Discordant Twins Research Articles

Considerations on genetic engineering: regarding the birth of twins subjected to gene edition

In this essay, the bioethical implications of the recent genetic manipulation in human embryos with CRISPR-Cas9 to eliminate the CCR5 gene and the birth of a pair of discordant twin girls are analyzed. The experiment was disseminated via social media. The main bioethical flaws identified include the justification of the model, the informed consent process and the lack of disclosure of evident conflicts of interest. The consequences of the experiment on the life of the twins that were born were not properly evaluated, such as the impact on their autonomy, the alleged benefits to be received and the future risks of harm during their lifetime. Having manipulated the germ cell line, the effects on their future offspring were not considered. This type of actions negatively affects the way society conceives science. Genetic engineering should be reserved to the basic experimental context or as clinical research for the correction of known serious diseases of genetic origin under strict regulatory and bioethical supervision and using a gradualist approach in accordance with the advances of gene editing techniques.

The association between night shift work and breast cancer risk in the Finnish twins cohort

Breast cancer is highly prevalent yet a more complete understanding of the interplay between genes and probable environmental risk factors, such as night work, remains lagging. Using a discordant twin pair design, we examined the association between night shift work and breast cancer risk, controlling for familial confounding. Shift work pattern was prospectively assessed by mailed questionnaires among 5,781 female twins from the Older Finnish Twin Cohort. Over the study period (1990–2018), 407 incident breast cancer cases were recorded using the Finnish Cancer Registry. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for potential confounders. Within-pair co-twin analyses were employed in 57 pairs to account for potential familial confounding. Compared to women who worked days only, women with shift work that included night shifts had a 1.58-fold higher risk of breast cancer (HR = 1.58; 95%CI, 1.16–2.15, highest among the youngest women i.e. born 1950–1957, HR = 2.08; 95%CI, 1.32–3.28), whereas 2-shift workers not including night shifts, did not (HR = 0.84; 95%CI, 0.59–1.21). Women with longer sleep (average sleep duration > 8 h/night) appeared at greatest risk of breast cancer if they worked night shifts (HR = 2.91; 95%CI, 1.55–5.46; Pintx=0.32). Results did not vary by chronotype (Pintx=0.74). Co-twin analyses, though with limited power, suggested that night work may be associated with breast cancer risk independent of early environmental and genetic factors. These results confirm a previously described association between night shift work and breast cancer risk. Genetic influences only partially explain these associations.

Prediction of Monochorionic Diamniotic Twin Pregnancy Outcomes Based on Early Second Trimester Ultrasound

Background: Association between second trimester ultrasound findings and twin pregnancy outcome is still unclear. Study aimed to evaluate the performance of second trimester ultrasound scan in the prediction of monochorionic diamniotic twin pregnancies outcomes. Methods: Prospective-cohort study of all consecutive healthy women with monochorionic twin pregnancies followed-up and delivered in five years was undertaken. During second trimester screening (16–18 weeks) fetal biometry was measured (biparietal diameter–BPD, abdominal circumference–AC, femur length–FL, estimated fetal weight–EFW) and inter-twin discordance noted. Amniotic fluid amount was determined. Pregnancy outcomes were having live-born twins, Apgar sores and birth-weights, pregnancy complications and gestational week of delivery. Results: Receiver operating characteristics (ROC) analysis showed that BPD (p = 0.018), AC (p = 0.019) and FL (p = 0.015) were good predictors of having live-born twins. Regression analysis showed that the most important factors influencing twins’ survival to term were inter-twin AC, BPD and FL differences. Fetal discordance in BPD, AC and FL explained correctly 76.3%, 76.5% and 58% of pregnancy outcomes. If second trimester inter-twin BPD difference was <2.5 mm, AC difference was <17 mm and FL difference was <1.5 mm survival of twins was better, complications were less frequent, delivery mostly occurred closer to term, twins had higher birth-weights and better Apgar scores. Second trimester EFW of twin and its difference as well as the amniotic fluid amount were not associated with examined pregnancy outcomes. Conclusions: Discordant twins’ growth in the second trimester registered by ultrasound reliably implies on adverse monochorionic diamniotic twin pregnancy outcome.

