Association of cardiovascular disease risk factors with socioeconomic position during childhood and during adulthood.

OBJECTIVE: To investigate strength of associations between risk factors for cardiovascular disease and socioeconomic position during childhood and adulthood. DESIGN: Cross sectional analysis of status of cardiovascular risk factors and past and present social circumstances. SUBJECTS: 5645 male participants in the west of Scotland collaborative study, a workplace screening study. MAIN OUTCOME MEASURES: Strength of association between each risk factor for cardiovascular disease (diastolic blood pressure, serum cholesterol concentration, level of recreational physical exercise, cigarette smoking, body mass index, and FEV1 score (forced expiratory volume in one second as percentage of expected value) and social class during childhood (based on father''s main occupation) and adulthood (based on own occupation at time of screening). RESULTS: All the measured risk factors were significantly associated with both father''s and own social class (P < 0.05), apart from exercise and smoking (not significantly associated with father''s social class) and body mass index (not significantly associated with own social class). For all risk factors except body mass index, the regression coefficient of own social class was larger than the regression coefficient of father''s social class. The difference between the coefficients was significant for serum cholesterol concentration, cigarette smoking, body mass index, and FEV1 score (all P < 0.001). CONCLUSIONS: Subjects'' status for behavioural risk factors (exercise and smoking) was associated primarily with current socioeconomic circumstances, while status for physiological risk factors (serum cholesterol, blood pressure, body mass index, and FEV1) was associated to varying extents with both past and present socioeconomic circumstances.     

Blood pressure in prospective population based cohort of newborn and infant twins.

OBJECTIVE--To describe blood pressure in twins during infancy. DESIGN--Prospective study of cohort of twins. SETTING--Teaching hospital in Florida. SUBJECTS--166 viable twin pairs born between July 1976 and December 1989. MAIN OUTCOME MEASURES--Blood pressure and body weight at birth, at 14 days, and at 1, 3, 6, 9, and 12 months. RESULTS--Both systolic and diastolic pressure correlated with body weight throughout infancy (at birth r = 0.41, P < 0.001 and r = 0.42, P < 0.001 respectively; at 1 year r = 0.23, P < 0.001 and r = 0.26, P < 0.001 respectively). In infants weighing < 1500 g at birth mean blood pressure rose from about 45/25 mm Hg to 101/55 mm Hg from birth to the age of 1 year, while in infants weighing > 3000 g at birth it rose from 63/39 mm Hg to 100/61 mm Hg; corresponding mean body weights at 1 year were 7.86 kg and 9.88 kg. Differences in birth weight within pairs of monozygotic twins were negatively correlated with such differences in systolic blood pressure at 1 year (r = -0.37, P < 0.01). CONCLUSIONS--Blood pressure and body weights in twins showed strongly positive but generally declining correlations throughout infancy. Twins of lower birth weight showed a more rapid rate of rise in blood pressure during infancy. At 1 year the catch up in blood pressure exceeded that in body weight. Greater differences in birth weights between monozygotic twins were associated with smaller differences in systolic blood pressure at 1 year, suggesting that intrauterine environmental factors related to birth weight are important in determining blood pressure in infancy.     

Relative contributions of maternal social and biological characteristics to birth weight and gestation among mothers of different childhood socioeconomic status

Abstract

There has been no reported systematic attempt to quantify the relative unique contribution of multiple social and biologic maternal characteristics to birth weight and gestational time among mothers of differing childhood socioeconomic backgrounds. We examined this issue in three nativity cohorts from a population of 766 black prenatal clinic patients in New York City using a series of stepwise hierarchical multiple regression analyses. Different variable sets contributed to birth weight variance in each group, although total variance explained was similar for the three. Since the foreign‐born cohort represented a different higher childhood socioeconomic background, but was similar to the other groups in current SES, the differing observed associations of variable sets to birth weight may be related to childhood socioeconomic status. In all groups, social factors show more effect on gestation among births more than 2,500 grams than for smaller babies and thus account for more total explained birth weight variance for births over 2,500 grams.     

Relation between birth weight and blood pressure: longitudinal study of infants and children.

