Can routine antenatal blood pressure measurements between 20 and 36 weeks' gestation contribu... more Can routine antenatal blood pressure measurements between 20 and 36 weeks' gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes? This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women's Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks. The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared wit...
Greater adiposity is an important risk factor for nonalcoholic fatty liver disease (NAFLD). Thus,... more Greater adiposity is an important risk factor for nonalcoholic fatty liver disease (NAFLD). Thus, it is likely that dietary intake is involved in the development of the disease. Prospective studies assessing the relation between childhood dietary intake and risk of NAFLD are lacking. This study was designed to explore associations between energy, carbohydrate, sugar, starch, protein, monounsaturated fat, polyunsaturated fat, saturated fat, and total fat intake by youth at ages 3, 7, and 13 y and subsequent (mean age: 17.8 y) ultrasound scan (USS)-measured liver fat and stiffness and serum alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase. We assessed whether observed associations were mediated through fat mass at the time of outcome assessment. Participants were from the Avon Longitudinal Study of Parents and Children. Trajectories of energy and macronutrient intake from ages 3-13 y were obtained with linear-spline multilevel models. Linear and logistic...
Objectives To obtain valid estimates of the association between body mass index (BMI) and mortali... more Objectives To obtain valid estimates of the association between body mass index (BMI) and mortality by using offspring BMI as an instrumental variable for own BMI.Design Cohort study based on record linkage, with 50 years of follow-up for mortality. Associations of offspring BMI with all cause and cause specific maternal and paternal mortality were estimated as hazard ratios per standard
Results from studies examining associations of maternal diabetes in pregnancy with offspring cogn... more Results from studies examining associations of maternal diabetes in pregnancy with offspring cognitive outcomes have been inconclusive. Methods. We used data from the Avon Longitudinal Study of Parents and Children, a UK prospective pregnancy cohort. Outcomes were School Entry Assessment (SEA) scores (age 4, N = 6, 032) and WISC-III IQ (age 8, N = 5, 282-5, 307) and General Certificate of Secondary Education (GCSE) results (age 16, N = 7, 615). Results. Existing diabetes, gestational diabetes, and, to a lesser extent, glycosuria were associated with lower offspring SEA scores (age 4), IQ (age 8), and GCSE results (age 16) even when adjusting for offspring sex, maternal age, prepregnancy BMI, smoking in pregnancy, parity, caesarean section, maternal education, and occupational social class. Offspring of mothers with existing diabetes had a threefold risk of achieving no GCSEs graded A * -C, whilst offspring of women with gestational diabetes had, on average, a five point lower IQ compared to offspring of women with no diabetes or glycosuria. Conclusions. Maternal diabetes in pregnancy is consistently associated with lower offspring cognition and educational attainment though confidence intervals were wide. The weaker associations with glycosuria suggest a dose-dependent adverse association with IQ.
Hypertensive disorders of pregnancy are associated with intrauterine growth restriction and prete... more Hypertensive disorders of pregnancy are associated with intrauterine growth restriction and preterm birth. However, the associations of patterns of blood pressure change during pregnancy with these outcomes have not been studied in detail. We studied repeat antenatal blood pressure measurements of 9697 women in the Avon Longitudinal Study of Parents and Children (median [interquartile range], 10 [9-11] measurements per woman). Bivariate linear spline models were used to relate blood pressure changes to perinatal outcomes. Higher systolic, but not diastolic, blood pressure at baseline (8 weeks of gestation) and a greater increase in systolic and diastolic blood pressure between 18 and 36 weeks of gestation were associated with lower offspring birth weight and being smaller for gestational age in confounder-adjusted models. For example, the mean difference (95% confidence interval) in birth weight per 1 mm Hg/wk greater increase in systolic blood pressure between 18 and 30 weeks was -71 g (-134 to -14) and between 30 and 36 weeks was -175 g (-208 to -145). A smaller decrease in systolic and diastolic blood pressure before 18 weeks and a greater increase between 18 and 36 weeks were associated with a shorter gestation (percentage difference in gestational duration per 1 mm Hg/wk greater increase in systolic blood pressure between 18 and 30 weeks was -0.60% [-1.01 to -0.18] and between 30 and 36 weeks was -1.01% [-1.36 to -0.74]). Associations remained strong when restricting to normotensive women. We conclude that greater increases in blood pressure, from the 18-week nadir, are related to reduced fetal growth and shorter gestation even in women whose blood pressure does not cross the threshold for hypertensive disorders of pregnancy.
Adiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of i... more Adiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of infant and childhood adiposity with subsequent NAFLD risk. We examined associations of weight-for-height trajectories from birth to age 10 with liver outcomes in adolescence, and assessed the extent to which associations are mediated through fat mass at the time of outcome assessment. Individual trajectories of weight and height were estimated for participants in the Avon Longitudinal Study of Parents and Children using random-effects linear-spline models. Associations of birthweight (adjusted for birth length) and weight change (adjusted for length/height change) from 0-3 months, 3 months-1 y, 1-3 y, 3-7 y, and 7-10 y with ultrasound scan (USS) determined liver fat and stiffness, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) at mean age 17.8 y were assessed with linear and logistic regressions. Mediation by concurrent fat mass was assessed with adjustment for fat mass at mean age 17.8 y. Birth weight was positively associated with liver stiffness and negatively with ALT and AST. Weight change from birth to 1 y was not associated with outcomes. Weight change from 1-3 y, 3-7 y, and 7-10 y was consistently positively associated with USS and blood-based liver outcomes. Adjusting for fat mass at mean age 17.8 y attenuated associations toward the null, suggesting associations are largely mediated by concurrent body fatness. Greater rates of weight-for-height change between 1 y and 10 y are consistently associated with adverse liver outcomes in adolescence. These associations are largely mediated through concurrent fatness.
Objectives: To assess the effect of quinolone prophylaxis following chemotherapy for malignancies... more Objectives: To assess the effect of quinolone prophylaxis following chemotherapy for malignancies on the emergence of resistant bacteria in neutropenic patients.
We compared patterns of blood pressure (BP) change between normotensive women, women who develope... more We compared patterns of blood pressure (BP) change between normotensive women, women who developed gestational hypertension or preeclampsia and women who had essential hypertension to examine how distinct these conditions are and whether rates of BP change may help to identify women at risk of hypertensive disorders. We used antenatal clinic BP measurements (median 14 per woman) of 13,016 women from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had a singleton or twin live birth surviving until at least 1 year. Linear spline models were used to describe changes in systolic and diastolic BP in different periods of pregnancy (8-18, 18-30, 30-36 and 36+ weeks gestation). Women who had essential hypertension, and those who developed gestational hypertension or preeclampsia had higher BP at 8 weeks gestation (baseline) compared with normotensive women. The decrease in BP until 18 weeks was smaller in gestational hypertensive compared with normotensive pregnancies. BP rose more rapidly from 18 weeks onwards in gestational hypertensive and preeclamptic pregnancies and from 30 weeks onwards in essential hypertensive compared with normotensive pregnancies. Women who developed preeclampsia had a more rapid increase in BP from 30 weeks onwards than those who developed gestational hypertension or had essential hypertension. Our findings indicate notable patterns of BP change that distinguish women with essential hypertension, gestational hypertension and preeclampsia from each other and from normotensive women, even from early pregnancy. These distinct patterns may be useful for identifying women at risk of developing a hypertensive disorder later in pregnancy.
Associations between biomarkers of nonalcoholic fatty liver disease (NAFLD) alanine aminotransfer... more Associations between biomarkers of nonalcoholic fatty liver disease (NAFLD) alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), with 3 separate measures of glucose homeostasis: fasting glucose, fasting insulin and glycated hemoglobin (HbA1c) were studied and compared between women with and without diabetes in order to gain insight into the documented associations between NAFLD, insulin resistance and diabetes. Data from the British Women's Health and Heart Study, a random sample of British women aged 60-79 years (N = 3394; 3086 without diabetes and 308 with diabetes) was used. Associations of ALT and GGT with fasting glucose and HbA1c and of ALT with fasting insulin (and homeostasis model assessment of insulin resistance [HOMA]) are stronger in women with diabetes compared to women without diabetes (P for interaction < 0.001). GGT is associated with fasting insulin (and HOMA) to the same extent in all women, irrespective of diabetes status. Results excluding hyperinsulinemic women, i.e., in the highest fourth of the fasting insulin distribution, were similar to those obtained for all non-diabetic women as were results excluding women in the highest quartile of the alcohol consumption distribution and for women with ALT and GGT levels within the normal range. Associations did not differ substantially between obese and non-obese non-diabetic women. elevation of liver enzymes and hepatic insulin resistance as reflected by fasting insulin occur in the early stages of insulin resistance and highlight the central role of the liver in insulin resistance in the general population.