First-trimester biomarkers and ultrasound biometries in relation to growth discordance in monochorionic diamniotic twins

Objective The aim of this study was to investigate the association and predictive value between intertwin discordance in first trimester biometries crown-rump length (CRL) and nuchal translucency (NT), and the first trimester biochemical markers PAPP-A and free β-hCG in relation to birth weight discordance (BWD) ≥25% in monochorionic diamniotic (MCDA) twin pregnancies. Methods First trimester screening information and pregnancy outcome data on MCDA twin pregnancies with delivery from July 2008 to July 2017 were retrieved from the Danish Fetal Medicine Database. CRL discordance was divided into: <10% (reference group) and ≥10%. NT discordance was divided into: <20% (reference group) and ≥20%. The twin pregnancies were classified according to BWD into the following groups: <10% (reference group), 10–24.9%, and ≥25% including cases undergoing umbilical cord occlusion due to selective fetal growth restriction (sFGR). The twin pregnancies with the most severe BWD (BWD ≥25%) were subdivided into three groups including cases with only one growth-restricted (<10th centile) infant defined as sFGR, and cases where both twins were <10th centile. Median multiples of the median (MoM) values of PAPP-A and free ß-hCG were compared with the group with BWD <10% using the Wilcoxon two-sample test. The ability of CRL discordance and NT discordance to predict BWD ≥25% was examined by the area under the receiver operator characteristic (ROC) curve. Results A total of 762 MCDA pregnancies were included. The proportion of pregnancies with CRL discordance ≥10% and NT discordance ≥20% was significantly higher in the group with severe BWD discordance (27.0% vs. 4.7% (p < 0.001) and 40.9% vs. 23.9% (p = 0.001), respectively). When examining the three subgroups of severe BWD, we found a significantly higher percentage of pregnancies with CRL discordance ≥10% in the group where umbilical cord occlusion was performed (52.6% vs. 4.7% in the group with BWD <10% (p < 0.001)) and in the group of BWD ≥25% with sFGR (21.7% vs. 4.7% (p < 0.001)). Additionally, a significantly higher percentage of pregnancies with NT discordance ≥20% was found in the group where umbilical cord occlusion was performed (52.6% vs. 23.9% (p = 0.005)) and in the group with both twins <10th centile (66.7% vs. 23.9% (p = 0.003)). No statistically significant differences were found when comparing levels of PAPP-A and free β-hCG MoMs with the group with BWD <10%. In ROC curves, CRL discordance yielded an AUC for prediction of BWD ≥25% of 0.70 (95% CI 0.63–0.76), and for NT discordance AUC was 0.59 (95% CI 0.52–0.66)). OR for any BWD ≥ 25% was 6.7 (95% CI 3.8–12.0) for pregnancies with a CRL discordance ≥10% compared to pregnancies with a CRL discordance <10%. Conclusions This study shows that a discordance in CRL and NT in MCDA twins are both significantly associated with development of BWD. The most important predictor remains CRL discordance ≥10%, thereby suggesting the unequal growth pattern in many cases with BWD is evident already in the first trimester of the pregnancy. No association was found between first trimester biochemical markers and severe BWD.

Perinatal Outcomes and Neurodevelopment 1 Year after Birth in Discordant Twins According to Chorionicity.