OBJECTIVE--To study the relation between birth weight and systolic blood pressure in infancy and early childhood. DESIGN--Longitudinal study of infants from birth to 4 years of age. SETTING--A middle class community in the Netherlands. PARTICIPANTS--476 Dutch infants born in 1980 to healthy women after uncomplicated pregnancies. MAIN OUTCOME MEASURES--Systolic blood pressure and body weight measured at birth and at 3 months and 4 years of age; the relation between systolic blood pressure and birth weight as estimated by multiple regression models that include current weight and previous blood pressure and control for gestational age, length at birth, and sex. RESULTS--Complete data were available on 392 infants. At 4 years of age the relation between blood pressure and birth weight appeared to be U shaped; low and high birthweight infants had raised blood pressure. Current weight and previous blood pressure were also positively associated with blood pressure at that age. Low birthweight infants (birth weight < 3100 g) had a greater gain in blood pressure and weight in early infancy. High birthweight infants (birth weight > or = 3700 g) had high blood pressure at birth, and weight and blood pressure tended to remain high thereafter. CONCLUSIONS--Even among normal infants there seem to be subgroups defined by birth weight in which blood pressure is regulated differently. Future investigations are needed to examine the physiological basis of these differences. Studies of correlates of adult disease related to birth weight should investigate mechanisms related to increased risk separately in infants of low and high birth weight.     

United Kingdom Prospective Diabetes Study (UKPDS). 13: Relative efficacy of randomly allocated diet,sulphonylurea, insulin,or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years.

OBJECTIVE--To assess the relative efficacy of treatments for non-insulin dependent diabetes over three years from diagnosis. DESIGN--Multicentre, randomised, controlled trial allocating patients to treatment with diet alone or additional chlorpropamide, glibenclamide, insulin, or metformin (if obese) to achieve fasting plasma glucose concentrations < or = 6 mmol/l. SETTING--Outpatient diabetic clinics in 15 British hospitals. SUBJECTS--2520 subjects who, after a three month dietary run in period, had fasting plasma glucose concentrations of 6.1-14.9 mmol/l but no hyperglycaemic symptoms. MAIN OUTCOME MEASURES--Fasting plasma glucose, glycated haemoglobin, and fasting plasma insulin concentrations; body weight; compliance; and hypoglycaemia. RESULTS--Median fasting plasma glucose concentrations were significantly lower at three years in patients allocated to chlorpropamide, glibenclamide, or insulin rather than diet alone (7.0, 7.6, 7.4, and 9.0 mmol/l respectively; P < 0.001) with lower mean glycated haemoglobin values (6.8%, 6.9%, 7.0%, and 7.6%, respectively; P < 0.001). Mean body weight increased significantly with chlorpropamide, glibenclamide, and insulin but not diet (by 3.5, 4.8, 4.8, and 1.7 kg; P < 0.001). A similar pattern was seen for mean fasting plasma insulin concentration (by 0.9, 1.2, 2.4, and -0.1 mU/l; P < 0.001). In obese subjects metformin was as effective as the other drugs with no change in mean body weight and significant reduction in mean fasting plasma insulin concentration (-2.5 mU/l; P < 0.001). More hypoglycaemic episodes occurred with sulphonylurea or insulin than with diet or metformin. CONCLUSION--The drugs had similar glucose lowering efficacy, although most patients remained hyperglycaemic. Long term follow up is required to determine the risk-benefit ratio of the glycaemic improvement, side effects, changes in body weight, and plasma insulin concentration.     

