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Prior theoretical and empirical research has highlighted links between positive parenting and the socioeconomic characteristics of the family's neighborhood, but has yet to illuminate the etiologic origins of this association. One possibility is that the various predictors of parenting outlined by Belsky (1984; e.g., characteristics of the child, characteristics of the parent, and contextual influences) may matter more in some neighborhood contexts than in others. To examine this possibility, we conducted etiologic moderation analyses in a sample of 1,030 families of twins (average age 8 years; 51% male, 49% female; racial composition: 82% White, 10% Black, 1% Asian, 1% Indigenous, and 6% multiracial) from the Twin Study of Behavioral and Emotional Development in Children in the Michigan State University Twin Registry. Neighborhood and parenting were assessed using multiple informants and assessment strategies (neighborhood and family informants, administrative data, and videotaped parent–child interactions). Results pointed to strong evidence of etiologic moderation, such that child effects on positive mothering were prominent in neighborhoods with little opportunity and near zero in neighborhoods with ample opportunity. Such findings not only reframe the magnitude of child effects on the parenting they receive as context-dependent, but also indicate that mothers in impoverished neighborhoods may be more responsive to their children's characteristics than mothers in neighborhoods with ample opportunity. Public Significance Statement: Our findings confirm the long-running notion that children are active participants in the parenting they receive. However, we find that child effects on positive parenting are also context-dependent, such that child effects on positive parenting are especially pronounced in underresourced neighborhood contexts. [ABSTRACT FROM AUTHOR]

Background: Stress is a universal phenomenon and one of the most common precipitants of insomnia. However, not everyone develops insomnia after experiencing a stressful life event. This study aims to test aspects of Spielman's '3P model of insomnia' (during adolescence) by exploring the extent to which: (a) insomnia symptoms are predicted by polygenic scores (PGS); (b) life events predict insomnia symptoms; (c) the interaction between PGS and life events contribute to the prediction of insomnia symptoms; (d) gene–environment interaction effects remain after controlling for sex. Methods: The sample comprised 4,629 twins aged 16 from the Twin Early Development Study who reported on their insomnia symptoms and life events. PGS for insomnia were calculated. In order to test the main hypothesis of this study (a significant interaction between PGS and negative life events), we fitted a series of mixed effect regressions. Results: The best fit was provided by the model including sex, PGS for insomnia, negative life events, and their interactions (AIC = 26,158.7). Our results show that the association between insomnia symptoms and negative life events is stronger for those with a higher genetic risk for insomnia. Conclusions: This work sheds light on the complex relationship between genetic and environmental factors implicated for insomnia. This study has tested for the first time the interaction between genetic predisposition (PGS) for insomnia and environmental stressors (negative life events) in adolescents. This work represents a direct test of components of Spielman's 3P model for insomnia which is supported by our results. [ABSTRACT FROM AUTHOR]

Background: Due to different assessment modes employed, a clear picture of the prevalence of sleep bruxism across time cannot be formed. Moreover, studies on the persistent or fluctuating nature of sleep bruxism have yielded divergent and even contradictory results. The aim of the present study was to evaluate in a nationwide twin cohort whether self‐reported sleep bruxism was correlated longitudinally, pairwise and cross‐twin over a 20‐year period. Objectives: Self‐reported bruxism was assessed in 1990 and 2011 by mailed questionnaires in the Finnish Twin Cohort study of same‐sex twins born 1945–1957. Methods: We assessed the phenotypic stability over time for all participating individuals (n = 4992). Among zygosity verified pairs (n = 516 MZ and n = 837 DZ), we estimated the cross‐sectional zygosity correlations and the zygosity‐specific cross‐twin cross‐time correlations. Results: Reported bruxism appeared rather persistent over time without significant difference regarding zygosity. The overall phenotypic longitudinal correlation was 0.540 and somewhat higher in men (0.596) than in women (0.507). Pairwise trait correlations in 1990 and 2011 were higher in MZ than in DZ pairs. The cross‐twin cross‐time correlations were higher in MZ twins than in DZ twins, but less than the cross‐sectional MZ and DZ pairwise correlations. Conclusions: The higher correlation of reported sleep bruxism in the cross‐twin cross‐time analyses in MZ than in DZ pairs implies a genetic background for bruxism persistence. Also, bruxism over time in individual twins appears to be fairly persistent and somewhat higher in men than women. [ABSTRACT FROM AUTHOR]

This study explored whether high autistic traits, high attention deficit hyperactivity disorder (ADHD) traits and their interaction were associated with quality of life (QoL) in a sample of 556 of young-adult twins (Mean age 22 years 5 months, 52% Female). Four participant groups were created: high autistic traits, high ADHD traits, high autistic/ADHD traits, and low ADHD/autistic traits. High autistic traits were associated with lower QoL across domains (physical, psychological, social, and environmental). High ADHD traits associated with lower physical, psychological, and environmental QoL. The interaction of autistic and ADHD traits was not significant in any domain. While mental health difficulties were associated with lower QoL, after accounting for mental health, most relationships between autistic traits, ADHD traits and QoL remained. [ABSTRACT FROM AUTHOR]

Objective The aim of the study is to examine the association between the risk of preterm delivery among women with twin pregnancies and their obstetric history. Study Design We designed a retrospective cohort study of live twin births in 2008 in the United States that delivered after 24 0/7 weeks. Women were categorized into nulliparas, multiparas with prior term delivery, and multiparas with prior preterm delivery. The incidence of preterm birth was compared using Chi-square test and multivariable logistic regression models. Results A total of 32,895 nulliparous and 64,701 multiparous women with twin pregnancies were included in the study. Of the multiparous women, 2,505 (4%) had a history of a prior preterm delivery. Multiparous women with prior term birth were more likely to deliver at term (43%) in the index twin pregnancy than nulliparous women (40%) and multiparous women with a prior preterm birth (21%; p < 0.001). Compared with nulliparous women, prior term birth was protective against preterm delivery (adjusted odds ratio [aOR] = 0.67 [95% confidence interval: 0.60–0.74] for delivery <28 weeks and aOR = 0.79 [0.71–0.77] for delivery <34 weeks). Conclusion Among multiparous women with twins, a prior term delivery appeared to be protective against preterm delivery compared with nulliparous women with twins. Key Points Prior term birth is protective against preterm birth in subsequent twin pregnancy. A prior term birth confers an OR of 0.66 for delivery prior to 28 weeks in twin pregnancies. A prior preterm birth renders a twin pregnancy nearly twice as likely to deliver before 28 weeks. [ABSTRACT FROM AUTHOR]

Objective: In singleton pregnancies, delivery of large for gestational age (LGA) newborn is associated with various adverse maternal and neonatal outcomes, yet data regarding LGA in twin pregnancies is scarce. We aimed at evaluating maternal and neonatal outcomes associated with LGA presenting twin.Study Design: A multicenter retrospective computerized database study in two university-affiliated obstetrical centers, between 2005 and 2021. Parturients with di-amniotic twin pregnancy who had a trial of vaginal delivery were included. Maternal and neonatal outcomes of parturients with LGA presenting twin were compared to parturients with non-LGA presenting twin.Results: During the study period, 2,491 parturients with twin pregnancies were found eligible, of those 287 (11.5%) had LGA presenting twin. Parturients with LGA presenting twin were of higher gravidity and parity, had higher rates of previous cesarean deliveries and diabetes (pre-gestational & gestational). Mode of delivery of both presenting and second twin did not differ between the study groups. Maternal outcomes were comparable, specifically, rates of shoulder dystocia, and postpartum hemorrhage did not differ. Neonatal outcomes did not differ significantly between the groups other than a single case of clavicular fracture and a single case of encephalopathy in the group of LGA presenting twin.Conclusion: In our study, delivery of LGA presenting twin was found safe to both, mother and neonate. Our findings provide reassurance regarding the safety of vaginal labor in this specific population and should be presented during counseling prior to twins' delivery. [ABSTRACT FROM AUTHOR]

