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Consistent positive relationships have been found between birth weight and grip strength in adults but evidence in children is limited. In a prospective general population birth cohort (Southampton Women's Survey), grip strength and anthropometry (height and weight) were measured in 968 children at the age of 4 years. Mean (standard deviation (s.d.)) birth weight was 3.48 (0.52) kg. Birth weight, adjusted for sex and gestational age, was positively associated with grip strength (β = 0.22 kg/s.d. increase in adjusted birth weight; 95% CI 0.11, 0.34). The relationship was attenuated after adjustment for current height and weight such that it became non-significant (β = 0.03 kg/s.d. increase in adjusted birth weight; 95% CI−0.08, 0.14), suggesting that body size may be on the causal pathway. Early influences on muscle development appear to impact on grip strength in children, as well as adults. [ABSTRACT FROM PUBLISHER]

Objective Consistent positive relationships have been found between birthweight and grip strength in young, middle-aged and older adults, suggesting that early influences on the growth and development of muscle are important for muscle function later in the lifecourse. However there are limited data in children. We aimed to assess the relationship between birthweight and grip strength in children aged 4 years. Design Prospective general population birth cohort study with data from birth to four years, drawn from the Southampton Women's Survey. Grip strength was measured using a Jamar handgrip dynamometer at age four years. We also measured height and weight and assessed body composition (lean mass) using dual energy x-ray absorptiometry. Multiple regression was used to relate grip strength to birthweight allowing for adjustment for confounding factors. Setting Southampton, UK. Participants 968 children took part in a sub-study assessing body composition and had their grip strength measured at age four years. Their socio-demographic characteristics were similar to the remainder of the cohort. Main outcome measure Grip strength in kilograms. Results Birthweight was positively associated with grip strength, with each kilogram of birthweight being associated with a 0.5 kg increase in grip strength (95% CI 0.30 to 0.70). Grip strength was also strongly related to current body size and adjustment of the birthweight relationship for height and weight attenuated the relationship such that it became non-significant with a 1kg increase in birthweight being associated with 0.15kg (95% CI -0.05 to 0.34kg) increase in grip strength. Adjustment for absolute and percentage lean mass instead of height and weight attenuated the relationship still further such that only a 0.07kg (95% CI −0.16 to 0.30) increase in grip strength was seen in relation to a 1kg increase in birthweight. Conclusion Birthweight is associated with muscle strength in children aged 4 years. Adjustment for current body size or lean mass explains the relationship suggesting that muscle size is on the causal pathway. Early influences on muscle growth and development appear to impact on grip strength in children as well as adults. [ABSTRACT FROM PUBLISHER]

Background: Normothermic ex situ liver perfusion is increasingly used to assess donor livers, but there remains a paucity of evidence regarding criteria upon which to base a viability assessment or criteria predicting early allograft function., Methods: Perfusate variables from livers undergoing normothermic ex situ liver perfusion were analyzed to see which best predicted the Model for Early Allograft Function score., Results: One hundred fifty-four of 203 perfused livers were transplanted following our previously defined criteria. These comprised 84/123 donation after circulatory death livers and 70/80 donation after brain death livers. Multivariable analysis suggested that 2-h alanine transaminase, 2-h lactate, 11 to 29 mmol supplementary bicarbonate in the first 4 h, and peak bile pH were associated with early allograft function as defined by the Model for Early Allograft Function score. Nonanastomotic biliary strictures occurred in 11% of transplants, predominantly affected first- and second-order ducts, despite selection based on bile glucose and pH., Conclusions: This work confirms the importance of perfusate alanine transaminase and lactate at 2-h, as well as the amount of supplementary bicarbonate required to keep the perfusate pH > 7.2, in the assessment of livers undergoing perfusion. It cautions against the use of lactate as a sole indicator of viability and also suggests a role for cholangiocyte function markers in predicting early allograft function., Competing Interests: C.J.E.W. participated in advisory boards with Nefro Health and Jazz Pharmaceuticals and has received speaker fees from OrganOx. A.J.B. is coholder of a patent on the circuit used in the OrganOx metra. C.D.L.C. has received income from OrganOx Ltd for teaching and training and for carrying out normothermic preservations after normal working hours. The other authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

