RESUMEN
Many epidemiological studies have linked low birthweight to an increased risk of non-communicable diseases (NCDs) in later life, with epigenetic proceseses suggested as an underlying mechanism. Here, we sought to identify neonatal methylation changes associated with birthweight, at the individual CpG and genomic regional level, and whether the birthweight-associated methylation signatures were associated with specific maternal factors. Using the Illumina Human Methylation EPIC array, we assessed DNA methylation in the cord blood of 557 and 483 infants from the UK Pregnancies Better Eating and Activity Trial and Southampton Women's Survey, respectively. Adjusting for gestational age and other covariates, an epigenome-wide association study identified 2911 (FDR≤0.05) and 236 (Bonferroni corrected p ≤ 6.45×10-8) differentially methylated CpGs (dmCpGs), and 1230 differentially methylated regions (DMRs) (Stouffer ≤0.05) associated with birthweight. The top birthweight-associated dmCpG was located within the Homeobox Telomere-Binding Protein 1 (HMBOX1) gene with a 195 g (95%CI: -241, -149 g) decrease in birthweight per 10% increase in methylation, while the top DMR was located within the promoter of corticotropin-releasing hormone-binding protein (CRHBP). Furthermore, the birthweight-related dmCpGs were enriched for dmCpGs previously associated with gestational hypertension/pre-eclampsia (14.51%, p = 1.37×10-255), maternal smoking (7.71%, p = 1.50 x 10-57) and maternal plasma folate levels during pregnancy (0.33%, p = 0.029). The identification of birthweight-associated methylation markers, particularly those connected to specific pregnancy complications and exposures, may provide insights into the developmental pathways that affect birthweight and suggest surrogate markers to identify adverse prenatal exposures for stratifying for individuals at risk of later NCDs.
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Hipertensión , Preeclampsia , Peso al Nacer/genética , Metilación de ADN , Femenino , Sangre Fetal/metabolismo , Ácido Fólico , Estudio de Asociación del Genoma Completo , Proteínas de Homeodominio/genética , Humanos , Lactante , Recién Nacido , Preeclampsia/epidemiología , Preeclampsia/genética , Preeclampsia/metabolismo , Embarazo , Fumar/efectos adversosRESUMEN
AIM: To investigate the associations between indices of bone health in childhood and corresponding parental measures. METHODS: The Southampton Women's Survey characterised 12,583 non-pregnant women aged 20-34 years; 3158 subsequently had singleton live births. In a subset, dual-energy X-ray absorptiometry (DXA) measurements of bone area (BA), bone mineral content (BMC) and areal bone mineral density (aBMD) lumbar spine and total hip were obtained in the parent/offspring (aged 8-9 years) trios. Another subset of children (aged 6-7 years), and their parents, had peripheral quantitative computed tomography (pQCT; 4% and 38% tibia) measures. Using multivariable linear regression we examined relationships between mother/father and offspring, adjusting for parental age, habitual walking speed and education; offspring age and sex; and the corresponding bone measure in the other parent (ß-coefficients (95%CI) unit/unit for each bone measure). RESULTS: Data were available for 260 trios with DXA and 99 with pQCT. There were positive associations for BA, BMC and aBMD between either parent and offspring. Mother-child associations were of greater magnitude than father-child; for example, mother-child aBMD (ß = 0.26 g·cm-2/g·cm-2 (0.21,0.32)) and father-child aBMD (ß = 0.16 g·cm-2/g·cm-2 (0.11,0.21)), P-difference in ß = 0.007. In the subset with pQCT there was a positive association for mother-offspring 4% tibial total area (ß = 0.33 mm2/mm2 (0.17,0.48)), but little evidence of a father-offspring association (ß = -0.06 mm2/mm2 (-0.17,0.06)). In contrast offspring 38% cortical density was more strongly associated with this measure in fathers (ß = 0.48 mg·cm-3/mg·cm-3 (0.15,0.82)) than mothers (ß = 0.27 mg·cm-3/mg·cm-3 (-0.03,0.56)). In general mother-father differences were attenuated by adjustment for height. CONCLUSIONS: Whilst offspring bone measures are independently associated with those of either parent, the magnitude of the association is often greater for maternal than paternal relationships. These findings are consistent with an in utero influence on offspring growth but might also reflect genetic and/or epigenetic parent of origin effects. SUMMARY: In an established parent-offspring cohort, associations between parent and offspring bone indices were generally greater in magnitude for mother-offspring than father-offspring relationships.