Background and Objectives: This study aimed to compare maternal complications, perinatal outcomes, and neurodevelopment 1 year after the birth between concordant and discordant twins in monochorionic and dichorionic twins. Materials and Methods: This retrospective study included twin pregnancies delivered between 24 + 1 and 38 + 2 weeks of gestation between January 2011 and September 2019. Chorionicity was confirmed by ultrasonography and was categorized into monochorionic and dichorionic. Each was then divided into two groups (concordant and discordant) according to birth weight discordancy. Maternal complications and neonatal outcomes, including neurodevelopmental delays, were compared between the two groups. Results: A total of 298 pairs of twin pregnancies were enrolled, of which 58 (19.26%) women were pregnant with monochorionic diamniotic twins and 240 (80.54%) with dichorionic diamniotic twins. In both monochorionic and dichorionic twins, the discordant twins had a greater incidence of emergency deliveries because of iatrogenic causes than the concordant twins. Among dichorionic twins, discordant twins had lower birth weight rates and higher hospitalization rates and morbidities than concordant twins. Among monochorionic twins, discordant twins had a lower birth weight and higher neonatal mortality than concordant twins. The neonatal size was not a predictor of neurodevelopment in this group. Based on the logistic regression analysis, male sex, respiratory distress syndrome, and bronchopulmonary dysplasia were risk factors for the neurodevelopmental delay; birth weight discordancy was significant only in dichorionic twins. Conclusions: Perinatal outcomes in discordant twins may be poor, and neurodevelopment 1 year after birth was worse in discordant twins than in concordant twins. Discordancy in twins can be a risk factor for neurodevelopmental delay.

Impact of Gestational Diabetes and Hypertension Disorders of Pregnancy on Neonatal Outcomes in Twin Pregnancies Based on Chorionicity.

The objective of this study was to investigate the impact of the co-existence of gestational diabetes (GDM) and hypertension disorders of pregnancy (HDP) on neonatal outcomes in twin pregnancies based on chorionicity. A retrospective study of 1398 women with twin pregnancies was performed between January 2016 and December 2021. The effects of GDM and HDP on neonatal outcomes were assessed by logistic regression models. An additional stratified analysis was conducted to estimate the effects based on chorionicity (monochorionic (MC) and dichorionic (DC)). The incidence of the co-existence of GDM and HDP was 3.8%. The presence of GDM increased the likelihood of HDP only in women with MC twin pregnancies (OR, 2.13; 95% CI 1.08-4.19). After adjustments, co-existence of GDM and HDP was positively associated with gestational age (β, 1.06; 95% CI 0.43-1.69) and birthweight (β, 174.90; 95% CI 8.91-340.89) in MC twin pregnancies, while no associations were found between co-existence of GDM and HDP and neonatal outcomes in DC twin pregnancies. However, HDP was negatively associated with birthweight (β, -156.97; 95% CI (-257.92, -56.02)) and positively associated with small-for-gestational-age (SGA) (OR, 2.03; 95% CI 1.02-4.03) and discordant twins (OR, 2.83; 95% CI 1.78-4.48) in DC twin pregnant women without GDM. Our results suggested that GDM leads to an increased risk of HDP only in MC twin pregnancies, but GDM seemed to attenuate the adverse effects of HDP on perinatal outcomes in both MC and DC twin pregnancies. Further investigation is needed to explain these intriguing findings.

Exocrine Proteins Including Trypsin(ogen) as a Key Biomarker in Type 1 Diabetes.

