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Systematic investigation of intramolecular silyloxypyrone-based [5 + 2] cycloadditions revealed three significant factors impacting conversion to cycloadduct: (1) the silyl transfer group has a substantial influence on the rate of reaction, and the robust t -butyldiphenylsilyl group was found to be more effective overall than the conventional t -butyldimethylsilyl group; (2) α,β-unsaturated esters were generally more reactive than terminal olefins and afforded appreciable quantity of cycloadduct even at room temperature; and (3) the proximity of the tether to the silyl transfer group revealed a critical alignment trend between the pyrone and the alkene. Taken together, these investigations provided insight regarding the steric and electronic parameters that impact the scope and limitation of these reactions.

Oxidopyrylium-alkene [5 + 2] cycloaddition conjugate addition cascade (C 3 ) sequences are described. Intramolecular cycloadditions involving terminal alkenes, enals, and enones were investigated. Substrates with tethers of varying lengths delivered five- and six-membered carbocycles and heterocycles thus demonstrating the scope and limitation of the cycloaddition-conjugate addition cascade. Several experiments and theoretical calculations provide evidence for the proposed mechanistic pathway.

Background: Early life may be a "critical period" when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects., Objective: The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey)., Design: Five risk factors were defined: maternal obesity [prepregnant body mass index (BMI; in kg/m(2)) >30], excess gestational weight gain (Institute of Medicine, 2009), smoking during pregnancy, low maternal vitamin D status (<64 nmol/L), and short duration of breastfeeding (none or <1 mo). Obesity outcomes examined when the children were aged 4 and 6 y were BMI, dual-energy X-ray absorptiometry-assessed fat mass, overweight, or obesity (International Obesity Task Force). Data were available for 991 mother-child pairs, with children born between 1998 and 2003., Results: Of the children, 148 (15%) had no early-life risk factors, 330 (33%) had 1, 296 (30%) had 2, 160 (16%) had 3, and 57 (6%) had 4 or 5. At both 4 and 6 y, there were positive graded associations between number of early-life risk factors and each obesity outcome (all P < 0.001). After taking account of confounders, the relative risk of being overweight or obese for children who had 4 or 5 risk factors was 3.99 (95% CI: 1.83, 8.67) at 4 y and 4.65 (95% CI: 2.29, 9.43) at 6 y compared with children who had none (both P < 0.001)., Conclusions: Having a greater number of early-life risk factors was associated with large differences in adiposity and risk of overweight and obesity in later childhood. These findings suggest that early intervention to change these modifiable risk factors could make a significant contribution to the prevention of childhood obesity.

Novel oxidopyrylium-alkene [5+2] cycloaddition conjugate addition cascade (C(3)) sequences are described. Various acetoxypyranone-alkenes with pendant nucleophiles undergo [5+2] cycloaddition followed by conjugate addition from the concave face of the intermediate pyranone toward bridged, tetracyclic ethers. In several cases, 3 new rings, 4 new bonds, and 6 new contiguous stereocenters are constructed with excellent diastereoselectivity. Finally, an asynchronous concerted reaction pathway is proposed to explain the high diastereoselectivity of the oxidopyrylium-alkene [5+2] C(3).

Objectives: To assess whether changes in measures of fat distribution and body size during early life are associated with blood pressure at 36 months of age., Design: Analysis of data collected from a prospective cohort study., Setting: Community-based investigation in Southampton, UK., Participants: 761 children with valid blood pressure measurements, born to women participating in the Southampton Women's Survey., Primary and Secondary Outcome Measures: Anthropometric measurements were collected at 0, 6, 12, 24 and 36 months and conditional changes between the time points calculated. Blood pressure was measured at 36 months. Factors possibly influencing the blood pressure were assessed using linear regression. All independent variables of interest and confounding variables were included in stepwise multiple regression to identify the model that best predicted blood pressure at 36 months., Results: Greater conditional gains in abdominal circumference (AC) between 0-6 and 24-36 months were associated with higher systolic and diastolic blood pressures at 36 months (p<0.001). Subscapular skinfold and height gains were weakly associated with higher blood pressures, while greater weight gains between 0-6, 12-24 and 24-36 months were more strongly associated, but the dominant influences were AC gains, particularly from 0-6 to 24-36 months. Thus one SD score increases in AC between 0-6 and 24-36 months were associated with 1.59 mm Hg (95% CI 0.97 to 2.21) and 1.84 mm Hg (1.24 to 2.46) higher systolic blood pressures, respectively, and 1.04 mm Hg (0.57 to 1.51) and 1.02 mm Hg (0.56, 1.48) higher diastolic pressures, respectively., Conclusions: Conditional gains in abdominal circumference, particularly within 6 months of birth and in the year preceding measurement, were more positively associated with blood pressure at 36 months than gains in other anthropometric measures. Above-average AC gains in early childhood may contribute to adult hypertension and increased cardiovascular disease risk., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aim: To determine if the benefit of early confirmation of permanent childhood hearing impairment (PCHI) on children's receptive language development is associated with fewer behavioural problems., Method: Follow-up of a total population cohort of 120 children with PCHI of moderate or greater severity (≥ 40 decibels relative to hearing threshold level) (67 males, 53 females; mean age 7 y 11 mo, range 5 y 5 mo-11 y 8 mo) and 63 hearing children (37 males, 26 females; mean age 8 y 1 mo, range 6 y 4 mo-9 y 10 mo). The main outcome measures were the Strengths and Difficulties Questionnaire (SDQ) completed by teachers and parents and the Vineland Adaptive Behaviour Scales (VABS) which are completed on the basis of a parental interview., Results: Children with PCHI had lower standard scores than hearing children on the Daily Living Skills (p=0.001) and the Socialisation (p=0.001) scales of the VABS. They had significantly higher Total Behaviour Problem scores on the parent-rated (p=0.002) and teacher-rated SDQ (p=0.03). Children for whom PCHI was confirmed by 9 months did not have significantly fewer problems on the behavioural measures than those confirmed after that age (p=0.635 and p=0.196)., Interpretation: Early confirmation has a beneficial effect on receptive language development but no significant impact in reducing behavioural problems in children with PCHI., (© The Authors. Journal compilation © Mac Keith Press 2010.)

