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Accurate placenta pathology assessment is essential for managing maternal and newborn health, but the placenta’s heterogeneity and temporal variability pose challenges for histology analysis. To address this issue, we developed the ‘Histology Analysis Pipeline.PY’ (HAPPY), a deep learning hierarchical method for quantifying the variability of cells and micro-anatomical tissue structures across placenta histology whole slide images. HAPPY differs from patch-based features or segmentation approaches by following an interpretable biological hierarchy, representing cells and cellular communities within tissues at a single-cell resolution across whole slide images. We present a set of quantitative metrics from healthy term placentas as a baseline for future assessments of placenta health and we show how these metrics deviate in placentas with clinically significant placental infarction. HAPPY’s cell and tissue predictions closely replicate those from independent clinical experts and placental biology literature.

Measures of biological age (BA) integrate information across organ systems to quantify “biological aging,” i.e., inter-individual differences in aging-related health decline. While longevity and lifespan aggregate in families, reflecting transmission of genes and environments across generations, little is known about intergenerational continuity of biological aging or the extent to which this continuity may be modified by environmental factors. Using data from the Jerusalem Perinatal Study (JPS), we tested if differences in offspring BA were related to mortality in their parents. We measured BA using biomarker data collected from 1473 offspring during clinical exams in 2007–2009, at age 32 ± 1.1. Parental mortality was obtained from population registry data for the years 2004–2016. We fitted parametric survival models to investigate the associations between offspring BA and parental all-cause and cause-specific mortality. We explored potential differences in these relationships by socioeconomic position (SEP) and offspring sex. Participants’ BAs widely varied (SD = 6.95). Among those measured to be biologically older, parents had increased all-cause mortality (HR = 1.10, 95% CI: 1.08, 1.13), diabetes mortality (HR = 1.19, 95% CI: 1.08, 1.30), and cancer mortality (HR = 1.07, 95% CI: 1.02, 1.13). The association with all-cause mortality was stronger for families with low compared with high SEP (P(interaction) = 0.04) and for daughters as compared to sons (P(interaction)

It is of great interest to identify parent-of-origin effects (POEs) since POEs play an important role in many human heritable disorders and human early life growth and development. POE is sometimes referred to as imprinting effect in the literature. Compared with the standard logistic regression analyses, retrospective likelihood-based statistical methods are more powerful in identifying POEs when data are collected from related individuals retrospectively. However, none of existing retrospective-based methods can appropriately incorporate covariates that should be adjusted for if they are confounding factors. In this paper, a novel semiparametric statistical method, M-HAP, is developed to detect POEs by fully exploring available information from multilocus genotypes of case-control mother-child pairs and covariates. Some large sample properties are established for M-HAP. Finite sample properties of M-HAP are illustrated by extensive simulation studies and real data applications to the Jerusalem Perinatal Study and the Danish National Birth Cohort study, which confirm the desired superiority of M-HAP over some existing methods. M-HAP has been implemented in the updated R package CCMO.

Among the challenges presented by the SARS-CoV2 pandemic are those related to balancing societal priorities with averting threats to population health. In this exceptional context a group of Israeli physicians and public health scholars (multidisciplinary academic group on children and coronavirus [MACC]) coalesced, examining the role of children in viral transmission and assessing the necessity and consequences of restricted in-class education. Combining critical appraisal and analytical skills with public health experience, MACC advocated for safe and monitored school re-opening, stressing the importance of education as a determinant of health, continuously weighing this stance against evolving COVID-19-risk data. MACC’s activities included offering research-based advice to government agencies including Ministries of Health, Finance, and Education. In a setting where government bodies were faced with providing practical solutions to both decreasing disease transmission and maintaining society’s vital activities, and various advisors presented decision-makers with disparate views, MACC contributed epidemiological, clinical and health policy expertise to the debate regarding school closure as a pandemic control measure, and adaptations required for safe re-opening. In this paper, we describe the evolution, activities, policy inputs and media profile of MACC, and discuss the role of academics in advocacy and activism in the midst of an unprecedented public health crisis. A general lesson learned is that academics, based on the rigor of their scientific work and their perceived objectivity, can and should be mobilized to pursue and promote policies based on shared societal values as well as empiric data, even when considerable uncertainty exists about the appropriate course of action. Mechanisms should be in place to open channels to multidisciplinary academic groups and bring their input to bear on decision-making.

OBJECTIVE Israel is one of the first countries to incorporate chromosomal microarray analysis into routine prenatal care. We explored attitudes of Israeli healthcare professionals (HCPs) towards the disclosure of challenging findings: variants of uncertain clinical significance (VUS), susceptibility loci (SL) for neurodevelopmental disorders and variants associated with adult-onset (AO) conditions. Particularly, we sought their views on providing parental choice regarding the disclosure of these findings. METHODS Twenty-nine in-depth interviews were conducted with genetic counselors (n = 19), medical geneticists (n = 4), medical geneticists that are trained in and practice fetal medicine (n = 3), and fetal medicine experts (n = 3). RESULTS Most participants (n = 24) supported parental choice regarding uncertain genetic information. Engaging parents in disclosure decisions allows avoidance from potentially anxiety-provoking information, practicing parental autonomy, and better preparation in cases where uncertain findings are identified. HCPs believed that given appropriate preparation, parents can make informed decisions. Four participants believed that disclosure should be based on professional judgment and one supported full-disclosure. Unlike VUS or SL, all interviewees agreed that in cases of medically actionable AO conditions, the benefit of disclosure outweighs the damage. CONCLUSION HCPs attitudes are largely in-line with the Israeli practice of involving parents in disclosure decisions regarding uncertain information. This may mitigate disclosure dilemmas and allow personalized disclosure based on parents' views.

