Biomedical subjects

Vera Mann

Publications and source records attributed to Vera Mann.

6 recordsLinked to original sources

PubMed2005

Statistical issues in life course epidemiology.

There is growing recognition that the risk of many diseases in later life, such as type 2 diabetes or breast cancer, is affected by adult as well as early-life variables, including those operating prior to conception and during the prenatal period. Most of these risk factors are correlated because of common biologic and/or social pathways, while some are intrinsically ordered over time. The study of how they jointly influence later ("distal") disease outcomes is referred to as life course epidemiology. This area of research raises several issues relevant to the current debate on causal inference in epidemiology. The authors give a brief overview of the main analytical and practical problems and consider a range of modeling approaches, their differences determined by the degree with which associations present (or presumed) among the correlated explanatory variables are explicitly acknowledged. Standard multiple regression (i.e., conditional) models are compared with joint models where more than one outcome is specified. Issues arising from measurement error and missing data are addressed. Examples from two cohorts in the United Kingdom are used to illustrate alternative modeling strategies. The authors conclude that more than one analytical approach should be adopted to gain more insight into the underlying mechanisms.

Causality↗

PubMed2005

Fetal, developmental, and parental influences on childhood systolic blood pressure in 600 sib pairs: the Uppsala Family study.

BACKGROUND: Little is known about the contribution of maternal and paternal factors to the inverse association between birth weight and later blood pressure in human offspring. A study of within- and between-family associations of birth weight with blood pressure, which collected data on both parents, would address this gap in our knowledge. METHODS AND RESULTS: The study examined families composed of mother, father, and 2 full sibs delivered between 38 and 41 weeks' gestation within 36 months of each other. A total of 1967 families meeting our inclusion criteria were contacted and 602 were examined (children 5 to 14 years old, 1998 to 2000). Birth weight and gestational age were available from obstetric records. Systolic blood pressure in childhood was inversely associated with birth weight within families (-2.3 mm Hg/kg, 95% CI -4.4 to -0.3) after adjustment for gestational age, sex, height, and weight at examination. The between-family effect (-1.5 mm Hg/kg, -3.1 to 0.0) was strengthened on adjustment for maternal and paternal height and weight, whereas adjustment for paternal and maternal systolic blood pressure at examination independently attenuated the effect. CONCLUSIONS: The existence of an inverse association of birth weight with systolic blood pressure within families (adjusted for height and weight at examination) demonstrates that factors that vary between pregnancies in the same woman (including fetal genotype) can influence the later blood pressure of offspring. We conclude that this apparent fetal programming effect on blood pressure will not be eliminated solely by interventions aimed at modifying growth and cumulative nutritional status from conception through childhood or other fixed characteristics of future mothers.

Adolescent↗

PubMed2005

Morning cortisol does not mediate the association of size at birth with blood pressure in children born from full-term pregnancies.

OBJECTIVE: It had been suggested that programming of the hypothalamo-pituitary-adrenal axis may underlie the associations of reduced size at birth with raised blood pressure in later life. We investigated whether morning salivary cortisol mediates the inverse association of birthweight with systolic blood pressure in children. DESIGN: Subjects and measurements--a historical cohort study involving 1152 Swedish children aged 5-14 years, who took part in a family study comprised of mother, father, and two full-sibs delivered in 1987-1995 after 38-41 weeks gestation within 36 months of each other. Birthweight and gestational age were available from obstetric records. Blood pressure, weight, height and puberty stage were measured at a clinic. Cortisol was measured by radioimmunoassay in morning salivary samples taken at home, within 30 min of waking. RESULTS: Morning cortisol showed a weak negative association with length of gestation in siblings, was not related to birthweight or to systolic or diastolic blood pressure. There was no change in the strength of the negative association between birthweight and systolic blood pressure on adjustment for cortisol (-1.4 mmHg/kg, 95% CI -2.7, -0.2; adjusted for age, sex, puberty stage, weight and height, and cortisol). CONCLUSIONS: Morning cortisol was not associated with size at birth, and did not mediate the birthweight-blood pressure association in children born from full-term pregnancies. It is possible that basal cortisol levels are of more importance in explaining associations of size at birth with later blood pressure in older subjects, or in populations with more varied length of gestation. Alternatively, our results may be caused by misclassification of the hypothalamo-pituitary-adrenal activity.

