Little is known about preschool-aged children’s levels of physical activity (PA) over the course of the day. Using time-stamped data, we describe the levels and patterns of PA in a population-based sample of four-year-old British children.
Within the Southampton Women’s Survey the PA levels of 593 4-year-old children (51% female) were measured using (Actiheart) accelerometry for up to 7 days. Three outcome measures: minutes spent sedentary (<20 cpm); in light (LPA: ≥20 – 399 cpm) and in moderate-to-vigorous activity (MVPA: ≥400 cpm) were derived. Average daily activity levels were calculated and then segmented across the day (morning, afternoon and evening). MVPA was log-transformed. Two-level random intercept models were used to analyse associations between activity level and temporal and demographic factors.
Children were active for 67% (mean 568.5 SD 79.5 minutes) of their daily registered time on average, with 88% of active time spent in LPA. All children met current UK guidelines of 180 minutes of daily activity. There were no differences in children’s average daily levels of sedentary activity and LPA by temporal and demographic factors: differences did emerge when activity was segmented across the day. Sex differences were largest in the morning, with girls being more sedentary, spending fewer minutes in LPA and 18% less time in MVPA than boys. Children were more sedentary and less active (LPA and MVPA) in the morning if they attended childcare full-time compared to part-time, and on weekend mornings compared to weekdays. The reverse was true for weekend afternoons and evenings. Children with more educated mothers were less active in the evenings. Children were less sedentary and did more MVPA on summer evenings compared to winter evenings.
Preschool-aged children meet current physical activity guidelines, but with the majority of their active time spent in LPA, investigation of the importance of activity intensity in younger children is needed. Activity levels over the day differed by demographic and temporal factors, highlighting the need to consider temporality in future interventions. Increasing girls’ morning activity and providing opportunities for daytime activity in winter months may be worthwhile.
In 1995 the Tucson Children’s Respiratory Study (TCRS) identified clinically distinct phenotypes amongst early wheezers; the Avon Longitudinal Study of Parents And Children (ALSPAC) has recently re-examined these.
To validate statistically derived ALSPAC phenotypes in the Southampton Women’s Survey (SWS) using infant and 6 year lung function, and allergic sensitisation at 1, 3 and 6 years, comparing these with TCRS phenotypes.
Complete 6 year follow-up data were available for 926 children, selected from 1973 infants born to 12,579 women characterised pre-conception. 95 children had V’maxFRC and FEV0.4 measured age 5-14 weeks using rapid compression/raised volume techniques. At 6 years we performed spirometry (n=791), fractional exhaled nitric oxide (FeNO, n=589) and methacholine challenge (n=234). Skin prick testing was performed at 12m, 3 and 6 years (n=1494, 1255, 699, respectively). Using wheeze status questionnaire data at 6m, 12m, 2, 3 and 6 years we classified children into TCRS (never, transient early, persistent, late-onset) and ALSPAC based groups (never, early, transient, intermediate-onset, late-onset, persistent).
Amongst ALSPAC groups, persistent and late-onset wheeze were associated with atopy at 3 and 6 years, whilst intermediate-onset wheeze showed earlier atopic association at 1 year; all three were associated with FeNO at 6 years. Persistent wheezers had lower infant (V’maxFRC p<0.05) and 6 year lung function (FEV1, FEV1/FVC and FEF25-75, p<0.05), whilst late and intermediate-onset wheezers showed no lung function deficits. Transient wheezers were non-atopic but showed persistent lung function deficits (V’maxFRC in infancy, FEV1 and FEF25-75 at 6 years, all p<0.05). Those who wheezed only in the first year (early phenotype) showed no lung function deficits. No associations were seen with 6 years bronchial hyper-responsiveness or infancy FEV0.4.
SWS cohort data validates the statistically derived ALSPAC 6-class model. In particular, lung function and atopy successfully differentiate persistent, late-onset and intermediate-onset wheeze, whilst the Tucson ‘transient early’ wheeze phenotype can be sub-classified into groups that reflect early lung function. Since the 4-class model fails to adequately differentiate phenotypes based on lung function and atopy, we propose that strong consideration be given to using the 6-class paradigm for longitudinal outcome work in wheezing with onset in early life.