BACKGROUND According to the hypothesis of Gluckman and Hanson, mismatch between the developmental and postdevelopmental environments may lead to detrimental health impacts such as obesity. While several animal studies support the mismatch theory, there is a scarcity of evidence from human-based studies. OBJECTIVES Our study aims to examine whether a mismatch between the developmental and young-adult environments affect obesity in young adults of the Jerusalem Perinatal Family Follow-Up Study. METHODS Data from The Jerusalem Perinatal Family Follow-Up Study birth cohort was used to characterize early and late environments using offspring and parental sociodemographic and lifestyle information at birth, age 32 (n = 1140) and 42 (n = 404). Scores characterizing the early and late environments were constructed using factor analysis. To assess associations of mismatch with obesity, regression models were fitted using the first factor of each environment and adiposity measures at age 32 and 42. RESULTS Having a stable non-beneficial environment at birth and young-adulthood was most strongly associated with increased adiposity, while a stable beneficial environment was most favorable. The transition from a beneficial environment at birth to a less beneficial environment at young-adulthood was associated with higher obesity measures, including higher BMI (β = 0.979; 95% CI: 0.029, 1.929), waist circumference (β = 2.729; 95% CI: 0.317, 5.140) and waist-hip ratio (β = 0.017; 95% CI: 0.004, 0.029) compared with those experiencing a beneficial environment at both time points. Transition from a less beneficial environment at birth to a beneficial environment at adulthood was also associated with higher obesity measurements (BMI -β = 1.116; 95% CI: 0.085, 2.148; waist circumference -β = 2.736; 95% CI: 0.215, 5.256). CONCLUSIONS This study provides some support for the mismatch hypothesis. While there is indication that an accumulation of the effects of the non-beneficial environment has the strongest detrimental impact on obesity outcomes, our results also indicate that a mismatch between the developmental and later environments may result in maladaptation of the individual leading to obesity.

Advanced prenatal genomic technologies can identify risks for adult-onset (AO) conditions in the fetus, challenging the traditional purpose of prenatal testing. Professional guidelines commonly support disclosure of high-penetrance AO actionable conditions, yet attitudes of women/parents to these findings and factors affecting their attitudes are understudied.We explored 941 (77% response rate) postpartum women's attitudes towards receiving prenatal genetic information, and associations of sociodemographic, medical and psychological characteristics with their choices, focusing on AO conditions.Women largely support the disclosure of actionable AO findings (58.4%), in line with professional guidelines. A third of the women also supported the disclosure of non-actionable AO conditions. Stronger religious observance (p 0.001) and higher psychological distress (p = 0.024) were associated with decreased interest in receiving actionable AO conditions, whereas higher concern for fetal health yielded increased interest (p = 0.032). Attitudes towards disclosure were strongly associated with women's perceived benefit of such information for their own, partner's, and future child's health. Termination of pregnancy based on such information received very little support.In-light of the demonstrated understanding of nuanced genetic information and the observed diversity in attitudes, a culturally competent opt-in/out policy could be considered. If full-disclosure is practiced, support should be provided to those expressing higher levels of distress.

To investigate the effect of birth weight (BW) and maternal pre-pregnancy BMI (mBMI) on blood pressure (BP) in adolescence. A Population-based cohort of 11,729 births in Jerusalem during 1974–1976, with archival data on maternal and birth characteristics was performed. Measurements at age 17 were assessed and linear regression models were used to evaluate the associations of birth characteristics with BP outcomes. BW was inversely associated with both systolic (SBP) and diastolic (DBP) BP at age 17 (SBP: B = − 0.829, p = 0.002; DBP: B = − 0.397, p = 0.033). The interaction term between BW and weight at age 17 was significant for DBP (p = 0.017) and pulse pressure (p = 0.005). mBMI yielded significant positive associations with BP, independent of BW. Our findings indicate that there are at least two distinct pathways linking early life characteristics with subsequent BP: Intrauterine growth, as reflected by BW and other genetic or environmental factors, reflected by mBMI and maternal education, contribute to offspring adolescent BP. These results warrant replication in other birth cohorts and underline the need to explore specific mechanisms that account for these associations.

To identify factors responsible for variation in health among married individuals, we investigated the independent associations of gaps in spousal age and education (or "heterogamy") with all-cause and cause-specific mortality as well as with survival of cancer patients.Using over four decades of follow-up data on 36,717 couples from Jerusalem (1964-2016), we compared heterogamous with homogamous couples.Having a less educated spouse was associated with an increased risk for several outcomes in both genders, such as all-cause mortality in males (hazard ratio [HR] = 1.18, 95% confidence interval [CI]: 1.12, 1.25) and in females (HR = 1.11, CI: 1.01, 1.22). Having a more educated spouse was associated with decreased all-cause mortality in males (HR = 0.93, CI: 0.87, 0.99), but not in females. Having an older spouse was detrimental for health of both genders. For example, increased all-cause mortality was seen in men (HR = 1.22, CI: 1.10, 1.34) and in women (HR = 1.10, CI: 1.02, 1.19). A younger spouse was beneficial for some of the outcomes in males, such as decreased cancer-specific mortality (HR = 0.88, CI: 0.78, 0.99), but not in females.Spousal gaps in education and age may be independently associated with health outcomes. The observed relationships may be driven by combined amounts of marital strain as well as shared spousal resources (such as knowledge or income) depending on gender.

BackgroundGait speed, a central marker of aging, has been linked to various health outcomes, such as cognitive and physical functions in middle-aged adults. Although long-term systemic low-grade inflammation is considered a mechanism underlying a variety of aging-related risk factors, the longitudinal associations between inflammation markers and gait speed are yet to be fully investigated.ObjectiveTo explore the associations of CRP and fibrinogen levels, measured two decades ago, with gait speed among community dwelling adults, considering the contribution of cardio-metabolic factors and cognition.MethodsStudy participants took part in two phases of the of the “Kibbutzim Family Study” (i.e., Phase II, 1999–2000 and Phase III, 2017–2019). Blood samples collected in Phase II (baseline) were used to determine level of inflammatory markers. Gait speed was assessed under single-task (ST) and dual-task (DT) conditions in Phase III. Demographic, anthropometric and clinical data were collected in both phases. Linear regression models were used to assess the adjusted associations of inflammation and gait speed.ResultsA total of 373 individuals aged 34–99 (mean 64 ± 13 years) in Phase III were included in the study. Gait speed under ST was negatively associated with baseline levels of fibrinogen (b per standard deviation (SD) = −0.053, p = 0.0007) and CRP (b per SD = −0.043, p = 0.010), after adjusting for baseline and concurrent cardiometabolic risk factors. Accounting for executive functions, associations of fibrinogen with gait under ST were somewhat attenuated, yet associations remained statistically significant (p < 0.05). Associations with CRP were attenuated to the null. In contrast, there were no associations between inflammation markers and gait under DT.ConclusionOur findings demonstrate that in a sample including younger to older adults, higher systemic inflammatory activity was linked with gait 20 years later, beyond age and cardiometabolic health, and to a certain extent, beyond executive functions. Thus, systemic inflammation may serve as an early marker to identify individuals at risk for gait decline.