Proteomic profiling can identify useful biomarkers. Monozygotic (MZ) twins discordant for a condition represent an ideal test population. We aimed to investigate and validate proteomic profiling in twins with type 1 diabetes and in other well-characterized cohorts. A broad, multiplex analysis of 4,068 proteins in serum samples from MZ twins concordant (n = 43) and discordant (n = 27) for type 1 diabetes identified major differences that were subsequently validated by a trypsin(ogen) assay in MZ pairs concordant (n = 39) and discordant (n = 42) for type 1 diabetes, individuals at risk for (n = 195) and with (n = 990) type 1 diabetes, as well as individuals with non-insulin-requiring adult-onset diabetes diagnosed as either autoimmune (n = 96) or type 2 (n = 291). Proteomic analysis identified major differences between exocrine enzyme levels in discordant MZ twin pairs despite a strong correlation between twins, whether concordant or discordant for type 1 diabetes (P < 0.01 for both). In validation experiments, trypsin(ogen) levels were lower in twins with diabetes than in the co-twin without diabetes (P < 0.0001) and healthy control participants (P < 0.0001). In recently diagnosed participants, trypsin(ogen) levels were lower than in control participants across a broad age range. In at-risk relatives, levels <15 ng/mL were associated with an increased risk of progression (uncorrected P = 0.009). Multiple linear regression in recently diagnosed participants showed that trypsin(ogen) levels were associated with insulin dose and diabetic ketoacidosis, while age and BMI were confounders. Type 1 diabetes is associated with altered exocrine function, even before onset. Twin data suggest roles for genetic and nongenetically determined factors. Exocrine/endocrine interactions are important underinvestigated factors in type 1 diabetes.

Genome-wide DNA methylation analysis of discordant monozygotic twins reveals consistent sites of differential methylation associated with congenital heart disease

BackgroundDespite being essentially genetically identical, monozygotic (MZ) twins can be discordant for congenital heart disease (CHD), thus highlighting the importance of in utero environmental factors for CHD pathogenesis. This study aimed to identify the epigenetic variations between discordant MZ twin pairs that are associated with CHD at birth. MethodsCord blood of CHD-discordant MZ twins from the Chongqing Longitudinal Twin Study Cohort was subjected to whole-genome bisulfite sequencing, then validated by MeDIP-qPCR and qRT-PCR. Results379 DMRs mapped to 175 differentially methylated genes (DMGs) were associated with CHD. Functional enrichment analysis identified these DMGs are involved in histone methylation, actin cytoskeleton organization, the regulation of cell differentiation, and adrenergic signaling in cardiomyocytes. Of note, SPESP1 and NOX5 were hypermethylated in CHD, and associated with lower gene expression levels. ConclusionsSpecific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD. Trial registrationChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.

Clinical implications of first trimester crown-rump length discordance in dichorionic twin gestations

First trimester crown-rump length (CRL) discordance (≥10% difference in CRL) in monochorionic twins is associated with adverse perinatal outcomes (APO). However, data are limited on clinical implications of CRL discordance in dichorionic (DC) twins. We therefore aimed to evaluate if first trimester CRL discordance in DC twins is associated with APOs or aneuploidy in either twin. This is a secondary analysis of data from a multicenter retrospective cohort study, evaluating cfDNA performance for common trisomies in patients with twin pregnancies from 12/2011-02/2020. We included live DC pregnancies with CRL measurements between 11-14 weeks gestation. The primary composite APO outcome was defined as any 1 of the following: preterm birth or severe preeclampsia < 34 weeks, birthweight discordance ≥ 20%, birthweight < 10%ile of either twin, or stillbirth >20 weeks in one or both twins. The secondary outcome was the rate of composite aneuploidy (T21, T18, T13) in either twin. Outcomes between twin pairs were compared via chi-squared and t-test as appropriate. Multivariable logistic regression was used to calculate odds ratios and adjust for confounders. Of the 1,110 DC twin gestations meeting inclusion criteria, 156 (14.1%) had discordant CRLs. There were no differences in demographics between twins with and without CRL discordance (Table 1). The mean maternal age for the cohort was 35 and 33% were nulliparous. The rate of APO was higher with discordant CRLs after adjusting for aneuploidy (73.1% vs 60.0%, aOR 1.73, 95% CI 1.18-2.53), driven mostly by birthweight outcomes (Table 2). The overall rate of aneuploidy was 3.9% and twins with discordant CRLs had more than 3-fold increased odds of aneuploidy (9.6% vs 3.2%, OR 3.16, 95% CI 1.66-6.01). CRL discordance in DC twin pregnancies is associated with increased risk for adverse perinatal outcomes and aneuploidy. This data may prove useful in decisions about aneuploidy screening or diagnostic testing, and in the identification of DC pregnancies that require increased surveillance.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Brain morphological alterations associated with vulnerability to psychopathology: a discordant twin 7T MRI study