Socio-environmental factors play an important role in adolescent well-being, but potential genetic contributions to these associations are rarely assessed. To address this gap in the literature, associations between well-being and family conflict and functioning, number of friends, friendship importance and satisfaction, and leisure time variables were studied in N = ~ 4700 twin pairs from the Netherlands Twin Register, us ing generalized estimating equations and twin-difference scores. When twin-difference scores indicated a role for genetic factors, we used bivariate genetic models to quantify genetic and environmental contributions to these associations. We identify significant associations between well-being and family functioning, family conflict, different leisure time activities, number of friends, and satisfaction with friendships. Additionally, we find evidence for large (73–91%) genetic influence on the associations between well-being and family conflict and functioning, leisure time sport/scouting clubs, and satisfaction with friendships. Finally, findings support the hypothesis of a causal association between well-being and family conflict and functioning. These findings have important implications for research into the social correlates of well-being in adolescence, as not taking genetic factors into account leads to overestimations of the influence of identified correlates and consequently to recommendations of these correlates as intervention targets. [ABSTRACT FROM AUTHOR]

Tau accumulation starts during the preclinical phase of Alzheimer's disease and is closely associated with cognitive decline. For preventive purposes, it is important to identify factors associated with tau accumulation and spread. Studying genetically identical twin-pairs may give insight into genetic and environmental contributions to tau pathology, as similarities in identical twin-pairs largely result from genetic factors, while differences in identical twin-pairs can largely be attributed to non-shared, environmental factors. This study aimed to examine similarities and dissimilarities in a cohort of genetically identical older twin-pairs in (i) tau load; and (ii) spatial distribution of tau, measured with 18F-flortaucipir PET. We selected 78 genetically identical twins (39 pairs; average age 73 ± 6 years), enriched for amyloid-β pathology and APOE ε4 carriership, who underwent dynamic 18F-flortaucipir PET. We extracted binding potentials (BPND) in entorhinal, temporal, widespread neocortical and global regions, and examined within-pair similarities in BPND using age and sex corrected intra-class correlations. Furthermore, we tested whether twin-pairs showed a more similar spatial 18F-flortaucipir distribution compared to non-twin pairs, and whether the participant's co-twin could be identified solely based on the spatial 18F-flortaucipir distribution. Last, we explored whether environmental (e.g. physical activity, obesity) factors could explain observed differences in twins of a pair in 18F-flortaucipir BPND. On visual inspection, Alzheimer's disease-like 18F-flortaucipir PET patterns were observed, and although we mainly identified similarities in twin-pairs, some pairs showed strong dissimilarities. 18F-flortaucipir BPND was correlated in twins in the entorhinal (r = 0.40; P = 0.01), neocortical (r = 0.59; P < 0.01) and global (r = 0.56; P < 0.01) regions, but not in the temporal region (r = 0.20; P = 0.10). The 18F-flortaucipir distribution pattern was significantly more similar between twins of the same pair [mean r = 0.27; standard deviation (SD) = 0.09] than between non-twin pairings of participants (mean r = 0.01; SD = 0.10) (P < 0.01), also after correcting for proxies of off-target binding. Based on the spatial 18F-flortaucipir distribution, we could identify with an accuracy of 86% which twins belonged to the same pair. Finally, within-pair differences in 18F-flortaucipir BPND were associated with within-pair differences in depressive symptoms (0.37 < β < 0.56), physical activity (-0.41 < β < -0.42) and social activity (-0.32 < β < -0.36) (all P < 0.05). Overall, identical twin-pairs were comparable in tau load and spatial distribution, highlighting the important role of genetic factors in the accumulation and spreading of tau pathology. Considering also the presence of dissimilarities in tau pathology in identical twin-pairs, our results additionally support a role for (potentially modifiable) environmental factors in the onset of Alzheimer's disease pathological processes, which may be of interest for future prevention strategies. [ABSTRACT FROM AUTHOR]

Background: We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well‐being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. Method: The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self‐rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co‐twin comparison models were applied and included covariates from adolescence and early midlife. Results: There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (β = 0.03, 95% CI [0.03, 0.04]), self‐rated health (β = −0.02, 95% CI [−0.03, −0.01]), and life satisfaction (β = −0.03, CI [−0.04, −0.02]). These serial mediation effects were robust in co‐twin comparison analyses. Conclusions: These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan. [ABSTRACT FROM AUTHOR]

Background: The sex gap in life expectancy has been narrowing in Finland over the past 4-5 decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging which predict life span. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults.Methods: Our sample consists of younger and older twins (21‒42 years, n = 1 477; 50‒76 years, n = 763) including 151 complete younger opposite-sex twin pairs (21‒30 years). Blood-based DNA methylation was used to compute epigenetic age acceleration by 4 epigenetic clocks as a measure of biological aging. Path modeling was used to study whether the association between sex and biological aging is mediated through lifestyle-related factors, that is, education, body mass index, smoking, alcohol use, and physical activity.Results: In comparison to women, men were biologically older and, in general, they had unhealthier life habits. The effect of sex on biological aging was partly mediated by body mass index and, in older twins, by smoking. Sex was directly associated with biological aging and the association was stronger in older twins.Conclusions: Previously reported sex differences in life span are also evident in biological aging. Declining smoking prevalence among men is a plausible explanation for the narrowing of the difference in life expectancy between the sexes. Data generated by the epigenetic clocks may help in estimating the effects of lifestyle and environmental factors on aging and in predicting aging in future generations. [ABSTRACT FROM AUTHOR]

Purpose. To assess possible neurodevelopmental delay (NDD) following intravitreal antivascular endothelial growth factor (VEGF) injection in neonates with retinopathy of prematurity (ROP). Methods. In this retrospective cohort study, neurodevelopmental milestones in patients with a history of ROP and intravitreal bevacizumab (IVB) injection were compared with other gestations that received either no treatment or only a laser for treatment. Results. One hundred and twenty-five neonates (of 59 multi-gestation pregnancies) were included in this study (with the range of age 1–7 years old). Sixty-five (51.18%) were male and sixty-two (48.81%) were female. The mean gestational age (GA) and birth weight of all neonates were 29.69 ± 1.57 weeks (ranges: 26–33 weeks) and 1312.50 ± 269.33 grs (ranges: 730–2100 grs). None of the neurodevelopmental outcomes were statistically different when two subgroups in group A (IVB vs. control) were compared. None of the differences between IVB and laser treated subgroups is statistically significant, except for "reaching for toys," which was delayed in the laser treated subgroup (6.6 ± 2.5 and 6.9 ± 2.5 months in IVB and laser treated subgroups, respectively). Conclusion. In neonates with ROP, there is no linear correlation between intravitreal anti-VEGF injection and neurodevelopmental delay. [ABSTRACT FROM AUTHOR]

Objective: To assess whether antenatal corticosteroid treatment is associated with improved neonatal outcomes in twins.Data Sources: We searched MEDLINE, PubMed, EMBASE, and the Cochrane Library, from inception through August 12, 2021. We did not search ClinicalTrials.gov because our inclusion criteria were restricted to nonrandomized studies.Methods Of Study Selection: Records (n=7,802) were screened in Rayyan by two independent reviewers. We included all nonrandomized studies that compared antenatal corticosteroid treatment with no treatment in twins. Our outcomes of interest were neonatal mortality, respiratory distress syndrome (RDS), intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, periventricular leukomalacia, and retinopathy of prematurity.Tabulation, Integration, and Results: We used the ROBINS-I tool (Risk Of Bias In Non-randomised Studies - of Interventions) to assess risk of bias. We performed random-effects meta-analyses of estimates from studies without critical risk of bias due to confounding, and reported summary adjusted odds ratios (aORs) and 95% CIs. Eighteen cohort studies (that reported on 33,152 neonates) met inclusion criteria. Sixteen studies restricted to preterm gestational ages, and 11 defined exposed neonates based on an optimal corticosteroid administration-to-birth interval. Limitations due to confounding and selection bias were common concerns for the risk-of-bias assessments (n=14 at critical or higher), and 11 studies did not account for clustering within twin pairs in their analyses. All included studies had at least moderate risk of bias. Meta-analysis showed that antenatal corticosteroid administration was associated with lower odds of neonatal mortality (aOR 0.59, 95% CI 0.43-0.80, I2 69%, five studies, 20,312 neonates) and RDS (aOR 0.70, 95% CI 0.57-0.86, I2 67%, seven studies, 20,628 neonates) in twins. Results were inconclusive for the other outcomes.Conclusion: Evidence from nonrandomized studies suggests antenatal corticosteroids are associated with lower incidence of neonatal mortality and RDS in twins.Systematic Review Registration: PROSPERO, CRD42020205302. [ABSTRACT FROM AUTHOR]