AIM: This study aims to examine whether early-life factors are associated with adult ovarian reserve, measured by anti-Müllerian hormone (AMH) levels. METHODS: The work is based on the Jerusalem Perinatal Study (JPS), an extensive birth cohort with detailed information on all pregnancies and deliveries in Jerusalem between 1974 and 1976. A subset of individuals participated in a follow-up study that took place between 2007 and 2009 in which they completed questionnaires and were physically examined at mean age of 32. A blood sample was additionally drawn from each participant, and AMH was measured in a sample of 239 women. The associations between each early-life factors, including birth weight, maternal pre-pregnancy weight, gestational weight gain (GWG), socioeconomic position at birth, and parental smoking during pregnancy, were assessed with AMH levels at the age of 32.Multivariable regression models were used to examine the associations with AMH, adjusting for potential confounders at birth and at the age of 32. RESULTS: Low birth weight was significantly associated with lower ovarian reserve reflected by lower levels of AMH at age 32 (range 30–36), independent of other early-life factors and after adjusting for confounders (β = 0.180, p = 0.03). CONCLUSIONS: This prospective study demonstrates the association of birth weight and adult ovarian reserve. Underlying mechanisms are yet to be fully understood.

Objective The purpose of this study was to investigate whether obstetric and perinatal socio-behavioral characteristics at the time of pregnancy predict obesity phenotypes of adult offspring. Methods The Jerusalem Perinatal Study was conducted among 17,003 deliveries during 1974 to 1976. Follow-up studies were conducted during 2007 to 2009 and 2017 to 2019 among 1,440 offspring undergoing examinations. Offspring were classified into four phenotypes according to obesity and metabolic status: metabolically healthy normal weight (MHNW, reference group), unhealthy normal weight, healthy obesity (MHO), and unhealthy obesity (MUO). Regression models were carried out to identify perinatal predictors for risk phenotypes at age 30 to 35 years, emphasizing the differentiation between socio-behavioral and obstetric features. Results A total of 15.7% of participants were classified as MUO, and 5.4% were classified as MHO. Low socioeconomic status was associated with both obesity phenotypes (e.g., odds ratio [OR]MHO/MHNW = 2.98, p Conclusions Perinatal socio-behavioral characteristics are associated with adult obesity phenotypes. The findings point to possible mechanisms underlying the development of obesity in young adults and, thus, contribute toward identifying high-risk groups that would mostly benefit from obesity risk-reduction interventions.

Background Pre- and perinatal events may be associated with an increased risk of inflammatory bowel disease [IBD]. We aimed to investigate the role of pre- and perinatal factors as potential risk factors for the development of IBD in a population with a follow-up of 50 years. Methods We conducted a nested case-control study, reporting IBD incidence among individuals born in 1964–76, for whom pre- and perinatal exposures were reported as part of the Jerusalem Perinatal Study [JPS], by linking them to the database of the epidemiology group of the Israeli IBD Research Nucleus [epi-IIRN], including all IBD patients in Israel since 2005 and their matched controls. Results We identified 2789 individuals within the epi-IIRN cohort who were also included in the JPS cohort [n = 90 079]: 746 IBD patients (405 with Crohn’s disease [CD] and 341 with ulcerative colitis [UC]) and 2043 non-IBD controls. Those with a ‘Non-western’ family origin had decreased odds of developing CD and UC. High socioeconomic status was associated with CD but not UC. Low birth weight [≤2500 g] occurred less frequently in IBD cases compared to controls, especially in UC patients, showing a protective effect. Being the first born was associated with CD, and having older siblings lowered the odds of developing CD, decreasing 7% with each additional sibling. Smoking and breastfeeding data were available for a subset of individuals, but neither was associated with IBD development. Conclusion This population-based study identifies several pre- and perinatal variables as predictors of IBD development. This information may be helpful to facilitate implementation of early diagnosis interventions and family follow-up protocols.

© 2021 American Academy of Sleep Medicine, Study objectives: The stress imposed by the COVID-19 pandemic and ensuing social isolation could adversely affect sleep. As sleep problems may persist and hurt health, it is important to identify which populations have experienced changes in sleeping patterns during the pandemic and their extent. Methods: In Study 1, 3,062 responders from 49 countries accessed the survey website voluntarily between March 26 and April 26, 2020, and 2,562 (84%; age: 45.2 ± 14.5, 68% women) completed the study. In Study 2, 1,022 adult US responders were recruited for pay through Mechanical Turk, and 971 (95%; age 40.4 ± 13.6, 52% women) completed the study. The survey tool included demographics and items adapted from validated sleep questionnaires on sleep duration, quality and timing, and sleeping pills consumption. Results: In Study 1, 58% of the responders were unsatisfied with their sleep. Forty percent of the responders reported a decreased sleep quality vs before COVID-19 crisis. Self-reported sleeping pill consumption increased by 20% (P < .001). Multivariable analysis indicated that female sex, being in quarantine, and 31- to 45-years age group, reduced physical activity and adverse impact on livelihood were independently associated with more severe worsening of sleep quality during the pandemic. The majority of findings were reproduced in the independent cohort of Study 2. Conclusions: Changes imposed due to the pandemic have led to a surge in individuals reporting sleep problems across the globe. The findings raise the need to screen for worsening sleep patterns and use of sleeping aids, especially in more susceptible populations, namely, women and people with insecure livelihoods subjected to social isolation.

Case-control mother–offspring pair design has been widely adopted for studying early-life and women’s pregnancy health. It allows assessment of pre- and perinatal environmental risk factors as well as both maternal and offspring genetic risk factors. Data arising from this design is routinely analyzed using standard prospective logistic regression. Such data has two unique features: the offspring genotypes are not correlated with maternal environmental risk factors given maternal genotypes, and offspring and maternal genotypes are related through mendelian transmission. In this work, built upon a novel regression model relating maternal genotypes to environmental risk factors, we proposed a novel retrospective likelihood method that effectively utilized the two data features to increase statistical efficiency for detecting maternal and offspring genetic effects. The inference procedure was based on a profile likelihood derived using the Lagrange multiplier method, but we replaced the multipliers with their large sample limits to enable highly efficient and computationally stable estimation. We showed that our proposed estimates of odds ratio association parameters are consistent and asymptotically normally distributed and demonstrated the finite sample performance through extensive simulation studies and application to genetic association studies of birth weight and gestational diabetes mellitus.