We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospit... more We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospital stay in medical inpatients with bacterial infections. SUBJECTS AND METHODS: Two cohorts of febrile adult patients (excluding patients with acquired immune deficiency syndrome and organ transplant recipients), hospitalized in three medical centers in Israel, Italy, and Germany, were included. Patients' data were collected prospectively. Initial empirical treatment was defined as appropriate if an antibiotic prescribed within 24 hours of the first encounter with the patient matched the in vitro susceptibility of a pathogen deemed to be the likely cause of infection. The results of cultures and serologic or direct tests, and data on outcomes were collected 30 days after initiation of empirical treatment. RESULTS: A total of 920 patients (26% of 3529 included patients) had microbiologically documented infections, and mortality data were available for 895 patients (97%). Inappropriate initial antibiotic treatment was prescribed in 36% of patients (N ϭ 319). All-cause 30-day mortality rates were 20.1% (N ϭ 64) and 11.8% (N ϭ 68) in patients who received inappropriate and appropriate treatment, respectively (odds ratio ϭ 1.88, 95% confidence interval [CI], 1.29-2.72, P ϭ .001). When adjustment was made for medical center and other variables, the association between inappropriate with mortality was significant (odds ratio ϭ 1.58, 95% CI, 0.99-2.54, P ϭ .058). In all 3 medical centers, the mean duration of hospital stay was at least 2 days longer for patients who were prescribed inappropriate antibiotic treatment (overall P ϭ .002). This association was consistent after adjusting for other variables (P ϭ .006). CONCLUSION: Appropriate empirical antibiotic treatment is associated with a better survival and shortened duration of hospital stay in medical patients with bacterial infections.
OBJECTIVE -To estimate and compare associations of alanine aminotransferase (ALT) and ␥-glutamylt... more OBJECTIVE -To estimate and compare associations of alanine aminotransferase (ALT) and ␥-glutamyltransferase (GGT) with incident diabetes.
Methods for the assessment of changes in dietary intake across the life course are underdeveloped... more Methods for the assessment of changes in dietary intake across the life course are underdeveloped. We demonstrate the use of linear-spline multilevel models to summarize energy-intake trajectories through childhood and adolescence and their application as exposures, outcomes, or mediators. The Avon Longitudinal Study of Parents and Children assessed children's dietary intake several times between ages 3 and 13 years, using both food frequency questionnaires (FFQs) and 3-day food diaries. We estimated energy-intake trajectories for 12,032 children using linear-spline multilevel models. We then assessed the associations of these trajectories with maternal body mass index (BMI), and later offspring BMI, and also their role in mediating the relation between maternal and offspring BMIs. Models estimated average and individual energy intake at 3 years, and linear changes in energy intake from age 3 to 7 years and from age 7 to 13 years. By including the exposure (in this example, maternal BMI) in the multilevel model, we were able to estimate the average energy-intake trajectories across levels of the exposure. When energy-intake trajectories are the exposure for a later outcome (in this case offspring BMI) or a mediator (between maternal and offspring BMI), results were similar, whether using a two-step process (exporting individual-level intercepts and slopes from multilevel models and using these in linear regression/path analysis), or a single-step process (multivariate multilevel models). Trajectories were similar when FFQs and food diaries were assessed either separately, or when combined into one model. Linear-spline multilevel models provide useful summaries of trajectories of dietary intake that can be used as an exposure, outcome, or mediator.
