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Biomedical subjects

Mark S Pearce

Publications and source records attributed to Mark S Pearce.

At least 19 recordsLinked to original sources

Examination of gender effect in birth weight and miscarriage associations with childhood cancer (United Kingdom).

BACKGROUND: Higher birth weight and maternal history of miscarriage has been associated with an increased risk of childhood leukemia. The possibility that this association may be sex-specific has not been explored in detail in previous studies. METHODS: In a retrospective case-control study, 732 childhood (< or =14 years) cancer cases from a population-based Registry in Northern England whose hospital birth records could be accessed and 3,723 controls matched for date and hospital of birth to the cases were compared. We examined birth weight for sex-specific associations with childhood cancer. Conditional logistic regression analysis was used for statistical evaluation of associations. RESULTS: In acute lymphoblastic leukemia (ALL) (225 cases and 1,163 matched controls), birth weight and sex showed a strong interaction (P = 0.003). In boys with ALL, but not in girls, there was a nonlinear association with birth weight (P for trend = 0.008; OR = 3.05 for the highest quintile compared to the second lowest quintile, 95% CI = 1.40-6.64; P = 0.005). When birth weights were adjusted using UK standards for gestational age and sex, the risk associations were similar in statistical significance and magnitude. Maternal history of miscarriage showed an association with all cancers and individually with ALL. The miscarriage association with ALL was statistically significant in boys only (OR = 1.91, 95% CI = 1.07-3.42; P = 0.03). A multivariable model for ALL containing other examined maternal and reproductive variables confirmed the independence of the birth weight and miscarriage associations. There was no birth weight or miscarriage associations in other cancers. CONCLUSIONS: This study confirmed the risk associations with birth weight and miscarriages in childhood ALL. Statistically significant association of size at birth suggested marked differences in etiology between girls and boys.

Abortion, Habitual↗

Paternal occupational exposure to electro-magnetic fields as a risk factor for cancer in children and young adults: a case-control study from the North of England.

BACKGROUND: Numerous studies have implied that paternal occupational exposures, in particular electromagnetic fields (EMF) and ionizing radiation, may be involved in the etiology of childhood cancers. We investigated whether an association exists between paternal occupations at birth involving such exposures and cancer risk in offspring, using data from the Northern Region Young Persons' Malignant Disease Registry (NRYPMDR). PROCEDURE: Cases (n=4,723) were matched, on sex and year of birth, to controls from two independent sources: (i) all other patients from the NRYPMDR with a different cancer, (ii) 100 cancer-free individuals per case from the Cumbrian Births Database. An occupational exposure matrix was used to assign individuals to exposure groups. RESULTS: There was an increased risk of leukemia among the offspring of men employed in occupations likely to be associated with EMF or radiation exposures (OR 1.31, 95% CI 1.02-1.69), particularly in males aged less than 6 years (OR 1.81, 95% 1.19-2.75). No significant association was seen in females. Increased risks were also seen for chondrosarcoma (OR 8.7, 95% CI 1.55-49.4) and renal carcinoma (OR 6.75, 95% CI 1.73-26.0). These associations were consistent between control groups and remained after adjustment for socio-economic status. CONCLUSIONS: This large case-control study identified a significantly increased risk of leukemia among the offspring of men likely to have been occupationally exposed to EMF, with differing associations between males and females. Increased risks of chondrosarcoma and renal carcinoma were also seen, although based on smaller numbers. Further detailed investigations in this area are required to understand this association.

Adolescent↗

No association between socio-economic status and white blood cell telomere length.

It has been hypothesized that more socio-economically deprived individuals age faster and, thus, have shorter telomeres than their more affluent counterparts. A weak association between white blood cell telomere length and socio-economic status in a large heterogeneous sample of females has recently been reported. In 318 individuals from a homogeneous birth cohort, we found no evidence of an association between any measure of socio-economic status and peripheral blood mononucleocyte telomere length at age 50 after control for lifestyle variables, gender and paternal age at birth. The results of this, and the previous study, suggest that there is little evidence of a strong or consistent correlation between white blood cell telomere length and markers of socio-economic status.

