Perinatal light exposure predisposes towards health and behaviour in adulthood. Season of birth is associated with psychiatric, allergic, cardiovascular and metabolic problems. It has been proposed that early-life environmental light disrupts the development of biological rhythms which, in turn, influence later-life health. However, the mechanisms linking perinatal seasonal light to later-life biological rhythm and health in humans are unknown. In this study, we investigated the association between season of birth and epigenome-wide DNA methylation of two postmortem human brain regions (16 hypothalamus, 14 temporal cortex). We did not find statistically significant differences at the whole epigenome level, either because we lacked statistical power or that no association exists. However, when we examined 24 CpG sites that had the highest significance or differential methylation, we identified regions which may be associated with circadian rhythm entrainment, cholinergic neurotransmission and neural development. Amongst methylation of the core clock genes, we identified that hypothalamus Neuronal PAS Domain Protein 2 (NPAS2) gene has hypermethylated regions in long photoperiod-born individuals. In addition, we found nominal associations between season of birth and genes linked to chronotype and narcolepsy. Season of birth-related brain DNA methylation profile was different than a previously reported blood methylation profile, suggesting a tissue-specific mechanism of perinatal light programming. Overall, we are the first to analyse the relationship between season of birth and human brain DNA methylation. Further studies with larger sample sizes are required to confirm an imprinting effect of perinatal light on the circadian clock.

Perimenopausal disorders (PDs) are prevalent and importantly affect quality of life among middle-aged women. Yet, very little is known about the developmental origins of these disorders. The objective of this study was to investigate the associations of birth characteristics with PDs. This cohort study is based on archived birth records for birth weight and gestational age, and followed prospectively in Swedish inpatient and outpatient registers for 8 years (n=3212). The main outcomes were menopausal and climacteric states (e.g. flushing, sleeplessness), perimenopausal bleeding and other PDs (e.g. atrophic vaginitis). Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) for three subtypes of PDs separately. During the follow-up, 218 women had PDs, among whom 125 had menopausal and climacteric states, 61 had perimenopausal bleeding and 58 had other PDs as first recorded disorder. Birth weight was linearly associated with incidence rate of menopausal and climacteric states [HR=1.66 per 1 kg increase, 95% confidence interval (95% CI)=1.14–2.41]. Gestational age (rather than birth weight) was associated with incidence rate of other PDs (HR=0.87 per 1 week increase, 95% CI=0.79–0.95). Neither birth weight nor gestational age was associated with perimenopausal bleeding. Similar results were found after adjustment for other early-life and adult socio-demographic characteristics. This observational study provides, for the first time, evidence regarding the developmental origins of PDs. Future research is required to investigate the underlying causal mechanisms, which may shed further light on the etiology of this class of disorders.

Experimental data on the effects of lifestyle interventions on fetal neurodevelopment in humans remain scarce. This study assessed the impact of a pregnancy nutrition+exercise intervention on offspring neurodevelopment at 12 months of age. The Be Healthy in Pregnancy (BHIP) randomized controlled trial (RCT) randomly assigned pregnant persons with stratification by site and body mass index (BMI) to bi-weekly nutrition counselling and high dairy protein diet, walking goal of 10,000 steps/day plus usual prenatal care (UPC; intervention group) or UPC alone (control group). This study examined a subset of these mothers (> 18 years, singleton pregnancy, BMI <40 kg/m2, and enrolled by ≤12 weeks gestation) and their infants (intervention = 42, control = 32), assessing cognition, language, motor, social-emotional, and adaptive functioning at 12 months using the Bayley Scales of Infant and Toddler Development third edition (BSID-III) as the outcome measure. We also examined if maternal factors (prepregnancy BMI, gestational weight gain (GWG)) moderated associations. Expressive language (MD = 9.62, 95% CI = (9.05–10.18), p = 0.03, ƞ2p = 0.07) and general adaptive composite (GAC) scores (MD = 103.97, 95% CI = (100.31–107.63), p = 0.04, ƞ2p = 0.06) were higher in infants of mothers in the intervention group. Effect sizes were medium. However, mean cognitive, receptive language, motor, and social-emotional scale scores did not differ between groups. A structured and monitored nutrition+exercise intervention during pregnancy led to improved expressive language and general adaptive behavior in 12-month-olds, but not cognitive, receptive language, motor, or socioemotional functioning. While these experimental data are promising, further research is needed to determine the clinical utility of nutrition+exercise interventions for optimizing infant neurodevelopment.

