Twin Population Research Articles

Cognitive Divergence in the Womb: An Analysis of IQ and Developmental Indicators in Twin Fetuses

The study of cognitive divergence in twin fetuses offers a unique window into the interplay of genetic, environmental, and developmental factors influencing early brain development. This research investigates the prenatal origins of cognitive differences, focusing on indicators such as brain volume asymmetry, neural connectivity, and behavioral patterns. By examining these factors through advanced imaging techniques like fetal MRI and ultrasound, the study explores how cognitive divergence manifests in twin fetuses, potentially affecting postnatal IQ and developmental trajectories. Key areas of focus include the role of genetic variance, in-utero environmental disparities, and the impact of placental sharing on neural development. Additionally, the research addresses methodological challenges in assessing cognitive markers during the prenatal period and explores implications for early intervention strategies. By shedding light on the earliest stages of cognitive differentiation, this study aims to advance our understanding of developmental neuroscience and inform approaches to optimize cognitive outcomes in twin populations.

Anorexia nervosa polygenic risk, beyond diagnoses: relationship with adolescent disordered eating and behaviors in an Australian female twin population.

It is well established that there is a substantial genetic component to eating disorders (EDs). Polygenic risk scores (PRSs) can be used to quantify cumulative genetic risk for a trait at an individual level. Recent studies suggest PRSs for anorexia nervosa (AN) may also predict risk for other disordered eating behaviors, but no study has examined if PRS for AN can predict disordered eating as a global continuous measure. This study aimed to investigate whether PRS for AN predicted overall levels of disordered eating, or specific lifetime disordered eating behaviors, in an Australian adolescent female population. PRSs were calculated based on summary statistics from the largest Psychiatric Genomics Consortium AN genome-wide association study to date. Analyses were performed using genome-wide complex trait analysis to test the associations between AN PRS and disordered eating global scores, avoidance of eating, objective bulimic episodes, self-induced vomiting, and driven exercise in a sample of Australian adolescent female twins recruited from the Australian Twin Registry (N = 383). After applying the false-discovery rate correction, the AN PRS was significantly associated with all disordered eating outcomes. Findings suggest shared genetic etiology across disordered eating presentations and provide insight into the utility of AN PRS for predicting disordered eating behaviors in the general population. In the future, PRSs for EDs may have clinical utility in early disordered eating risk identification, prevention, and intervention.

Necrotizing enterocolitis in monochorionic twins: Insights from an identical twin model

Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality in preterm neonates, yet its pathophysiology remains unclear. The aim of this study is to evaluate risk factors for NEC using an identical twin model. In this case-control study, all monochorionic twin pairs born in our center in 2002–2020 were retrospectively reviewed for NEC. Potential risk factors for NEC were studied. For within-pair comparison, outcomes were compared between affected and unaffected twins. Within-pair analyses showed that the twin with NEC had a lower birth weight compared to its unaffected co-twin (1100 (913–1364) vs. 1339 (1093–1755) grams). Median gestational age at birth and birth weight were lower in twin pairs in the NEC-group compared to the no-NEC group, 29.1 weeks (27.8–30.8) versus 33.6 (30.7–36.0) and 1221 g (1010–1488) versus 1865 (1356–2355) respectively. Twin pregnancies in the NEC-group were more often complicated by twin-to-twin transfusion syndrome compared to the no-NEC-group (70 % (14/20) vs. 49 % (472/962)), particularly when treated with amnioreduction. This unique population of identical twins confirms that preterm neonates with a relatively lower birth weight are more prone to develop NEC compared to their co-twin, regardless of other genetic, maternal and obstetrical factors.

Energy and macronutrient intake heritability: A systematic review and meta-analysis of twin and family-based studies

