Incretin-based drugs and risk of lung cancer among individuals with type 2 diabetes.

AIM: To assess whether dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists are associated with an increased lung cancer risk among individuals with type 2 diabetes. METHODS: We conducted a population-based cohort study using the UK Clinical Practice Research Datalink. We identified 130 340 individuals newly treated with antidiabetes drugs between January 2007 and March 2017, with follow-up until March 2018. We used a time-varying approach to model use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists compared with use of other second- or third-line antidiabetes drugs. We used Cox proportional hazards models to estimate the adjusted hazard ratios, with 95% CIs, of incident lung cancer associated with use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists, separately, by cumulative duration of use, and by time since initiation. RESULTS: A total of 790 individuals were newly diagnosed with lung cancer (median follow-up 4.6 years, incidence rate 1.5/1000 person-years, 95% CI 1.4-1.6). Compared with use of second-/third-line drugs, use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists was not associated with an increased lung cancer risk (hazard ratio 1.07, 95% CI 0.87-1.32, and hazard ratio 1.02, 95% CI 0.68-1.54, respectively). There was no evidence of duration-response relationships. CONCLUSIONS: In individuals with type 2 diabetes, use of incretin-based drugs was not associated with increased lung cancer risk.

Obstetric haemorrhage and risk of cardiovascular disease after three decades: a population-based cohort study.

OBJECTIVE: To investigate the association between obstetric haemorrhage and cardiovascular disease up to three decades after pregnancy. DESIGN: Population-based cohort study. SETTING AND POPULATION: All women who delivered between 1989 and 2016 in Quebec, Canada. METHODS: Using hospital admissions data, 1 224 975 women were followed from their first delivery until March 2018. The main exposure measures were antenatal (placenta praevia, placental abruption, peripartum haemorrhage) or postpartum haemorrhage, with or without transfusion. Adjusted Cox regression models were used to assess the association between obstetric haemorrhage and future cardiovascular disease. MAIN OUTCOME MEASURE: Cardiovascular hospitalisation. RESULTS: Among 104 291 (8.5%) women with haemorrhage, 4612 (4.4%) required transfusion. Women with haemorrhage had a higher incidence of cardiovascular hospitalisation than women without haemorrhage (15.5 versus 14.1 per 10 000 person-years; 2437 versus 28 432 events). Risk of cardiovascular hospitalisation was higher for obstetric haemorrhage, with or without transfusion, compared with no haemorrhage (adjusted hazard ratio [aHR] 1.06, 95% CI 1.02-1.10). Women with haemorrhage and transfusion had a substantially greater risk of cardiovascular hospitalisation (aHR 1.47, 95% CI 1.23-1.76). Among transfused women, placental abruption (aHR 1.79, 95% CI 1.06-3.00) and postpartum haemorrhage (aHR 1.38, 95% CI 1.13-1.68) were both associated with risk of cardiovascular hospitalisation. Antenatal haemorrhage with transfusion was associated with 2.46 times the risk of cardiovascular hospitalisation at 5 years (95% CI 1.59-3.80) and 2.14 times the risk at 10 years (95% CI 1.47-3.12). CONCLUSIONS: Obstetric haemorrhage requiring transfusion is associated with maternal cardiovascular disease. The benefit of cardiovascular risk prevention in pregnant women with obstetric haemorrhage requires further investigation. TWEETABLE ABSTRACT: Risk of future cardiovascular disease is increased for women with obstetric haemorrhage who require transfusion.

A systematic review of observational studies of the association between pioglitazone use and bladder cancer.

AIM: To conduct a systematic review of all observational studies on the effect of pioglitazone on the risk of bladder cancer. METHODS: The MEDLINE and EMBASE databases were queried for papers published between 1 January 2000 and 30 October 2017. We took into consideration observational studies (both retrospective and prospective) that included participants with Type 2 diabetes prescribed anti-hyperglycaemic drugs. RESULTS: While some studies reported an association, others did not, and meta-analyses of these studies showed a significantly increased risk; however, while meta-analysis is a powerful and practical statistical tool, its results should be considered with caution when applied to widely heterogeneous studies. We describe how many of these studies are affected by different types of bias, most notably time-related biases, which should preclude a pooled analysis that would result in biased estimation of the risk. CONCLUSIONS: Given existing data, it is not appropriate to pool the outcomes of highly heterogeneous studies and further rigorously conducted observational research is needed to clarify the role of pioglitazone use on the incidence of bladder cancer.

