Ductus venosus flow at 11-13 weeks in the prediction of birth weight discordance in monochorionic twins.

OBJECTIVE: To examine if assessment of ductus venosus (DV) flow, crown-rump length (CRL) and nuchal translucency (NT) thickness can predict the discordance in birth weight in monochorionic (MC) twin pregnancies resulting in two live births. METHODS: In this prospective study, we assessed CRL, NT and DV flow at 11(+0)-13(+6) weeks' gestation in 326 MC twin pregnancies. The study population included 237 pregnancies without major abnormalities or prenatal interventions resulting in two live births. We examined the value of DV flow and discordance in NT and CRL in the prediction of discordance in birth weight. RESULTS: In the 237 MC twin pregnancies the median discordance in birth weight was 8.0% (range 0-42.2%). There was no significant association between discordance in either CRL or NT and discordance in birth weight (P=0.116 and P=0.332). In pregnancies with abnormal DV flow in at least one of the fetuses the median discordance in birth weight was higher than in those with normal DV flow in both twins (13.2% vs. 7.8%, P=0.006). CONCLUSIONS: In uncomplicated MC twin pregnancies, abnormal DV flow in at least one of the fetuses is associated with a higher discordance in birth weight than in those with normal flow in both fetuses.

Inflammation is related to coronary flow reserve detected by positron emission tomography in asymptomatic male twins.

OBJECTIVES: This study sought to examine the relationship between inflammation and coronary microvascular function in asymptomatic individuals using positron emission tomography (PET) and assessment of coronary flow reserve (CFR). BACKGROUND: Coronary microvascular dysfunction is an early precursor of coronary artery disease (CAD) thought to result from endothelial cell activation and inflammation, but data are limited. METHODS: We examined 268 asymptomatic male monozygotic and dizygotic twins. Plasma biomarkers of inflammation and endothelial cell activation included C-reactive protein (CRP), interleukin (IL)-6, white blood cell count (WBC), vascular cell adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1. Blood flow quantitation was obtained with [¹³N] ammonia PET at rest and after adenosine stress. CFR was measured as the ratio of maximum flow to baseline flow at rest; abnormal CFR was defined as a ratio < 2.5. A summed stress score for visible perfusion defects was calculated. RESULTS: In within-pair analyses, all biomarkers, except VCAM-1, were higher in twins with lower CFR than their brothers with higher CFR (p < 0.05). This was observed in the entire sample, as well as within pairs discordant for a CFR of <2.5. Associations persisted after adjusting for summed stress score and CAD risk factors. In contrast no biomarker, except IL-6, was related to the summed stress score of visible defects. CONCLUSIONS: Even in asymptomatic subjects, a decrease in coronary microvascular function is accompanied by a systemic inflammatory response, independent of CAD risk factors. Our results, using a controlled twin design, highlight the importance of coronary microvascular function in the early phases of CAD.

Leisure-time physical activity and nutrition: a twin study.

OBJECTIVE: To determine the association between long-term leisure-time physical activity/inactivity and eating behaviours in twin pairs discordant for physical activity for 30 years. DESIGN: Co-twin control design with cross-sectional data collection using questionnaire on eating habits and 5 d food diary. Differences in eating behaviours between physically active and inactive co-twins were analysed with pairwise tests. SETTING: Finland. SUBJECTS: Sixteen same-sex twin pairs (seven monozygotic and nine dizygotic, mean age 60 years) discordant for physical activity, selected from the Finnish Twin Cohort on the basis of physical activity discordance for 30 years, blinded to their possible differences in eating behaviours. RESULTS: The eating habits questionnaire revealed that physically active co-twins more frequently reported that it is easy to eat according to need, whereas overeating and/or restrictive eating was more common among the inactive co-twins (P = 0·035). Avoiding calories was more common among the active than inactive co-twins (P = 0·034). Based on food diaries the physically active co-twins had daily energy intake on average 15·5 kJ/kg higher than their inactive co-twins (P = 0·030). The active co-twins also had a higher intake of vitamin C (P = 0·004), total water (P = 0·044), legumes and nuts (P = 0·015) and sweets (P = 0·036), as well as a lower energy-adjusted intake of meat (P = 0·013). CONCLUSIONS: The physically active persons seem to eat more but not necessarily healthier food. However, habitual physical activity may help in eating according to need and in reaching and maintaining a healthy body composition. Therefore, it is necessary to incorporate both dietary and physical activity advice into health counselling.

