Vanishing twins, spared cohorts, and the birthweight of periviable infants born to Black and white women in the United States.

Pregnancies ending before 26 weeks contribute 1% of births but 40% of infant deaths in the United States. The rate of these "periviable" births to non-Hispanic (NH) Black women exceeds four times that for NH whites. Small male periviable infants remain most likely to die. NH white periviable males weigh more than their NH Black counterparts. We argue that male infants born from twin gestations, in which one fetus died in utero (i.e., the vanishing twin syndrome), contribute to the disparity. We cannot directly test our argument because "vanishing" typically occurs before clinical recognition of pregnancy. We, however, describe and find associations that would emerge in vital statistics were our argument correct. Among male periviable singleton births from 288 monthly conception cohorts (January 1995 through December 2018), we found an average NH white advantage of 30 grams (759 grams versus 729 grams). Consistent with our argument, however, cohorts signaling relatively few survivors of the vanishing twin syndrome showed no disparity.

A twin-driven analysis on early aging biomarkers and associations with sitting-time and physical activity.

BACKGROUND: Current physical activity guidelines may be insufficient to address health consequences in a world increasing in sedentary behavior. Physical activity is a key lifestyle factor to promote healthy aging, but few studies examine activity in conjunction with sitting. We examine how activity intensity and sitting behavior influence health and the extent to which physical activity might counter sitting. METHODS: We analyzed data from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife) in adults aged 28-49 years (M = 33.16, SD = 4.93). We fit a linear mixed-effect model for body mass index (BMI) and total cholesterol/high-density lipoprotein ratio (TC/HDL). Leveraging the co-twin control approach, we explore the trade-off between sitting and physical activity. RESULTS: Across established adulthood, TC/HDL and BMI demonstrated increasing age trends with prolonged sitting and vigorous activity inversely associated. Moreover, after considering sitting time, we found an age-equivalent benefit of vigorous exercise where those performing 30 minutes daily had expected TC/HDL and BMI estimates that mirrored sedentary individuals 5 and 10 years younger, respectively. Co-twin control analysis suggests partial exposure effects for TC/HDL, indicating greater vigorous activity may counter sitting-health effects but with diminishing returns. CONCLUSIONS: Our findings support the counteracting influence of prolonged sitting and physical activity on indicators of cardiovascular and metabolic health. A compensating role of vigorous activity on sitting health links is indicated while reducing sitting time appears paramount. Public health initiatives should consider sitting and vigorous activity in tandem in guidelines to promote health maintenance and combat accelerated aging.

Calculating Within-Pair Difference Scores in the Co-twin Control Design. Effects of Alternative Strategies.

Co-twin studies are an elegant and powerful design that allows controlling for the effect of confounding variables, including genetic and a range of environmental factors. There are several approaches to carry out this design. One of the methods commonly used, when contrasting continuous variables, is to calculate difference scores between members of a twin pair on two associated variables, in order to analyse the covariation of such differences. However, information regarding whether and how the different ways of estimating within-pair difference scores may impact the results is scant. This study aimed to compare the results obtained by different methods of data transformation when performing a co-twin study and test how the magnitude of the association changes using each of those approaches. Data was simulated using a direction of causation model and by fixing the effect size of causal path to low, medium, and high values. Within-pair difference scores were calculated as relative scores for diverse within-pair ordering conditions or absolute scores. Pearson's correlations using relative difference scores vary across the established scenarios (how twins were ordered within pairs) and these discrepancies become larger as the within-twin correlation increases. Absolute difference scores tended to produce the lowest correlation in every condition. Our results show that both using absolute difference scores or ordering twins within pairs, may produce an artificial decrease in the magnitude of the studied association, obscuring the ability to detect patterns compatible with causation, which could lead to discrepancies across studies and erroneous conclusions.

Age at separation, residential mobility, and depressive symptoms among twins in late adolescence and young adulthood: a FinnTwin12 cohort study.