A cautionary note about estimating effects of secondary exposures in cohort studies.

Cohort studies are often enriched for a primary exposure of interest to improve cost-effectiveness, which presents analytical challenges not commonly discussed in epidemiology. In this paper, we use causal diagrams to represent exposure-enriched cohort studies, illustrate a scenario wherein the risk ratio for the effect of a secondary exposure on an outcome is biased, and propose an analytical method for correcting for such bias. In our motivating example, maternal smoking (Z) is a cause of fetal growth restriction (X), which subsequently affects preterm birth (Y) (i.e., Z → X → Y); strong positive associations exist between both Z, X and X, Y; and enrichment for X increases its prevalence from 10% to 50%. In the X-enriched cohort, unadjusted and X-adjusted analyses lead to bias in the risk ratio for the total effect of Z on Y. After application of inverse probability weights, the bias is corrected, with a small loss of efficiency in comparison with a same-sized study without X-enrichment. With increasing interest in conducting secondary analyses to reduce research costs, caution should be employed when analyzing studies that have already been enriched, intentionally or unintentionally, for a primary exposure of interest. Causal diagrams can help identify scenarios in which secondary analyses may be biased. Inverse probability weights can be used to remove the bias.

Fetal death and preterm birth associated with maternal influenza vaccination: systematic review.

BACKGROUND: Before 2012, few studies had addressed pregnancy outcomes following maternal influenza vaccination; however, the number of publications on this topic has increased recently. OBJECTIVES: To review comparative studies evaluating fetal death or preterm birth associated with influenza vaccination during pregnancy. SEARCH STRATEGY: We searched bibliographic databases from inception to April 2014. SELECTION CRITERIA: Experimental or observational studies assessing the relationship between influenza vaccination during pregnancy and fetal death or preterm birth. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data from studies meeting the inclusion criteria. MAIN RESULTS: We included one randomised clinical trial and 26 observational studies. Meta-analyses were not considered appropriate because of high clinical and statistical heterogeneity. Three studies of fetal death at any gestational age reported adjusted effect estimates in the range 0.56-0.79, and four of five studies of fetal death at <20 weeks reported adjusted estimates between 0.89 and 1.23, all with confidence intervals including 1.0. Adjusted effect estimates for four of five studies of fetal death at ≥20 weeks ranged from 0.44 to 0.77 (two with confidence intervals not crossing 1.0), whereas a fifth reported a non-significant effect in the opposite direction. Among 19 studies of preterm birth, there was no strong evidence suggesting any increased risk, and meta-regression did not explain the moderate between-study heterogeneity (I(2) = 57%). AUTHORS' CONCLUSIONS: Most studies reported no association between fetal death or preterm birth and influenza vaccination during pregnancy. Although several reported risk reductions, results may be biased by methodological shortcomings of observational studies of influenza vaccine effectiveness.

Small-for-gestational-age birth and maternal plasma antioxidant levels in mid-gestation: a nested case-control study.

OBJECTIVE: To assess whether maternal plasma antioxidant levels in mid-pregnancy are associated with small-for-gestational-age (SGA) birth. DESIGN: Case-control study nested within a population-based cohort study. SETTING: Four hospitals in Montreal, Canada. POPULATION: Pregnant women recruited before 24 weeks of gestation, whose pregnancies were not complicated by pre-eclampsia or preterm delivery. METHODS: Blood samples were obtained at 24-26 weeks and assayed for nutritionally derived antioxidant levels in SGA cases (n = 324) and randomly selected controls with birthweights between the 25th and 75th centiles (n = 672). We performed logistic regression analyses using the standardised z-score of each antioxidant as the main independent variable, after summing highly correlated antioxidants or combining via principle component analysis. We adjusted for risk factors for SGA that were associated with antioxidant levels. MAIN OUTCOME MEASURES: SGA, birthweight <10th centile for gestational age and sex. RESULTS: Retinol was positively associated with risk of SGA (adjusted odds ratio [OR] 1.41; 95% confidence interval [95% CI] 1.22-1.63, per SD increase). Carotenoids (log of the sum of ß-carotene, lutein/zeaxanthin, α- and ß-cryptoxanthin) were negatively associated with SGA (adjusted OR 0.64; 95% CI 0.54-0.78, per SD increase). We found no significant associations between SGA and lycopene or any of the forms of vitamin E assessed, including α-tocopherol, corrected α-tocopherol (per nmol/l of low-density lipoprotein articles), or γ-tocopherol. CONCLUSIONS: Elevated retinol may be associated with an increased risk of SGA, whereas elevated carotenoid levels may reduce the risk. A better understanding of the nature of these associations is required, however, before recommending specific nutritional interventions in an attempt to prevent SGA birth.

