Sibling Study Research Articles

Maternal Residential Mobility Between Pregnancies: A California Statewide Sibling Study

Maternal Residential Mobility Between Pregnancies: A California Statewide Sibling Study

Familial Recurrence of Autism: Updates From the Baby Siblings Research Consortium.

Autism spectrum disorder (ASD) is estimated to be ∼10 times higher in children with versus without an autistic sibling in population-based studies. Prospective studies of infant siblings have revealed even higher familial recurrence rates. In the current prospective longitudinal study, we provide updated estimates of familial ASD recurrence using a multinational database of infants with older autistic siblings. Data were collated across 18 sites of the Baby Siblings Research Consortium, an international network studying the earliest manifestations of ASD. A total of 1605 infants with an older autistic sibling were followed from early in life to 3 years, when they were classified as ASD or non-ASD. Hierarchical generalized linear modeling, with site as a random effect, was used to examine predictors of recurrence in families and calculate likelihood ratios. A total of 20.2% of siblings developed ASD, which is not significantly higher than the previously reported rate of 18.7%. Male infant sex and >1 older affected sibling were significant predictors of familial recurrence. Proband sex also influenced recurrence rates, with siblings of female probands significantly more likely to develop ASD than siblings of male probands. Race and maternal education were also associated with recurrence in families. The familial recurrence rate of ASD, as measured in infant sibling studies, has not changed appreciably since previous estimates were made in 2011. Younger siblings of autistic children, particularly those who are male, have an affected female sibling, multiple affected siblings, or are impacted by social inequities, should be closely monitored and promptly referred for diagnostic evaluation.

Fetal Exposure to Tobacco Metabolites and Depression During Adulthood: Beyond Binary Measures.

Sibling studies of maternal smoking during pregnancy and subsequent risk of depression have produced mixed results. A recent study identified not considering the amount of maternal smoking and age of onset as potentially masking a true association. We examine these issues and also the amount of maternal smoking during pregnancy as a determinant of the severity of depressive symptoms. We analyzed data from the community-based National Longitudinal Survey of Youth (US, 1994-2016). Mothers reported smoking during pregnancy (none, <1 pack/day, ≥1 pack/day). We assessed offspring's lifetime depression (i.e., ≥8 symptoms) and symptom counts with the Centers for Epidemiologic Studies Depression scale. We estimated the risk of these two outcomes in the full sample (n = 7172) and among siblings (n = 6145) using generalized linear mixed-effects models with random intercepts by family and family-averaged means for sibling analyses. Among siblings, we observed dose-dependent elevations for both risk of depression (smoking during pregnancy <1 pack/day adjusted risk ratio [aRR] = 1.18; 95% confidence interval [CI] = 1.07, 1.30; smoking ≥1 aRR = 1.36; 95% CI = 1.19, 1.56) and severity of depressive symptoms (smoking <1 pack/day aRR = 1.12; 95% CI = 1.08, 1.16); smoking ≥1 pack/day aRR = 1.25; 95% CI = 1.18, 1.31). Among both samples, the P for trend was <0.01. In analysis limited to offspring diagnosed before age 18, results for severity were attenuated. This evidence supports the existence of an independent association between maternal smoking during pregnancy and both the risk of depression and the severity of depressive symptoms. The results highlight the utility of considering the amount of smoking, severity of symptoms, and age of onset.

P-176 A novel electrophoretic sperm isolation system achieves equivalent ICSI outcomes to the combined density gradient centrifugation and swim-up method in a significantly shorter processing time