Adolescent↗

Carotid sinus hypersensitivity in asymptomatic older persons: implications for diagnosis of syncope and falls.

BACKGROUND: Carotid sinus hypersensitivity is the most commonly reported cause of falls and syncope in older persons. Recent guidelines recommend 5 to 10 seconds of carotid sinus massage in supine and upright positions with beat-to-beat monitoring. The aim of this study was to determine the prevalence of carotid sinus hypersensitivity in (1) an unselected community sample of older people and (2) a subsample with no history of syncope, dizziness, or falls using recently standardized diagnostic criteria. METHODS: One thousand individuals older than 65 years were randomly sampled from a single general practice register; 272 participants underwent supine and upright carotid sinus massage with continuous heart rate and phasic blood pressure monitoring. Carotid sinus hypersensitivity was defined as asystole of 3 seconds or greater and/or a drop in systolic blood pressure of 50 mm Hg or greater. RESULTS: Carotid sinus hypersensitivity was present in 107 individuals (39%); 24% had asystole of 3 seconds or greater during carotid sinus massage; and 16% had symptoms (including syncope) with carotid sinus hypersensitivity. Age (odds ratio, 1.05; 95% confidence interval, 1.00-1.09) and male sex (odds ratio, 1.71; 95% confidence intervals, 1.04-2.82) were the only predictors of carotid sinus hypersensitivity. In 80 previously asymptomatic individuals, carotid sinus hypersensitivity was present in 28 (35%) and accompanied by symptoms in 10. The 95th percentile for carotid sinus massage response was 7.3 seconds' asystole and a 77-mm Hg drop in systolic blood pressure. CONCLUSIONS: Carotid sinus hypersensitivity is common in older persons, even those with no history of syncope, dizziness, or falls. The finding of a hypersensitive response should not necessarily preclude further investigation for other causes of syncope.

Accidental Falls↗

Intrauterine growth and cerebral palsy in twins: a European multicenter study.

Population-based studies in twins have been of insufficient size to explore the relationship between risk of cerebral palsy and intrauterine growth. Earlier studies in singletons have suggested an optimum size at birth for minimum cerebral palsy risk between the 75th and 90th percentiles of weight for gestational age. We aggregated data from nine European cerebral palsy registers for 1976 to 1990. Using sex-specific fetal growth standards for twins, a z score of weight-for-gestation was derived for each of the 373 twin cases. The rates of cerebral palsy in each z-score band were compared to the rate in the a priori reference band of 0.67 to less than 1.28 (equivalent to the 75th to less than 90th percentiles). In twins born at 32 weeks' gestation or more (92% of all twins), cerebral palsy rates were higher for both light and heavy-for-gestation babies compared to an optimum (i.e., minimum risk) in the reference band. However, the rate ratio for heavy babies (90th percentile or greater) did not reach conventional (95% confidence intervals [CI]) statistical significance (rate ratios = 1.76; 90% CI 1.02-3.03). For twins born at less than 32 weeks, the significantly higher risk for cerebral palsy was observed consistently in all z-score bands less than average compared to the reference band. This multi-center study demonstrates that for twins born at 32 weeks' gestation or more, an increased risk of cerebral palsy is associated with deviations from optimal intrauterine growth at about 1 standard deviation above mean weight, as was earlier reported for singletons. For twins born at less than 32 weeks' gestation, this pattern is only demonstrable for babies weighing below the optimum weight-for-gestation.

Birth Weight↗

Cancer in adolescents and young adults aged 15-24 years: a report from the North of England young person's malignant disease registry, UK.