BACKGROUND: Separating with close siblings and leaving the parental home at an early age represents a major life event for an adolescent (reflected by age at separation in a twin pair) and may predispose them to poor mental health. This study aims to examine the association of age at separation and residential mobility on depressive symptoms in late adolescence and young adulthood and to explore possible underlying genetic effects. METHODS: Residential mobility consisted of the number and total distance of moves before age 17. Based on 3071 twins from the FinnTwin12 cohort, we used linear regression to assess the association of age at separation and residential mobility with General Behavior Inventory (GBI) scores at age 17 and in young adulthood. A higher GBI score indicated more depressive symptoms occurred. Then, the mixed model for repeated measures (MMRM) was used to visualize the scores' trajectory and test the associations, controlling for "baseline" state. Twin analyses with a bivariate cross-lagged path model were performed between the difference in GBI scores, between cotwins, and separation status for the potential genetic influence. RESULTS: Compared to twins separated before age 17, twins who separated later had significantly lower GBI scores at age 17 and in young adulthood. In MMRM, separation at a later age and a higher number of moves were associated with a higher GBI score in young adulthood. A small genetic effect was detected wherein GBI within-pair differences at age 17 were associated with separation status before age 22 (coefficient: 0.01). CONCLUSION: The study provides valid evidence about the influence of siblings and family on depressive symptoms in later adolescence and young adulthood while finding some evidence for a reverse direction effect. This suggests more caution in the interpretation of results. A strong association between residential mobility and depressive symptoms was affirmed, although further detailed research is needed.

Mothers of twins had higher old-age survival than mothers of singletons in Estonian 19th-century birth cohorts.

STUDY QUESTION: Do the mothers of twins and singletons differ regarding post-partum and old-age mortality? SUMMARY ANSWER: Twin deliveries were associated with higher post-partum maternal mortality than singleton deliveries, but the lifetime post-partum mortality risk was similar for mothers of twins and singletons; survival of twinners was higher than survival of the mothers of singletons after the 67th lifespan percentile. WHAT IS KNOWN ALREADY: Twinning is typically associated with higher post-partum maternal mortality. The evidence about whether twinning incurs long-term survival costs of reproduction or is a trait pertinent to long-lived women is scarce and contradictory. STUDY DESIGN, SIZE, DURATION: The study is based on the data of the Estonian Family Register (operating from 1926 to 1943) and involves 5565 mothers of twins and 119 613 mothers of singletons born between 1850 and 1899. The subset for comparing maternal lifespans included 1703-1884 mothers of twins and 19 747-36 690 mothers of singletons. PARTICIPANTS/MATERIALS, SETTING, METHODS: Post-partum maternal mortality was analyzed in the whole sample (including mothers of a single child) by logistic regression. Most of the analyses were performed in samples where each mother of twins was matched against mothers of singletons based on parity (or number of deliveries), urban versus rural and inland versus coastal origin, whether their lifespan was known, date of birth and age at first birth. Lifespans were compared in linear mixed models. Quantile regression was used to analyze age-dependent variations in maternal mortality rates. All models were adjusted for relevant biodemographic covariates. MAIN RESULTS AND THE ROLE OF CHANCE: The twinning rate in the whole sample was 4.4%. During the year after giving birth, maternal mortality for twin deliveries was 0.75% (17/2273) and 0.37% (449/122 750) for singleton deliveries (OR = 2.05, 95% CI = 1.21-3.23). However, the lifetime post-partum mortality risk for mothers of twins (0.51%; 28/5557) and singletons (0.37%; 438/119 466) did not differ significantly (OR = 1.38, 95% CI = 0.91-1.98). The life spans of the mothers of twins and singletons did not differ in matched samples. Past the 67th lifespan percentile, the odds of survival were significantly higher for mothers of twins than mothers of singletons, as indicated by non-overlapping 95% confidence intervals. LIMITATIONS, REASONS FOR CAUTION: Relatively low number of individuals (22 802-28 335) with known age at death in matched datasets due to discontinuation of the register after 1943. WIDER IMPLICATIONS OF THE FINDINGS: The finding that mothers of twins had higher odds of old-age survival than mothers of singletons is consistent with the contention that twinners represent a non-random subset of women whose robust phenotypic quality allows them to outlive the mothers of singletons in old age. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Estonian Research Council grants PRG1137, PRG2248, and PSG669. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Literary tastes are as heritable as other human phenotypes: Evidence from twins' library borrowing.