The incidence of gestational hypertension (GH) and pre-eclampsia (PE) is increasing. Use of blood pressure (BP) change patterns may improve early detection of BP abnormalities. We used Linear spline random-effects models to estimate BP patterns across pregnancy for white British and Pakistani women. Pakistani women compared to white British women had lower BP during the first two trimesters of pregnancy, irrespective of the development of GH or PE or presence of a risk factor. Pakistani compared to white British women with GH and PE showed steeper BP increases towards the end of pregnancy. Pakistani women were half as likely to develop GH, but as likely to develop PE than white British women. To conclude; BP trajectories differ by ethnicity. Because GH developed evenly from 20 weeks gestation, and PE occurred more commonly after 36 weeks in both ethnic groups, the lower BP up to the third trimester in Pakistani women resulted in a lower GH rate, whereas PE rates, influenced by the steep third trimester BP increase were similar. Criteria for diagnosing GH and PE may benefit from considering ethnic differences in BP change across pregnancy.

Background: Many statistical methods are available to model longitudinal growth data and relate derived summary measures to later outcomes., Aim: To apply and compare commonly used methods to a realistic scenario including pre- and postnatal data, missing data, and confounders., Subjects and Methods: Data were collected from 753 offspring in the Southampton Women's Survey with measurements of bone mineral content (BMC) at age 6 years. Ultrasound measures included crown-rump length (11 weeks' gestation) and femur length (19 and 34 weeks' gestation); postnatally, infant length (birth, 6 and 12 months) and height (2 and 3 years) were measured. A residual growth model, two-stage multilevel linear spline model, joint multilevel linear spline model, SITAR and a growth mixture model were used to relate growth to 6-year BMC., Results: Results from the residual growth, two-stage and joint multilevel linear spline models were most comparable: an increase in length at all ages was positively associated with BMC, the strongest association being with later growth. Both SITAR and the growth mixture model demonstrated that length was positively associated with BMC., Conclusions: Similarities and differences in results from a variety of analytic strategies need to be understood in the context of each statistical methodology.

We examined the association between pregnancy and life-course lipid trajectories. Linked data from the Nord-Trøndelag Health Study and the Medical Birth Registry of Norway yielded 19,987 parous and 1,625 nulliparous women. Using mixed-effects spline models, we estimated differences in nonfasting lipid levels from before to after first birth in parous women and between parous and nulliparous women. HDL cholesterol (HDL-C) dropped by -4.2 mg/dl (95% CI: -5.0, -3.3) from before to after first birth in adjusted models, a 7% change, and the total cholesterol (TC) to HDL-C ratio increased by 0.18 (95% CI: 0.11, 0.25), with no change in non-HDL-C or triglycerides. Changes in HDL-C and the TC/HDL-C ratio associated with pregnancy persisted for decades, leading to altered life-course lipid trajectories. For example, parous women had a lower HDL-C than nulliparous women at the age of 50 years (-1.4 mg/dl; 95% CI: -2.3, -0.4). Adverse changes in lipids were greatest after first birth, with small changes after subsequent births, and were larger in women who did not breastfeed. Findings suggest that pregnancy is associated with long-lasting adverse changes in HDL-C, potentially setting parous women on a more atherogenic trajectory than prior to pregnancy., (Copyright © 2018 Markovitz et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.)

The article was originally published electronically on the publisher's internet portal (currently SpringerLink) on 24 January 2018 without open access.

Background Women with hypertensive pregnancy disorders have adverse levels of cardiovascular risk factors. It is unclear how this adverse risk factor profile evolves during adult life. We compared life course trajectories of cardiovascular risk factors in women with preeclampsia or gestational hypertension in their first pregnancy to normotensive women. Methods and Results We linked information on cardiovascular risk factors from the population-based HUNT (Nord-Trøndelag Health Study) surveys with pregnancy information from the Medical Birth Registry of Norway. Trajectories of cardiovascular risk factors were constructed for 22 308 women with a normotensive first pregnancy; 1092 with preeclampsia, and 478 with gestational hypertension in first pregnancy. Already before first pregnancy, women with preeclampsia in their first pregnancy had higher measures of adiposity, blood pressure, heart rate, and serum lipids and glucose compared with women with a normotensive first pregnancy. After first pregnancy, there was a parallel development in cardiovascular risk factor levels, but women with a normotensive first pregnancy had a time lag of >10 years compared with the preeclampsia group. There were no clear differences in risk factor trajectories between women with gestational hypertension and women with preeclampsia. Conclusions Women with hypertensive pregnancy disorders in their first pregnancy had an adverse cardiovascular risk factor profile before pregnancy compared with normotensive women, and the differences persisted beyond 50 years of age. Hypertensive disorders in pregnancy signal long-term increases in modifiable cardiovascular risk factors, and may be used to identify women who would benefit from early prevention strategies.

