Barry J. Milne

Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism

Childrens intellectual development is influenced by both genetic inheritance and environmental experiences. Breastfeeding is one of the earliest such postnatal experiences. Breastfed children attain higher IQ scores than children not fed breast milk, presumably because of the fatty acids uniquely available in breast milk. Here we show that the association between breastfeeding and IQ is moderated by a genetic variant in FADS2, a gene involved in the genetic control of fatty acid pathways. We confirmed this gene–environment interaction in two birth cohorts, and we ruled out alternative explanations of the finding involving gene–exposure correlation, intrauterine growth, social class, and maternal cognitive ability, as well as maternal genotype effects on breastfeeding and breast milk. The finding shows that environmental exposures can be used to uncover novel candidate genes in complex phenotypes. It also shows that genes may work via the environment to shape the IQ, helping to close the nature versus nurture debate.

A Replicated Molecular Genetic Basis for Subtyping Antisocial Behavior in Children With Attention-Deficit/Hyperactivity Disorder

CONTEXT Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder that in some cases is accompanied by antisocial behavior. OBJECTIVE To test if variations in the catechol O-methyltransferase gene (COMT) would prove useful in identifying the subset of children with ADHD who exhibit antisocial behavior. DESIGN Three independent samples composed of 1 clinical sample of ADHD cases and 2 birth cohort studies. PARTICIPANTS Participants in the clinical sample were drawn from child psychiatry and child health clinics in England and Wales. The 2 birth cohort studies included 1 sample of 2232 British children born in 1994-1995 and a second sample of 1037 New Zealander children born in 1972-1973. MAIN OUTCOME MEASURES Diagnosis of ADHD and measures of antisocial behavior. RESULTS We present replicated evidence that the COMT valine/methionine polymorphism at codon 158 (COMT Val158Met) was associated with phenotypic variation among children with ADHD. Across the 3 samples, valine/valine homozygotes had more symptoms of conduct disorder, were more aggressive, and were more likely to be convicted of criminal offenses compared with methionine carriers. CONCLUSIONS The findings confirm the presence of genetic heterogeneity in ADHD and illustrate how genetic information may provide biological evidence pointing to clinical subtypes.

Migraine and cognitive function A life-course study

Objective To investigate the association between migraine and cognitive ability among members of a longitudinal birth cohort study. MethodsHeadache status was determined at age 26 (migraine, tension-type headache [TTH], headache-free control subjects) according to International Headache Society criteria, and data relating to cognitive and academic performance from ages 3 to 26 years were analyzed. ResultsStudy members diagnosed with migraine were subtly but significantly impaired, compared with those with TTH and headache-free control subjects, on tests of verbal ability (especially language reception) from ages 3 to 13, independent of headache history. Performance on other tasks, including reading, arithmetic, motor, and spatial ability, was normal. The association between migraine and verbal functioning also appeared to impact on later academic success. ConclusionFindings suggest that the poorer verbal performance was unlikely to have resulted from cumulative attacks and may be due to developmental factors beginning in utero.

Childhood to Early-Midlife Systolic Blood Pressure Trajectories Early-Life Predictors, Effect Modifiers, and Adult Cardiovascular Outcomes

