Predicting Early Allograft Function After Normothermic Machine Perfusion.

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.

Blood pressure change across pregnancy in white British and Pakistani women: analysis of data from the Born in Bradford cohort.

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.

A discussion of statistical methods to characterise early growth and its impact on bone mineral content later in childhood.

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.

Life Course Trajectories of Cardiovascular Risk Factors in Women With and Without Hypertensive Disorders in First Pregnancy: The HUNT Study in Norway.

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.

Does pregnancy alter life-course lipid trajectories? Evidence from the HUNT Study in Norway.

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.

Correction to: The impact of parity on life course blood pressure trajectories: the HUNT study in Norway.

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

Derivative estimation for longitudinal data analysis: Examining features of blood pressure measured repeatedly during pregnancy.

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.

The impact of parity on life course blood pressure trajectories: the HUNT study in Norway.

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.

Negative control exposure studies in the presence of measurement error: implications for attempted effect estimate calibration.

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.

A longitudinal study of the associations of children's body mass index and physical activity with blood pressure.

Childhood blood pressure is a marker of cardiovascular disease risk in later life. We examined how body mass index (BMI) and physical activity, and changes in these, are associated with blood pressure in primary school-aged children. Data are from 1223 children aged 9 years (Year 4) in Bristol, UK, 685 of whom had been assessed at 6 years (Year 1). Child height and weight were measured, and children wore accelerometers for five days, from which average counts per minute, and moderate-to-vigorous-intensity physical activity and sedentary minutes per day were derived. At age 9 years, blood pressure was measured. Multiple imputation of missing data and adjusted linear regression models were used to examine associations. Child BMI at 9 years was cross-sectionally associated with higher systolic (SBP) and diastolic (DBP) blood pressure (mean difference [95% CI]: 1.10 [0.34, 1.87] mmHg and 0.86 [0.13, 1.60] mmHg, respectively, per SD of BMI). Prospective associations of BMI at age 6 with blood pressure at age 9 were consistent with these cross-sectional associations. However, change in BMI between 6 and 9 years was not strongly associated with subsequent SBP or DBP (0.68 [-0.61, 1.98] mmHg and 1.23 [-0.09, 2.54] mmHg, respectively). There was little evidence that physical activity or sedentary time were associated with blood pressure in either cross-sectional or prospective analyses. Greater childhood BMI is associated with higher blood pressure, and this association persists over several years. Prevention of excessive bodyweight from early childhood may be important in stemming the development of cardiovascular risk.

Associations between participation in organised physical activity in the school or community outside school hours and neighbourhood play with child physical activity and sedentary time: a cross-sectional analysis of primary school-aged children from the UK.

OBJECTIVES: To assess the extent to which participation in organised physical activity in the school or community outside school hours and neighbourhood play was associated with children's physical activity and sedentary time. DESIGN: Cross-sectional study. SETTING: Children were recruited from 47 state-funded primary schools in South West England. PARTICIPANTS: 1223 children aged 8-9 years old. OUTCOME MEASURES: Accelerometer-assessed moderate-to-vigorous-intensity physical activity (MVPA) and sedentary time. METHODS: Children wore an accelerometer, and the mean minutes of MVPA and sedentary time per day were derived. Children reported their attendance at organised physical activity in the school or community outside school hours and neighbourhood play using a piloted questionnaire. Cross-sectional linear and logistic regression were used to examine if attendance frequency at each setting (and all settings combined) was associated with MVPA and sedentary time. Multiple imputation methods were used to account for missing data and increase sample size. RESULTS: Children who attended clubs at school 3-4 days per week obtained an average of 7.58 (95% CI 2.7 to 12.4) more minutes of MVPA per day than children who never attended. Participation in the three other non-school-based activities was similarly associated with MVPA. Evidence for associations with sedentary time was generally weaker. Associations were similar in girls and boys. When the four different contexts were combined, each additional one to two activities participated in per week increased participants' odds (OR: 1.18, 95% CI 1.12 to 1.25) of meeting the government recommendations for 60 min of MVPA per day. CONCLUSION: Participating in organised physical activity at school and in the community is associated with greater physical activity and reduced sedentary time among both boys and girls. All four types of activity contribute to overall physical activity, which provides parents with a range of settings in which to help their child be active.

Association of parents' and children's physical activity and sedentary time in Year 4 (8-9) and change between Year 1 (5-6) and Year 4: a longitudinal study.