AIMS/HYPOTHESIS: There are established relationships between adiposity (obesity) and higher dementia risk, faster cognitive decline and associated neural injury. Type 2 diabetes is strongly linked to greater adiposity and has been consistently associated with neural injury and poor cognitive outcomes. However, although obesity is a major cause of type 2 diabetes, there is limited evidence on the association of adiposity with brain atrophy among individuals with type 2 diabetes. METHODS: We examined the association of BMI (a measure of adiposity), and of long-term trajectories of BMI (three empirically identified groups of trajectories—’normal’, ‘overweight’ and ‘obese’—using SAS macro PROC TRAJ), with regional brain volume, in a sample of older individuals (aged 64–84) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline Study (n=198). RESULTS: Using linear regression, we found that greater BMI was associated with smaller volumes of the inferior frontal gyrus (IFG) (r=−0.25, p=0.001) and the middle temporal gyrus (r=−0.19; p=0.010) after adjusting for sociodemographic covariates and total intracranial volume. In addition, there were significant differences between BMI trajectory groups in IFG volume (F=4.34, p=0.014), such that a long-term trajectory of obesity was associated with a smaller volume. Additional adjustment for cardiovascular and diabetes-related potential confounders did not substantively alter the results. There were no associations of adiposity with superior frontal gyrus, middle frontal gyrus or total grey matter volumes. CONCLUSIONS/INTERPRETATION: In older adults with type 2 diabetes, long-term adiposity may have a detrimental impact on volume of brain regions relevant to cognitive functioning. Further studies to identify the underlying mechanisms are warranted.

IntroductionScarce research is available regarding the association between interbirth intervals (IBI) and long-term maternal health outcomes, particularly cardiovascular disease (CVD) mortality. We aimed to assess whether IBIs were associated with all-cause, CVD-related and cancer-related mortality.MethodsWe conducted a cohort study in the setting of the Jerusalem Perinatal Study. Women with at least two consecutive singleton live births in 1964–1976 (N=18 294) were followed through 2016. IBIs were calculated as the interval between women’s first and second cohort birth. We estimated associations between IBIs and mortality using Cox’s proportional hazards models, adjusting for age, parity, maternal education, maternal origin and paternal socioeconomic status. Date of last menstrual period was available for a subset of women. We assessed the interpregnancy interval (IPI) for these women and compared the models using IPI and IBI.ResultsDuring 868 079 years of follow up (median follow-up: 49.0 years), 3337 women died. Women with IBIs ConclusionOur results support the WHO recommendations for IPIs of ≥24 months and add additional evidence regarding long-term CVD mortality.

Objective To examine the choices of women with both high-risk and low-risk pregnancies who are undergoing prenatal chromosomal microarray analysis in a clinical setting regarding three challenging types of findings: variants of uncertain clinical significance, susceptibility loci for neurodevelopmental disorders, and copy number variants associated with risks for adult-onset conditions. We assessed whether women's choices were associated with indications for testing or with one-on-one pretest genetic counseling. Methods In this cross-sectional study, medical records of women who underwent invasive prenatal chromosomal microarray analysis testing (N=1,070) at Hadassah Medical Center between June 2017 and February 2018 were examined for testing indications, choices regarding chromosomal microarray analysis findings, and type of pretest genetic counseling. Multivariable analyses to assess associations with testing indication and prior genetic counseling were carried out using logistic regression models. Results In total, 56% of women (n=593) chose to be informed of all three types of findings and 20% (n=218) chose not to be informed of any of the findings beyond high-penetrance childhood-onset pathogenic findings. Variants of uncertain clinical significance as a single choice was the least-selected finding (2.5%, n=27). Low-risk pregnancies (ie, those with normal biochemical screening and fetal ultrasound examinations) were associated with increased interest in receiving genetic information about adult-onset conditions (adjusted odds ratio [aOR] 1.7; 95% CI 1.18-2.33) and susceptibility loci (aOR 1.5; 95% CI 1.08-2.10). Conclusion Women with both high-risk and low-risk pregnancies were generally more likely to choose to receive additional genetic information, albeit differences in preferences depend on testing indication and type of pretest counseling.

Aim: To investigate the role of maternal gestational weight gain (GWG) and prepregnancy BMI on programming offspring DNA methylation. Methods: Among 589 adult (age = 32) women participants of the Jerusalem Perinatal Study, we quantified DNA methylation in five candidate genes. We used inverse probability-weighting and parametric g-formula to estimate direct effects of maternal prepregnancy BMI and GWG on methylation. Results: Higher maternal GWG, but not prepregnancy BMI, was inversely related to offspring ABCA1 methylation (β = -1.1% per quartile; 95% CI: -2.0, -0.3) after accounting for ancestry, parental and offspring exposures. Total and controlled direct effects were nearly identical suggesting included offspring exposures did not mediate this relationship. Results were robust to sensitivity analyses for missing data and model specification. Conclusion: We find some support for epigenetic programming and highlight strengths and limitations of these methods relative to other prevailing approaches.

Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.

ObjectiveTo study the association between mode of delivery and offspring BMI in late adolescence in a large cohort that predated the obesity epidemic, and assess the role of maternal pre-pregnancy BMI (ppBMI) in this association.Study designWe conducted a historical prospective study in the setting of the Jerusalem Perinatal Study (JPS), a population-based cohort that includes all 17,003 births to residents of West Jerusalem, between 1974 and 1976. Offspring's BMI at age 17 was obtained upon army recruitment and was available for 11,001 of cohort participants. The associations were examined using logistic regressions, adjusting for socio-demographic characteristics and for proxies for indication for C-Section birth. Analyses were then stratified by quartiles of ppBMI.ResultsC-Section was associated with offspring overweight/obesity, with adjusted OR of 1.44 (95%CI:1.14-1.82). Significant interaction of ppBMI with mode of delivery was observed, such that the associations of C-Section with overweight/obesity were limited to the upper quartile of ppBMI (adjusted OR = 1.70, 95%CI:1.18-2.43). Restricting the analyses to singleton first births and excluding pregnancies complicated with toxemia and gestational diabetes yielded similar findings.ConclusionsC-Section was positively associated with being overweight/obese at age 17. Importantly, ppBMI modified this association, with a significant association between C-Section and overweight/obesity evident only among offspring born to mothers in the highest ppBMI quartile. In light of the growing rates of obesity in women of reproductive age, these results should be considered in patient-doctor shared decisions related to selection of mode of delivery, in the absence of a clear medical indication.