We sought to examine the association of gestational weight gain (GWG) and prepregnancy weight wit... more We sought to examine the association of gestational weight gain (GWG) and prepregnancy weight with offspring adiposity and cardiovascular risk factors. Data from 5154 (for adiposity and blood pressure) and 3457 (for blood assays) mother-offspring pairs from a UK prospective pregnancy cohort were used. Random-effects multilevel models were used to assess incremental GWG (median and range of repeat weight measures per woman: 10 [1, 17]). Women who exceeded the 2009 Institute of Medicine-recommended GWG were more likely to have offspring with greater body mass index, waist, fat mass, leptin, systolic blood pressure, C-reactive protein, and interleukin-6 levels and lower high-density lipoprotein cholesterol and apolipoprotein A1 levels. Children of women who gained less than the recommended amounts had lower levels of adiposity, but other cardiovascular risk factors tended to be similar in this group to those of offspring of women gaining recommended amounts. When examined in more detail, greater prepregnancy weight was associated with greater offspring adiposity and more adverse cardiovascular risk factors at age 9 years. GWG in early pregnancy (0 to 14 weeks) was positively associated with offspring adiposity across the entire distribution but strengthened in women gaining >500 g/wk. By contrast, between 14 and 36 weeks, GWG was only associated with offspring adiposity in women gaining >500 g/wk. GWG between 14 and 36 weeks was positively and linearly associated with adverse lipid and inflammatory profiles, with these associations largely mediated by the associations with offspring adiposity. Greater maternal prepregnancy weight and GWG up to 36 weeks of gestation are associated with greater offspring adiposity and adverse cardiovascular risk factors. Before any GWG recommendations are implemented, the balance of risks and benefits of attempts to control GWG for short- and long-term outcomes in mother and child should be ascertained.
International journal of epidemiology, Jan 8, 2015
Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposi... more Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposity in later life. Epigenetic modification is suggested as a plausible mediating mechanism. We used multivariable linear regression and a negative control design to examine offspring epigenome-wide DNA methylation in relation to maternal and offspring adiposity in 1018 participants. Compared with neonatal offspring of normal weight mothers, 28 and 1621 CpG sites were differentially methylated in offspring of obese and underweight mothers, respectively [false discovert rate (FDR)-corrected P-value < 0.05), with no overlap in the sites that maternal obesity and underweight relate to. A positive association, where higher methylation is associated with a body mass index (BMI) outside the normal range, was seen at 78.6% of the sites associated with obesity and 87.9% of the sites associated with underweight. Associations of maternal obesity with offspring methylation were stronger than assoc...
The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how ge... more The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19-22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17-18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on 410 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.
Can routine antenatal blood pressure measurements between 20 and 36 weeks' gestation contribu... more Can routine antenatal blood pressure measurements between 20 and 36 weeks' gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes? This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women's Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks. The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared wit...
Greater adiposity is an important risk factor for nonalcoholic fatty liver disease (NAFLD). Thus,... more Greater adiposity is an important risk factor for nonalcoholic fatty liver disease (NAFLD). Thus, it is likely that dietary intake is involved in the development of the disease. Prospective studies assessing the relation between childhood dietary intake and risk of NAFLD are lacking. This study was designed to explore associations between energy, carbohydrate, sugar, starch, protein, monounsaturated fat, polyunsaturated fat, saturated fat, and total fat intake by youth at ages 3, 7, and 13 y and subsequent (mean age: 17.8 y) ultrasound scan (USS)-measured liver fat and stiffness and serum alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase. We assessed whether observed associations were mediated through fat mass at the time of outcome assessment. Participants were from the Avon Longitudinal Study of Parents and Children. Trajectories of energy and macronutrient intake from ages 3-13 y were obtained with linear-spline multilevel models. Linear and logistic...
Objectives To obtain valid estimates of the association between body mass index (BMI) and mortali... more Objectives To obtain valid estimates of the association between body mass index (BMI) and mortality by using offspring BMI as an instrumental variable for own BMI.Design Cohort study based on record linkage, with 50 years of follow-up for mortality. Associations of offspring BMI with all cause and cause specific maternal and paternal mortality were estimated as hazard ratios per standard
Results from studies examining associations of maternal diabetes in pregnancy with offspring cogn... more Results from studies examining associations of maternal diabetes in pregnancy with offspring cognitive outcomes have been inconclusive. Methods. We used data from the Avon Longitudinal Study of Parents and Children, a UK prospective pregnancy cohort. Outcomes were School Entry Assessment (SEA) scores (age 4, N = 6, 032) and WISC-III IQ (age 8, N = 5, 282-5, 307) and General Certificate of Secondary Education (GCSE) results (age 16, N = 7, 615). Results. Existing diabetes, gestational diabetes, and, to a lesser extent, glycosuria were associated with lower offspring SEA scores (age 4), IQ (age 8), and GCSE results (age 16) even when adjusting for offspring sex, maternal age, prepregnancy BMI, smoking in pregnancy, parity, caesarean section, maternal education, and occupational social class. Offspring of mothers with existing diabetes had a threefold risk of achieving no GCSEs graded A * -C, whilst offspring of women with gestational diabetes had, on average, a five point lower IQ compared to offspring of women with no diabetes or glycosuria. Conclusions. Maternal diabetes in pregnancy is consistently associated with lower offspring cognition and educational attainment though confidence intervals were wide. The weaker associations with glycosuria suggest a dose-dependent adverse association with IQ.