Background/Aims: The current meta-analysis aimed to examine the heritability and familial resemblance of dietary intakes, including energy and macronutrients in both twin and family-based studies. MethodsThe online literature databases, including PubMed, Scopus, and Web of Science were searched comprehensively until 2023 to identify the relevant studies. The heritability index in family studies was h2 and the heritability indices for twin studies were h2, A2, and E2. Three weighted methods were used to calculate the mean and SE of heritability dietary intakes. ResultsEighteen papers including 8 studies on familial population and 12 for twin population studies were included in the present meta-analysis. The heritability of dietary intakes in twin studies(range of pooled estimated h2, A2, and E2 was 30-55%, 14-42%, and 52-79%, respectively) was higher than family studies (range of pooled estimated h2= 16-39%). In family studies, the highest and lowest heritability for various nutrients was observed for the fat (%Kcal)(h2 range:36-38%) and carbohydrate in g(h2 range:16-18%), respectively. In twin studies, based on mean h2, the highest and lowest heritability for various nutrients was reported for the fat (%Kcal)(h2 range:49-55%) and protein intake in g(h2 range:30-35%), respectively. Also, based on the mean of A2, the highest and lowest heritability was observed for carbohydrates(% Kcal) (A2 range:42-42%), and protein(% Kcal)(A2 range:14-16%), respectively. Furthermore, in twin studies, the highest and lowest mean of E2 was shown for saturated fats(E2 range:74-79%) and energy intake (E2 range:52-57%), respectively. ConclusionOur analysis indicated that both environmental factors and genetics have remarkable contributions in determining the heritability of dietary intakes. Also, we observed higher heritability in twins compared to family studies.

Validation of Ultrasound Dating Protocols Using Data From Twins Conceived Through In Vitro Fertilization in Nova Scotia: A Retrospective Cohort Study

ObjectivesClinical practice guidelines recommend determining gestational age (GA) for twin pregnancies using the fetal crown rump length (CRL) of the larger fetus. This study investigated whether the CRL of the larger or smaller fetus at 11–14 weeks best predicted in vitro fertilization (IVF) assigned GA. MethodsA retrospective cohort study of twin pregnancies conceived by IVF ± intracytoplasmic sperm injection, 2004–2022, generated GA estimations for each co-twin CRL at the 11–14 week ultrasound, to determine which fetus (smaller or larger) more consistently predicted IVF-assigned GA. Monoamniotic twins and twins with known structural or vascular abnormalities were excluded. Paired t tests evaluated the ability of CRL to predict GA, and logistic regression evaluated the predictive ability of each of the co-twin groups with increasing size differences. Statistical significance was set at P < 0.05. ResultsViewpoint 6 identified 359 eligible twin pairs. CRL was closest with the smaller fetus (0.38 days); CRL for both the smaller (95% CI 0.16–0.61) and the larger (2.25 days, 95% CI 2.04–2.46) fetus showed deviation from IVF-assigned GA. As the absolute difference between the small and large fetus increased, the ultrasound-estimated GA of the smaller fetus was still consistently closer to IVF-assigned GA. ConclusionsIn this selected population of twins with known GA, the CRL of the smaller fetus more accurately predicted IVF-assigned GA even with increasing differences in fetal size. These findings provide important information for appropriately dating pregnancies to facilitate adherence to national guidelines to monitor for pregnancy complications, and plan frequency and type of fetal surveillance, as well as timing of delivery.

Genetic, vascular and amyloid components of cerebral blood flow in a preclinical population

Aging-related cognitive decline can be accelerated by a combination of genetic factors, cardiovascular and cerebrovascular dysfunction, and amyloid-β burden. Whereas cerebral blood flow (CBF) has been studied as a potential early biomarker of cognitive decline, its normal variability in healthy elderly is less known. In this study, we investigated the contribution of genetic, vascular, and amyloid-β components of CBF in a cognitively unimpaired (CU) population of monozygotic older twins. We included 134 participants who underwent arterial spin labeling (ASL) MRI and [18F]flutemetamol amyloid-PET imaging at baseline and after a four-year follow-up. Generalized estimating equations were used to investigate the associations of amyloid burden and white matter hyperintensities with CBF. We showed that, in CU individuals, CBF: 1) has a genetic component, as within-pair similarities in CBF values were moderate and significant (ICC > 0.40); 2) is negatively associated with cerebrovascular damage; and 3) is positively associated with the interaction between cardiovascular risk scores and early amyloid-β burden, which may reflect a vascular compensatory response of CBF to early amyloid-β accumulation. These findings encourage future studies to account for multiple interactions with CBF in disease trajectory analyses.