Impact of HLA mismatch at first kidney transplant on lifetime with graft function in young recipients.

As HLA matching has been progressively de-emphasized in the American deceased donor (DD) kidney allocation algorithm, concerns have been raised that poor matching at first transplant may lead to greater sensitization and more difficulty finding an acceptable donor for a second transplant should the first transplant fail. We compared proportion of total observed lifetime with graft function after first transplant, and waiting times for a second transplant between individuals with different levels of HLA mismatch (MM) at first transplant. We studied patients recorded in the United States Renal Data System (1988-2009) who received a first DD transplant at age ≤21 years (n = 8433), and the subgroup who were listed for a second DD transplant following first graft failure (n = 2498). Compared with recipients of 2-3 MM first grafts, 4-6 MM graft recipients spent 12% less of their time and 0-1 MM recipients 15% more time with a functioning graft after the first transplant (both p < 0.0001); 4-6 MM recipients were significantly less likely (hazard ratio [HR] 0.87 [95% confidence interval 0.76, 0.98]; p = 0.03), and 0-1 MM recipients more likely (HR 1.26 [0.99, 1.60]; p = 0.06) to receive a second transplant after listing. The benefits of better HLA matching at first transplant on lifetime with graft function are significant, but relatively small.

Measuring antimicrobial use in hospitalized patients: a systematic review of available measures applicable to paediatrics.

OBJECTIVES: The optimal measure to use for surveillance of antimicrobial usage in hospital settings, especially when including paediatric populations, is unknown. This systematic review of literature aims to list, define and compare existing measures of antimicrobial use that have been applied in settings that included paediatric inpatients, to complement surveillance of resistance. METHODS: We identified cohort studies and repeated point-prevalence studies presenting data on antimicrobial use in populations of inpatients or validations/comparisons of antimicrobial measures through a systematic search of literature using MEDLINE, EMBASE, CINAHL and LILACS (1975-2011) and citation tracking. Study populations needed to include hospitalized paediatric patients. Two reviewers independently extracted data on study characteristics and results. RESULTS: Overall, 3878 records were screened and 79 studies met selection criteria. Twenty-six distinct measures were found, the most frequently used being defined daily doses (DDD)/patient-days and exposed patients/patients. Only two studies compared different measures quantitatively, showing (i) a positive correlation between proportion of exposed patients and antimicrobial-days/patient-days and (ii) a strong correlation between doses/patient-days and agent-days/patient-days (r = 0.98), with doses/patient-days correlating more with resistance rates (r = 0.80 versus 0.55). CONCLUSIONS: The measure of antimicrobial use that best predicts antimicrobial resistance prevalence and rates, for surveillance purposes, has still not been identified; additional evidence on this topic is a necessity.

Neurodevelopmental disorders in children born to mothers with systemic lupus erythematosus.

Children born to women with systemic lupus erythematosus seem to have a potentially increased risk of neurodevelopmental disorders compared to children born to healthy women. Recent experimental data suggest in utero exposure to maternal antibodies and cytokines as important risk factors for neurodevelopmental disorders. Interestingly, women with systemic lupus erythematosus display high levels of autoantibodies and cytokines, which have been shown, in animal models, to alter fetal brain development and induce behavioral anomalies in offspring. Furthermore, subjects with systemic lupus erythematosus and neurodevelopmental disorders share a common genetic predisposition, which could impair the fetal immune response to in utero immunologic insults. Moreover, systemic lupus erythematosus pregnancies are at increased risk of adverse obstetrical outcomes and medication exposures, which have been implicated as potential risk factors for neurodevelopmental disorders. In this article, we review the current state of knowledge on neurodevelopmental disorders and their potential determinants in systemic lupus erythematosus offspring.