Hypertensive disorders of pregnancy are associated with intrauterine growth restriction and prete... more Hypertensive disorders of pregnancy are associated with intrauterine growth restriction and preterm birth. However, the associations of patterns of blood pressure change during pregnancy with these outcomes have not been studied in detail. We studied repeat antenatal blood pressure measurements of 9697 women in the Avon Longitudinal Study of Parents and Children (median [interquartile range], 10 [9-11] measurements per woman). Bivariate linear spline models were used to relate blood pressure changes to perinatal outcomes. Higher systolic, but not diastolic, blood pressure at baseline (8 weeks of gestation) and a greater increase in systolic and diastolic blood pressure between 18 and 36 weeks of gestation were associated with lower offspring birth weight and being smaller for gestational age in confounder-adjusted models. For example, the mean difference (95% confidence interval) in birth weight per 1 mm Hg/wk greater increase in systolic blood pressure between 18 and 30 weeks was -71 g (-134 to -14) and between 30 and 36 weeks was -175 g (-208 to -145). A smaller decrease in systolic and diastolic blood pressure before 18 weeks and a greater increase between 18 and 36 weeks were associated with a shorter gestation (percentage difference in gestational duration per 1 mm Hg/wk greater increase in systolic blood pressure between 18 and 30 weeks was -0.60% [-1.01 to -0.18] and between 30 and 36 weeks was -1.01% [-1.36 to -0.74]). Associations remained strong when restricting to normotensive women. We conclude that greater increases in blood pressure, from the 18-week nadir, are related to reduced fetal growth and shorter gestation even in women whose blood pressure does not cross the threshold for hypertensive disorders of pregnancy.
Adiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of i... more Adiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of infant and childhood adiposity with subsequent NAFLD risk. We examined associations of weight-for-height trajectories from birth to age 10 with liver outcomes in adolescence, and assessed the extent to which associations are mediated through fat mass at the time of outcome assessment. Individual trajectories of weight and height were estimated for participants in the Avon Longitudinal Study of Parents and Children using random-effects linear-spline models. Associations of birthweight (adjusted for birth length) and weight change (adjusted for length/height change) from 0-3 months, 3 months-1 y, 1-3 y, 3-7 y, and 7-10 y with ultrasound scan (USS) determined liver fat and stiffness, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) at mean age 17.8 y were assessed with linear and logistic regressions. Mediation by concurrent fat mass was assessed with adjustment for fat mass at mean age 17.8 y. Birth weight was positively associated with liver stiffness and negatively with ALT and AST. Weight change from birth to 1 y was not associated with outcomes. Weight change from 1-3 y, 3-7 y, and 7-10 y was consistently positively associated with USS and blood-based liver outcomes. Adjusting for fat mass at mean age 17.8 y attenuated associations toward the null, suggesting associations are largely mediated by concurrent body fatness. Greater rates of weight-for-height change between 1 y and 10 y are consistently associated with adverse liver outcomes in adolescence. These associations are largely mediated through concurrent fatness.
Objectives: To assess the effect of quinolone prophylaxis following chemotherapy for malignancies... more Objectives: To assess the effect of quinolone prophylaxis following chemotherapy for malignancies on the emergence of resistant bacteria in neutropenic patients.