Earlier, we reported that antenatal micronutrient supplementation reduced the risk of metabolic syndrome and microalbuminuria among offspring at 6–8 years of age in rural Nepal. In the same birth cohort, we examined associations of size at birth (weight, length and ponderal index), and gestational age, with cardiometabolic risk factors in childhood across all antenatal micronutrient interventions. There was an inverse association between birth weight and systolic blood pressure (SBP, β = −1.20 mm Hg/kg; 95% confidence interval (CI): −1.93, −0.46) and diastolic blood pressure (DBP, β = −1.24 mm Hg/kg; 95% CI: −2.00, −0.49). Current child body mass index was positively associated with SBP but not with DBP. Birth weight was unassociated with insulin resistance, but each kilogram of increase was associated with a reduced risk of high triglycerides (odds ratio (OR) = 0.64/kg; 95% CI: 0.41, 0.97) and an increased risk of high waist circumference (OR = 3.16/kg; 95% CI: 2.47, 4.41). In this rural Nepalese population of children 6–8 years of age with a high prevalence of undernutrition, size at birth was inversely associated with blood pressure and triglycerides and positively associated with waist circumference.

There is an accumulating data that shows relation between childhood adversity and vulnerability to chronic diseases as well as epigenetic influences that in turn give rise to these diseases. Asthma is one of the chronic diseases that is influenced from genetic regulation of the inflammatory biomolecules and therefore the hypothesis in this research was childhood adversity might have caused epigenetic differentiation in the asthma-related genes in the population who had childhood trauma. To test this hypothesis, the literature was systematically reviewed to extract epigenetically modified gene data of the adults who had childhood adversity, and affected genes were further evaluated for their association with asthma. PRISMA guidelines were adopted and PubMed and Google Scholar were included in the searched databases, to evaluate epigenetic modifications in asthma-related genes of physically, emotionally or sexually abused children. After retrieving a total of 5245 articles, 36 of them were included in the study. Several genes and pathways that may contribute to pathogenesis of asthma development, increased inflammation, or response to asthma treatment were found epigenetically affected by childhood traumas. Childhood adversity, causing epigenetic changes in DNA, may lead to asthma development or influence the course of the disease and therefore should be taken into account for the prolonged health consequences.

Maternal nutrition is critical in mammalian development, influencing the epigenetic reprogramming of gametes, embryos, and fetal programming. We evaluated the effects of different levels of sulfur (S) and cobalt (Co) in the maternal diet throughout the pre- and periconceptional periods on the biochemical and reproductive parameters of the donors and the DNA methylome of the progeny in Bos indicus cattle. The low-S/Co group differed from the control with respect to homocysteine, folic acid, B12, insulin growth factor 1, and glucose. The oocyte yield was lower in heifers from the low S/Co group than that in the control heifers. Embryos from the low-S/Co group exhibited 2320 differentially methylated regions (DMRs) across the genome compared with the control embryos. We also characterized candidate DMRs linked to the DNMT1 and DNMT3B genes in the blood and sperm cells of the adult progeny. A DMR located in DNMT1 that was identified in embryos remained differentially methylated in the sperm of the progeny from the low-S/Co group. Therefore, we associated changes in specific compounds in the maternal diet with DNA methylation modifications in the progeny. Our results help to elucidate the impact of maternal nutrition on epigenetic reprogramming in livestock, opening new avenues of research to study the effect of disturbed epigenetic patterns in early life on health and fertility in adulthood. Considering that cattle are physiologically similar to humans with respect to gestational length, our study may serve as a model for studies related to the developmental origin of health and disease in humans.