The drop in blood pressure during pregnancy may persist postpartum, but the impact of pregnancy on blood pressure across the life course is not known. In this study we examined blood pressure trajectories for women in the years preceding and following pregnancy and compared life course trajectories of blood pressure for parous and nulliparous women. We linked information on all women who participated in the population-based, longitudinal HUNT Study, Norway with pregnancy information from the Medical Birth Registry of Norway. A total of 23,438 women were included with up to 3 blood pressure measurements per woman. Blood pressure trajectories were compared using a mixed effects linear spline model. Before first pregnancy, women who later gave birth had similar mean blood pressure to women who never gave birth. Women who delivered experienced a drop after their first birth of - 3.32 mmHg (95% CI, - 3.93, - 2.71) and - 1.98 mmHg (95% CI, - 2.43, - 1.53) in systolic and diastolic blood pressure, respectively. Subsequent pregnancies were associated with smaller reductions. These pregnancy-related reductions in blood pressure led to persistent differences in mean blood pressure, and at age 50, parous women still had lower systolic (- 1.93 mmHg; 95% CI, - 3.33, - 0.53) and diastolic (- 1.36 mmHg; 95% CI, - 2.26, - 0.46) blood pressure compared to nulliparous women. The findings suggest that the first pregnancy and, to a lesser extent, successive pregnancies are associated with lasting and clinically relevant reductions in systolic and diastolic blood pressure.

Estimating velocity and acceleration trajectories allows novel inferences in the field of longitudinal data analysis, such as estimating change regions rather than change points, and testing group effects on nonlinear change in an outcome (ie, a nonlinear interaction). In this article, we develop derivative estimation for 2 standard approaches-polynomial mixed models and spline mixed models. We compare their performance with an established method-principal component analysis through conditional expectation through a simulation study. We then apply the methods to repeated blood pressure (BP) measurements in a UK cohort of pregnant women, where the goals of analysis are to (i) identify and estimate regions of BP change for each individual and (ii) investigate the association between parity and BP change at the population level. The penalized spline mixed model had the lowest bias in our simulation study, and we identified evidence for BP change regions in over 75% of pregnant women. Using mean velocity difference revealed differences in BP change between women in their first pregnancy compared with those who had at least 1 previous pregnancy. We recommend the use of penalized spline mixed models for derivative estimation in longitudinal data analysis., (© 2018 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Background: Negative control exposure studies are increasingly being used in epidemiological studies to strengthen causal inference regarding an exposure-outcome association when unobserved confounding is thought to be present. Negative control exposure studies contrast the magnitude of association of the negative control, which has no causal effect on the outcome but is associated with the unmeasured confounders in the same way as the exposure, with the magnitude of the association of the exposure with the outcome. A markedly larger effect of the exposure on the outcome than the negative control on the outcome strengthens inference that the exposure has a causal effect on the outcome., Methods: We investigate the effect of measurement error in the exposure and negative control variables on the results obtained from a negative control exposure study. We do this in models with continuous and binary exposure and negative control variables using analysis of the bias of the estimated coefficients and Monte Carlo simulations., Results: Our results show that measurement error in either the exposure or negative control variables can bias the estimated results from the negative control exposure study., Conclusions: Measurement error is common in the variables used in epidemiological studies; these results show that negative control exposure studies cannot be used to precisely determine the size of the effect of the exposure variable, or adequately adjust for unobserved confounding; however, they can be used as part of a body of evidence to aid inference as to whether a causal effect of the exposure on the outcome is present.