BACKGROUND: Descriptions of population-based data have rarely been published specifically for adolescents and young adults with cancer. PROCEDURE: Data on young adults (15-24 years) diagnosed with cancer in the North of England from 1968 to 1997 were obtained from the Northern Region Young Person's Malignant Disease Registry. Temporal changes in incidence and survival rates were investigated. RESULTS: There were 2,329 first cancers diagnosed over the study period (M:F 1.22:1). Overall age standardized incidence was 174 cases per million 15-24 years old, per year, 190 for males and 157 for females. The most common cancers in young adults were Hodgkin disease (19%), carcinomas (15%), central nervous system tumors (14%), germ cell tumors (13%), and leukemia (11%). Comparing incidence for 1968-1977 with 1988-1997 there were significant increases in the incidence of bone tumors (rate ratio 1.72, 95% CI 1.10-2.68), testicular tumors (rate ratio 1.64, 95% CI 1.16-2.32), thyroid cancer (rate ratio 2.63, 95% CI 1.37-5.02), and malignant melanoma (rate ratio 2.04, 95% CI 1.36-3.08). Survival rates improved significantly (P < 0.001) over the study period; 5-year survival rates over the three time periods 1968-1977, 1978-1987, 1988-1997 for all cancers were 45% (95% CI 41%-49%), 62% (95% CI 58%-65%), and 74% (95% CI 71%-77%) respectively. CONCLUSIONS: Survival rates improved and there were significant increases in incidence for specific cancers in young adults in the North of England. Further research is required to identify the reasons for changing incidence and to investigate the late effects of treatment among survivors.

Adolescent↗

Self-report overestimates true height loss: implications for diagnosis of osteoporosis.

The Newcastle Thousand Families birth cohort dates from 1947; assessments have included height measurement at 22 and 50 years, when height loss was also assessed by self-report. A total of 388 attended for 50-year review of bone health, of whom 57 reported a median height loss of 2.5 cm, and 8 reported height loss of >3.5 cm. However, of 24 subjects for whom true height loss could be calculated, 7 had gained height, 9 were unchanged and only 8 had lost height since age 22 years. Self-report leads to over-reporting of height loss, and therefore should not be the sole measure of height loss. In clinical practice, objective confirmation of reported height loss should be undertaken, wherever possible, prior to further investigation.

Adult↗

Growth in early life and childhood IQ at age 11 years: the Newcastle Thousand Families Study.

BACKGROUND: It has been suggested that in addition to genetic factors, fetal and post-natal growth influence childhood cognition, although it is unclear whether such an effect continues throughout childhood. This study aimed at investigating the potential relationships between childhood IQ at age 11 years and birth weight and height at the ages of 9 and 13 years, after adjusting for the confounding factors available to this investigation. METHODS: The Newcastle Thousand Families study, a prospectively followed cohort, originally consisted of all 1142 births in the city of Newcastle in May and June 1947. Using data on 733 members of this cohort, we investigated the associations between IQ at age 11, and birth weight and height at ages 9 and 13 years. RESULTS: Birth weight showed no association with childhood IQ. However, height at age 9 years was a significant predictor of childhood IQ after adjusting for socioeconomic status (standardized regression coefficient b = 2.6, 95% CI 1.6-3.6, P < 0.0001). Height at age 13 was also a significant predictor of IQ after adjusting for socioeconomic status (b = 3.4, 95% CI 2.3-4.4, P = 0.001), and explained an additional 2.5% of the variation in IQ scores to that already explained by socioeconomic status and height at age nine. CONCLUSIONS: These results suggest a continuing effect of post-natal growth on childhood cognition beyond the age of 9 years. Post-natal growth, which may be influenced by genetic factors and nutrition and socioeconomic circumstances in childhood, may be more important than fetal growth in terms of childhood cognition.

Adolescent↗

Temporal changes in the distribution of population risk factors attenuate the reduction in perinatal mortality.