Objective: To investigate the relation between breastfeeding, use of docosahexaenoic acid (DHA)-fortified formula and neuropsychological function in children., Design: Prospective cohort study., Setting: Southampton, UK., Subjects: 241 children aged 4 years followed up from birth., Main Outcome Measures: IQ measured by the Wechsler Pre-School and Primary Scale of Intelligence (3rd edn), visual attention, visuomotor precision, sentence repetition and verbal fluency measured by the NEPSY, and visual form-constancy measured by the Test of Visual-Perceptual Skills (Non-Motor)., Results: In unadjusted analyses, children for whom breast milk or DHA-fortified formula was the main method of feeding throughout the first 6 months of life had higher mean full-scale and verbal IQ scores at age 4 years than those fed mainly unfortified formula. After adjustment for potential confounding factors, particularly maternal IQ and educational attainment, the differences in IQ between children in the breast milk and unfortified formula groups were severely attenuated, but children who were fed DHA-fortified formula had full-scale and verbal IQ scores that were respectively 5.62 (0.98 to 10.2) and 7.02 (1.56 to 12.4) points higher than children fed unfortified formula. However, estimated total intake of DHA in milk up to age 6 months was not associated with subsequent IQ or with score on any other test., Conclusions: Differences in children's intelligence according to type of milk fed in infancy may be due more to confounding by maternal or family characteristics than to the amount of long-chain polyunsaturated fatty acids they receive in milk.

Context: Most studies of infant diet and later body composition focus on milk feeding; few consider the influence of variations in the weaning diet., Objective: Our objective was to examine how variations in milk feeding and the weaning diet relate to body composition at 4 yr., Study Population: A total of 536 children participating in a prospective birth cohort study., Design: Diet was assessed at 6 and 12 months of age. Compliance with weaning guidance was defined by the infant's score for a principal component analysis-defined dietary pattern (infant guidelines) at 12 months. Infants with high infant guidelines scores had diets characterized by high consumption of fruit, vegetables, and home-prepared foods. Body composition was assessed at 4 yr by dual x-ray absorptiometry., Results: Longer duration of breastfeeding was associated with lower fat mass at 4 yr [4.5 kg, 95% confidence interval (CI) of 4.3-4.7 kg, in children breastfed for 12 months or more, compared with 5.0 (95% CI 4.7-5.3) kg in children never breastfed (P = 0.002)] but was not related to body mass index. Children with high infant guidelines scores had a higher lean mass [12.6 (95% CI 12.3-12.9) kg in children in the top quarter of the distribution, compared with 12.0 (95% CI 11.7-12.4) kg in children in the bottom quarter (P = 0.001)]. These associations were independent and were little changed by adjustment for confounding factors., Conclusions: These data suggest that variations in both milk feeding and in the weaning diet are linked to differences in growth and development, and they have independent influences on body composition in early childhood.

Objective: To evaluate the relative validity of an FFQ for assessing nutrient intakes in 12-month-old infants., Design and Setting: The FFQ was developed to assess the diets of infants born to women in the Southampton Women's Survey (SWS), a population-based survey of young women and their offspring. The energy and nutrient intakes obtained from an interviewer-administered FFQ were compared with those obtained from 4 d weighed diaries (WD)., Subjects and Methods: A sub-sample of fifty infants (aged 1 year) from the SWS had their diets assessed by both methods. The FFQ recorded the frequencies and amounts of foods and drinks consumed by the infants over the previous 28 d; milk consumption was recorded separately. The WD recorded the weights of all foods and drinks consumed by the infants on 4 d following the FFQ completion., Results: The Spearman rank correlation coefficients for intakes of energy, macronutrients and eighteen micronutrients, determined by the two methods, ranged from r = 0.25 to 0.66. Bland-Altman statistics showed that mean differences between methods were in the range +5% to +60% except for vitamin D (+106%). Differences in micronutrient intake were partly explained by changes in patterns of milk consumption between the two assessments., Conclusion: Although there were differences in absolute energy and nutrient intakes between methods, there was reasonable agreement in the ranking of intakes. The FFQ is a useful tool for assessing energy and nutrient intakes of healthy infants aged around 12 months.

Background: Trials in developing countries suggest that improving young children's diet may benefit cognitive development. Whether dietary composition influences young children's cognition in developed countries is unclear. Although many studies have examined the relation between type of milk received in infancy and subsequent cognition, there has been no investigation of the possible effect of variations in the weaning diet., Methods: We studied 241 children aged 4 years, whose diet had been assessed at age 6 and 12 months. We measured IQ with the Wechsler Pre-School and Primary Scale of Intelligence, visual attention, visuomotor precision, sentence repetition and verbal fluency with the Developmental Neuropsychological Assessment (NEPSY), and visual form-constancy with the Test of Visual Perceptual Skills., Results: In sex-adjusted analyses, children whose diet in infancy was characterised by high consumption of fruit, vegetables and home-prepared foods ('infant guidelines' dietary pattern) had higher full-scale and verbal IQ and better memory performance at age 4 years. Further adjustment for maternal education, intelligence, social class, quality of the home environment and other potential confounding factors attenuated these associations but the relations between higher 'infant guidelines' diet score and full-scale and verbal IQ remained significant. For a standard deviation increase in 'infant guidelines' diet score at 6 or 12 months full-scale IQ rose by .18 (95% CI .04 to .31) of a standard deviation. For a standard deviation increase in 'infant guidelines' diet score at 6 months verbal IQ rose by .14 (.01 to .27) of a standard deviation. There were no associations between dietary patterns in infancy and 4-year performance on the other tests., Conclusions: These findings suggest that dietary patterns in early life may have some effect on cognitive development. It is also possible that they reflect the influence of unmeasured confounding factors.

Background: Birth in periods with universal newborn screening (UNS) for permanent childhood hearing impairment (PCHI) and early confirmation of PCHI have been associated with superior subsequent language ability in children with PCHI. However their effects on reading and communication skills have not been addressed in a population-based study., Methods: In a follow-up study of a large birth cohort in southern England, we measured reading by direct assessment and communication skills by parent report in 120 children with bilateral moderate, severe or profound PCHI aged 5.4-11.7 years, of whom 61 had been born in periods with UNS, and in a comparison group of 63 children with normal hearing., Results: Compared with birth during periods without UNS, birth during periods with UNS was associated with better reading scores (inter-group difference 0.39 SDs, 95% CI 0.02 to 0.76, p = 0.042) and communication skills scores (difference 0.51 SDs, 95% CI 0.06 to 0.95, p = 0.026). Compared with later confirmation, confirmation of PCHI by age 9 months was also associated with better reading (difference 0.51 SDs, 95% CI 0.15 to 0.87, p = 0.006) and communication skills (difference 0.56 SDs, 95% CI 0.12 to 1.00, p = 0.013). In the children with PCHI, reading, communication and language ability were highly correlated (r = 0.62-0.84, p<0.001)., Conclusion: Birth during periods with UNS and early confirmation of PCHI predict better reading and communication abilities at primary school age. These benefits represent functional gains of sufficient magnitude to be important in children with PCHI.

