Methods Within a population-based birth cohort, both mothers and fathers reported on their smoking habits at several time-points during pregnancy. Behavioural problems were measured with the Child Behavior Checklist in 4680 children at the age of 18 months.

Results With adjustment for age and gender only, children of mothers who continued smoking during pregnancy had higher risk of Total Problems [odds ratio (OR) 1.59, 95% confidence interval (CI): 1.21–2.08] and Externalizing problems (OR 1.45, 95% CI: 1.15–1.84), compared with children of mothers who never smoked. Smoking by father when mother did not smoke, was also related to a higher risk of behavioural problems. The statistical association of parental smoking with behavioural problems was strongly confounded by parental characteristics, chiefly socioeconomic status and parental psychopathology; adjustment for these factors accounted entirely for the effect of both maternal and paternal smoking on child behavioural problems.

Conclusions Maternal smoking during pregnancy, as well as paternal smoking, occurs in the context of other factors that place the child at increased developmental risk, but may not be causally related to the child's behaviour. It is essential to include sufficient information on parental psychiatric symptoms in studies exploring the association between pre-natal cigarette smoke exposure and behavioural disorders.

Methods Children (n = 384) from a prospective population-based birth cohort were assessed at 4 years. The McCarthy Scales of Children's Abilities (MCSA) was administrated. Maternal smoking was measured by questionnaire. Genotyping was conducted for null alleles from GSTM1 and GSTT1. Multivariable linear regression models were used to examine the association between active maternal smoking during pregnancy and MCSA outcomes by GSTM1 and GSTT1 genotypes.

Results Maternal smoking during pregnancy (reporting, yes) was inversely associated with global cognitive score among children having null allele for GSTM1 (β = –4.73, 95% CI –9.45 to –0.02); but not among children with present allele (β = –1.04, 95% CI –7.88 to 5.81) (P for interaction 0.089). The interaction remained after adjusting by post-natal maternal smoking (P = 0.081). The effect was stronger for perceptual-performance (β = –3.68, 95% CI –8.39 to 1.03; P for interaction 0.087), quantitative (β = –7.00, 95% CI –17.39 to 3.39; P for interaction 0.048), verbal (β = –3.63, 95% CI –8.43 to 1.17; P for interaction 0.264) and executive function (β = –4.87, 95% CI –9.55 to –0.20; P for interaction 0.127). No interaction was found for GSTT1.

Conclusions GSTM1 deficiency increases the adverse effects of active maternal smoking during pregnancy on cognition in preschoolers, suggesting a biological interaction between child metabolic genes and tobacco smoke components in detoxification process during foetal neurodevelopment.

Methods A total of 20 936 women with singleton pregnancies were identified within three population-based pregnancy cohorts in Northern Finland (1985–1986) and in Denmark (1984–1987 and 1989–1991). We collected self-reported data on their pre-pregnancy and pregnancy smoking habits and followed the children to school age where teachers and parents rated hyperactivity and inattention symptoms.

Results Children, whose mothers smoked during pregnancy, had an increased prevalence of a high hyperactivity-inattention score compared with children of nonsmokers in each of the cohorts after adjustment for confounders but we found no statistical significant difference between the associations across the cohorts.

Conclusion The estimated association was not strongest in the population with the fewest smokers which does not support the hypothesis that the association is entirely due to genetic confounding.

Methods To examine whether prenatal exposure to acetaminophen reduces the risk of adverse pregnancy outcomes, we used data from the Danish National Birth Cohort. We also examined the combined potential effects of acetaminophen, coffee and tobacco use on pre-eclampsia and preterm birth. The study population consisted of women who provided information on acetaminophen use during pregnancy and gave birth to singletons (n = 98 140). The cohort was linked to the Danish National Hospital Registry and the Medical Birth Registry, which covers all Danish hospitals, miscarriages and births in Denmark.

Results Women using acetaminophen during the third trimester of pregnancy had an increased risk of preterm birth [adjusted hazard ratio (HR) = 1.14, 95% CI: 1.03–1.26]. The risk of preterm birth was increased in mothers with pre-eclampsia (HR = 1.55, 95% CI: 1.16–2.07) but not in women without pre-eclampsia (HR = 1.08, 95% CI: 0.97–1.20). Tobacco smoking and coffee consumption did not modify the effect of acetaminophen in any consistent pattern. No association was found between acetaminophen use and risk of preterm complications, miscarriages, stillbirths, low birth weight or small size for gestational age.

Conclusion Findings do not provide strong support for a change in clinical practice regarding use of acetaminophen during pregnancy, but the increased risk of preterm birth among women with pre-eclampsia should be further investigated.

Methods We carried out a case–control study nested in a large (n = 5337) prospective, multicentre cohort. All cohort women had an interview, examination and venipuncture at 24–26 weeks. Frozen plasma samples in spontaneous preterm births (n = 207) and 444 term controls were analysed for plasma homocysteine, folate, cholesterol (total, low-density lipoprotein and high-density lipoprotein) and thrombin–antithrombin (TAT) complexes. DNA was extracted and analysed for seven gene polymorphisms involved in thrombophilia or folate or homocysteine metabolism. Fresh placentas were fixed, stained and blindly assessed for histologic evidence of infarction and decidual vasculopathy.

Results High (above the median) plasma homocysteine and HDL cholesterol were significantly and independently associated with the risk of spontaneous preterm birth [adjusted odds ratios (OR)s = 1.9 (95% 1.1–3.3) and 0.5 (0.3–0.9), respectively]. A higher proportion of women with high homocysteine concentrations had decidual vasculopathy [(13.0 vs 6.8%; OR = 1.9 (1.1–3.5)], although the positive association between decidual vasculopathy and preterm birth did not achieve statistical significance [OR = 1.5 (0.9–2.7)]. No significant associations were observed with the DNA polymorphisms or with plasma TAT or folate levels.

Conclusions Similar vasculopathic risk factors may underlie preterm birth and adult coronary heart disease and stroke.

Methods In 1982, all 5914 hospital births (over 99% of all deliveries) occurring in Pelotas, Southern Brazil, were identified and studied prospectively on several occasions. In 2004–05, we attempted to trace the whole cohort and information on offspring birthweight was collected. Conditional growth modelling was used to assess the association between offspring birthweight and weight gain from birth to 20 months, and from 20 to 42 months.

Results In 2004–05, we interviewed 4297 subjects, with a follow-up rate of 77.4%. This manuscript includes data from 848 women who had already delivered a child and 525 men who were fathers at the mean age of 23 years. Maternal birthweight, weight and length for age Z-score at 20 months of age were positively associated with next-generation birthweight, whereas paternal variables were not related to the outcome. Conditional growth modelling analyses showed that women whose weight gain in the first 20 months of life was faster than predicted had heavier babies, whereas paternal weight gain was not associated. The association was strongest for mothers whose birthweight for gestational age was in the lowest tertile.

Conclusion Maternal, but not paternal birthweight and weight gain in early childhood are positively associated with next-generation birthweight.

Methods The database used was UBCoS Multigen, which combines existing data on an Uppsala cohort born 1915–29 with information on several subsequent generations. We analysed young men in the third generation with complete information about the earnings of paternal (n = 3577) and maternal (n = 4142) ancestors of the two preceding generations using OLS-regression.

Results On the paternal side, father's and grandfather's, but not grandmother's, earnings predicted cognitive ability and BMI. In the mutually adjusted models, the associations with cognitive ability largely remained for young men whose fathers [b = –0.96 (95% CI: –1.25, –0.66)] and grandfathers [b = –0.60 (–0.87, –0.33)] were poor rather than well-off, whereas for BMI, only the association with grandfather's earnings [b = 0.78 (0.37, 1.19)] persisted. On the maternal side, the mutually adjusted models indicated that the mother's [b = –0.89 (–1.14, –0.65)] and the grandfather's [b = –0.65 (–0.89, –0.41)], but not the grandmother's, earnings were predictive of cognitive ability, whereas only the grandfather's [b = 0.56 (0.18, 0.94)] earnings seemed to be important for BMI.

Conclusions The results suggest that the long arm of the family reaches beyond the second generation in its effect on health. Although this study has only scratched the surface of how health inequalities is reproduced, it suggests that policies that reduce social inequalities may have ramifications across several generations.

Methods We analysed data from a large programmatic cohort across 18 primary care centres providing ART in Lusaka, Zambia. Patients were stratified into three categories based on MPR-calculated adherence over the first 12 months: optimal (≥95%), suboptimal (80–94%) and poor (<80%).

