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1.
Int J Gynaecol Obstet ; 147(2): 140-146, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31571230

RESUMO

OBJECTIVE: To explore the knowledge of Developmental Origins of Health and Disease (DOHaD) concepts among midwives and obstetricians and to identify barriers and facilitators for clinicians to engage women and their partners before or early in pregnancy on risk factors associated with DOHaD, and thus to embed the concept of DOHaD in routine clinical practice. METHODS: A qualitative study using semi-structured interviews will be conducted in Ghana, India, Pakistan, Brazil, the UK, and USA in collaboration with the International Confederation of Midwives and the International Federation of Obstetricians and Gynecologists. Participants will be contacted via email and telephone interviews will be conducted until data saturation followed by inductive thematic analysis. RESULTS: Findings from this exploratory study will provide new knowledge about the perspectives of midwives and obstetricians on DOHaD and their role in preventing the intergenerational passage of non-communicable disease (NCD) risk and improving preconception care. CONCLUSION: This study will help us understand the current use of DOHaD principles in international maternity care and how this can be improved. Bringing DOHaD to clinical practice will help healthcare practitioners adopt a long-term approach in the prevention of NCDs and childhood obesity and will help women to enter pregnancy in optimum health.

2.
JAMA ; 321(17): 1702-1715, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063572

RESUMO

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, Setting, and Participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures: Gestational weight gain. Main Outcomes and Measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79). Conclusions and Relevance: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.


Assuntos
Índice de Massa Corporal , Ganho de Peso na Gestação , Complicações na Gravidez , Resultado da Gravidez , Adulto , Peso ao Nascer , Cesárea/estatística & dados numéricos , Diabetes Gestacional , Feminino , Humanos , Hipertensão Induzida pela Gravidez , Recém-Nascido , Obesidade , Gravidez , Nascimento Prematuro
3.
Paediatr Perinat Epidemiol ; 33(3): 195-203, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31034663

RESUMO

BACKGROUND: In England, nearly one child in ten lives in overcrowded housing. Crowding is likely to worsen with increasing population size, urbanisation, and the ongoing concerns about housing shortages. Children with behavioural difficulties are at increased risk of mental and physical health problems and poorer employment prospects. OBJECTIVE: To test the association between the level of crowding in the home and behavioural problems in children, and to explore what factors might explain the relationship. METHODS: Mothers of 2576 children from the Southampton Women's Survey population-based mother-offspring cohort were interviewed. Crowding was measured at age 2 years by people per room (PPR) and behavioural problems assessed at age 3 years with the Strengths and Difficulties Questionnaire (SDQ). Both were analysed as continuous measures, and multivariable linear regression models were fitted, adjusting for confounding factors: gender, age, single-parent family, maternal education, receipt of benefits, and social class. Potential mediators were assessed with formal mediation analysis. RESULTS: The characteristics of the sample were broadly representative of the population in England. Median (IQR) SDQ score was 9 (6-12) and PPR was 0.75 (0.6-1). In households that were more crowded, children tended to have more behavioural problems (by 0.20 SDQ points (95% CI 0.08, 0.32) per additional 0.2 PPR, adjusting for confounding factors). This relationship was partially mediated by greater maternal stress, less sleep, and strained parent-child interactions. CONCLUSIONS: Living in a more crowded home was associated with a greater risk of behavioural problems, independent of confounding factors. The findings suggest that improved housing might reduce childhood behavioural problems and that families living in crowded circumstances might benefit from greater support.

