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1.
J Med Genet ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054688

RESUMO

BACKGROUND: Silver-Russell syndrome is an imprinting disorder that restricts growth, resulting in short adult stature that may be ameliorated by treatment. Approximately 50% of patients have loss of methylation of the imprinting control region (H19/IGF2:IG-DMR) on 11p15.5 and 5%-10% have maternal uniparental disomy of chromosome 7. Most published research focuses on the childhood phenotype. Our aim was to describe the phenotypic characteristics of older patients with SRS. METHODS: A retrospective cohort of 33 individuals with a confirmed molecular diagnosis of SRS aged 13 years or above were carefully phenotyped. RESULTS: The median age of the cohort was 29.6 years; 60.6% had a height SD score (SDS) ≤-2 SDS despite 70% having received growth hormone treatment. Relative macrocephaly, feeding difficulties and a facial appearance typical of children with SRS were no longer discriminatory diagnostic features. In those aged ≥18 years, impaired glucose tolerance in 25%, hypertension in 33% and hypercholesterolaemia in 52% were noted. While 9/33 accessed special education support, university degrees were completed in 40.0% (>21 years). There was no significant correlation between quality of life and height SDS. 9/25 were parents and none of the 17 offsprings had SRS. CONCLUSION: Historical treatment regimens for SRS were not sufficient for normal adult growth and further research to optimise treatment is justified. Clinical childhood diagnostic scoring systems are not applicable to patients presenting in adulthood and SRS diagnosis requires molecular confirmation. Metabolic ill-health warrants further investigation but SRS is compatible with a normal quality of life including normal fertility in many cases.

2.
Nutrients ; 11(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835868

RESUMO

Compared with omnivorous mothers, vegetarian mothers have lower intakes of some nutrients required for neurological development. However, there is a lack of information about the impact of vegetarianism during pregnancy on subsequent cognitive function in children. The aim of this study was to investigate whether vegetarianism during pregnancy is associated with altered maternal nutritional status and with cognitive function in children at six to seven years of age. Women aged 20-34 years participating in a prospective observational study who provided dietary data and blood samples in early pregnancy (11 weeks; 78 vegetarians and 2144 omnivores) or late pregnancy (34 weeks; 91 vegetarians and 2552 omnivores). Compared with omnivorous women, vegetarian women had lower blood concentrations of arachidonic acid, docosahexaenoic acid, and cobalamin in early and late pregnancy. Vegetarianism in pregnancy was linked to higher maternal educational attainment, longer breastfeeding duration, lower incidence of smoking during pregnancy and a tendency towards higher IQ in the mothers. Concentrations of some nutrients required for neurodevelopment were lower in maternal blood during gestation; however, after controlling for confounders consuming a vegetarian diet during pregnancy was not associated with poorer neurocognitive development of the children in this study.

3.
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.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Tocologia/métodos , Obstetrícia/métodos , Cuidado Pré-Concepcional/métodos , Brasil , Feminino , Gana , Humanos , Índia , Tocologia/educação , Obstetrícia/educação , Paquistão , Gravidez , Pesquisa Qualitativa , Melhoria de Qualidade
4.
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
5.
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
6.
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.

7.
Int J Obes (Lond) ; 43(5): 974-988, 2019 05.
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.

8.
J Bone Miner Res ; 34(2): 231-240, 2019 02.
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. In this study, we used an existing randomized 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 multicenter, double-blind, randomized, placebo-controlled trial of 1000 IU/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 (Encyclopedia of DNA Elements) evidence supports the 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. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

9.
J Infect Dis ; 219(5): 836-843, 2019 02 15.
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.


Assuntos
Diarreia/genética , Fucosiltransferases/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Infecções Respiratórias/genética , Diarreia/epidemiologia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Infecções Respiratórias/epidemiologia
10.
Clin Epidemiol ; 10: 1851-1864, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588116