Brain morphological alterations associated with vulnerability to psychopathology: a discordant twin 7T MRI study

Challenges following Prenatal Diagnosis of Bilateral Renal Agenesis and Spontaneous Therapy of Fetal Renal Replacement, or Transplant by Auto-Amnioinfusion in a Monoamniotic Twin Discordant Twin with Associated Postnatal Diagnosis of Anorectal Malformation

Bilateral renal agenesis (BRA) is often diagnosed on prenatal diagnosis by ultrasound because it leads to an oligohydramnios. When both kidneys are absent this condition is not compatible with life. 40% of babies with bilateral renal agenesis will be stillborn, and if born alive, the baby will live only a few hours.

Abnormal umbilical cord insertion and birth weight discordancy in monochorionic diamniotic twins: A retrospective study

To investigate the relationship between abnormal umbilical cord insertion and birthweight discordance in monochorionic diamnionic (MCDA) twins. A total of 137 pairs of MCDAs were retrospectively analyzed who delivered and survived in Hangzhou Women's Hospital from January 2016 to December 2021. According to different insertion methods, they were divided into normal cord insertion group (n = 57), marginal cord insertion (MCI) group (n = 34) and velamentous cord insertion (VCI) group (n = 46). The correlation was analyzed between different insertion methods of umbilical cord and the discordant birth weight of MCDAs. The gestational age of delivery with velamentous cord insertion was significantly earlier than those with normal and marginal insertion (P < .05). There were significant differences in birthweight between large fetus (F1) and small fetus (F2) with different umbilical insertion methods (P < .05). The birthweight of F1 and F2 in normal insertion group was significantly higher than those in MCI and VCI group (P < .05). Logistic regression analysis showed that VCI was significantly associated with birth weight in F1/F2, birthweight discordance ≥ 20%, and birthweight discordance ≥ 25%, however MCI and VCI were not an independent factor for discordance in birthweight of MCDAs (P > .05). Umbilical cord insertion method can lead to inconsistency in birthweight of MCDA twins, however they were not an independent factor for discordance in birthweight.

Epigenome-wide association study of physical activity and physiological parameters in discordant monozygotic twins

An epigenome-wide association study (EWAS) was performed on buccal cells from monozygotic-twins (MZ) reared together as children, but who live apart as adults. Cohorts of twin pairs were used to investigate associations between neighborhood walkability and objectively measured physical activity (PA) levels. Due to dramatic cellular epigenetic sex differences, male and female MZ twin pairs were analyzed separately to identify differential DNA methylation regions (DMRs). A priori comparisons were made on MZ twin pairs discordant on body mass index (BMI), PA levels, and neighborhood walkability. In addition to direct comparative analysis to identify specific DMRs, a weighted genome coexpression network analysis (WGCNA) was performed to identify DNA methylation sites associated with the physiological traits of interest. The pairs discordant in PA levels had epigenetic alterations that correlated with reduced metabolic parameters (i.e., BMI and waist circumference). The DNA methylation sites are associated with over fifty genes previously found to be specific to vigorous PA, metabolic risk factors, and sex. Combined observations demonstrate that behavioral factors, such as physical activity, appear to promote systemic epigenetic alterations that impact metabolic risk factors. The epigenetic DNA methylation sites and associated genes identified provide insight into PA impacts on metabolic parameters and the etiology of obesity.

Age acquired skewed X chromosome inactivation is associated with adverse health outcomes in humans.

