[Show abstract][Hide abstract]ABSTRACT: Background:
The maternal and infant microbiome may influence infant cardiovascular risk through immune programming. The maternal vagino-enteric microbiome is often sampled for group B streptococcus (GBS) colonization during pregnancy. Our aim was to investigate the association between maternal GBS colonization, intrapartum antibiotics, antenatal pet exposure and infant aortic intima-media thickness (aIMT), an intermediate vascular phenotype, and whether this association varied by mode of delivery.
The Barwon Infant Study is a population-derived pre-birth cohort. Perinatal data were collected on participants. Women were tested for vagino-enteric group B streptococcus (GBS) colonization during third trimester. Six-week infant aIMT was measured by trans-abdominal ultrasound. Adjustment for confounders included maternal age, pre-pregnancy body mass index (BMI), smoking, socioeconomic status, gestational diabetes, length of gestation, infant sex, birthweight and aortic internal diameter.
Data were available on 835 mother-infant pairs. Of these, 574 (69%) women delivered vaginally; of those, 129 (22%) were GBS-colonized; and of these women, 111 (86%) received prophylactic intrapartum antibiotics. An association between maternal GBS colonization and infant aIMT was observed among those delivered vaginally (β = 19.5 µm, 95% CI 9.5, 29.4;P < 0.0001) but not by Caesarean section (Pfor interaction = 0.02). A similar pattern was seen for intrapartum antibiotics. There was a negative association between antenatal pet exposure and aIMT observed in those delivered vaginally.
Maternal GBS colonization and intrapartum antibiotics were associated with increased infant aIMT in those delivered vaginally, whereas antenatal pet exposure was associated with decreased aIMT. These data suggest that differences in early life microbial experience may contribute to an increased cardiovascular risk.
Full-text · Article · Apr 2016 · International Journal of Epidemiology
[Show abstract][Hide abstract]ABSTRACT: Multiple imputation (MI), a two-stage process whereby missing data are imputed multiple times and the resulting estimates of the parameter(s) of interest are combined across the completed datasets, is becoming increasingly popular for handling missing data. However, MI can result in biased inference if not carried out appropriately or if the underlying assumptions are not justifiable. Despite this, there remains a scarcity of guidelines for carrying out MI. In this paper we provide a tutorial on the main issues involved in employing MI, as well as highlighting some common pitfalls and misconceptions, and areas requiring further development. When contemplating using MI we must first consider whether it is likely to offer gains (reduced bias or increased precision) over alternative methods of analysis. Once it has been decided to use MI, there are a number of decisions that must be made during the imputation process; we discuss the extent to which these decisions can be guided by the current literature. Finally we highlight the importance of checking the fit of the imputation model. This process is illustrated using a case study in which we impute missing outcome data in a five-wave longitudinal study that compared extremely preterm individuals with term-born controls.
No preview · Article · Feb 2016 · International Journal of Social Research Methodology
[Show abstract][Hide abstract]ABSTRACT: Background and objectives:
Infant body composition and postnatal weight gain have been implicated in the development of adult obesity and cardiovascular disease, but there are limited prospective data regarding the association between infant adiposity, postnatal growth, and early cardiovascular parameters. Increased aortic intima-media thickness is an intermediate phenotype of early atherosclerosis. The aim of this study was to investigate the relationship between weight and adiposity at birth, postnatal growth, and aortic intima-media thickness.
The Barwon Infant Study (n=1074 mother-infant pairs) is a population-derived birth cohort. Infant weight and other anthropometry were measured at birth and 6 weeks of age. Aortic intima-media thickness was measured by trans-abdominal ultrasound at 6 weeks of age (n=835).
After adjustment for aortic size and other factors, markers of adiposity including increased birth weight (β=19.9μm/kg, 95%CI 11.1, 28.6 p<0.001) and birth skinfold thickness (β=6.9μm/mm, 95%CI 3.3, 10.5 p<0.001) were associated with aortic intima-media thickness at 6 weeks. The association between birth skin-fold thickness and aortic IMT was independent of birth weight. In addition, greater postnatal weight gain was associated with increased aortic intima-media thickness, independent of birth weight and age at time of scan (β=11.3μm/per kg increase, 95%CI 2.2, 20.3 p=0.01).