BACKGROUND: Parents could be important influences on child physical activity and parents are often encouraged to be more active with their child. This paper examined the association between parent and child physical activity and sedentary time in a UK cohort of children assessed when the children were in Year 1 (5-6 years old) and in Year 4 (8-9 years old). METHODS: One thousand two hundred twenty three children and parents provided data in Year 4 and of these 685 participated in Year 1. Children and parents wore an accelerometer for five days including a weekend. Mean minutes of sedentary time and moderate-to-vigorous intensity physical activity (MVPA) were derived. Multiple imputation was used to impute all missing data and create complete datasets. Linear regression models examined whether parent MVPA and sedentary time at Year 4 and at Year 1 predicted child MVPA and sedentary time at Year 4. Change in parent MVPA and sedentary time was used to predict change in child MVPA and sedentary time between Year 1 and Year 4. RESULTS: Imputed data showed that at Year 4, female parent sedentary time was associated with child sedentary time (0.13, 95% CI = 0.00 to 0.27 mins/day), with a similar association for male parents (0.15, 95% CI = -0.02 to 0.32 mins/day). Female parent and child MVPA at Year 4 were associated (0.16, 95% CI = 0.08 to 0.23 mins/day) with a smaller association for male parents (0.08, 95% CI = -0.01 to 0.17 mins/day). There was little evidence that either male or female parent MVPA at Year 1 predicted child MVPA at Year 4 with similar associations for sedentary time. There was little evidence that change in parent MVPA or sedentary time predicted change in child MVPA or sedentary time respectively. CONCLUSIONS: Parents who were more physically active when their child was 8-9 years old had a child who was more active, but the magnitude of association was generally small. There was little evidence that parental activity from three years earlier predicted child activity at age 8-9, or that change in parent activity predicted change in child activity.

Exploring parents' screen-viewing behaviours and sedentary time in association with their attitudes toward their young child's screen-viewing.

Sedentary time and screen-viewing (SV) are associated with chronic disease risk in adults. Parent and child sedentary time and SV are associated. Parents influence children's SV through parenting styles and role modelling. Understanding whether parents' attitudes toward child SV are associated with their own SV and sedentary time will aid development of family interventions to reduce sedentary behaviours. Cross-sectional data with 809 parents from Bristol, UK were collected in 2012-2013 and analysed in 2016. Parental total sedentary time was derived from accelerometer data. Parents self-reported daily television viewing, use of computers, games consoles, and smartphone/tablets (none, 1-59 min, 1-2 h, > 2 h) and attitudes toward child SV. Adjusted linear and logistic regression models were used to examine associations, separately for weekdays and weekend days. Having negative attitudes toward child SV was associated with lower weekend sedentary time (Coeff: - 6.41 [95% CI: - 12.37 to - 0.45] min/day). Limiting behaviours and having negative attitudes toward child SV were associated with lower weekday television viewing (OR: 0.72 [0.57-0.90] and 0.57 [0.47-0.70] respectively), weekend television viewing (0.75 [0.59-0.95] and 0.61 [0.50-0.75]), and weekend computer use (0.73 [0.58-0.92] and 0.80 [0.66-0.97]). Negative attitudes were also associated with lower smartphone use on weekdays (0.70 [0.57-0.85]) and weekends (0.70 [0.58-0.86]). Parent self-efficacy for limiting child SV and setting SV rules were not associated with sedentary time or SV. Reporting negative attitudes toward child SV was associated with lower accelerometer-assessed weekend total sedentary time and self-reported SV behaviours, while limiting child SV was also associated with lower self-reported SV.

Change in children's physical activity and sedentary time between Year 1 and Year 4 of primary school in the B-PROACT1V cohort.