We compared patterns of blood pressure (BP) change between normotensive women, women who develope... more We compared patterns of blood pressure (BP) change between normotensive women, women who developed gestational hypertension or preeclampsia and women who had essential hypertension to examine how distinct these conditions are and whether rates of BP change may help to identify women at risk of hypertensive disorders. We used antenatal clinic BP measurements (median 14 per woman) of 13,016 women from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had a singleton or twin live birth surviving until at least 1 year. Linear spline models were used to describe changes in systolic and diastolic BP in different periods of pregnancy (8-18, 18-30, 30-36 and 36+ weeks gestation). Women who had essential hypertension, and those who developed gestational hypertension or preeclampsia had higher BP at 8 weeks gestation (baseline) compared with normotensive women. The decrease in BP until 18 weeks was smaller in gestational hypertensive compared with normotensive pregnancies. BP rose more rapidly from 18 weeks onwards in gestational hypertensive and preeclamptic pregnancies and from 30 weeks onwards in essential hypertensive compared with normotensive pregnancies. Women who developed preeclampsia had a more rapid increase in BP from 30 weeks onwards than those who developed gestational hypertension or had essential hypertension. Our findings indicate notable patterns of BP change that distinguish women with essential hypertension, gestational hypertension and preeclampsia from each other and from normotensive women, even from early pregnancy. These distinct patterns may be useful for identifying women at risk of developing a hypertensive disorder later in pregnancy.
Associations between biomarkers of nonalcoholic fatty liver disease (NAFLD) alanine aminotransfer... more Associations between biomarkers of nonalcoholic fatty liver disease (NAFLD) alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), with 3 separate measures of glucose homeostasis: fasting glucose, fasting insulin and glycated hemoglobin (HbA1c) were studied and compared between women with and without diabetes in order to gain insight into the documented associations between NAFLD, insulin resistance and diabetes. Data from the British Women&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Health and Heart Study, a random sample of British women aged 60-79 years (N = 3394; 3086 without diabetes and 308 with diabetes) was used. Associations of ALT and GGT with fasting glucose and HbA1c and of ALT with fasting insulin (and homeostasis model assessment of insulin resistance [HOMA]) are stronger in women with diabetes compared to women without diabetes (P for interaction &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). GGT is associated with fasting insulin (and HOMA) to the same extent in all women, irrespective of diabetes status. Results excluding hyperinsulinemic women, i.e., in the highest fourth of the fasting insulin distribution, were similar to those obtained for all non-diabetic women as were results excluding women in the highest quartile of the alcohol consumption distribution and for women with ALT and GGT levels within the normal range. Associations did not differ substantially between obese and non-obese non-diabetic women. elevation of liver enzymes and hepatic insulin resistance as reflected by fasting insulin occur in the early stages of insulin resistance and highlight the central role of the liver in insulin resistance in the general population.
We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospit... more We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospital stay in medical inpatients with bacterial infections. SUBJECTS AND METHODS: Two cohorts of febrile adult patients (excluding patients with acquired immune deficiency syndrome and organ transplant recipients), hospitalized in three medical centers in Israel, Italy, and Germany, were included. Patients' data were collected prospectively. Initial empirical treatment was defined as appropriate if an antibiotic prescribed within 24 hours of the first encounter with the patient matched the in vitro susceptibility of a pathogen deemed to be the likely cause of infection. The results of cultures and serologic or direct tests, and data on outcomes were collected 30 days after initiation of empirical treatment. RESULTS: A total of 920 patients (26% of 3529 included patients) had microbiologically documented infections, and mortality data were available for 895 patients (97%). Inappropriate initial antibiotic treatment was prescribed in 36% of patients (N ϭ 319). All-cause 30-day mortality rates were 20.1% (N ϭ 64) and 11.8% (N ϭ 68) in patients who received inappropriate and appropriate treatment, respectively (odds ratio ϭ 1.88, 95% confidence interval [CI], 1.29-2.72, P ϭ .001). When adjustment was made for medical center and other variables, the association between inappropriate with mortality was significant (odds ratio ϭ 1.58, 95% CI, 0.99-2.54, P ϭ .058). In all 3 medical centers, the mean duration of hospital stay was at least 2 days longer for patients who were prescribed inappropriate antibiotic treatment (overall P ϭ .002). This association was consistent after adjusting for other variables (P ϭ .006). CONCLUSION: Appropriate empirical antibiotic treatment is associated with a better survival and shortened duration of hospital stay in medical patients with bacterial infections.
OBJECTIVE -To estimate and compare associations of alanine aminotransferase (ALT) and ␥-glutamylt... more OBJECTIVE -To estimate and compare associations of alanine aminotransferase (ALT) and ␥-glutamyltransferase (GGT) with incident diabetes.