Background: Long-chain omega-3 polyunsaturated fatty acids are thought to be important for fetal neurodevelopment. Animal studies suggest that a deficiency of omega-3 fatty acids may lead to behavioural or cognitive deficits. As oily fish is a major dietary source of omega-3 fatty acids, it is possible that low intake of fish during pregnancy may have adverse effects on the developing fetal brain., Methods: We used the Strengths and Difficulties Questionnaire and the Wechsler Abbreviated Scale of Intelligence to assess behavioural problems and intelligence in 217 nine-year-old children. The mothers of these children had participated in a study of nutrition during pregnancy during which fish intake was assessed in early and late gestation., Results: Children whose mothers had eaten oily fish in early pregnancy had a reduced risk of hyperactivity compared to those whose mothers did not eat oily fish: OR .34, 95% CI .15 to .78, after adjustment for potential confounding factors. Children whose mothers had eaten fish (whether oily or non-oily) in late pregnancy had a verbal IQ that was 7.55 points higher (95% CI .75 to 14.4) than those whose mothers did not eat fish. There were, however, no significant associations between fish intake in pregnancy and other behavioural problems or full-scale and performance intelligence, after adjustment for potential confounding factors., Conclusions: Although maternal fish intake in pregnancy was associated with hyperactivity scores and verbal IQ in children, in general, how much fish women ate during pregnancy appeared to have little long-term relation with neurodevelopmental outcomes in their child.

Objective: To evaluate the relative validity of a food frequency questionnaire (FFQ) for assessing nutrient intakes in 6-month-old infants., Design and Setting: The FFQ was developed to assess the diets of infants born to women in the Southampton Women's Survey (SWS), a population-based survey of young women and their offspring. The energy and nutrient intakes obtained from an interviewer-administered FFQ were compared with those obtained from a 4-day weighed diary., Subjects and Methods: A sub-sample of 50 infants aged 6 months from the SWS had their diets assessed by both methods. The FFQ recorded the frequencies and amounts of milks, baby foods, regular foods and drinks consumed by the infants over the previous seven days. The diaries recorded the weights of all foods and drinks consumed by the infants on four separate days within 15 days following FFQ completion., Results: Spearman rank correlation coefficients for intakes of energy, macronutrients and 18 micronutrients, determined by the two methods, ranged from r = 0.39 to 0.86; adjustment for energy intake tended to increase the correlation coefficients, range r(a) = 0.55 to 0.89. Bland-Altman statistics showed that mean differences between methods were in the range of -12.5% to +12.5% except for vitamin B12 (-18.9%)., Conclusion: Although there were differences in absolute energy and nutrient intakes between methods, Spearman rank correlation coefficients indicated reasonable agreement in the ranking of intakes. The interviewer-administered FFQ is a useful tool for assessing energy and nutrient intakes of healthy infants aged about 6 months.

Objective: The objective of this study was to describe the health status and health-related quality of life preference-based outcomes of children with diagnosed bilateral permanent childhood hearing impairment and a comparison group of English-speaking children with normal hearing., Methods: We studied 120 children who were aged 7 to 9 years and had bilateral permanent childhood hearing impairment of moderate or greater severity, identified from a cohort of 156,733 children who were born in 8 districts of southern England, and 63 English-speaking children with normal hearing and the same place of birth and age at assessment. Principal caregivers were interviewed by using the Health Utilities Index Mark III questionnaire for proxy-assessed usual health status assessment. Levels of function within each of the 8 attributes of the Health Utilities Index Mark III (cognition, vision, hearing, speech, ambulation, dexterity, emotion, and pain) were recorded., Results: Bilateral permanent childhood hearing impairment is associated with significantly increased proportions of suboptimal levels of function and significantly lower single-attribute utility scores in 6 of the 8 attributes of the Health Utilities Index Mark III: vision, hearing, speech, ambulation, dexterity, and cognition. Compared with the children with normal hearing, the mean multiattribute utility score for the children with hearing impairment was significantly lower for both the whole group and the moderate, severe, and profound severity subgroups. The differences in the distributions of the multiattribute utility scores between the children with hearing impairment as a group and the children with normal hearing and between each of the severity subgroups and the children with normal hearing all were statistically significant., Conclusions: This study provides rigorous evidence of an association between bilateral permanent childhood hearing impairment and diminished health status and health-related quality of life preference-based outcomes during midchildhood.

Context: Evidence suggests that babies' fat mass at birth is greater if their mothers were themselves fatter during pregnancy, but it is unclear whether this association persists into childhood., Objective: Our objective was to examine the relation between maternal size in pregnancy, early growth and body composition in children., Design and Setting: We conducted a prospective cohort study in Southampton, United Kingdom., Participants: Participants included 216 9-yr-old children whose mothers had participated in a study of nutrition during pregnancy., Main Outcome Measures: Fat mass and lean mass were measured by dual-energy x-ray absorptiometry and adjusted for height (fat mass index and lean mass index)., Results: Fat mass index at age 9 yr was greater in children whose mothers had a larger mid-upper arm circumference in late pregnancy or a higher prepregnant body mass index. For 1 sd increase in maternal mid-upper arm circumference in late pregnancy, fat mass index rose by 0.26 [95% confidence interval (CI) 0.06-0.46] sd in boys and by 0.44 (95% CI 0.31-0.57) sd in girls. For 1 sd increase in maternal prepregnant BMI, fat mass index rose by 0.26 (95% CI 0.04-0.48) sd in boys and by 0.42 (95% CI 0.29-0.56) sd in girls., Conclusions: Mothers with a higher prepregnant body mass index or a larger mid-upper arm circumference during pregnancy tend to have children with greater adiposity at age 9. The extent to which this is attributable to genetic factors, the influence of maternal lifestyle on that of her child, or maternal adiposity acting specifically during pregnancy on the child's fat mass cannot be determined in this study.

Background: Associations between growth and size during infancy and adult disease have led some to recommend that interventions in infancy might benefit lifelong health. Any such recommendations should be informed by both the scientific evidence for relationships between infancy and later outcomes and the views and opinions of those who care for babies., Methods: Separate, but interlinked, systematic reviews were conducted of the epidemiological evidence relating infant size or growth to later health and of lay perspectives on infant size and growth. Findings were compared and integrated to consider policy implications., Results: Lay and scientific perspectives both cast infant growth and size as an indicator of other aspects of an infant's life, rather than being of fundamental importance. While the scientific literature is most often concerned with infants at the extreme ends of the population distribution, and towards long-term outcomes, the literature on lay perspectives suggests a focus on defining the 'normal' range, and on current health., Conclusions: Differences and similarities between scientific and lay perspectives on health can highlight areas of agreement, as well as areas of potential misunderstanding or miscommunication.