Results Overall, 27 115 treatment-naïve adults initiated and continued ART for ≥12 months: 17 060 (62.9%) demonstrated optimal adherence, 7682 (28.3%) had suboptimal adherence and 2373 (8.8%) had poor adherence. When compared with those with optimal adherence, post-12-month mortality risk was similar among patients with sub-optimal adherence [adjusted hazard ratio (AHR) = 1.0; 95% CI: 0.9–1.2] but higher in patients with poor adherence (AHR = 1.7; 95% CI: 1.4–2.2). Those <80% MPR also appeared to have an attenuated CD4 response at 18 months (185 cells/µl vs 217 cells/µl; P < 0.001), 24 months (213 cells/µl vs 246 cells/µl; P < 0.001), 30 months (226 cells/µl vs 261 cells/µl; P < 0.001) and 36 months (245 cells/µl vs 275 cells/µl; P < 0.01) when compared with those above this threshold.

Conclusions MPR was predictive of clinical outcomes and immunologic response in this large public sector antiretroviral treatment program. This marker may have a role in guiding programmatic monitoring and clinical care in resource-constrained settings.

Methods A 1:1 matched case–control study was conducted in two ‘fever’ hospitals in Cairo. Acute hepatitis B cases were patients with acute hepatitis, positive HBs antigen, and high anti-HBc IgM titres. Control subjects were acute hepatitis A patients (positive anti-HAV IgM) or relatives of patients diagnosed with acute hepatitis C, identified at the same hospitals, with no past HBV infection (negative anti-HBc) and matched to cases on the same age and sex. Conditional logistic regression was used to identify factors associated with acute hepatitis B.

Results Between April 2002 and June 2006, 233 cases and 233 controls were recruited to the study. In multivariate analysis, factors associated with an increased HBV risk in males were illiteracy [odds ratio (OR) = 6.1, 95% confidence interval (CI) = 2.8–13.1], shaving at barbers (OR = 2.1, 95% CI = 1.1–3.9) and injecting drug use (IDU) (OR = 3.4, 95% CI = 1.0–11.4). In females, factors associated with an increased HBV risk were illiteracy (OR = 2.2, 95% CI = 1.0–5.0), recent (<1 year) marriage (OR = 42.0, 95% CI = 3.8–463.9 compared with single women) and giving birth (OR = 3.7, 95% CI = 1.0–13.9).

Conclusion In this study, HBV transmission took place primarily in the community, whether as a result of recent marriage (presumably first sexual intercourse), shaving at barbershops or IDU, and was more common among illiterates. Health promotion campaigns should be carried out to increase awareness about community transmission of HBV. In addition to routine immunization for infants and other populations, premarital screening might be useful to identify at-risk spouses in order to propose targeted immunization.

Methods We used a dynamic time-to-event analysis of data from two large child studies in low-income settings in Ghana and Brazil, with the cumulative diarrhoea prevalence over 2 weeks as the exposure and severe ALRI as outcome. The analysis was adjusted for baseline risk of ALRI and diarrhoea, seasonality and age.

Results The child population from Ghana had a much higher risk of diarrhoea, malnutrition and death than the children in Brazil. In the data from Ghana, every additional day of diarrhoea within 2 weeks increased the risk of ALRI by a factor of 1.08 (95% CI 1.00–1.15). In addition, we found a roughly linear relationship between the number of diarrhoea days over the last 28 days and the risk of ALRI. In the Ghana data, 26% of ALRI episodes may be due to recent exposure to diarrhoea. The Brazilian data gave no evidence for an association between diarrhoea and ALRI.

Conclusion Diarrhoea may contribute substantially to the burden of ALRI in malnourished child populations.

Methods We conducted a cross-sectional study of subjects ≥45 years of age, who were tested for seropositivity to CMV, HSV-1 or both pathogens and assessed for cardiovascular disease history in the National Health and Nutrition Examination Survey III. Cardiovascular disease history was defined as history of stroke, heart attack and/or congestive heart failure and SEP as education level.

Results SEP was associated with CMV, HSV-1 and seropositivity to both pathogens. CMV seropositivity was associated with cardiovascular disease history even after adjusting for confounders as well as SEP. The odds of reporting a history of cardiovascular disease for those with less than a high school education compared with those with more than a high school education decreased by 7.7% after adjusting for CMV (Sobel mediation test for CMV, P = 0.0006). In contrast, neither seropositivity to HSV-1 nor to both pathogens was associated with cardiovascular disease history after adjusting for SEP.

Conclusions Persistent pathogens such as CMV infection may explain a portion of the relationship between SEP and cardiovascular disease in the United States. Further studies examining additional pathogens and sociobiological mechanisms are warranted.

Methods Use of standardized 24-h sodium excretion estimates for adults from the international INTERSALT (1985–87) and INTERMAP (1996–99) studies, and recent dietary and urinary sodium data from observational or interventional studies—identified by a comprehensive search of peer-reviewed and ‘grey’ literature—presented separately for adults and children. Review of methods for the estimation of sodium intake/excretion. Main food sources of sodium are presented for several Asian, European and Northern American countries, including previously unpublished INTERMAP data.

Results Sodium intakes around the world are well in excess of physiological need (i.e. 10–20 mmol/day). Most adult populations have mean sodium intakes >100 mmol/day, and for many (particularly the Asian countries) mean intakes are >200 mmol/day. Possible exceptions include estimates from Cameroon, Ghana, Samoa, Spain, Taiwan, Tanzania, Uganda and Venezuela, though methodologies were sub-optimal and samples were not nationally representative. Sodium intakes were commonly >100 mmol/day in children over 5 years old, and increased with age. In European and Northern American countries, sodium intake is dominated by sodium added in manufactured foods (~75% of intake). Cereals and baked goods were the single largest contributor to dietary sodium intake in UK and US adults. In Japan and China, salt added at home (in cooking and at the table) and soy sauce were the largest sources.

Conclusions Unfavourably high sodium intakes remain prevalent around the world. Sources of dietary sodium vary largely worldwide. If policies for salt reduction at the population level are to be effective, policy development and implementation needs to target the main source of dietary sodium in the various populations.

Methods We performed a pooled analysis of 15 case–control studies (5700 melanoma cases and 7216 controls), correlating patterns of sun exposure, sunburn and solar keratoses (three studies) with melanoma risk. Pooled odds ratios (pORs) and 95% Bayesian confidence intervals (CIs) were estimated using Bayesian unconditional polytomous logistic random-coefficients models.

Results Recreational sun exposure was a risk factor for melanoma on the trunk (pOR = 1.7; 95% CI: 1.4–2.2) and limbs (pOR = 1.4; 95% CI: 1.1–1.7), but not head and neck (pOR = 1.1; 95% CI: 0.8–1.4), across latitudes. Occupational sun exposure was associated with risk of melanoma on the head and neck at low latitudes (pOR = 1.7; 95% CI: 1.0–3.0). Total sun exposure was associated with increased risk of melanoma on the limbs at low latitudes (pOR = 1.5; 95% CI: 1.0–2.2), but not at other body sites or other latitudes. The pORs for sunburn in childhood were 1.5 (95% CI: 1.3–1.7), 1.5 (95% CI: 1.3–1.7) and 1.4 (95% CI: 1.1–1.7) for melanoma on the trunk, limbs, and head and neck, respectively, showing little variation across latitudes. The presence of head and neck solar keratoses was associated with increased risk of melanoma on the head and neck (pOR = 4.0; 95% CI: 1.7–9.1) and limbs (pOR = 4.0; 95% CI: 1.9–8.4).

Conclusion Melanoma risk at different body sites is associated with different amounts and patterns of sun exposure. Recreational sun exposure and sunburn are strong predictors of melanoma at all latitudes, whereas measures of occupational and total sun exposure appear to predict melanoma predominately at low latitudes.

Methods The Whitehall II study of socioeconomic inequalities in health provided response status from five data collection surveys; Phase 1 (1985–88, n = 10 308), Phase 5 (1997–99, n = 6533), and all-cause mortality to 2006. Odd-numbered phases included a medical examination in addition to a questionnaire.

Results Non-response to baseline and to follow-up phases that included a medical examination was associated with a doubling of the mortality hazard in analyses adjusted for age and sex. Compared with complete responders, responders who missed one or more phases, but completed the last possible phase before they died, had a 38% excess risk of mortality. However, those who missed one or more phases including the last possible phase before death had an excess risk of 127%. There was no evidence that these associations differed by socioeconomic position.

Conclusion In studies with repeat data collections, non-response to follow-up is associated with the same doubling of the mortality risk as non-response to baseline; an association that is not modified by socioeconomic position.

Methods In this population-based prospective study, 1529 employees from several large Belgian companies were followed for a median observation period of 6.6 years with respect to the onset of the MetS and its separate components.