Social science research argues that differences in individuals' literary and cultural tastes originate in social environments. Yet, it might be that these differences are partly associated with genetic differences between individuals. To address this possibility, we use nation-scale registry data on library borrowing among Danish twins (N = 67,900) to assess the heritability of literary tastes. We measure literary tastes via borrowing of books of different genres (e.g., crime and biographical novels) and formats (physical, digital, and audio) and decompose the total variance in literary tastes into components attributable to shared genes (heritability), shared environments (social environment shared by siblings), and unique environments (social environments not shared by siblings). We find that genetic differences account for 45-70 percent of the total variance in literary tastes, shared environments account for almost none of the variance, and unique environments account for a moderate share. These results suggest that literary tastes are approximately as heritable as other human phenotypes (e.g., physical traits, cognition, and health). Moreover, heritability is higher for socioeconomically disadvantaged groups than for advantaged groups. Overall, our results suggest that research should consider the role of genetic differences in accounting for individual differences in literary and broader cultural tastes.

Five years of change in adult twins: longitudinal changes of genetic and environmental influence on epigenetic clocks.

BACKGROUND: Epigenetic clocks were known as promising biomarkers of aging, including original clocks trained by individual CpG sites and principal component (PC) clocks trained by PCs of CpG sites. The effects of genetic and environmental factors on epigenetic clocks are still unclear, especially for PC clocks. METHODS: We constructed univariate twin models in 477 same-sex twin pairs from the Chinese National Twin Registry (CNTR) to estimate the heritability of five epigenetic clocks (GrimAge, PhenoAge, DunedinPACE, PCGrimAge, and PCPhenoAge). Besides, we investigated the longitudinal changes of genetic and environmental influences on epigenetic clocks across 5 years in 134 same-sex twin pairs. RESULTS: Heritability of epigenetic clocks ranged from 0.45 to 0.70, and those for PC clocks were higher than those for original clocks. For five epigenetic clocks, the longitudinal stability was moderate to high and was largely due to genetic effects. The genetic correlations between baseline and follow-up epigenetic clocks were moderate to high. Special unique environmental factors emerged both at baseline and at follow-up. PC clocks showed higher longitudinal stability and unique environmental correlations than original clocks. CONCLUSIONS: For five epigenetic clocks, they have the potential to identify aging interventions. High longitudinal stability is mainly due to genetic factors, and changes of epigenetic clocks over time are primarily due to changes in unique environmental factors. Given the disparities in genetic and environmental factors as well as longitudinal stability between PC and original clocks, the results of studies with original clocks need to be further verified with PC clocks.

Overlapping genetic influences between creativity and borderline personality symptoms in a large Dutch sample.

Creativity and mental disorders are sometimes seen as intertwined, but research is still unclear on whether, how much, and why. Here we explore the potential role of shared genetic factors behind creativity and symptoms of borderline personality disorder (BPD, characterized by mood swings and randomness of thoughts). Data were collected from 6745 twins (2378 complete pairs) by the Netherlands Twin Register on BPD scores (PAI-BOR questionnaire) and working in a creative profession (proxy for creativity). First, we tested whether there is an association between BPD symptoms and creative professions. Results confirmed that individuals scoring higher on the BPD spectrum are more likely to have a creative profession (Cohen's d = 0.16). Next, we modeled how much of this association reflects underlying genetic and/or environmental correlations-by using a bivariate classical twin design. We found that creativity and BPD were each influenced by genetic factors (heritability = 0.45 for BPD and 0.67 for creativity) and that these traits are genetically correlated rG = 0.17. Environmental influences were not correlated. This is evidence for a common genetic mechanism between borderline personality scores and creativity which may reflect causal effects and shed light on mechanisms.

Association between trimester-specific prenatal air pollution exposure and placental weight of twins.