Objective: Autopsy studies show that intimal lipid accumulations in arteries are often present at birth, suggesting that the prenatal environment plays a role in the pathogenesis of atherosclerosis. In animal models, a restricted or unbalanced maternal diet during gestation can influence susceptibility to atherosclerosis, but the relation in humans between maternal diet during pregnancy and atherogenesis is unknown., Methods and Results: We measured carotid intima-media thickness (IMT) in 216 nine-year-old children whose mothers had participated in a study of nutrition during pregnancy. IMT was greater in boys, in children who were heavier, in those with higher systolic blood pressure, and in those who took less exercise. Increased IMT was associated with a lower maternal energy intake in early (P=0.029) or late (P=0.006) pregnancy, after adjustment for these factors. Mean IMT of children whose mothers were in the lowest quarter of the distribution of energy intake in late pregnancy was 0.027 mm (95% confidence interval, 0.004 to 0.049) greater than that of those whose mothers were in the highest quarter of the distribution., Conclusions: Lower maternal energy intake during pregnancy may increase the susceptibility to atherogenesis of the child.

Background: Children with bilateral permanent hearing impairment often have impaired language and speech abilities. However, the effects of universal newborn screening for permanent bilateral childhood hearing impairment and the effects of confirmation of hearing impairment by nine months of age on subsequent verbal abilities are uncertain., Methods: We studied 120 children with bilateral permanent hearing impairment identified from a large birth cohort in southern England, at a mean of 7.9 years of age. Of the 120 children, 61 were born during periods with universal newborn screening and 57 had hearing impairment that was confirmed by nine months of age. The primary outcomes were language as compared with nonverbal ability and speech expressed as z scores (the number of standard deviations by which the score differed from the mean score among 63 age-matched children with normal hearing), adjusted for the severity of the hearing impairment and for maternal education., Results: Confirmation of hearing impairment by nine months of age was associated with higher adjusted mean z scores for language as compared with nonverbal ability (adjusted mean difference for receptive language, 0.82; 95 percent confidence interval, 0.31 to 1.33; and adjusted mean difference for expressive language, 0.70; 95 percent confidence interval, 0.13 to 1.26). Birth during periods with universal newborn screening was also associated with higher adjusted z scores for receptive language as compared with nonverbal ability (adjusted mean difference, 0.60; 95 percent confidence interval, 0.07 to 1.13), although the z scores for expressive language as compared with nonverbal ability were not significantly higher. Speech scores did not differ significantly between those who were exposed to newborn screening or early confirmation and those who were not., Conclusions: Early detection of childhood hearing impairment was associated with higher scores for language but not for speech in midchildhood., (Copyright 2006 Massachusetts Medical Society.)

There is evidence that IQ tends to be higher in those who were heavier at birth or who grew taller in childhood and adolescence. Although these findings imply that growth in both foetal and postnatal life influences cognitive performance, little is known about the relative importance of brain growth during different periods of development. We investigated the relationship between brain growth in different periods of pre- and postnatal life and cognitive function in 221 9-year-old children whose mothers had taken part in a study of nutrition in pregnancy and whose head circumference had been measured at 18 weeks gestation, birth and 9 months of age. Cognitive function of the children and their mothers was assessed with the Wechsler Abbreviated Scale of Intelligence. Full-scale IQ at age 9 years rose by 1.98 points [95% confidence interval (CI) 0.34 to 3.62] for each SD increase in head circumference at 9 months and by 2.87 points (95% CI 1.05 to 4.69) for each SD increase in head circumference at 9 years of age, after adjustment for sex, number of older siblings, maternal IQ, age, education, social class, duration of breastfeeding and history of low mood in the post-partum period. Postnatal head growth was significantly greater in children whose mothers were educated to degree level or of higher socio-economic status. There was no relation between IQ and measurements of head size at 18 weeks gestation or at birth. These results suggest that brain growth during infancy and early childhood is more important than growth during foetal life in determining cognitive function.

Aim: To determine the relationship of birth weight to later glucose and insulin metabolism., Methods: Systematic review of the published literature. Data sources were Medline and Embase. Included studies were papers reporting the relationship of birth weight with a measure of glucose or insulin metabolism after 1 year of age, including the prevalence of Type 2 diabetes mellitus (DM). Three reviewers abstracted information from each paper according to specified criteria., Results: Forty-eight papers fulfilled the criteria for inclusion, mostly of adults in developed countries. Most studies reported an inverse relationship between birth weight and fasting plasma glucose concentrations (15 of 25 papers), fasting plasma insulin concentrations (20 of 26), plasma glucose concentrations 2 h after a glucose load (20 of 25), the prevalence of Type 2 DM (13 of 16), measures of insulin resistance (17 of 22), and measures of insulin secretion (16 of 24). The predominance of these inverse relationships and the demonstration in a minority of studies of other directions of the relationships could not generally be explained by differences between studies in the sex, age, or current size of the subjects. However, the relationship of birth weight with insulin secretion was inconsistent in studies of adults., Conclusions: The published literature shows that, generally, people who were light at birth have an adverse profile of later glucose and insulin metabolism. This is related to higher insulin resistance, but the relationship to insulin secretion in adults is less clear.

p0071, a member of the armadillo protein family, localizes to both adherens junctions and desmosomes in epithelial cells and exhibits homology to the adherens junction protein p120 and the desmosomal protein plakophilin-1. p0071 is also present at dermal microvascular endothelial intercellular junctions and colocalizes with VE-cadherin, an endothelium-specific cadherin that associates with both actin and intermediate filament networks. To define the role of p0071 in junction assembly, p0071 was tested for interactions with other components of the endothelial junctional complex. In transient expression assays, p0071 colocalized with and formed complexes with both VE-cadherin and desmoplakin. Deletion analysis using the yeast two-hybrid system revealed that the armadillo repeat domain of p0071 bound directly to VE-cadherin. Site-directed mutagenesis experiments demonstrated that p0071 and p120 bound to the same region on the cytoplasmic tail of VE-cadherin and that overexpression of p0071 could displace p120 from intercellular junctions. In contrast to VE-cadherin, desmoplakin was found to associate with the non-armadillo head domain of p0071. Cotransfections and triple-label immunofluorescence analysis revealed that VE-cadherin colocalization with desmoplakin in transfected COS cells required p0071, suggesting that p0071 may couple VE-cadherin to desmoplakin. Based on previous findings that both VE-cadherin and desmoplakin play central roles in vasculogenesis, these new results suggest that p0071 may play an important role in endothelial junction assembly and in the morphogenic events associated with vascular remodeling.