Abstract Study question Does an electrophoretically sperm isolation method, the Felix™ system, have clinical or operational advantages over the combined density gradient centrifugation and swim-up (DGCS) method? Summary answer The Felix™ system produces results that are comparable to the DGCS method, however, Felix™ has the ability to isolate spermatozoa more efficiently. What is known already The isolation of healthy spermatozoa to improve ART outcomes has received enormous attention in the literature recently. Although swim-up and density gradient centrifugation are the most common sperm separation methods, the optimal technique is still unclear. Recently, good sperm selection approaches using various non-centrifugal devices have emerged. Previous reports have shown that a quick and simple sperm separation device, the Felix™ system, can isolate high-quality spermatozoa and improve the results of ART. The Felix™ system combines electrophoresis and separation membranes to collect negatively charged mature normal sperm. Study design, size, duration A prospective oocyte sibling study was conducted between March 2023 and December 2023. The study involved infertile couples (n = 45) with a semen volume of 2.3 mL or more, a motile sperm concentration of 2 million/mL or more, maternal age under 43 years, and at least four mature oocytes at the time of oocyte retrieval. Ejaculated semen was prepared separately using DGCS and Felix™ on the day of oocyte retrieval and subsequent ICSI results were analyzed. Participants/materials, setting, methods In the DGCS group, semen was layered on a 45/90% of sperm grad and centrifuged for 15 minutes, followed by a 30 min swim-up. Subsequently, 0.3 mL of supernatant was collected. In the Felix™ group, 0.3 mL of sperm was collected following six minutes of membrane hydration and electrophoresis. Sperm concentration, total motility, progressive motility and DNA fragmentation (SDFR) were measured. Fertilization, blastocyst development, good-quality blastocyst development, and embryo utilisation rates were also assessed. Main results and the role of chance The average female age at the time of oocyte retrieval was 36.5±4.0 years, and the average male age was 38.1±5.9 years. Of 401 oocytes, 200 and 201 oocytes underwent ICSI using sperm prepared by DGCS and Felix™, respectively. The average processing time of Felix™ was significantly shorter than that of DGCS (54.0±4.3 vs. 7.4±0.2 minutes, p &amp;lt; 0.001, respectively). No significant difference was observed between the DGCS and Felix™ groups for sperm concentration (p = 0.49), motility (p = 0.05), progressive motility (p = 0.34), and SDFR (p = 0.09). Furthermore, there were no significant differences between the two groups with regards to fertilization rate (81.0% vs. 80.6%, p = 0.92), blastocyst development rate (52.9% vs. 58.4%, p = 0.60), good-quality blastocyst development rate (26.1% vs. 35.7%, p = 0.06), and embryo utilisation rate (54.3% vs 58.0%, p = 0.50). Limitations, reasons for caution Although the DGCS method was used as a comparison group, it is necessary to compare the Felix™ system with DGC alone, swim-up alone, or other sperm isolation methods. Larger, more powered studies are required to determine the impact on pregnancy and live birth outcomes. Wider implications of the findings The Felix™ system is a viable option for sperm isolation. While DGCS requires complicated procedures and time-consuming process including centrifugation and incubation; Felix™ requires six minutes only. The Felix™ system reduces processing times significantly and therefore can improve laboratory operations and workflow. Trial registration number Not Applicable

Neighborhood mobility and racial disparities in preterm birth: A sibling study in California

Recent work finds that upward neighborhood mobility—defined as reductions in neighborhood socioeconomic disadvantage due to moving—may improve birth outcomes. Less work, however, explores whether changes in socioeconomic context differentially impact birth outcomes by maternal race and ethnicity. In the US, mothers of minoritized racial and ethnic identity often experience worse neighborhood conditions and pregnancy outcomes than White mothers. Using a sibling-linked dataset, we examined whether neighborhood mobility corresponds with changes in preterm birth risk among Asian (N = 130,079), Black (N = 50,149), Hispanic (N = 429,938), and White (N = 233,428) mothers who delivered multiple live births in California between 2005 and 2015. We linked residential addresses at each birth to census-derived indices of neighborhood disadvantage and defined levels of neighborhood mobility as moving-induced changes in disadvantage between pregnancies. We mapped neighborhood mobility patterns and fit conditional logistic regression models estimating the odds of preterm birth in the sibling delivered after moving, controlling for the risk of preterm birth in the sibling delivered before moving, by maternal race and ethnicity. Dot density maps highlight racialized patterns of neighborhood mobility and segregation between Black and White mothers. Regression results show that Black and, in some cases, Asian and Hispanic mothers who experienced upward mobility (moves away from neighborhood disadvantage) exhibited reduced odds of preterm birth in the second delivery. Upward mobility did not reduce the odds of preterm birth among White mothers. Findings suggest that policies and programs that enable opportunities for neighborhood mobility may reduce persistent racial and ethnic disparities in adverse birth outcomes.