Change in mortality risk over time in young kidney transplant recipients.

Mortality risk for kidney transplant recipients may change with increasing accumulated exposure to the "transplantation milieu." We sought to characterize changes over time in mortality rate and in age-, sex- and race-standardized mortality ratios (SMR) relative to the general population, and to estimate the association between increasing time since first transplant and mortality risk. A total of 18 911 patients who received a first transplant at <21 years old (1983-2006), and whose data were recorded in the USRDS, were studied. There were 2713 deaths over a median follow-up of 8.9 (interquartile range 4.0-14.5; maximum 23) years. Among those with graft function, mortality was highest in the first post transplant year; beyond the first year of the first transplant, age-adjusted mortality rates and SMRs decreased slightly over follow-up. Cause of death was cardiovascular for 34.6%, infection for 19.5%, malignancy for 5.8%, other for 21.4% and unknown for 18.7%. For every 1-year time increment after the end of the first post transplant year, age-adjusted all-cause and cardiovascular mortality rates fell by 1% (p = 0.06) and 16% (p = 0.007), respectively; infection-related mortality rate did not change over time (p = 0.5). These results suggest that exposure to the transplantation milieu has no cumulative negative effects on cardiovascular health over the long term.

Influence of ultrasound-to-delivery interval and maternal-fetal characteristics on validity of estimated fetal weight.

OBJECTIVES: To explore the effects of ultrasound-to-delivery interval and maternal-fetal characteristics on the distribution of measurement error in estimated fetal weights (EFWs), and to determine the predictive ability of EFW for diagnosis of small-for-gestational age (SGA) and large-for-gestational age (LGA) among infants delivered within 1 day of an ultrasound examination. METHODS: Percentage differences between EFW and birth weights were calculated in 3697 pregnancies. Linear regression was used to compare the accuracy of EFW for births on each of the 6 days after an ultrasound scan with the accuracy observed among births on the same day. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value for diagnosis of SGA and LGA according to EFW was assessed. RESULTS: The mean +/- SD percentage difference among deliveries within 1 day of the last ultrasound scan was 0.2 +/- 9.0%. Mean percentage differences were not significantly different from day 0 on days 1, 2 and 3; however, combining the data from these 4 days obscured a slight bias towards an overestimation of weight evident on day 0 and day 1. Among deliveries within 1 day of an ultrasound scan, the PPV was 61% for SGA diagnosis and 54% for LGA diagnosis. CONCLUSION: Combining data from births > 1 day after the last ultrasound examination may lead to a false conclusion that there is systematic underestimation of weight. EFW tended to underestimate the weight of macrosomic fetuses and overestimate that of small fetuses which limited sensitivity and PPV. Maternal-fetal characteristics are weak predictors of individual errors in EFW.

The low prevalence of allergic disease in Eastern Europe: are risk factors consistent with the hygiene hypothesis?

BACKGROUND: The prevalence of allergic disease is known to be low in Eastern Europe. OBJECTIVE: To assess the association of suspected risk factors, including several closely linked to the hygiene hypothesis, with allergic symptoms and atopic sensitization in young school-aged children. METHODS: Observational study of 13 889 Belarusian children followed up at age 6.5 years in the Promotion of Breastfeeding Intervention Trial (PROBIT). Allergic symptoms and diseases were based on parental responses to the International Study of Asthma and Allergy in Childhood questionnaire, and prick tests to five common inhalant allergens were performed using standard methods. RESULTS: Significantly increased risks of wheezing and hayfever symptoms in the past 12 months, and of recurrent itchy rash were observed in boys, children with a positive first-degree family atopic history, and those who had received probiotics (especially as prophylaxis with antibiotic use). Pet ownership, contact with farm animals, the presence and number of younger and (especially) older siblings, and residency in rural areas of Western Belarus were associated with reduced risks. Maternal postnatal smoking was associated with wheezing and hayfever symptoms, while the duration of exclusive breastfeeding was not protective against any of the studied outcomes. The risk factors for allergic symptoms were similar in children with positive skin-prick tests to those in the overall cohort. CONCLUSION: Many of the risk and protective factors we identified are consistent with those reported in Western countries and with the hygiene hypothesis. Further research on dietary and other environmental and genetic factors is necessary to understand the low prevalence of allergic disease in Belarus and other Eastern European countries.