Background: People who are small at birth tend to have higher blood pressure in later life. However, it is not clear whether it is fetal growth restriction or the accelerated postnatal growth that often follows it that leads to higher blood pressure., Methods and Results: We studied blood pressure in 346 British men and women aged 22 years whose size had been measured at birth and for the first 10 years of life. Their childhood growth was characterized using a conditional method that, free from the effect of regression to the mean, estimated catch-up growth. People who had been small at birth but who gained weight rapidly during early childhood (1 to 5 years) had the highest adult blood pressures. Systolic pressure increased by 1.3 mm Hg (95% CI, 0.3 to 2.3) for every standard deviation score decrease in birth weight and, independently, increased by 1.6 mm Hg (95% CI, 0.6 to 2.7) for every standard deviation score increase in early childhood weight gain. Adjustment for adult body mass index attenuated the effect of early childhood weight gain but not of birth weight. Relationships were smaller for diastolic pressure. Weight gain in the first year of life did not influence adult blood pressure., Conclusions: Part of the risk of adult hypertension is set in fetal life. Accelerated weight gain in early childhood adds to this risk, which is partly mediated through the prediction of adult fatness. The primary prevention of hypertension may depend on strategies that promote fetal growth and reduce childhood obesity.

Background: Studies in developed countries have shown that reduced fetal growth is related to raised blood pressure in childhood and adult life. Little is known about this association in developing countries, where fetal growth retardation is common., Methods: In 1994-1995, we measured blood pressure in 1570 3-6-year-old children living in China, Guatemala, Chile, Nigeria and Sweden. We related their blood pressure to patterns of fetal growth, as measured by body proportions at birth. The children were all born after 37 weeks gestation and weighed more than 2.5 kg at birth., Results: In each country, blood pressure was positively related to the child's current weight. After adjusting for this and gender, systolic pressure was inversely related to size at birth in all countries except Nigeria. In Chile, China and Guatemala, children who were proportionately small at birth had raised systolic pressure. For example, in Chile, systolic pressure adjusted for current weight increased by 4.9 mmHg (95% CI : 2.1, 7.7) for every kilogram decrease in birthweight, by 1 mmHg (95% CI : 0.4, 1.6) for every centimetre decrease in birth length, and by 1.3 mmHg (95% CI : 0.4, 2.2) for every centimetre decrease in head circumference at birth. In Sweden, systolic pressure was higher in children who were disproportionately small, that is thin, at birth. Systolic pressure increased by 0.3 mmHg (95% CI : 0.0, 0.6) for every unit (kg/m3) decrease in ponderal index at birth. These associations were independent of the duration of gestation., Conclusions: Raised blood pressure among children in three samples from China, Central and South America is related to proportionate reduction in body size at birth, which results from reduced growth throughout gestation. The relation between fetal growth and blood pressure may be different in African populations. Proportionately reduced fetal growth is the prevalent pattern of fetal growth retardation in developing countries, and is associated with chronic undernutrition among women. Improvement in the nutrition and health of girls and young women may be important in preventing cardiovascular disease in developing countries.

Objective: To determine whether blood pressure levels in adult life are related to the mother's fetal growth and size at birth., Design: A follow-up study of men and women whose mothers' or fathers' size at birth was recorded in Preston, Lancashire, UK., Subjects: Two hundred and twenty-eight men and women born in Preston, Lancashire, UK, and still living in Lancashire., Main Outcome Measures: Blood pressure at 18-40 years of age., Results: Systolic and diastolic pressures fell with increasing mother's birthweight and head circumference. Systolic pressure fell by 2.4 mmHg (95% confidence interval (CI) 0.1-4.7) for each pound increase in mother's birthweight and by 4.0 mmHg (95% CI 0.2-7.8) for each one inch increase in head circumference. These associations were little changed by adjusting for length of gestation or for the subject's age, sex, body mass index or alcohol consumption. They were independent of the mother's blood pressure. As expected, mothers' birthweights were strongly related to their children's birthweights (P= 0.009), but the association between mother's birthweight and offspring's blood pressure was largely independent of this. Father's size at birth was not related to the offspring's blood pressure., Conclusions: If the growth of a female fetus is constrained by lack of nutrients, there are persisting changes in her physiology and metabolism which lead to reduced fetal growth and raised blood pressure in the next generation. Public health policies to improve fetal growth in one generation may therefore benefit succeeding generations as well.

Objectives: To study the relationship of 24-hour urinary growth hormone (GH) and IGF-I excretion in childhood to sex and body size. To test the hypothesis that small size at birth followed by postnatal catch-up growth is associated with elevated IGF-I production., Design and Subjects: Follow-up study of a cohort of 183 healthy children born in Salisbury, UK., Measurements: Weight and height, 24-h urinary growth hormone (uGH) and IGF-I (uIGF-I) excretion, and systolic and diastolic blood pressures., Results: At 9 years of age, 24-h uIGF-I excretion, but not uGH excretion, was strongly related to current weight (P < 0.001) and height (P < 0. 001). Urinary GH and IGF-I excretion were positively correlated (r = 0.15, P = 0.05). Boys excreted more uIGF-I per unit uGH than girls (uIGF-I/uGH molar ratio 32.1 compared to 21.0; P for difference = 0. 002). There were no significant relationships of uGH, uIGF-I or uIGF-I/uGH molar ratio with birthweight, birthlength or head circumference at birth, nor with blood pressure at 9 years. 'Catch-up' growth, indicated by an increase in height SD scores between birth and 9 years, was associated with higher IGF-I excretion (P = 0.01) and occurred in children with taller parents (P < 0.001)., Conclusions: Boys appear to be more sensitive to GH than girls, generating more uIGF-I in relation to uGH. Urinary IGF-I excretion at 9 years is related to both absolute height and to the degree of catch-up in height from birth. Our results suggest that IGF-I production is strongly influenced by genetic factors, but also by either the degree to which intrauterine growth falls short of genetic growth potential, or the process of postnatal catch-up growth that follows.

Objective: To conduct a systematic review in order to (i) summarize the relationship between birthweight and blood pressure, following numerous publications in the last 3 years, (ii) assess whether other measures of size at birth are related to blood pressure, and (iii) study the role of postnatal catch-up growth in predicting blood pressure., Data Identification: All papers published between March 1996 and March 2000 that examined the relationship between birth weight and systolic blood pressure were identified and combined with the papers examined in a previous review., Subjects: More than 444,000 male and female subjects aged 0-84 years of all ages and races., Results: Eighty studies described the relationship of blood pressure with birth weight The majority of the studies in children, adolescents and adults reported that blood pressure fell with increasing birth weight, the size of the effect being approximately 2 mmHg/kg. Head circumference was the only other birth measurement to be most consistently associated with blood pressure, the magnitude of the association being a decrease in blood pressure by approximately 0.5 mmHg/cm. Skeletal and non-skeletal postnatal catch-up growth were positively associated with blood pressure, with the highest blood pressures occurring in individuals of low birth weight but high rates of growth subsequently., Conclusions: Both birth weight and head circumference at birth are inversely related to systolic blood pressure. The relationship is present in adolescence but attenuated compared to both the pre- and post-adolescence periods. Accelerated postnatal growth is also associated with raised blood pressure.