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Densidad Ósea , Huesos , Absorciometría de Fotón , Huesos/diagnóstico por imagen , Femenino , Humanos , Vértebras Lumbares , Relaciones Padres-HijoRESUMEN
OBJECTIVES: To investigate associations between placental volume (PV) at 11 weeks' gestation and offspring bone outcomes at birth, 6 years and 8 years. METHODS: 3D ultrasound scanning was used to assess 11 week PV in a subset (n = 236) of the Southampton Women's Survey (a prospective mother-offspring cohort). Maternal anthropometric measures and lifestyle information were obtained pre-pregnancy and at 11 weeks' gestation. Offspring dual-energy x-ray absorptiometry scanning was performed within 2 weeks postnatally and at 6 and 8 years. Linear regression was used to assess associations between PV and bone outcomes, adjusting for offspring age at DXA and sex, and maternal age, height, smoking status, walking speed and triceps skinfold thickness. ß are SD change in bone outcome per SD change in PV. RESULTS: In adjusted models, 11 week PV was positively associated with bone area (BA) at all time points, with evidence of persisting associations with increasing childhood age (birth: n = 80, ß = 0.23 [95%CI = 0.03, 0.42], 6 years: n = 110, ß = 0.17 [-0.01, 0.36], 8 years: n = 85, ß = 0.13 [-0.09, 0.36]). Similar associations between 11 week PV and bone mineral content (BMC) were observed. Associations with size-corrected bone mineral content were weaker at birth but strengthened in later childhood (birth: n = 78, ß = 0.07 [-0.21, 0.35], 6 years: n = 107, ß = 0.13 [-0.08, 0.34], 8 years: n = 71, ß = 0.19 [-0.05, 0.43]). CONCLUSIONS: 11 week PV is associated with DXA bone measures at birth, with evidence of persisting associations into later childhood. Further work is required to elucidate the contributions of placental morphology and function to gestational influences on skeletal development.
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Huesos/diagnóstico por imagen , Placenta/diagnóstico por imagen , Absorciometría de Fotón , Adulto , Densidad Ósea/fisiología , Niño , Femenino , Estudios de Seguimiento , Encuestas Epidemiológicas , Humanos , Tamaño de los Órganos/fisiología , Embarazo , Primer Trimestre del Embarazo , Ultrasonografía PrenatalRESUMEN
In lifecourse studies that encompass the adolescent period, the assessment of pubertal status is important, but can be challenging. We aimed to identify current methods for pubertal assessment and assess their appropriateness for population-based research by combining a review of the literature with the views of experts in the field. We searched bibliographic databases, extracted data and assessed study quality to inform a workshop with 21 experts. Acceptability of different approaches was explored with a panel of ten adolescents. We screened 11,935 abstracts, assessed 157 articles and summarised results from 38 articles. Combining these with the opinions of experts, self-assessment was found to be a practical method for use in studies where agreement with the gold standard of clinical assessment by physical examination to within one Tanner stage was acceptable. Serial measures of height and foot size accurately indicated timing of the pubertal growth spurt and age at peak height velocity, and were seen as feasible within longitudinal studies. Hormonal and radiological methods did not offer a practical means of assessing pubertal status. Assessment of voice maturation was promising, but needed validation. Young people thought that self-assessment, foot size and voice assessments were acceptable, and preferred an assessor of the same sex for clinical assessment. This review thus informs researchers working in lifecourse and adolescent health, and identifies future directions in order to improve validity of the methods.
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Desarrollo del Adolescente/fisiología , Testimonio de Experto , Pubertad Tardía/diagnóstico , Pubertad Precoz/diagnóstico , Pubertad/fisiología , Adolescente , Salud del Adolescente , Autoevaluación Diagnóstica , Humanos , Pubertad/psicología , Pubertad Tardía/fisiopatología , Pubertad Precoz/fisiopatologíaRESUMEN
OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2 = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.