Environmental effects on brain functional networks in a juvenile twin population

The brain’s intrinsic organization into large-scale functional networks, the resting state networks (RSN), shows complex inter-individual variability, consolidated during development. Nevertheless, the role of gene and environment on developmental brain functional connectivity (FC) remains largely unknown. Twin design represents an optimal platform to shed light on these effects acting on RSN characteristics. In this study, we applied statistical twin methods to resting-state functional magnetic resonance imaging (rs-fMRI) scans from 50 young twin pairs (aged 10–30 years) to preliminarily explore developmental determinants of brain FC. Multi-scale FC features were extracted and tested for applicability of classical ACE and ADE twin designs. Epistatic genetic effects were also assessed. In our sample, genetic and environmental effects on the brain functional connections largely varied between brain regions and FC features, showing good consistency at multiple spatial scales. Although we found selective contributions of common environment on temporo-occipital connections and of genetics on frontotemporal connections, the unique environment showed a predominant effect on FC link- and node-level features. Despite the lack of accurate genetic modeling, our preliminary results showed complex relationships between genes, environment, and functional brain connections during development. A predominant role of the unique environment on multi-scale RSN characteristics was suggested, which needs replications on independent samples. Future investigations should especially focus on nonadditive genetic effects, which remain largely unexplored.

Reassessing the evidence of a survival advantage in Type 2 diabetes treated with metformin compared with controls without diabetes: a retrospective cohort study.

Previous research has suggested that individuals with Type 2 diabetes and initiated on metformin monotherapy present with a survival advantage compared with the general population without diabetes. This finding has generated considerable interest in the prophylactic use of metformin against age-related morbidity. Utilizing Danish National Health Registers, we assessed differences in survival associated with metformin monotherapy for Type 2 diabetes compared with no diagnosis of diabetes in both singleton and discordant twin populations between 1996 and 2012. Data were analysed in both nested case-control and matched cohort study designs, with incidence rate ratios (IRRs) and hazard ratios estimated using conditional logistic regression and Cox proportional hazards regression, respectively. In case-control pairs matched on birth year and sex or co-twin (sex, birth year and familial factors), incident Type 2 diabetes with treatment by metformin monotherapy initiation compared with no diagnosis of diabetes was associated with increased mortality in both singletons (IRR = 1.52, 95% CI: 1.37, 1.68) and discordant twin pairs (IRR = 1.90, 95%CI: 1.35, 2.67). After adjusting for co-morbidities and social indicators, these associations were attenuated to 1.32 (95% CI: 1.16, 1.50) and 1.64 (95% CI: 1.10, 2.46), respectively. Increased mortality was observed across all levels of cumulative use and invariant to a range of study designs and sensitivity analyses. Treatment initiation by metformin monotherapy in Type 2 diabetes was not associated with survival equal or superior to that of the general population without diabetes. Our contrasting findings compared with previous research are unlikely to be the result of differences in epidemiological or methodological parameters.

Heritability and environmental influences on the onset of aortic valve sclerosis: a twin population study

Abstract Background Aortic valve sclerosis (AVSc) is the earliest manifestation of a life-threatening cardiovascular disorder, namely aortic valve stenosis (AS). AVSc is also recognized as a red flag linked to worse cardiovascular outcomes in high-risk coronary artery disease patients. However, the genetic background of AVSc is still unknown. Purpose To examine whether the heritability and environmental contributions play a role in the onset of AVSc using a sample of Italian twins. Methods The present study is based on the classical twin design. Twins, aged 50 to 70 years, already enrolled in the Italian Twin Register, were contacted and invited to undergo a clinical, echocardiographic, and complete carotid artery ultrasound examination at the our Center, between July 2017 and December 2021. The presence of AVSc was recognized as non-uniform thickening with or without spotty calcified areas of the aortic valve leaflets without a significant transvalvular gradient (maximum aortic velocity &amp;lt;2.5 m/s). Twin zygosity was assessed through a questionnaire on physical similarity during childhood, known to be ∼95% accurate. Tetrachoric twin correlations by zygosity were estimated with Mx Software using liability threshold saturated models and incorporating age as a covariate. Liability-threshold structural equation modelling was performed to decompose the phenotypic variance into contributions due to additive genetic (A), common environmental (C), and unique environmental (E) effects. Results A total of 216 adult twins (66 monozygotic, MZ and 42 dizygotic pairs, DZ; mean age 59.9±6.2) were enrolled in the study. The estimated prevalence rate of AVSc in the total sample was 29.2%. As significant sex differences were detected (males 45.2% and females 22.7%, p&amp;lt;0.01), the additional twin analyses were performed as intra-sex analyses. Females showed a greater tetrachoric correlation in MZ twins (r=0.37) compared to DZ twins (r=0.23), suggesting the existence of a genetic influence. Genetic factors, under the best (AE) model, accounted for 38% of the variance in liability to AVSc with the remaining contribution due to unique environmental influences (E = 62%). The contribution of the common environment (C) to the goodness of fit was negligible. The male group was too small for statistical calculation. Conclusion To our knowledge, the present study is the first to document the involvement of genetic factors in the development of AVSc. Our data also warrant further studies to both validate the findings obtained and to better explore the heritability of AVSc. Furthermore, our results provide a first evidence that an echocardiographic screening in individuals with relatives affected by AVSc has a scientific rational basis. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Italian Ministry of Health