Determinants of infant growth in four age windows: a twin study.

OBJECTIVE: To identify determinants of growth during infancy. STUDY DESIGN: The sample included 424 twin pairs from the East Flanders Prospective Twin Survey. Multilevel regression analysis was performed and intrapair growth correlations were calculated. The main outcome measure was growth, measured in g/kg/d (0-1 month) or in change in weight z-score (0-6, 6-12 and 12-24 months). RESULTS: Growth during infancy was associated with birth weight and gestational age. One z-score increase in birth weight resulted in -1.77 g/kg/d less growth from 0-1 month (P < .0001). The effect size decreased with age until -0.02 (P = .70) z-scores less growth from 12 to 24 months. Corresponding numbers for one z-score increase in gestational age decreased from 0.78 (P = .001) to 0.06 (P = .40). From 12 to 24 months, paternal height had a significant positive effect. The difference in growth similarity within the twin pair between monozygotic and dizygotic twins increased from non-significant from 0 to 1 month (P = .49) to a monozygotic:dizygotic ratio approximating 2:1 from 12 to 24 months (P = .002). CONCLUSION: From 0 to 1 month, environmental factors are most important for growth, whereas genetic factors become more important over time. This is a first step in identifying age windows for future counseling and interventions on the effects of accelerated growth.

Birth weight discordance of twin pairs and their subsequent growth patterns.

BACKGROUND: Few studies have compared the growth of a twin with its co-twin and particularly in relation to birth weight discordance. AIM: The study investigated how the degree of birth weight discordance affected subsequent growth. METHODS: Birth weight discordance of 762 twin pairs was determined. Subsequent weight, height and occipital-frontal head circumference (OFC) measurements were obtained between the ages of 2-9 years. Corresponding standard deviations scores (SDS) were analysed according to birth weight discordance, sex and zygosity. Weight status was taken into account by assigning twins into sub-groups according to whether they were the heavier twin at birth and remained heavier, became the lighter of the twin pair or had the same weight, for subsequent measurements. RESULTS AND CONCLUSIONS: The degree of birth weight discordance had little effect on subsequent growth except in monozygotic (MZ) twins with >20% discordance. Severe low birth weight ( < 1.95 kg) is more significant in suppressing subsequent growth than the degree of discordance per se. A surprisingly high proportion of twins reversed their weight status when reviewed at an older age.

Genetic and environmental influences on blood pressure and body mass index in Han Chinese: a twin study.

The familial aggregation of blood pressure (BP) may be partly due to the familial aggregation of obesity, caused by genetic and/or environmental factors that influence both. Gene-obesity interactions are expected to result in different heritability estimates for BP at different obesity levels. However, the latter hypothesis has never been tested. The present study included 1243 monozygotic and 833 dizygotic Han Chinese twins (mean±s.d. age: 37.81 ± 9.82; range: 19.1-81.4) from the Chinese National Twin Registry. Body mass index (BMI) was used as the index of general obesity. The outcome measures were systolic BP (SBP) and diastolic BP (DBP). Quantitative genetic modeling was performed using Mx software. The SBP and DBP heritabilities were 46 and 30%, respectively. The positive correlations of BMI with SBP (r=0.26) and with DBP (r=0.27) were largely due to genetic factors (approximately 85%). Genetic factors, which also influence BMI, account for 6 and 7% of the total variance for SBP and DBP, respectively. The gene-obesity interaction analysis showed that both common and unique environmental influences on SBP increased with increasing levels of BMI, resulting in a lower heritability at higher BMI levels, whereas for DBP the heritability remained unchanged at higher BMI levels. Our results suggest that higher BMIs may reduce SBP heritability through a larger impact of environmental effects. These conclusions may be valuable for gene-finding studies.