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Peso al Nacer , Ejercicio Físico , Macrosomía Fetal/epidemiología , Recién Nacido Pequeño para la Edad Gestacional , Tejido Adiposo , Adulto , Estudios de Cohortes , Diabetes Gestacional/epidemiología , Metabolismo Energético , Femenino , Humanos , Recién Nacido , Modelos Lineales , Obesidad/epidemiología , Sobrepeso/epidemiología , Embarazo , Complicaciones del Embarazo/epidemiología , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Factores Protectores , Factores de Riesgo , Adulto JovenRESUMEN
We compared bone outcomes in children with breech and cephalic presentation at delivery. Neonatal whole-body bone mineral content (BMC) and area were lower in children with breech presentation. At 4 years, no differences in whole-body or spine measures were found, but hip BMC and area were lower after breech presentation. INTRODUCTION: Breech presentation is associated with altered joint shape and hip dysplasias, but effects on bone mineral content (BMC), area (BA) and density (BMD) are unknown. METHODS: In the prospective Southampton Women's Survey mother-offspring cohort, whole-body bone outcomes were measured using dual-energy X-ray absorptiometry (DXA) in 1430 offspring, as neonates (mean age 6 days, n = 965, 39 with a breech presentation at birth) and/or at age 4.1 years (n = 999, 39 breech). Hip and spine bone outcomes were also measured at age 4 years. RESULTS: Neonates with breech presentation had 4.2 g lower whole-body BMC (95% CI -7.4 to - 0.9 g, P = 0.012) and 5.9 cm2 lower BA (- 10.8 to - 1.0 cm2, P = 0.019), but BMD was similar between groups (mean difference - 0.007, - 0.016 to 0.002 g/cm2, P = 0.146) adjusting for sex, maternal smoking, gestational diabetes, mode of delivery, social class, parity, ethnicity, age at scan, birthweight, gestational age and crown-heel length. There were no associations between breech presentation and whole-body outcomes at age 4 years, but, in similarly adjusted models, regional DXA (not available in infants) showed that breech presentation was associated with lower hip BMC (- 0.51, - 0.98 to - 0.04 g, P = 0.034) and BA (- 0.67, - 1.28 to - 0.07 cm2, P = 0.03) but not with BMD (- 0.009, - 0.029 to 0.012 g, P = 0.408), or spine outcomes. CONCLUSIONS: These results suggest that breech presentation is associated with lower neonatal whole-body BMC and BA, which may relate to altered prenatal loading in babies occupying a breech position; these differences did not persist into later childhood. Modest differences in 4-year hip BMC and BA require further investigation.
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Densidad Ósea/fisiología , Presentación de Nalgas , Osteoporosis/etiología , Absorciometría de Fotón/métodos , Adulto , Femenino , Estudios de Seguimiento , Encuestas Epidemiológicas , Articulación de la Cadera/patología , Articulación de la Cadera/fisiopatología , Humanos , Recién Nacido , Osteoporosis/fisiopatología , Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND/OBJECTIVES: Pregnancy triggers a physiological change in weight status. Postpartum weight retention in the childbearing years can substantially alter a woman's weight gain trajectory, with several potential contributing factors identified. Most research has relied on women's recall of pre-pregnancy weight during pregnancy or later, and not considered risk factors in combination. Using measured pre-pregnancy weight, this study aimed to examine the associations of maternal postpartum weight retention with parity, pre-pregnancy BMI, excessive gestational weight gain (GWG), maternal serum vitamin D concentration and dietary Glycaemic Index in early and late pregnancy, and breastfeeding duration, including analysis of the combined impact of potentially modifiable risk factors. SUBJECTS/METHODS: Prospective cohort study of 12 583 non-pregnant women aged 20-34 years in Southampton (UK) who were assessed prior to pregnancy, with those who subsequently became pregnant followed up in early and late gestation, and after delivery (n=2559 in the final sample). Linear regression models examined potential predictors of weight retention in adjusted individual and multivariate analyses, and as a risk factor score. RESULTS: Compared with pre-pregnancy weight, 73% of women retained some weight at 6 months postpartum (mean (s.d.): 3.5 (6.2) kg). In the adjusted multivariate model, women who were primiparous, had a lower pre-pregnancy BMI, excessive GWG, a lower early pregnancy vitamin D concentration and breastfed for <6 months had greater weight retention 6 months postpartum (P<0.05 for all variables). For each additional modifiable risk factor (excessive GWG, low vitamin D concentration in early pregnancy and short breastfeeding duration; scale 0-3), women retained an additional 2.49 kg (95% CI: 2.16, 2.82; P<0.001). CONCLUSIONS: Having a greater number of modifiable risk factors was associated with greater weight retention 6 months postpartum. Initiatives supporting women to target these risk factors in the years prior to, during and after pregnancy could impact on their weight gain trajectory and later risk of adverse weight-related outcomes.