Genetic studies in isolated populations have provided increased power for identifying loci associated with complex diseases and traits. We present here the Kibbutzim Family Study (KFS), initiated for investigating environmental and genetic determinants of cardiometabolic traits in extended Israeli families living in communes characterized by long-term social stability and homogeneous environment. Extensive information on cardiometabolic traits, as well as genome-wide genetic data, was collected on 901 individuals, making this study, to the best of our knowledge, the largest of its kind in Israel. We have thoroughly characterized the KFS genetic structure, observing that most participants were of Ashkenazi Jewish (AJ) origin, and confirming a recent severe bottleneck in their recent history (point estimates: effective size ≈450 individuals, 23 generations ago). Focusing on genetic variants enriched in KFS compared with non-Finnish Europeans, we demonstrated that AJ-specific variants are largely involved in cancer-related pathways. Using linear mixed models, we conducted an association study of these enriched variants with 16 cardiometabolic traits. We found 24 variants to be significantly associated with cardiometabolic traits. The strongest association, which we also replicated, was between a variant upstream of the MSRA gene, ≈200-fold enriched in KFS, and weight (P=3.6·10−8). In summary, the KFS is a valuable resource for the study of the population genetics of Israel as well as the genetics of cardiometabolic traits in a homogeneous environment.

Cohort Profile: The Jerusalem Perinatal Family Follow-Up Study Gabriella M. Lawrence, David S. Siscovick, Ronit Calderon-Margalit, Daniel A. Enquobahrie, Einat Granot-Hershkovitz, Susan Harlap, Orly Manor, Vardiella Meiner, Ora Paltiel, Pui-Yan Kwok, Yechiel Friedlander and Hagit Hochner* Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel, New York Academy of Medicine, New York, NY, USA, Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, WA, Departments of Psychiatry and Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA, Department of Human Genetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel, Hematology Department, Hebrew University-Hadassah Medical Center, Jerusalem, Israel, Institute for Human Genetics, Cardiovascular Research Institute and Department of Dermatology, University of California, San Francisco, CA, USA

PURPOSE The aim of this study was to examine the prevalence of urinary incontinence (UI) among parous women of child-bearing age and compare their level of knowledge regarding UI to those women without the condition. METHODS A convenience sample of women aged 20 to 50 years who had given birth at least once completed questionnaires regarding (1) demographic information, (2) knowledge of UI (PIKQ-Prolapse and Incontinence Knowledge Quiz and PIKQ+), and (3) prevalence of UI (ICIQ-UI questionnaire-International Consultation on Incontinence Questionnaire-Urinary Incontinence short form). Women who were pregnant or 3 months or less postpartum were excluded from the analysis of the ICIQ-UI. RESULTS Three hundred twenty-three women, representing 89.7% of those approached, participated in the study. Their mean age was 35.3 ±5.0 years (mean ± SD), all completed the knowledge questionnaire while 260 (80.5%) completed the UI questionnaire. Eighty-three (31.9%) suffered from UI, and most (67.5%) were between 31 and 40 years of age. Participants' level of knowledge about UI was found to be moderate (mean = 7.37 ± 3.6) on the PIKQ+. Knowledge level was correlated with age (P = .017) and with higher levels of education (P < .001). There was a significantly higher level of UI knowledge (PIKQ+ scores) among women with UI (mean = 8.6; SD = 3.01) as compared to those who did not report UI (mean = 7.6; SD =±3.75; P < .001). CONCLUSION Approximately one-third of parous women aged 20 to 50 years reported UI. Knowledge related to the condition tends to be moderate, increasing with higher age and education.

Background Castor oil is a substance used for labor induction in an inpatient setting. However, its efficacy as an agent for the induction of labor, for post-date pregnancies in an outpatient setup is unknown. Objective Efficacy of castor oil as an agent for the induction of labor, for post-date pregnancies in outpatient settings. Methods Eighty-one women with a low-risk post-date singleton pregnancy with a Bishop score ≤ 7, without effective uterine contractions were randomized to the intervention, 60 ml of castor oil, or the control, 60 ml of sun-flower oil. The primary outcome was proportion of women entering the active phase of labor 24, 36, 48 h after ingestion. Secondary outcomes included meconium stained amniotic fluid, abnormal fetal heart rate tracing, cesarean section rate, instrumental deliveries, birth weight, 5 min Apgar score, chorioamnionitis, hypertensive complications, retained placenta, and post-partum hemorrhage. Findings Intervention and control groups included 38 and 43 women, respectively. No differences in baseline characteristics, except for age were noted. The observed interaction between castor oil and parity was significant (p interaction = 0.02). Multiparous women in the intervention group exhibited a significant beneficial effect on entering active labor within 24, 36 and 48 h after castor oil consumption compared with the placebo (Hazard Ratio = 2.93, p = 0.048; Hazard Ratio = 3.29, p = 0.026; Hazard Ratio = 2.78, p = 0.042 respectively). This effect was not noted among primiparous women. No differences in rate of obstetric complications or adverse neonatal outcomes were noted. Conclusion Castor oil is effective for labor induction, in post-date multiparous women in outpatient settings.

ObjectiveTo examine cross-sectional relationships between plasma vitamin D and cardiometabolic risk factors in young adults.DesignData were collected from interviews, physical examinations and biomarker measurements. Total plasma 25-hydroxyvitamin D (25(OH)D) was measured using LC–tandem MS. Associations between 25(OH)D and cardiometabolic risk factors were modelled using weighted linear regression with robust estimates of standard errors.SettingIndividuals born in Jerusalem during 1974–1976.SubjectsParticipants of the Jerusalem Perinatal Study (n 1204) interviewed and examined at age 32 years. Participants were oversampled for low and high birth weight and for maternal pre-pregnancy obesity.ResultsMean total 25(OH)D concentration among participants was 21·7 (sd 8·9) ng/ml. Among males, 25(OH)D was associated with homeostatic model assessment of insulin resistance (natural log-transformed, β=−0·011, P=0·004) after adjustment for BMI. However, these associations were not present among females (P for sex interaction=0·005).ConclusionsWe found evidence for inverse associations of 25(OH)D with markers of insulin resistance among males, but not females, in a healthy, young adult Caucasian population. Prospective studies and studies conducted on other populations investigating sex-specific effects of vitamin D on cardiometabolic risk factors are warranted.