Results At baseline, 309 men (20.2%) were rotating shift workers. The MetS incidence rate in these shift workers (60.6 per 1000 person-years) was increased in comparison with day workers (37.2 per 1000 person-years) with an odds ratio (95% CI) of 1.77 (1.34–2.32). Multivariate adjustment for potential lifestyle and work-related confounders did only marginally affect the strength of the association. The risk for the development of MetS gradually increased independently with accumulated years of shift work. Rotating shift work not only had an impact on MetS as a cluster of conditions but on each of its individual components as well.

Conclusions Hence, prospective evidence was found that rotating shift work increases the risk for developing the MetS over a period of 6 years.

Methods From 2003 to 2004, 1003 patients were repeatedly clinically examined. On every clinical visit (on average 5.8 times), blood EDTA-plasma samples were collected. High sensitivity C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen concentrations were measured based on standardized procedures. Dietary habits were evaluated through a semi-quantitative Food Frequency Questionnaire (FFQ), whereas adherence to the Mediterranean diet was assessed by a diet score.

Results A protective effect of adherence to the Mediterranean diet was found. For each unit of increasing adherence to the Mediterranean diet score there was a reduction of 3.1% in the average CRP levels (95% CI 0.5–5.7%) and of 1.9% in the average IL-6 levels (95% CI 0.5–3.4%) after adjusting for centre, age, sex, body mass index, physical activity, smoking status, diabetes and medication intake. No significant association was observed between the diet score and fibrinogen levels. Moderate intake of red wine (1–12 wine glasses per month) was associated with lower levels of CRP, IL-6 and fibrinogen.

Conclusions Adherence to the traditional Mediterranean diet was associated with a reduction of the concentrations of inflammatory markers in MI survivors. This may, in part, explain the beneficial effects of this diet on various chronic diseases such as atherosclerosis and cancer, and expands its role to secondary prevention level.

Methods Men aged 47–67 years had lung function measured between 1984 and 1988 and repeated between 2002 and 2004 (n = 827) as well as having carotid-femoral pulse wave velocity (PWV) measured.

Results Both forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) in mid-life and later life were inversely associated with PWV (P < 0.0001) but mid-life measures were stronger predictors. Only mid-life measures remained predictors after mutual adjustment (FEV₁ mid-life β coeff. –0.65, 95% CI –1.04, –0.26, P < 0.0001; FVC mid-life β coeff. –0.52, 95% CI –0.82, –0.23, P < 0.0001). Adjustment for smoking status, early life, inflammatory and metabolic factors in sub-groups did not markedly change the associations.

Conclusions Mid-life lung function is a stronger risk factor than in later life for arterial stiffness in men. It is possible that developmental factors influence both lung function and arterial stiffness. Lung function assessment in mid-life may identify individuals at greater risk of their future cardiovascular disease.

Methods Retrospective 5-year study of two fixed cohorts, homeless adults and an age- and sex-matched random sample of the local non-homeless population in Greater Glasgow National Health Service Board area for comparison.

Results Over 5 years of observation, 1.7% (209/12 451) of the general population and 7.2% (457/6323) of the homeless cohort died. The hazard ratio of all-cause mortality in homeless compared with non-homeless cohorts was 4.4 (95% CI: 3.8–5.2). After adjustment for age, sex and previous hospitalization, homelessness was associated with an all-cause mortality hazard ratio of 1.6 (95% CI: 1.3–1.9). Homelessness had differential effects on cause-specific mortality. Among patients who had been hospitalized for drug-related conditions, the homeless cohort experienced a 7-fold increase in risk of death from drugs compared with the general population.

Conclusions Homelessness is an independent risk factor for deaths from specific causes. Preventive programmes might be most effectively targeted at the homeless with these conditions.

Methods We applied a binomial multilevel logistic model to analyse variation in illiteracy as enumerated by the 1930 US. Census (the same data as used by Robinson). The outcome was log odds of being illiterate, while predictors were race/nativity (‘native whites’, ‘foreign-born whites’ and ‘negroes’) at the individual-level, and presence of Jim Crow segregation laws for education at the state-level. We conducted historical research to identify the social and scientific context within which Robinson's study was produced and favourably received.

Results Empirically, the substantial state variations in illiteracy could not be accounted by the states' race/nativity composition. Different approaches to modelling state-effects yielded considerably attenuated associations at the individual-level between illiteracy and race/nativity. Furthermore, state variation in illiteracy was different across the race/nativity groups, with state variation being largest for whites and least for foreign-born whites. Strong effects of Jim Crow education laws on illiteracy were observed with the effect being strongest for blacks. Historically, Robinson's study was consonant with the post-World War II ascendancy of methodological individualism.

Conclusion Applying a historically informed multilevel perspective to Robinson's profoundly influential study, we demonstrate that meaningful analysis of individual-level relationships requires attention to substantial heterogeneity in state characteristics. The implication is that perils are posed by not only ecological fallacy but also individualistic fallacy. Multilevel thinking, grounded in historical and spatiotemporal context, is thus a necessity, not an option.

Methods We conducted a cohort analysis of all children in New Zealand who were aged 6 months to <5 years at the time the vaccine became available for that age group in their area. We defined cases as children who were diagnosed with laboratory-confirmed epidemic strain meningococcal disease. We calculated person-days-at-risk using data from the National Immunization Register and population estimates from Statistics New Zealand. We estimated vaccine effectiveness as 1 – relative risk.

Results Compared with unvaccinated children, fully vaccinated children were five to six times less likely to contract epidemic strain meningococcal disease in the 24 months after they became eligible to receive a full vaccination series, corresponding to an estimated vaccine effectiveness of 80.0% (95% confidence interval: 52.5–91.6) for children aged 6 months to <5 years and 84.8% (95% confidence interval: 59.4–94.3) for children aged 6 months to <3 years.

Conclusions With over 3 million doses administered to individuals aged under 20 years throughout New Zealand, combined evidence from the Phase I and II clinical trials, the descriptive epidemiology of meningococcal disease, and this study provide evidence supporting the effectiveness of this vaccine in the 2 years following vaccination.

Methods Data were collected on allergic disease symptoms, forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), bronchial reactivity, allergen skin sensitization, serum IgE and H. pylori serological status in 2437 randomly selected adults.

Results Individuals with serological evidence of exposure to H. pylori had lower lung function, FEV₁ being lower by 53 ml (95% CI 1–106) and FVC 83 ml (95% CI 20–145) lower in the cross-sectional analysis. These differences ceased to be statistically significant after adjustment for height or socio-economic status. There was no association between H. pylori serological status and measures of asthma or atopy in the cross-sectional analysis, and there was no significant association between H. pylori serological status and decline in FEV₁ and FVC over 9 years.

Conclusion Although H. pylori exposure may be associated with lower cross-sectional FEV₁ and FVC, this association was not independent of height or socio-economic status. There was no association between H. pylori exposure and either chronic obstructive pulmonary disease (COPD), measures of allergic disease or decline in lung function.

Methods TB screening data were linked to information from the Norwegian Cause of Death Registry (1975–98) and the National Population and Housing Censuses (1960, 1970 and 1980). Analyses were done for 10 years cohorts born 1910–49, separately for men (~534 000 individuals) and women (608 000), using logistic and Cox regressions.

Results TB infection and X-ray data confirmed the strong regional pattern seen for TB mortality, with the highest rates in the three northernmost counties and higher rates in urban than rural areas. High socioeconomic status relates to lower odds both for TB infection and TB-related chest X-ray findings (odds ratios 0.6–0.7 for highest vs lowest educational groups). Those infected by TB, and especially those with chest X-ray findings, have increased all-cause mortality in at least a 20 years period following determination of tuberculin status (hazard ratios ~1.15 and 1.30, respectively, higher for late than early cohorts).

Conclusions TB particularly affected lower socioeconomic strata, but even those in higher strata were at high risk. The differences in all-cause mortality could partly be attributed to socioeconomic factors, but we hypothesize that developing TB infection may also indicate biological frailness.

Methods We searched seven electronic databases (Cinahl, Cochrane Controlled Trials Register, DARE, Embase, Medline, PsycINFO and SIGLE) without language restrictions from January 1990 to October 2007 and reference lists of retrieved articles to identify studies published before 1990. We included studies examining primary outcomes (pelvic inflammatory disease, ectopic pregnancy, infertility, adverse pregnancy outcomes, neonatal infection, chlamydia prevalence) and harms of chlamydia screening in men and non-pregnant and pregnant women. We extracted data in duplicate and synthesized the data narratively or used random effects meta-analysis, where appropriate.