Unlabelled: Epidemiological studies have shown that adults with low birthweight have a higher risk of cardiovascular disease and some others have shown that they have a less favourable serum lipid and lipoprotein profile. If cholesterol metabolism were programmed in utero, we would expect to see an influence of birthweight on blood lipids in children. In 422 children aged 11-15 y in Middlesborough, Cleveland, UK, we investigated the association between birthweight and serum lipids and plasma fibrinogen. We also investigated the influence of childhood social deprivation, measured using the Townsend deprivation index, on these measures., Conclusions: We found a significant inverse association between birthweight and serum triglyceride level, but not with other serum lipid levels. From a regression model we estimate that triglyceride rose by 1.1 mmol l(-1) kg(-1) fall in birthweight after adjustment for sex, current age and weight. Findings were similar in boys and girls separately. This could contribute to the observed inverse association between birthweight and cardiovascular mortality. Social deprivation was associated with higher fibrinogen, but not lipid levels. Our data highlight the importance of considering influences throughout the life course on adult disease.

The aim of this study was to evaluate the Dinamap 8100 and the Omron M1 (the test devices) against standard criteria for use in children in a fieldwork setting. Device calibration and validation were carried out in accordance with the British Hypertension Society protocol for special groups such as children. A total of 102 children, recruited from infant and junior schools in Southampton, had six sequential measurements made of their blood pressure-four measurements with a mercury sphygmomanometer and two with one of two test devices, 55 children with the Dinamap 8100 and 47 with the Omron M1. Systolic and diastolic readings with the Dinamap 8100 were on average 11 mmHg higher (95% confidence interval [CI] +9, +12 mmHg) and 3 mmHg lower (95% CI -5, -1 mmHg), respectively, than measurements with the mercury sphygmomanometer, overestimating systolic pressures and underestimating diastolic pressures across the whole range observed. The Omron M1 gave readings lower by 1 mmHg on average for systolic pressures and 2 mmHg for diastolic pressures compared with the sphygmomanometer (95% CIs -4, +1 mmHg and -5, +1 mmHg respectively), specifically overestimating higher pressures and underestimating lower pressures. According to the criteria of the British Hypertension Society, neither the Dinamap 8100 nor the Omron M1 can be recommended for use in children in clinical situations in which accuracy of the absolute measurement is required. In epidemiological surveys, in which differences in blood pressure between groups of people are more important than absolute levels, it may be more appropriate to use these devices. Of the two, its more consistent performance supports the Dinamap 8100 as the instrument of choice in such studies of children.

Several approaches to preventing burnout are compared. One hundred and fifty-four nurses in five Hong Kong hospitals completed the Maslach Burnout Inventory (MBI), the Organizational Socialization Inventory (OSI), and three measures of personal stress management. Results indicated that favourable evaluations on the four OSI domains (job training, organizational understanding, coworker support and future prospects) yielded strong negative correlations with the burnout components. Also, the personal stress management measures had strong negative correlations with depersonalization and decreased personal accomplishment, but none were related to emotional exhaustion. Stepwise regression analyses indicated that training was the only (inverse) predictor of emotional exhaustion, whereas interpersonal skills and understanding were strong (inverse) predictors of depersonalization. Additionally, interpersonal skills and coworker support were excellent (inverse) predictors of decreased personal accomplishment. The findings are discussed in terms of their relevance to nursing administration.

Objective: To explore if there was relationship between small body size at birth and type 2 diabetes and impaired glucose tolerance (IGT) during adulthood in China., Methods: Six hundred and twenty-eight singletons born in the Peking Union Medical College Hospital in Beijing during July 1948 to the end of 1954 were followed-up and their medical records at birth were abstracted. Anthropometry and standard oral glucose tolerance test were carried out for all of them. Plasma insulin level was measured with radioimmunoassay for them., Results: Prevalence of type 2 diabetes and IGT decreased with the increase in their birth weight, Ponderal index (PI) and head circumference at birth (for trend test, chi(2) = 6.7, P = 0.01; chi(2) = 4.8, P = 0.03; and chi(2) = 5.8, P = 0.02; respectively), with the highest of 43.8% in those with thin body size (PI < 24 kg/m(3)) at birth and obesity (BMI < 75 percentile) during adulthood, and the lowest of 8.3% in those with more fat at birth (PI >or= 28 kg/m(3)) and keeping relatively thin (BMI < 25th percentile) during adulthood. BMI of mothers in their early and late pregnancy correlated reversely with blood glucose levels two hours after sugar load for their children in adulthood. In addition, body weight, PI and head circumference at birth correlated reversely with their plasma insulin levels fasting and two hours after sugar load and levels of 32 -- 33 split pro-insulin during their adulthood. After adjustment for current BMI, lifestyle and economic status, body size at birth mentioned above still associated with their glucose tolerance and level of plasma insulin during adulthood., Conclusion: There was relationship between small body size at birth and prevalence of type 2 diabetes and IGT during adulthood. Prevalence of type 2 diabetes and IGT depended on the synergic effect of thin body size at birth and obesity during adulthood.

Objective: To determine whether women who are poorly nourished in early pregnancy, as determined by triceps skinfold thickness, or who have poor pregnancy weight gain have offspring with higher blood pressure (BP)., Methods: We evaluated 296 11-year-old children born to women who had taken part in a study of nutrition in pregnancy. Women had been weighed at 18 and 28 weeks' gestation and had had their triceps skinfold thickness measured at 18 weeks. In our follow-up study, their children were weighed and had their BP recorded. Blood pressure was adjusted for weight, gender, ethnic group, cuff size, and time of measurement., Results: The children's mean (standard deviation [SD]) systolic BP was 106 (12) mmHg and their mean (SD) diastolic BP was 62 (7) mmHg. Maternal triceps skinfold thickness at 18 weeks' gestation and maternal pregnancy weight gain between 18 and 28 weeks' gestation were weakly inversely related to the children's BP. However, among women with triceps skinfold thickness at 18 weeks below the group median (15 mm), reduced pregnancy weight gain was associated with significantly higher BP in the offspring; systolic pressure increased by 11.3 mmHg (95% confidence interval [CI] 2.2, 20.4) and diastolic pressure by 10.1 mmHg (95% CI 3.2, 17.1) for each kilogram-per-week decrease in pregnancy weight gain., Conclusion: In women who were poorly nourished in early pregnancy, reduced pregnancy weight gain was associated with higher BP in the 11-year-old offspring. We suggest that fetal adaptations to poor maternal nutrition lead to elevated BP in childhood but adequate maternal weight gain during pregnancy may protect against this.