To examine the association of maternal and/or paternal smoking during pregnancy with offspring cardio-metabolic risk (CMR) factors at adolescence and early adulthood, taking into account socio-demographic, medical and lifestyle characteristics of parents and offspring, as well as offspring common genetic variation.We used a population-based cohort of all 17 003 births in Jerusalem during 1974-76, with available archival data on parental and birth characteristics. Measurements at age 17 were assessed at military induction examinations for 11 530 offspring. 1440 offspring from the original 1974-1976 birth cohort were sampled using a stratified sampling approach, and were interviewed and examined at age 32. Parental smoking during pregnancy (i.e. maternal, paternal and any parent) was primarily defined dichotomously (any number of cigarettes smoked daily by mother or father during pregnancy vs. non-smokers). Additionally, smoking was assessed by quantity of cigarettes smoked daily. Linear regression models were used to evaluate the associations of parental smoking during pregnancy with various offspring CMR factors, after controlling for potential confounders and for genetic variation in candidate genes.Prevalence of exposure to parental smoking in-utero (i.e. smoking of any parent) was 53.2% and 48.4% among the 17 years old and 32 years old samples, respectively. At age 17, smoking of at least one parent during pregnancy was significantly associated with weight (B = 1.39), height (B = 0.59), BMI (B = 0.32) and pulse rate (B = -0.78) (p-values 0.001). At age 32, parental smoking, adjusted for covariates, was associated with 2.22 kg higher mean offspring weight, 0.95 cm higher mean offspring height, 0.57 kg/m(2) higher BMI, and 1.46 cm higher waist-circumference (p-values ≤ 0.02). Similar results, reflecting a dose response, were observed when maternal and paternal smokings were assessed by number of cigarettes smoked daily.This prospective study demonstrates a potential long-term adverse effect of parental smoking during pregnancy on offspring health and calls for increasing efforts to promote smoking cessation of both parents before pregnancy.

Objectives Studies demonstrate associations between changes in obesity-related phenotypes and cardiovascular risk. Although maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) may be associated with adult offspring adiposity, no study has examined associations with obesity changes. Associations of mppBMI and GWG with longitudinal change in offspring's BMI (ΔBMI) were examined, and whether associations are explained by offspring genetics was assessed. Methods A birth cohort of 1400 adults, with data at birth, age 17 and 32 years was used. After genotyping offspring, genetic scores, predictive of exposures and outcome were created, and linear regression models with and without scores were fit to examine the associations of mppBMI and GWG with ΔBMI. Results A one SD change in mppBMI and GWG was associated with a 0.83 and a 0.75 kg/m² increase in ΔBMI, respectively. The association between mppBMI and offspring ΔBMI was slightly attenuated (12%) with the addition of genetic scores. In the GWG model, a significant substantial 28.2% decrease in the coefficient was observed. Conclusions This study points to an association between maternal excess weight in pregnancy and offspring BMI change from adolescence to adulthood. Genetic factors may account, in part, for GWG/ΔBMI association. These findings broaden observations that maternal obesity-related phenotypes have long-term consequences for offspring health.

Summary Case-control mother–child pair design represents a unique advantage for dissecting genetic susceptibility of complex traits because it allows the assessment of both maternal and offspring genetic compositions. This design has been widely adopted in studies of obstetric complications and neonatal outcomes. In this work, we developed an efficient statistical method for evaluating joint genetic and environmental effects on a binary phenotype. Using a logistic regression model to describe the relationship between the phenotype and maternal and offspring genetic and environmental risk factors, we developed a semiparametric maximum likelihood method for the estimation of odds ratio association parameters. Our method is novel because it exploits two unique features of the study data for the parameter estimation. First, the correlation between maternal and offspring SNP genotypes can be specified under the assumptions of random mating, Hardy–Weinberg equilibrium, and Mendelian inheritance. Second, environmental exposures are often not affected by offspring genes conditional on maternal genes. Our method yields more efficient estimates compared with the standard prospective method for fitting logistic regression models to case-control data. We demonstrated the performance of our method through extensive simulation studies and the analysis of data from the Jerusalem Perinatal Study.

Background— Accumulating evidence demonstrates that both maternal prepregnancy body mass index (mppBMI) and gestational weight gain (GWG) are associated with adult offspring adiposity. However, whether these maternal attributes are related to other cardiometabolic risk factors in adulthood has not been comprehensively studied. Methods and Results— We used a birth cohort of 1400 young adults born in Jerusalem who had extensive archival data and clinical information at 32 years of age to prospectively examine the associations of mppBMI and GWG with adiposity and related cardiometabolic outcomes. Greater mppBMI, independently of GWG and confounders, was significantly associated with higher offspring BMI, waist circumference, systolic and diastolic blood pressures, insulin, and triglycerides and with lower high-density lipoprotein cholesterol. For example, the effect sizes were translated to nearly 5 kg/m 2 higher mean BMI, 8.4 cm higher waist circumference, 0.13 mmol/L (11.4 mg/dL) higher triglycerides, and 0.10 mmol/L (3.8 mg/dL) lower high-density lipoprotein cholesterol among offspring of mothers within the upper mppBMI quartile (mppBMI >26.4 kg/m 2 ) compared with the lower quartile (mppBMI 2 ). GWG, independently of mppBMI, was positively associated with offspring adiposity; differences of 1.6 kg/m 2 in BMI and 2.4 cm in waist were observed when offspring of mothers in the upper (GWG >14 kg) and lower (GWG Conclusions— Maternal size both before and during pregnancy is associated with cardiometabolic risk factors in young adult offspring. The associations appear to be driven mainly by offspring adiposity. Future studies that explore mechanisms underlying the intergenerational cycle of obesity are warranted to identify potentially novel targets for cardiometabolic risk-reduction interventions.