Background: Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16–50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. Methods: Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. The primary outcome was a composite of adverse perinatal outcomes. Results: Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p < 0.01), higher gestational age at delivery (p < 0.01), Caucasian race (p 0.04), ART use (p < 0.01), gestational diabetes (p < 0.01), vaginal bleeding (p < 0.01), antenatal corticosteroids (p < 0.01), diagnosis of fetal growth restriction (FGR) (p < 0.01), and monochorionic (p < 0.01). Two hundred twenty-six pregnancies (65.3%) had at least one fetus experiencing one composite of adverse perinatal outcome. Multivariate analysis confirmed that delivery indication did not affect the composite of adverse perinatal outcomes; the only characteristic that affect the outcome after controlling for confounding was gestational age at delivery (p < 0.01). Moreover, there was at least one adverse neonatal outcome for 94% of babies born at 34 weeks, for 73% of those born at 35 weeks and for 46% of those born at 36 weeks (p < 0.01). Conclusion: Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants' prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications. [ABSTRACT FROM AUTHOR]

Background: Educational achievement is an independent predictor of many life outcomes and so it is important to understand its causes and correlates. Internalising symptoms, encompassing anxiety and depression symptoms, are one candidate influence.Methods: Using a prospective and genetically-informative design, the present study investigated the associations between internalising symptoms and educational achievement, controlling for IQ at age 7 years and socioeconomic status, among participants of the Twin and Early Development Study (up to N = 10,791). Internalising symptoms were measured by the parent-rated Anxiety Related Behaviours Questionnaire (ages 7, 9, 16 years), and educational attainment were indexed by UK-wide standardized examination results at ages 16 and 18 years, and self-reported transition to university education.Results: Negative affect was the only internalising symptom subtype that was uniquely associated with academic underachievement at all timepoints, from mid-adolescence to early adulthood. The association between negative affect and achievement became non-significant when using MZ twin difference scores, suggesting that the majority of the relationship is accounted for by genetic and shared environmental effects.Limitations: Limitations include the reliance on parent-reported internalising symptoms.Conclusions: Negative affect in youth may be an important marker of later academic underachievement. Findings suggest that academic underachievement is not simply a consequence of the disruption caused by negative affect symptoms and therefore educational interventions may be required to optimise outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to report the prevalence of adverse psychological symptoms and health behaviours of parents who had a baby admitted to a regional neonatal intensive care unit to spotlight mental health care in these unique settings. Design: This was a prospective, prevalence‐based study using quantitative data. Setting: The study was conducted at the Townsville University Hospital, Queensland. Participants: Participants comprised 114 parents of 79 infants enrolled in the study (mothers = 69 and fathers = 45). Main outcome measures: Trauma, depression, anxiety, stress, alcohol and drug use, prior mental health history and bonding experience were assessed by standardised self‐report questionnaires and a structured diagnostic interview within 2 weeks and at 3 months post‐admission to neonatal intensive care unit. Results: Clinically significant acute trauma symptoms (16% of mothers only), depression (22% mothers; 4% of fathers), anxiety (27% mothers; 11% fathers) and stress (24% mothers; 13% fathers) were reported within the first 2 weeks after their baby was admitted to the neonatal intensive care unit. Notably, 18% of parents reported engaging in harmful alcohol use behaviour within 2 weeks post‐birth; 29% of fathers continued to report risky drinking at 3 months. At 3 months, 21%, 8% and 6% of mothers met diagnostic criteria for generalised anxiety disorder, major depressive disorder and post‐traumatic stress disorder, respectively. Conclusion: Screening for psychological distress and alcohol use of parents of neonatal intensive care unit babies can ensure that support services are made available post‐discharge to optimise family function and development of the preterm infant. [ABSTRACT FROM AUTHOR]

The relationship between pitch-naming ability and childhood onset of music training is well established and thought to reflect both genetic predisposition and music training during a critical period. However, the importance of the amount of practice during this period has not been investigated. In a population sample of twins (N = 1447, 39% male, 367 complete twin pairs) and a sample of 290 professional musicians (51% male), we investigated the role of genes, age of onset of playing music and accumulated childhood practice on pitch-naming ability. A significant correlation between pitch-naming scores for monozygotic (r = .27, p < .001) but not dizygotic twin pairs (r = -.04, p = .63) supported the role of genetic factors. In professional musicians, the amount of practice accumulated between ages 6 and 11 predicted pitch-naming accuracy (p = .025). In twins, age of onset was no longer a significant predictor once practice was considered. Combined, these findings are in line with the notion that pitch-naming ability is associated with both genetic factors and amount of early practice, rather than just age of onset per se. This may reflect a dose-response relation between practice and pitch-naming ability in genetically predisposed individuals. Alternatively, children who excel at pitch-naming may have an increased tendency to practice. [ABSTRACT FROM AUTHOR]

Objective: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies.Data Sources: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded.Methods Of Study Selection: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs.Tabulation, Integration, and Results: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward.Conclusion: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone.Systematic Review Registration: PROSPERO, CRD42018090866. [ABSTRACT FROM AUTHOR]

Background: A large literature demonstrates associations between socioeconomic status (SES) and health, including physiological health and well-being. Moreover, gender differences are often observed among measures of both SES and health. However, relationships between SES and health are sometimes questioned given the lack of true experiments, and the potential biological and SES mechanisms explaining gender differences in health are rarely examined simultaneously.Purpose: To use a national sample of twins to investigate lifetime socioeconomic adversity and a measure of physiological dysregulation separately by sex.Methods: Using the twin sample in the second wave of the Midlife in the United States survey (MIDUS II), biometric regression analysis was conducted to determine whether the established SES-physiological health association is observed among twins both before and after adjusting for potential familial-level confounds (additive genetic and shared environmental influences that may underly the SES-health link), and whether this association differs among men and women.Results: Although individuals with less socioeconomic adversity over the lifespan exhibited less physiological dysregulation among this sample of twins, this association only persisted among male twins after adjusting for familial influences.Conclusions: Findings from the present study suggest that, particularly for men, links between socioeconomic adversity and health are not spurious or better explained by additive genetic or early shared environmental influences. Furthermore, gender-specific role demands may create differential associations between SES and health. [ABSTRACT FROM AUTHOR]

Background: Medical guidelines recommend vaginal delivery for low‐risk twin pregnancies because cesareans increase the probability of maternal morbidity and mortality. Yet, vaginal delivery rates for twins are considerably lower than for comparable singletons. One explanation for this disparity argues that greater risk associated with twins warrants increased surgical intervention. An alternative explanation is that twin deliveries are more likely to deviate from protocols that advise vaginal birth. Methods: Using the 2017 Natality Detail File (N = 3,197,401), we measured alignment of vaginal birth and trial of labor (TOL) with the American College of Obstetricians and Gynecologists' guidelines for twin and singleton no‐indicated‐risk births. We calculated predicted probabilities for the population and by maternal race/ethnicity to assess whether low rates of vaginal births among twins are explained by associated risk factors, or by deviations from recommended delivery methods. Results: Overall, 31.2% of twins were born vaginally compared with 79.4% of singletons. Controlling for indicated risks, the predicted probability of vaginal birth for twins was 0.49 and 0.85 for singletons. The predicted probability of TOL for twins was 0.18 and 0.47 for singletons. Maternal race/ethnicity was only weakly associated with mode of delivery. These findings indicate that no‐indicated‐risk twin pregnancies, across maternal racial/ethnic categories, have lower probabilities of vaginal birth and TOL than would be expected with widespread adherence to current guidelines. Conclusions: Given the life‐threatening consequences that may result from unnecessary surgical procedures, our findings highlight the need for further research to illuminate medical and nonmedical mechanisms driving nonadherence to clinical guidelines for twin births. [ABSTRACT FROM AUTHOR]

There is increasing concern regarding additional psychiatric problems that co-occur with Autism Spectrum Disorder (ASD), as reflected in recent changes to diagnostic schemes. However, there remains little research with population-based samples across childhood. We report on additional problems, as measured by the Strengths and Difficulties Questionnaire, in a population-based sample of 135 twins with ASD, 55 non-ASD co-twins, and 144 comparison twins low in ASD traits. Frequencies, associated demographic factors, and changes in mental health difficulties from age 4 to 13 years are presented. Our data confirm the high rates of additional difficulties reported in previous studies, and suggest that the profile, associated risk factors and longitudinal course of additional difficulties in ASD may differ from those in typically-developing populations. [ABSTRACT FROM AUTHOR]