BACKGROUND AND OBJECTIVE: To examine and quantify the changing contribution of some risk factors to the perinatal mortality rate. METHODS: A population-based retrospective cohort study in Northern England compared stillbirth, neonatal, and perinatal mortality rates by birthweight, maternal age, plurality, and gender between 1982-1990 and 1991-2000. RESULTS: Atlhough the perinatal mortality rate fell by 20% between 1982-1990 and 1991-2000, the proportion of births in high risk groups (low and high birthweight, older mothers, and multiple births) increased. Standardizing the rates for 2000 to the risk factor distribution in 1982 resulted in lower rates. Changes in the birthweight distribution had the largest impact, particularly on neonatal mortality. Nearly a quarter of neonatal deaths in Northern England in 2000 can be attributed to the shift in the birthweight distribution since 1982, especially to the increase in low birthweight births. CONCLUSION: Changes in the distribution of birthweight, maternal age, and plurality over the study period attenuated the observed reduction in perinatal mortality. It is important to consider differences in the population prevalence of such risk factors to make valid geographic or temporal comparisons. Reasons for the secular shift in birthweight and the implications of any contributing change in obstetric practice require further investigation.

Birth Weight↗

The influence of erythrocyte folate and serum vitamin B12 status on birth weight.

The extent to which maternal folate and vitamin B12 modulate infant birth weight is unclear. The present study investigated mothers in early gestation (mean 11.5 (sd 5.8) weeks) and neonates, at delivery. Erythrocyte (RBC) folate (mothers: n 683; neonates: n 614) and vitamin B12 (mothers: n 534; neonates: n 614) were measured. Data on smoking habits were available for 44 % of pregnancies (n 443). The relationship between vitamin levels and birth weight standardized for gender and gestational age was investigated, using linear regression and adjusting for possible confounding variables (maternal age, parity). Results are presented as standardized regression coefficients (b). Increasing maternal age was associated with elevated RBC folate (b 0.11 (95 % CI 0.08, 0.15), P<0.001; n 674) and smoking was associated with a decrease in maternal RBC folate (b -1.38 (95 % CI -1.92, -0.86), P=0.001; n 319). Neonatal RBC folate was predicted by maternal RBC folate (b 0.08 (95 % CI 0.04, 0.11), P=0.001; n 315) and maternal vitamin B12 (b 0.08 (95 % CI 0.01, 0.16), P=0.02; n 252). Smoking influenced maternal vitamin B12 status (b -0.88 (95 % CI -1.49, -0.27), P=0.005; n 231). Using univariate regression, smoking significantly influenced infant birth weight (b -2.15 (95 % CI -3.24, -1.04), P<0.001; n 437). However, the effect of smoking on birth weight was statistically non-significant when considered in a multivariate regression model, leaving maternal RBC folate as the only significant predictor of birth weight (b 0.25 (95 % CI 0.08, 0.42), P=0.005; n 145). These findings suggest that maternal folate status is an important determinant of infant birth weight. The combined effects of smoking and reduced RBC status on birth weight require further investigation.

Birth Weight↗

Does increased duration of exclusive breastfeeding protect against Helicobacter pylori Infection? The Newcastle Thousand Families Cohort Study at age 49-51 years.

OBJECTIVE: Helicobacter pylori acquired in childhood is an important risk factor for gastric carcinoma. Once colonization is established, infection may be carried for life. This study used prospectively recorded, detailed information on infant feeding and investigated the potential link between duration of exclusive breastfeeding in infancy and seropositivity at age 50 years, as measured by enzyme-linked immunosorbent assay. METHODS: H. pylori seropositivity at age 50 years was investigated among 407 individuals born in Newcastle in May and June 1947 and related to the duration of exclusive breastfeeding after adjusting for measures of socioeconomic status and adverse housing conditions at birth. RESULTS: Duration of exclusive breastfeeding in infancy was significantly associated with H. pylori seropositivity (odds ratio per 30 days, 0.88; 95% confidence interval, 0.78 to 0.98). The significant protective trend was only seen among men (odds ratio per 30 days, 0.78; 95% confidence interval, 0.65 to 0.95), with no significant effect seen among women. CONCLUSION: Increased duration of exclusive breastfeeding in infancy may have a long-term protective effect against chronic H. pylori infection and hence the risk of gastric carcinoma. Although further research is required, particularly as to why a significant effect was only seen among men, the results provide additional support for the concept that breastfeeding may have long-term influences on health and that human milk is the ideal complete first diet for human infants.