4.
BMC Public Health ; 19(1): 316, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30917803

RESUMO

BACKGROUND: In contrast to our knowledge about the number of cancers attributed to smoking, the number of cancers attributed to alcohol is poorly understood by the public. We estimate the increase in absolute risk of cancer (number of cases per 1000) attributed to moderate levels of alcohol, and compare these to the absolute risk of cancer attributed to low levels of smoking, creating a 'cigarette-equivalent of population cancer harm'. METHODS: Alcohol and tobacco attributable fractions were subtracted from lifetime general population risks of developing alcohol- and smoking-related cancers, to estimate the lifetime cancer risk in alcohol-abstaining non-smokers. This was multiplied by the relative risk of drinking ten units of alcohol or smoking ten cigarettes per week, and increasing levels of consumption. RESULTS: One bottle of wine per week is associated with an increased absolute lifetime cancer risk for non-smokers of 1.0% (men) and 1.4% (women). The overall absolute increase in cancer risk for one bottle of wine per week equals that of five (men) or ten cigarettes per week (women). Gender differences result from levels of moderate drinking leading to a 0.8% absolute risk of breast cancer in female non-smokers. CONCLUSIONS: One bottle of wine per week is associated with an increased absolute lifetime risk of alcohol-related cancers in women, driven by breast cancer, equivalent to the increased absolute cancer risk associated with ten cigarettes per week. These findings can help communicate that moderate levels of drinking are an important public health risk for women. The risks for men, equivalent to five cigarettes per week, are also of note.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Fumar Cigarros/efeitos adversos , Neoplasias/epidemiologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias da Mama/epidemiologia , Fumar Cigarros/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Produtos do Tabaco/efeitos adversos , Vinho/efeitos adversos
5.
PLoS Med ; 16(2): e1002744, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30742624

RESUMO

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.


Assuntos
Índice de Massa Corporal , Análise de Dados , Ganho de Peso na Gestação/fisiologia , Obesidade Pediátrica/epidemiologia , Austrália/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , América do Norte/epidemiologia , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Obesidade Pediátrica/diagnóstico , Gravidez , Fatores de Risco
7.
Int J Behav Nutr Phys Act ; 16(1): 23, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30786904

RESUMO

BACKGROUND: Physical activity decreases through childhood, adolescence and into adulthood: parents of young children are particularly inactive, potentially negatively impacting their children's activity levels. This study aimed to determine the association between objectively measured maternal and 6-year-old children's physical activity; explore how this association differed by demographic and temporal factors; and identify change during the transition to school (from age 4-6). METHODS: Data were from the UK Southampton Women's Survey. Physical activity of 530 6-year-olds and their mothers was measured concurrently using accelerometry for ≤7 days. Cross-sectionally, two-level mixed-effects linear regression was used to model the association between maternal-child daily activity behaviour at age 6 [minutes sedentary (SED); in moderate-to-vigorous physical activity (MVPA)]. Interactions with demographic factors and time of the week were tested; how the association differed across the day was also explored. Change in the association between maternal-child physical activity (from age 4-6) was assessed in a subset (n = 170) [outcomes: SED, MVPA and light physical activity (LPA)]. RESULTS: Mother-child daily activity levels were positively associated (SED: ß = 0.23 [0.20, 0.26] minutes/day; MVPA: 0.53 [0.43, 0.64] minutes/day). The association was stronger at weekends (vs. weekdays) (interaction term: SED: ßi = 0.07 [0.02, 0.12]; MVPA: 0.44 [0.24, 0.64]). For SED, the association was stronger for those children with older siblings (vs. none); for MVPA, a stronger association was observed for those who had both younger and older siblings (vs. none) and a weaker relationship existed in spring compared to winter. Longitudinally, the association between mother-child activity levels did not change for SED and LPA. At age 6 (vs. age 4) the association between mother-child MVPA was weaker across the whole day (ßi: - 0.16 [- 0.31, - 0.01]), but remained similar at both ages between 3 and 11 pm. CONCLUSIONS: More active mothers have more active 6-year-olds; this association was similar for boys and girls but differed by time of week, season and by age of siblings at home. Longitudinally, the association weakened for MVPA between 4 and 6 years, likely reflecting the differing activities children engage in during school hours and increased independence. Family-based physical activity remains an important element of children's activity behaviour regardless of age. This could be exploited in interventions to increase physical activity within families.


Assuntos
Comportamento Infantil , Exercício , Mães , Estudantes , Acelerometria , Criança , Pré-Escolar , Estudos Transversais , Feminino , Monitores de Aptidão Física , Humanos , Relações Mãe-Filho , Estudos Prospectivos , Instituições Acadêmicas
8.
Ann Hum Biol ; 46(1): 17-26, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30719940