The Effect of Prenatal and Childhood Development on Hearing,Vision and Cognition in Adulthood

It is unclear what the contribution of prenatal versus childhood development is for adult cognitive and sensory function and age-related decline in function. We examined hearing, vision and cognitive function in adulthood according to self-reported birth weight (an index of prenatal development) and adult height (an index of early childhood development). Subsets (N = 37,505 to 433,390) of the UK Biobank resource were analysed according to visual and hearing acuity, reaction time and fluid IQ. Sensory and cognitive performance was reassessed after ~4 years (N = 2,438 to 17,659). In statistical modelling including age, sex, socioeconomic status, educational level, smoking, maternal smoking and comorbid disease, adult height was positively associated with sensory and cognitive function (partial correlations; pr 0.05 to 0.12, p < 0.001). Within the normal range of birth weight (10^th to 90^th percentile), there was a positive association between birth weight and sensory and cognitive function (pr 0.06 to 0.14, p < 0.001). Neither adult height nor birth weight was associated with change in sensory or cognitive function. These results suggest that adverse prenatal and childhood experiences are a risk for poorer sensory and cognitive function and earlier development of sensory and cognitive impairment in adulthood. This finding could have significant implications for preventing sensory and cognitive impairment in older age.     

Role of glycaemic control in development of microalbuminuria in patients with insulin dependent diabetes.

OBJECTIVE--To ascertain which factors determine the progression from very low rates of albumin excretion to persistent microalbuminuria in patients with insulin dependent diabetes mellitus. DESIGN--A 10 year prospective study of a cohort of diabetic patients. SETTING--Outpatient department of the Portsmouth District Hospitals. SUBJECTS--97 patients with insulin dependent diabetes mellitus who were initially free of microalbuminuria and hypertension. MAIN OUTCOME MEASURE--Urinary albumin: creatinine ratio. RESULTS--Eight of the 97 patients had developed microalbuminuria (urinary albumin:creatinine ratio > 3 mg/mmol in three consecutive early morning samples) by the 10 year follow up. The group who developed microalbuminuria had higher baseline log10 plasma glucose concentrations (mean (SD), 1.210 (0.122) v 0.984 (0.196) mmol/l, P < 0.001) and glycated haemoglobin concentrations (1.112% (0.069%) v 0.997% (0.076%), P < 0.001) and a younger age at onset of diabetes (10.0 (5.5) v 15.6 (7.8) years, P < 0.05). There was no difference in baseline duration of diabetes, smoking, sex, insulin dose, body mass index, serum creatinine concentration, or systolic, diastolic, or mean arterial blood pressure between the two groups. Multiple linear regression analysis showed that urinary albumin:creatinine ratio at 10 years was influenced by initial albumin:creatinine ratio (P = 0.006), initial glycated haemoglobin concentration (P = 0.002), and duration of diabetes (P = 0.045). Genotype for angiotensin converting enzyme was not related to the development of microalbuminuria nor, in a larger group of patients, the presence of any degree of diabetic nephropathy. CONCLUSION--In patients with insulin dependent diabetes mellitus the progression of minimal albuminuria and the development of microalbuminuria is determined primarily by poor long term glycaemic control. There is a weaker relation with longer duration of disease and younger age at onset of diabetes, but blood pressure does not seem to be implicated. Gene polymorphism for angiotensin converting enzyme is not linked to the development of microalbuminuria or established diabetic nephropathy.     

Relation between maternal haemoglobin concentration and birth weight in different ethnic groups.

OBJECTIVE--To assess the relation of the lowest haemoglobin concentration in pregnancy with birth weight and the rates of low birth weight and preterm delivery in different ethnic groups. DESIGN--Retrospective analysis of 153,602 pregnancies with ethnic group and birth weight recorded on a regional pregnancy database during 1988-91. The haemoglobin measurement used was the lowest recorded during pregnancy. SETTING--North West Thames region. SUBJECTS--115,262 white women, 22,206 Indo-Pakistanis, 4570 Afro-Caribbeans, 2642 mediterraneans, 3905 black Africans, 2351 orientals, and 2666 others. MAIN OUTCOME MEASURES--Birth weight and rates of low birth weight (< 2500 g) and preterm delivery (< 37 completed weeks). RESULTS--Maximum mean birth weight in white women was achieved with a lowest haemoglobin concentration in pregnancy of 85-95 g/l; the lowest incidence of low birth weight and preterm labour occurred with a lowest haemoglobin of 95-105 g/l. A similar pattern occurred in all ethnic groups. CONCLUSIONS--The magnitude of the fall in haemoglobin concentration in pregnancy is related to birth weight; failure of the haemoglobin concentration to fall below 105 g/l indicates an increased risk of low birth weight and preterm delivery. This phenomenon is seen in all ethnic groups. Some ethnic groups have higher rates of low birth weight and preterm delivery than white women, and they also have higher rates of low haemoglobin concentrations. This increased rate of "anaemia," however, does not account for their higher rates of low birth weight, which occurs at all haemoglobin concentrations.     

Adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer

The aim of the present study was to examine the relationship between adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer (NSCLC). Measurement of anthropometry, acute phase proteins, interleukin-6, leptin (total and free) and adiponectin were carried out on healthy subjects (n = 13) and non-small cell lung cancer patients with weight loss (n = 20). The groups were age and sex matched. Compared with the controls the cancer group had a lower BMI (p < 0.01), mid-upper arm circumference (p < 0.001), triceps skinfold thickness (p < 0.05) and circulating concentrations of albumin (p < 0.001), haemoglobin (p < 0.05), free and total leptin (p < 0.05) and adiponectin (p < 0.01). In contrast, the cancer group had elevated circulating concentrations of interleukin-6 and C-reactive protein concentrations (p < 0.001). In the cancer group circulating adiponectin concentrations were significantly inversely correlated with both free (rs = -0.675, p = 0.001) and total leptin concentrations (rs = -0.690, p = 0.001). However, neither weight loss, interleukin-6 or C-reactive protein concentrations were correlated with either adiponectin, free or total leptin concentrations in the cancer group. These results suggest that adipokine production is normal and is unlikely to play a major role in the abnormal fat metabolism in weight-losing cancer patients.     

Is Parental Control over Children's Eating Associated with Childhood Obesity? Results from a Population‐Based Sample of Third Graders

Objective: Identifying parental behaviors that influence childhood obesity is critical for the development of effective prevention and treatment programs. Findings from a prior laboratory study suggest that parents who impose control over their children's eating may interfere with their children's ability to regulate intake, potentially resulting in overweight. These findings have been widely endorsed; however, the direct relationship between parental control of children's intake and their children's degree of overweight has not been shown in a generalized sample. Research Methods and Procedures: This study surveyed 792 third‐grade children with diverse ethnic and socioeconomic backgrounds from 13 public elementary schools. Parental control over children's intake was assessed through telephone interviews using a state‐of‐the‐art instrument, and children were measured for height, weight, and triceps skinfold thickness. Results: Counter to the hypothesis, parental control over children's intake was inversely associated with overweight in girls, as measured by body mass index, r = ?0.12, p < 0.05, and triceps skinfolds, r = ?0.11, p < 0.05. This weak relationship became only marginally significant when controlling for parents’ perceptions of their own weight, level of household education, and children's age. No relationship between parental control of children's intake and their children's degree of overweight was found in boys. Discussion: Previous observations of the influence of parental control over children's intake in middle‐class white families did not generalize to 8‐ to 9‐year‐olds in families with diverse socioeconomic and ethnic backgrounds. The present findings reveal a more complex relationship between parental behaviors and children's weight status.     

Differences in nutritional status between rural and urban Yucatec Maya children: The importance of early life conditions

Early-life conditions shape childhood growth and are affected by urbanization and the nutritional transition. To investigate how early-life conditions (across the “first” and “second” 1000 days) are associated with rural and urban children's nutritional status, we analyzed anthropometric data from Maya children in Yucatan, Mexico. We collected weight, height and triceps skinfold measures, then computed body mass and fat mass indices (BMI/FMI), in a cross-sectional sample of 6-year-olds (urban n = 72, rural n = 66). Demographic, socioeconomic and early-life variables (birthweight/mode, rural/urban residence, household crowding) were collected by maternal interview. We statistically analyzed rural-urban differences in demographic, socioeconomic, early-life, and anthropometric variables, then created linear mixed models to evaluate associations between early-life variables and child anthropometric outcomes. Two-way interactions were tested between early-life variables and child sex, and between early-life variables and rural-urban residence. Results showed that rural children were shorter-statured, with lower overweight/obesity and cesarean delivery rates, compared to urban children. Household crowding was a negative predictor of anthropometric outcomes; the strongest effect was in boys and in urban children. Birthweight positively predicted anthropometric outcomes, especially weight/BMI. Birth mode was positively (not statistically) associated with any anthropometric outcome. Cesarean delivery was more common in boys than in girls, and predicted increased height in urban boys. In conclusion, urbanization and household crowding were the most powerful predictors of Maya 6-year-old anthropometry. The negative effects of crowding may disproportionately affect Maya boys versus girls and urban versus rural children. Early-life conditions shape Maya children's nutritional status both in the “first” and “second” 1000 days.     