Antibodies, Bacterial↗

Perinatal mortality rates: adjusting for risk factor profile is essential.

Perinatal mortality has long been used as a comparative measure of health and health care across regions, countries and over time. Recently, the validity of the measure has been questioned. Using data from a population-based survey of late fetal losses, stillbirths and infant deaths, the Northern Perinatal Mortality Survey, we demonstrate the potential for inaccuracy of crude measures of perinatal mortality. Such measures are generally not adjusted for characteristics of the population (e.g. birthweight, maternal age, plurality, gender) which are known to affect risk of adverse pregnancy outcome when comparing temporal or geographical trends. We also show the effect of standardising for these factors on the most frequent causes of perinatal death. We recommend the construction of a 'standard birth population' for calculating standardised perinatal mortality rates that would improve direct comparisons between populations.

Birth Weight↗

An investigation of folate-related genetic factors in the determination of birthweight.

Recent evidence suggests that maternal folate status in early gestation is a significant determinant of infant birthweight. Folate metabolism is known to be controlled by genetic factors, with a number of polymorphic variations in folate metabolising genes identified, several of which have well-documented functional effects. The current study investigated whether folate-related polymorphic variation, in association with low maternal folate status, influences birthweight. Red blood cell (RBC) folate analysis and genotyping of five polymorphisms in folate-related genes [Methylenetetrahydrofolate reductase (MTHFR) 677C>T; MTHFR 1298A>C; cystathionine-beta-synthase (CbetaS) 844ins68bp; serine hydroxymethyltransferase (SHMT) 1420C>T; reduced folate carrier-1 (RFC-1) 80G>A] were undertaken in mothers and infants from 998 pregnancies. These data were analysed in relation to infant birthweight, adjusted for gender and gestational age (z-score). Low maternal RBC folate status was associated with reduced infant birthweight. None of the genetic variants studied showed an independent association with infant birthweight. However, two genetic variants were shown to have a significant effect on birthweight when found in association with low maternal RBC folate status. When individuals with variant genotypes and mothers with folate in the lowest quintile were compared with wild-type individuals and mothers with folate in the highest quintile, the following differences in mean birthweight (z-score) were observed; maternal MTHFR 677C>T (-0.56 [95% CI -1.00, -0.12]P=0.01) and infant CbetaS 844ins68bp (-0.71 [95% CI -1.97, -0.07]P=0.03). The findings of this study suggest that folate-related genetic polymorphisms do not directly influence infant birthweight. However, when placed on a background of deficient maternal nutritional status, they may detrimentally affect fetal growth.

Birth Weight↗

Tooth loss and Helicobacter pylori seropositivity: the Newcastle Thousand Families Cohort Study at age 49-51 years.

BACKGROUND: Helicobacter pylori, one of the commonest chronic bacterial infections of humankind, is an important risk factor for gastric carcinoma. It has also been suggested to be present in dental plaque. This study investigated the potential link between the number of teeth lost and H. pylori seropositivity at age 50 years. METHODS: H. pylori seropositivity at age 50 years was investigated among 334 individuals born in Newcastle upon Tyne, United Kingdom, in May and June 1947 and related to the number of teeth lost, after adjusting for socioeconomic status. RESULTS: The unadjusted risk of being seropositive for H. pylori increased with increasing number of teeth lost (odds ratio per tooth 1.03, 95% confidence interval 1.01-1.06, p = .019). However, after adjustment for socioeconomic status at birth and at age 50 years, the relationship was no longer significant (p = .36). CONCLUSIONS: Our results, obtained using prospectively collected data, suggest that any relationship between poor oral health and seropositivity to H. pylori may be due to both tooth loss and H. pylori colonization being associated with socioeconomic status and related factors.

Female↗

Lifecourse study of bone health at age 49-51 years: the Newcastle thousand families cohort study.

