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Background: Systematic reviews of randomised controlled trials (RCTs) have suggested that maternal vitamin D (25[OH]D) and calcium supplementation increase birth weight. However, limitations of many trials were highlighted in the reviews. Our aim was to combine genetic and RCT data to estimate causal effects of these two maternal traits on offspring birth weight.Methods and Findings: We performed two-sample mendelian randomisation (MR) using genetic instrumental variables associated with 25(OH)D and calcium that had been identified in genome-wide association studies (GWAS; sample 1; N = 122,123 for 25[OH]D and N = 61,275 for calcium). Associations between these maternal genetic variants and offspring birth weight were calculated in the UK Biobank (UKB) (sample 2; N = 190,406). We used data on mother-child pairs from two United Kingdom birth cohorts (combined N = 5,223) in sensitivity analyses to check whether results were influenced by fetal genotype, which is correlated with the maternal genotype (r ≈ 0.5). Further sensitivity analyses to test the reliability of the results included MR-Egger, weighted-median estimator, 'leave-one-out', and multivariable MR analyses. We triangulated MR results with those from RCTs, in which we used randomisation to supplementation with vitamin D (24 RCTs, combined N = 5,276) and calcium (6 RCTs, combined N = 543) as an instrumental variable to determine the effects of 25(OH)D and calcium on birth weight. In the main MR analysis, there was no strong evidence of an effect of maternal 25(OH)D on birth weight (difference in mean birth weight -0.03 g [95% CI -2.48 to 2.42 g, p = 0.981] per 10% higher maternal 25[OH]D). The effect estimate was consistent across our MR sensitivity analyses. Instrumental variable analyses applied to RCTs suggested a weak positive causal effect (5.94 g [95% CI 2.15-9.73, p = 0.002] per 10% higher maternal 25[OH]D), but this result may be exaggerated because of risk of bias in the included RCTs. The main MR analysis for maternal calcium also suggested no strong evidence of an effect on birth weight (-20 g [95% CI -44 to 5 g, p = 0.116] per 1 SD higher maternal calcium level). Some sensitivity analyses suggested that the genetic instrument for calcium was associated with birth weight via exposures that are independent of calcium levels (horizontal pleiotropy). Application of instrumental variable analyses to RCTs suggested that calcium has a substantial effect on birth weight (178 g [95% CI 121-236 g, p = 1.43 × 10-9] per 1 SD higher maternal calcium level) that was not consistent with any of the MR results. However, the RCT instrumental variable estimate may have been exaggerated because of risk of bias in the included RCTs. Other study limitations include the low response rate of UK Biobank, which may bias MR estimates, and the lack of suitable data to test whether the effects of genetic instruments on maternal calcium levels during pregnancy were the same as those outside of pregnancy.Conclusions: Our results suggest that maternal circulating 25(OH)D does not influence birth weight in otherwise healthy newborns. However, the effect of maternal circulating calcium on birth weight is unclear and requires further exploration with more research including RCT and/or MR analyses with more valid instruments. [ABSTRACT FROM AUTHOR]

Objectives: Maternal lifestyles, including diet, have been linked to infant birthweight. However, customised birthweight centiles (CBWC), which more accurately identify small babies that have increased fetal growth restriction and are at higher risk of newborn morbidity and later life health complications, are rarely considered when studying maternal diet. This study investigated maternal dietary patterns and their impact on infant CBWC within a cohort of women living in South Wales. Methods: This study utilised cross-sectional data from the longitudinal Grown in Wales (GiW) cohort. Women 18–45 years old were recruited the morning prior to an elective caesarean section (ELCS). Women completed a food frequency questionnaire (FFQ). Additional data on pregnancy and birth outcomes was extracted from medical notes. Data from 303 participants was analysed. Results: ‘Western’ and ‘Health conscious dietary patterns were identified. The ‘Health Conscious’ dietary pattern was significantly associated with maternal BMI, age, education, income and exercise. Adjusted regression analyses indicated that greater adherence to a ‘Health Conscious’ dietary pattern was significantly associated with increased CBWC (AOR = 4.75 [95% CI: 1.17, 8.33] p = .010) and reduced risk of delivering a small-for-gestational age (SGA) infant (AOR = .51 [95% CI: .26, .99] p = .046). Conclusion: A healthier diet was significantly associated with higher birthweight using CBWC and a reduced risk of delivering an SGA infant suggesting that birthweight will be improved in areas of Wales by focused support encouraging healthier dietary habits. [ABSTRACT FROM AUTHOR]

Background: Wrist-worn accelerometers are emerging as the most common instrument for measuring physical activity in large-scale epidemiological studies, though little is known about the relationship between wrist acceleration and physical activity energy expenditure (PAEE). Methods: 1695 UK adults wore two devices simultaneously for six days; a combined sensor and a wrist accelerometer. The combined sensor measured heart rate and trunk acceleration, which was combined with a treadmill test to yield a signal of individually-calibrated PAEE. Multi-level regression models were used to characterise the relationship between the two time-series, and their estimations were evaluated in an independent holdout sample. Finally, the relationship between PAEE and BMI was described separately for each source of PAEE estimate (wrist acceleration models and combined-sensing). Results: Wrist acceleration explained 44–47% between-individual variance in PAEE, with RMSE between 34–39 J•min-1•kg-1. Estimations agreed well with PAEE in cross-validation (mean bias [95% limits of agreement]: 0.07 [-70.6:70.7]) but overestimated in women by 3% and underestimated in men by 4%. Estimation error was inversely related to age (-2.3 J•min-1•kg-1 per 10y) and BMI (-0.3 J•min-1•kg-1 per kg/m2). Associations with BMI were similar for all PAEE estimates (approximately -0.08 kg/m2 per J•min-1•kg-1). Conclusions: A strong relationship exists between wrist acceleration and PAEE in free-living adults, such that irrespective of the objective method of PAEE assessment, a strong inverse association between PAEE and BMI was observed. [ABSTRACT FROM AUTHOR]