Maternal prenatal psychological distress, including depression and anxiety, may affect offspring’s motor/cognitive development. However, research findings have been inconsistent. We used a dataset from the Japan Environment and Children’s Study to evaluate associations between maternal six-item Kessler Psychological Distress Scale (K6) scores and motor/cognitive development among offspring at two years of age. Their offspring’s motor/cognitive development was assessed using the Kyoto Scale of Psychological Development 2001. Records for 1859 male and 1817 female offspring were analyzed. The maternal K6 was administered twice during pregnancy: at a median of 14.6 weeks (M-T1) and 27.3 weeks (M-T2) of gestation. Multiple regression analysis was performed with the group with K6 scores ≤4 at both M-T1 and M-T2 as a reference. In the group with K6 scores ≥5 at both M-T1 and M-T2, male offspring had significantly lower developmental quotients (DQ) in the posture-motor area (partial regression coefficient [B]: −3.68, 95% confidence interval [CI]: −5.92 to −1.44) and language-social area (B: −1.93; 95%CI: −3.73 to −0.12), while female offspring had a lower DQ for the language-social area (B: −1.95; 95%CI: −3.73 to −0.17). In those with K6 scores ≥5 only at M-T1 or M-T2, male and female offspring did not differ significantly in DQ for any area. Continuous maternal psychological distress from the first to the second half of pregnancy was associated with lower motor and verbal cognitive development in male offspring and lower verbal cognitive development in female offspring at 2 years compared with the group without persistent maternal prenatal psychological distress.

This study was undertaken to compare amino acid concentrations in maternal and newborn infants’ serum in normal pregnancy and two groups of obese women who were born themselves with normal and small for gestational age (SGA) birth weight. Maternal cholesterol, lipoproteins concentrations and maternal and infants amino acid concentrations were evaluated at the time of delivery in 28 normal pregnancies, 46 obese pregnant women with normal birth weight (Ob-AGA group) and 44 obese pregnant women born themselves SGA (Ob-SGA group). Mean birth weight of newborn infants in Ob-SGA group was significantly less than in normal and Ob-AGA groups. Cholesterol and lipoproteins were significantly elevated in obese women (more prominent in Ob-SGA group). Most amino acid concentrations and fetal–maternal amino acid gradients were significantly lower in Ob-SGA group. These data suggest significant changes in placental amino acid transport/synthetic function in obese women who were born themselves SGA.

Sugar sweetened beverages (SSB) are thought to play an important role in weight gain. We examined the relationship between the intake of caloric and noncaloric beverages (SSB and water) and the nutritional status of children. In 2014, we randomly selected 16 public health clinics in four cities of Northwest Argentina and conducted a survey among mothers of children 0–6 years of age. Children’s beverage intake was ascertained by 24-h dietary recall provided by the mothers. Children’s weight and height measures were obtained from clinic’s registries. We calculated the body mass index using the International Obesity Task Force standards. The analysis included 562 children 25 months to 6 years of age with normal or above normal nutritional status. Children’s beverage consumption was as follows, water 81.8%, carbonated soft drinks (CSD) 49.7%, coffee/tea/cocoa 44.0%, artificial fruit drinks 35.6%, flavored water 17.9%, natural fruit juice 14.5%. In multivariate logistic regression models the likelihood of being obese v. being overweight or having normal weight doubled with an intake of one to five glasses of CSD (OR=2.2) and increased by more than three-fold with an intake of more than five glasses (OR=3.5). Drinking more than five glasses of water decreased the likelihood of being obese by less than half (OR=0.3). The percentage of children drinking more than five glasses of other beverages was low (3.3–0.9%) and regression models did not yield significant results. The study contributed evidence for reducing children’s CSD intake and for promoting water consumption, together with the implementation of comprehensive regulatory public health policies.