BACKGROUND: The aim of this study was to examine how children's and parents' physical activity changes from Year 1 (5-6) to Year 4 (8-9 years of age). METHODS: Data are from the Bristol (UK) B-PROACT1V cohort. Fifty-seven primary schools were recruited when the children were in Year 1, with 1299 children and their parents providing data. Forty-seven schools were re-recruited in Year 4, with 1223 children and parents providing data (685 of whom participated in Year 1). Children and at least one parent wore an accelerometer for 5 days including a weekend and mean minutes of sedentary time, moderate-to-vigorous intensity physical activity (MVPA) and accelerometer counts per minute (CPM) were derived. Multiple imputation was used to impute missing data for all 1837 families who took part, including those who participated at just one time. Paired t-tests examined if there was statistical evidence of change in accelerometer measures. RESULTS: Multiple imputation and observed data were comparable and results using complete observed data were mostly the same as those using imputed data. Imputed data showed that mean boys' CPM decreased from 747 to 673 (difference in mean 74 [95% CI 45 to 103]) and girls' from 686 to 587 (99 [79 to 119]). Boys' time spent in MVPA reduced from 72 to 69 (3 [0 to 6]) and girls' from 62 to 56 (7 [4 to 9]) minutes per day. There were increases in sedentary time for both boys (354 to 428 min, 74 [61 to 88]) and girls (365 to 448, 83 [71 to 96]). There was no evidence of change in parent CPM or MVPA. Mothers' sedentary time increased by 26 min per day [16 to 35]. CONCLUSIONS: There were similar increases in sedentary time in girls and boys between age 5-6 and 8-9, and decreases in MVPA that were more marked in girls. The similarity of multiple-imputed and complete observed data suggest that these findings may not be markedly affected by selection bias. Result support early interventions to prevent the age-related decline in children's physical activity.

Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis.

Background: : Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother, placenta and fetus. This may lead to different adaptive mechanisms during pregnancy. Methods: We performed an individual participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating in a worldwide consortium of international research groups focusing on pregnancy. Results: Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered ≥ 37 weeks). Preterm PE (delivered < 37 weeks) was slightly more prevalent among pregnancies with a female fetus than in pregnancies with a male fetus [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02-1.21]. Very preterm PE (delivered < 34 weeks) was even more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59). Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences with respect to term PE.

Hypertensive Disorders of Pregnancy and Offspring Cardiac Structure and Function in Adolescence.

BACKGROUND: Fetal exposure to preeclampsia is associated with higher blood pressure and later risk of stroke. We aimed to investigate the associations of maternal preeclampsia, gestational hypertension, and maternal blood pressure change in pregnancy with offspring cardiac structure and function in adolescence. METHODS AND RESULTS: Using data from a prospective birth cohort study, we included offspring who underwent echocardiography (mean age, 17.7 years; SD, 0.3; N=1592). We examined whether hypertensive disorders of pregnancy were associated with offspring cardiac structure and systolic/diastolic function using linear regression. Using multilevel linear spline models (measurement occasions within women), we also investigated whether rate of maternal systolic/diastolic blood pressure change during pregnancy (weeks 8-18, 18-30, 30-36, and 36 or more) were associated with offspring outcomes. Main models were typically adjusted for maternal age, offspring age and sex, prepregnancy body mass index, parity, glycosuria/diabetes mellitus, education, and maternal smoking. Exposure to maternal preeclampsia (0.025; 95% CI, 0.008-0.043) and gestational hypertension (0.010; 0.002-0.017) were associated with greater relative wall thickness. Furthermore, preeclampsia was also associated with a smaller left ventricular end-diastolic volume (-9.0 mL; -15 to -3.1). No associations were found between hypertensive disorders of pregnancy and offspring cardiac function. Positive rate of maternal systolic blood pressure change during weeks 8 to 18 was associated with greater offspring left ventricular end-diastolic volume, left ventricular mass indexed to height2.7, and E/A. CONCLUSIONS: Adolescent offspring exposed to maternal preeclampsia had greater relative wall thickness and reduced left ventricular end-diastolic volume, which could be early signs of concentric remodeling and affect future cardiac function as well as risk of cardiovascular disease.

Relationship between mediation analysis and the structured life course approach.

Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome).

A structured approach to hypotheses involving continuous exposures over the life course.