OBJECTIVE: To quantify the direct and indirect effects of fetal (position in family, weight, and social class at birth), childhood (breast feeding, growth, infections, and social class in childhood, age at menarche), and adult life (social class, alcohol consumption, smoking, diet, reproductive history, exercise, hormone replacement therapy use), and adult size (height, weight) on bone health at age 49-51 years, as measured by bone mineral density, total scanned bone area of the hip and lumbar spine, and femoral neck shaft angle. DESIGN: Follow up study of the Newcastle thousand families birth cohort established in 1947. PARTICIPANTS: 171 men and 218 women who attended for dual energy x ray absorptiometry scanning. MAIN RESULTS: Fetal life explained around 6% of variation in adult bone mineral density for men, but accounted for less than 1% for women. Adult lifestyle, including effects mediated through adult weight accounted for over 10% of variation in density for men and around 6% for women. Almost half of variation in bone area for men was explained by early life. However, most of this was mediated through achieved adult height and weight. In women, less than 5% of variation in bone area was accounted for by early life, after adjusting for adult size. Most of the variation in each of the indicators for both sexes was contributed either directly or indirectly by adult lifestyle and achieved adult height and weight. CONCLUSIONS: The effect of fetal life on bone health in adulthood seems to be mediated through achieved adult height.

Absorptiometry, Photon↗

Social mobility over the lifecourse and self reported mental health at age 50: prospective cohort study.

STUDY OBJECTIVE: To investigate the effect of socioeconomic status throughout the lifecourse on self reported mental health at age 50 years. DESIGN: Prospective cohort study SETTING: Community setting in Newcastle upon Tyne, north east England. PARTICIPANTS: 503 subjects from a birth cohort assembled in 1947 who completed the 28 item version of the general health questionnaire (GHQ-28). MAIN RESULTS: There was an association between socioeconomic group at birth and reporting a clinically significant GHQ-28 score at age 50 (OR 5.5 95% CI 1.2 to 25.4 comparing the least with the most advantaged socioeconomic group). A downward socioeconomic trajectory over the whole lifecourse was associated with poorer self reported mental health in men (p<0.001) but not women (p=0.8). CONCLUSIONS: Socioeconomic position throughout the lifecourse may act differently on mental health at middle age depending on a person's sex.

England↗

Self-reported smoking status and exhaled carbon monoxide: results from two population-based epidemiologic studies in the North of England.

STUDY OBJECTIVES: To investigate the validity of self-reported responses to questions on current smoking in two cohorts based in Northern England. DESIGN: A cross-sectional population-based study (the Newcastle Heart Project [NHP]) and a follow-up of the Newcastle Thousand Families birth cohort established in 1947. PATIENTS OR PARTICIPANTS: Participants included 1,189 members of the NHP and 410 members of the Newcastle Thousand Families cohort who completed a health and lifestyle questionnaire, including questions on current smoking, and attended a clinical examination, including testing for exhaled carbon monoxide between April 1993 and December 1998. RESULTS: The number of self-reporting smokers for whom very low (ie, < 6 ppm) exhaled carbon monoxide levels were recorded varied between 9% in the Newcastle Thousand Families Study and 26% among the members of the NHP who were of South Asian origin. Using a cutoff of 8 ppm, 80% of self-reported smokers were identified in both the Newcastle Thousand Families study and in the NHP European population, but only 60% were identified in the NHP South Asian population. In each population, < 7% of nonsmokers had exhaled carbon monoxide measurements of > 6 ppm, with nonsmoking men more likely to have higher levels than nonsmoking women. Among the nonsmokers, the levels of exhaled carbon monoxide did not vary with respect to the smoking status of a partner or socioeconomic status. CONCLUSIONS: Using a cutoff value of 6 ppm would potentially miss a large number of smokers, although this may vary with ethnicity. Epidemiologic studies should continue to use biochemical markers to validate responses to smoking surveys. However, the use of exhaled carbon monoxide measurements as a method of assessing the validity of self-reported smoking status may require additional analyses of whether the cutoff level should vary for different populations.

Adult↗