RESUMO

BACKGROUND: Many statistical methods are available to model longitudinal growth data and relate derived summary measures to later outcomes. AIM: To apply and compare commonly used methods to a realistic scenario including pre- and postnatal data, missing data, and confounders. SUBJECTS AND METHODS: Data were collected from 753 offspring in the Southampton Women's Survey with measurements of bone mineral content (BMC) at age 6 years. Ultrasound measures included crown-rump length (11 weeks' gestation) and femur length (19 and 34 weeks' gestation); postnatally, infant length (birth, 6 and 12 months) and height (2 and 3 years) were measured. A residual growth model, two-stage multilevel linear spline model, joint multilevel linear spline model, SITAR and a growth mixture model were used to relate growth to 6-year BMC. RESULTS: Results from the residual growth, two-stage and joint multilevel linear spline models were most comparable: an increase in length at all ages was positively associated with BMC, the strongest association being with later growth. Both SITAR and the growth mixture model demonstrated that length was positively associated with BMC. CONCLUSIONS: Similarities and differences in results from a variety of analytic strategies need to be understood in the context of each statistical methodology.


Assuntos
Antropometria/métodos , Densidade Óssea , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Biológicos , Modelos Estatísticos , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez
9.
Int J Obes (Lond) ; 43(5): 974-988, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30622309

RESUMO

BACKGROUND: The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, and has a key role in energy balance. We tested the hypothesis that methylation of the SLC6A4 gene predicts adiposity across the life course. METHODS: DNA methylation at 5 CpGs within the SLC6A4 gene identified from a previous methyl binding domain array was measured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the Southampton Women's Survey cohort (n = 680), in peripheral blood from adolescents in the Western Australian Pregnancy Cohort Study (n = 812), and in adipose tissue from lean and obese adults from the UK BIOCLAIMS cohort (n = 81). Real-time PCR was performed to assess whether there were corresponding alterations in gene expression in the adipose tissue. RESULTS: Lower UC methylation of CpG5 was associated with higher total fat mass at 4 years (p = 0.031), total fat mass at 6-7 years (p = 0.0001) and % fat mass at 6-7 years (p = 0.004). Lower UC methylation of CpG5 was also associated with higher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3 years (p = 0.00004) and 6-7 years (p = 0.013). Higher maternal pregnancy weight gain (p = 0.046) and lower parity (p = 0.029) were both associated with lower SLC6A4 CpG5 methylation. In adolescents, lower methylation of CpG5 in peripheral blood was associated with greater concurrent measures of adiposity including BMI (p ≤ 0.001), waist circumference (p = 0.011), subcutaneous fat (p ≤ 0.001) and subscapular, abdominal and suprailiac skinfold thicknesses (p = 0.002, p = 0.008, p = 0.004, respectively). In adipose tissue, methylation of both SLC6A4 CpG5 (p = 0.019) and expression of SLC6A4 (p = 0.008) was lower in obese compared with lean adults. CONCLUSIONS: These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.

10.
Int J Epidemiol ; 48(2): 433-444, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649331

RESUMO

BACKGROUND: Choline status has been positively associated with weight and fat mass in animal and human studies. As evidence examining maternal circulating choline concentrations and offspring body composition in human infants/children is lacking, we investigated this in two cohorts. METHODS: Maternal choline concentrations were measured in the UK Southampton Women's Survey (SWS; serum, n = 985, 11 weeks' gestation) and Singapore Growing Up Towards healthy Outcomes (GUSTO); n = 955, 26-28 weeks' gestation) mother-offspring cohorts. Offspring anthropometry was measured at birth and up to age 5 years. Body fat mass was determined using dual-energy x-ray absorptiometry at birth and age 4 years for SWS; and using air-displacement plethysmography at birth and age 5 years for GUSTO. Linear-regression analyses were performed, adjusting for confounders. RESULTS: In SWS, higher maternal choline concentrations were associated with higher neonatal total body fat mass {ß = 0.60 standard deviation [SD]/5 µmol/L maternal choline [95% confidence interval (CI) 0.04-1.16]} and higher subscapular skinfold thickness [ß = 0.55 mm/5 µmol/L (95% CI, 0.12-1.00)] at birth. In GUSTO, higher maternal choline concentrations were associated with higher neonatal body mass index-for-age z-score [ß = 0.31 SD/5 µmol/L (0.10-0.51)] and higher triceps [ß = 0.38 mm/5 µmol/L (95% CI, 0.11-0.65)] and subscapular skinfold thicknesses [ß = 0.26 mm/5 µmol/L (95% CI, 0.01-0.50)] at birth. No consistent trends were observed between maternal choline and offspring gain in body mass index, skinfold thicknesses, abdominal circumference, weight, length/height and adiposity measures in later infancy and early childhood. CONCLUSION: Our study provides evidence that maternal circulating choline concentrations during pregnancy are positively associated with offspring BMI, skinfold thicknesses and adiposity at birth, but not with growth and adiposity through infancy and early childhood to the age of 5 years.