BACKGROUND: Epidemiologists are often interested in examining different hypotheses for how exposures measured repeatedly over the life course relate to later-life outcomes. A structured approach for selecting the hypotheses most supported by theory and observed data has been developed for binary exposures. The aim of this paper is to extend this to include continuous exposures and allow for confounding and missing data. METHODS: We studied two examples, the association between: (i) maternal weight during pregnancy and birthweight; and (ii) stressful family events throughout childhood and depression in adolescence. In each example we considered several plausible hypotheses including accumulation, critical periods, sensitive periods, change and effect modification. We used least angle regression to select the hypothesis that explained the most variation in the outcome, demonstrating appropriate methods for adjusting for confounders and dealing with missing data. RESULTS: The structured approach identified a combination of sensitive periods: pre-pregnancy weight, and gestational weight gain 0-20 weeks and 20-40 weeks, as the best explanation for variation in birthweight after adjusting for maternal height. A sensitive period hypothesis best explained variation in adolescent depression, with the association strengthening with the proximity of stressful family events. For each example, these models have theoretical support at least as strong as any competing hypothesis. CONCLUSIONS: We have extended the structured approach to incorporate continuous exposures, confounding and missing data. This approach can be used in either an exploratory or a confirmatory setting. The interpretation, plausibility and consistency with causal assumptions should all be considered when proposing and choosing life course hypotheses.

Association of maternal diabetes/glycosuria and pre-pregnancy body mass index with offspring indicators of non-alcoholic fatty liver disease.

BACKGROUND: Little is known about early life determinants of non-alcoholic fatty liver disease (NAFLD). We examined associations of maternal pregnancy diabetes/glycosuria and pre-pregnancy body mass index (BMI) with offspring markers of NAFLD and liver pathology and examined mediation by birthweight and concurrent offspring adiposity. METHODS: We used data from a UK prospective pregnancy cohort. Offspring underwent abdominal ultrasonography (USS) at mean age 17.8 years. Outcomes included USS-assessed fatty liver, estimated liver volume and shear velocity, a variant of elastography (a marker of liver fibrosis) (N = 1 215) and blood-based markers of liver pathology [alanine amino transferase, aspartate amino transferase, gamma- glutamyltransferase and haptoglobin] (N = 2 359). RESULTS: 2.1 % (N = 25) of participants had USS-assessed fatty liver [maternal diabetes/glycosuria (N = 7) and no diabetes/glycosuria (N = 18)]. Maternal diabetes/glycosuria was associated with greater odds of offspring USS fatty liver in confounder adjusted models [adjusted odds ratio (aOR) 6.74 (95 % confidence interval (CI) 2.47, 18.40)] and higher shear velocity [adjusted ratio of geometric mean (aRGM):1.10 (95 % CI 1.05, 1.15)]. These associations were not mediated by offspring birthweight or concurrent adiposity. Maternal diabetes/glycosuria was not associated with liver volume or blood-based outcomes. Greater maternal pre-pregnancy BMI was associated with greater odds of offspring USS fatty liver [aOR 2.72 (95 % CI: 1.20, 6.15)], higher liver volume [aRGM 1.03 (95 % CI 1.00, 1.07)] and shear velocity [aRGM1.03 (95 % CI: 1.01, 1.06)] in confounder adjusted models. These associations were largely mediated by offspring adiposity. Maternal pre-pregnancy BMI was not consistently associated with blood-based outcomes. CONCLUSIONS: Results suggest that maternal pregnancy diabetes/glycosuria is associated with offspring NAFLD through mechanisms other than offspring's own adiposity.

Hypertensive disorders of pregnancy, respiratory outcomes and atopy in childhood.

Few epidemiological studies have investigated the role of hypertensive disorders of pregnancy in the aetiology of childhood respiratory and atopic outcomes.In the Avon Longitudinal Study of Parents and Children we examined associations of maternal gestational hypertension, hypertension before pregnancy and pre-eclampsia with wheezing at 18 months, wheezing and asthma at 7 years and lung function at 8-9 years, after controlling for potential confounders (n=5322-8734, depending on outcome).Gestational hypertension was not associated with any of the outcomes. There was weak evidence for a positive association between pre-eclampsia and early wheezing (adjusted OR 1.31, 95% CI 0.94-1.82, compared to normotensive pregnancies) and for negative associations between pre-eclampsia and forced expiratory volume in 1 s (adjusted mean difference in sd score -0.14, 95% CI -0.33-0.06) and maximal mid-expiratory flow (-0.15, 95% CI -0.34-0.04). Hypertension before pregnancy was positively associated with wheezing (OR 1.63, 95% CI 1.16-2.31) and asthma (OR 1.34, 95% CI 1.00-1.79).Gestational hypertension is unlikely to be a risk factor for childhood respiratory disorders; hypertension before pregnancy may be a risk factor for childhood wheezing and asthma, but this finding needs replication. Larger studies are needed to confirm whether pre-eclampsia is associated with impaired childhood lung function.