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Mantenimiento del Peso Corporal/fisiología , Sobrepeso/prevención & control , Periodo Posparto/fisiología , Complicaciones del Embarazo/prevención & control , Aumento de Peso/fisiología , Adulto , Índice de Masa Corporal , Inglaterra/epidemiología , Femenino , Índice Glucémico/fisiología , Humanos , Sobrepeso/sangre , Sobrepeso/epidemiología , Paridad/fisiología , Atención Preconceptiva , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/epidemiología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Vitamina D/sangre , Adulto JovenRESUMEN
BACKGROUND: Perinatal maternal stress and low mood have been linked to offspring atopic eczema. OBJECTIVES: To examine the relation of maternal stress/mood with atopic eczema in the offspring, focusing particularly on stress/psychological distress preconception. METHODS: At recruitment in the UK Southampton Women's Survey, preconception maternal reports of perceived stress in daily living and the effect of stress on health were recorded; in a subsample, psychological distress was assessed (12-item General Health Questionnaire). Infants were followed up at ages 6 (n = 2956) and 12 (n = 2872) months and atopic eczema ascertained (based on UK Working Party Criteria for the Definition of Atopic Dermatitis). At 6 months post-partum, mothers were asked if they had experienced symptoms of low mood since childbirth and completed the Edinburgh Postnatal Depression Scale. RESULTS: Preconception perceived stress affecting health [OR 1.21 (95% CI 1.08-1.35), P = 0.001] and stress in daily living [OR 1.16 (1.03-1.30), P = 0.014] were associated with an increased risk of offspring atopic eczema at age 12 months but not at 6 months, robust to adjustment for potentially confounding variables. Findings were similar for maternal psychological distress preconception. Low maternal mood between delivery and 6 months post-partum was associated with an increased risk of infantile atopic eczema at age 12 months, but no significant association between post-natal mood and atopic eczema was seen after taking account of preconception stress. CONCLUSION AND CLINICAL RELEVANCE: Our data provide novel evidence linking maternal stress at preconception to atopic eczema risk, supporting a developmental contribution to the aetiology of atopic eczema and pointing to potentially modifiable influences.
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Dermatitis Atópica/epidemiología , Madres/psicología , Efectos Tardíos de la Exposición Prenatal , Estrés Psicológico/complicaciones , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Embarazo , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Evidence that atopic eczema partly originates in utero is increasing, with some studies linking the risk of developing the condition with aspects of maternal diet during pregnancy. Nicotinamide, a naturally occurring nutrient that is maintained through the dietary intakes of vitamin B3 and tryptophan, has been used in the treatment of some skin conditions including atopic eczema. OBJECTIVE: To examine the relation of maternal serum concentrations of nicotinamide and related tryptophan metabolites to the risk of atopic eczema in the offspring. METHODS: Within the UK Southampton Women Survey, infantile atopic eczema at ages 6 and 12 months was ascertained (modified UK Working Party Criteria for the Definition of Atopic Dermatitis). Maternal serum levels of kynurenine, kynurenic acid, anthranilic acid, tryptophan, nicotinamide and N1-methylnicotinamide were measured in late pregnancy by mass spectrometry (n = 497) and related to the odds ratio of infantile atopic eczema. RESULTS: Maternal nicotinamide and related metabolite concentrations were not associated with offspring atopic eczema at age 6 months. Higher concentrations of nicotinamide and anthranilic acid were, however, associated with a lower risk of eczema at age 12 months (odds ratios 0.69, 95% CI 0.53-0.91/SD change, P = 0.007 and 0.63, 0.48-0.83, P = 0.001, respectively). The associations were robust to adjustment for potentially confounding variables. CONCLUSION AND CLINICAL RELEVANCE: This is the first study linking maternal serum concentrations of nicotinamide and related metabolites to the risk of atopic eczema in the offspring. The findings point to potentially modifiable maternal influences on this complex and highly prevalent condition.
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Dermatitis Atópica/epidemiología , Dermatitis Atópica/etiología , Exposición Materna , Niacinamida/sangre , Efectos Tardíos de la Exposición Prenatal , Adulto , Factores de Edad , Biomarcadores , Comorbilidad , Femenino , Humanos , Lactante , Quinurenina/metabolismo , Masculino , Exposición Materna/efectos adversos , Redes y Vías Metabólicas , Niacinamida/análogos & derivados , Oportunidad Relativa , Embarazo , Pronóstico , Riesgo , Factores de RiesgoRESUMEN
This study aimed to determine whether age at introduction of solid foods was associated with feeding difficulties at 3 years of age. The present study was carried out using data from the Southampton Women's Survey (SWS). Women enrolled in the SWS who subsequently became pregnant were followed-up during pregnancy and postpartum, and the offspring have been studied through childhood. Maternal socio-demographic and anthropometric data and child anthropometric and feeding data were collected through interviews and self-administered questionnaires. When the children were 3 years of age, mothers/carers rated six potential child feeding difficulty questions on a four-point Likert scale, including one general question and five specific feeding difficulty questions. Age at introduction of solids as a predictor of feeding difficulties was examined in 2389 mother-child pairs, adjusting for child (age last breast fed, sex, gestation) and maternal characteristics (parity, pre-pregnancy BMI, age, education, employment, parenting difficulties, diet quality). The majority of mothers/carers (61 %) reported some feeding difficulties (general feeding difficulty question) at 3 years of age, specifically with their child eating enough food (61 %), eating the right food (66 %) and being choosy with food (74 %). Children who were introduced to solids ≥6 months had a lower risk of feeding difficulties (RR 0·73; 95 % CI 0·59, 0·91, P=0·004) than children who were introduced to solids between 4 and 6 months. No other significant associations were found. There were few associations between feeding difficulties in relation to age at introduction of solid foods. However, general feeding difficulties were less common among infants introduced to solid foods ≥6 months of age.