Wheeze; asthma; phenotype; lung function; cohort; atopy
We investigated relationships between early growth and proximal femoral geometry at age six years in a prospective population-based cohort, the Southampton Women’s Survey.
In 493 mother-offspring pairs we assessed linear size (individual measure dependent on developmental stage) using high-resolution ultrasound at 11, 19 and 34 weeks gestation (femur length) and at birth, 1, 2, 3, 4 and 6 years (crown-heel length/height). Standard deviation (SD)-scores were created and conditional regression modelling generated mutually independent growth variables. Children underwent hip DXA (Dual X-ray absorptiometry) at 6 years (Hologic Discovery, Hologic Inc., MA); hip structure analysis software yielded measures of geometry and strength.
There were strong associations between early linear growth and femoral neck section modulus (Z) at 6 years, with the strongest relationships observed for femur growth from 19-34 weeks gestation (β=0.26 cm3/SD, p<0.0001), and for height growth from birth to 1 year (β=0.25 cm3/SD, p<0.0001) and 1-2 years (β=0.33 cm3/SD, p<0.0001), with progressively weaker relationships over years 3 (β=0.23 cm3/SD, p=0.0002) and 4 (β=0.10 cm3/SD, p=0.18).
These results demonstrate that growth before age 3 years predicts proximal femoral geometry at six years old. The data suggest critical periods in which there is capacity for long term influence on the later skeletal growth trajectory.
We have demonstrated previously that higher birth weight is associated with greater peak and later-life bone mineral content and that maternal body build, diet, and lifestyle influence prenatal bone mineral accrual. To examine prenatal influences on bone health further, we related ultrasound measures of fetal growth to childhood bone size and density. We derived Z-scores for fetal femur length and abdominal circumference and conditional growth velocity from 19 to 34 weeks’ gestation from ultrasound measurements in participants in the Southampton Women’s Survey. A total of 380 of the offspring underwent dual-energy X-ray absorptiometry (DXA) at age 4 years [whole body minus head bone area (BA), bone mineral content (BMC), areal bone mineral density (aBMD), and estimated volumetric BMD (vBMD)]. Volumetric bone mineral density was estimated using BMC adjusted for BA, height, and weight. A higher velocity of 19- to 34-week fetal femur growth was strongly associated with greater childhood skeletal size (BA: r = 0.30, p < .0001) but not with volumetric density (vBMD: r = 0.03, p = .51). Conversely, a higher velocity of 19- to 34-week fetal abdominal growth was associated with greater childhood volumetric density (vBMD: r = 0.15, p = .004) but not with skeletal size (BA: r = 0.06, p = .21). Both fetal measurements were positively associated with BMC and aBMD, indices influenced by both size and density. The velocity of fetal femur length growth from 19 to 34 weeks’ gestation predicted childhood skeletal size at age 4 years, whereas the velocity of abdominal growth (a measure of liver volume and adiposity) predicted volumetric density. These results suggest a discordance between influences on skeletal size and volumetric density.
EPIDEMIOLOGY; OSTEOPOROSIS; PROGRAMMING; DEVELOPMENTAL ORIGINS
Factors associated with parental awareness of children’s physical activity (PA) levels have not been explored in preschool-aged children. This paper investigates maternal awareness of preschool-aged children’s PA levels and determined correlates associated with maternal overestimation of PA.
Data from the Southampton Women’s Survey, a UK population-based study, were collected March 2006 through June 2009. Daily minutes of moderate-to-vigorous PA (MVPA) were derived using accelerometry in 478 4-year-old children. Mothers who were realistic or overestimated their child’s PA were identified. Log-binomial regression was used to analyse correlates of maternal overestimation of PA levels in children whose mothers perceived them to be active (n = 438).
40.8% of children were classified as inactive: 89.7% of these were perceived to be active by their mothers (over-estimators). These mothers were more likely to think their child sometimes lacked skills required to be physically active (RR (95% CI) = 1.29(1.03-1.63)) and their child was more likely to attend nursery full-time (RR = 1.53(1.14-2.04)). They were less likely to have older children at home (RR = 0.71(0.56-0.90)).
