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Background It is suggested amino acids are critical for fetal growth, but analyses assessing causality are lacking. Mendelian randomisation (MR) can be used to examine causal effects under instrumental variable (IV) assumptions. Methods We conducted a two-sample MR study utilizing summary data from genome-wide association studies (GWAS) of amino acids (sample 1, n = 86,507) and of offspring birthweight (sample 2, combined UK Biobank and Early Growth Genetics Consortium, n = 406,063). Seventy-five independent single nucleotide polymorphisms (SNPs) robustly associated with 18 amino acids (p Results There was evidence of positive causal effects of maternal alanine (51.9 g birthweight increase per SD increase in amino acid level, 95% CI: 24.2, 79.5), glutamine (51.3 g, 95% CI: 33.5, 69.0), glycine (10.4 g, 95% CI: 1.3, 19.6) and serine (27.1 g, 95% CI: 11.2, 43.0) on birthweight and inverse causal effects of maternal isoleucine (-109.7 g, 95% CI: -194.6, -24.9) and histidine (-41.1 g, 95% CI: -78.5, -3.7) on birthweight. Sensitivity analyses to explore reverse causality and bias due to horizontal pleiotropy supported our findings. Conclusions Some maternal circulating amino acids have causal effects on birthweight. Key messages MR can be extended to probe effects of maternal nutrition on offspring development.

Background In children being taller is associated with higher blood pressure (BP), but few studies have divided height into its components: trunk and leg length. We examined the associations of total height, trunk length and leg length with systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) at early childhood and mid-childhood visits, as well as change between the two visits. Methods We obtained five measures of SBP and DBP at the early childhood visit (N = 1153, follow-up rate = 54%) and at the mid-childhood visit (N = 1086, follow-up rate = 51%) respectively, in Project Viva, a US cohort study. We measured total height and sitting height (a measure of trunk length that includes head and neck) and calculated leg length as the difference between the two. Using mixed models, we adjusted the cross-sectional analyses for leg length when trunk length was the exposure of interest, and vice versa. We also adjusted for maternal race/ethnicity, child age, sex, overall adiposity and BP measurement conditions. Results At the mid-childhood visit, total height was positively associated with SBP [0.34 (0.24; 0.45) mmHg/cm] but not with DBP [0.07 (−0.003; 0.15)]. In models examining trunk and leg length separately, each was positively associated with SBP [0.72 (0.52; 0.92) and 0.33 (0.16; 0.49) respectively]. In a fully adjusted model with both leg and trunk length, only trunk length remained associated with BP. For a given leg length, a 1-cm increment in trunk length was associated with a 0.63-mmHg (0.42; 0.83) higher SBP and a 0.17-mmHg (0.02; 0.31) higher DBP. For a given trunk length, however, the associations of leg length with SBP [0.13 (−0.03; 0.30)] and with DBP [0.002 (−0.11; 0.12)] were null. These patterns were similar at the early childhood visit. Conclusions Children with greater trunk lengths have higher BPs, perhaps because of the additional pressure needed to overcome gravity to perfuse the brain.

Background Previous cross-sectional analyses of this cohort have shown that short height and leg length are associated with higher pulse pressure and systolic blood pressure in middle age. It is unclear how these adult measures of childhood growth influence the change in blood pressure as it increases with age. Methods Multilevel models were fitted to investigate associations between components of height and the change in blood pressure between 36, 43, and 53 years in a prospective national cohort of 1472 men and 1563 women followed-up since birth in 1946. Results Shorter height and leg length, but not trunk length, were associated with higher blood pressure, similarly in men and women. Longitudinal analyses showed that the effects of both height and leg length on pulse pressure and systolic blood pressure became significantly stronger with age. For example, the change in systolic blood pressure was found to be � 0.021 mm Hg (95% confidence interval � 0.029 to � 0.013) per year lower for every centimetre increase in leg length (P � 0.001). In other words, the increase in systolic blood pressure over a 10 year period of a participant whose legs were 10 centimetres shorter was 2.1 mm Hg higher (P � 0.001), compared with a taller participant. Associations were independent of a number of potential confounders. Conclusions These results support the hypothesis that short people may be more susceptible to the effects of ageing on the arterial tree. Childhood growth may contribute to the tracking of cardiovascular risk throughout life.

Previous studies have suggested that shorter leg length, not trunk length, may explain the inverse association between height and coronary heart disease (CHD) risk. However, investigation of the importance of birth weight for these associations has been limited. This study examines associations of measures of stature and birth weight with CHD risk factors (measures of blood pressure and lipids, 2 h glucose, waist-hip ratio and fibrinogen) and incident non-fatal coronary events in middle age.Data were derived mostly from the Phase 5 (1997-99) clinical screening of the Whitehall II study of British civil servants. The main cross-sectional analyses included 1084 women and 2290 men with complete data.In women total height and leg length were the measures that tended to be most strongly associated with CHD risk factors, while in men leg length demonstrated the closest associations. Although associations between trunk length and CHD risk factors were weaker, trunk length was the component of height that appeared to be most closely associated with coronary events. Associations between birth weight and CHD risk factors and coronary events were generally weaker than for any measure of stature. Adjustment for birth weight had little effect on associations between components of stature and CHD risk factors or events.Findings from this relatively privileged cohort confirmed that shorter leg length underlies the inverse association between height and CHD risk factors in middle-aged women and men. Furthermore, in this study population shorter trunk length was more closely associated with incident, non-fatal coronary events.

BACKGROUND Low birthweight is associated with high blood pressure in later life, but it is unclear whether the association is confounded with or modified by maternal and socioeconomic factors or childhood growth. METHODS A total of 3157 men and women from a British birth cohort study where the survey members have been followed up regularly since their birth in 1946 were included in analyses. The associations between birthweight, childhood growth and blood pressure at 43 years of age were assessed using multiple regression models. RESULTS Systolic blood pressure (SBP) decreased by 2.3 mmHg (95% CI: 0.8, 3.5) for men and 1.8 mmHg (95% CI: 0.1, 3.5) for women per 1-kg increase in birthweight. The effect was stronger in first born or those born to younger mothers. There was no confounding with any maternal, socioeconomic, or childhood growth variable. SBP increased by 1.45 mmHg (95% CI: 0.11, 2.78) in women and 0.46 mmHg (95% CI: -0.70, 1.62) in men per standard deviation of body mass index (BMI) change between ages 7 and 15 years. Among women this effect was not completely accounted for by adult size and was independent of birthweight. CONCLUSIONS The determinants of birthweight, possibly related to maternal health during pregnancy, may impact on the relationship with SBP in middle life. The importance of tackling the increasing levels of childhood obesity seen in later cohorts is highlighted by the detrimental impact on SBP of large increases in BMI during adolescence.