Developmental trends in intelligence revisited with novel kinships: Monozygotic twins reared apart v. same-age unrelated siblings reared together

Prior research has reported convergence of monozygotic (MZ) cotwins' intelligence scores over time, with divergence observed between dizygotic (DZ) cotwins. These patterns have been variously explained with reference to the increased influence of genetic factors (MZ and DZ twins) and nonshared environmental factors (DZ twins), and the reduced effects of shared environmental events (DZ twins). Studies of unrelated siblings have found modest within-pair resemblance in intelligence, with increasing divergence over time. This subject is revisited in a study using three novel kinships: young reared-apart MZ twins from China (CTA-MZ), adult reared-apart twins from Denmark (D-MZA) and findings from a previous study of same-age unrelated siblings (virtual twins or VTs). Despite modest sample sizes, the anticipated trends described above were observed, replicating extant findings. Intraclass correlations for overall IQ score at Time 1 and Time 2, respectively, were ris = 0.51, 0.81 (CTA-MZs) and ris = 0.64, 0.74 (D-MZAs). The hypothesis that VTs would show score divergence at Time 2 was confirmed. Increased genetic influence (CTA-MZ, D-MZA and VT), reduced impact of shared environments (VT), and increased effects of nonshared environments (VT) appear to best explain the findings. These results also inform parent and educator expectations regarding twins' and siblings' academic performance.

Reliability of a short diet and vitamin supplement questionnaire for retrospective collection of maternal nutrient intake

BackgroundGestational nutrition can protect against adverse neurodevelopmental outcomes. ObjectivesWe developed a short tool for collecting maternal nutritional intake during pregnancy to facilitate research in this area and compared its retrospective use to prospectively-collected food frequency questionnaires (FFQ). MethodsMaternal nutritional intake was retrospectively assessed using three versions (full interview, full self-administered online, and shortened interview) of the Early Life Exposure Assessment Tool (ELEAT) among participants of the MARBLES pregnancy cohort study of younger siblings of autistic children. Retrospective responses were compared with responses to supplement questions and the validated 2005 Block FFQ prospectively collected in MARBLES during pregnancies 2–7 years prior. ELEAT nutrient values were calculated using reported food intake frequencies and nutrient values from the USDA nutrient database. Correlations between retrospectively- and prospectively-reported intake were evaluated using Kappa coefficients, Youden's J, and Spearman Rank Correlation Coefficients (rs). ResultsMARBLES FFQ dietary intakes were compared among 54 women who completed the ELEAT full form including 12 online, and among 23 who completed the ELEAT short form. Correlations across most foods were fair to moderate. Most ELEAT quantified nutrient values were moderately correlated (rs = 0.3–0.6) with those on the Block FFQ. Supplement questions in both MARBLES and the ELEAT were completed by 114 women. Kappas were moderate for whether or not supplements were taken, but modest for timing. Correlations varied by version and child diagnosis or concerns, and were higher when mothers completed the ELEAT when their child was 4 years old or younger. ConclusionsWith recall up to several years, ELEAT dietary and supplement module responses were modestly to moderately reliable and produced nutrient values moderately correlated with prospectively-collected measures. The ELEAT dietary and vitamin supplements modules can be used to rank participants in terms of intake of several nutrients relevant for neurodevelopment.