RESUMO

Background: Infants with atopic eczema have an increased risk of impaired growth, but the origin of this impairment is unclear. The aim of this study was to examine fetal and infant growth in relation to infantile atopic eczema. Methods: Within the UK Southampton Women's Survey, 1,759 infants with known maternal menstrual data had anthropometric measurements at 11, 19, and 34 weeks' gestation, birth, and ages 6 and 12 months, enabling derivation of growth velocity SD scores. Infantile atopic eczema at ages 6 and/or 12 months was ascertained using modified UK Working Party diagnostic criteria. Results: Expressed per SD increase, higher femur length and abdominal circumference at 34 weeks' gestation were associated with decreased risks of atopic eczema (eczema OR/SD increase 0.81 [95% CI 0.69-0.96], P=0.017 and 0.78 [95% CI 0.65-0.93], P=0.006, respectively), while every SD increase in head to abdominal circumference ratio (indicating disproportionate growth) was associated with an increase in risk of atopic eczema (1.37 [1.15-1.63], P=0.001). Lower velocities of linear growth from 11 weeks' gestation to birth and birth to age 6 months were associated with atopic eczema (atopic eczema OR/SD increase 0.80 [0.65-0.98], P=0.034 and 0.8 [1 0.66-1.00], P=0.051, respectively). Infants with atopic eczema at age 12 months had a larger head circumference in early gestation and faltering of abdominal growth velocity from 19 to 34 weeks' gestation (atopic eczema OR/SD increase 0.67 [0.51-0.88], P=0.003). Conclusion: Infants with atopic eczema demonstrate altered patterns of fetal growth, including faltering of linear growth in utero, prior to the clinical onset of atopic eczema. These findings suggest growth falters prior to the start of clinical atopic eczema and its treatment.

11.
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.


Assuntos
Tecido Adiposo/fisiologia , Vasos Sanguíneos/fisiologia , Composição Corporal , Hemodinâmica , Músculo Esquelético/fisiologia , Rigidez Vascular , Absorciometria de Fóton , Tecido Adiposo/diagnóstico por imagem , Adiposidade , Fatores Etários , Pressão Sanguínea , Vasos Sanguíneos/diagnóstico por imagem , Índice de Massa Corporal , Espessura Intima-Media Carotídea , Criança , Feminino , Frequência Cardíaca , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Estudos Prospectivos , Análise de Onda de Pulso
12.
Int J Obes (Lond) ; 42(6): 1202-1210, 2018 06.
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.


Assuntos
Fosfatase Alcalina/metabolismo , Isoenzimas/metabolismo , Obesidade/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Proteínas Supressoras de Tumor/metabolismo , Adulto , Transporte Biológico , Composição Corporal , Desenvolvimento Infantil , Estudos de Coortes , Feminino , Proteínas Ligadas por GPI/metabolismo , Humanos , Recém-Nascido , Obesidade/fisiopatologia , Gravidez , Nascimento a Termo
13.
Br J Nutr ; 119(12): 1400-1407, 2018 06.
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.


Assuntos
Ácido Araquidônico/sangue , Cognição/fisiologia , Ácidos Docosa-Hexaenoicos/sangue , Adulto , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Estudos de Coortes , Inglaterra , Feminino , Humanos , Masculino , Troca Materno-Fetal/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estudos Prospectivos , Escalas de Wechsler
14.
J Nutr ; 148(6): 959-966, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29767745