Adolescent↗

PubMed2005

Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene.

Rare mutations in the glucokinase (GCK) gene cause fasting hyperglycemia and considerably influence birth weight when present in a mother or her offspring. The role of common variation of GCK is uncertain. A polymorphism at position -30 of the GCK beta-cell-specific promoter, present in 30% of the population, has been variably associated with type 2 diabetes and diabetes-related quantitative traits. Using 1,763 U.K. Caucasian normoglycemic adult subjects, we demonstrated that the A allele at GCK(-30) is associated with a 0.06-mmol/l increase in fasting plasma glucose (FPG) (P = 0.003). The A allele was also associated with an increase in FPG in 755 women who were 28 weeks pregnant (0.075 mmol/l, P = 0.003). We then went on to analyze the effect of GCK(-30) on birth weight using 2,689 mother/child pairs. The presence of the A allele in the mother was associated with a 64-g (25-102 g) increase in offspring birth weight (P = 0.001). We did not detect a fetal genotype effect. The increase in offspring birth weight in the 30% of mothers carrying an A allele at GCK(-30) is likely to reflect an elevated FPG during pregnancy. This study establishes that common genetic variation, in addition to rare mutations and environmental factors, can affect both FPG and birth weight.

Adult↗

PubMed2004

Separating within and between effects in family studies: an application to the study of blood pressure in children.

In epidemiology the analyses of family or twin studies do not always fully exploit the data, as information on differences between siblings is often used while between-families effect are not considered. We show how cross-sectional time-series linear regression analysis can be easily implemented to estimate within- and between-families effects simultaneously and how these effects can then be compared using the Hausman test. We illustrate this approach with data from the Uppsala family study on blood pressure in children with age ranging from 5.5 to 12.3 years for the younger and from 7.5 to 13.8 years for the older siblings. Comparing the effect of differences in birth weight on blood pressure within-family (in full siblings) and between-families (in unrelated children) allows us to study the contributions of fixed and pregnancy-specific maternal effects on birth weight and consequently on blood pressure. Our data showed a 0.88 mmHg decrease (95 per cent confidence interval: -1.7 to -0.03 mmHg) in systolic blood pressure for one standard deviation increase in birth weight between siblings within a family and 0.88 mmHg (95 per cent confidence interval: -1.6 to -0.2 mmHg) decrease in systolic blood pressure for one standard deviation increase in birth weight between unrelated children. These estimates were controlled for sex, age, pubertal stage, body size and pulse rate of the children at examination and for maternal body size and systolic blood pressure. The within- and between-families effects were not significantly different, p = 0.19, suggesting that fixed and pregnancy-specific factors have similar effects on childhood systolic blood pressure.

Adolescent↗

PubMed2002

Prenatal factors, childhood growth trajectories and age at menarche.

BACKGROUND: In recent studies a larger birth size has been shown to delay the timing of menarche. The mechanisms underlying this association are not clear, however, as birthweight is a predictor of body size in childhood, and a large body size is known to be associated with an early onset of menarche. METHODS: Data from a representative British cohort of 2547 girls born in 1946 who were followed prospectively throughout childhood were used. Information was available on prenatal characteristics, birthweight, height, weight and social circumstances during childhood, and on age at menarche. Random coefficients models were used to estimate the individual trajectories in height and body mass index (BMI) up to age 7 years. The parameters identified by these models were then included in Weibull survival models for the timing of menarche together with birthweight. RESULTS: Birthweight was found to positively influence height and BMI values at age 2 years, but not to affect their rates of change from age 2 to 7 years. Initial analyses showed low birthweight to be associated with an early onset of menarche, but after controlling for growth in infancy this effect was reversed, with girls who were heavy at birth reaching menarche earlier than others with similar infant growth. Rapid growth in infancy was also related to early pubertal maturation. The effects of birthweight and infant growth disappeared, however, when further controlled for growth from age 2 to 7 years. CONCLUSIONS: The effects of birthweight and growth in infancy on the timing of menarche seem to be mediated through growth in early childhood. These findings are consistent with the possibility that timing of menarche may be set in utero or early in life, although it may be modified by changes in body size and composition in childhood.

Birth Weight↗