Liver and pancreatic fat content and metabolism in healthy monozygotic twins with discordant physical activity.

BACKGROUND & AIMS: Ectopic fat in muscle and liver is linked to obesity and type 2 diabetes. Recently, pancreatic lipid accumulation has also been associated with ß-cell dysfunction and reduced insulin production, leading to the development of type 2 diabetes. Physical exercise training has been shown to attenuate ß-cell dysfunction in patients, but little is known about its effects on pancreatic and hepatic fat accumulation. In this study, we validated in-vivo proton magnetic resonance spectroscopy ((1)H MRS) in pancreatic fat measurement with biochemical measurements in a pig model. Thereafter, the effects of increased physical activity on the amounts of pancreatic and liver fat were studied in eight monozygotic twin pairs who have discordant physical activity and fitness. METHODS: Pancreatic fat content was studied in 15 pigs using (1)H MRS and/or biochemical analyses. In addition, liver and pancreatic fat were assessed using (1)H MRS in eight monozygotic male twin pairs with 18% mean difference in VO(2max) between the twin brothers. RESULTS: Twins with higher physical fitness had 23% less liver fat (1.3±1.3% vs. 2.1±2.6%, p=0.022) but no such difference was observed in the pancreatic fat (8.2±9.3% vs. 9.8±8.5%, respectively, p=0.3). Hepatic fat content was inversely associated with VO(2max). A positive association was found between pancreatic and liver fat contents (ß=5.18, p=0.012). Pancreatic fat content was also associated with insulin sensitivity indexes and plasma adiponectin and glutamyltransferase concentrations. CONCLUSIONS: Pancreatic fat content is associated with insulin resistance and hepatic fat content. An active lifestyle seems to beneficially influence hepatic fat metabolism.

An investigation into the relationship between soft tissue body composition and bone mineral density in a young adult twin sample.

The purpose of this study was to investigate the relationship of fat mass (FM) and lean mass (LM) with bone mineral density (BMD) independent of genetic effects. We also assessed the extent to which genetic and environmental influences explain the associations between these phenotypes. Body composition and BMD were measured using dual-energy X-ray absorptiometry in 57 monozygotic and 92 same-sex dizygotic twin pairs, aged 23 to 31 years, chosen to represent a wide range of intrapair differences in body mass index (BMI; 0 to 15.2 kg/m(2)). Heritability estimates were adjusted for height and gender. In multiple linear regression analysis, intrapair differences in both FM and LM were independently associated with intrapair differences in BMD at most skeletal sites after adjustment for gender and differences in height. Within monozygotic and dizygotic pairs, LM was a significantly stronger predictor of whole-body BMD than FM (p < .01). Additive genetic factors explained 87% [95% confidence interval (CI) 80%-91%), 81% (95% CI 70%-88%), and 61% (95% CI 41%-75%) of the variation in whole-body BMD, LM, and FM, respectively. Additive genetic factors also accounted for 69% to 88% of the covariance between LM and BMD and for 42% to 72% of the covariance between FM and BMD depending on the skeletal site. The genetic correlation between LM and whole-body BMD (r(g) = 0.46, 95% CI 0.32-0.58) was greater than that of FM and whole-body BMD (r(g) = 0.25, 95% CI 0.05-0.42). In conclusion, our data indicate that peak BMD is influenced by acquired body weight as well as genetic factors. In young adulthood, LM and BMD may have more genes in common than do FM and BMD.

Primary tooth emergence in Australian children: timing, sequence and patterns of asymmetry.