Results We included six systematic reviews, five randomized trials, one non-randomized comparative study and one time trend study. Five reviews recommended screening of women at high risk of chlamydia. Two randomized trials found that register-based screening of women at high risk of chlamydia and of female and male high school students reduced the incidence of pelvic inflammatory disease in women at 1 year. Methodological inadequacies could have overestimated the observed benefits. One randomized trial showed that opportunistic screening in women undergoing surgical termination of pregnancy reduced post-abortal rates of pelvic inflammatory disease compared with no screening. We found no randomized trials showing a benefit of opportunistic screening in other populations, no trial examining the effects of more than one screening round and no trials examining the harms of chlamydia screening.

Conclusion There is an absence of evidence supporting opportunistic chlamydia screening in the general population younger than 25 years, the most commonly recommended approach. Equipoise remains, so high-quality randomized trials of multiple rounds of screening with biological outcome measures are still needed to determine the balance of benefits and harms of chlamydia screening.

Methods Complete data on 8927 patients from 46 countries from the corticosteroid randomization after significant head injury (CRASH) trial were analysed to explore whether outcomes 6 months after TBI differed between high-income countries and LAMIC.

Results Just under half of patients experienced a good recovery, one-third moderate or severe disability and one-quarter died within 6 months of their injury. Univariate analyses showed that patients in LAMIC were more likely to die following severe TBI, but were less likely to be disabled following mild and moderate TBI. These results were confirmed in multivariate analyses. Compared to patients in high-income countries, patients in LAMIC have over twice the odds of dying following severe TBI (OR 2.23, 95% CI 1.51–3.30) but half the odds of disability following mild (OR 0.41, 95% CI 0.23–0.72) and moderate TBI (OR 0.53, 95% CI 0.35–0.81). There were no differences between settings in the odds of death following either mild or moderate TBI.

Conclusions Reduced death rates following severe TBI in patients from high-income countries may be due to differences in medical care which may result in a higher proportion of patients surviving with a disability. Socio-cultural factors may explain the lower levels of disability after mild and moderate TBI in LAMIC.

Method and findings Cross-sectional study of 3662 youth (16–24 years) from rural and urban communities in Goa, India. Suicidal behaviour during the recent 3 months and associated factors were assessed using a structured interview. Overall 144; 3.9% [95% confidence interval (CI) 3.3–4.6] youth reported any suicidal behaviour in the previous 3 months. Suicidal behaviour was found to be associated with female gender Odds ratio (OR) 6.5 (95% CI 3.9–10.8), not attending school or college OR 1.6 (95% CI, 1.01–2.6), independent decision making OR 2.5 (95% CI 1.5–4.3), premarital sex OR 3.2 (95% CI 1.6–6.3), physical abuse at home OR 3.3 (95% CI 1.8–6.1), life time experience of sexual abuse OR 3.3 (95% CI 1.8-6.0) and probable common mental disorders (CMD) OR 9.5 (95% CI 6.3–14.5). Gender segregated analysis found independent decision making (P = 0.68 for interaction), rural residence (P = 0.01 for interaction) and premarital sex (P = 0.41 for interaction) retained association with suicidal behaviour only among females (P < 0.05). The population attributable fraction estimates were largest for CMD (42.8% for females; 35.9% for males); physical abuse in one's home (12.5% for females; 12.4% for males); sexual abuse (12.1% in females; 22.3% in males); and making independent decisions (22.9% for females). Analyses of the risk factors for the relatively less common outcome of suicide attempts found a similar set of factors as for suicidal behaviour; in addition, alcohol use was also an independent risk factor.

Conclusion Violence and psychological distress are independently associated with suicidal behaviour; factors associated with gender disadvantage—in particular for rural women, may increase their vulnerabilities. Prevention programs for youth suicide in India need to address both the structural determinants of gender disadvantage, and the individual experiences of violence and poor mental health.

Methods We applied the burden of disease approach to national population health datasets and Indigenous-specific epidemiological studies. The main outcome measure is the Indigenous health gap, i.e. the difference between current rates of Disability-Adjusted Life Years (DALYs) by age, sex and cause for Indigenous Australians and DALY rates if the same level of mortality and disability as in the total Australian population had applied.

Results The Indigenous health gap accounted for 59% of the total burden of disease for Indigenous Australians in 2003 indicating a very large potential for health gain. Non-communicable diseases explained 70% of the health gap. Tobacco (17%), high body mass (16%), physical inactivity (12%), high blood cholesterol (7%) and alcohol (4%) were the main risk factors contributing to the health gap. While the 26% of Indigenous Australians residing in remote areas experienced a disproportionate amount of the health gap (40%) compared with non-remote areas, the majority of the health gap affects residents of non-remote areas.

Discussion Comprehensive information on the burden of disease for Indigenous Australians is essential for informed health priority setting. This assessment has identified large health gaps which translate into opportunities for large health gains. It provides the empirical base to determine a more equitable and efficient funding of Indigenous health in Australia. The methods are replicable and would benefit priority setting in other countries with great disparities in health experienced by Indigenous peoples or other disadvantaged population groups.

Methods Stillbirth and infant mortality rates were compared for singleton births at ≥22 weeks and newborns weighing ≥500 g in the United States and Canada (1996–2000). Since menstrual-based gestational age appears to misclassify gestational duration and overestimate both preterm and postterm birth rates, and because a clinical estimate of gestation is the only available measure of gestational age in Canada, all comparisons were based on the clinical estimate. Data for California were excluded because they lacked a clinical estimate. Gestational age-specific comparisons were based on the foetuses-at-risk approach.

Results The overall stillbirth rate in the United States (37.9 per 10 000 births) was similar to that in Canada (38.2 per 10 000 births), while the overall infant mortality rate was 23% (95% CI 19–26%) higher (50.8 vs 41.4 per 10 000 births, respectively). The gestational age distribution was left-shifted in the United States relative to Canada; consequently, preterm birth rates were 8.0 and 6.0%, respectively. Stillbirth and early neonatal mortality rates in the United States were lower at term gestation only. However, gestational age-specific late neonatal, post-neonatal and infant mortality rates were higher in the United States at virtually every gestation. The overall stillbirth rates (per 10 000 foetuses at risk) among Blacks and Whites in the United States, and in Canada were 59.6, 35.0 and 38.3, respectively, whereas the corresponding infant mortality rates were 85.6, 49.7 and 42.2, respectively.

Conclusions Differences in gestational age distributions and in gestational age-specific stillbirth and infant mortality in the United States and Canada underscore substantial differences in healthcare services, population health status and health policy between the two neighbouring countries.

Methods We studied 32 776 singleton term infants presenting breech excluding anomalous and antepartum losses in Scotland between 1985 and 2004, using linked Scottish national registries of pregnancy outcome data and perinatal death data. The event was delivery-related perinatal and neonatal death (i.e. intrauterine fetal death during labour or death of infant in the first 4 weeks of life), subdivided according to intrapartum anoxia or mechanical cause of death. Analysis was by multivariate logistic regression.

Results During the study period, the risk of delivery-related perinatal and neonatal death decreased by 72% (95% CI –1% to 93%), due to a 90% (95% CI 33–99%) reduction in anoxic or mechanical deaths. Both intrapartum (OR 0.16, 95% CI 0.02–0.75) and planned (OR 0.01, 95% CI 0.00–0.09) caesarean delivery were protective against anoxic or mechanical deaths and increased use of planned caesarean delivery accounted for 16% of the decline in anoxic and mechanical deaths over the study period.

Conclusion Increased use of planned caesarean delivery only partly explains the decline in delivery-related perinatal and neonatal death between 1985 and 2004 in Scotland.

Methods We used panel data from the nationally representative Monitoring the Future Study (1986–2004) to examine social disparities in trajectories of body mass index (BMI) over adulthood (age 18–45). Self-reported height and weight were collected in this annual US survey of high-school seniors, followed biennially since 1976. Using growth curve models, we analysed BMI trajectories over adulthood by gender, race/ethnicity and lifetime SEP (measured by parents’ education and respondent's education).

Results BMI trajectories exhibit a curvilinear rate of change from age 18 to 45, but there was a strong period effect, such that weight gain was more rapid for more recent cohorts. As a result, successive cohorts become overweight (BMI > 25) at increasingly earlier points in the life course. BMI scores were also consistently higher for women, racial/ethnic minority groups and those from a lower SEP. However, BMI scores for socially advantaged groups in recent cohorts were actually higher than those for their socially disadvantaged counterparts who were born 10 years earlier.

Conclusions Results highlight the importance of social status and socio-economic resources for maintaining optimal weight. Yet, even those in advantaged social positions have experienced an increase in BMI in recent years.

Methods Cross-sectional data for the years around 1990 and 2000 were used. Age-standardized mortality rates and mortality rate ratios (for total mortality only) were calculated for men and women aged 35–64 in three educational categories, for five broad cause-of-death groups and for five (seven among women) specific causes of death.