Increased infant weight and adiposity at birth, as well as increased early weight gain, were positively associated with aortic intima-media thickness. Excessive accumulation of adiposity during gestation and early infancy may have adverse effects on cardiovascular risk.
No preview · Article · Dec 2015 · Clinical Science
[Show abstract][Hide abstract]ABSTRACT: Background Multiple imputation (MI) is a well-recognised statistical technique for handling missing data. As usually implemented in standard statistical software, MI assumes that data are ‘Missing at random’ (MAR); an assumption that in many settings is implausible. It is not possible to distinguish whether data are MAR or ‘Missing not at random’ (MNAR) using the observed data, so it is desirable to discover the impact of departures from the MAR assumption on the MI results by conducting sensitivity analyses. A weighting approach based on a selection model has been proposed for performing MNAR analyses to assess the robustness of results obtained under standard MI to departures from MAR. Methods In this article, we use simulation to evaluate the weighting approach as a method for exploring possible departures from MAR, with missingness in a single variable, where the parameters of interest are the marginal mean (and probability) of a partially observed outcome variable and a measure of association between the outcome and a fully observed exposure. The simulation studies compare the weighting-based MNAR estimates for various numbers of imputations in small and large samples, for moderate to large magnitudes of departure from MAR, where the degree of departure from MAR was assumed known. Further, we evaluated a proposed graphical method, which uses the dataset with missing data, for obtaining a plausible range of values for the parameter that quantifies the magnitude of departure from MAR. Results Our simulation studies confirm that the weighting approach outperformed the MAR approach, but it still suffered from bias. In particular, our findings demonstrate that the weighting approach provides biased parameter estimates, even when a large number of imputations is performed. In the examples presented, the graphical approach for selecting a range of values for the possible departures from MAR did not capture the true parameter value of departure used in generating the data. Conclusions Overall, the weighting approach is not recommended for sensitivity analyses following MI, and further research is required to develop more appropriate methods to perform such sensitivity analyses.
Preview · Article · Dec 2015 · BMC Medical Research Methodology
[Show abstract][Hide abstract]ABSTRACT: Purpose Mental and behavioral disorders increase in prevalence with the passage through puberty. Yet the first symptoms for many children emerge between seven and 11 years, before the pubertal rise in gonadal hormones. A possibility that symptom onset may be linked to the adrenarchal rise in androgens has been little explored. Methods The Childhood to Adolescence Transition Study recruited a stratified random sample of 1,239 eight-nine year olds from primary schools in Melbourne, Australia. Saliva samples were assayed for dehydroepiandrosterone, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. Emotional and behavioral problems were assessed through parental report on the Strengths and Difficulties Questionnaire. Results In males, high levels of all androgens were associated with greater total difficulties and peer problems. Higher dehydroepiandrosterone and testosterone were associated with emotional symptoms and DHEA-S with conduct problems. In females, DHEA-S was associated with peer problems. Conclusions In late childhood, androgens are associated with emotional and behavioral problems in males, raising a possibility that the adrenarchal transition plays a contributing role. If so, the late primary school years may prove to be an important phase for preventing the onset of mental health and behavioral problems in boys.
No preview · Article · Dec 2015 · Journal of Adolescent Health
[Show abstract][Hide abstract]ABSTRACT: Background:
There are limited longitudinal data on the associations between different social contexts of alcohol use and risky adolescent drinking.
Australian prospective longitudinal cohort of 1943 adolescents with 6 assessment waves at ages 14-17 years. Drinkers were asked where and how frequently they drank. Contexts were: at home with family, at home alone, at a party with friends, in a park/car, or at a bar/nightclub. The outcomes were prevalence and incidence of risky drinking (≥5 standard drinks (10g alcohol) on a day, past week) and very risky drinking (>20 standard drinks for males and >11 for females) in early (waves 1-2) and late (waves 3-6) adolescence.
Forty-four percent (95 % CI: 41-46 %) reported past-week risky drinking on at least one wave during adolescence (waves 1-6). Drinking at a party was the most common repeated drinking context in early adolescence (28 %, 95 % CI 26-30 %); 15 % reported drinking repeatedly (3+ times) with their family in early adolescence (95 % CI: 14-17 %). For all contexts (including drinking with family), drinking 3+ times in a given context was associated with increased the risk of risky drinking in later adolescence. These effects remained apparent after adjustment for potential confounders (e.g. for drinking with family, adjusted RR 1.9; 95 % CI: 1.5-2.4). Similar patterns were observed for very risky drinking.