Previous studies examining blood pressure change over time have modeled an average population trajectory. Recent research among older adults suggests there may be subgroups with different blood pressure trajectories. Identifying subgroups at risk of developing adult hypertension early in life can inform effective risk reduction efforts. We sought to identify different systolic blood pressure trajectories from childhood, their correlated risk factors, and early-midlife cardiovascular outcomes. Blood pressure data at ages 7, 11, 18, 26, 32, and 38 years from a longitudinal, representative birth cohort study (n=975) were used to identify 4 distinct trajectory groups via group-based trajectory modeling: normal (21.8%), high-normal (43.3%), prehypertensive (31.6%), and hypertensive (4.2%). The categories refer to blood pressure beginning at the age of 7 years and most recently measured at the age of 38 years. Family history of high blood pressure (odds ratio [OR], 43.23; 95% confidence interval [CI], 5.27–354.65), male sex (OR, 109.48; 95% CI, 26.82–446.96), being first born (OR, 2.5; 95% CI, 1.00–8.69) and low birth weight (OR, 2.79; 95% CI, 2.49–3.09) were associated with hypertensive group membership (compared with the normal group). Higher body mass index and cigarette smoking resulted in increasing blood pressure across trajectories, particularly for the higher blood pressure groups. Prehypertensive and hypertensive trajectory groups had worse cardiovascular outcomes by early midlife. Harmful blood pressure trajectories are identifiable in childhood, associated with both antecedent and modifiable risk factors over time, and predict adult cardiovascular disease risk. Early detection and subsequent targeted prevention and intervention may reduce the lifecourse burden associated with higher blood pressure. # Novelty and Significance {#article-title-34}Previous studies examining blood pressure change over time have modeled an average population trajectory. Recent research among older adults suggests there may be subgroups with different blood pressure trajectories. Identifying subgroups at risk of developing adult hypertension early in life can inform effective risk reduction efforts. We sought to identify different systolic blood pressure trajectories from childhood, their correlated risk factors, and early-midlife cardiovascular outcomes. Blood pressure data at ages 7, 11, 18, 26, 32, and 38 years from a longitudinal, representative birth cohort study (n=975) were used to identify 4 distinct trajectory groups via group-based trajectory modeling: normal (21.8%), high-normal (43.3%), prehypertensive (31.6%), and hypertensive (4.2%). The categories refer to blood pressure beginning at the age of 7 years and most recently measured at the age of 38 years. Family history of high blood pressure (odds ratio [OR], 43.23; 95% confidence interval [CI], 5.27–354.65), male sex (OR, 109.48; 95% CI, 26.82–446.96), being first born (OR, 2.5; 95% CI, 1.00–8.69) and low birth weight (OR, 2.79; 95% CI, 2.49–3.09) were associated with hypertensive group membership (compared with the normal group). Higher body mass index and cigarette smoking resulted in increasing blood pressure across trajectories, particularly for the higher blood pressure groups. Prehypertensive and hypertensive trajectory groups had worse cardiovascular outcomes by early midlife. Harmful blood pressure trajectories are identifiable in childhood, associated with both antecedent and modifiable risk factors over time, and predict adult cardiovascular disease risk. Early detection and subsequent targeted prevention and intervention may reduce the lifecourse burden associated with higher blood pressure.

Worlds apart: a comparison between physical activities among youth in Glasgow, Scotland and Dunedin, New Zealand.

Against the background of increasing concern about levels of physical activity among young people, this paper reports the results of a cross-national comparison between two longitudinal studies of young people in Glasgow, Scotland and Dunedin, New Zealand, which used similar methods of assessment at 15 and 18 years of age. The comparison revealed that, on average, young people in Dunedin participated in a greater range of activities, encompassing both organised sports and informal activities such as cycling, and with greater frequency than those in Glasgow at both ages, but particularly so at age 18. The difference was especially marked for females, among whom one in three in Glasgow reported no physical activity at all at age 18. By contrast, in both sexes among those who did participate, much less difference in levels of involvement was observed between the two locations. Of 35 activities, only in respect of soccer, and only for males, did participation and involvement in Glasgow exceed that of Dunedin. Neither climatic factors, natural features of the environment, socio-economic composition, nor different proportions in single-sex/co-educational schooling explain the difference in levels of participation between the two locations. Participation rates in selected physical activities do, however, reflect different opportunity structures in Dunedin and Glasgow, with an advantage accruing to the former in respect of both school and post-school provision. Cultural factors, which underpin such differences, also appear to have an additional influence on participation, most notably in relation to the gender gap in physical activities, much bigger in Glasgow than Dunedin. To redress these differences requires an increase in levels of participation generally, particularly among females, which depends as much on a shift in values about physical activity as on the provision of better resources.

