%CI 2.45-3.53) for overall first-degree relatives, 4.52 (95%CI 3.61-5.65) for patients' parents and 2.10 (95%CI 1.63-2.69) for patients' siblings. Age of proband and proband status for hypertension influenced the chance of having a parent with a history of stroke whereas the likelihood of having a concordant sibling increased with sibship size. CONCLUSIONS: We found an increased genetic relative risk of stroke in first-degree relatives of patients with lacunar stroke. Our data warrant further genomic research in this well-defined high risk population for stroke

Blood pressure in young adulthood and residential greenness in the early-life environment of twins

Background: Previous research shows that, besides risk factors in adult life, the early-life environment can influence blood pressure and hypertension in adults. However, the effects of residential traffic exposure and residential greenness in the early-life on blood pressure in young adulthood are currently unknown. Methods: Ambulatory (24-h) blood pressures of 278 twins (132 pairs) of the East Flanders Prospective Twins Study were obtained at the age of 18 to 25 years. Prenatal and adulthood residential addresses were geocoded and used to assign prenatal and postnatal traffic and greenness indicators. Mixed modelling was performed to investigate blood pressure in association with greenness while adjusting for potential confounding factors. Results: Night-time systolic blood pressure was inversely associated with greenness at the residential address in twins living at the same address their entire life (non-movers, n = 97, 34.9%). An interquartile increase in residential greenness exposure (1000 m radius) was associated with a 3.59 mmHg (95% CI: -6.0 to -1.23; p = 0.005) lower adult night systolic blood pressure. Among twins who were living at a different address than their birth address at time of the measurement (n = 181, 65.1%), night-time blood pressure was inversely associated with residential surrounding greenness at adult age as well as with residential greenness in early-life. However after additional adjustment for residential greenness exposure in adulthood, only residential greenness exposure in early-life was significantly associated with night systolic blood pressure. While no significant effect of adult residential greenness with adult blood pressure was observed, while accounting for the early-life greenness exposure. Conclusions: Lower residential greenness in the early-life environment was independently associated with a higher adult blood pressure. This indicates that residential greenness has persistent effects on blood pressure

Differences in Tumor-Associated Protein Levels among Middle-Age Flemish Women in Association with Area of Residence and Exposure to Pollutants

We measured tumor-associated proteins (TAPs) and pollutants in blood, serum, and urine of 200 nonsmoking women 50–65 years of age, residing in the rural municipality of Peer or in Hoboken or Wilrijk, industrial suburbs of Antwerp, Belgium. Persons with occupational exposures or commuting to other towns were excluded. Residents from Hoboken had significantly higher levels of blood lead and serum zinc and polychlorinated biphenyls. Surprisingly, residents of Peer had significantly higher levels of serum cadmium, dioxin-like activity in blood fat, and urinary 1-hydroxypyrene. For 5 of the 12 TAPs assessed in this study, we observed significant differences in serum levels among residents of the three municipalities after adjusting for personal or lifestyle parameters. Although we found levels of internal exposure to pollutants to be quite homogeneous in Flanders, we found significantly higher levels of TAPs only in the industrial suburbs. In multiple regression with all 29 available personal, lifestyle, and internal exposure parameters, blood lead levels showed a positive association with serum levels of anti-p53, carcino-embryonic antigen (CEA), and tissue polypeptide–specific antigen (TPS) and with an index for mean TAP level (I(tap)); dioxin-like activity in serum and serum copper showed a positive association with serum CA 125 (cancer antigen 125); and serum zinc showed a positive association with serum levels of c-erbB-2 ectodomain and TPS. An index of internal exposure showed a positive association with serum levels of both CEA and anti-p53 and with I(tap). This study provides some evidence that levels of internal exposure such as those present in Flanders, in particular concerning lead, are indeed associated with biologic effects

Serum Dioxin-like Activity Is Associated with Reproductive Parameters in Young Men from the General Flemish Population

BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and some related environmental contaminants are aryl hydrocarbon receptor (AhR) ligands that exert reproductive and developmental toxicity in laboratory animals. In humans, fertility-related effects are less documented. OBJECTIVE: The aim of this study was to investigate the relationship between dioxin-like biological activity in serum and parameters of reproductive status in men from the general population 5 months after a polychlorinated biphenyl and dioxin food-contamination episode in Belgium. DESIGN: In the framework of the cross-sectional Flemish Environment and Health Study (FLEHS), we recruited 101 men 20–40 years of age and evaluated sperm parameters, measured sex hormones, and gathered information on a number of lifestyle factors. In addition, we determined the AhR-mediated enzymatic response elicited by individual serum samples and expressed it as TCDD equivalent concentrations (CALUX-TEQs) using an established transactivation assay. RESULTS: Age (p = 0.04) and the frequency of fish (p = 0.02) and egg (p = 0.001) consumption were independent positive determinants of serum dioxin-like activity. After correcting for possible confounders, we found that a 2-fold increase in CALUX-TEQ > 16 pg/L was associated with a 7.1% and 6.8% (both p = 0.04) decrease in total and free testosterone, respectively. We also observed a more pronounced drop in semen volume of 16.0% (p = 0.03), whereas sperm concentration rose by 25.2% (p = 0.07). No relationship was found with total sperm count or sperm morphology. CONCLUSIONS: These data suggest an interaction of dioxin-like compounds with the secretory function of the seminal vesicles or prostate, possibly indirectly through an effect on testosterone secretion, at levels not affecting spermatogenesis as such