11.
BMC Med ; 16(1): 201, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30396358

RESUMO

BACKGROUND: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. METHODS: We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape. RESULTS: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications. CONCLUSIONS: Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

12.
BMJ Open ; 8(11): e022062, 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30420345

RESUMO

OBJECTIVES: (1) To identify national policies for England and local policies for Southampton City that are relevant to maternal and child health. (2) To quantify the extent to which these policies meet the international standards for nutrition and physical activity initiatives set out in the WHO Global Action Plan for the Prevention and Control of Non-Communicable Diseases (WHO Action Plan). DESIGN: The policy appraisal process involved three steps: (1) identifying policy documents relevant to maternal and infant health, (2) developing a policy appraisal framework from the WHO Action Plan, and (3) analysing the policies using the framework. SETTING: England and Southampton City. PARTICIPANTS: 57 national and 10 local policies. RESULTS: Across both national and local policies, priority areas supporting public health processes, such as evidence-based practice, were adopted more frequently than the action-oriented areas targeting maternal and child dietary and physical activity behaviours. However, the policy option managing conflicts of interest was rarely considered in the national policies (12%), particularly in white papers or evidence-based guidelines. For the action-oriented priority areas, maternal health policy options were more frequently considered than those related to child health or strengthening health systems. Complementary feeding guidance (9%) and workforce training in empowerment skills (14%) were the least frequent action-oriented policy options adopted among the national policies. The maternal nutrition-focused and workforce development policy options were least frequent among local policies adopted in 10% or fewer. Macroenvironmental policy options tended to have a lower priority than organisational or individual options among national policies (p=0.1) but had higher priority among local policies (p=0.02). CONCLUSIONS: Further action is needed to manage conflicts of interest and adopt policy options that promote a system-wide approach to address non-communicable diseases caused by poor diet and physical inactivity.

13.
J Bone Miner Res ; 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30321476

RESUMO

We have previously demonstrated inverse associations between maternal 25(OH)-vitamin D status and perinatal DNA methylation at the retinoid-X-receptor-alpha (RXRA) locus and between RXRA methylation and offspring bone mass. We therefore used an existing randomised trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial of 1000IU/day cholecalciferol or matched placebo from 14 weeks' gestation until delivery. Umbilical cord (fetal) tissue was collected at birth and frozen at -80° C (n = 453). Pyrosequencing was used to undertake DNA methylation analysis at 10 CpG sites within the RXRA locus (identified previously). T-tests were used to assess differences between treatment groups in methylation at the three most representative CpG sites. Overall, methylation levels were significantly lower in the umbilical cord from offspring of cholecalciferol-supplemented mothers, reaching statistical significance at four CpG sites, represented by CpG5: mean difference in % methylation between the supplemented and placebo groups was -1.98% (95%CI: -3.65 to -0.32, p = 0.02). ENCODE evidence supports functionality of this locus with strong DNase hypersensitivity and enhancer chromatin within biologically relevant cell types including osteoblasts. Enrichment of the enhancer-related H3K4me1 histone mark is also seen in this region, as are binding sites for a range of transcription factors with roles in cell proliferation, response to stress and growth factors. Our findings are consistent with previous observational results and provide new evidence that maternal gestational supplementation with cholecalciferol leads to altered perinatal epigenetic marking, informing mechanistic understanding of early life mechanisms related to maternal vitamin D status, epigenetic marks and bone development. This article is protected by copyright. All rights reserved.