INTRODUCTION: This study investigates the association between maternal exposure to particulate matter (PM10) and nitric dioxide (NO2) during the first, second and third trimester and placental weight and birth weight/placental weight (BW/PW) ratio in twins at birth. METHODS: Cross-sectional data of 3340 twins from the East Flanders Prospective Twin Survey was used. Air pollutant exposure was estimated via spatial temporal interpolation. Univariable and multivariable mixed model analyses with a random intercept to account for the relatedness of newborns were conducted for twins with separate placentas. Twin pairs with one placental mass were studied with linear and logistic regression. RESULTS: In the third trimester, for each 10 µm/m3 increase in PM10 or NO2 placental weight decreased -19.7 g (95%-C.I. -35.1; -4.3) and -17.7 g (95%-C.I. -30.4; -0.5) respectively, in moderate to late preterm twins with separate placentas. Consequently, BW/PW ratio increased with higher air pollution exposure. PM10 exposure in the last week of pregnancy was associated with a higher odds ratio (OR) of 1.20 (95%-C.I. 1.00; 1.44) for a "small for gestational age placenta" (placental weight <10th percentile). Conversely, first trimester air pollutant exposure was associated with lower ORs of 0.55 (95%-C.I. 0.35; 0.88) and 0.60 (95%-C.I. 0.42; 0.84). DISCUSSION: The association of PM10 and NO2 on placental weight is trimester-specific, differs for twins with one versus two placentas and is most pronounced in moderate to late preterm twins. Longitudinal studies are needed to better understand the relationship between air pollutant exposure and placental weight evolution across different trimesters.

The effect of perceived social support on fatigue in mothers having twin infants: the mediating role of sleep quality.

The aim of this study is to investigate the mediating role of sleep quality in the relationship between multidimensional perceived social support and fatigue among mothers of twin infants. One hundred and six (106) twin mothers participated in this cross-sectional study, who completed the Descriptive Information Form, Multidimensional Scale of Perceived Social Support, Pittsburgh Sleep Quality Index, and Checklist Individual Strength. The scale score averages of the mothers in the study are as follows: social support, 61.41 ± 23.86; fatigue, 77.64 ± 28.68; and sleep quality, 8.26 ± 2.38. According to the path model, perceived social support has a negative effect on poor sleep quality (p = .001, Beta = -0.411), and poor sleep quality has a positive effect on fatigue (p = .001, Beta = 0.335). Sleep quality also mediates the effect of multidimensional perceived social support on mothers' fatigue levels (p = .001, Beta = -0.138). The study results suggest that the perceived social support and fatigue levels of twin mothers are moderate, while their sleep quality is poor. Therefore, mothers of twin infants may benefit from increased social support to alleviate fatigue and enhance sleep quality.

Characteristics of unilateral and bilateral bovine twin foetuses.

Twin pregnancy in cattle is undesirable for a number of reasons, including a higher abortion risk compared to pregnancies with a single foetus. Yet, the abortion risk is significantly influenced by the intrauterine location of the foetuses, that is, the abortion risk is several times higher if they are implanted in the same uterine horn (unilateral twin pregnancy) than if they are implanted with one foetus in each uterine horn (bilateral twin pregnancy). The reason for the higher abortion risk in unilateral twin pregnancies is unknown, but it may be related to malnutrition of the outermost foetus due to a limited placental capacity, as is the case for equine twin foetuses. A slaughterhouse study was performed and the foetuses of cattle pregnant with twins were measured. We identified 65 cases of twin pregnancies, of which 35 were unilateral twin pregnancies and 30 were bilateral twin pregnancies. There was no significant difference between the outermost and the more centrally located foetus in unilateral twin pregnancies in terms of body weight and length of the metacarpal diaphysis. Growth retardation of the outermost foetus could therefore not be confirmed as the cause of the higher abortion risk in unilateral bovine twin pregnancies. Four cases of pre-slaughter foetal mortality were identified. In three of these cases, both twins were dead, of equal size and at a comparable level of degradation. In the fourth case, with approximately 40-day-old twin foetuses of equal size, only one of the foetuses showed signs of pre-slaughter death.

Male twinning after the 2008 Obama election: A test of symbolic empowerment.

On November 4, 2008, Barack Obama was elected the first Black President of the United States. His campaign and electoral win served as a symbol of hope for a more just future, fostering an "Obama effect" that appears associated with improved well-being among non-Hispanic (NH) Black communities. Situating the Obama election within the symbolic empowerment framework, we consider the potentially protective role of the Obama election on NH Black fetal death, an important but understudied measure of perinatal health that has stark racial disparities. Using restricted-use natality files from the National Center for Health Statistics, we proxy fetal death using the male twin rate (number of twins per 1000 male live births). Male twins have a relatively high risk of in utero selection that is sensitive to maternal and environmental stressors, making the twin rate an important marker of fetal death. We then estimate interrupted time-series models to assess the relation between the Obama election and male twin rates among NH Black births across monthly conception cohorts (February 2003-October 2008). Greater-than-expected male twin rates signal less susceptibility to fetal loss. Results indicate a 4.5% higher male twin rate among all NH Black cohorts exposed in utero to the Obama election, after accounting for historical and NH white trends (p < 0.005). The greater-than-expected rates concentrated among births conceived in the months preceding Obama's nomination at the Democratic National Convention and Obama's presidential win. These results suggest a salutary perinatal response to election events that likely reduced NH Black fetal loss. They also indicate the possibility that sociopolitical shifts can mitigate persisting NH Black-NH white disparities in perinatal health.