Results Educational inequalities in mortality increased in all four countries but in two completely different ways. In Poland and Hungary, mortality rates decreased or remained the same in all educational groups. In Estonia and Lithuania, mortality rates decreased among the highly educated, but increased among those of low education. In Estonia and Lithuania, for men and women combined, external causes and circulatory diseases contributed most to the increasing educational gap in total mortality.

Conclusions Different trends were observed between the two former Soviet republics and the two Central Eastern European countries. This divergence can be related to differences in socioeconomic development during the 1990s and in particular, to the spread of poverty, deprivation and marginalization. Alcohol and psychosocial stress may also have been important mediating factors.

Methods We propose a model-building framework that can be used to formally compare alternative hypotheses on the effect of multiple binary exposure measurements collected across the life course. The saturated model where the order and value of the binary variable at each time point influence the outcome of interest is compared with nested alternative specifications corresponding to the critical period, cumulative risk or hypotheses about the effect of changes in environment. This framework is illustrated with data on adult body mass index and socioeconomic position measured once in childhood and twice in adulthood from the Medical Research Council National Survey of Health and Development, using a series of liner regression models.

Results We demonstrate how analyses that only consider the association of a cumulative score with a later outcome may produce misleading results.

Conclusion We recommend comparing a set of nested models—each corresponding to the accumulation, critical period and effect modification hypotheses—to an all-inclusive (saturated) model. This approach can provide a formal and clearer understanding of the relative merits of these alternative hypotheses.

Methods We modelled fetal environment as a latent variable determined by maternal height and arm fat area (AFA) during pregnancy using structural equation modelling. We tested for associations between latent fetal environment (LFE) and systolic blood pressure (SBP) while controlling for birth weight (BW) and current weight (CW). Data are from 1435 male and 1218 female young adult Filipinos (2005; mean age 21 years) enrolled in the Cebu Longitudinal Heath and Nutrition Survey, an ongoing, community-based study of a one-year birth cohort. Using AMOS 6.0, LFE was modelled as a determinant of BW, CW and SBP; CW was modelled as a determinant of SBP.

Results Overall model fit was excellent (²: 32.14, 27 df, P = 0.23). The estimated direct relationship between LFE and SBP was inverse for both males (_–0.43 –0.26 _–0.10) and females (_–0.29 –0.18 _–0.07).

Conclusions These results are consistent with the hypothesis that maternal height and AFA impact fetal development in a manner that is positively associated with fetal growth (as reflected by BW) and inversely associated with SBP in young adulthood.

Methods We conducted a case-crossover study in which women provided information about their most recent unprotected and protected sexual encounters. Conditional logistic regression was used to estimate paired odds ratios and 95% confidence intervals for the association between situation-specific factors and condom use.

Results A subject-based or mutual decision about condom use (compared with partner based), casual partner type, a first-time sexual encounter and receiving gifts in exchange for sex were independently associated with increased odds of condom use, while sex at home and sex with a partner more than 10 years older was associated with reduced odds of use. There was also effect modification between partner type and decision-making: subject-based or mutual decisions were more protective with casual than regular partners; also, when the partner made the decisions about condom use, the type of partner had no effect.

Conclusions Decision-making about condom use is a potentially modifiable predictor of unprotected sex, but its effect varies by partner type. Behavioural interventions are needed that encourage discussion about condom use and increase women's self-efficacy, but other types of interventions as well as female-controlled HIV prevention methods are needed for women in regular partnerships.

Methods We examined a cohort of 718 children interviewed in the early 1990s and again in 2004. Detailed survey questionnaires and anthropometric measurements were administered at baseline and during a follow-up survey. Final attained height and education (at adulthood) between children who lost a parent before the age of 15 and those who did not were compared.

Results On average, children who lose their mother before the age of 15 suffer a deficit of around 2 cm in final attained height (mean 1.96; 95% CI 0.06–3.77) and 1 year of final attained schooling (mean 1.01; 95% CI 0.39–1.81). This effect is permanent and the hypothesis that it is causal cannot be rejected by our study. Although father's death is a predictor of lower height and schooling as well, we reject the hypothesis of a causal link.

Conclusions The African orphan crisis, exacerbated by the HIV/AIDS epidemic will have important negative intergenerational effects.

Methods To explore the mediating role of breastfeeding cessation in this relationship, we compared marginal structural models of maternal CD4 count on child death with and without adjustment for breastfeeding.

Results In crude analyses, children of mothers with CD4 < 200 during pregnancy were 3.2 times more likely to die by 18 months (CI 1.3–8.1) as children whose mothers had CD4 > 500. Earlier breastfeeding cessation was also associated with low CD4 (HR 1.8; CI 1.2–2.7). After adjusting for breastfeeding and low birth weight using a marginal structural model, the low CD4 count-child mortality association through 18 months was reduced 17%. The change was overestimated using a traditional Cox proportional hazards model (35% reduction in HR from 3.4 to 2.5).

Conclusions Our analysis suggests that only a small part of the effect of low vs high CD4 count on child mortality through 18 months is mediated through breastfeeding cessation. Our results must be taken into account when deciding whether or not to recommend breastfeeding for infants of HIV-infected mothers.

Methods Data were collected from 744 young married women in slum areas of Bangalore, India. Unadjusted and adjusted multivariable logistic regression models were used to determine factors associated with having been hit, kicked or beaten by one's husband in the past 6 months.

Results Over half (56%) of the study participants reported having ever experienced physical domestic violence; about a quarter (27%) reported violence in the past 6 months. In a full multivariable model, women in ‘love’ marriages (OR = 1.7, 95% CI 1.1–2.5) and those whose families were asked for additional dowry after marriage (OR = 2.3, 95% CI 1.5–3.4) were more likely to report domestic violence. Women who participated in social groups (OR = 1.6, 95% CI 1.0–2.4) and vocational training (OR = 3.1, 95% CI 1.7–5.8) were also at higher risk.

Conclusions Efforts to help women empower themselves through vocational training, employment opportunities and social groups need to consider the potential unintended consequences for these women, such as an increased risk of domestic violence. The study findings suggest that the effectiveness of anti-dowry laws may be limited without additional strategies that mobilize women, families and communities to challenge the widespread acceptance of dowry and to promote gender equity. Longitudinal studies are needed to elucidate the complex causal relationships between ‘love’ marriages and domestic violence.

Methods Based on the published papers, we calculated age- and sex-specific mortality estimates. No vaccination status data were provided.

Results Both zinc/FA and iron seemed to have a sex- and age-differential effect, the effect being less beneficial in the youngest girls who are most likely to have DTP vaccine as their most recent vaccination.

Conclusions Like vitamin A, zinc/FA and iron may not benefit the youngest girls. The question is whether this is inherent in girls or due to an interaction with some environmental factor like DTP.

Methods We interviewed 225 cases (aged 20–75 years) notified to the New Zealand Cancer Registry during 2003–04, and 471 controls randomly selected from the Electoral Roll collecting demographic details, information on potential confounders and a comprehensive employment history. Associations between occupation and leukaemia were analysed using logistic regression adjusted for gender, age, ethnicity and smoking.

Results Elevated odds ratios (ORs) were observed in agricultural sectors including horticulture/fruit growing (OR: 2.62, 95% confidence interval (CI): 1.51, 4.55), plant nurseries (OR: 7.51, 95% CI: 1.85, 30.38) and vegetable growing (OR: 3.14, 95% CI: 1.18, 8.40); and appeared greater in women (ORs: 4.71, 7.75 and 7.98, respectively). Elevated ORs were also observed in market farmers/crop growers (OR: 1.84, 95% CI: 1.12, 3.02), field crop/vegetable growers (OR: 3.98, 95% CI: 1.46, 10.85), market gardeners (OR: 5.50, 95% CI: 1.59, 19.02), and nursery growers/workers (OR: 4.23, 95% CI: 1.34, 13.35); also greater in women (ORs: 3.48, 7.62, 15.74 and 11.70, respectively). These elevated ORs were predominantly for chronic lymphocytic leukaemia (CLL). Several associations persisted after semi-Bayes adjustment. Elevated ORs were observed in rubber/plastics products machine operators (OR: 3.76, 95% CI: 1.08, 13.08), predominantly in plastic product manufacturing. CLL was also elevated in tailors and dressmakers (OR: 7.01, 95% CI: 1.78, 27.68), cleaners (OR: 2.04, 95% CI: 1.00, 4.14) and builder's labourers (OR: 4.03, 95% CI: 1.30, 12.53).

Conclusions These findings suggest increased leukaemia risks associated with certain agricultural, manufacturing, construction and service occupations in New Zealand.