Efficiency, effectiveness, equity (E3). Evaluating hospital performance in three dimensions

There are well-established frameworks for comparing the performance of health systems cross-nationally on multiple dimensions. A sub-set of such comprehensive schema is taken up by criteria specifically applied to health service delivery, including hospital performance. We focus on evaluating hospital performance, using the New Zealand public hospital sector over the period 2001-2009 as a pragmatic and illustrative case study for cross-national application. We apply a broad three-dimensional matrix--efficiency, effectiveness, equity--each based on two measures, and we undertake ranking comparisons of 35 hospitals. On the efficiency dimension--relative stay, day surgery--we find coefficients of variation of 10.8% and 8.5% respectively in the pooled data, and a slight trend towards a narrowing of inter-hospital variation over time. The correlation between these indicators is low (.20). For effectiveness--post-admission mortality, unplanned readmission--the coefficient of variation is generally higher (24.1% and 12.2%), and the trend is flat. The correlation is again low (.21). The equity dimension is assessed by quantifying the degree of ethnic and socio-economic variation for each hospital. The coefficient of variation is much higher--40.7-66.5% for ethnicity, 55.8-84.4% for socio-economic position--the trend over time is mixed, and the correlation is moderate (.41). On averaging the rank of hospitals across all measures it is evident that there is limited consistency across the three constituent dimensions. While it is possible to assess hospital performance across three dimensions using an illustrative set of standard measures derived from routine data, there appears to be little consistency in hospital rankings on these New Zealand data for the period 2001-2009. However, the methodology of using rankings derived from readily available data--possibly allied with multiple or composite indicator models--has potential for the cross-national comparison of hospital profiles, and assessments in three dimensions provide a more holistic and rounded account of performance.

Cumulative mental health consequences of acne: 23-year follow-up in a general population birth cohort study.

DEAR EDITOR, Acne is a highly prevalent condition during adolescence and young adulthood worldwide, with rates between 12% and 99%. Rates in adulthood range up to 50%. The effects of acne, regardless of severity, can be debilitating, affecting many life domains. Cross-sectional studies report associations between acne and anxiety, depression symptoms and suicide ideation compared with those having little or no acne. However, no study has examined the relationship of acne with psychiatric disorder (i.e. psychological distress of greatest severity and clinical interest), nor has research ascertained the cumulative life course effects of acne on psychiatric disorder. Here, we report data from a prospective-longitudinal study of a general population sample to determine whether acne preceded poor mental health at the disorder level, from adolescence to adulthood. The specific aim of this study was to examine the association between acne and the development of the most common psychiatric disorders of anxiety, depression, alcohol and cannabis dependence. Data were from the Dunedin Multidisciplinary Health and Development Study, a longitudinal investigation of the health, development and behaviour of a general population birth cohort. Study participants were born between April 1972 and March 1973 in Dunedin, New Zealand. The cohort represents the full range of socioeconomic status in the general population of New Zealand’s South Island and is primarily white. The longitudinal study was established at age three when those who were still resident in the province were followed up, and 91% (n = 1037; 52% male) participated. Subsequent assessments took place at ages 5 (96% of those alive participated), 7 (92%), 9 (92%), 11 (90%), 13 (82%), 15 (95%), 18 (97%), 21 (97%), 26 (97%) and 32 (96%), and most recently at 38 years, when 95% participated. At each age, a range of physical, mental and psychosocial measures were assessed on site by professional staff trained in each of the domains. Ethical approval was obtained for each phase of the study. At all the assessments, professional staff with specific training in the relevant domains received further training standardized to protocol. Health professionals administered the general health interview (which included questions about acne) and the mental health interview. At the age 21 assessment, study participants were asked if, since age 15, they had ‘a bad problem acne’; this was repeated at the next three assessments, i.e. at age 26 for the period from 21 to 26 years, at age 32 (26– 32 years) and at age 38 (32–38 years). Mental health data were collected using the Diagnostic Interview Schedule, allowing disorder status to be made according to standardized Diagnostic and Statistical Manual of Mental Disorders criteria. Each disorder (anxiety, depression, alcohol dependence and cannabis dependence disorders) was diagnosed regardless of the presence of other disorders using the past year as the reporting period. Adjustment was made for potential confounders: sex, socioeconomic status and prior adolescent psychiatric disorder (11–18 years).