14.
Arterioscler Thromb Vasc Biol ; 38(10): 2528-2537, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30354210

RESUMO

Objective- Childhood body mass index (BMI) has been related to vascular structure and function. However, little is known about the differing contributions of fat and lean mass to this relationship. Our objectives were to relate the fat and lean mass (bone excluded) components of BMI (fat mass index and lean mass index; mass [kg]/height [m]2) to vascular measures in prepubertal children. Approach and Results- In the UK Southampton Women's Survey mother-offspring cohort, 983 children had dual x-ray absorptiometry and vascular measurements at 8 to 9 years. Using linear regression analyses, we found that most vascular measures were related to BMI, but fat and lean mass contributed differently. Systolic blood pressure was positively associated with both fat mass index (ß=0.91 [95% CI, 0.52-1.30] mm Hg) and lean mass index (ß=2.16 [95% CI, 1.47-2.85] mm Hg), whereas pulse rate was positively associated with fat mass index (ß=0.93 [95% CI, 0.48-1.38] b/min) but negatively associated with lean mass index (ß=-1.79 [95% CI, -2.59 to -0.99] b/min). The positive relation between BMI and carotid intima-media thickness was mainly due to a positive association with lean mass index (ß=0.013 [95% CI, 0.008-0.019] mm). Carotid-femoral pulse wave velocity, but not carotid-radial pulse wave velocity, was positively associated with fat mass index (ß=0.06 [95% CI, 0.03-0.09] m/s). For systolic blood pressure, carotid-femoral pulse wave velocity and reactive hyperemia significant interactions indicated that the association with fat mass depended on the amount of lean mass. Conclusions- In prepubertal children, differences in vascular structure and function in relation to BMI probably represent combinations of adverse effects of fat mass, adaptive effects of body size, and relatively protective effects of lean mass.

15.
J Infect Dis ; 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376117

RESUMO

Background: Fucosyltransferase 2 (FUT2) controls the production of digestive and respiratory epithelia of histo-blood group antigens involved in the attachment of pathogens. The aim of our study was to relate FUT2 variants to reported gastrointestinal and respiratory illnesses in infancy. Methods: In the Southampton Women's Survey, FUT2 genetic variants (single-nucleotide polymorphisms [SNPs] rs601338 and rs602662) were genotyped in 1831 infants and related to infant illnesses, after adjustment for sex, breastfeeding duration, and potential confounders. Results: For FUT2 SNP rs601338, the risk ratios for ≥1 bout of diarrhea during ages 6-12 months and ages 12-24 months per additional risk (G) allele were 1.23 (95% confidence interval [CI], 1.08-1.4; P = .002) and 1.41 (95% CI, 1.24-1.61; P = 1.7 × 10-7), respectively; the risk ratio for ≥1 diagnosis of a lower respiratory illness (ie, pneumonia or bronchiolitis) during ages 12-24 months per additional G allele was 2.66 (95% CI, 1.64-4.3; P = .00007). Similar associations were found between rs602662 and gastrointestinal and respiratory illnesses, owing to the high linkage disequilibrium with rs601338 (R2 = 0.92). Longer breastfeeding duration predicted a lower risk of diarrhea, independent of infant FUT2 genotype. Conclusions: We confirmed that FUT2 G alleles are associated with a higher risk of infant gastrointestinal illnesses and identified novel associations with respiratory illnesses. FUT2 locus variants need consideration in future studies of gastrointestinal and respiratory illnesses among infants.

16.
Eur Respir J ; 52(3)2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30209194

RESUMO

The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18-2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31-3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08-2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood.

17.
Arch Dis Child ; 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29954740

RESUMO

OBJECTIVE: There is limited information on the psychosocial impact of growing up with Silver-Russell syndrome (SRS), characterised by slow growth in utero leading to short stature in adulthood. Such information could aid families in making difficult treatment decisions and guide management strategies for health professionals. We aimed to explore the lived experience of people with SRS across the lifespan. DESIGN/SETTING/PATIENTS: In-depth, semi-structured interviews were conducted between January 2015 and October 2016 with a sample of 15 adults (six women) with genetically confirmed SRS from the UK. Qualitative interviews were transcribed and coded to identify similarities and differences: codes were then grouped to form overarching themes. RESULTS: Four themes were identified from participant accounts: (1) appearance-related concerns extending beyond height; (2) strategies to deal with real and perceived threats; (3) women's experiences of pain, disability and feeling older than their years; and (4) feeling overlooked in romantic relationships. These themes show that other factors, beyond short stature, affect patient well-being and indicate a mismatch between patient need and healthcare provision. CONCLUSIONS: Challenges in SRS during childhood and adolescence were central to the psychosocial impact of SRS, and were not limited to height. These challenges, as well as symptoms such as pain and fatigue for women, have not previously been documented. To help individuals with SRS develop strategies to manage psychosocial issues, we recommend clinicians incorporate psychological services as an integral part of multidisciplinary teams managing individuals with SRS during childhood, adolescence and adulthood.