RESUMO

Background: Adverse effects of severe maternal iodine deficiency in pregnancy on fetal brain development are well-established, but the effects of milder deficiency are uncertain. Most studies examine iodine status in pregnancy; less is known about iodine nutrition before conception. Objective: We examined relations between maternal preconception iodine status and offspring cognitive function, within a prospective mother-offspring cohort. Methods: Maternal iodine status was assessed through the use of the ratio of iodine:creatinine concentrations (I/Cr) in spot urine samples [median (IQR) period before conception 3.3 y (2.2-4.7 y)]. Childhood cognitive function was assessed at age 6-7 y. Full-scale IQ was assessed via the Wechsler Abbreviated Scale of Intelligence, and executive function through the use of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses (n = 654 mother-child dyads) were adjusted for potential confounders including maternal intelligence, education, and breastfeeding duration. Results: The median (IQR) urinary iodine concentration was 108.4 µg/L (62.2-167.8 µg/L) and the I/Cr ratio 114 µg/g (76-164 µg/g). The preconception I/Cr ratio was positively associated with child IQ, before and after adjustment for potential confounding influences [ß = 0.13 (95% CI: 0.04, 0.21)/SD, P = 0.003]. 8.9% of women had a preconception urinary I/Cr ratio <50 µg/g; compared with those with an I/Cr ratio ≥150 µg/g, the IQ of their offspring was 0.49 (95% CI: 0.79, 0.18) SD lower. There were no associations with the executive function outcomes assessed via CANTAB, before or after adjustment for confounders. Conclusion: The positive association between iodine status before conception and child IQ provides some support for demonstrated links between low maternal iodine status in pregnancy and poorer cognitive function reported in other studies. However, given the negative effects on school performance previously observed in children born to iodine-deficient mothers, the lack of associations with measures of executive function in the present study was unexpected. Further data are needed to establish the public health importance of low preconception iodine status.


Assuntos
Cognição , Iodo/urina , Adulto , Criança , Pré-Escolar , Creatinina/urina , Função Executiva , Feminino , Humanos , Testes Neuropsicológicos , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Estudos Prospectivos , Adulto Jovem
15.
BMJ Open ; 8(3): e019490, 2018 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-29661913

RESUMO

OBJECTIVE: Premenstrual syndrome (PMS) is a very common disorder worldwide which carries an important economic burden. We conducted a systematic review and a meta-analysis to assess the role of alcohol in the occurrence of PMS. METHODS: We searched MEDLINE, EMBASE, the five regional bibliographic databases of the WHO, the Proceedings database and the Open Access Thesis and Dissertations (OATD) from inception to May 2017. We also reviewed the references of every article retrieved and established personal contact with researchers to trace further publications or reports. We did not include any language limitations. Studies were included if: (1) they presented original data from cohort, case-control or cross-sectional studies, (2) PMS was clearly defined as the outcome of interest, (3) one of the exposure factors was alcohol consumption, (4) they provided estimates of odds ratios, relative risks, or any other effect measure and their confidence intervals, or enough data to calculate them. RESULTS: We identified 39 studies of which 19 were eligible. Intake of alcohol was associated with a moderate increase in the risk of PMS (OR=1.45, 95% CI: 1.17 to 1.79). Heavy drinking yielded a larger increase in the risk than any drinking (OR=1.79, 95% CI: 1.39 to 2.32). DISCUSSION: Our results suggest that alcohol intake presents a moderate association with PMS risk. Future studies should avoid cross-sectional designs and focus on determining whether there is a threshold of alcohol intake under which the harmful effect on PMS is non-existent.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos Relacionados ao Uso de Álcool/complicações , Síndrome Pré-Menstrual/etiologia , Feminino , Humanos , Fatores de Risco
16.
Hum Mol Genet ; 27(4): 742-756, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29309628

RESUMO

Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.


Assuntos
Peso ao Nascer/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Actinas/genética , Alelos , Peso ao Nascer/fisiologia , Citocromo P-450 CYP3A/genética , Proteínas de Ligação a DNA/genética , Feminino , Variação Genética/genética , Genótipo , Idade Gestacional , Proteína HMGA2/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Canal de Potássio Kv1.3/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas/genética , Receptor MT2 de Melatonina/genética , Transativadores/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética
17.
Pediatr Pulmonol ; 52(10): 1291-1299, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28816002