Ageing is a heterogenous process characterised by cellular and molecular hallmarks, including changes to haematopoietic stem cells and is a primary risk factor for chronic diseases. X chromosome inactivation (XCI) randomly transcriptionally silences either the maternal or paternal X in each cell of 46, XX females to balance the gene expression with 46, XY males. Age acquired XCI-skew describes the preferential selection of cells across a tissue resulting in an imbalance of XCI, which is particularly prevalent in blood tissues of ageing females, and yet its clinical consequences are unknown. We assayed XCI in 1575 females from the TwinsUK population cohort using DNA extracted from whole blood. We employed prospective, cross-sectional, and intra-twin study designs to characterise the relationship of XCI-skew with molecular and cellular measures of ageing, cardiovascular disease risk, and cancer diagnosis. We demonstrate that XCI-skew is independent of traditional markers of biological ageing and is associated with a haematopoietic bias towards the myeloid lineage. Using an atherosclerotic cardiovascular disease risk score, which captures traditional risk factors, XCI-skew is associated with an increased cardiovascular disease risk both cross-sectionally and within XCI-skew discordant twin pairs. In a prospective 10 year follow-up study, XCI-skew is predictive of future cancer incidence. Our study demonstrates that age acquired XCI-skew captures changes to the haematopoietic stem cell population and has clinical potential as a unique biomarker of chronic disease risk. KSS acknowledges funding from the Medical Research Council [MR/M004422/1 and MR/R023131/1]. JTB acknowledges funding from the ESRC [ES/N000404/1]. MM acknowledges funding from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London.

Fetomaternal Outcome of Patients with Multiple Pregnancy: A Single Centre Experience

Background: Multiple pregnancies are prone to be associated with adverse maternal and perinatal outcome. The incidence of multiple pregnancies has shown a significant increase over the last decades. Aim of the Study: This study aimed to describe the maternal and perinatal outcomes in multiple pregnancies delivered in a tertiary care hospital, Bangladesh. Methods: This was a prospective observational study; 23 patients were enrolled and analyzed. The study conducted with 23 women with twin pregnancies, over 2 year’s months from January 2020 December 2021 in the department of Gynecology and Obstetrics, Chittagong Medical College and Hospital, Chittagong, Bangladesh. Result: Out of 23 cases, 8 patients had intrapartum complications like PPH, mal-presentation, cord prolapse, low-lying placenta, and placental abruption. In this, 4(23.53%) had mal-presentation, and only one had PPH. These intrapartum complications were also categorized according to their chronicity. Mal presentations were seen in 23.53% of DCDA and 33.3% of MCDA with p=0.47. Both were not statistically significant, as shown in Table 4. These twin-specific complications were noted according to their chronicity. Discordant twin was seen in 11.76% of DCDA and 16.67% MCDA. Single IUD in 7.9% of DCDA. The complications and outcomes of the study population; more than 65% of patients needed NICU. In our study, we noted 4 perinatal death caused by intrauterine death, twin-to-twin transfusion syndrome, birth asphyxia, and respiratory distress. Conclusion: Majority of the multiple pregnancy is high risk one. So, all multiple pregnancies need early diagnosis, adequate antenatal, intra-natal and post-partum care to improve the outcome and should have mandatory hospital delivery.

Discordance in twins: Association versus prediction.

Weight discordance is among the major determinants of perinatal outcome in twin pregnancies. Weight discordance can occur in each trimester of pregnancy, though the clinical meaning of such finding and the association with adverse perinatal outcome can vary according to the gestational age (GA) at detection of growth discrepancy. Discrepancy in fetal size in the first trimester of pregnancy is associated with an increased risk of anomalies, aneuploidy, and fetal loss, though the predictive accuracy of using discordance to predict perinatal outcome is low. Conversely, discordance in the third trimester of pregnancy can be associated with fetal growth restriction, perinatal mortality, and morbidity. In view of these associations, twin pregnancies should be monitored for the occurrence of growth discrepancy. The present review aims to provide an up-to-date critical appraisal of the diagnosis and clinical management of twin pregnancies complicated by growth discordance according to the trimester at presentation.