Predictive adaptive responses (PARs) are a form of developmental plasticity in which the developmental response to an environmental cue experienced early in life is delayed and yet, at the same time, the induced phenotype anticipates (i.e., is completely developed before) exposure to the eventual environmental state predicted by the cue, in which the phenotype is adaptive. We model this sequence of events to discover, under various assumptions concerning the cost of development, what lengths of delay, developmental time, and anticipation are optimal. We find that in many scenarios modeled, development of the induced phenotype should be completed at the exact same time that the environmental exposure relevant to the induced phenotype begins: that is, in contrast to our observed cases of PARs, there should be no anticipation. Moreover, unless slow development is costly, development should commence immediately after the cue: there should be no delay. Thus, PARs, which normally have non-zero delays and/or anticipation, are highly unusual. Importantly, the exceptions to these predictions of zero delays and anticipation occurred when developmental time was fixed and delaying development was increasingly costly. We suggest, therefore, that PARs will only evolve under three kinds of circumstances: (i) there are strong timing constraints on the cue and the environmental status, (ii) delaying development is costly, and development time is either fixed or slow development is costly, or (iii) when the period between the cue and the eventual environmental change is variable and the cost of not completing development before the change is high. These predictions are empirically testable.

Prenatal glucocorticoids, commonly used in women at risk of preterm delivery, can predispose the newborn to disease in later life. Since male reproductive function is likely to reflect testis development during fetal life, we studied the effects of prenatal glucocorticoids on two key intra-testicular factors that play roles in cellular proliferation and differentiation, 3β-hydroxysteroid dehydrogenase (3β-HSD) and inhibin-α. Pregnant sheep (n=42) were treated with betamethasone (0.5 mg/kg) or saline (control) at 104, 111 and 118 days of gestation (DG). Testicular tissue was sampled from fetuses at 121 and 132DG, and from lambs at 45 and 90 postnatal days (PD). Within the betamethasone treated group, 3β-HSD immunostaining area was greater at 121DG than at 90PD (P=0.04), but the intensity of immunostaining was higher at 90PD than at 121DG (P=0.04), 132DG (P=0.04) and 45PD (P=0.03). Control animals showed no changes in 3β-HSD area or intensity of immunostaining. No significant differences were observed between treated and control animals in immunostaining area, but immunostaining was more intense in the treated group than in the control group at 90PD (P=0.03). For inhibin-α, the proportion of immunostaining area declined in treated offspring from 121DG to 45PD, in contrast to control values, but recovered fully by 90PD, concomitantly with the onset of spermatogenesis. In conclusion, prenatal betamethasone increased the postnatal testicular expression of inhibin-α but reduced the expression of 3β-HSD. These effects could compromise androgen-mediated testicular development and therefore adult capacity for spermatogenesis.

Little is known about the consequences of viral infection for pregnant woman or for the fetus. This issue became important with the appearance of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The infection with SARS-CoV-2 causes a respiratory syndrome known as COVID-19. The fast spreading around the world and the fact that without a treatment or vaccine humans are completely exposed, converts emerging viral diseases in a significant risk for pregnant women and their infants. At this time, during SARS-CoV-2 pandemics pregnant women are not considered as a risk population and little is known about the effects of viral infections over the offspring although the amount of emerging evidence showing detrimental effects for the mother and the fetus. This issue highlights the importance to understand the effects of viral infections during pregnancy. In this work, we analyze the effects of viral infections, like SARS-CoV-2 and other related viruses during pregnancy over the mother and the consequences for the offspring.

Our primary objectives are to empirically identify distinct childhood groups based on trajectories of waist circumference (WC) and waist circumference index measurements, and then to estimate associations between these groups and adult diabetes incidence, as well as other outcomes, including blood pressure, body size, body composition, and hemoglobin levels. Childhood WC and height measurements as well as various adult measurements are taken from participants in the Fels Longitudinal Study. Childhood groups are identified using group-based trajectory modeling. Associations between the resulting group probabilities and adult outcomes are examined using mixed models. Our results show that distinct childhood groups are identifiable for both waist size measurements, with growth curves exhibited by these groups becoming distinguishably separate at around 4 years of age. Higher probabilities for groups exhibiting the larger waist size for either measurement were estimated to have higher risks of developing diabetes in adulthood. Associations were also observed between group probabilities and systolic blood pressure, diastolic blood pressure, and various anthropomorphic measurements, with most associations consistently occurring in early adulthood. These findings expand upon the existing literature, showing that childhood trends in waist size, distinguishable at ages as early as 4 years, are associated with adult Type-2 diabetes.