Methods In a cross-sectional study of 9998 adults from the Guangzhou Biobank Cohort Study (phase 2) examined in 2005–06, we used multivariable linear regression to assess the association of SEP at three life stages (proxied by parental possessions, education and longest held occupation) with obesity [body mass index (BMI) and waist–hip ratio (WHR)] in men and women.

Results There was no evidence that socio-economic position trajectory had supra-additive effects on BMI or WHR. Instead in women, higher SEP at any life stage usually contributed to lower BMI and WHR; e.g. women with higher early adult SEP had lower BMI [–0.45; 95% confidence interval (CI) –0.71 to –0.19) and WHR (–0.02; 95% CI –0.02 to –0.012]. In contrast, in men, higher childhood SEP was associated with higher BMI (0.53; 95% CI 0.18 to 0.88) and WHR (0.01; 95% CI 0.003 to 0.02) as was high late adulthood SEP with BMI (0.36; 95% CI 0.07 to 0.64).

Conclusions This study provides little support for environmental mismatch over the life course increasing obesity in this rapidly transitioning southern Chinese population. However, our findings highlight different effects of the epidemiologic transition in men and women, perhaps with pre-adult exposures as a critical window for sex-specific effects.

Methods We analysed data from the NNS-J for subjects aged 20–69 years. BMI during 1956–2005 and the prevalence of overweight and obesity (BMI ≥ 25 kg/m²) during 1976–2005 were estimated.

Results The BMI increased with age in every birth cohort, with similar increments, and did not peak until 60–69 years of age. However, with cross-sectional age, the BMI usually peaked before 60–69 years of age. The differences among cohorts already existed at 20–29 years of age, and slightly increased in men between 20–29 and 30–39 years of age. The BMI in all male age groups increased from the 1891–1900 through 1971–80 cohorts. However, in women, the figure increased until the 1931–40 cohorts, but later decreased. Changes in prevalence were generally consistent with changes in BMI. The recent increase (decrease in young women) in the mean BMI is attributable to birth cohort, indicating that thinner (fatter) and less recent birth cohorts have been replaced by fatter (thinner) ones.

Conclusions A cohort effect was quantitatively demonstrated based on a repeated annual survey. In Japan, the differences in BMI among cohorts were already established by young adulthood.

Methods Literature overview.

Results In economically developed countries, official healthy eating advice is to eat more fish, particularly that rich in omega-3 oils. In many less economically developed countries, fish is a key human health asset, contributing >20% of animal protein intake for 2.6 billion people. Marine ecologists predict on current trends that fish stocks are set to collapse in 40 years, and propose increased restrictions on fishing, including no-take zones, in order to restore marine ecosystem health. Production of fishmeal for aquaculture and other non-food uses (22 MT in 2003) appears to be unsustainable. Differences in fish consumption probably contribute to within-country and international health inequalities. Such inequalities are likely to increase if fish stocks continue to decline, while increasing demand for fish will accelerate declines in fish stocks and the health of marine ecosystems.

Conclusions Urgent national and international action is necessary to address the tensions arising from increasing human demand for fish and seafood, and rapidly declining marine ecosystem health.

Methods We obtained Md15 from 577 Dutch adults (aged 58.9 years, SD 1.1) whose births in 1943–47 were documented in maternity records and from 260 of their same-sex siblings for whom birth weights were not available. Of these 837 participants, complete anthropometry and diabetes status (from history or glucose tolerance test) were obtained for 819.

Results After adjustment for age, sex, parental diabetes and adult anthropometry, fingerprint Md15 was associated with prevalent diabetes [odds ratio (OR) = 1.37 per 1 SD (95% confidence interval 1.02–1.84)]. This relationship held [OR = 1.40 (1.03–1.92)] for diabetic cases restricted to those recently diagnosed (within 7 years). In the birth series restricted to recently diagnosed cases, the mutually adjusted ORs were 1.34 (1.00–1.79) per SD of Md15 and 0.83 (0.62–1.10) per SD of birth weight. Further adjustments for maternal smoking, conception season or prenatal famine exposure in 1944–45 did not alter these estimates. Among 42 sibling pairs discordant for diabetes, the diabetic sibling had higher Md15 by 3.5 (0.6–6.3) after multivariable adjustment.

Conclusions Diabetes diagnosed at age 50+ years was associated with a fingerprint marker established in early gestation, irrespective of birth weight. Fingerprints may provide a useful tool to investigate prenatal developmental plasticity.

Methods Height, weight, systolic (SBP) and diastolic blood pressure (DBP), elbow flexion, hand grip and knee extension strength were measured in young adulthood in 1 145 467 Swedish men born between 1951 and 1976. Information on own and parental social position was derived from censuses. During the register-based follow-up until the end of 2006, 12 323 CHD and 8865 stroke cases emerged, including 1431 intracerebral haemorrhage, 1316 subarachoid haemorrhage and 2944 intracerebral infarction cases. Hazard ratios (HR) per 1 SD in the exposures of interest were computed using Cox proportional hazard model.

Results Body mass index (BMI, kg/m²) showed increased risk with CHD and intracerebral infarction, whereas for intracerebral and subarachoid haemorrhage both under- and overweight was associated with increased risk. Height was inversely associated with CHD and all types of stroke. After adjustment for height, BMI, SBP, DBP and social position, all strength indicators were inversely associated with disease risk. For CHD and intracerebral infarction, grip strength showed the strongest association (HR = 0.89 and 0.91, respectively) whereas for intracerebral and subarachoid haemorrhage, knee extension strength was the best predictor (HR = 0.88 and 0.92, respectively).

Conclusion Body size and muscle strength in young adulthood are important predictors of risk of CHD and stroke in later life. In addition to adiposity, underweight needs attention since it may predispose to cerebrovascular complications.

Methods The offspring from a maternal prenatal protein-energy supplementation trial were enrolled into a follow-up study of chronic disease risk factors including blood pressure. Subjects were 11–17 years of age and blood pressure was measured in triplicate using an automated monitor (Omron 705IT). One-thousand two-hundred sixty seven individuals (71% of potential participants) were included in the analysis.

Results There was no difference in blood pressure between those whose mothers had consumed protein-energy biscuits during pregnancy and those whose mothers had consumed the same supplement post-partum. For systolic blood pressure the intention-to-treat regression coefficient was 0.46 (95% CI: –1.12, 2.04). Mean systolic blood pressure for control children was 110.2 (SD ± 9.3) mmHg and for intervention children was 110.8 (SD ± 8.8) mmHg. Mean diastolic blood pressure for control children was 64.7 (SD ± 7.7) mmHg and for intervention children was 64.6 (SD ± 7.6) mmHg.

Conclusions We have found no association between maternal prenatal protein-energy supplementation and offspring blood pressure in adolescence amongst rural Gambians. We found some evidence to suggest that offspring body composition may interact with the effect of maternal supplementation on blood pressure.

Methods Data from the first two sweeps of the nationally representative prospective UK Millennium Cohort study were used. Drinking patterns during pregnancy and behavioural and cognitive outcomes were assessed during interviews and home visits. Behavioural problems were indicated by scores falling above defined clinically relevant cut-offs on the parent-report version of the Strengths and Difficulties Questionnaire (SDQ). Cognitive ability was assessed using the naming vocabulary subscale from the British Ability Scale (BAS) and the Bracken School Readiness Assessment (BSRA).

Results There was a J-shaped relationship between mothers drinking during pregnancy and the likelihood of high scores (above the cut-off) on the total difficulties scale of the SDQ and the conduct problems, hyperactivity and emotional symptom SDQ subscales. Children born to light drinkers were less likely to score above the cut-offs compared with children of abstinent mothers. Children born to heavy drinkers were more likely to score above the cut-offs compared with children of abstinent mothers. Boys born to mothers who had up to 1–2 drinks per week or per occasion were less likely to have conduct problems (OR 0.59, 95% CI 0.45–0.77) and hyperactivity (OR 0.71, 95% CI 0.54–0.94). These effects remained in fully adjusted models. Girls were less likely to have emotional symptoms (OR 0.72, 95% CI 0.51–1.01) and peer problems (OR 0.68, 95% CI 0.52–0.92) compared with those born to abstainers. These effects were attenuated in fully adjusted models. Boys born to light drinkers had higher cognitive ability test scores [standard deviations, (95% CI)] BAS 0.15 (0.08–0.23) BSRA 0.24 (0.16–0.32) compared with boys born to abstainers. The difference for BAS was attenuated on adjustment for socio-economic factors, whilst the difference for BSRA remained statistically significant.

Conclusions Children born to mothers who drank up to 1–2 drinks per week or per occasion during pregnancy were not at increased risk of clinically relevant behavioural difficulties or cognitive deficits compared with children of abstinent mothers. Heavy drinking during pregnancy appears to be associated with behavioural problems and cognitive deficits in offspring at age 3 years whereas light drinking does not.