Almost 90% of mothers of inactive preschool-aged children perceive their child to be active. Nursery-school attendance and having older siblings at home may be important to consider when designing behavioural interventions to increase PA in preschool children.
Physical activity; Awareness; Preschool children
Obesity and asthma have increased in westernised countries. Maternal obesity may increase childhood asthma risk. If this relation is causal it may be mediated through factors associated with maternal adiposity, such as fetal development, pregnancy complications or infant adiposity. We investigated the relationships of maternal BMI and fat mass with childhood wheeze and examined the influences of infant weight gain and childhood obesity.
Maternal pre-pregnancy BMI and estimated fat mass (from skinfold thicknesses) were related to asthma, wheeze and atopy in 940 children. Transient or persistent/late wheeze was classified using questionnaire data collected at ages 6, 12, 24 and 36 months and 6 years. At 6 years, skin prick testing was conducted and exhaled nitric oxide and spirometry measured. Infant adiposity gain was calculated from skinfold thickness at birth and 6 months.
Greater maternal BMI and fat mass were associated with increased childhood wheeze (RR 1.08 per 5 kg m−2, p=0.006; RR 1.09 per 10 kg, p=0.003); these reflected associations with transient wheeze (RR 1.11, p=0.003; RR 1.13, p=0.002, respectively) but not with persistent wheeze or asthma. Infant adiposity gain was associated with persistent wheeze but not significantly. Adjusting for infant adiposity gain or BMI at 3 or 6 years did not reduce the association between maternal adiposity and transient wheeze. Maternal adiposity was not associated with offspring atopy, exhaled nitric oxide, or spirometry.
Greater maternal adiposity is associated with transient wheeze but not asthma or atopy, suggesting effects upon airway structure/function but not allergic predisposition.
adiposity; body mass index; obesity; asthma; allergic sensitisation
Detailed associations between physical activity (PA) subcomponents, sedentary time, and body composition in preschoolers remain unclear.
We examined the magnitude of associations between objectively measured PA subcomponents and sedentary time with body composition in 4-y-old children.
We conducted a cross-sectional study in 398 preschool children recruited from the Southampton Women’s Survey. PA was measured by using accelerometry, and body composition was measured by using dual-energy X-ray absorptiometry. Associations between light physical activity, moderate physical activity (MPA), vigorous physical activity (VPA), and moderate-to-vigorous physical activity (MVPA) intensity; sedentary time; and body composition were analyzed by using repeated-measures linear regression with adjustment for age, sex, birth weight, maternal education, maternal BMI, smoking during pregnancy, and sleep duration. Sedentary time and PA were also mutually adjusted for one another to determine whether they were independently related to adiposity.
VPA was the only intensity of PA to exhibit strong inverse associations with both total adiposity [P < 0.001 for percentage of body fat and fat mass index (FMI)] and abdominal adiposity (P = 0.002 for trunk FMI). MVPA was inversely associated with total adiposity (P = 0.018 for percentage of body fat; P = 0.022 for FMI) but only because of the contribution of VPA, because MPA was unrelated to fatness (P ≥ 0.077). No associations were shown between the time spent sedentary and body composition (P ≥ 0.11).
In preschoolers, the time spent in VPA is strongly and independently associated with lower adiposity. In contrast, the time spent sedentary and in low-to-moderate–intensity PA was unrelated to adiposity. These results indicate that efforts to challenge pediatric obesity may benefit from prioritizing VPA.
Correlates of physical activity (PA) are hypothesized to be context and behaviour specific, but there is limited evidence of this in young children. The aim of the current study is to investigate associations between personal, social and environmental factors and objectively measured light and moderate-to-vigorous PA (LPA and MVPA, respectively) in four-year-old children.
Cross-sectional data were used from the Southampton Women’s Survey, a UK population-based longitudinal study. Four-year old children (n = 487, 47.0% male) had valid PA data assessed using accelerometry (Actiheart) and exposure data collected with a validated maternal questionnaire (including data on child personality, family demographics, maternal behaviour, rules and restrictions, and perceived local environment). Linear regression modelling was used to analyse associations with LPA and MVPA separately, interactions with sex were explored.