ObjectivesImmune response to cytomegalovirus (CMV) impacts adult chronic disease. This study investigates associations of childhood and adulthood social environment, socioeconomic position (SEP) and social mobility with CMV response in young adults.DesignHistorical prospective study design.SettingSubcohort of all 17 003 births to residents of Jerusalem between 1974 and 1976.ParticipantsParticipants included 1319 young adults born in Jerusalem with extensive archival and follow-up data, including childhood and adulthood SEP-related factors and anti-CMV IgG titre levels and seroprevalence measured at age 32.Main exposure and outcome measuresPrincipal component analysis was used to transform correlated social environment and SEP-related variables at two time points (childhood and adulthood) into two major scores reflecting household (eg, number of siblings/children, religiosity) and socioeconomic (eg, occupation, education) components. Based on these components, social mobility variables were created. Linear and Poisson regression models were used to investigate associations of components and mobility with anti-CMV IgG titre level and seroprevalence, adjusted for confounders.ResultsLower levels of household and socioeconomic components in either childhood or adulthood were associated with higher anti-CMV IgG titre level and seropositivity at age 32. Compared with individuals with stable favourable components, anti-CMV IgG titre level and risk for seropositivity were higher in stable unfavourable household and socioeconomic components (household: β=3.23, PConclusionsOur study provides evidence that accumulating low SEP from childhood through adulthood and social mobility may compromise immune response in young adulthood.

Purpose To explore the association between birth weight in offspring, a marker of the intrauterine environment, and mortality in their mothers, taking into account maternal pre-pregnancy characteristics, including maternal body mass index (BMI), smoking, and socioeconomic status. Distinguishing the effects of offspring's birth weight and pre-pregnancy characteristics on maternal outcome may provide clues regarding mechanisms underlying the association between birth weight and maternal mortality. Methods We studied long-term total mortality (average follow-up period, 29.1 years) in a population-based cohort of 13,185 mothers, aged 15 to 48 years at their offspring's birth, who delivered in West Jerusalem during 1974 through 1976. Results Univariate and multivariate Cox-proportional hazard models used to estimate the hazard of overall mortality among mothers indicated a nonlinear relationship with birth weight of offspring when introduced into the models as a continuous variable, and a linear positive association with maternal pre-pregnancy BMI. Inclusion of maternal BMI and other pre-pregnancy characteristics in the model did not alter the association between offspring's birth weight and mothers’ all-cause mortality. When birth weight was introduced as a categorical variable, higher mortality was observed among mothers who gave birth to babies with birth weight less than 2500 g (hazard ratio [HR] = 1.90; 95% confidence interval [95%CI], 1.23–2.94) as compared to mothers whose offspring had birth weight between 3000 and 3499 g. The HR for mothers who gave birth to babies with birth weight 4000 g or more was 1.30 (95%CI, 0.88–1.91). Conclusions Independent of pre-pregnancy maternal BMI and other characteristics, birth weight of offspring was associated with mortality in their mothers, suggesting that intrauterine metabolic events reflected by birth weight and not explained by maternal obesity, smoking, and socioeconomic status have remote consequences for maternal health. These findings underline the need to explore specific genetic and/or environmental mechanisms that account for these associations.

Familial cancers may be due to shared genes or environment, or chance aggregation. We explored the possibility that ascertainment bias influences cancer detection in families, bearing upon the time interval between diagnosis of affected mothers and offspring. The Jerusalem Perinatal Study (JPS) comprises all mothers (n = 39,734) from Western Jerusalem who gave birth 1964 –1976 and their offspring (n = 88,829). After linking identification numbers with Israel’s Cancer Registry we measured the absolute time interval between initial cancer diagnoses in affected mother-offspring pairs. We tested the probability of obtaining intervals as short as those observed by chance alone, using a permutation test on the median interval. By June 2003 cancer had developed in 105 mother-offspring pairs within the cohort. Common sites among mothers were breast (47%), colorectal (9%), non-Hodgkin lymphoma (NHL) (8%) and cervix (7%), while for offspring in affected pairs common cancers were leukemia (12.4%), thyroid (13.3%), NHL (10.5%), breast (10.5%) and melanoma (7.6%). The median interval between diagnoses was 5.9 years, but for 33% of affected pairs the interval was ≤3 years. The probability of this occurring by chance alone was 0.03. This held true whether the offspring’s or mother’s diagnosis was first (P

Recent studies suggest that epigenetic programming may mediate the relationship between early life environment, including parental socioeconomic position, and adult cardiometabolic health. However, interpreting associations between early environment and adult DNA methylation may be difficult because of time-dependent confounding by life-course exposures. Among 613 adult women (mean age = 32 years) of the Jerusalem Perinatal Study Family Follow-up (2007–2009), we investigated associations between early life socioeconomic position (paternal occupation and parental education) and mean adult DNA methylation at 5 frequently studied cardiometabolic and stress-response genes ( ABCA1 , INS-IGF2 , LEP , HSD11B2 , and NR3C1 ). We used multivariable linear regression and marginal structural models to estimate associations under 2 causal structures for life-course exposures and timing of methylation measurement. We also examined whether methylation was associated with adult cardiometabolic phenotype. Higher maternal education was consistently associated with higher HSD11B2 methylation (e.g., 0.5%-point higher in 9–12 years vs. ≤8 years, 95% confidence interval: 0.1, 0.8). Higher HSD11B2 methylation was also associated with lower adult weight and total and low-density lipoprotein cholesterol. We found that associations with early life socioeconomic position measures were insensitive to different causal assumption; however, exploratory analysis did not find evidence for a mediating role of methylation in socioeconomic position-cardiometabolic risk associations.