Methods for the assessment of changes in dietary intake across the life course are underdeveloped... more Methods for the assessment of changes in dietary intake across the life course are underdeveloped. We demonstrate the use of linear-spline multilevel models to summarize energy-intake trajectories through childhood and adolescence and their application as exposures, outcomes, or mediators. The Avon Longitudinal Study of Parents and Children assessed children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s dietary intake several times between ages 3 and 13 years, using both food frequency questionnaires (FFQs) and 3-day food diaries. We estimated energy-intake trajectories for 12,032 children using linear-spline multilevel models. We then assessed the associations of these trajectories with maternal body mass index (BMI), and later offspring BMI, and also their role in mediating the relation between maternal and offspring BMIs. Models estimated average and individual energy intake at 3 years, and linear changes in energy intake from age 3 to 7 years and from age 7 to 13 years. By including the exposure (in this example, maternal BMI) in the multilevel model, we were able to estimate the average energy-intake trajectories across levels of the exposure. When energy-intake trajectories are the exposure for a later outcome (in this case offspring BMI) or a mediator (between maternal and offspring BMI), results were similar, whether using a two-step process (exporting individual-level intercepts and slopes from multilevel models and using these in linear regression/path analysis), or a single-step process (multivariate multilevel models). Trajectories were similar when FFQs and food diaries were assessed either separately, or when combined into one model. Linear-spline multilevel models provide useful summaries of trajectories of dietary intake that can be used as an exposure, outcome, or mediator.
We sought to examine the association of gestational weight gain (GWG) and prepregnancy weight wit... more We sought to examine the association of gestational weight gain (GWG) and prepregnancy weight with offspring adiposity and cardiovascular risk factors. Data from 5154 (for adiposity and blood pressure) and 3457 (for blood assays) mother-offspring pairs from a UK prospective pregnancy cohort were used. Random-effects multilevel models were used to assess incremental GWG (median and range of repeat weight measures per woman: 10 [1, 17]). Women who exceeded the 2009 Institute of Medicine-recommended GWG were more likely to have offspring with greater body mass index, waist, fat mass, leptin, systolic blood pressure, C-reactive protein, and interleukin-6 levels and lower high-density lipoprotein cholesterol and apolipoprotein A1 levels. Children of women who gained less than the recommended amounts had lower levels of adiposity, but other cardiovascular risk factors tended to be similar in this group to those of offspring of women gaining recommended amounts. When examined in more detail, greater prepregnancy weight was associated with greater offspring adiposity and more adverse cardiovascular risk factors at age 9 years. GWG in early pregnancy (0 to 14 weeks) was positively associated with offspring adiposity across the entire distribution but strengthened in women gaining &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;500 g/wk. By contrast, between 14 and 36 weeks, GWG was only associated with offspring adiposity in women gaining &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;500 g/wk. GWG between 14 and 36 weeks was positively and linearly associated with adverse lipid and inflammatory profiles, with these associations largely mediated by the associations with offspring adiposity. Greater maternal prepregnancy weight and GWG up to 36 weeks of gestation are associated with greater offspring adiposity and adverse cardiovascular risk factors. Before any GWG recommendations are implemented, the balance of risks and benefits of attempts to control GWG for short- and long-term outcomes in mother and child should be ascertained.
International journal of epidemiology, Jan 8, 2015
Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposi... more Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposity in later life. Epigenetic modification is suggested as a plausible mediating mechanism. We used multivariable linear regression and a negative control design to examine offspring epigenome-wide DNA methylation in relation to maternal and offspring adiposity in 1018 participants. Compared with neonatal offspring of normal weight mothers, 28 and 1621 CpG sites were differentially methylated in offspring of obese and underweight mothers, respectively [false discovert rate (FDR)-corrected P-value < 0.05), with no overlap in the sites that maternal obesity and underweight relate to. A positive association, where higher methylation is associated with a body mass index (BMI) outside the normal range, was seen at 78.6% of the sites associated with obesity and 87.9% of the sites associated with underweight. Associations of maternal obesity with offspring methylation were stronger than assoc...
The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how ge... more The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19-22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17-18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on 410 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.
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Papers by Abigail Fraser