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Factores de Edad , Ingestión de Alimentos , Conducta Alimentaria , Alimentos Infantiles , Fenómenos Fisiológicos Nutricionales del Lactante , Preescolar , Dieta/métodos , Femenino , Humanos , Lactante , Masculino , Madres , Encuestas y Cuestionarios , Reino UnidoRESUMEN
INTRODUCTION: Placental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression. METHODS: Southampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth. RESULTS: Fetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002-0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference. DISCUSSION: FTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Desarrollo Fetal/genética , Peso al Nacer/genética , Cefalometría , Estudios Transversales , Femenino , Feto/metabolismo , Predisposición Genética a la Enfermedad , Edad Gestacional , Humanos , Recién Nacido , Masculino , Obesidad/genética , Polimorfismo de Nucleótido Simple , Embarazo , Factores de Riesgo , Reino UnidoRESUMEN
BACKGROUND: Indian babies are characterised by the 'thin-fat phenotype' which comprises a 'muscle-thin but adipose' body composition compared with European babies. This body phenotype is of concern because it is associated with an increased risk of diabetes and cardiovascular disease. We examined whether the 'thin-fat phenotype' persists through early childhood, comparing Indian children with white Caucasians in the UK at birth, infancy and childhood, using comparable measurement protocols. METHODS: We used data from two cohorts, the Pune Maternal Nutrition Study (N=631) and the Southampton Women's Survey (N=2643). Measurements of weight, head circumference, mid-upper arm circumference, height, triceps and subscapular skinfold thickness were compared at birth, 1, 2, 3 and 6â years of age. SD scores were generated for the Pune children, using the Southampton children as a reference. Generalised estimating equations were used to examine the changes in SD scores across the children's ages. RESULTS: The Indian children were smaller at birth in all body measurements than the Southampton children and became relatively even smaller from birth to 2â years, before 'catching up' to some extent at 3â years, and more so by 6â years. The deficit for both skinfolds was markedly less than for other measurements at all ages; triceps skinfold showed the least difference between the two cohorts at birth, and subscapular skinfold at all ages after birth. CONCLUSIONS: The 'thin-fat phenotype' previously found in Indian newborns, remains through infancy and early childhood. Despite being shorter and lighter than UK children, Indian children are relatively adipose.
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Composición Corporal/genética , Tamaño Corporal/genética , Grosor de los Pliegues Cutáneos , Adulto , Lactancia Materna/estadística & datos numéricos , Niño , Preescolar , Inglaterra , Femenino , Humanos , India , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Edad Materna , Madres/estadística & datos numéricos , Fenotipo , Adulto JovenRESUMEN
BACKGROUND: Poor diet quality in early childhood is inconsistently linked to obesity risk. Understanding may be limited by the use of cross-sectional data and the use of body mass index (BMI) to define adiposity in childhood. OBJECTIVE: The objective of this study is to examine the effects of continued exposure to diets of varying quality across early childhood in relation to adiposity at 6 years. METHODS: One thousand and eighteen children from a prospective UK birth cohort were studied. Diet was assessed using food frequency questionnaires when the children were aged 6 and 12 months, and 3 and 6 years; diet quality was determined according to scores for a principal component analysis-defined dietary pattern at each age (characterized by frequent consumption of fruits, vegetables and fish). At each age, children were allocated a value of 0/1/2 according to third of the distribution (bottom/middle/top) their diet quality score was in; values were summed to calculate an overall diet quality index (DQI) for early childhood (range 0-8). Obesity outcomes considered at 6 years were dual-energy X-ray absorptiometry-assessed fat mass and BMI. RESULTS: One hundred and seven (11%) children had a DQI=0, indicating a consistently low diet quality, 339 (33%) had a DQI=1-3, 378 (37%) had a DQI=4-6 and 194 (19%) had a DQI=7-8. There was a strong association between lower DQI and higher fat mass z-score at 6 years that was robust to adjustment for confounders (fat mass s.d. per 1-unit DQI increase: ß=-0.05 (95% confidence interval (CI): -0.09, -0.01), P=0.01). In comparison with children who had the highest diet quality (DQI=7-8), this amounted to a difference in fat mass of 14% (95% CI: 2%, 28%) at 6 years for children with the poorest diets (DQI=0). In contrast, no independent associations were observed between DQI and BMI. CONCLUSIONS: Continued exposure to diets of low quality across early childhood is linked to adiposity at the age of 6 years.