Purpose The study objective was to investigate whether child loss is related to mortality, cancer incidence, and cancer survival in parents. Methods We used a population-based birth cohort (1964–1976) in Jerusalem and ascertained mortality (average follow-up of 39.1 years) and any cancer (average follow-up of 35.6 years) among parents who lost a child (2838 mothers and 2532 fathers) and among nonbereaved parents (38,212 mothers and 36,433 fathers). We also assessed mortality among parents with cancer. Time-dependent Cox models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results Overall mortality rates among bereaved parents were modestly increased when compared with nonbereaved parents (HR = 1.18, 95% CI: 1.05–1.32 in mothers; HR = 1.10, 95% CI: 1.01–1.20 in fathers). Hazard models indicated a significant relationship between bereavement and deaths from coronary heart disease in mothers (HR = 1.90, 95% CI: 1.23–2.95) and circulatory causes in both parents (HR = 1.69; 95% CI: 1.22–2.34 in mothers and HR = 1.25; 95% CI: 1.02–1.54 in fathers). Bereavement was not associated with parental risk of cancer disease and with survival from cancer. The association between bereavement and parental overall mortality was similar in the different parental sociodemographic characteristics. We observed a decrease in HRs for parental mortality associated with bereavement, with increasing time since the death of the child (HRs = 9–10, 0–3 years; HRs = 0.9–1.0, 9+ years; P heterogeneity ≤3 × 10 −32 ). A similar decrease in HRs was observed for parental survival from cancer (HRs = 6.7–8.7, 0–3 years; HRs = 0.9–1.0, 9+ years). Conclusions Our study suggests that child loss was associated with slightly increased risk of all-cause and circulatory mortality in parents but not with incidence of cancer and cancer survival. The considerable increased parental mortality during a short period after child loss support the involvement of pathways related to psychological stress.

Aims and objectives The aims of this systematic review and meta-analysis were to summarise current knowledge regarding gum chewing intervention for activation of the gastrointestinal (GI) system following caesarean delivery. Background GI symptoms such as nausea, vomiting and defecatory difficulties are bothersome for women following a caesarean delivery. There is category A recommendation to not withhold oral intake postoperatively. However, current practice guidelines vary widely on time to initiate oral feeding post caesarean delivery, and additional research is needed. Gum chewing has been shown to stimulate the GI system in other postoperative patient populations. Design A systematic review and meta-analysis. Methods An electronic review was undertaken using the following resources: PubMed (Medline), CINAHL, EMBASE and ClinicalTrials.gov databases. Key words used in various combinations included cesarean section; cesarean delivery; postoperative chewing gum; bowel movement; bowel function and complications. Results A total of 171 articles were found of which 166 were excluded: 157 were duplicates and the remainder did not meet the inclusion criteria. Five randomised control trials were included in the meta-analysis, focusing on gum chewing as an intervention as compared with a nongum chewing intervention, with a total of 846 participants. Compared with the nongum chewing group, gum chewing showed a beneficial impact on the major outcomes of digestive system activation, including bowel sound, gas passage and defecation. Conclusions This meta-analysis supports the effectiveness of gum chewing post caesarean delivery as a noninvasive/nonpharmacological intervention for reactivation of bowel movement. Relevance to clinical practice Gum chewing in the immediate postoperative period following caesarean delivery may provide a socially acceptable, low-cost and safe intervention to reduce postcaesarean delivery GI complications and restore GI function.

RING finger (C3HC4-type zinc finger) is a variant zinc finger motif present in a large family of functionally distinct proteins. We describe the cloning and characterization of a novel human transcript RNF38 encoding a new member of the RING finger protein family. The complete mRNA consists of about 6.8 kb widely expressed in human tissues as a single transcript, most abundantly in testis. The predicted proline-rich protein consists of 432 amino acid residues with a coiled-coil motif and a RING-H2 motif (C3H2C2) at its carboxy-terminus. High degree homology was found between the human protein and hypothetical peptides from several other species including Rattus norvegicus, Mus musculus, and Drosophila melanogaster, indicating a significant conservation throughout evolution. The RNF38 genomic structure was determined and comprises at least 13 exons extending over more than 65 kb in the genome, 78 kb centromeric to the GNE gene on human chromosome 9p12-p13. The involvement of this chromosomal segment in a large number of human diseases and in particular in various types of malignancies urges the assessment of the potential functional role of RNF38 in these disorders.

The human RECK gene, mapped at 9p13→p12, is known as a tumor suppressor gene and as a key regulator of extracellular matrix integrity and angiogenesis. We have established the entire genomic structure of this gene, which spans more than 87 kb and consists of 21 exons and 20 introns, and identified thirteen single nucleotide polymorphisms (SNPs). Four SNPs were identified in the coding region of the gene (exons 1, 9, 13 and 15), and the remaining nine in introns 5, 8, 10, 12, 15 and 17. The availability of the genomic organization of the RECK gene and the identification of polymorphisms throughout its entire genome will facilitate the evaluation of its role in several disorders and also contribute to the assignment of genes to the several diseases mapped to this chromosomal region.

Background Several stages in the life course have been identified as important to the development of cardiovascular disease. This study aimed to assess the associations of childhood and adulthood socioeconomic position (SEP) and social mobility with cardiometabolic risk factors (CMRs) later in life. Methods We conducted follow-up examinations of 1132 offspring, aged 32, within a population-based cohort of all births in Jerusalem from 1974 to 1976. SEP was indicated by parents’ occupation and education, and adulthood SEP was based on offspring9s occupation and education recorded at age 32. Linear regression models were used to investigate the associations of SEP and social mobility with CMRs. Results Childhood-occupational SEP was negatively associated with body mass index (BMI; β=−0.29, p=0.031), fat percentage (fat%; β=−0.58, p=0.005), insulin (β=−0.01, p=0.031), triglycerides (β=−0.02, p=0.024) and low-density lipoprotein cholesterol (LDL-C; β=−1.91, p=0.015), independent of adulthood SEP. Adulthood-occupational SEP was negatively associated with waist-to-hip ratio (WHR; β=−0.01, p=0.002), and positively with high-density lipoprotein cholesterol (HDL-C; β=0.87, p=0.030). Results remained similar after adjustment for smoking and inactivity. Childhood-educational SEP was associated with decreased WHR and LDL-C level (p=0.0002), and adulthood-educational SEP was inversely associated with BMI (p=0.001), waist circumference (p=0.008), WHR (p=0.001) and fat% (p=0.0002) and positively associated with HDL-C (p=0.030). Additionally, social mobility (mainly upward) was shown to have adverse cardiometabolic outcomes. Conclusions Both childhood and adulthood SEP contribute independently to CMR. The match–mismatch hypothesis may explain the elevated CMRs among participants experiencing social mobility. Identification of life-course SEP-related aspects that translate into social inequality in cardiovascular risk may facilitate efforts for improving health and for reducing disparities in cardiovascular disease.