Familial confounding or measurement error? How to interpret findings from sibling and co-twin control studies

Epidemiological researchers often examine associations between risk factors and health outcomes in non-experimental designs. Observed associations may be causal or confounded by unmeasured factors. Sibling and co-twin control studies account for familial confounding by comparing exposure levels among siblings (or twins). If the exposure-outcome association is causal, the siblings should also differ regarding the outcome. However, such studies may sometimes introduce more bias than they alleviate. Measurement error in the exposure may bias results and lead to erroneous conclusions that truly causal exposure-outcome associations are confounded by familial factors. The current study used Monte Carlo simulations to examine bias due to measurement error in sibling control models when the observed exposure-outcome association is truly causal. The results showed that decreasing exposure reliability and increasing sibling-correlations in the exposure led to deflated exposure-outcome associations and inflated associations between the family mean of the exposure and the outcome. The risk of falsely concluding that causal associations were confounded was high in many situations. For example, when exposure reliability was 0.7 and the observed sibling-correlation was r = 0.4, about 30–90% of the samples (n = 2,000) provided results supporting a false conclusion of confounding, depending on how p-values were interpreted as evidence for a family effect on the outcome. The current results have practical importance for epidemiological researchers conducting or reviewing sibling and co-twin control studies and may improve our understanding of observed associations between risk factors and health outcomes. We have developed an app (SibSim) providing simulations of many situations not presented in this paper.

Neighborhood built environment, obesity, and diabetes: A Utah siblings study

BackgroundThis study utilizes innovative computer vision methods alongside Google Street View images to characterize neighborhood built environments across Utah. MethodsConvolutional Neural Networks were used to create indicators of street greenness, crosswalks, and building type on 1.4 million Google Street View images. The demographic and medical profiles of Utah residents came from the Utah Population Database (UPDB). We implemented hierarchical linear models with individuals nested within zip codes to estimate associations between neighborhood built environment features and individual-level obesity and diabetes, controlling for individual- and zip code-level characteristics (n = 1,899,175 adults living in Utah in 2015). Sibling random effects models were implemented to account for shared family attributes among siblings (n = 972,150) and twins (n = 14,122). ResultsConsistent with prior neighborhood research, the variance partition coefficients (VPC) of our unadjusted models nesting individuals within zip codes were relatively small (0.5%–5.3%), except for HbA1c (VPC = 23%), suggesting a small percentage of the outcome variance is at the zip code-level. However, proportional change in variance (PCV) attributable to zip codes after the inclusion of neighborhood built environment variables and covariates ranged between 11% and 67%, suggesting that these characteristics account for a substantial portion of the zip code-level effects. Non-single-family homes (indicator of mixed land use), sidewalks (indicator of walkability), and green streets (indicator of neighborhood aesthetics) were associated with reduced diabetes and obesity. Zip codes in the third tertile for non-single-family homes were associated with a 15% reduction (PR: 0.85; 95% CI: 0.79, 0.91) in obesity and a 20% reduction (PR: 0.80; 95% CI: 0.70, 0.91) in diabetes. This tertile was also associated with a BMI reduction of −0.68 kg/m2 (95% CI: −0.95, −0.40) ConclusionWe observe associations between neighborhood characteristics and chronic diseases, accounting for biological, social, and cultural factors shared among siblings in this large population-based study.

Comorbidities in women with polycystic ovary syndrome: a sibling study

BackgroundPolycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. PCOS may be influenced by prenatal androgen excess, poor intrauterine or childhood environmental factors, childhood obesity and learned health risk behaviors. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors.MethodsThis total-population register-based cohort study included 333,999 full sisters, born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjects´ early-life and social characteristics. In the main analysis, sister fixed effects (FE) models were used to control for all time-invariant factors that are shared among sisters, thereby testing whether the association between PCOS and examined comorbidities is influenced by unobserved familial environmental, social or genetic factors.ResultsThree thousand five hundred seventy women in the Sister sample were diagnosed with PCOS, of whom 14% had obesity, 8% had depression, 7% had anxiety and 4% experienced sleeping, sexual and eating disorders (SSE). Having PCOS increased the odds of obesity nearly 6-fold (adjusted OR (aOR): 5.9 [95% CI:5.4-6.5]). This association was attenuated in models accounting for unobserved characteristics shared between full sisters, but remained considerable in size (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). For depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when controlling for factors shared between sisters. Being diagnosed with SSE disorders yielded a 2.4 aOR (95% CI:2.0-2.6) when controlling for a comprehensive set of individual-level confounders, which only decreased slightly when controlling for factors at the family level such as shared genes or parenting style. Accounting for differences between sisters in observed early-life circumstances influenced the estimated associations marginally.ConclusionHaving been diagnosed with PCOS is associated with a markedly increased risk of obesity and sleeping, sexual and eating disorders, also after accounting for factors shared between sisters and early-life conditions.