LPA minutes were greater in children whose mothers reported more PA (vs. inactive: regression coefficient±standard error: 6.70±2.94 minutes), and without other children in the neighbourhood to play with (−6.33±2.44). MVPA minutes were greater in children with older siblings (vs. none: 5.81±2.80) and those whose mothers used active transport for short trips (vs. inactive: 6.24±2.95). Children accumulated more MVPA in spring (vs. winter: 9.50±4.03) and, in boys only, less MVPA with availability of other children in the neighbourhood (−3.98±1.70).
Young children’s LPA and MVPA have differing associations with a number of social and environmental variables. Interventions targeting PA promotion in young children outside of formal care settings should consider including intensity specific factors.
Our previous work found that perceived control over life was a significant predictor of the quality of diet of women of lower educational attainment. In this paper, we explore the influence on quality of diet of a range of psychological and social factors identified during focus group discussions, and specify the way this differs in women of lower and higher educational attainment. We assessed educational attainment, quality of diet, and psycho-social factors in 378 women attending Sure Start Children’s Centres and baby clinics in Southampton, UK. Multiple-group path analysis showed that in women of lower educational attainment, the effect of general self-efficacy on quality of diet was mediated through perceptions of control and through food involvement, but that there were also direct effects of social support for healthy eating and having positive outcome expectancies. There was no effect of self-efficacy, perceived control or outcome expectancies on the quality of diet of women of higher educational attainment, though having more social support and food involvement were associated with improved quality of diet in these women. Our analysis confirms our hypothesis that control-related factors are more important in determining dietary quality in women of lower educational attainment than in women of higher educational attainment.
educational attainment; diet; disadvantage; self-efficacy; perceived control
In order to assess the extent to which children in the United Kingdom (UK) will follow the UK-WHO head circumference standard, we used head circumference data from the Southampton Women’s Survey (SWS; n=3159) and the Avon Longitudinal Study of Parents and Children (ALSPAC; n=15,208) in children age 0-36 months, converted into z-scores using both the UK-WHO or UK1990 references. Rapid head growth was defined as crossing upwards through 2 major centile bands (1.33 SD). The UK-WHO standard identified many more infants with heads above the 98th centile compared to the UK1990 reference (UK-WHO 6% to 16% of infants at various ages, UK1990 1% to 4%). Rapid head growth in the first 6 to 9 months was also much more common using the UK-WHO standard (UK-WHO: 14.6% to 15.3%; UK1990: 4.8% to 5.1%). Practitioners should be aware of these findings to avoid unnecessary referrals.
ALSPAC; head circumference; growth charts; macrocephaly; microcephaly; hydrocephalus
Relationships between birthweight and grip strength throughout the lifecourse suggest that early influences on the growth and development of muscle are important for long-term muscle function. However, little is known about parental influences on children’s grip strength. We have explored this in the Southampton Women’s Survey, a prospective general population cohort study from before conception through childhood. Grip strength was measured using a Jamar handgrip dynamometer in the mother at 19 weeks’ gestation and her partner, and in the child at age four years. Pre-pregnancy heights and weights were measured in the mothers; reported weights and measured heights were available for the fathers. Complete data on parents and children were available for 444 trios. In univariate analyses, both parents’ grip strengths were significantly associated with that of the child (r=0.17, p<0.001 for mothers, r=0.15, p=0.002 for fathers). These correlations were similar to that between the grip strength of the mothers and the father (r=0.17, P<0.001). In the multivariate model, after adjustment for child’s height and physical activity, the correlations with the child’s grip strength were attenuated, being 0.10 (P=0.02) and 0.11 (P=0.01) for mothers’ and fathers’ grip strength respectively. The findings show that grip strength of both parents is associated with that of their child, indicating that heritable influences and the shared family environment influence the development of muscle strength. This contributes to our understanding of the role of heritable and environmental factors on early muscle growth and development, which are important for muscle function across the lifecourse.