Abstract: Data on the etiological factors underlying the co-occurrence of common adolescent pain with anxiety and depression symptoms are very limited. Opioid prescriptions for adolescent pain problems are on the rise in North America and constitute a risk factor for diversion, misuse, and substance use. In this study, we aimed to investigate the phenotypic and etiological association among pain, depression, and anxiety and to test their link to substance use in adolescents. By taking advantage of the Italian National Twin Registry and of the relatively low incidence of opioid prescriptions in Italy, we applied multivariate modelling analyses to 748 Italian adolescent twins (374 pairs, mean age 16 ± 1.24 years). Twins' responses to the Achenbach Youth Self-Report questionnaire were used to build a composite adolescent pain index and to measure anxiety, depression, and substance use. All monozygotic within-pair correlations were higher than the dizygotic correlations, indicating genetic influences for adolescent pain, anxiety, and depressive problems. A common latent liability factor influenced by genetic and environmental elements shared among pain, depression, and anxiety provided the best fit to explain the co-occurrence of adolescent pain, anxiety, and depression problems. A common phenotypic factor capturing all 3 phenotypes was positively associated (β = 0.19, P < 0.001, confidence interval: 0.10-0.27) with substance use. These findings indicate that several intertwined mechanisms, including genetic factors, can explain a shared liability to common adolescent pain, anxiety, and depression problems. Their association with substance use remains traceable even in societies with relatively low prevalence of opioid prescriptions. [ABSTRACT FROM AUTHOR]

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph  = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA  = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (βself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (βco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown associations between major depression and C-reactive protein (CRP) levels. Few studies have considered the extent to which shared genetic and environmental factors contribute to this association, nor have they considered the relationship outside of European populations. We examined the association between CRP levels and depression and their aetiology in a Sri Lankan population.Methods: Data were collected from 2577 twins and 899 singletons in Colombo, Sri Lanka. Depression symptoms were assessed using the revised Beck Depression Inventory (BDI-II). High-sensitive CRP blood levels were assessed using immunoturbidimetry. Linear regressions were performed to test the association between CRP and depression. The heritability of CRP levels was estimated using Structural Equation Modelling.Results: CRP was significantly associated with BMI (p < 0.01) but not depression (p > 0.05). In males, variance in CRP levels was explained by shared environment (51% 95%CIs: 13-62) and non-shared environment (45% 95%CIs: 36-54). In contrast, in females, CRP variance was explained by genetic (41% 95%CIs: 10-52) and non-shared environment (56% 95%CIs: 47-67). A genetic correlation between CRP and BMI was observed in females only.Limitations: CRP level was based on a single data collection point, longer term data collection would give a more accurate picture of an individual's state of inflammation.Conclusions: The lack of association between depression and CRP strengthens the hypothesis that inflammation might contribute to the development of some, but not all types of depression. CRP levels were moderated by the environment, suggesting interventions aimed at reducing CRP levels and risk for inflammatory conditions, particularly in males. [ABSTRACT FROM AUTHOR]

Objective: The authors examined the extent to which the genetic and environmental etiology of suicide attempt and suicide death is shared or unique.Methods: The authors used Swedish national registry data for a large cohort of twins, full siblings, and half siblings (N=1,314,990) born between 1960 and 1990 and followed through 2015. They conducted twin-family modeling of suicide attempt and suicide death to estimate heritability for each outcome, along with genetic and environmental correlations between them. They further assessed the relationship between suicide attempt by young people compared with adults.Results: In bivariate models, suicide attempt and death were moderately heritable among both women (attempt: additive genetic variance component [A]=0.52, 95% CI=0.44, 0.56; death: A=0.45, 95% CI=0.39, 0.59) and men (attempt: A=0.41, 95% CI=0.38, 0.49; death: A=0.44, 95% CI=0.43, 0.44). The outcomes were substantially, but incompletely, genetically correlated (women: rA=0.67, 95% CI=0.55, 0.67; men: rA=0.74, 95% CI=0.63, 0.87). Environmental correlations were weaker (women: rE=0.36, 95% CI=0.29, 0.45; men: rE=0.21, 95% CI=0.19, 0.27). Heritability of suicide attempt was stronger among people ages 10-24 (A=0.55-0.62) than among those age 25 and older (A=0.36-0.38), and the genetic correlation between attempt during youth and during adulthood was stronger for women (rA=0.79, 95% CI=0.72, 0.79) than for men (rA=0.39, 95% CI=0.26, 0.47).Conclusions: The genetic and environmental etiologies of suicide attempt and death are partially overlapping, exhibit modest sex differences, and shift across the life course. These differences must be considered when developing prevention efforts and risk prediction algorithms. Where feasible, suicide attempt and death should be considered separately rather than collapsed, including in the context of gene identification efforts. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes (T2D) is increasing worldwide, but current treatments have limitations. miRNAs may play a key role in the development of T2D and can be targets for novel therapies. Here, we examined whether T2D is associated with altered expression and DNA methylation of miRNAs using adipose tissue from 14 monozygotic twin pairs discordant for T2D. Four members each of the miR-30 and let-7-families were downregulated in adipose tissue of subjects with T2D versus control subjects, which was confirmed in an independent T2D case-control cohort. Further, DNA methylation of five CpG sites annotated to gene promoters of differentially expressed miRNAs, including miR-30a and let-7a-3, was increased in T2D versus control subjects. Luciferase experiments showed that increased DNA methylation of the miR-30a promoter reduced its transcription in vitro. Silencing of miR-30 in adipocytes resulted in reduced glucose uptake and TBC1D4 phosphorylation; downregulation of genes involved in demethylation and carbohydrate/lipid/amino acid metabolism; and upregulation of immune system genes. In conclusion, T2D is associated with differential DNA methylation and expression of miRNAs in adipose tissue. Downregulation of the miR-30 family may lead to reduced glucose uptake and altered expression of key genes associated with T2D. [ABSTRACT FROM AUTHOR]