HUBUNGAN JARAK KELAHIRAN DAN POLA ASUH DENGAN PENANGANAN SIBLING RIVALRY PADA USIA 3-5 TAHUN DI DESA LAMPAHAN BARAT

In Indonesia, 75% of children experience sibling rivalry. The child’s reaction appears to be more agressive, misbehaves, hits, fusses, experiences descriptions, often unnecessary cries, and is more dependent on their mother. Based on case studies of siblings that have occurred to injure and even cause death to other siblings, the highest trigger is due to the parenting style of parents who often distinguish the treatment of their children, so it is a concern to do handling. A preliminary survey that was carried out in Desa Lampahan Barat on 30 mothers who had children aged 3-5 years with more than one child obtained 70% of the mothers revealed that their children felt sibling rivalry. The population in the research was 30 respondents who were taken as samples by using the total sampling methode. This research was Quantitative through cross-sectionsl design. The result showed that 19 respondents (63,3%) were authoritative parenting. It found that 20 respondents (66,7%) were close to birth spacing. In brief, there was a correlation between birth spacing and parenting with sibling rivalry management in aged 3-5 years children. Therefore, a researcher expected that respondents should monitor their birth spacing and create parenting properly

Psychological study of siblings subsystems – methodological considerations

Introduction: The analysis of the literature devoted to scientific considerations on the relational aspect of the functioning of siblings, especially those who are in adulthood, allows us to draw the conclusion that they are relatively rarely undertaken by researchers. It is noticed that nowadays there is an increase in interest in this issue. The aims of the work were to consider some of the limitations occurring in the process of conducting psychological research on the sibling subsystem and to present tools for psychological measurement of the quality and dimension of the interpersonal relationship between siblings.&#x0D; Method: The method of content analysis of publications in this field was used and a comparative analysis of issues undertaken in the context of psychological research on the relational aspects of the functioning of siblings was carried out.&#x0D; Results: Five self-report questionnaire tools that were developed in 2014-2017 were presented along with their psychometric properties: Adult Sibling Relationships Questionnaire, Adult Sibling Family Relations Scale, STQ - Now, STQ – Then and Relationships Questionnaire with Siblings.&#x0D; Conclusions: The specificity of research on interpersonal relationships in the sibling subsystem is related to methodological awareness of the high complexity of the family environment and knowledge of the uniqueness of sibling relationships. The researcher's consideration of both issues creates space for searching for new methodological solutions.

Better off in the city? Economic outcomes of rural out‐migration in Sweden—sibling study of cohorts 1960–1984

AbstractThis study examines disparities in income levels and employment status between individuals who migrate from rural areas and their siblings who remained in rural settings in Sweden for cohorts born 1960–1984. Utilizing comprehensive Swedish register data, we track the economic outcomes at age 35 or rural residents who migrated between ages 15 and 25, comparing them to non‐migrating siblings. Our analysis, employing binomial logit and log‐linear models for employment odds and income levels, respectively, reveals that while rural out‐migration generally leads to higher income, it does not significantly impact employment status. The study underscores the role of individual and family‐specific factors—such as gender and education—and broader time‐ and place‐dependent structures in mediating migration's effects. We find that income disparity between migrants and non‐migrants has increased since the 1990s and that the differences increase with the urbanization level of the destination.