muscle; grip strength; growth and development; genetic and environmental influences; height
People who were small at birth and had poor infant growth have an increased risk of adult cardiovascular disease, osteoporosis and type 2 diabetes, particularly if their restricted early growth is followed by increased childhood weight gain. These relations extend across the normal range of birth size in a graded manner, so reduced size is not a prerequisite. In addition larger birth size is associated with risks of obesity and type 2 diabetes. The associations appear to reflect developmental plastic responses made by the fetus and infant based on cues about the environment, influenced by maternal characteristics including diet, body composition, stress and exercise levels. These responses involve epigenetic processes which modify the offspring’s phenotype. Vulnerability to ill-health results if the environment in infancy, childhood and later life is mismatched to the phenotype induced in development, informed by the developmental cues. This mismatch may arise through unbalanced diet or body composition of the mother, or change in lifestyle factors between generations. These insights offer new possibilities for early diagnosis and prevention of chronic disease.
Nutrition; fetal growth; metabolic disease; epigenetics
Little is known about whether patterns of growth are associated with altered respiratory and immune development. This study relates prenatal and infant growth patterns to wheeze and atopy at age 3 years
Birth weight and length were measured in 1548 children born at term. Conditional fetal head and abdominal circumference growth velocities were calculated from antenatal ultrasound measurements. Conditional postnatal growth velocities were calculated from infant weight, length and adiposity data. .Measures of size and conditional growth were related to parentally-reported infant and early childhood wheeze and to atopic status at age 3.
Atopy risk increased by 46% per standard deviation (SD) increase in abdominal circumference growth velocity from 11-19 weeks’ gestation but by 20% per SD decrease in abdominal growth velocity from 19-34 weeks (p=0.007 and p=0.011). Atopic wheeze risk increased by 20% per SD decrease in 19-34 week abdominal growth (p=0.046). Non-atopic wheeze risk increased by 10% per SD decrease in 11-19 week head circumference growth. Greater relative infant weight and adiposity gains were associated with both atopic and non-atopic wheeze.
Rapid growth during 11-19 weeks’ gestation followed by growth faltering is associated with atopy, suggesting that influences affecting fetal growth may also alter immune development. A lower early fetal growth trajectory is associated with non-atopic wheeze, possibly reflecting an association with smaller airways. An association between postnatal adiposity gain and wheeze may partly reflect prenatal influences that cause fetal growth to falter but are then followed by postnatal adiposity gain.
asthma; preschool-wheeze; allergic sensitisation; growth; nutrition
The ‘Southampton Initiative for Health’ (SIH) is a training intervention with Sure Start Children’s Centre staff designed to improve the diets and physical activity levels of women of child-bearing age. Training aims to help staff to support women in making changes to their lifestyles by improving three skills: reflection on current practice; asking ‘open discovery’ questions; and goal setting. The impact of the training on staff practice is being assessed. A before and after non-randomised controlled trial is being used to evaluate the effectiveness and cost-effectiveness of the intervention in improving women’s diets and increasing their physical activity levels.
diet; physical activity; reflexive practice; goal setting; self-efficacy; intervention, disadvantage
Studies exploring the relationship between prenatal vitamin D exposure and childhood asthma have yielded conflicting results. Higher vitamin D intake during pregnancy has been shown to lower the risk of childhood wheeze, yet a study of maternal late-pregnancy serum 25-hydroxyvitamin D suggested higher serum concentrations may be associated with increased childhood asthma.
To assess the relationship between mothers’ serum 25-hydroxyvitamin D status and asthma and wheeze phenotypes in their children at age 6 years. Secondly, to explore the relationship between maternal 25-hydroxyvitamin D status and objective measures of childhood atopy and lung function.
Serum 25-hydroxyvitamin D was measured at 34 weeks’ gestation in the mothers of 860 children born at term. Wheeze was classified as either transient or persistent/late using questionnaire data collated from 6, 12, 24 and 36 months and 6 years. At 6 years spirometry was performed and atopic status was determined by skin prick testing, exhaled nitric oxide was measured in 451 and bronchial hyperresponsiveness in 216 children.
There were no significant associations between maternal late-pregnancy 25-hydroxyvitamin D status and either asthma or wheeze at age 6 years. Maternal vitamin D status was not associated with transient or persistent/late wheeze; no significant association was found between persistent/late wheeze when subdivided according to atopic status. No associations were found with skin sensitisation or lung function.