Customised birthweight percentiles: does adjusting for maternal characteristics matter?

OBJECTIVE: The objective of this study was to determine whether the improved prediction of risk for perinatal mortality obtained with the use of a customised birthweight standard can also be obtained with the use of a non-customised but intrauterine-based standard. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: Births in the Swedish Medical Birth Register between 1992 and 2001 (n = 782 303) with complete data on birthweight, gestational age, sex, maternal age, pre-pregnancy body mass index, height, parity, and ethnicity. METHODS: We calculated the relative risks (RRs) of stillbirth and early neonatal mortality among small-for-gestational-age (SGA) births as established by (1) a customised standard, (2) a population standard based on birthweights, and (3) a population standard based on a best estimate of intrauterine weights. MAIN OUTCOME MEASURES: Stillbirth and early neonatal mortality (<7 days). RESULTS: The RRs of stillbirth and early neonatal mortality among SGA births as classified by the intrauterine standard were similar to those among SGA births as classified by the customised standard and much higher than those among SGA births as classified by the birthweight standard. CONCLUSIONS: A non-customised but intrauterine-based standard has a similar ability to predict risk for stillbirth and early neonatal mortality as a customised birthweight standard. The process of customising population weight-for-gestational-age standards to account for maternal characteristics does little to improve prediction of perinatal mortality.

Maternal anthropometric risk factors for caesarean delivery before or after onset of labour.

OBJECTIVE: To quantify the effects of pre-pregnancy body mass and gestational weight gain, above and beyond their known effects on birthweight, on the risk of primary and repeat caesarean delivery performed before or after the onset of labour. DESIGN: Hospital-based historical cohort study. SETTING: Canadian university-affiliated hospital. POPULATION: A total of 63 390 singleton term (> or = 37 weeks gestation) infants with cephalic presentation. METHODS: We studied prospectively archived deliveries at the Royal Victoria Hospital in Montreal, Canada, from 1 January 1978 to 31 March 2001 using multiple logistic regression models to estimate relative odds of caesarean delivery. MAIN OUTCOME MEASURE: Caesarean delivery, primary or repeat and before or after the onset of labour. RESULTS: Pregravid obesity (body mass index > or = 30 kg/m2) increased the likelihood of primary caesarean delivery before (OR = 2.01, 95% CI 1.39-2.90) and after (OR = 2.12, 95% CI 1.86-2.42) the onset of labour. High net rate of gestational weight gain (> 0.50 kg/week) increased the risk but only after labour onset (OR = 1.40, 95% CI 1.23-1.60). Among women with a previous caesarean, high weight gain modestly increased risk but only before labour (OR = 1.38, 95% CI 1.04-1.83), whereas obesity increased the risk of caesarean delivery both before (OR = 1.85, 95% CI 1.44-2.37) and after (OR = 1.96, 95% CI 1.11-3.47) labour onset. Increased risks of macrosomia accounted for the association between pregravid adiposity and repeat caesarean delivery performed after but not before the onset of labour. CONCLUSIONS: Pregravid obesity increases the risk of caesarean delivery both before and after the onset of labour and both with and without a history of caesarean.

The effect of prolonged and exclusive breast-feeding on dental caries in early school-age children. New evidence from a large randomized trial.

To study the effects of prolonged and exclusive breast-feeding on dental caries, we followed up children participating in the Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial of a breast-feeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative. A total of 17,046 healthy, mother-infant breast-feeding pairs were enrolled from 31 Belarussian maternity hospitals and affiliated polyclinics, of whom 13,889 (81.5%) were followed up at 6.5 years. At follow-up, polyclinic pediatricians transcribed the reports of a standard dental examination performed by public health dentists at age 6 years and recorded in the children's polyclinic charts. Analysis was based on intention to treat, with a statistical model that accounts for clustering within hospitals/clinics to permit inferences at the individual level. The experimental intervention led to a large increase in exclusive breast-feeding at 3 months (43.3 vs. 6.4%, p < 0.001) and a significantly higher prevalence of any breast-feeding at all ages up to and including 12 months. No significant intervention effects were observed on dental caries. Our results, based on the largest randomized trial ever conducted in the area of human lactation, provide no evidence of beneficial or harmful effects of prolonged and exclusive breast-feeding on dental caries at early school age.