Determinants and disparities: A simulation approach to the case of child health care

Though there is much agreement on the importance of the social determinants of health, debate continues on suitable empirically-based models to underpin efforts to tackle health and health care disparities. We demonstrate an approach that uses a dynamic micro-simulation model of the early life course, based on longitudinal data from a New Zealand cohort of children born in 1977, and counterfactual reasoning applied to a range of outcomes. The focus is on health service use with a comparison to outcomes in non-health domains, namely educational attainment and antisocial behaviour. We show an application of the model to test scenarios based on modifying key determinants and assessing the impact on putative outcomes. We found that appreciable improvement was only effected by modifying multiple determinants; structural determinants were relatively more important than intermediary ones as potential policy levers; there was a social gradient of effect; and interventions bestowed the greatest benefit to the most disadvantaged groups with a corresponding reduction in disparities between the worst-off and the best-off. Our findings provide evidence on how public policy initiatives might be more effective acting broadly across sectors and across social groups, and thus make a real difference to the most disadvantaged.

Improving rates of overweight, obesity and extreme obesity in New Zealand 4-year-old children in 2010–2016

Prevalence of childhood obesity is high in developed countries, and there is a growing concern regarding increasing socio‐economic disparities.

Childhood to Early-Midlife Systolic Blood Pressure Trajectories

Previous studies examining blood pressure change over time have modeled an average population trajectory. Recent research among older adults suggests there may be subgroups with different blood pressure trajectories. Identifying subgroups at risk of developing adult hypertension early in life can inform effective risk reduction efforts. We sought to identify different systolic blood pressure trajectories from childhood, their correlated risk factors, and early-midlife cardiovascular outcomes. Blood pressure data at ages 7, 11, 18, 26, 32, and 38 years from a longitudinal, representative birth cohort study (n=975) were used to identify 4 distinct trajectory groups via group-based trajectory modeling: normal (21.8%), high-normal (43.3%), prehypertensive (31.6%), and hypertensive (4.2%). The categories refer to blood pressure beginning at the age of 7 years and most recently measured at the age of 38 years. Family history of high blood pressure (odds ratio [OR], 43.23; 95% confidence interval [CI], 5.27–354.65), male sex (OR, 109.48; 95% CI, 26.82–446.96), being first born (OR, 2.5; 95% CI, 1.00–8.69) and low birth weight (OR, 2.79; 95% CI, 2.49–3.09) were associated with hypertensive group membership (compared with the normal group). Higher body mass index and cigarette smoking resulted in increasing blood pressure across trajectories, particularly for the higher blood pressure groups. Prehypertensive and hypertensive trajectory groups had worse cardiovascular outcomes by early midlife. Harmful blood pressure trajectories are identifiable in childhood, associated with both antecedent and modifiable risk factors over time, and predict adult cardiovascular disease risk. Early detection and subsequent targeted prevention and intervention may reduce the lifecourse burden associated with higher blood pressure. # Novelty and Significance {#article-title-34}Previous studies examining blood pressure change over time have modeled an average population trajectory. Recent research among older adults suggests there may be subgroups with different blood pressure trajectories. Identifying subgroups at risk of developing adult hypertension early in life can inform effective risk reduction efforts. We sought to identify different systolic blood pressure trajectories from childhood, their correlated risk factors, and early-midlife cardiovascular outcomes. Blood pressure data at ages 7, 11, 18, 26, 32, and 38 years from a longitudinal, representative birth cohort study (n=975) were used to identify 4 distinct trajectory groups via group-based trajectory modeling: normal (21.8%), high-normal (43.3%), prehypertensive (31.6%), and hypertensive (4.2%). The categories refer to blood pressure beginning at the age of 7 years and most recently measured at the age of 38 years. Family history of high blood pressure (odds ratio [OR], 43.23; 95% confidence interval [CI], 5.27–354.65), male sex (OR, 109.48; 95% CI, 26.82–446.96), being first born (OR, 2.5; 95% CI, 1.00–8.69) and low birth weight (OR, 2.79; 95% CI, 2.49–3.09) were associated with hypertensive group membership (compared with the normal group). Higher body mass index and cigarette smoking resulted in increasing blood pressure across trajectories, particularly for the higher blood pressure groups. Prehypertensive and hypertensive trajectory groups had worse cardiovascular outcomes by early midlife. Harmful blood pressure trajectories are identifiable in childhood, associated with both antecedent and modifiable risk factors over time, and predict adult cardiovascular disease risk. Early detection and subsequent targeted prevention and intervention may reduce the lifecourse burden associated with higher blood pressure.