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Adiposidad , Dieta/normas , Conducta Alimentaria , Obesidad Infantil/epidemiología , Absorciometría de Fotón , Adulto , Actitud Frente a la Salud , Índice de Masa Corporal , Fenómenos Fisiológicos Nutricionales Infantiles , Preescolar , Registros de Dieta , Ingestión de Energía , Metabolismo Energético , Inglaterra/epidemiología , Femenino , Preferencias Alimentarias , Frutas , Encuestas Epidemiológicas , Humanos , Lactante , Recién Nacido , Masculino , Evaluación Nutricional , Política Nutricional , Necesidades Nutricionales , Obesidad Infantil/etiología , Obesidad Infantil/prevención & control , Embarazo , Estudios Prospectivos , Factores Socioeconómicos , VerdurasRESUMEN
Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms of body composition and bone structure. Several amino acid transporter genes have vitamin D response elements in their promoters suggesting the possible linkage of these two mechanisms. We aimed to establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels relate to expression of placental amino acid transporters. RNA was extracted from 102 placental samples collected in the Southampton Women's Survey, and gene expression was analysed using quantitative real-time PCR. Gene expression data were normalised to the geometric mean of three housekeeping genes, and related to maternal factors and childhood body composition. Maternal serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal 25(OH)D and VDBP levels were positively associated with placental expression of specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP concentrations were correlated with the expression of specific placental amino acid transporters, and thus may be involved in the regulation of amino acid transfer to the fetus. The positive correlation of VDBP levels and placental transporter expression suggests that delivery of vitamin D to the placenta may be important. This exploratory study identifies placental amino acid transporters which may be altered in response to modifiable maternal factors and provides a basis for further studies.
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Aminoácidos/metabolismo , Placenta/metabolismo , Proteína de Unión a Vitamina D/fisiología , Vitamina D/fisiología , Adulto , Sistemas de Transporte de Aminoácidos/genética , Transporte Biológico , Composición Corporal , Estudios de Cohortes , Femenino , Expresión Génica/fisiología , Edad Gestacional , Encuestas Epidemiológicas , Humanos , Recién Nacido , Masculino , Intercambio Materno-Fetal , Placenta/química , Embarazo , ARN Mensajero/análisis , Reino Unido , Vitamina D/análogos & derivados , Vitamina D/sangre , Proteína de Unión a Vitamina D/sangre , Salud de la Mujer , Adulto JovenRESUMEN
Various environmental factors have been associated with the timing of eruption of primary dentition, but the evidence to date comes from small studies with limited information on potential risk factors. We aimed to investigate associations between tooth emergence patterns and pre-conception, pregnancy and postnatal influences. Dentition patterns were recorded at ages 1 and 2 years in 2915 children born to women in the Southampton Women's Survey from whom information had been collected on maternal factors before conception and during pregnancy. In mutually adjusted regression models we found that: children were more dentally advanced at ages 1 and 2 years if their mothers had smoked during pregnancy or they were longer at birth; mothers of children whose dental development was advanced at age 2 years tended to have poorer socioeconomic circumstances, and to have reported a slower walking speed pre-pregnancy; and children of mothers of Asian ethnicity had later tooth development than those of white mothers. The findings add to the evidence of environmental impacts on the timing of the eruption of primary dentition in indicating that maternal smoking during pregnancy, socio-economic status and physical activity (assessed by reported walking speed) may influence the child's primary dentition. Early life factors, including size at birth are also associated with dentition patterns, as is maternal ethnicity.