BACKGROUND: Information on the timing and sequence of human tooth emergence is valuable when analysing human growth and development, predicting the age of individuals, and for understanding the effects of genetic and environmental influences on growth processes. This paper provides updated data on the timing and sequence of primary tooth emergence in Australian children for both clinicians and researchers. METHODS: Twins were recruited from around Australia with data collected through parental recording of twins' primary tooth emergence. One twin from each pair was then randomly selected to enable the calculation of descriptive statistics for timing, sequence and asymmetry in tooth emergence. RESULTS: The first and last primary teeth emerged, on average, at 8.6 months and 27.9 months, respectively, with teeth emerging in the order: central incisor, lateral incisor, first molar, canine, second molar. Left-side antimeric teeth were more likely to emerge before their right-side counterparts but this was not statistically significant. At least 35% of all antimeric pairs had emerged within two weeks of each other, serving as a useful guideline for assessing symmetrical versus asymmetrical development. CONCLUSIONS: Primary tooth emergence in Australian twins is occurring later than reported previously for Australian singletons but is consistent with findings for singletons in other ethnic groups. The most common sequence of primary tooth emergence appears to be consistent in twins and singletons and has not changed over time.

A longitudinal study on genetic and environmental influences on leisure time physical activity in the Finnish Twin Cohort.

The purpose of this study was to examine changes in the contribution of genetic and environmental influences to leisure time physical activity among male and female twins over a 6-year follow-up. At baseline the sample comprised 4,280 monozygotic and 9,276 dizygotic twin individuals, and at follow-up 4,383 monozygotic and 9,439 dizygotic twin individuals. Participants were aged 18-54 years at baseline. Genetic modeling results showed that genetic influences on leisure time physical activity declined from baseline (44%) to follow-up (34%). Most of the genetic influences identified at baseline were present at followup (r(g) = 0.72). Specific environmental influences increased from baseline (56%) to follow-up (66%) while at follow-up new environmental time-specific influences were observed (r(e) = 0.23). The model with sex differences showed a higher estimate of genetic influences for men than women both at baseline (men 47% vs. women 42%) and at follow-up (men 38% vs. women 31%). The additive genetic correlation for this phenotype was greater for men (r(g) = 0.79) than women (r(g) = 0.64). The specific environmental influences were corresponding; at baseline men 53% and women 56% and at follow-up men 62 % and women 69%. The environmental correlations between the two time points were similar for men (r(e)= 0.21) and for women (r(e)= 0.24). In conclusion, in a sample of healthy twins most of the genetic influences on leisure time physical activity expressed at baseline were present at 6 years of follow-up. New specific environmental factors underlying follow-up leisure time physical activity were observed.

Monochorionic diamniotic twin pregnancies pregnancy outcome, risk stratification and lessons learnt from placental examination.

Monochorionic diamniotic twin pregnancies have a more hazardous intrauterine stay than their dichorionic counterparts because of the vascular anastomoses that connect the two fetal circulations. The survival of monochorionic twins diagnosed in the first trimester is 89%. Twin-to-twin transfusion syndrome (TTTS) occurs in 9% and is the most important cause of death. Risk assessment by ultrasound scan in the first and early second trimester identifies a subgroup of monochorionic twins with a more than 70% risk of a complicated outcome and a survival rate of only 69%. For complicated monochorionic twin pregnancies, umbilical cord coagulation for selective feticide has a survival rate of 83% with a normal development in 92%. Umbilical cord coagulation also results in a good outcome for the healthy co-twin of a heterokaryotypic monochorionic pair. Unequally shared placentas have a more elaborate blood exchange, which reduces the birthweight discordance. In these cases, the anastomoses fulfill a beneficial role by increasing the availability of oxygen and nutrients to the twin on the smaller placental share. Pairs with early onset discordant growth have a higher mortality and a more unequally shared placenta than pairs with late onset discordant growth. Unequal placental sharing therefore appears to be the cause of early onset discordant growth, whereas a late intertwin transfusion imbalance may be involved in some cases with late onset discordant growth. Finally, placental examination after laser treatment for TTTS demonstrated that successful coagulation of all visible anastomoses cures TTTS. However, anastomoses can be missed and lead to a complicated pregnancy outcome.

Monozygotic twins are discordant for chronic periodontitis: clinical and bacteriological findings.