Study Question: Does having a male co-twin, older brothers, or sons lead to an increased probability of persistent male microchimerism in female members of twin pedigrees?Summary Answer: The presence of a male co-twin did not increase risk of male microchimerism and the prevalence of male microchimerism was not explained by having male offspring or by having an older brother.What Is Known Already: Microchimerism describes the presence of cells within an organism that originate from another zygote and is commonly described as resulting from pregnancy in placental mammals. It is associated with diseases with a female predilection including autoimmune diseases and pregnancy-related complications. However, microchimerism also occurs in nulliparous women; signifying gaps in the understanding of risk factors contributing to persistent microchimerism and the origin of the minor cell population.Study Design, Size, Duration: This cross-sectional study composed of 446 adult female participants of the Netherlands Twin Register (NTR).Participants/materials, Setting, Methods: Participants included in the study were female monozygotic (MZ) twins, female dizygotic same-sex twins and females of dizygotic opposite-sex twin pairs, along with the mothers and sisters of these twins. Peripheral blood samples collected from adult female participants underwent DNA extraction and were biobanked prior to the study. To detect the presence of male-origin microchimerism, DNA samples were tested for the relative quantity of male specific Y chromosome gene DYS14 compared to a common β-globin gene using a highly sensitive quantitative PCR assay.Main Results and the Role Of Chance: We observed a large number of women (26.9%) having detectable male microchimerism in their peripheral blood samples. The presence of a male co-twin did not increase risk of male microchimerism (odds ratio (OR) = 1.23: SE 0.40, P = 0.61) and the prevalence of male microchimerism was not explained by having male offspring (OR 0.90: SE 0.19, P = 0.63) or by having an older brother (OR = 1.46: SE 0.32, P = 0.09). The resemblance (correlation) for the presence of microchimerism was similar (P = 0.66) in MZ pairs (0.27; SE 0.37) and in first-degree relatives (0.091; SE 0.092). However, age had a positive relationship with the presence of male microchimerism (P = 0.02).Limitations, Reasons For Caution: After stratifying for variables of interest, some participant groups resulted in a low numbers of subjects. We investigated microchimerism in peripheral blood due to the proposed mechanism of cell acquisition via transplacental blood exchange; however, this does not represent global chimerism in the individual and microchimerism may localize to numerous other tissues.Wider Implications Of the Findings: Immune regulation during pregnancy is known to mitigate allosensitization and support tolerance to non-inherited antigens found on donor cells. While unable to identify a specific source that promotes microchimerism prevalence within pedigrees, this study points to the underlying complexities of natural microchimerism in the general population. These findings support previous studies which have identified the presence of male microchimerism among women with no history of pregnancy, suggesting alternative sources of microchimerism. The association of detectable male microchimerism with age is suggestive of additional factors including time, molecular characteristics and environment playing a critical role in the prevalence of persistent microchimerism. The present study necessitates investigation into the molecular underpinnings of natural chimerism to provide insight into women's health, transplant medicine and immunology.Study Funding/competing Interest(s): This work is funded by Royal Netherlands Academy of Science Professor Award (PAH/6635 to D.I.B.); The Netherlands Organisation for Health Research and Development (ZonMw)-Genotype/phenotype database for behavior genetic and genetic epidemiological studies (ZonMw 911-09-032); Biobanking and Biomolecular Research Infrastructure (BBMRI-NL, 184.021.007; 184.033.111); The Netherlands Organisation for Scientific Research (NWO)-Netherlands Twin Registry Repository (NWO-Groot 480-15-001/674); the National Institutes of Health-The Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06), Grand Opportunity grants Integration of genomics and transcriptomics in normal twins and major depression (NIMH 1RC2 MH089951-01), and Developmental trajectories of psychopathology (NIMH 1RC2 MH089995); and European Research Council-Genetics of Mental Illness (ERC 230374). C.B.L. declares a competing interest as editor-in-chief of Human Reproduction and his department receives unrestricted research grants from Ferring, Merck and Guerbet. All remaining authors have no conflict-of-interest to declare in regards to this work.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background/aims: Research linking orbitofrontal cortex (OFC) structure and substance use disorders (SUDs) is largely correlational and often implies a causal effect of addiction/substance exposure on the brain, but familial risk factors (e.g. genetic liability) may confound these associations. We tested whether associations between alcohol, cannabis and tobacco use disorders and OFC thickness reflected the potential causal effects of familial risk or SUDs‐related consequences (e.g. substance exposure). Design A co‐twin control/discordant twin design separated familial risk confounding from SUD‐related consequences. Setting/participants: A population‐based sample of 436 24‐year‐old twins (62% monozygotic) from the Minnesota Twin Family Study, USA. Measurements Alcohol, cannabis and tobacco use disorders were assessed using the Composite International Diagnostic Interview—Substance Abuse Module. Cortical thickness of the medial and lateral OFC (mOFC and lOFC, respectively) was assessed using magnetic resonance imaging (MRI). Findings Lower mOFC (P‐values ≤ 0.006) but not lOFC (P‐values ≥ 0.190) thickness was observed in diagnosed individuals (n = 185) relative to non‐SUD controls (n = 251). Co‐twin control analyses offered evidence that mOFC associations were consistent with familial risk across SUDs (between‐pair effect: P‐values ≤ 0.047) and the independent consequences of having an alcohol or cannabis use disorder (within‐pair effect: P‐values ≤ 0.024). That is, within alcohol/cannabis discordant twin pairs, affected twins had significantly lower mOFC thickness compared with their unaffected co‐twins. Conclusions: A confounder‐adjusted analysis of the Minnesota Twin Family Study appeared to indicate that, beyond a substance use disorders general familial risk effect, the experience of an alcohol or cannabis use disorder in emerging adulthood reduces the thickness of the medial orbitofrontal cortex, a region associated with value‐guided decision‐making. [ABSTRACT FROM AUTHOR]

Aim: Twin studies allow for the investigation of genetic and environmental influences on human brain development. The generalizability of their findings depends on the developmental similarity between twins and singletons. This study aimed to evaluate the structural and functional differences in a cohort of preterm-born twins and singletons at term-equivalent age. Materials and Methods: Eighteen twins and forty-seven singletons were included and scanned at the term-equivalent age. Brain volumes from 3D T1-weighted images, quantitative metrics and structural connectivity from diffusion tensor imaging, and low-frequency brain activity and functional connectivity from resting-state functional MRI (rs-fMRI) were obtained from these neonates. Results: We found no significant volumetric differences after multiple comparison correction. The diffusivity values in the cingulum cingular part, cingulate gyrus, lateral fronto-orbital gyrus, gyrus rectus, as well as medial fronto-orbital gyrus were significantly higher in the twin group than in the singleton group. Structural connectivity analysis showed higher transitivity in the twin group compared to the singletons, indicating increased local connectivity. For rs-fMRI, the twin group showed greater fractional amplitude of low-frequency fluctuation (fALFF) values in the salience network and several fronto-temporal regions compared with the singleton group. It is worth noting that we found differences both in structural and functional measurements (MD and fALFF) in the prefrontal and cingulate cortex. Conclusion: The structural and functional differences collectively indicated that preterm-born twins may have delayed brain development compared with gestational age-matched singletons at term-equivalent age, which may be related to perinatal-neonatal problems. [ABSTRACT FROM AUTHOR]

The objective of this study was to comprehensively assess fetal hemodynamic adaptions to occlusive procedures. Twin pregnancies complicated with acardiac twin and hydrops fetalis of the pump twin were recruited. The occlusive procedures - either alcoholization, radiofrequency ablation, coil embolization or occlusive glue - were performed under ultrasound guidance. Various hemodynamic parameters were assessed before, shortly after, then every 6 h for 48 h and 2-4 weeks after the procedures. Seven pregnancies were recruited. The median (range) gestational age of intervention was 21 (17-26) weeks of gestation. Before the procedures, all cases showed normal cardiac function. Just after the procedures, all cases showed an increase in Tei index and isovolumic relaxation time but returned to preocclusion levels within 6-48 h, except for two cases that were persistently high. Increased preload and poor shortening fraction were observed in two cases, leading to heart failure, with one recovery and one death in utero. Five out of the seven cases got through the critical period with a gradual return to normal hemodynamics, ending with the disappearance of hydrops and successful outcomes. It was concluded that the occlusive procedure could aggravate the overworked heart, leading to heart failure. Preocclusion preload index and Tei index may predict risk of heart failure due to the occlusion. This small series strongly suggests that the occlusion should be performed before the deterioration of cardiac function. [ABSTRACT FROM AUTHOR]

Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5-36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years. [ABSTRACT FROM AUTHOR]

The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1-2 years), preschool (3-5 years), primary or elementary school (6-11 years), and adolescence (10-18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0-18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC. [ABSTRACT FROM AUTHOR]

Study Question: Are the decreasing multiple birth rates after ART associated with a simultaneous drop in the incidence of cerebral palsy (CP) in ART children over time?Summary Answer: The relative odds of CP in ART children have declined in the Nordic countries over the past two decades concurrently with declining multiple birth rates.What Is Known Already: In the Nordic countries, the rate of twin pregnancies after ART has decreased from 30% in the early 1990s to 4-13% in 2014, following the implementation of elective single embryo transfer (SET). Consequently, preterm birth rates have declined substantially in ART pregnancies. However, whether the risk of CP, a known consequence of preterm birth, has decreased correspondingly is still unknown.Study Design, Size, Duration: Retrospective register-based cohort study based on data on all singletons, twins, and higher-order multiples born in Denmark (birth year 1994-2010), Finland (1990-2010), and Sweden (1990-2014), corresponding to 111 844 ART children and 4 679 351 spontaneously conceived children.Participants/material, Setting, Methods: Data were obtained from a large Nordic cohort of children born after ART and spontaneous conception initiated by the Committee of Nordic ART and Safety-CoNARTaS. The CoNARTaS cohort was established by cross-linking national register data using the unique personal identification number, allocated to every citizen in the Nordic countries. Data from the National Medical Birth Registers, where information on maternal, obstetric, and perinatal outcomes is recorded, were cross-linked to data from the National ART- and Patients Registers to obtain information on fertility treatments and CP diagnoses. Relative risks of CP for ART compared to spontaneous conception were estimated as odds ratios from multivariate logistic regression analyses across all birth years, as well as for the following birth year categories: 1990-1993, 1994-1998, 1999-2002, 2003-2006, 2007-2010, and 2011-2014. Analyses were made for all children and for singletons and twins, separately.Main Results and the Role Of Chance: The main outcome measure was the relative odds of CP in different time periods for ART versus spontaneously conceived children. CP was diagnosed in 661 ART children and 16 478 spontaneously conceived children born between 1990 and 2014. In 1990-1993, the relative odds of CP were substantially higher in all ART children (adjusted odds ratio (aOR) 2.76 (95% CI 2.03-3.67)) compared with all spontaneously conceived children, while in 2011-2014, it was only moderately higher (aOR 1.39 (95% CI 1.01-1.87)). In singletons, the higher relative odds of CP in ART children diminished over time from 1990 to 1993 (aOR 2.02 (95% CI 1.22-3.14)) to 2003-2006 (aOR 1.18 (95% CI 0.91-1. 49)) and was not significantly increased for birth cohorts 2007-2010 and 2011-2014. For ART twins versus spontaneously conceived twins, the relative odds of CP was not statistically significantly increased throughout the study period.Limitations, Reasons For Caution: The main limitation of the study was a shorter follow-up time and younger age at first CP diagnosis for ART children compared with spontaneously conceived children. However, analyses ensuring a minimum of bias from differences in age at CP diagnosis and follow-up time confirmed the results, hence, we do not consider this to cause substantial bias.Wider Implications Of the Findings: A SET policy in ART treatments has the potential to reduce the increased risk of cerebral palsy in the ART population due to lower rates of multiple deliveries. At a time with high survival rates of frozen/thawed embryos, this study provides a strong argument against the continued use of multiple embryo transfer in most ART settings. Larger cohort studies including also the number of gestational sacs in early pregnancy will be preferable to show an effect of vanishing twins on the risk of CP in the ART population.Study Funding/competing Interest(s): The study was financed by grants from NordForsk (grant number 71450), Elsass Foundation (19-3-0444), the ALF-agreement (ALFGBG 70940), and The Research Fund of Rigshospitalet, Copenhagen University Hospital. There are no conflicts of interest to declare.Trial Registration Number: ISRCTN11780826. [ABSTRACT FROM AUTHOR]