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Efectos Tardíos de la Exposición Prenatal , Diente Primario , Adulto , Desarrollo Infantil , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Embarazo , Fumar , Factores Socioeconómicos , CaminataRESUMEN
CONTEXT: Maternal diet during pregnancy has been linked to offspring adiposity, but it is unclear whether maternal polyunsaturated fatty acid (PUFA) status during pregnancy affects offspring body composition. OBJECTIVE: We investigated the associations between maternal plasma n-3 and n-6 PUFA status at 34 wk gestation and offspring body composition. DESIGN AND SETTING: A prospective United Kingdom population-based mother-offspring cohort, the Southampton Women's Survey (SWS), was studied. PARTICIPANTS: A total of 12,583 nonpregnant women were recruited into the SWS, among whom 1987 delivered a baby before December 31, 2003; 293 mother-child pairs had complete measurements of maternal plasma PUFA concentrations in late pregnancy and offspring body composition at both ages 4 and 6 yr. MAIN OUTCOMES MEASURED: We measured offspring body composition by dual-energy x-ray absorptiometry, yielding fat mass, lean mass, percentage fat mass, and percentage lean mass. Results are presented as ß-coefficients for standardized variables, therefore reflecting the sd change of the outcome for every 1 sd of the predictor. RESULTS: After adjustment for maternal factors and child factors including height and duration of breast-feeding, maternal plasma n-6 PUFA concentration positively predicted offspring fat mass at 4 yr (ß = 0.14 SD/SD; P = 0.01) and 6 yr (ß = 0.11 SD/SD; P = 0.04), but there was no association with offspring lean mass at either age (ß = 0.005 SD/SD, P = 0.89; and ß = 0.008 SD/SD, P = 0.81, respectively). Maternal plasma n-3 PUFA concentration was not associated with offspring fat mass at 4 yr (ß = 0.057 SD/SD; P = 0.34) or 6 yr (ß = 0.069 SD/SD; P = 0.21). Maternal plasma n-3 PUFA status was positively associated with offspring lean mass on univariate analysis (4 yr, ß = 0.11, P = 0.06; 6 yr, ß = 0.14; P = 0.02); however, this was confounded by a positive association with offspring height. CONCLUSIONS: This observational study suggests that maternal n-6 PUFA status during pregnancy might influence offspring adiposity in childhood.
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Composición Corporal , Desarrollo Infantil , Ácidos Grasos Insaturados/sangre , Tercer Trimestre del Embarazo/sangre , Efectos Tardíos de la Exposición Prenatal/sangre , Adulto , Composición Corporal/efectos de los fármacos , Composición Corporal/fisiología , Niño , Desarrollo Infantil/efectos de los fármacos , Desarrollo Infantil/fisiología , Preescolar , Estudios de Cohortes , Ácidos Grasos Insaturados/farmacología , Femenino , Humanos , Recién Nacido , Masculino , Madres , Embarazo/sangre , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Fenómenos Fisiologicos de la Nutrición Prenatal/efectos de los fármacos , Adulto JovenRESUMEN
OBJECTIVES: In this study we investigate the relationships between placental size and neonatal bone mass and body composition, in a population-based cohort. STUDY DESIGN: 914 mother-neonate pairs were included. Placental dimensions were measured via ultrasound at 19 weeks gestation. Dual X-ray absorptiometry (DXA) was performed on the neonates within the first two weeks of life. RESULTS: We observed positive relationships between placental volume at 19 weeks, and neonatal bone area (BA; r = 0.26, p < 0.001), bone mineral content (BMC; r = 0.25, p < 0.001) and bone mineral density (BMD; r = 0.10, p = 0.001). Thus placental volume accounted for 6.25% and 1.2% of the variation in neonatal BMC and BMD respectively at birth. These associations remained after adjustment for maternal factors previously shown to be associated with neonatal bone mineral accrual (maternal height, smoking, walking speed in late pregnancy, serum 25(OH) vitamin D and triceps skinfold thickness). CONCLUSIONS: We found that placental volume at 19 weeks gestation was positively associated with neonatal bone size and mineral content. These relationships appeared independent of those maternal factors known to be associated with neonatal bone mass, consistent with notion that such maternal influences might act through modulation of aspects of placental function, e.g. utero-placental blood flow or maternal nutrient concentrations, rather than placental size itself. Low placental volume early in pregnancy may be a marker of a reduced postnatal skeletal size and increased risk of later fracture.
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Osteogénesis , Placenta/anatomía & histología , Placentación , Adulto , Densidad Ósea , Calcificación Fisiológica , Estudios de Cohortes , Inglaterra , Femenino , Retardo del Crecimiento Fetal/etiología , Encuestas Epidemiológicas , Humanos , Recién Nacido , Estudios Longitudinales , Masculino , Tamaño de los Órganos , Placenta/diagnóstico por imagen , Insuficiencia Placentaria/fisiopatología , Embarazo , Segundo Trimestre del Embarazo , Estudios Prospectivos , Ultrasonografía PrenatalRESUMEN
Maternal thinness leads to metabolic challenges in the offspring, but it is unclear whether reduced maternal fat mass or muscle mass drives these metabolic changes. Recently, it has been shown that low maternal muscle mass--as measured by arm muscle area (AMA)--is associated with depressed nutrient transport to the fetus. To determine the role of maternal muscle mass on placental function, we analyzed the gene expression profiles of 30 human placentas over the range of AMA (25.2-90.8 cm(2)) from uncomplicated term pregnancies from the Southampton Women's Survey cohort. Eighteen percent of the â¼60 genes that were highly expressed in less muscular women were related to immune system processes and the interferon-γ (IFNG) signaling pathway in particular. Those transcripts related to the IFNG pathway included IRF1, IFI27, IFI30, and GBP6. Placentas from women with low muscularity are, perhaps, more sensitive to the effects of inflammatory cytokines than those from more muscular women.