Relative contributions of maternal social and biological characteristics to birth weight and gestation among mothers of different childhood socioeconomic status

There has been no reported systematic attempt to quantify the relative unique contribution of multiple social and biologic maternal characteristics to birthweight and gestational time among mothers of differing childhood socioeconomic backgrounds. This issue was examined in 3 nativity cohorts from a population of 766 black prenatal clinic patients in New York City using a series of stepwise hierarchical multiple regression analyses. Different variable sets contributed to birthweight variance in each group, although total variance explained was similar for the 3. Since the foreign-born cohort represented a different higher childhood socioeconomic background, but was similar to the other groups in current socioeconomic status, the differing observed associations of variable sets to birthweight may be related to childhood socioeconomic status. In all groups, social factors show more effect on gestation among those births more than 2500 grams than for smaller babies and thus account for more total explained birthweight variance for births over 2500 grams. Future research is necessary to replicate these results in the general population since this is the 1st study using multivariate techniques to look at social and biological factors associated with birthweight in groups with different childhood social backgrounds.     

Perinatal characteristics in relation to incidence of and mortality from prostate cancer.

OBJECTIVE--To test the hypothesis that factors causing morbidity and mortality from prostate cancer may operate in utero. DESIGN--Matched case-control study of singleton men born between 1874 and 1946 at one hospital. SETTING--Uppsala University Hospital. SUBJECTS--250 patients with prostate cancer and 691 controls, including 80 patients who died from prostate cancer and their 196 matched controls. MAIN OUTCOME MEASURES--Mother''s age at menarche, parity, pre-eclampsia or eclampsia before delivery, age at delivery and socioeconomic status; case or control''s birth length and weight, placental weight, prematurity derived from gestational age, and presence of jaundice. RESULTS--Both pre-eclampsia (odds ratio 0, 95% confidence interval 0 to 0.71) and prematurity (0.31, 0.09 to 1.04) were inversely associated with incidence of prostate cancer. Among subjects born full term, placental weight, birth weight, and ponderal index (weight/height 3) showed non-significant positive associations with prostate cancer incidence, and stronger associations with mortality. CONCLUSION--Prenatal exposures that are likely correlates of pregnancy hormones and other growth factors are important in prostate carcinogenesis and influence the natural course as well as the occurrence of this cancer.     

Impact of Placental Plasmodium falciparum Malaria on the Profile of Some Oxidative Stress Biomarkers in Women Living in Yaoundé, Cameroon

Background

Impact of the pathophysiology of Plasmodium falciparum placental malaria (PM) on the profile of some oxidative stress biomarkers and their relationship with poor pregnancy outcomes in women remain unknown.

Methods

Between 2013 and 2014, peripheral blood and placenta tissue from 120 Cameroonian women at delivery were assessed for maternal haemoglobin and, parasitaemia respectively. Parasite accumulation in the placenta was investigated histologically. The levels of oxidative stress biomarkers Malondialdehyde (MDA), Nitric Oxide (NO), Superoxide dismutase (SOD), Catalase (CAT) and Gluthatione (GSH) in the supernatant of teased placenta tissues were determined by Colorimetric enzymatic assays.