Background. Age-related hearing impairment (ARHI) is considered an unpreventable disorder. We aimed to detect specific genetic variants that are potentially related to ARHI via genome-wide association study (GWAS). Methods. A sample of 131 dizygotic twins was genotyped for single-nucleotide polymorphism- (SNP-) based GWAS. Gene-based test was performed using VEGAS2. Pathway enrichment analysis was conducted by PASCAL. Results. The twins are with a median age of 49 years, of which 128 were females and 134 were males. rs6633657 was the only SNP that reached the genome-wide significance level for better ear hearing level (BEHL) at 2.0 kHz (P = 1.19 × 10 − 8 ). Totally, 9, 10, 42, 7, 17, and 5 SNPs were suggestive evidence level for (P < 1 × 10 − 5 ) BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and pure tone average (PTA), respectively. Several promising genetic regions in chromosomes (near the C20orf196, AQPEP, UBQLN3, OR51B5, OR51I2, OR52D1, GLTP, GIT2, and PARK2) nominally associated with ARHI were identified. Gene-based analysis revealed 165, 173, 77, 178, 170, and 145 genes nominally associated with BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and PTA, respectively (P < 0.05). For BEHLs at 0.5, 1.0, and 2.0 kHz, the main enriched pathways were phosphatidylinositol signaling system, regulation of ornithine decarboxylase, eukaryotic translation initiation factor (EIF) pathway, amine compound solute carrier (SLC) transporters, synthesis of phosphoinositides (PIPS) at the plasma membrane, and phosphatidylinositols (PI) metabolism. Conclusions. The genetic variations reported herein are significantly involved in functional genes and regulatory domains that mediate ARHI pathogenesis. These findings provide clues for the further unraveling of the molecular physiology of hearing functions and identifying novel diagnostic biomarkers and therapeutic targets of ARHI. [ABSTRACT FROM AUTHOR]

Objective: Parent anxiety is associated with offspring internalizing problems (emotional problems related to anxiety and depression). This may reflect causal processes, whereby exposure to parent anxiety directly influences offspring internalizing (and/or vice versa). However, parent-offspring associations could also be attributable to their genetic relatedness. A systematic review and meta-analysis were conducted to investigate whether exposure to parent anxiety is associated with offspring internalizing after controlling for genetic relatedness.Method: A literature search across 5 databases identified 429 unique records. Publications were retained if they used a quasi-experimental design in a general population sample to control for participant relatedness in associations between parent anxiety and offspring internalizing outcomes. Publications were excluded if they involved an experimental exposure or intervention. Studies of prenatal and postnatal anxiety exposure were meta-analyzed separately. Pearson's correlation coefficient estimates (r) were pooled using multilevel random-effects models.Results: Eight publications were retained. Data were drawn from 4 population cohorts, each unique to a quasi-experimental design: adoption, sibling-comparison, children-of-twins or in vitro fertilization. Cohorts were located in northern Europe or America. Families were predominantly of European ancestry. Three publications (Nfamilies >11,700; offspring age range, 0.5-10 years) showed no association between prenatal anxiety exposure and offspring internalizing outcomes after accounting for participant relatedness (r = .04; 95% CI: -.07, .14). Six publications (Nfamilies >12,700; offspring age range, 0.75-22 years) showed a small but significant association between concurrent symptoms in parents and offspring after accounting for participant relatedness (r = .13; 95% CI: .04, .21).Conclusion: Initial literature, derived from homogeneous populations, suggests that prenatal anxiety exposure does not cause offspring internalizing outcomes. However, postnatal anxiety exposure may be causally associated with concurrent offspring internalizing via nongenetic pathways. Longitudinal stability, child-to-parent effects, and the role of moderators and methodological biases require attention. [ABSTRACT FROM AUTHOR]

Objective  To compare admission and emergency visits of late preterm (34 0/7 –36 6/7 weeks) versus term infants (37 0/7 –41 6/7 weeks) in the first 5 years. Study Design  This population-based cohort study included all singletons and twins born alive at 34 0/7 to 41 6/7 weeks' gestation registered in a health administrative database in Ontario, Canada, between April 1, 2002 and December 31, 2012. Admissions and emergency visits from initial postnatal discharge to 5 years were compared between late preterm and term infants adjusting for maternal and infant characteristics. Results  A total of 1,316,931 infants (75,364 late preterm infants) were included. Late preterm infants had more frequent admissions than term infants in the first 5 years in both singletons (adjusted incidence rate ratio [95% confidence interval] = 1.46 [1.42–1.49]) and twins (1.21 [1.11–1.31]). The difference in admissions between late preterm and term infants were smaller in twins than singletons and decreased with children's ages. Twins had less frequent admissions than singletons for late preterm infants, but not for term infants. The emergency visits were more frequent in late preterm than term infants in all the periods. Conclusion  Admissions and emergency visits were more frequent in late preterm than term infants through the first 5 years. Admissions were less frequent in late preterm twins than singletons. [ABSTRACT FROM AUTHOR]

Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation. [ABSTRACT FROM AUTHOR]

Accurate zygosity determination is a fundamental step in twin research. Although DNA-based testing is the gold standard for determining zygosity, collecting biological samples is not feasible in all research settings or all families. Previous work has demonstrated the feasibility of zygosity estimation based on questionnaire (physical similarity) data in older twins, but the extent to which this is also a reliable approach in infancy is less well established. Here, we report the accuracy of different questionnaire-based zygosity determination approaches (traditional and machine learning) in 5.5 month-old twins. The participant cohort comprised 284 infant twin pairs (128 dizygotic and 156 monozygotic) who participated in the Babytwins Study Sweden (BATSS). Manual scoring based on an established technique validated in older twins accurately predicted 90.49% of the zygosities with a sensitivity of 91.65% and specificity of 89.06%. The machine learning approach improved the prediction accuracy to 93.10%, with a sensitivity of 91.30% and specificity of 94.29%. Additionally, we quantified the systematic impact of zygosity misclassification on estimates of genetic and environmental influences using simulation-based sensitivity analysis on a separate data set to show the implication of our machine learning accuracy gain. In conclusion, our study demonstrates the feasibility of determining zygosity in very young infant twins using a questionnaire with four items and builds a scalable machine learning model with better metrics, thus a viable alternative to DNA tests in large-scale infant twin studies. [ABSTRACT FROM AUTHOR]