Unveiling the epigenetic impact of vegan vs. omnivorous diets on aging: insights from the Twins Nutrition Study (TwiNS).

BACKGROUND: Geroscience focuses on interventions to mitigate molecular changes associated with aging. Lifestyle modifications, medications, and social factors influence the aging process, yet the complex molecular mechanisms require an in-depth exploration of the epigenetic landscape. The specific epigenetic clock and predictor effects of a vegan diet, compared to an omnivorous diet, remain underexplored despite potential impacts on aging-related outcomes. METHODS: This study examined the impact of an entirely plant-based or healthy omnivorous diet over 8 weeks on blood DNA methylation in paired twins. Various measures of epigenetic age acceleration (PC GrimAge, PC PhenoAge, DunedinPACE) were assessed, along with system-specific effects (Inflammation, Heart, Hormone, Liver, and Metabolic). Methylation surrogates of clinical, metabolite, and protein markers were analyzed to observe diet-specific shifts. RESULTS: Distinct responses were observed, with the vegan cohort exhibiting significant decreases in overall epigenetic age acceleration, aligning with anti-aging effects of plant-based diets. Diet-specific shifts were noted in the analysis of methylation surrogates, demonstrating the influence of diet on complex trait prediction through DNA methylation markers. An epigenome-wide analysis revealed differentially methylated loci specific to each diet, providing insights into the affected pathways. CONCLUSIONS: This study suggests that a short-term vegan diet is associated with epigenetic age benefits and reduced calorie intake. The use of epigenetic biomarker proxies (EBPs) highlights their potential for assessing dietary impacts and facilitating personalized nutrition strategies for healthy aging. Future research should explore the long-term effects of vegan diets on epigenetic health and overall well-being, considering the importance of proper nutrient supplementation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05297825.

Heritability of white matter in twins: A diffusion neuroimaging review.

Diffusion neuroimaging has emerged as an essential non-invasive technique to explore in vivo microstructural characteristics of white matter (WM), whose integrity allows complex behaviors and cognitive abilities. Studying the factors contributing to inter-individual variability in WM microstructure can provide valuable insight into structural and functional differences of brain among individuals. Genetic influence on this variation has been largely investigated in twin studies employing different measures derived from diffusion neuroimaging. In this context, we performed a comprehensive literature search across PubMed, Scopus and Web of Science of original twin studies focused on the heritability of WM. Overall, our results highlighted a consistent heritability of diffusion indices (i.e., fractional anisotropy, mean, axial and radial diffusivity), and network topology among twins. The genetic influence resulted prominent in frontal and occipital regions, in the limbic system, and in commissural fibers. To enhance the understanding of genetic influence on WM microstructure further studies in less heterogeneous experimental settings, encompassing all diffusion indices, are warranted.

A case of a twin surviving to term following the abortion of its co-twin at 9 months in an Arabian mare.

Twin pregnancy in mares is one of the leading causes of abortions. Abortion invariably impacts both fetuses. This report describes an unusual case of a twin surviving to term following the abortion of its co-twin at 9 months in a 7-year-old Egyptian Arabian mare. At the time of abortion at 9 months of gestation, the size of the aborted fetus was equivalent to one of approximately 5 months of age while the age of the live co-twin was 9 months. Both fetuses were males. A skin sample was collected from the aborted fetus and hair samples were collected from the dam, sire and live foal for parentage analysis. The parentage analysis confirmed that both fetuses were by the same dam and sire stallion. The authors suggest several scenarios to explain this condition. This report describes a unique case of a twin surviving to term following the abortion of its co-twin at 9 months in a mare.