Results

Parasitaemia was inversely related to haemoglobin levels and birth weight (P <0.001 and 0.012, respectively). The level of lipid peroxide product (MDA) was significantly higher in the malaria infected (P = 0.0047) and anaemic (P = 0.024) women compared to their non-infected and non-anaemic counterparts, respectively. A similar trend was observed with SOD levels, though not significant. The levels of MDA also correlated positively with parasitaemia (P = 0.0024) but negatively with haemoglobin levels (P = 0.002). There was no association between parasitaemia, haemoglobin level and the other oxidative stress biomarkers. From histological studies, levels of MDA associated positively and significantly with placenta malaria infection and the presence of malaria pigments. The levels of SOD, NO and CAT increased with decreasing leukocyte accumulation in the intervillous space. Baby birth weight increased significantly with SOD and CAT levels, but decreased with levels of GSH.

Conclusions

Placental P. falciparum infection may cause oxidative stress of the placenta tissue with MDA as a potential biomarker of PM, which alongside GSH could lead to poor pregnancy outcomes (anaemia and low birth weight). This finding contributes to the understanding of the pathophysiology of P. falciparum placental malaria in women.     

Risk factors for perinatal mortality in Canada

A population-based computer record-linkage study of infant births and deaths in 1978 and 1979 in eight Canadian provinces (Quebec and Newfoundland were excluded) was undertaken to permit analysis of perinatal mortality in relation to maternal and infant characteristics. Perinatal mortality rates were significantly higher in nonurban than in urban areas (p < 0.05). A logistic regression model was used to assess the effects on perinatal mortality of variables reported on birth and stillbirth records. This model included length of gestation, infant''s birth weight and sex, number of previous births and number of previous stillbirths as well as an interaction term for length of gestation and birth weight. For early-neonatal mortality, odds ratios over 8 were observed for birth weight less than 2500 g or gestation less than 35 weeks. About 75% of early-neonatal mortality was attributable to low birth weight or fetal immaturity. Greater emphasis should be placed on the prevention of low birth weight.     

Relation between birth weight at term and systolic blood pressure in adolescence.

OBJECTIVE--To examine whether birth weight is related to systolic blood pressure during adolescence. DESIGN--Retrospective (comparative) cohort study. The observers who traced and studied the subjects were unaware of their case-control status. SUBJECTS--330 subjects were born in Cardiff in 1975-7. Cases who were low birth weight at term (< 2500 g) were matched with controls of normal birth weight (3000-3800 g) at term. MAIN OUTCOME MEASURES--Systolic blood pressure measured by random zero sphygmomanometry in the subject''s right arm with the subject supine, corrected for size and age. RESULTS--The mean age at examination was 15.7 years. The mean systolic blood pressure of the cases was 105.8 mm Hg and of the controls 107.5 mm Hg. The corrected difference (95% confidence interval) in systolic blood pressure between the cases and controls was 1 mm Hg (-3 to +1 mm Hg; two tailed probability 0.33). CONCLUSION--Systolic blood pressure in adolescents of low birth weight is not significantly different from that of adolescents of normal birth weights.     

Effects on birth weight and perinatal mortality of maternal dietary supplements in rural Gambia: 5 year randomised controlled trial .

OBJECTIVE: To test the efficacy in terms of birth weight and infant survival of a diet supplement programme in pregnant African women through a primary healthcare system. DESIGN: 5 year controlled trial of all pregnant women in 28 villages randomised to daily supplementation with high energy groundnut biscuits (4.3 MJ/day) for about 20 weeks before delivery (intervention) or after delivery (control). SETTING: Rural Gambia. SUBJECTS: Chronically undernourished women (twin bearers excluded), yielding 2047 singleton live births and 35 stillbirths. MAIN OUTCOME MEASURES: Birth weight; prevalence of low birth weight (< 2500 g); head circumference; birth length; gestational age; prevalence of stillbirths; neonatal and postneonatal mortality. RESULTS: Supplementation increased weight gain in pregnancy and significantly increased birth weight, particularly during the nutritionally debilitating hungry season (June to October). Weight gain increased by 201 g (P < 0.001) in the hungry season, by 94 g (P < 0.01) in the harvest season (November to May), and by 136 g (P < 0.001) over the whole year. The odds ratio for low birthweight babies in supplemented women was 0.61 (95% confidence interval 0.47 to 0.79, P < 0.001). Head circumference was significantly increased (P < 0.01), but by only 3.1 mm. Birth length and duration of gestation were not affected. Supplementation significantly reduced perinatal mortality: the odds ratio was 0.47 (0.23 to 0.99, P < 0.05) for stillbirths and 0.54 (0.35 to 0.85, P < 0.01) for all deaths in first week of life. Mortality after 7 days was unaffected. CONCLUSION: Prenatal dietary supplementation reduced retardation in intrauterine growth when effectively targeted at genuinely at-risk mothers. This was associated with a substantial reduction in the prevalence of stillbirths and in early neonatal mortality. The intervention can be successfully delivered through a primary healthcare system.     