Other than obesity, no definitive insights have been gained regarding the apparent association between mode of delivery and long-term endocrine and metabolic outcomes in the offspring. We aimed to determine whether elective cesarean delivery (CD) impacts on long-term endocrine and metabolic morbidity of the offspring. A population-based cohort analysis was performed including all singleton-term deliveries occurring between 1991 and 2014 at a single tertiary medical center. A comparison was performed between children delivered via a non-emergent CD and those delivered vaginally (VD). Hospitalizations of the offspring up to the age of 18 years involving endocrine morbidity were evaluated. A Kaplan–Meier survival curve was used to compare cumulative morbidity incidence. Cox and a Weibull regression models were used to control for confounders. During the study period 131,880 term deliveries met the inclusion criteria; 8.9% were elective non-urgent CDs (n=11,768) and 91.1% (n=120,112) were VDs. The survival curve demonstrated a significantly higher cumulative incidence of endo-metabolic morbidity in offspring born via CD (P=0.010). In the regression models, adjusted for maternal obesity, CD was not noted as an independent risk factor for long-term pediatric endocrine and metabolic morbidity of the offspring while maternal obesity emerged as a strong predictor. We therefore conclude that CD per-se does not appear to increase the risk for long-term pediatric endo-metabolic morbidity of the offspring.

It was hypothesized that exposure of the fetus to adverse conditions in utero due to either maternal constraint or nutrition may result in developmental adaptations altering metabolism and postnatal growth of the offspring. Heavy (H) and light (L) Romney dams (G0) were allocated to ad libitum (A) or maintenance (M) nutritional regimens, from day 21–day 140 of pregnancy. Female twin-born offspring (G1) born to the dams in the four treatment groups will be referred to as HA-ewes, LA-ewes, HM-ewes and LM-ewes. At 16 months of age, offspring were catheterized and given intravenous insulin tolerance test (ITT), glucose tolerance test (GTT) and epinephrine tolerance test challenges to assess their glucose and fat metabolism in relation to their birth weight and postnatal growth. In HA-ewes, the regression coefficients of growth rates prior to puberty on insulin and glucose curves in response to GTT (InsAUCGTT) and ITT (GluAUCITT), respectively, were different from 0 (P < 0.05) and were different from the regression coefficients of HM-ewes. This may indicate that HA-ewes may have showed puberty-related insulin resistance at 16 months of age with increasing growth rates prior to puberty compared to HM- or LM-ewes. In HM-ewes, the regression coefficients of growth rates after puberty on InsAUCGTT and GluAUCITT were different from 0 (P < 0.05) and were different from those of HA-ewes. These results may indicate that offspring born to heavy dams fed maintenance during pregnancy and with greater postnatal growth rates after puberty could develop glucose intolerance and insulin resistance in later life.

Individuals born small have an increased risk for developing type 2 diabetes. Altered food preferences in these subjects seem to play a role; however, limited evidence is available on the association between being born small-for-gestational-age (SGA) at term and food intake in adolescence. Alterations in leptin, ghrelin and dopamine levels are suggested mechanisms linking SGA with later food intake. From a large prospective Danish National Birth Cohort, we compared dietary intake of adolescents being born SGA with normal-for-gestational-age (NGA) adolescents. Intake of foods and nutrients was assessed by a validated food frequency questionnaire in a subsample of 15,607 14-year-old individuals born at term. SGA was defined by birth weight (BW) <10th percentile (n = 1470) and NGA as BW between 10 and 90th percentile (n = 14,137) according to sex and gestational age-specific BW standard curves. Girls born SGA had a 7% (95% CI: 3–12%, P = 0.002) higher intake of added sugar and a 2–8% lower intake of dietary fibre, vegetables, polyunsaturated fatty acids, and total n−6, compared with NGA girls (P < 0.05). Adjusting for parental socio-occupational status, maternal smoking and diet in pregnancy did not substantially change the differences in dietary intake, except from dietary fibre, which were no longer statistically significant. No significant differences in dietary intake between SGA and NGA boys were found. In summary, girls born SGA had an unfavourable dietary intake compared with NGA girls. These differences persisted after controlling for potential confounders, thus supporting a fetal programming effect on dietary intake in girls born SGA at term. However, residual confounding by other factors operating early in childhood cannot be excluded.