Our results suggest that consumption with family does not protect against risky drinking. Furthermore, parents who wish to minimise high risk drinking by their adolescent children might also limit their children's opportunities to consume alcohol in unsupervised settings.
Full-text · Article · Nov 2015 · BMC Public Health
[Show abstract][Hide abstract]ABSTRACT: Background.—Distinguishing pathological from physiological relationships between vessel size and aortic intima-media thickness (aIMT) is an important challenge, especially in growing children. We examined the relationship between childhood vessel diameter and aIMT and assessed common analytic approaches used to address this relationship.Methods.—We analyzed aIMT in two population-derived cohorts; 6-week-old infants and 19-year-olds. We simulated datasets in which we assumed a simple physiological relationship between vessel diameter and aIMT, and then superimposed possible pathological effects on aIMT; (a) intrauterine growth retardation, (b) macrosomia and (c) both intrauterine growth retardation and macrosomia. Using simulated datasets and cohorts, we evaluated analytic strategies including those in which the relationship between vessel diameter and aIMT was (a) ignored, (b) adjusted for by dividing aIMT by weight, or (c) adjusted for using varying regression techniques.Results.—aIMT was found to increase in proportion to vessel diameter in both cohorts (138 μm/mm at 6 weeks and 52 μm/mm at 19 years of age). Simply dividing aIMT by weight produced negative associations with weight across all datasets. By contrast, adjusting for vessel diameter as a covariate enabled accurate distinction of the direction of the association between aIMT and weight in all simulated datasets. These results were replicated in the cohort studies for both aIMT and carotid intima-media thickness.Conclusion.—There is a physiological relationship between vessel diameter and aIMT. Simply dividing aIMT by weight may lead to incorrect assumptions regarding the relationship between weight and aIMT. However, the physiological relationship is appropriately estimated by including vessel diameter as a covariate in regression.
[Show abstract][Hide abstract]ABSTRACT: Perinatal depression is a neglected global health priority, affecting 10–15% of women in high-income countries and a greater proportion in low-income countries. Outcomes for children include cognitive, behavioural, and emotional difficulties and, in low-income settings, perinatal depression is associated with stunting and physical illness. In the Victorian Intergenerational Health Cohort Study (VIHCS), we aimed to assess the extent to which women with perinatal depressive symptoms had a history of mental health problems before conception.
[Show abstract][Hide abstract]ABSTRACT: Stepped wedge randomized trials are increasingly popular. Here we derive the optimal design for a fixed number of periods; this does not allocate an equal number of cluster units to each treatment sequence as might otherwise have been expected.
No preview · Article · Apr 2015 · Statistics [?] Probability Letters
[Show abstract][Hide abstract]ABSTRACT: As there is limited knowledge regarding the longitudinal development and early ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naïve (thymic and central) and regulatory (resting and activated) CD4(+) T-cell populations during the first postnatal year. Blood samples were collected and analyzed at birth, 6 and 12 months of age from a population-derived sample of 130 infants. The proportion of naïve and regulatory CD4(+) T-cell populations was determined by flow cytometry, and the thymic and central naïve populations were sorted and their phenotype confirmed by relative expression of T cell-receptor excision circle DNA (TREC). At birth, the majority (94%) of CD4(+) T cells were naïve (CD45RA(+)), and of these, ~80% had a thymic naïve phenotype (CD31(+) and high TREC), with the remainder already central naïve cells (CD31(-) and low TREC). During the first year of life, the naïve CD4(+) T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naïve T regulatory cells (rTreg; CD4(+)CD45RA(+)FoxP3(+)) and activated Treg (aTreg, CD4(+)CD45RA(-)FoxP3(high)) increased markedly. The ratio of thymic to central naïve CD4(+) T cells was lower in males throughout the first postnatal year indicating early sexual dimorphism in immune development. This longitudinal study defines proportions of CD4(+) T-cell populations during the first year of postnatal life that provide a better understanding of normal immune development.