Maternal Cadmium Levels during Pregnancy Associated with Lower Birth Weight in Infants in a North Carolina Cohort

Cadmium (Cd) is a ubiquitous environmental contaminant, a known carcinogen, and understudied as a developmental toxicant. In the present study, we examined the relationships between Cd levels during pregnancy and infant birth outcomes in a prospective pregnancy cohort in Durham, North Carolina. The study participants (n = 1027) had a mean Cd level of 0.46 µg/L with a range of <0.08 to 2.52 µg/L. Multivariable models were used to establish relationships between blood Cd tertiles and fetal growth parameters, namely birth weight, low birth weight, birth weight percentile by gestational age, small for gestational age, pre-term birth, length, and head circumference. In multivariable models, high maternal blood Cd levels (≥0.50 µg/L) during pregnancy were inversely associated with birth weight percentile by gestational age (p = 0.007) and associated with increased odds of infants being born small for gestational age (p<0.001). These observed effects were independent of cotinine-defined smoking status. The results from this study provide further evidence of health risks associated with early life exposure to Cd among a large pregnancy cohort.     

Childhood Hospitalisation with Infection and Cardiovascular Disease in Early-Mid Adulthood: A Longitudinal Population-Based Study

BackgroundPathogen-specific and overall infection burden may contribute to atherosclerosis and cardiovascular disease (CVD), but the effect of infection severity and timing is unknown. We investigated whether childhood infection-related hospitalisation (IRH, a marker of severity) was associated with subsequent adult CVD hospitalisation.MethodsUsing longitudinal population-based statutorily-collected administrative health data from Western Australia (1970-2009), we identified adults hospitalised with CVD (ischaemic heart disease, ischaemic stroke, and peripheral vascular disease) and matched them (10:1) to population controls. We used Cox regression to assess relationships between number and type of childhood IRH and adulthood CVD hospitalisation, adjusting for sex, age, Indigenous status, socioeconomic status, and birth weight.Results631 subjects with CVD-related hospitalisation in adulthood (≥ 18 years) were matched with 6310 controls. One or more childhood (< 18 years) IRH was predictive of adult CVD-related hospitalisation (adjusted hazard ratio, 1.3; 95% CI 1.1-1.6; P < 0.001). The association showed a dose-response; ≥ 3 childhood IRH was associated with a 2.2 times increased risk of CVD-related hospitalisation in adulthood (adjusted hazard ratio, 2.2; 95% CI 1.7-2.9; P < 0.001). The association was observed across all clinical diagnostic groups of infection (upper respiratory tract infection, lower respiratory tract infection, infectious gastroenteritis, urinary tract infection, skin and soft tissue infection, and other viral infection), and individually with CVD diagnostic categories (ischaemic heart disease, ischaemic stroke and peripheral vascular disease).ConclusionsSevere childhood infection is associated with CVD hospitalisations in adulthood in a dose-dependent manner, independent of population-level risk factors.     

Birth size and breast cancer risk: re-analysis of individual participant data from 32 studies

Background

Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size–breast cancer association.

Methods and Findings

Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02–1.09) and parental recall when the participants were children (1.02; 95% CI 0.99–1.05), but not in those based on adult self-reports, or maternal recall during the woman''s adulthood (0.98; 95% CI 0.95–1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000–3.499 kg, the risk was 0.96 (CI 0.80–1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00–1.25) in those who weighed ≥ 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03–1.10] and 1.09 [95% CI 1.03–1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution.

Conclusions

This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.