OBJECTIVES: The aim of this study was to assess, in monozygotic (MZ) and dizygotic (DZ) twin pairs in whom the proband of the twin pair was suffering from moderate to severe chronic periodontitis, the contribution of genetics, periodontal pathogens and lifestyle factors towards the clinical phenotype. MATERIAL AND METHODS: For this study, 18 adult twin pairs were selected on the basis of interproximal attachment loss (AL) >or=5 mm in >or=2 non-adjacent teeth in one twin member. The study included 10 MZ and eight DZ twin pairs, in whom the periodontal condition, presence of periodontal pathogens, educational level, smoking behaviour and body mass index (BMI) were evaluated. RESULTS: Both MZ and DZ twins were discordant regarding AL and alveolar bone loss. Discordance was greater in DZ compared with MZ twins. In MZ twins, the discordance could not be explained by education, smoking, BMI and periodontal pathogens. In DZ twins, 45.6% of the discordance could be explained by more pack-years of the probands. CONCLUSION: The results confirm a possible role of genetic factors in periodontitis. However, the magnitude of the genetic effects on disease severity may have been overestimated previously.

Cerebral asymmetries in monozygotic twins: an fMRI study.

Lateralization for language, spatial judgment and face processing was assessed in 42 pairs of identical twins, 21 discordant and 21 concordant pairs for handedness, using fMRI. Individual laterality indices were calculated based on the observed activation patterns. All tasks showed expected asymmetry, favoring the left-hemisphere for language and the right-hemisphere for spatial judgment and face processing. The intra-class correlations on the laterality indices were significant only on the language task and only for the concordant group, but not the discordant group, suggesting a stronger genetic influence for language asymmetry in concordant twins. The expected asymmetry was greater for the concordant group only on the language task. The difference was not significant, but conformed quite well to Annett's genetic model, which assumes a right-shift (RS) gene with one allele (RS+) biasing toward right-handedness and left-cerebral language dominance, and the other (RS-) leaving both asymmetries to chance. The model also assumes that the genetic influence is additive for handedness but dominant-recessive for left-cerebral language dominance, which explains the high concordance for language dominance in twins discordant for handedness. Our data suggest that the same gene has no influence on right-hemisphere dominance for spatial judgment or face processing, and offer little support for mirror-imaging in MZ twins other than that due to chance.

Cerebellar asymmetry in a pair of monozygotic handedness-discordant twins.

Increasing evidence for a cerebellar role in human cognition has accrued with respect to anatomically and functionally distinct lobules. Questions of laterality, however, have been largely overlooked. This study therefore introduced and applied a novel measurement protocol for comparatively bias-free analysis of cerebellar asymmetries. Volumetric measurements were performed on magnetic resonance images from a single pair of monozygotic handedness-discordant twins. Against a background of functional cortical asymmetry for verbal and visuo-spatial functional magnetic resonance imaging activation, which was mirrored in the left-handed twin (Lux et al. 2008), between-twin differences in cerebellar asymmetry are described. Interestingly, asymmetry measures for the whole cerebellum did not correspond to either the direction of hand preference or to the weaker (functional magnetic resonance imaging) lateralization of the left-handed twin. The twins both showed clockwise cerebellar torques. This mirrored a counter-clockwise cerebral torque in the right-handed twin only. Selected single cerebellar lobules V and VII displayed between-twin laterality differences that partially reflected their discrepant handedness. Whole cerebellum anatomical measures appeared to be unrelated to single functional cortical asymmetries. These analyses contribute further anatomical evidence pertaining to the existence of multiple structurally and functionally distinct cortico-cerebellar networks of the healthy human brain in vivo.

Neuregulin 1-induced AKT phosphorylation in monozygotic twins discordant for schizophrenia.