18.
Int J Obes (Lond) ; 42(6): 1202-1210, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29899523

RESUMO

INTRODUCTION: Alkaline phosphatase is implicated in intestinal lipid transport and in the development of obesity. Placental alkaline phosphatase is localised to the microvillous plasma membrane of the placental syncytiotrophoblast at the maternal-fetal interface, but its role is unclear. We investigated the relations of placental alkaline phosphatase activity and mRNA expression with maternal body composition and offspring fat mass in humans. METHODS: Term human placentas from the UK Birthright cohort (n = 52) and the Southampton Women's Survey (SWS) (n = 95) were studied. In the Birthright cohort, alkaline phosphatase activity was measured in placental microvillous plasma membrane vesicles. In the SWS, alkaline phosphatase mRNA was measured using Nanostring. Alkaline phosphatase gene expression was compared to other lipid-related genes. RESULTS: In Birthright samples placental microvillous plasma membrane alkaline phosphatase activity was positively associated with maternal triceps skinfold thickness and BMI (ß = 0.04 (95% CI: 0.01-0.06) and ß = 0.02 (0.00-0.03) µmol/mg protein/min per SD, P = 0.002 and P = 0.05, respectively) after adjusting for potential confounders. In SWS samples placental alkaline phosphatase mRNA expression in term placenta was positively associated with maternal triceps skinfold (ß = 0.24 (0.04, 0.44) SD/SD, P = 0.02), had no association with neonatal %fat mass (ß = 0.01 (-0.20 to 0.21) SD/SD, P = 0.93) and was negatively correlated with %fat mass at ages 4 (ß = -0.28 (-0.52 to -0.04) SD/SD, P = 0.02), 6-7 (ß = -0.25 (-0.49 to -0.02) SD/SD, P = 0.03) years. When compared with placental expression of other genes, alkaline phosphatase expression was positively related to genes including the lysophosphatidylcholine transporter MFSD2A (major facilitator superfamily domain containing 2A, P < 0.001) and negatively related to genes including the fatty acid transport proteins 2 and 3 (P = 0.001, P < 0.001). CONCLUSIONS: Our findings suggest relationships between placental alkaline phosphatase and both maternal and childhood adiposity. The inverse relationship between placental alkaline phosphatase gene expression and childhood %fat mass suggests that placental alkaline phosphatase may help to protect the foetus from the adverse effects of maternal obesity.

19.
Br J Nutr ; 119(12): 1400-1407, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29734952

RESUMO

Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6-7 years in 724 mother-child pairs from the Southampton Women's Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (ß=0·36, P<0·001). DHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (ß=0·46, P<0·001). Children's cognitive function at the age of 4 years was assessed by the Wechsler Preschool and Primary Scale of Intelligence and at the age of 6-7 years by the Wechsler Abbreviated Scale of Intelligence. Executive function at the age of 6-7 years was assessed using elements of the Cambridge Neuropsychological Test Automated Battery. Neither DHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6-7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.

20.
Artigo em Inglês | MEDLINE | ID: mdl-29741284

RESUMO

OBJECTIVE: Osteoarthritis-related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change (RC) index determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RC index as a novel approach to estimating osteoarthritis progression. METHODS: Data from 167 men and 392 women with knee osteoarthritis (diagnosed using the ACR criteria) randomised to the placebo arm of the 3-year Strontium Ranelate Efficacy in Knee Osteoarthritis triAl (SEKOIA) and assessed annually. The RC index was used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error. RESULTS: Between consecutive years, 57 to 69% of participants had an apparent (change less than 0) decrease in JSW, while 31% to 43% of participants had annual changes indicating improvement in JSW. The RC index identified decreases in JSW in only 6.0% between baseline and year 1 and 4.5% between the remaining study years. The apparent increases in JSW were almost eliminated between baseline and year 1, and between years 1 and 2 only 1.3% had a statistically significant increase, dropping to 0.9% between years 2 and 3. CONCLUSION: The RC index provides a method to identify change in JSW, removing many apparent changes that are likely to be due to measurement error. This method appears to be useful for assessing change in JSW in clinical and research settings from radiographs. This article is protected by copyright. All rights reserved.

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