This study provides no evidence that exposure to higher concentrations of 25-hydroxyvitamin D in maternal serum during late pregnancy increases the risk of childhood asthma, wheeze or atopy.
asthma epidemiology; asthma; paediatric asthma
Effective communication is necessary for good relationships between healthcare practitioners and clients. This study examined barriers and facilitators to implementing new communication skills.
One hundred and one Sure Start Children’s Centre staff attended one of 13 follow-up workshops to reflect on the use of new skills following a training course in communication, reflection and problem-solving. Barriers and facilitators were assessed with an adapted Problematic Experiences of Therapy scale (PETS). Staff reported frequency of skill use, and described what made it more difficult or easier to use the skills.
The PETS indicated that staff had confidence in using the skills, but felt there were practical barriers to using them, such as lack of time. Skills were used less often when staff perceived parents not to be engaging with them (rs=−0.42, p<.001), when staff felt less confident to use the skills (rs =−0.37, p<.001), and when there were more practical barriers (rs =−0.37, p<.001). In support of findings from the PETS, content analysis of free text responses suggested that the main barrier was a perceived lack of time to implement new skills. Facilitators included seeing the benefits of using the skills, finding opportunities and having good relationships with parents.
Understanding the range of barriers and facilitators to implementation is essential when developing training to facilitate on-going support and sustain skill use. Special attention should be given to exploring trainees’ perceptions of time, in order to be able to address this significant barrier to skill implementation. Staff training requires a multifaceted approach to address the range of perceived barriers.
barriers; communication; epidemiology; Sure Start; training
Maternal diet in pregnancy has been linked to childhood bone mass, but the mechanisms and nutrients involved are uncertain. Long-chain polyunsaturated fatty acids (LCPUFAs) have been shown to affect bone metabolism, but the relationship between maternal fatty acid status and bone mass in the offspring remains unknown.
We evaluated the association between maternal LCPUFA status in late pregnancy (34 weeks gestation) and bone density in their children at age four years, within 727 mother-child pairs taking part in the Southampton Women’s Survey.
Concentrations of the n-3 LCPUFA component of maternal plasma phosphatidylcholine were positively associated with a number of bone mineral measures at the age of 4 years; these associations persisted after adjustment for maternal body build, walking speed and infant feeding. Relationships were most evident for eicosapentaenoic acid (r=0.09, p=0.02 for whole body areal bone mineral density [aBMD] and r=0.1, p=0.008 for lumbar spine aBMD) and for docosapentaenoic acid (r=0.09, p=0.02 for whole body aBMD and r=0.12, p=0.002 for lumbar spine aBMD).
These findings suggest that variation in early exposure to n-3 and n-6 LCPUFA may have potential consequences for bone development and that the effects appear to persist into early childhood.
Epidemiology; osteoporosis; development; nutrition; bone mass
Little is known about food insecurity in the UK. The aims of this study were to assess the prevalence and factors associated with food insecurity in a UK cohort, and to examine whether the diets, reported health and anthropometry of young food insecure children differed from those of other children.
The Southampton Women’s Survey is a prospective cohort study in which detailed information about the diet, lifestyle and body composition of 3000 women was collected before and during pregnancy. Between 2002-2006, 1618 families were followed up when the child was 3 years old. Food insecurity was determined using the Household Food Security scale. The child’s height and weight were measured; diet was assessed by food frequency questionnaire.
4.6% of the households were food insecure. Food insecurity was more common in families where the mothers were younger, smokers, of lower social class, in receipt of financial benefits, and who had a higher deprivation score (all p<0.05). In comparison with other 3-year-old children, those living in food insecure households were likely to have worse parent-reported health and to have a diet of poorer quality, characterised by greater consumption of white bread, processed meat and chips, and by a lower consumption of vegetables (all p<0.05). They did not differ in height or body mass index.
Our data suggest that there are significant numbers of food insecure families in the UK. The poorer reported health and diets of young food insecure children have important implications for their development and lifelong health.
food insecurity; body composition; dietary quality; children
Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year old children.
We used Sequenom MassARRAY to assess the methylation status of 2 CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument).
Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553+, after taking account of age and sex there was a strong positive association between methylation status and the child’s whole body bone area (r=0.28,p=0.02), bone mineral content (r=0.34,p=0.005) and areal bone mineral density (r=0.34,p=0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass.
Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development.
Epigenetic; methylation; umbilical cord; eNOS; DXA
Statistical analysis of genome-wide microarrays can result in many thousands of identical statistical tests being performed as each probe is tested for an association with a phenotype of interest. If there were no association between any of the probes and the phenotype, the distribution of P values obtained from statistical tests would resemble a Uniform distribution. If a selection of probes were significantly associated with the phenotype we would expect to observe P values for these probes of less than the designated significance level, alpha, resulting in more P values of less than alpha than expected by chance.
In data from a whole genome methylation promoter array we unexpectedly observed P value distributions where there were fewer P values less than alpha than would be expected by chance. Our data suggest that a possible reason for this is a violation of the statistical assumptions required for these tests arising from heteroskedasticity. A simple but statistically sound remedy (a heteroskedasticity–consistent covariance matrix estimator to calculate standard errors of regression coefficients that are robust to heteroskedasticity) rectified this violation and resulted in meaningful P value distributions.
The statistical analysis of ‘omics data requires careful handling, especially in the choice of statistical test. To obtain meaningful results it is essential that the assumptions behind these tests are carefully examined and any violations rectified where possible, or a more appropriate statistical test chosen.
P values; Distributions; Statistical analysis; Statistical assumptions; Whole genome methylation promoter arrays; Epigenome
Objective This study examined longitudinal relationships between maternal red-cell folate status and dietary intakes of vitamins B6, B12 and folate before and during pregnancy and subsequent postpartum depressive symptoms.
Study design and setting Within a cohort study of women aged 20–34 years (the Southampton Women's Survey) dietary data were obtained before pregnancy and at 11 and 34 weeks' gestation. Red-cell folate was measured before pregnancy and at 11 weeks' gestation. We derived relative risks of postpartum depressive symptoms using an Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 13 administered from 6 months to 1 year postpartum.
Results No significant differences were found between those with postpartum depressive symptoms (n = 905) and those without (n = 1951) in relation to red-cell folate concentration or dietary intake of folate, vitamin B12 and vitamin B6, before or during pregnancy. A prior history of mental illness (relative risk (RR) 1.83; 95% confidence interval (CI) 1.53–2.19) was associated with postpartum depressive symptoms, and women who breastfed until 6 months were less likely to experience postpartum depressive symptoms (RR 0.68; 95% CI 0.55–0.84).
Conclusion This study suggests that folate status and dietary folate, B6 and B12 intakes before and during pregnancy are not associated with postpartum depressive symptoms. A history of mental illness, however, was a strong risk factor.
B-vitamin intake; folate status; postpartum depression
Variation in exposure to polyunsaturated fatty acids (PUFAs) might influence the development of atopy, asthma, and wheeze. This study aimed to determine whether differences in PUFA concentrations in maternal plasma phosphatidylcholine are associated with the risk of childhood wheeze or atopy. For 865 term-born children, we measured phosphatidylcholine fatty acid composition in maternal plasma collected at 34 weeks' gestation. Wheezing was classified using questionnaires at 6, 12, 24, and 36 months and 6 years. At age of 6 years, the children underwent skin prick testing, fractional exhaled nitric oxide (FENO) measurement, and spirometry. Maternal n-6 fatty acids and the ratio of n-3 to n-6 fatty acids were not associated with childhood wheeze. However, higher maternal eicosapentaenoic acid, docosahexaenoic acid, and total n-3 fatty acids were associated with reduced risk of non-atopic persistent/late wheeze (RR 0.57, 0.67 and 0.69, resp. P = 0.01, 0.015, and 0.021, resp.). Maternal arachidonic acid was positively associated with FENO (P = 0.024). A higher ratio of linoleic acid to its unsaturated metabolic products was associated with reduced risk of skin sensitisation (RR 0.82, P = 0.013). These associations provide some support for the hypothesis that variation in exposure to n-6 and n-3 fatty acids during pregnancy influences the risk of childhood wheeze and atopy.