Posttraumatic Stress Disorder and Obstructive Sleep Apnea in Twins.

Importance: Obstructive sleep apnea (OSA) is a common condition in older adult (aged >65 years) populations, but more mechanistic research is needed to individualize treatments. Previous evidence has suggested an association between OSA and posttraumatic stress disorder (PTSD) but is limited by possible selection bias. High-quality research on this association with a careful evaluation of possible confounders may yield important mechanistic insight into both conditions and improve treatment efforts. Objective: To investigate the association of current PTSD symptoms and PTSD diagnosis with OSA. Design, Setting, and Participants: This cross-sectional study of twin pairs discordant for PTSD, which allows for adjustment for familial factors, was conducted using in-laboratory polysomnography from March 20, 2017, to June 3, 2019. The study sample comprised male veteran twins recruited from the Vietnam Era Twin Registry. The data analysis was performed between June 11, 2022, and January 30, 2023. Exposure: Symptoms of PTSD in twins who served in the Vietnam War. Diagnosis of PTSD was a secondary exposure. Main Outcomes and Measures: Obstructive sleep apnea was assessed using the apnea-hypopnea index (AHI) (≥4% oxygen saturation criterion as measured by events per hour) with overnight polysomnography. Symptoms of PTSD were assessed using the PTSD Checklist (PCL) and structured clinical interview for PTSD diagnosis. Results: A total of 181 male twins (mean [SD] age, 68.4 [2.0] years) including 66 pairs discordant for PTSD symptoms and 15 pairs discordant for a current PTSD diagnosis were evaluated. In models examining the PCL and OSA within pairs and adjusted for body mass index (BMI) and other sociodemographic, cardiovascular, and psychiatric risk factors (including depression), each 15-point increase in PCL was associated with a 4.6 (95% CI, 0.1-9.1) events-per-hour higher AHI. Current PTSD diagnosis was associated with an adjusted 10.5 (95% CI, 5.7-15.3) events-per-hour higher AHI per sleep-hour. Comparable standardized estimates of the association of PTSD symptoms and BMI with AHI per SD increase (1.9 events per hour; 95% CI, 0.5-3.3 events per hour) were found. Conclusions and Relevance: This cross-sectional study found an association between PTSD and sleep-disordered breathing. The findings have important public health implications and may also enhance understanding of the many factors that potentially affect OSA pathophysiology.

The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1-6. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study7, JAXA CFE study8,9, SpaceX Inspiration4 crew10-12, Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions.

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.

Neonatal respiratory complications in twins at 36-38 weeks of gestation.

BACKGROUND: Twin pregnancies are associated with a high risk of perinatal mortality and morbidity. Late preterm or early term delivery is frequently performed to avoid unexpected fetal death in uncomplicated twin pregnancies. Nonetheless, delivery before full term is associated with neonatal respiratory complications. This study aimed to evaluate perinatal respiratory complications in twins delivered between 36 and 38 weeks of gestation. METHODS: A retrospective cohort study was conducted on twins delivered between 36 and 38 weeks of gestation from January 2008 to June 2020. The primary outcomes were the incidence of composite neonatal respiratory morbidity, which included respiratory distress syndrome, transient tachypnea of the newborn, meconium aspiration syndrome, mechanical ventilation or continuous positive airway pressure according to gestational age at delivery, and chorionicity. The relationship between gestational age at delivery and composite neonatal respiratory morbidity was evaluated using multivariate logistic regression analysis adjusted for potential confounders. RESULTS: This study included 1608 twins (614 monochorionic diamniotic twins, 994 dichorionic diamniotic twins). At 36, 37, and 38 weeks of gestation, the frequencies of composite neonatal respiratory morbidity were 19.4%, 10.7%, and 9.2% in dichorionic diamniotic twins and 13.6%, 8.7%, and 9.4% in monochorionic diamniotic twins, respectively. In dichorionic diamniotic twins, the composite neonatal respiratory morbidity rate was higher for twins delivered at 36 weeks of gestation than for those delivered at 37 weeks. No significant differences between monochorionic diamniotic twins were detected. CONCLUSIONS: In uncomplicated dichorionic diamniotic twin pregnancies, delivery should be considered after 37 weeks of gestation to reduce neonatal respiratory complications.