Methods We analysed trends in total and cause-specific mortality in Russia for 1991–2006. The records of 24 836 forensic autopsies carried out during the period 1990–2004 in the city of Barnaul were analysed with respect to blood alcohol level.

Results Diseases of the circulatory system (in the age group 35–69 years) and external causes (in the age group 15–34 years) were the main contributors to the fluctuations in Russian mortality rates observed in 1991–2006. The largest relative changes were for conditions directly related to alcohol intake. Among cardiovascular diseases, fluctuations were due to ‘other forms’ of acute and chronic ischaemia, and to atherosclerotic heart disease, while rates of myocardial infarction were low and relatively constant. In the autopsy series a very high proportion of decedents whose death was attributed to ‘other’ or ‘not classified’ cardiovascular diseases had lethal or potentially lethal concentrations of ethanol in blood.

Conclusions The increases in mortality in 1991–94 and in 1998–2003 coincided with economic and societal crisis, while decreases in 1994–98 and 2003–06 correlate with improvement in the economic situation. Excessive alcohol intake is a major cause of premature male Russian mortality, although many alcohol-related deaths are wrongly attributed to diseases of the circulatory system.

Methods Non-exposed adolescents (controls) were matched to exposed adolescents (cases) by maternal education and school attended. Cognitive abilities were evaluated using a neuropsychological battery consisting of 33 tasks measuring verbal abilities, visuo-spatial skills, verbal and visual memory, processing speed, resistance to interference and motor dexterity.

Results We found no differences between cases and controls in any of the cognitive domains whether potential confounders were included in the model or not. In addition to maternal smoking during pregnancy, we also evaluated the effect of sex and age on the various cognitive abilities in this large adolescent sample and found that most of the abilities continue to improve during adolescence to the same extent in girls and boys, with several age-independent sex differences.

Conclusions We found no effect of maternal cigarette smoking during pregnancy on cognitive abilities of the adolescent offspring when matching cases and controls by maternal education, the most common confounder of maternal cigarette smoking during pregnancy.

Methods The participants were from two British national birth cohorts: 3325 women aged 33 years from the 1958 National Child Development Study and 1971 women aged 34 years from the 1970 British Cohort Study. We used structural equation modelling to examine the direct and indirect effects of intelligence measured at age 10–11 years, parental and current social class, educational attainment and age at first birth on smoking during pregnancy and current smoking status.

Results Forty per cent of women in the 1958 cohort smoked during pregnancy, compared with 28% of those from the 1970 cohort. In both cohorts, women with lower IQ in childhood were more likely as adults to smoke during pregnancy and to be a smoker currently. Structural equation modelling showed that the effects of childhood IQ on smoking behaviour were indirect, as they were statistically mediated by educational attainment and age at first birth. There was some effect of educational attainment and age at first birth on smoking behaviour over and above the effect of intelligence.

Conclusion Childhood intelligence influenced women's smoking behaviour as mothers primarily through its contributions to educational attainment and age at first birth.

Methods We reviewed national measles and rubella surveillance and vaccination coverage data, focusing on the 2004–05 outbreaks, and conducted a measles vaccine effectiveness (VE) study using data from a 2004 school-based outbreak.

Results Before 2004, the last large measles outbreak after measles vaccination was introduced (in 1966) in Georgia, was in 1988 (incidence rate, 36/100 000); the highest year for rubella was 1985 (110/100 000). During 2004–05, 8391 measles cases and 5151 rubella cases were reported (most of them diagnosed clinically). Of 358 suspected measles cases tested, 181 (51%) were positive for measles-IgM antibody; of 240 suspected rubella cases tested, 50 (21%) were positive for rubella-IgM antibody. Over 90% of measles cases were in persons born after 1979; 90% of rubella cases were in persons born after 1987. Approximately 41% of measles cases and 88% of rubella cases were unvaccinated. Estimated measles VE (≥1 vs 0 doses) was 86% (95% CI, 58–96%).

Conclusions The outbreak likely resulted from failure to vaccinate rather than vaccine failure. Susceptible persons likely accumulated due to the long absence of large outbreaks and decreased coverage after the collapse of Soviet Union. To interrupt measles and rubella transmission in Georgia and achieve disease elimination goals by 2010, supplementary immunization activities should target children and young adults.

Methods To understand better the variations in CFRs, we reviewed community-based studies published between 1980 and 2008 reporting age-specific measles CFRs.

Results The results of the search consistently document that measles CFRs are highest in unvaccinated children under age 5 years; in outbreaks; the lowest CFRs occur in vaccinated children regardless of setting. The broad range of case and death definitions, study populations and geography highlight the complexities in extrapolating results for global public health planning.

Conclusions Values for measles CFRs remain imprecise, resulting in continued uncertainty about the actual toll measles exacts.

Methods Probability sample survey of 11 161 men and women aged 16–44 resident in Britain, 1999–2001. Computer-assisted self-interviews asked respondents about partner numbers and detailed questions about their three most recent partnerships. We weight these data to represent partnerships for which detailed questions were not asked to present estimates for the population of partnerships.

Results Of 15 488 heterosexuals partnerships, 39.1% (95% CI 36.6–41.7%) of men's partnerships were ‘not (yet) regular’ vs 20.0% (95% CI 18.2–21.9%) of women's partnerships. While condoms were used at last sex in 37.1% (95% CI 35.0–39.3%) of men's and 28.8% (95% CI 27.1–30.6%) of women's partnerships, and for 55.3% (95% CI 52.6–58.0%) of first sex with new partners, these proportions declined with age. When partnerships involved an age difference of 5+ years [26.2% (95% CI 23.0–29.6%) of men's and 36.5% (95% CI 33.0–40.1%) of women's partnerships], condoms were less commonly used at first sex than when partners were closer in age [44.1% (95% CI 39.1–48.4%) vs 60.8% (95% CI 57.3–64.2%)]. Sex occurred within 24 h in 23.4% (95% CI 19.7–27.5%) of men's and 10.7% (95% CI 8.3–13.6%) of women's partnerships.

Conclusions A substantial minority of partnerships in the population is casual. The proportion of partnerships not protected by condoms is high, especially for partnerships involving larger age differences and people in their 30s and 40s. Condom use with new partners needs to be promoted among all age-groups.

Methods We evaluated the predictive performance of CRP in the Northwick Park Heart Study (NPHS-II) and the Edinburgh Artery Study (EAS) comparing discrimination by area under the ROC curve (AUC), calibration and reclassification. We set the findings in the context of a systematic review of published studies comparing different available and imputed measures of prediction. Risk estimates per-quantile of CRP were pooled using a random effects model to infer the shape of the CRP-coronary event relationship.

Results NPHS-II and EAS (3441 individuals, 309 coronary events): CRP alone provided modest discrimination for coronary heart disease (AUC 0.61 and 0.62 in NPHS-II and EAS, respectively) and only modest improvement in the discrimination of a Framingham-based risk score (FRS) (increment in AUC 0.04 and –0.01, respectively). Risk models based on FRS alone and FRS + CRP were both well calibrated and the net reclassification improvement (NRI) was 8.5% in NPHS-II and 8.8% in EAS with four risk categories, falling to 4.9% and 3.0% for 10-year coronary disease risk threshold of 15%. Systematic review (31 prospective studies 84 063 individuals, 11 252 coronary events): pooled inferred values for the AUC for CRP alone were 0.59 (0.57, 0.61), 0.59 (0.57, 0.61) and 0.57 (0.54, 0.61) for studies of <5, 5–10 and >10 years follow up, respectively. Evidence from 13 studies (7201 cases) indicated that CRP did not consistently improve performance of the Framingham risk score when assessed by discrimination, with AUC increments in the range 0–0.15. Evidence from six studies (2430 cases) showed that CRP provided statistically significant but quantitatively small improvement in calibration of models based on established risk factors in some but not all studies. The wide overlap of CRP values among people who later suffered events and those who did not appeared to be explained by the consistently log-normal distribution of CRP and a graded continuous increment in coronary risk across the whole range of values without a threshold, such that a large proportion of events occurred among the many individuals with near average levels of CRP.

Conclusions CRP does not perform better than the Framingham risk equation for discrimination. The improvement in risk stratification or reclassification from addition of CRP to models based on established risk factors is small and inconsistent. Guidance on the clinical use of CRP measurement in the prediction of coronary events may require updating in light of this large comparative analysis.

Methods Using data from the 1958 British birth cohort (7847 singletons), the associations between gestational age and blood pressure, glycosylated haemoglobin (HbA1c), lipid levels and body mass index (BMI) at age 44–45 years were examined.