‘People don’t realise how much their past experiences affect them in adulthood’: A qualitative study of adult siblings’ experiences of growing-up with a sister/brother with a childhood life-limiting condition and their perceived support needs

Background: There is a lack of research about the experiences and impact of having a sibling with a life-limiting condition. Studies focus on the sibling experience during childhood but the experience and impact during adulthood is unknown despite the increased life-expectancy of children with life-limiting conditions. Aim: To explore adult siblings’ perspectives on the experience of having a sister/brother with a childhood life-limiting condition and to identify their perceived needs and preferences for support. Design: A qualitative exploratory study design with data generated by semi-structured interviews and analysed using reflexive thematic analysis, underpinned by interpretivism. Setting/participants: Twenty-two siblings (17–42 years old) were recruited via a children’s hospice in England. Results: The experience of having a sibling with a life-limiting condition changes over time in response to how understandings of the meaning of a life-limiting condition develop and changing roles/relationships with parents and siblings. These experiences have an enduring impact on adult sibling’s mental health which is compounded by their unmet (and sometimes unrecognised) support needs in adolescence and adulthood. Siblings described the importance of support continuing into adulthood with a focus on the provision of psychotherapy and peer support. Conclusions: Having a sister/brother with a childhood life-limiting condition appeared to have a significant and ongoing impact on adult siblings but their support needs, particularly for psychotherapy and peer support, are overlooked. The findings highlight the importance of ensuring siblings are included in family assessments and that family-based interventions are developed to promote sibling-parent relationships.

Utility of the Language Use Inventory in Young Children at Elevated Likelihood of Autism.

The aims of this study were (a) to evaluate the convergent validity of the Language Use Inventory (LUI) with measures of autism spectrum disorder (ASD) symptoms, language, and social skills and (b) to assess discriminant validity of the LUI with measures of nonlanguage skills, including daily living skills and motor development. This study sample included participants from a longitudinal study (n = 239) of infant siblings with elevated familial likelihood of ASD and lower familial likelihood. Assessment measures completed at 36 months included the LUI, the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2), the Mullen Scales of Early Learning, and the Vineland Adaptive Behavior Scales-Second Edition. Bivariate Pearson correlations were estimated between ADOS-2 comparison scores and four language and social skills measures. Additional correlations were estimated between LUI total scores and standard scores from nonlanguage measures. A series of Fisher's Z transformations were applied to evaluate whether bivariate correlations were significantly different. All four language and social skill measures were moderately to strongly associated with each other and ASD symptom severity scores. The correlation between ADOS-2 comparison scores and LUI total scores was significantly stronger than ADOS-2 correlations with all other measures. Our findings provide support for the LUI as a feasible, pragmatic language-targeted instrument for inclusion in early developmental evaluations prompted by language concerns. Administration of the LUI may accelerate earlier referral for a comprehensive assessment of ASD symptoms. Given the high correlation with ADOS-2 scores, an LUI total score in a clinical range of concern may encourage a clinician to refer families for a full diagnostic evaluation of ASD.

Educational outcomes in siblings of childhood leukemia survivors: Factors associated with school difficulties and comparison with general population.

To investigate the educational outcomes of siblings of childhood leukemia survivors, explore determinants of school difficulties, and compare the rates of repeating grades between siblings and the general population. A cross-sectional study of childhood leukemia survivors' siblings recruited through the Leucémies de l'Enfant et de l'Adolescent cohort, a French long-term follow-up program, was conducted, and education-related data were obtained via self-report questionnaires. Adjusted logistic regression models were used to identify variables associated with school difficulties and time since diagnosis. Rates of repeating a grade in middle school were compared between siblings and the general population of the same generation. A total of 564 siblings with a mean time from diagnosis of 14.1 ± 6.4 years were included, among whom 139 (24.6%) repeated a grade, at an average of 6.4 ± 4.5 years after diagnosis. In multivariate analysis, the risk factors for repeating a grade were older siblings (odds ratio [OR] 2.3, p = 0.006), family financial difficulties (OR 2.8, p = 0.008), and history of repetition in survivors (OR, 2.5, p = 0.001). Sibling hematopoietic stem cell donors were at greater risk of repeating a grade long-term after diagnosis (p = 0.018). Overall, siblings did not have a higher risk of educational delays at the end of middle school than the general population. Although the results are reassuring, socioeconomic and cancer-related factors may have an impact on siblings' schooling long after diagnosis. Paying attention to siblings contributes to identifying the most vulnerable families, allowing more attention and appropriate resources to avoid long-term repercussions. Additionally, supportive and targeted interventions can be developed to improve the organization of education and the health care system.