RESUMO

BACKGROUND: Maternal obesity is increasingly prevalent in many westernized countries. Many studies report associations between maternal obesity and childhood wheeze or asthma but few have considered maternal obesity in relation to respiratory infections or symptoms other than wheeze during infancy. This study assesses the relationship between maternal BMI and reported wheeze, cough and respiratory infections during the first year of life. METHODS: In 2799 mother-child pairs, we examined the relations between maternal pre-pregnancy BMI and pregnancy weight gain and reported offspring wheeze, prolonged cough, lower respiratory tract infection, croup, and ear infection before age 1 year, along with reported diarrhea or vomiting. Maternally reported paternal BMI was included in the models as a proxy for unmeasured confounding by shared familial factors. RESULTS: Higher maternal BMI was associated with increased risks of offspring wheeze, prolonged cough and lower respiratory tract infection (relative risks (95%CI) per 5 kg/m2 1.09 (1.05-1.13), 1.09 (1.03-1.14), and 1.13 (1.07-1.20), respectively). These associations remained after adjusting for maternally reported paternal BMI. No associations were found with croup, ear infection, or diarrhea or vomiting. Pregnancy weight gain was not associated with any of the offspring symptoms or illnesses. DISCUSSION: Higher maternal BMI is associated with increased risk of wheeze, cough, and maternally reported lower respiratory tract infection in infancy. These associations were independent of maternally reported paternal BMI. These observations might be explained by intrauterine effects of maternal obesity upon respiratory or immune development.


Assuntos
Índice de Massa Corporal , Sons Respiratórios , Infecções Respiratórias/epidemiologia , Adulto , Tosse/epidemiologia , Pai , Feminino , Humanos , Lactente , Masculino , Mães , Obesidade/epidemiologia , Gravidez , Prevalência , Fatores de Risco , Ganho de Peso
18.
J Clin Endocrinol Metab ; 102(8): 2941-2949, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28575224

RESUMO

Context: Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. Objective: To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation. Design: Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation. Setting: Hospital antenatal clinics. Participants: In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped. Interventions: 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery. Main Outcome Measure: 25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [ß represents the change in 25(OH)D per additional common allele]. Results: Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [ß = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (ß = -5.2 nmol/L; 95% CI, -8.2 to -2.2 nmol/L; P = 0.001) and rs2282679 (GC) (ß = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not. Conclusions: Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity.


Assuntos
Colecalciferol/uso terapêutico , Deficiência de Vitamina D/prevenção & controle , Vitaminas/uso terapêutico , Adulto , Alelos , Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Genótipo , Humanos , Modelos Lineares , Análise Multivariada , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Polimorfismo de Nucleotídeo Único , Gravidez , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Proteína de Ligação a Vitamina D/genética , Vitamina D3 24-Hidroxilase/genética , Adulto Jovem
20.
EBioMedicine ; 19: 60-72, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28473239

RESUMO

Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth tissues associated with child's adiposity. We identified a novel association between the level of CpG methylation at birth within the promoter of the long non-coding RNA ANRIL (encoded at CDKN2A) and childhood adiposity at age 6-years. An association between ANRIL methylation and adiposity was also observed in three additional populations; in birth tissues from ethnically diverse neonates, in peripheral blood from adolescents, and in adipose tissue from adults. Additionally, CpG methylation was associated with ANRIL expression in vivo, and CpG mutagenesis in vitro inhibited ANRIL promoter activity. Furthermore, CpG methylation enhanced binding to an Estrogen Response Element within the ANRIL promoter. Our findings demonstrate that perinatal methylation at loci relevant to gene function may be a robust marker of later adiposity, providing substantial support for epigenetic processes in mediating long-term consequences of early life environment on human health.


Assuntos
Adiposidade/genética , Inibidor de Quinase Dependente de Ciclina p18/genética , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Adolescente , Adulto , Idoso , Biomarcadores , Linhagem Celular Tumoral , Criança , Ilhas de CpG , Inibidor p16 de Quinase Dependente de Ciclina , Metilação de DNA , Epigênese Genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Adulto Jovem
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