Objective: The mechanisms underlying the association between reduced size at birth and cardiovascular disease and non-insulin-dependent diabetes mellitus in adult life are not known. One possibility is that the intra-uterine environment has permanent effects on the function or activity of the hypothalamo-pituitary-adrenal axis. We tested this by relating size at birth to the urinary excretion of adrenal androgen and glucocorticoid metabolites in a population sample of 9-year-old children., Subjects and Methods: One hundred and ninety children (89 boys and 101 girls) of known present height, weight and size at birth collected a 24-hour urine sample. The urinary breakdown products of dehydroepiandrosterone sulphate and of cortisol and cortisone were measured by gas chromatography and their respective breakdown products summed ('adrenal androgen metabolites' and 'glucocorticoid metabolites'). Excretion was expressed in microgram/day., Results: Urinary adrenal androgen metabolite excretion was higher in children who had been light at birth. A 1-kg decrease in birthweight was associated with a 40% (95% CI 9-79%) increase in metabolite excretion. Excretion was positively associated with current weight and age, but the relation with birth weight was independent of weight, age or sex. Urinary glucocorticoid metabolite excretion was positively associated with current weight, but not independently with age. The urinary excretion of total glucocorticoid metabolites was higher in children who had been light at birth, but the relation was best described as U-shaped, with the highest average urinary glucocorticoid metabolite excretion being found in children who had been either light or heavy at birth. The U-shaped (quadratic) relation persisted after adjustment for sex and current weight (P for quadratic term 0.006)., Conclusion: These findings suggests that the intra-uterine environment, as measured by fetal size at birth, has long-lasting effects on the function of the hypothalamo-pituitary-adrenal axis.

The 'thrifty phenotype' hypothesis states that impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) are the result of adaptation to undernutrition in the fetal and infant environment. In adapting the fetus and infant have to be nutritionally 'thrifty'. If poor nutrition continues throughout life these adaptations are not detrimental. However, if adult nutrition is better, the ability of the pancreas to maintain homeostasis is exceeded, with resulting diabetes. The hypothesis has been tested by a series of longitudinal studies which relate early growth with IGT and NIDDM in adult life. The studies show that babies who are small at birth or during infancy have increased rates of IGT and NIDDM. These relations are independent of social class and are seen at all levels of current body mass. More detailed anthropometric measurements at birth show that the baby at risk of glucose intolerance is characterized by disproportionate fetal growth, particularly relative thinness. Direct measurements have shown that this is a function of insulin resistance rather than deficiency. Reduced fetal growth is also associated with higher levels of plasma glucose in children. The aetiology of IGT and NIDDM may lie in undernutrition in utero or during infancy. This has major implications for their prevention.

Objective: To assess the strength of evidence for an inverse relationship between blood pressure and birth weight., Design: A systematic review of the published literature., Setting: Published studies describing the relationship between blood pressure and birth weight since 1956., Subjects: More than 66,000 subjects aged 0-71 years., Results: Thirty-four studies described the relationship of blood pressure with birth weight. The majority of the studies of children and adults showed that blood pressure fell with increasing birth weight. Studies of adolescents were inconsistent. In neonates there was a positive relationship between blood pressure and birth weight. The pattern with age was supported by the limited number of studies with repeated measures and was dependent neither on the method of analysis nor on work from a single academic group or country., Conclusions: Blood pressure is inversely related to birth weight in children and in adults. The positive results in neonates and the inconsistency in adolescence may be related to the unusual growth dynamics during these phases of growth. Further studies should concentrate on the mechanisms which underlie the relationship.

Objective: To test the hypothesis that reduced fetal growth leads to altered plasma insulin-like growth factor-1 (IGF-1) concentrations in childhood., Design: A follow up study of 4 year old children whose birth weights were recorded, and of 7 year old children whose weight, length, head circumference, and placental weight were measured at birth., Setting: Pune, India, and Salisbury, England., Subjects: 200 children born during October 1987 to April 1989 in the King Edward Memorial Hospital, Pune, weighing over 2.0 kg at birth and not requiring special care, and 244 children born during July 1984 to February 1985 in the Salisbury Health District and still living there., Main Outcome Measure: Plasma IGF-1 concentrations., Results: In both groups of children, and consistent with findings in other studies, plasma IGF-1 concentrations were higher in taller and heavier children, and higher in girls than boys. Allowing for sex and current size, concentrations were inversely related to birth weight (Pune p = 0.002; Salisbury p = 0.003). Thus at any level of weight or height, children of lower birth weight had higher IGF-1 concentrations. The highest concentrations were in children who were below average birth weight and above average weight or height when studied. Systolic blood pressures were higher in children with higher IGF-1 concentrations (Pune p = 0.01; Salisbury p = 0.04)., Conclusions: Children of lower birth weight develop higher circulating concentrations of IGF-1 than expected for their height and weight. This is consistent with the hypothesis that under-nutrition in utero leads to reprogramming of the IGF-1 axis. The increase of plasma IGF-1 concentrations in low birthweight children may also be linked to postnatal catch-up growth. High IGF-1 concentrations may be one of the mechanisms linking reduced fetal growth and high blood pressure in later life.

Adults who had low birthweight and were thin at birth have an increased risk of Type 2 diabetes and impaired glucose tolerance. To discover whether thinness at birth is associated with reduced glucose tolerance in children, 250 7-year-old children underwent an abbreviated oral glucose tolerance test. Children who were thin at birth, as measured by a low ponderal index (birthweight length-3) had higher plasma glucose concentrations. Plasma glucose concentration 30 min after a glucose load rose by 0.07 mmol l-1 (95% confidence interval 0.00 to 0.14; p = 0.04) for every unit (kg m-3) fall in ponderal index. Children in the lowest quarter of the distribution of ponderal index (23 kg m-3 or less) had a mean 30 min plasma glucose concentration of 8.49 mmol l-1 compared to a mean of 7.97 mmol l-1 for those in the highest quarter (> 27.5 kg m-3). These associations were independent of duration of gestation, gender, social class or the child's current weight. This is consistent with the hypothesis that Type 2 diabetes originates in utero.