Long-term effects of selective fetal growth restriction (LEMON): a cohort study of neurodevelopmental outcome in growth discordant identical twins in the Netherlands

Singletons born after fetal growth restriction (FGR) are at increased risk of poor neurodevelopmental outcomes. Studies of singletons with FGR usually compare outcomes with those without FGR, a comparison that is inherently biased by obstetrical, parental, and genetic factors. We aim to compare neurodevelopmental outcomes between the smaller and larger twin in a population of discordant identical twins who shared a single placenta (monochorionic diamniotic), naturally eliminating these confounders. This study is part of the cohort study LEMON of monochorionic diamniotic twins with selective FGR. All monochorionic diamniotic twins with selective FGR who were born in Leiden University Medical Center (Leiden, Netherlands) between March 1, 2002, and Dec 31, 2017, were eligible for inclusion. Twin pregnancies that were complicated by twin-twin transfusion syndrome, twin anaemia polycythaemia sequence, or monoamnionicity were excluded. Cognitive performance was evaluated with two standardised psychometric age-appropriate tests, producing a full-scale intelligence quotient (FSIQ). Motor functioning was assessed with a standardised neurological examination. A composite outcome of neurodevelopmental impairment (NDI) was used, subdivided into mild NDI (defined as FSIQ <85, minor neurological dysfunction or cerebral palsy grade 1, or mild visual or hearing impairment) and severe NDI (defined as FSIQ <70, severe neurological dysfunction, or severe visual or hearing impairment). Between Jan 25, 2021, and March 15, 2022, 47 twin pairs were enrolled in the study and underwent neurodevelopmental assessment. The median gestational age at birth was 33·9 weeks (IQR 31·3-36·0) for the 47 included twin pairs, with median birthweights of 1400 g (1111-1875) in the smaller twin and 2003 g (1600-2680) in the larger twin. The median age at neurodevelopmental assessment was 11 years (8-13). Median FSIQ was 94 (86-101) for the smaller twin and 100 (92-108) for the larger twin (p<0·0001). More smaller twins had mild NDI (17 [36%] of 47) than did the larger twins (five [11%] of 47; odds ratio 4·8 [95% CI 1·6-14·1]; p=0·0049). There was no difference in the proportion of children with severe NDI (two [4%] of 47 in both groups, p=1·0). As mild NDI can impede children in their daily functioning, we recommend standardised long-term follow-up, including neurodevelopmental testing, for monochorionic diamniotic twins with selective FGR to facilitate early identification of children at risk. The Dutch Heart Foundation.

Heritability and genetic correlation of body mass index and coronary heart disease in Chinese adult twins

Objective: To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation. Methods: Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD. Results: A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95%CI: 0.49-0.55) and 0.76 (95%CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD (rA=0.10, 95%CI:0.02-0.17). Conclusion: In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

The Heritability of Kidney Function Using an Older Australian Twin Population

IntroductionTwin studies are unique population models which estimate observed rather than inferred genetic components of complex traits. Nonmonogenic chronic kidney disease (CKD) is a complex disease process with strong genetic and environmental influences, amenable to twin studies. We aimed to assess the heritability of CKD using twin analysis and modeling within Older Australian Twin Study (OATS) data.MethodsOATS had 109 dizygotic (DZ) and 126 monozygotic (MZ) twin pairs with paired serum creatinine levels. Heritability of kidney function as estimated glomerular filtration rate (eGFR CKD Epidemiology Collaboration [CKD-EPI]) was modeled using the ACE model to estimate additive heritability (A), common (C), and unique (E) environmental factors. Intratwin pair analysis using mixed effects logistic regression allowed analysis of variation in eGFR from established CKD risk factors.ResultsThe median age was 69.71 (interquartile range 78.4–83.0) years, with 65% female, and a mean CKD-EPI of 82.8 ml/min (SD 6.7). The unadjusted ACE model determined kidney function to be 33% genetically determined (A), 18% shared genetic-environmental (C), and 49% because of unique environment (E). This remained unchanged when adjusted for age, hypertension, and sex. Hypertension was associated with eGFR; however, intertwin variance in hypertension did not explain variance in eGFR. Two or more hypertension medications were associated with decreased eGFR (P = 0.009).ConclusionThis study estimates observed heritability at 33%, notably higher than inferred heritability in genome-wide association study (GWAS) (7.1%–18%). Epigenetics and other genomic phenomena may explain this heritability gap. Difference in antihypertension medications explains part of unique environmental exposures, though discordance in hypertension and diabetes does not.