Preterm birth and exposure to childhood sexual abuse (CSA) are early physiological and psychological adversities that have been linked to reduced social functioning across the lifespan. However, the joint effects of being born preterm and being exposed to CSA on adult social outcomes remains unclear. We sought to determine the impact of exposure to both preterm birth and CSA on adult social functioning in a group of 179 extremely low birth weight (ELBW; <1000 g) survivors and 145 matched normal birth weight (>2500 g) participants in the fourth decade of life. Social outcome data from a prospective, longitudinal, population-based Canadian birth cohort initiated between the years of 1977 and 1982 were examined. At age 29–36 years, ELBW survivors who experienced CSA reported poorer relationships with their partner, worse family functioning, greater loneliness, lower self-esteem and had higher rates of avoidant personality problems than those who had not experienced CSA. Birth weight status was also found to moderate associations between CSA and self-esteem (P=0.032), loneliness (P=0.021) and family functioning (P=0.060), such that the adverse effects of CSA were amplified in ELBW survivors. Exposure to CSA appears to augment the adult social risks associated with perinatal adversity. Individuals born preterm and exposed to CSA appear to be a group at particularly high risk for adverse social outcomes in adulthood.

Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler’s Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother−child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; −2.01 [−3.43, −0.59], p = 0.006), verbal composite (−1.93 [−3.33, −0.53], p = 0.007), and information scale (−0.41 [−0.70, −0.14], p = 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%–41% and 7%–22%, respectively, and accounted for approximately 5%–10% greater variation in male children’s cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life.

Increased population longevity could be influenced by early life factors. Some areas have long-lived populations, also in a historical perspective. We aimed to study these factors in Halland, an area with the highest life expectancy in Sweden. We collected archival data on gestational age and birth characteristics from 995 live singleton full-term births at the Halmstad Hospital, Halland, from the period 1936 to 1938 and compared these to 3364 births from three hospitals in nearby Scania for the period 1935–1945. In addition, data were obtained on maternal and offspring characteristics from the national Swedish Medical Birth Register during 1973–2013. The results show that when controlling for background maternal and offspring characteristics, mean birth weight (BW) and mean birth length were higher in Halland than in Scania, but the proportion of low birth weight (LBW) and small for gestational age (SGA) was lower. However, mean BW for Halland did not differ from the rest of Sweden in recent years 2004–2013. We also conducted a mortality follow-up for children born in Scania, which showed that LBW, being born SGA, or short birth length reduced survival. In conclusion, the high mean life expectancy in Halland compared to the rest of Sweden could have been associated with beneficial early life factors influencing birth size in the past. In more recent decades the mean BW of Halland is not different from the national mean. Thus, longevity could be expected to become more equal to the national mean in the future.

Early-life environmental and nutritional exposures are considered to contribute to the differences in cardiovascular disease (CVD) burden. Among sub-Saharan African populations, the association between markers of early-life exposures such as leg length and sitting height and CVD risk is yet to be investigated. This study assessed the association between leg length, sitting height, and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk among Ghanaian-born populations in Europe and Ghana. We constructed sex-specific quintiles for sitting height and leg length for 3250 participants aged 40–70 years (mean age 52 years; men 39.6%; women 60.4%) in the cross-sectional multicenter Research on Diabetes and Obesity among African Migrants study. Ten-year risk of ASCVD was estimated using the Pooled Cohort Equations; risk ≥7.5% was defined as “elevated” CVD risk. Prevalence ratios (PR) were estimated to determine the associations between sitting height, leg length, and estimated 10-year ASCVD risk. For both men and women, mean sitting height and leg length were highest in Europe and lowest in rural Ghana. Sitting height was inversely associated with 10-year ASCVD risk among all women (PR for 1 standard deviation increase of sitting height: 0.75; 95% confidence interval: 0.67, 0.85). Among men, an inverse association between sitting height and 10-year ASCVD risk was significant on adjustment for study site, adult, and parental education but attenuated when further adjusted for height. No association was found between leg length and estimated 10-year ASCVD risk. Early-life and childhood exposures that influence sitting height could be the important determinants of ASCVD risk in this adult population.