Disconnected by design: analytic approach in treatment networks having no common comparator.

In a network meta-analysis, comparators of interest are ideally connected either directly or via one or more common comparators. However, in some therapeutic areas, the evidence base can produce networks that are disconnected, in which there is neither direct evidence nor an indirect route for comparing certain treatments within the network. Disconnected networks may occur when there is no accepted standard of care, when there has been a major paradigm shift in treatment, when use of a standard of care or placebo is debated, when a product receives orphan drug designation, or when there is a large number of available treatments and many accepted standards of care. These networks pose a challenge to decision makers and clinicians who want to estimate the relative efficacy and safety of newly available agents against alternatives. A currently recommended approach is to insert a distribution for the unknown treatment effect(s) into a network meta-analysis model of treatment effect. In this paper, we describe this approach along with two alternative Bayesian models that can accommodate disconnected networks. Additionally, we present a theoretical framework to guide the choice between modeling approaches. This paper presents researchers with the tools and framework for selecting appropriate models for indirect comparison of treatment efficacies when challenged with a disconnected framework. Copyright © 2016 John Wiley & Sons, Ltd.

Predicting the risk of Clostridium difficile infection following an outpatient visit: development and external validation of a pragmatic, prognostic risk score.

Increasing morbidity related to Clostridium difficile infection (CDI) has heightened interest in the identification of patients who would most benefit from recognition of risk and intervention. We sought to develop and validate a prognostic risk score to predict CDI risk for individual patients following an outpatient healthcare visit. We assembled a cohort of Kaiser Permanente Northwest (KPNW) patients with an index outpatient visit between 2005 and 2008, and identified CDI in the year following that visit. Applying Cox regression, we synthesized a priori predictors into a CDI risk score, which we validated among a Kaiser Permanente Colorado (KPCO) cohort. We calculated and plotted the observed 1-year CDI risk for each decile of predicted risk for both cohorts. Among 356 920 KPNW patients, 608 experienced CDI, giving a 1-year incidence of 2.2 CDIs per 1000 patients. The Cox model differentiated between patients who do and do not develop CDI: there was a C-statistic of 0.83 for KPNW. The simpler points-based risk score, derived from the Cox model, was validated successfully among 296 550 KPCO patients, with no decline in the area under the receiver operating characteristic curve: 0.785 (KPNW) vs. 0.790 (KPCO). The predicted risk for CDI agreed closely with the observed risk. Our CDI risk score utilized data collected during usual care to successfully identify patients who developed CDI, discriminating them from patients at the lowest risk for CDI. Our prognostic CDI risk score provides a decision-making tool for clinicians in the outpatient setting.

Do gastrointestinal tract infections in infancy increase blood pressure in childhood? A cohort study.

BACKGROUND: It has been hypothesised that dehydration in infancy could permanently increase sodium retention, raising blood pressure in later life. In this study, the association between gastrointestinal tract infection in infancy, a clinically relevant exposure often accompanied by dehydration, and raised blood pressure in childhood was investigated. METHODS: Data from a cohort study nested within a cluster-randomised trial of breastfeeding promotion in the Republic of Belarus were analysed. 17 046 healthy breastfed infants were enrolled from 31 maternity hospitals. 13 889 (81.5%) children were followed-up at 6.5 years. Exposure measures were any gastrointestinal infection in infancy (to 1 year) and hospitalisations for gastrointestinal infection in infancy and in childhood (1-6.5 years). The outcomes were systolic and diastolic blood pressure at age 6.5 years. RESULTS: The prevalence of any gastrointestinal infection in infancy, and of hospitalisation for gastrointestinal infection in infancy or childhood, was 11.4%, 3.2% and 6.0%, respectively. No associations were observed between systolic blood pressure and any gastrointestinal infection (mean difference in those with minus those without infection -0.04 mm Hg; 95% CI -0.52 to 0.43) or hospitalisation for gastrointestinal infection (difference=-0.22 mm Hg; -1.07 to 0.64) in infancy. Nor were associations observed between diastolic blood pressure and any gastrointestinal infection during infancy or hospitalisation for gastrointestinal infection during infancy or childhood. CONCLUSION: No evidence was found to prove that hospitalisation for gastrointestinal infection in infancy or childhood leads to raised blood pressure at age 6.5 years in a developed country setting.