Selective termination is the term used for the elimination of an abnormal fetus. In contrast, multifetal pregnancy reduction refers to the termination of one or more members of a twin or higher-order multiple birth set, respectively, to reduce the high risks associated with these pregnancies. The procedure can also be used when a serious physical condition is detected prenatally in a member of a multiple birth set. In a minority of cases, selective termination has reduced two healthy fetuses to one when parents wanted just one additional child in the family. In the present article, the perspectives of a surviving twin whose family wished to terminate both healthy fetuses are examined. Next, past and present twin studies of primordial dwarfism, public service motivation, an analytical model, the global twinning rate and germline differences are summarized. The article concludes with a synopsis of twin-related news that covers twins and Dyngus Day, triplets born in an Austrian displaced persons' camp, the film Superior - about estranged identical twin sisters, a couple adopting their own twins after surrogacy and a new case of twins and primordial dwarfism, a condition introduced in the research reviews. [ABSTRACT FROM AUTHOR]

Purpose: Numbers of planned cesarean deliveries are increasing in twin pregnancies, despite the lack of evidence for this approach, and the second twin is thought to be at risk for a poorer outcome. The aim of this study was to examine whether twins have a poorer outcome if an attempted vaginal delivery is changed to a cesarean section or combined delivery.Methods: This retrospective data analysis included all women with dichorionic twin pregnancies attempting vaginal delivery over a 10-year period. Outcome parameters for the first and second twins relative to their mode of birth were compared. A correlation model between the interdelivery time interval and Apgar scores was calculated. Subgroup analyses assessing the birth mode of the first and second twins were conducted.Results: A total of 248 women were enrolled in the study. The second twins had significantly lower values for outcome parameters, such as umbilical artery cord pH and Apgar scores in comparison with the first twins (P < 0.01). The subgroup analysis of birth modes in first and second twins showed a significantly poorer outcome in the cesarean section and combined delivery group (P < 0.05). The interdelivery time interval was significantly longer in the second twin cesarean section group (P < 0.01). There was no significant correlation between the interdelivery time intervals and Apgar scores (P > 0.05).Conclusion: Although outcome parameters were significantly lower in second twins and twins born via secondary cesarean section, the clinical relevance of this appears to be negligible. [ABSTRACT FROM AUTHOR]

Study Question: How many twins are born in human populations and how has this changed over recent decades?Summary Answer: Since the 1980s, the global twinning rate has increased by a third, from 9.1 to 12.0 twin deliveries per 1000 deliveries, to about 1.6 million twin pairs each year.What Is Known Already: It was already known that in the 1980s natural twinning rates were low in (East) Asia and South America, at an intermediate level in Europe and North America, and high in many African countries. It was also known that in recent decades, twinning rates have been increasing in the wealthier parts of our world as a result of the rise in medically assisted reproduction (MAR) and delayed childbearing.Study Design, Size, Duration: We have brought together all information on national twinning rates available from statistical offices, demographic research institutes, individual survey data and the medical literature for the 1980-1985 and the 2010-2015 periods.Participants/materials, Setting, Methods: For 165 countries, covering over 99% of the global population, we were able to collect or estimate twinning rates for the 2010-2015 period. For 112 countries, we were also able to obtain twinning rates for 1980-1985.Main Results and the Role Of Chance: Substantial increases in twinning rates were observed in many countries in Europe, North America and Asia. For 74 out of 112 countries the increase was more than 10%. Africa is still the continent with highest twinning rates, but Europe, North America and Oceania are catching up rapidly. Asia and Africa are currently home to 80% of all twin deliveries in the world.Limitations, Reasons For Caution: For some countries, data were derived from reports and papers based on hospital registrations which are less representative for the country as a whole than data based on public administrations and national surveys.Wider Implications Of the Findings: The absolute and relative number of twins for the world as a whole is peaking at an unprecedented level. An important reason for this is the tremendous increase in medically assisted reproduction in recent decades. This is highly relevant, as twin deliveries are associated with higher infant and child mortality rates and increased complications for mother and child during pregnancy and during and after delivery.Study Funding/competing Interest(s): The contribution of CM was partially supported by the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (grant No 681546, FAMSIZEMATTERS), Nuffield College, and the Leverhulme Trust. The contribution of GP was partially supported by the French Agence Nationale de la Recherche (grant No ANR-18-CE36-0007-07). The authors declare no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Objective Previous studies have indicated that Behçet's disease (BD) has a genetic component, however population-level familial risk estimates are unavailable. We quantified the familial incidence and risk of BD in first-degree relatives (FDR) according to age, sex and type of family relationship. Methods Using the Korean National Health Insurance database, which has full population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 individuals comprising 12 million families, which were followed for a familial occurrence of BD from 2002 to 2017. Age- and sex-adjusted incidence risk ratios for BD were calculated in individuals with affected FDR compared with those without affected FDR. Results Among the total study population, 53 687 individuals had affected FDR, of whom 284 familial cases developed BD with an incidence of 3.57/104 person-years. The familial risk (incidence) for BD was increased to 13.1-fold (2.71/104 person-years) in individuals with an affected father, 13.9-fold (3.11/104 person-years) with affected mother, 15.2-fold (4.9/104 person-years) with an affected sibling and the highest risk was 165-fold (46/104 person-years) with an affected twin. Familial risks showed age dependence, being higher in younger age groups. The sex-specific familial risk was similar in males and females. Conclusion This study provides quantified estimates of familial incidence and risk in FDR of BD patients in an entire population. Familial risks were higher within generation (sibling–sibling) vs between generations (parent–offspring). This implicates complex interactions between genetic factors and shared childhood environmental exposures in the pathogenesis of BD. [ABSTRACT FROM AUTHOR]

Aims: To identify drug use typologies based on substances used and persistence of use over two time points, use a genetically informed design to explore twin concordance of and genetic influence on the use typologies and compare patterns of declined/discontinued ("desistant") and persistent drug use on drug use correlates. Design Latent class analysis was applied to data from a cross‐sectional self‐report survey on current and past drug use. Use characteristics, use disorder, and psychiatric problems were compared across classes. Setting: Computer‐assisted telephone interview in respondents' homes. Participants: A total of 3785 individual twins and siblings (1365 men, 2420 women; Mage = 32) from the Australian Twin Registry Cohort III. Measurements A comprehensive interview assessed prior to past year and past year use of cannabis, stimulants, cocaine/crack, hallucinogens, opioids, sedatives, inhalants, dissociatives, and solvents; age of first use; opportunity to use; peer drug use; attention deficit/hyperactivity, conduct, antisocial personality, depressive, and substance use disorders; and suicidality. Findings A five‐class solution emerged: no/low use (50%), desistant cannabis use (23%), desistant party drug use (18%), persistent prescription drug misuse (4%), and persistent polydrug use (5%). Twin concordances were higher among monozygotic (k = 0.30–0.35) than dizygotic pairs (same‐sex k = 0.19–0.20; opposite sex k = 0.07), and biometric modeling suggested that the persistent polydrug use class, in particular, was highly heritable (a2 = 0.94). Conduct disorder (OR = 2.40), antisocial personality disorder (OR = 3.27), and suicidal ideation (OR = 1.98) increased persistent polydrug use risk; depression (OR = 2.38) and lifetime suicide attempt (OR = 2.31) increased persistent prescription misuse risk. Relative to persistent prescription drug misuse, persistent polydrug use was associated with higher rates of cannabis and stimulant use disorder (OR = 6.14–28.01), younger first substance use (OR = 0.82–0.83), more drug use opportunity (OR = 10.66–66.06), and more drug‐using peers (OR = 4.66–9.20). Conclusions: Unique patterns of declined/discontinued ("desistant") and persistent drug use are differentially heritable and differentially associated with risk factors, psychiatric symptoms, and substance use disorder outcomes. [ABSTRACT FROM AUTHOR]