#27 : A Sibling Study: How Individual Culture Strategy Affects Embryo Ploidy Status in IVF/PGT-A Cycles?

Background and Aims: The result of individual and group culture embryo studies remained conflicting. Several studies assumed that the blastulation rate was lower when culturing embryos separately. Meanwhile, there has been little information on whether individual culture can affect embryo ploidy status. This study was designed to find a relationship between culture strategies and the embryo’s ploidy status in IVF/PGT-A cycles. Method: 91 IVF/PGT-A cycles with at least four zygotes enrolled in a randomized control trial from September 2021 to June 2022 in Tam Anh general hospital. Zygotes from each cycle were randomly assigned to individual culture(10 ul/drop) or group cultured of 3-5 zygotes (50 ul/drop). Among those, 280 blastocysts derived from biopsy-all cycles (137 from individual culture and 143 from group culture) and already determined for ploidy status were to be analyzed. Information of the embryo, including maternal age, paternal age, day of the biopsy, embryo quality (excellent, good, fair, poor), blastocoele expansion (2-6), ICM score (A, B, C), TE score (A, B, C), and PGT-A result (euploid, aneuploidy or else) was collected and analyzed along with the type of culture. Simple and multiple regression analyses using generalized linear mixed model were applied to evaluate the relation between embryo ploidy status as the dependent variable and independent factors. Results: The rates of euploid, aneuploidy and other results of embryos cultured individually were 39.4%, 37.2%, and 23.4%, respectively. These results did not yield a significant difference compared with the cultured group. There was no relationship between culture strategies and the aneuploidy rate of the embryos (OR = 1.16, CI 0.64-2.13). However, biopsy days 6-7 and decreasing grade of TE might be related factors for a higher rate of aneuploidy. Conclusion: Culture embryos individually or in groups hadnot yet shown any effect on embryo’s ploidy status.

Retention of Study Partners in Longitudinal Studies of Alzheimer Disease

AbstractBackgroundAlzheimer Disease Research Centers (ADRCs) require study partners (SPs) for all participants. SPs accompany participants to study visits, ensure protocol compliance and serve as informants for outcomes and adverse event reporting. Their attitudes and beliefs may therefore affect longitudinal data collection and retention for AD studies. However, little research has examined barriers and facilitators to SP participation in longitudinal AD investigations.ObjectiveA random sample of study partners (N = 212) of participants who had no or mild symptoms (global Clinical Dementia Rating [CDR]≤1) at four ADRCs were surveyed to examine facilitators and barriers to continued participation in AD studies.MethodsReasons for participation were analyzed with factor analysis and regression analysis. Effects of complaints and goal fulfillment on attendance were estimated with fractional logistic models.ResultsStudy partners most often participated in ADRC research for personal benefit and altruism. A majority of study partners rated ADRC participation as positive and meeting their goals. Although half reported at least one complaint, few regretted participating. When the participants had a CDR&gt;0, spouse study partners (p&lt;.01) and sibling study partners (p&lt;.01) were more likely to emphasize personal benefits than were children of participants (p&lt;.01) Spousal caregivers of participants with CDR&gt;0, cited personal benefit as their primary motivation to participate while adult children of cognitively normal participants (CDR = 0) cited personal benefit. Respondents whose personal goals were met had fewer complaints and were more likely to have perfect attendance. More feedback about test results and study findings and better management of study visits were the most common recommendations.ConclusionStudy partners are motivated by both personal and altruistic goals. The salience of each goal depends on study partner type and the participant’s cognitive status. Fulfilling these goals may improve retention and reduce study partner complaints.