Incidence and Implications of Twin Gestational Surrogacy at Two Large U.S. Military Hospitals: A 10-Year Retrospective Cohort Study.

Individuals seeking a gestational surrogate often turn to U.S. military dependents due to favorable insurance coverage. Surrogate pregnancies, including multiple gestations, may be at increased risk for adverse outcomes. The objectives of this study were to determine the incidence of surrogacy in a twin population conceived by assisted reproductive technology (ART), assess the impact on the military healthcare system, and determine if there is an increased rate of complications in twin surrogacy pregnancies. We conducted a 10-year retrospective cohort study of ART-conceived twin gestations at two military hospitals. Charts were reviewed for demographic data, surrogacy status, and obstetric complications. Number of prenatal visits and formal sonograms were tabulated for surrogate pregnancies. Complication rates were compared between groups using Fisher's exact test. Over the 10-year period, 36 of the 249 pregnancies were identified as gestational surrogates, equating to a rate of 14.4%. Surrogate mothers were younger than non-surrogates (29.58 years vs. 33.11 years, P < .001). Care of surrogate pregnancies required a total of 306 prenatal visits and 98 formal ultrasounds. The incidence of gestational diabetes was higher among surrogates compared to other ART-conceived twin pregnancies at 27.8% vs. 12.2% (P < .05), while other complications did not significantly differ. Approximately one in seven ART-conceived twin gestations were surrogacy pregnancies, requiring significant clinical resources. The incidence of gestational diabetes was higher among surrogate gestations.

Conducting Clinical Trials in Twin Populations: A Review of Design, Analysis, Recruitment and Ethical Issues for Twin-Only Trials.

Although twins often participate in medical research, few clinical trials are conducted entirely in twin populations. The purpose of this review is to demonstrate the substantial benefits and address the key challenges of conducting clinical trials in twin populations, or 'twin-only trials'. We consider the unique design, analysis, recruitment and ethical issues that arise in such trials. In particular, we describe the different approaches available for randomizing twin pairs, highlight the similarity or correlation that exists between outcomes of twins, and discuss the impact of this correlation on sample size calculations and statistical analysis methods for estimating treatment effects. We also consider the role of both monozygotic and dizygotic twins for studying variation in outcomes, the factors that may affect recruitment of twins, and the ethics of conducting trials entirely in twin populations. The advantages and disadvantages of conducting twin-only trials are also discussed. Finally, we recommend that twin-only trials should be considered more often.

A Modified Approach in Lip Repositioning Surgery: A Prospective Study in a Twin Population with a 3-Year Follow-up.

This study evaluated long-term clinical and patient satisfaction outcomes following a modified lip repositioning technique that utilized periosteal sutures in a twin population. Twin sisters diagnosed with maxillary lip hypermobility were randomly assigned to either the control group (original LipStaT technique) or test group (addition of periosteal sutures). The participants (n = 12; 6 per group) were evaluated at intervals for up to 3 years postoperative. Clinical measurements, digital images, and patient satisfaction surveys were collected. Descriptive statistics were used to assess outcome variables: average lip width at rest (ALW), vertical lip translation (VLT), and average gingival display (AGD). Student t test, one-way analysis of variance, and Spearman rank correlation tests were used to compare mean values of variables at five time points for both groups. The level of significance was α = .05. In the control group, mean VLT and AGD values showed statistically significant decreases from baseline (14.8 mm and 7.0 mm, respectively) to 2 years (5.7 mm and 2.4 mm, respectively), but a slight increase was seen at 3 years (7.5 mm and 5.0 mm, respectively; P < .0001). In the test group, mean VLT and AGD values showed statistically significant decreases from baseline (14.8 mm and 6.9 mm, respectively) to 3 years (5.5 mm and 3.5 mm, respectively; P < .0001). A higher participant satisfaction score at 3-year follow-up was observed in the test group. The modified lip repositioning technique in a population of twins resulted in more stable outcomes that lasted up to 3 years postoperatively.