Results After adjustment for sex, birthweight standardized for gestational age and sex and current BMI there was a reduction in systolic blood pressure of 0.53 mmHg (95% CI: 0.32, 0.75) for every 1 week increase in gestational age. There was a non-linear association between gestational age and diastolic blood pressure, with those cohort members born at earlier gestational ages found to have higher diastolic blood pressure than those born at term. These associations remained after adjustments. A ‘U’-shaped association was found between gestational age and BMI among women (P = 0.02 for sex x gestational age interaction) which attenuated after adjustment. There was also a weak inverse association between gestational age and total cholesterol specific to women (P = 0.01 for sex x gestational age interaction). No clear associations were found between gestational age and BMI or total cholesterol in men, or between gestational age and HbA1c or other lipid levels in either sex.

Conclusions In the 1958 British birth cohort duration of gestation was associated with blood pressure in mid-life. Understanding this association is necessary to inform policy and preventative interventions.

Methods A cohort study of 19 462 Californian Seventh-Day Adventist women followed-up from 1976 to 1988. A total of 3313 deaths occurred during follow-up, of which 809 were due to ischaemic heart disease and 378 due to stroke.

Results An early menarche was associated with increased total mortality (P-value for linear trend <0.001), ischaemic heart disease (P-value for linear trend = 0.01) and stroke (P-value for linear trend = 0.02) mortality. There were, however, also some indications of an increased ischaemic heart disease mortality in women aged 16–18 at menarche (5% of the women). When assessed as a linear relationship, a 1-year delay in menarche was associated with 4.5% (95% CI 2.3–6.7) lower total mortality. The association was stronger for ischaemic heart disease [6.0% (95% CI 1.2–10.6)] and stroke [8.6% (95% CI 1.6–15.1)] mortality.

Conclusions The results suggest that there is a linear, inverse relationship between age at menarche and total mortality as well as with ischaemic heart disease and stroke mortality.

Methods Nested case–control study from the Prospective Study of Pravastatin in the Elderly (PROSPER). Subjects were aged 70–82 years and followed up for a mean of 3.2 years: 266 incident stroke cases (179 confirmed as ischaemic) were compared with 532 controls matched for age, gender and treatment allocation (pravastatin or placebo). Adipocytokines [adiponectin, interleukin- (IL-)18 and tumour necrosis factor (TNF)] were measured on stored baseline plasma samples.

Results Elevated plasma adiponectin was associated with lower risk of ischaemic stroke on univariate analysis: odds ratio (OR) 0.78 per 1 SD increase (95% CI 0.62–0.97). There were no associations of IL-18 or TNF with risk for ischaemic or total strokes. In multivariate models the independent predictors of ischaemic stroke were prior cerebrovascular accident (OR 2.68, 95% CI 1.60–4.50), any alcohol use (1.98, 1.33–2.94), triglycerides (1.40, 1.11–1.77), Barthel score (0.75, 0.58–0.96) and known diabetes (1.72, 1.04–2.83); adiponectin, IL-18 and TNF did not contribute. A similar pattern of risk was seen for total stroke.

Conclusions Reduced adiponectin may have a modest role in the aetiology of ischaemic stroke in older people, however IL-18 and TNF are unlikely to play any important part. These adipocytokines do not have clinical predictive utility; history of prior cerebrovascular accident, known diabetes mellitus, prior disability and higher alcohol intake explain much of the stroke risk.

Methods Conventional power calculations for case–control studies disregard many basic elements of analytic complexity—e.g. errors in clinical assessment, and the impact of unmeasured aetiological determinants—and can seriously underestimate true sample size requirements. This article describes, and applies, a rigorous simulation-based approach to power calculation that deals more comprehensively with analytic complexity and has been implemented on the web as ESPRESSO: (www.p3gobservatory.org/powercalculator.htm).

Results Using this approach, the article explores the realistic power profile of stand-alone and nested case–control studies in a variety of settings and provides a robust quantitative foundation for determining the required sample size both of individual biobanks and of large disease-based consortia. Despite universal acknowledgment of the importance of large sample sizes, our results suggest that contemporary initiatives are still, at best, at the lower end of the range of desirable sample size. Insufficient power remains particularly problematic for studies exploring gene–gene or gene–environment interactions.

Discussion Sample size calculation must be both accurate and realistic, and we must continue to strengthen national and international cooperation in the design, conduct, harmonization and integration of studies in human genome epidemiology.

Methods We analysed 33 meta-analyses with a sufficient IS to detect a treatment effect of 15% relative risk reduction (RRR). We successively monitored the results of the meta-analyses by generating interim cumulative meta-analyses after each included trial and evaluated their results using a conventional statistical criterion ( = 0.05) and two-sided Lan-DeMets monitoring boundaries. We examined the proportion of false positive results and important inaccuracies in estimates of treatment effects that resulted from the two approaches.

Results Using the random-effects model and final data, 12 of the meta-analyses yielded P > = 0.05, and 21 yielded P ≤ = 0.05. False positive interim results were observed in 3 out of 12 meta-analyses with P > = 0.05. The monitoring boundaries eliminated all false positives. Important inaccuracies in estimates were observed in 6 out of 21 meta-analyses using the conventional P ≤ = 0.05 and 0 out of 21 using the monitoring boundaries.

Conclusions Evaluating statistical inference with trial sequential monitoring boundaries when meta-analyses fall short of a required IS may reduce the risk of false positive results and important inaccurate effect estimates.

Methods We selected apparently conclusive (P ≤ 0.05) Cochrane neonatal meta-analyses. We applied heterogeneity-adjusted and unadjusted TSA on these meta-analyses by calculating the information size, the monitoring boundaries, and the cumulative Z-statistic after each trial. We identified the proportion of meta-analyses that did not reach the required information size and the proportion of these meta-analyses in which the Z-curve did not cross the monitoring boundaries.

Results Of 54 apparently conclusive meta-analyses, 39 (72%) did not reach the heterogeneity-adjusted information size required to accept or reject an intervention effect of 25% relative risk reduction. Of these 39, 19 meta-analyses (49%) were considered inconclusive, because the cumulative Z-curve did not cross the monitoring boundaries. The median number of participants required to reach the required information size was 1591 (range, 339–6149). TSA without heterogeneity adjustment largely confirmed these results.

Conclusions Many apparently conclusive Cochrane neonatal meta-analyses may become inconclusive when the statistical analyses take into account the risk of random error due to repetitive testing.

Methods In 2003, VAS was distributed during NIDs in Guinea-Bissau. Children 6 months or older were given VAS, and if they were missing vaccines, these were often given as well. We compared survival between children who had received VAS alone, VAS with DTP or DTP + MV, or VAS with MV. We also compared the survival between participants and non-participants. We followed 6- to 17-month old children until 18 months of age and analysed survival in Cox models.

Results Twenty of 982 VAS-recipients died during follow-up. The mortality rate ratio (MRR) for VAS with DTP + MV or VAS with DTP was 3.43 (1.36–8.61) compared with VAS only. There were no deaths among those who received VAS with MV alone (P = 0.0005 for homogeneity of VAS effects). Children who received VAS with DTP had higher mortality than non-participants who did not receive VAS [MRR = 3.04 (1.31–7.07)].

Conclusion The study design does not allow for definite conclusions. However, the results are compatible with our a priori hypothesis that VAS is more beneficial when given with MV and potentially harmful when given with DTP. Randomized trials testing the impact on mortality of the current WHO policy seem warranted.

Methods The Million Women Study is a prospective cohort study of 1.3 million middle-aged women in England and Scotland recruited from 1996 to 2001. Participants were followed-up by record-linkage for a mean of 6.1 years for admissions to hospital. The adjusted relative risk of hospital admission for cholelithiasis, cholecystitis or cholecystectomy according to parity, breastfeeding, age at menarche and age at menopause was examined.

Results During follow-up of 1 289 029 eligible women, 25 111 were admitted to hospital for gallbladder disease, of whom 21 735 (87%) had a cholecystectomy. The hospital admission rate over 5 years for gallbladder disease was 1.6/100 women and for cholecystectomy was 1.4/100 women. The adjusted relative risk of gallbladder disease increased with increasing parity by 8% (95% CI 7–9%, P < 0.0001) for each birth. Among women of a given parity, breastfeeding reduced the risk of gallbladder disease, the relative risk decreasing by 7% (95% CI 5–10%, P < 0.0001) per year of breastfeeding. Women's age of menarche and age at menopause did not alter the risk of gallbladder disease (P = 0.4 and P = 0.3, respectively for linear trend).

Conclusion Hospitalization for gallbladder disease is common in middle-aged women. The risk increases the more children a woman has had, but decreases the longer she breastfeeds. The increased risk of gallbladder disease associated with having children can be offset by breastfeeding.