Patients with schizophrenia exhibit decreased neuregulin 1 (NRG1)-stimulated AKT phosphorylation in peripheral lymphoblasts. Here, we examined this peripheral marker in monozygotic twins discordant for schizophrenia and in healthy monozygotic twins without psychiatric disorders. B lymphoblasts were stimulated with NRG1a (65 amino-acid residue recombinant protein from the epidermal growth factor [EGF] domain) for 30min. The protein isolated from the cells was analysed by Western blotting. The dependent measure was the ratio of phosphorylated AKT (pAKT) and total AKT at baseline (without NRG1 stimulation) and after NRG1 stimulation (pAKT/AKT). The results revealed that in the case of the unaffected co-twins of patients with schizophrenia, NRG1-stimulated pAKT/AKT ratio was in between the values of their co-twins with schizophrenia and that of the healthy control twin pairs. When the affected twins with schizophrenia were compared with their unaffected co-twins using a Mann-Whitney U-test, we found significantly lower NRG1-induced pAKT/AKT ratios in the patients relative to their unaffected co-twins (p=0.004). However, using a more conservative analysis (Kruskal-Wallis ANOVA followed tests for multiple comparisons), this difference was not significant. The unaffected co-twins of patients with schizophrenia did not differ significantly from the healthy control twins. In the baseline condition, the pAKT/AKT ratios were similar in all groups. These results indicate that impaired AKT-related intracellular signaling is partly related to the developed illness and cannot fully be explained by the genetic background of schizophrenia.

Placental characteristics of selective birth weight discordance in diamniotic-monochorionic twin gestations.

Up to 21% of diamniotic-monochorionic twin pregnancies are complicated by severe birth weight discordance in the absence of twin-to-twin transfusion syndrome, a serious condition termed 'selective' birth weight discordance. While its pathogenesis remains incompletely understood, the development of selective intertwin growth discordance, related to fetal growth restriction of one twin, is generally attributed to aberrant placental characteristics. The aim of this study was to characterize the placental markers of selective birth weight discordance, with special emphasis on the choriovascular architecture. A prospective cohort of 319 consecutive diamniotic/monochorionic twin placentas was examined at Women and Infants Hospital between 2001 and 2009. After exclusion of placentas from pregnancies complicated by twin-to-twin transfusion syndrome (TTTS), monoamniotic, multiple and disrupted placentas, 216 placentas (36 birth weight (BW)-discordant and 180 BW-concordant) formed the subject of this study. Following dye injection, the anatomic characteristics and choriovascular anastomotic patterns of BW-discordant and BW-concordant placentas were compared. The BW-discordant placentas showed significantly higher frequencies of velamentous cord insertion (22% versus 8%, P < 0.001) and uneven placental sharing (56% versus 19%, P < 0.0001) compared with BW-concordant placentas. The frequencies of intertwin AA, VV and AV anastomoses, the net number of AV anastomoses, and the net cross-sectional area of AV anastomoses were similar in both groups. There was no correlation between the frequency of velamentous cord insertion and degree of placental sharing or patterns of choriovascular anastomoses in either group. In conclusion, velamentous cord insertion and uneven placental sharing are the two major placental determinants of selective birth weight discordance in diamniotic-monochorionic twins. The role of the intertwin anastomoses, even when unbalanced, is likely negligible. Elucidation of the mechanisms whereby velamentous cord insertion affects fetal growth may lead to more focused and effective therapeutic strategies for twin and singleton pregnancies complicated by dysregulated fetal growth.

Physical features observation: is it repeatable in zygosity determination of Chinese adult twins?

This study reports on the inter- and intrarater reliability of physical features observation. Study subjects were 176 Chinese adult persons, consisting of 89 males and 87 females. Three trained research assistants responded simultaneously and respectively to 12 items regarding the subject's physical features including 'hair', 'Mongoloid folds', left and right 'ear lobes', 'earwax', 'nostril shape', 'tongue rolling', left and right 'hitchhiker's thumb', 'mid-digital hair' and left and right 'simian crease' at the moment of interview. And 14 days later, these subjects received the same observation once again. The results showed that the inter- and intra-observer agreements of 'hair', 'earwax', 'tongue rolling', 'mid-digital hair' and 'simian crease' were almost perfect with most kappa (kappa) coefficients >or= .80, while 'Mongoloid fold' and 'nostril shape' showed poor inter-observer agreement and 'nostril shape' showed poor intra-observer agreement (kappa < .40). Two other physical features, 'hitchhiker's thumb' and 'ear lobes' showed moderate inter-observer agreement and three features, 'hitchhiker's thumb', 'ear lobes' and 'Mongoloid fold', showed moderate intra-observer agreement (.40