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Músculo Esquelético/anatomía & histología , Placenta/anatomía & histología , Placenta/inmunología , Delgadez/inmunología , Transcriptoma , Brazo , Estudios de Cohortes , Femenino , Humanos , Inmunidad/genética , Factor 1 Regulador del Interferón/genética , Factor 1 Regulador del Interferón/inmunología , Interferón gamma/genética , Interferón gamma/inmunología , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Tamaño de los Órganos , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/genética , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/inmunología , Embarazo , Transducción de Señal/genética , Transducción de Señal/inmunología , Delgadez/genéticaRESUMEN
UNLABELLED: In a free-living cohort of 4-year old children, mean daily time in moderate-vigorous physical activity and daily calcium intake at 3 years, were positively related to hip bone size and density. Relationships between physical activity and bone indices were stronger when calcium intake was above compared with below median (966 mg/day). INTRODUCTION: We examined the cross-sectional relationships between childhood physical activity, dietary calcium intake and bone size and density. METHODS: Children aged 4 years were recruited from the Southampton Women's Survey. They underwent measurement of bone mass by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart, Cambridge Neurotechnology Ltd, Cambridge, UK) for seven continuous days. RESULTS: Four hundred twenty-two children (212 boys) participated. In a cross-sectional analysis, after adjusting for gender, daily mean time(minutes per day) spent in moderate to very vigorous activity (MVPA) was positively related to hip BA (R(2) = 3%, p < 0.001), BMC (R(2) = 4%, p < 0.001), aBMD (R (2) = 3%, p = 0.001) and estimated vBMD (R(2) = 2%, p = 0.01), but not height (r (s) = 0.04, p = 0.42) or weight (r(s) = 0.01, p = 0.76). Mean daily calcium intake (assessed at 3 years old) positively predicted bone indices in those with a calcium intake below the median (966 mg/day), but there was a much attenuated relationship in those above this. These associations persisted after inclusion of total energy, protein and phosphorus in multivariate models. The relationships between MVPA and bone indices were stronger in children with calcium intakes above the median. Thus, for aBMD, the variance explained by MVPA when daily calcium intake was below the median was 2% (p = 0.1) and above median was 6% (p = 0.001). CONCLUSIONS: These results support the notion that adequate calcium intake may be required for optimal action of physical activity on bone development and that improving levels of physical activity and calcium intake in childhood may help to optimise accrual of bone mass.
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Densidad Ósea/fisiología , Calcio de la Dieta/administración & dosificación , Actividad Motora/fisiología , Absorciometría de Fotón/métodos , Adulto , Densidad Ósea/efectos de los fármacos , Calcio de la Dieta/farmacología , Preescolar , Estudios Transversales , Femenino , Articulación de la Cadera/anatomía & histología , Articulación de la Cadera/fisiología , Humanos , Estilo de Vida , Masculino , Factores Sexuales , Factores de Tiempo , Adulto JovenRESUMEN
Recent studies have shown that obesity is associated with an increased risk of fracture in both adults and children. It has been suggested that, despite greater bone size, obese individuals may have reduced true volumetric density; however this is difficult to assess using two dimensional techniques such as DXA. We evaluated the relationship between fat mass, and bone size and density, in a population cohort of children in whom DXA and pQCT measurements had been acquired. We recruited 530 children at 6 years old from the Southampton Women's Survey. The children underwent measurement of bone mass at the whole body, lumbar spine and hip, together with body composition, by DXA (Hologic Discovery, Hologic Inc., Bedford, MA, USA). In addition 132 of these children underwent pQCT measurements at the tibia (Stratec XCT2000, Stratec Biomedical Systems, Birkenfeld, Germany). Significant positive associations were observed between total fat mass and both bone area (BA) and bone mineral content (BMC) at the whole body minus head, lumbar spine and hip sites (all p<0.0001). When true volumetric density was assessed using pQCT data from the tibia, fat mass (adjusted for lean mass) was negatively associated with both trabecular and cortical density (ß=-14.6 mg/mm(3) per sd, p=0.003; ß=-7.7 mg/mm(3) per sd, p=0.02 respectively). These results suggest that fat mass is negatively associated with volumetric bone density at 6 years old, independent of lean mass, despite positive associations with bone size.