Background: The practice of breastfeeding is related to socio-demographic characteristics: both show marked variation by place within the United Kingdom. This study set out to test the commonly held assumption that geographical variations in breastfeeding practices are explained by socio-demographic differences., Methods: The mothers of 326 six-week-old babies living in Salisbury or Durham Health Districts were interviewed to determine attitudes to breastfeeding practice., Results: More mothers in Salisbury breastfed than mothers in Durham, both immediately after birth (Salisbury 79 per cent, Durham 54 per cent) and at six weeks (50 per cent and 26 per cent). Higher rates of breastfeeding after birth were associated with higher level of qualification, encouragement to breastfeed antenatally and the mother having been breastfed herself. Higher rates at six weeks were associated with higher level of qualification, higher parity and willingness to breastfeed away from home. The differences between districts persisted after adjustment for these variables, but were diminished when willingness to breastfeed away from home was taken into account., Conclusion: Differences between the two districts in breastfeeding practice cannot be wholly explained by traditional socio-demographic characteristics, and may be related to local culture. Health education is unlikely to change breastfeeding practices unless prevailing cultural attitudes also change.

Objective: To determine whether babies in an area of Britain with unusually high perinatal mortality have different patterns of fetal growth to those born elsewhere in the country., Design: Measurement of body size in newborn babies., Setting: Burnley (perinatal mortality in 1988 15.9/1000 total births) and Salisbury (perinatal mortality 10.8/1000 total births), England., Subjects: Subjects comprised 1544 babies born in Burnley, Pendle, and Rossendale Health District, and 1025 babies born in Salisbury Health District., Main Outcome Measures: Birthweight, length, head, arm and abdominal circumferences, and placental weight were determined., Results: Compared with babies born in Salisbury, Burnley babies had lower mean birthweight (difference 116 g, 95% confidence interval (CI) 77,154), smaller head circumferences (difference 0.3 cm, 95% CI 0.2, 0.4), and were thinner as measured by arm circumference (difference 0.3 cm, 95% CI 0.3, 0.4), abdominal circumference (difference 0.5 cm, 95% CI 0.4, 0.6) and ponderal index (difference 0.8 kg/m3, 95% CI 0.6, 1.0). The ratio of placental weight to birthweight was higher in Burnley (difference 0.6%, 95% CI 0.4, 0.9). These differences were found in boys and girls and did not depend on differences in duration of gestation or on the different ethnic mix of the two districts. Mothers in Burnley were younger, shorter in stature, had had more children, were of lower social class, and more of them smoked during pregnancy than mothers in Salisbury. These differences did not explain the greater thinness of their babies., Conclusions: Babies born in Burnley, an area with high perinatal mortality, are thin. The reason is unknown. Poor maternal nutrition is suspected because Burnley babies have a higher ratio of placental weight to birthweight. The greater thinness at birth of Burnley babies could have long term consequences, including higher rates of cardiovascular disease.

Objective: To determine whether the relation between high blood pressure and low birth weight is initiated in utero or during infancy, and whether it changes with age., Design: A longitudinal study of children and three follow up studies of adults., Setting: Farnborough, Preston, and Hertfordshire, England, and a national sample in Britain., Subjects: 1895 children aged 0-10 years, 3240 men and women aged 36 years, 459 men and women aged 46-54 years, and 1231 men and women aged 59-71 years. The birth weight of all subjects had been recorded., Main Outcome Measure: Systolic blood pressure., Results: At all ages beyond infancy people who had lower birth weight had higher systolic blood pressure. Systolic blood pressure was not related to growth during infancy independently of birth weight. The relation between systolic pressure and birth weight became larger with increasing age so that, after current body mass was allowed for, systolic pressure at ages 64-71 years decreased by 5.2 mm Hg (95% confidence interval 1.8 to 8.6) for every kg increase in birth weight., Conclusions: Essential hypertension is initiated in fetal life. A raised blood pressure is then amplified from infancy to old age, perhaps by a positive feedback mechanism.

Study Objective: The aim was to determine whether abdominal fatness in adult men is associated with retarded growth in fetal life and infancy., Design: This was a follow up study of (1) men born during 1920-30 whose birthweights and weights at one year were recorded at the time by health visitors; and (2) men born during 1935-43 whose size at birth was measured in detail. The main outcome measure was the ratio of waist circumference to hip girth., Setting: Hertfordshire and Preston, England., Subjects: Subjects were 845 men born in east Hertfordshire who still live there; and 239 men born in Preston who still live in or close to the city., Main Results: After allowing for body mass index, mean waist to hip ratio fell with increasing birthweight and rose as the ratio of placental weight to birthweight increased. These trends were independent of duration of gestation and therefore reflected retarded fetal growth. Waist to hip ratio also fell with increasing weight at one year. All these trends were independent of adult height, alcohol consumption, smoking, social class, and age., Conclusions: The tendency to store fat abdominally, which is known to increase the risk of cardiovascular disease and diabetes independently of obesity, may be a persisting response to adverse conditions and growth failure in fetal life and infancy.

To study maternal and fetal influences on blood pressure in childhood 405 children aged 4 years who were born and still resident in the Salisbury health district were visited at home for blood pressure and growth measurements. Information on the pregnancy, delivery, and baby was abstracted from the routine obstetric notes. Similar to recent findings in adults, the child's systolic pressure was inversely related to birth weight and positively related to placental weight. Systolic pressure at 4 years increased by 1.2 mm Hg for every SD decrease in the ratio of head circumference to length at birth, and by 1.1 mm Hg for every SD decrease in ponderal index at birth. Mothers whose haemoglobin concentrations fell below 100g/l during pregnancy had children whose systolic pressures were on average 2.9 mm Hg higher than the children of mothers with higher haemoglobin concentrations. Patterns of placental weight, birth weight, head circumference, and length that are associated with high blood pressure in adults are also associated with higher blood pressure in 4 year old children. Identification of the intrauterine influences that lead to these patterns of fetal growth could lead to the primary prevention of hypertension.

Geographical differences in mortality from cardiovascular disease and chronic bronchitis within England and Wales are closely related to past differences in infant mortality. This paper examines the separate relations of mortality during 1968-78 with neonatal and post-neonatal mortality during 1911-25. These divisions of infant mortality are indicators of the intrauterine and early postnatal environments respectively. Stroke is related to neonatal mortality and therefore to the intrauterine environment. Prenatal determinants of blood pressure levels may be one mechanism underlying this. Bronchitis is related to postnatal mortality and therefore to the postnatal environment. This may reflect the long term effects of lower respiratory tract infection in early childhood. Ischaemic heart disease is related to both neonatal and post-neonatal mortality and therefore to the intrauterine and postnatal environments. The links may include blood pressure and as yet unknown processes established in early postnatal life.