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.

Life events as predictors of unsustainable working life trajectories from a life course perspective

Abstract Background The association between family-related life events (e.g., getting married or having children) and unsustainable working life in terms of unemployment, sickness absence and disability pension (SA/DP) are rarely studied from a life-course perspective although having public health importance. We investigated trajectories of unsustainable working life, and the associations between change in family-related life events and unsustainable working life trajectories by controlling for familial factors. Methods This is a prospective cohort study of 37,867 Swedish twins aged between 20-40 years on 31st December 1994. Data on trajectories of annual unemployment, SA/DP, and a combined measure of unsustainable working life months was collected from the Swedish national registers. The trajectories over a 23-year period were analysed by group-based trajectory modelling. Associations of change in family-related life events with trajectory groups in the whole sample were estimated by multinomial logistic regression and in discordant twin pairs (n = 4,647 pairs) with conditional models. Results Most participants had no or low levels of unemployment, SA/DP or combined unsustainable working life during 1994-2016. Individuals who were stably married or changed from being single living without children to married living with children had a decreased risk of unsustainable working life compared to individuals with stable family-related life events. The risk of unsustainable working life months over time was higher among individuals who changed from married to single status regardless of having children (range of HRs:1.31-4.44). Conclusions Family-related life events such as maintaining the relationship or getting married and having children decreases the risk of unsustainable working life while divorce is a risk factor for unsustainable working life. From a public health perspective, actions to support family formation or life would consequently promote a sustainable working life. Key messages • Unsustainable working life was less likely among married and among those who changed from single living without children to married with children compared to those with stable family life events. • Individuals who changed from being married to divorced status had an increased risk of unsustainable working life over time and therefore being potentially an important group for public health.

RNA SEQUENCING IDENTIFIESHOXB9ANDE2F1TRANSCRIPTIONAL DIFFERENCES IN IDENTICAL TWINS WITH DIFFERENT REPRODUCTIVE CAPACITIES

To assess genetic differences between azoospermia and oligospermia, we performed miRNA expression profiling in the peripheral blood of monozygotic discordant twins. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnosis and treatment prognosis of men with infertility.

Insecure attachment and internalizing behavior problems in growth discordant identical twins

BackgroundPsychosocial development in monochorionic (MC) twins born after selective fetal growth restriction (sFGR) has been unreported to date, despite its importance for daily functioning and future relationships. AimsTo investigate psychosocial development, attachment and school functioning in MC twins with sFGR and compare outcomes with the general population and between smaller and larger twins. Study designObservational cohort study. SubjectsMC twins with sFGR (defined as a birth weight discordance ≥20 %) born between 2002 and 2017 and aged 3–17 years. Outcome measuresMultiple parent report questionnaires: the Child Behavior Checklist (social-emotional development and behavior), the (Early) Childhood Behavior Questionnaire Very Short Form (temperament), the Attachment Insecurity Screening Inventory (attachment) and a school functioning questionnaire. ResultsMedian age for the 48 twin pairs was 11 (interquartile range (IQR) 8–13) years. Attachment insecurity for both twins was higher than in the general population for ambivalence/resistance (34 % (21/62) vs. 16 %, p = 0.024) and total attachment insecurity (35 % (22/62) vs. 16 %, p = 0.016). Smaller twins had more internalizing behavioral problems, i.e. negative emotions and behaviors turned inwards (22 % (10/46) vs. 11 % (5/46), p = 0.021) and a higher negative affect, i.e. more likely to experience negative emotions (3.2 (2.9–3.7) vs. 2.9 (2.2–3.2), p = 0.009) than larger twins, as well as a lower secondary school level (p = 0.031). ConclusionMC twins with sFGR have more ambivalent/resistant attachment insecurity following the complicated pregnancy course. Smaller twins have a tendency towards negative emotions and internalizing behaviors compared to larger twins, indicating an increased sensitivity for depression and anxiety.