Safety and Efficacy of Mitapivat in Adult Patients with Erythrocyte Membranopathies (SATISFY)

Background: Membranopathies encompass hemolytic disorders arising from genetic defects in erythrocyte membrane proteins and include hereditary spherocytosis and stomatocytosis. Congenital dyserythropoietic anemia type II (CDA II) is associated with SEC23B gene variants and its phenotype may be similar to hereditary spherocytosis. Anemia with or without the need for chronic transfusion, jaundice, splenomegaly, iron overload are complications common in both hereditary membranopathies and CDA II. Current treatment options for membranopathies and CDA II 1, apart from splenectomy, are primarily supportive. Mitapivat, an investigational pyruvate kinase-R (PKR) activator, has demonstrated efficacy in improving anemia and reducing hemolysis in adult patients with PK deficiency, thalassemia, sickle cell disease, and a mouse model of hereditary spherocytosis. Study Design and Methods: This study (NCT05935202) is an investigator initiated, prospective, multicenter, single-arm phase 2 trial. The study will be conducted in the European Union in Denmark and The Netherlands. It is the first clinical study in the context of the European Reference Network EuroBloodNet and will be sponsored by its closely associated non-for-profit EuroBloodNet Association. A sibling study in Toronto, Canada will be registered separately, and data will be pooled in a prespecified statistical analysis plan. The study will include approximately twenty-five adult patients (aged 18 years and older) diagnosed with a membranopathy or CDA II. Diagnosis must be confirmed genetically. Average hemoglobin concentration (Hb) must be less than 13.0 g/dL for males and 11.0 g/dL for females. Patients with average Hb &amp;gt;10.0 g/dL for males and females at screening must meet at least one of the following additional criteria: Splenomegaly, fatigue attributed to hemolysis, or paraclinical hemolysis. Adequate organ function is required. Patients cannot be included if they have a diagnosis of PK deficiency or if they have received red blood cell (RBC) transfusions (≥5 units the last 12 months or any within the last 3 months). During the 8-week Dose Escalation Period, subjects will receive an initial dose of 50 mg mitapivat twice daily (BID). Based on safety and changes in Hb levels, dosing may be increased to 100 mg BID at week 4. Patients who tolerate mitapivat may be eligible to continue in two consecutive 24-week Fixed Dose Periods, with an interim analysis in between the two fixed dose periods. The primary objective of this study is to evaluate the safety of mitapivat, assessed through the occurrence of treatment-emergent adverse events. Secondary objectives include assessing the effects of mitapivat on Hb concentration (≥1.0 g/dL increase sustained at two scheduled visits), hemolysis, erythropoiesis, patient-reported outcome measures, and spleen size. Exploratory endpoints include enzyme activity and stability of PK, Hb oxygen affinity, proteomics and metabolomics. To assess how activation of PK will impact RBC function we will measure RBC deformability (osmotic gradient ektacytometry and cell membrane stability) in whole blood and in different RBC subpopulations. Acknowledgement: This project is carried out within the framework of European Reference Network on Rare Haematological Diseases (ERN-EuroBloodNet)-Project ID No 101085717. ERN-EuroBloodNet is partly co-funded by the European Union within the framework of the Fourth EU Health Programme. The study is funded by a grant from Agios Pharmaceuticals.

Comorbidities in women with polycystic ovary syndrome: a sibling study

Abstract Background Polycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors. Methods This total-population register-based cohort study included 857,757 singleton females (333,999 with at least one full sister) born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjectś early-life and social characteristics. In the main analysis, sibling fixed effects (FE) models were used to control for all factors that are shared and time-invariant among sisters, thereby testing whether PCOS and examined comorbidities are determined by unobserved familial; environmental, social or genetic factors. Results 9,321 women were diagnosed with PCOS, of whom 15% had obesity, 9% had depression, 8% had anxiety and 4% suffered from sleeping, sexual and eating disorders (SSE). Having PCOS was associated with the odds of obesity increasing nearly 6-fold (adjusted OR (aOR): 5.8 [95%CI:5.5-6.2]). This association was attenuated considerably when accounting for characteristics shared between full sisters (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). Among the psychiatric comorbidities, depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when also controlling for factors shared between sisters. Conclusions Having been diagnosed with PCOS is associated with an increased risk of obesity and psychiatric comorbidities and a substantial part of this risk can be attributed to factors shared between sisters. Key messages • PCOS is associated with an increased risk of obesity, depression and anxiety. • Among women with PCOS, 16% of the increased risk for obesity, 20% for depression and 29% for anxiety can be attributed to shared family factors between sisters.