Kinetics of cyclically-induced mechanical twinning in γ-TiAl unveiled by a combination of acoustic emission, neutron diffraction and electron microscopy

The cyclic response and the microstructure evolution of the near γ-TiAl alloy are investigated by a blend of contemporary experimental techniques centred around in-situ acoustic emission (AE) measurements reflecting the cyclically-induced structural changes in the real-time scale. TEM and SEM – ECCI/EBSD examinations provided an adequate qualitative description of microstructural features associated with populations of dislocations and mechanical twins evolving concurrently in the course of cyclic deformation. Since the TEM offers only local and post-mortem information, the in-situ neutron diffraction technique scanning a large part of the gauge length was employed to characterise the lattice strain distributions with cycling. The volume fraction of twins as a function of loading cycles was obtained after loading or unloading half-cycles. The processes controlling the cyclic strain hardening during each deformation cycle were assessed by (i) the statistical analysis of the shape of the hysteresis loop aiming at the characterisation of distribution internal stress barriers for deformation mechanisms involved and (ii) the spectral and statistical analysis of AE data providing information on the kinetics of these mechanisms. Each of the used experimental methods brings its own set of advantages and limitations in terms of characterisation and interpretation. Their unique combination ensures a host of benefits that promote a comprehensive understanding of primary deformation mechanisms - deformation twinning, dislocation slip and detwinning. It is shown that the cyclic mechanical behaviour of the TiAl alloy can be comprehensively explained by the interplay between these mechanisms co-operating during each loading cycle. This interplay governs the behaviour of underlying mechanisms in the early stages of the fatigue damage evolution and likely determines the overall fatigue response of near γ-TiAl alloy at room temperature.

Associations of Metabolic/Obesity Phenotypes with Insulin Resistance and C-Reactive Protein: Results from the CNTR Study.

BackgroundObesity is a heterogeneous condition in terms of metabolic status. Different obesity phenotypes have various health risks. The aim of this work was to define different subtypes of obesity and investigate their relationship with inflammatory-cardiometabolic abnormalities among Chinese adult twins.MethodsThe analyses used data from 1113 adult twins in 4 provinces (Shandong, Zhejiang, Jiangsu and Sichuan) from Chinese National Twin Registry (CNTR) which collected detailed information. We defined those with 0 or 1 metabolic syndrome (MetS) components excluding waist circumference as metabolically healthy, and those with waist circumference ≥90 cm (for men) and ≥85 cm (for women) as obese. The two-category obesity status and metabolic states are combined to generate four metabolic/obesity phenotypes. High sensitivity C reactive protein (hsCRP) was measured to assess underlying inflammation and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as surrogate measure of insulin resistance. Mixed-effect linear regression models and fixed-effect linear regression models were used to analyse the correlation between HOMA-IR, hsCRP and different metabolic/obesity phenotypes.ResultsIn cross-sectional analyses of 1113 individuals (mean [SD] age, 46.6 [12.9] years; 463 obese [41.6%]), 20.3% obese twins were metabolic healthy and 64.2% non-obese twins were metabolic unhealthy. Serum HOMA-IR level was higher in metabolically unhealthy non-obesity (MUNO) (β=0.42, 95% CI: 0.21–0.64), metabolically healthy obesity (MHO) (β=0.68, 95% CI: 0.36–1.00) and metabolically unhealthy obesity (MUO) (β=0.69, 95% CI: 0.46–0.91) twins, compared with their metabolically healthy non-obesity (MHNO) counterparts. HsCRP was similar between MHO and MUO, which differed significantly to metabolic healthy non-obesity (MHNO).ConclusionMHO and MUNO phenotypes were common in Chinese twin population. Both phenotypes were associated with elevated IR and hsCRP which may not be benign and need to be concerned.

Differences and Correlation Analysis of Birth Weight and Overweight/Obesity in Shanghai Twin Cohort.

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.

Perinatal outcomes of twin pregnancies complicated by late twin-twin transfusion syndrome: A systematic review and meta-analysis.