Background: Selective fetal growth restriction (sFGR) is a condition of twin pregnancy in which the development of one fetus is restricted, despite normal growth of the other fetus. A method of intrauterine therapy for sFGR does not currently exist. The only treatment for sFGR is to terminate the pregnancy before the FGR worsens. In twin pregnancies, maternal and intrauterine environments are common in both fetuses, thus a placental factor is considered the cause of FGR in fetuses. Tadalafil is a phosphodiesterase (PDE)-5 inhibitor that induces an increase in uterine blood flow by dilatation of blood vessels in cases of FGR with placental dysfunction, which improves FGR.Purpose: The aim of this study was to investigate the safety and maximum tolerated dose (MTD) of tadalafil administered for twin pregnancy (diamniotic-monochorionic twin or diamniotic-dichorionic twin).Methods: In this phase I, open-label, dose-escalation trial, sequential patient cohorts (3 + 3 dose-escalation design) for twin pregnancy received tadalafil (20 or 40 mg/d) as a single dose by oral administration from the day they were diagnosed with sFGR, defined as estimated fetal weight (EFW) < 3% tiles, that is, -1.8 SD the mean EFW for gestational age (GA) to unacceptable toxicity or the day of delivery. This study evaluated the safety of maternally administered tadalafil for sFGR, examining maternal, fetal, and neonatal adverse events. Maternal adverse events were graded on the basis of the Common Terminology Criteria for Adverse Events v4.0.Results: Six women with sFGR who were pregnant with twins were treated with tadalafil. There were no severe adverse events in either cohort, although the most common (≥3 patients) drug-related adverse events were headache and heart failure. The MTD of tadalafil among Japanese patients was 40 mg.Conclusions: Tadalafil has a manageable safety profile up to an MTD of 40 mg/d. [ABSTRACT FROM AUTHOR]

Background: Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women's Health Initiative (WHI) and the TwinsUK cohort.Design: The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction.Results: Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P = 2.7x10-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L).Conclusions: Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) and body mass index (BMI) are associated. However, it remains unclear whether this association reflects causal relationships in either direction or confounding. Here, we implemented genetically informed methods to examine bidirectional causality and potential confounding.Methods: Three genetically informed methods were employed: (i) cross-lagged twin-differences analyses to assess bidirectional effects of ADHD symptoms and BMI at ages 8, 12, 14 and 16 years in 2386 pairs of monozygotic twins from the Twins Early Development Study (TEDS); (ii) within- and between-family ADHD and BMI polygenic score (PS) analyses in 3320 pairs of dizygotic TEDS twins; and (iii) two-sample bidirectional Mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) on ADHD (N = 55,374) and BMI (N = 806,834).Results: Mixed results were obtained across the three methods. Twin-difference analyses provided little support for cross-lagged associations between ADHD symptoms and BMI over time. PS analyses were consistent with bidirectional relationships between ADHD and BMI, with plausible time-varying effects from childhood to adolescence. MR findings also suggested bidirectional causal effects between ADHD and BMI. Multivariable MR indicated the presence of substantial confounding in bidirectional relationships.Conclusions: The three methods converged to highlight multiple sources of confounding in the association between ADHD and BMI. PS and MR analyses suggested plausible causal relationships in both directions. Possible explanations for mixed causal findings across methods are discussed. [ABSTRACT FROM AUTHOR]

Background: Development of the gut-brain axis in early life may be disturbed by antibiotic use. It has been hypothesized that this disturbance may contribute to development of neurodevelopmental disorders, including autism spectrum disorder and attention-deficit hyperactivity disorder. We aimed to assess the association between antibiotic use in early life and the risk of developing attention-deficit hyperactivity disorder or autism spectrum disorder, while controlling for shared genetic and environmental factors in a discordant twin design.Methods: We conducted a cohort study in twins (7-12 years; 25 781 twins) from the Netherlands Twin Register (NTR) and a replication study in the Childhood and Adolescent Twin Study in Sweden (CATSS; 7946 9-year-old twins). Antibiotic use was recorded before age 2 years. Attention-deficit hyperactivity disorder and autism spectrum disorder were parent-reported in the Netherlands Twin Register and register-based in the Childhood and Adolescent Twin Study in Sweden.Results: Early-life antibiotic use was associated with increased risk of attention-deficit hyperactivity disorder development [pooled odds ratio (OR) 1.10, 95% confidence interval (CI) 1.02-1.17] and autism spectrum disorder (pooled OR 1.15, 95% CI 1.06-1.25) in a case-control design. When restricting to monozygotic twin pairs discordant for the outcome, associations disappeared for both disorders in both cohorts (attention-deficit hyperactivity disorder OR 0.90, 95% CI 0.48-1.69 and OR 0.80, 95% CI 0.37-1.76, and autism spectrum disorder OR 0.66, 95% CI 0.38-1.16 and OR 0.29, 95% CI 0.02-4.50, respectively).Conclusions: Our findings suggest that the association between early-life antibiotic use and risk of attention-deficit hyperactivity and autism spectrum disorder may be confounded by shared familial environment and genetics. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the length of the second stage of labor in twin deliveries and to compare the length of the second stage in twin and singleton gestations.Methods: This is a retrospective cohort study from three large hospitals in Israel. Clinical data were collected from the electronic medical record. The primary outcome was the length of the second stage (the time from documented 10-cm dilation until spontaneous vaginal delivery of the first twin). Multivariable linear regression was used to examine the association of clinical factors with the length of the second stage. The length of the second stage in twin and singleton pregnancies was compared.Results: From 2011 to June, 2020, there were 2,009 twin deliveries and 135,217 singleton deliveries. Of the twin deliveries, 655 (32.6%) of the patients were nulliparous (95th percentile length of the second stage 3 hours and 51 minutes), 1,235 (61.5%) were parous (95th percentile 1 hour 56 minutes), and 119 (5.9%) were grand multiparous (five or more prior deliveries) (95th percentile 1 hour 24 minutes). In women delivering twins, epidural use was associated with a statistically significant increase in the length of the second stage of 40 minutes in nulliparous patients and 15 minutes in parous patients. In all groups, the length of the second stage was longer in patients delivering twins compared with singletons. Second-stage length longer than the 95th percentile in twins was associated with admission to the neonatal intensive care unit and need for phototherapy.Conclusion: Second-stage labor is longer in twins than singletons and is associated with obstetric history. Normal ranges for the second stage may be useful in guiding clinical practice. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the genetic and environmental etiology of the association between childhood negative emotionality (NE) and hyperactivity/inattention problems (HIP) using South Korean elementary school twins (mean age = 10.19 years, SD = 1.79 years). Telephone interviews were given to mothers of 919 twins (229 monozygotic males: 112 pairs and 5 individuals; 148 dizygotic males: 73 pairs and 2 individuals; 180 monozygotic females: 87 pairs and 6 individuals; 103 dizygotic females: 50 pairs and 3 individuals; 259 opposite-sex dizygotic twins: 127 pairs and 5 individuals) to assess their children's NE and HIP. Consistent with prior studies, the phenotypic correlation between NE and the HIP was moderate (r = .29; 95% CI = .24, .34). Model-fitting analysis revealed that additive genetic and nonshared environmental influences on NE were .45 (95% CI [.34, .54]) and .55 (95% CI [.46, .66]), respectively, and that additive and nonadditive genetic, and nonshared environmental influences on HIP were .08 (95% CI [.03, .26]), .41 (95% CI [.21, .51]) and .51 (95% CI = .42, .61), respectively. In addition, the additive genetic correlation between NE and HIP was 1.0 (95% CI [.52, 1.00]), indicating that additive genetic factors are entirely shared between the two phenotypes. Nonadditive genetic influences were unique to HIP and not responsible for the NE-HIP association. Nonshared environmental correlation was significant but modest (re = .18, 95% CI [.06, .30]). [ABSTRACT FROM AUTHOR]

The objective of this study was to analyze differences in birth weight and overweight/obesity in a Shanghai twin cohort. We also wanted to study their association and explore possible risk factors for the discordance of overweight/obesity within twins. This was an internal case-control study designed for twins. The 2012 Shanghai Twin Registration System baseline survey data of a total of 3417 twin pairs were statistically analyzed using SPSS22 software. Results show that the body mass index (BMI) of the Shanghai twin population increased with age. Twins with a high birth weight had a higher BMI and a higher rate of overweight and obesity; 0- to 6-year-old twins, male twins and dizygotic (DZ) twins had higher rates of overweight/obesity than other groups. The greater the discordant birth weight rate of twins, the more obvious the difference in BMI (p < .05). There was a significant difference in overweight/obesity between twins with a relative difference of birth weight ≥15% in DZ twins (p < .05). DZ twins, male twins and 0- to 6-year-old twins were more likely to be discordant in overweight/obese than others. The discordant birth weight within twins was not a risk factor for discordant overweight/obesity. However, attention should be paid to childhood obesity, and appropriate interventions should be made at the appropriate time. Genetics may play an important role in the occurrence and development of overweight/obesity. In conclusion, discordant growth and development in the uterus early in life may not lead to discordant weight development in the future. [ABSTRACT FROM AUTHOR]