Untreated twin-to-twin transfusion syndrome (TTTS) is associated with a high risk of perinatal mortality and morbidity. Laser surgery is recommended before 26weeks of gestation. However, the optimal management in case of late TTTS (occurring after 26weeks of gestation) is yet to be established. We conducted a systematic review and meta-analysis to evaluate the outcomes of monochorionic-diamniotic twin pregnancies complicated by late TTTS according to different management options (expectant, laser therapy, amnioreduction, or delivery). The primary outcome was mortality, including single and double intrauterine, neonatal, and perinatal death. Secondary outcomes were composite morbidity, neuromorbidity, respiratory distress syndrome, admission to neonatal intensive care unit, intact survival (ie, free from neurological complications), and preterm birth before <32weeks of gestation. Outcomes were reviewed according to the management and reported for the overall population of twins and disease status (ie, donor and recipient separately). Random-effect meta-analyses of proportions were used to analyze the data. Nine studies including 796 twin pregnancies affected by TTTS were included. No randomized controlled trials were available for inclusion. TTTS occurred at ≥26weeks of gestation in 8.7% (95% CI 6.9%-10.9%; 67/769) of cases reporting TTTS at all gestations. Intrauterine death occurred in 17.7% (95% CI 4.9%-36.2%) of pregnancies managed expectantly, 5.3% (95% CI 0.9%-12.9%) of pregnancies treated with laser, and 0% (95% CI 0%-9%) after amnioreduction. Neonatal death occurred in 42.5% (95% CI 17.5%-69.7%) of pregnancies managed expectantly, in 2.8% (95% CI 0.3%-7.7%) of cases treated with laser, and in 20.2% (95% CI 6%-40%) after amnioreduction. Only one study (10 cases) reported data on immediate delivery after diagnosis with no perinatal deaths. Perinatal death incidence was 55.7% (95% CI 31.4%-78.6%) in twin pregnancies managed expectantly, 5.6% (95% CI 0.5%-15.3%) in those treated with laser, and 20.2% (95% CI 6%-40%) in those after amnioreduction. Intact survival was reported in 44.4%, 96.4%, and 78% of fetuses managed expectantly, with laser or amnioreduction, respectively. Evidence regarding perinatal mortality and morbidity in twin pregnancies complicated by late TTTS according to the different managements was of very low quality. Therefore further high-quality research in this field is needed to elucidate the optimal management of these pregnancies.

Birthweight is an independent predictor of birth asphyxia in twins: A retrospective cross-sectional cohort study of 5337 Chinese twins

ObjectiveFew studies are available on birth asphyxia risks in twin neonates. This retrospective multi-center cross-sectional study determined the birthweight percentiles of 5337twins and birth asphyxia incidence of the twin population. MethodsWe retrieved sociodemographic and obstetric data from the electronic records systems of participating centers. Neonate birthweight was measured within 24 h of birth. Perinatal asphyxia was diagnosed if 5-minute Apgar score was ≤5, or resuscitation was required 10 min after birth. The primary outcome was the incidence of birth asphyxia. ResultsTotally 5337 neonates were eligible. The mean neonatal birthweight was 2227.1 ± 608.99 g and the 5th, 50th, and 95th percentiles of birthweight were 970, 2400, and 3080 g, respectively. The mean Apgar score was 9.06 ± 1.73 at 1 min and 8.99 ± 1.74 at 5 min. Totally 13.5 % (705/5222) twins had asphyxia and 9.35 % and 4.16 % twins had moderate and severe asphyxia, respectively. Twins with a birthweight< 1500 g had the highest asphyxia rate (64.8 %) and twins with a birthweight between 2500 and 3000 g had the lowest asphyxia rate (3.6 %). Stepwise logistic regression analysis revealed that higher birthweight was associated with a significantly reduced risk of asphyxia [OR 0.772 (95 %CI 0.755, 0.789), P < 0.001]. The AUROC for mean twin birthweight was 0.86±0.01 (95 %CI 0.84, 0.88) using a cutoff of 1950 g, with a sensitivity of 0.84 and a specificity of 0.78. ConclusionTwins have lower birthweight versus singletons and a significant proportion of twins, especially twins with lower birthweight, are at risk of birth asphyxia. Birthweight is an independent predictor of asphyxia and should be further explored as a predictive marker for stratifying asphyxia risks in twin neonates.