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1.
Nutrients ; 11(11)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717283

RESUMO

The ALPHABET consortium aims to examine the interplays between maternal diet quality, epigenetics and offspring health in seven pregnancy/birth cohorts from five European countries. We aimed to use the Dietary Approaches to Stop Hypertension (DASH) score to assess diet quality, but different versions have been published. To derive a single DASH score allowing cross-country, cross-cohort and cross-period comparison and limiting data heterogeneity within the ALPHABET consortium, we harmonised food frequency questionnaire (FFQ) data collected before and during pregnancy in ≥26,500 women. Although FFQs differed strongly in length and content, we derived a consortium DASH score composed of eight food components by combining the prescriptive original DASH and the DASH described by Fung et al. Statistical issues tied to the nature of the FFQs led us to re-classify two food groups (grains and dairy products). Most DASH food components exhibited pronounced between-cohort variability, including non-full-fat dairy products (median intake ranging from 0.1 to 2.2 servings/day), sugar-sweetened beverages/sweets/added sugars (0.3-1.7 servings/day), fruits (1.1-3.1 servings/day), and vegetables (1.5-3.6 servings/day). We successfully developed a harmonized DASH score adapted to all cohorts being part of the ALPHABET consortium. This methodological work may benefit other research teams in adapting the DASH to their study's specificities.

2.
JAMA Netw Open ; 2(9): e1910915, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31539074

RESUMO

Importance: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. Objective: To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. Design, Setting, and Participants: This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Main Outcomes and Measures: Type 2 diabetes and glycemic traits. Results: This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (ß = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. Conclusions and Relevance: In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.

3.
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
4.
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.

5.
Nutrients ; 11(1)2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30669280

RESUMO

Iron and vitamin D deficiencies are common during pregnancy. Our aim was to identify whether antenatal vitamin D3 supplementation affects iron status (via hepcidin suppression) and/or inflammation. Using a subset of the UK multicenter Maternal Vitamin D Osteoporosis Study (MAVIDOS)-a double-blinded, randomized, placebo-controlled trial (ISRCTN82927713; EudraCT2007-001716-23)-we performed a secondary laboratory analysis. Women with blood samples from early and late pregnancy (vitamin D3 (1000 IU/day from ~14 weeks gestation n = 93; placebo n = 102) who gave birth in the springtime (March⁻May) were selected as we anticipated seeing the greatest treatment group difference in change in 25-hydroxyvitamin D (25OHD) concentration. Outcomes were hepcidin, ferritin, C-reactive protein, and α1-acid glycoprotein concentration in late pregnancy (25OHD concentration was measured previously). By late pregnancy, 25OHD concentration increased by 17 nmol/L in the vitamin D3 group and decreased by 11 nmol/L in the placebo group; hepcidin, ferritin, and inflammatory markers decreased but no treatment group differences were seen. In late pregnancy, positive relationships between 25OHD and hepcidin and 25OHD and ferritin in the placebo group were observed but not in the treatment group (group × 25OHD interaction, p < 0.02). Vitamin D3 supplementation had no effect on hepcidin, ferritin, or inflammatory status suggesting no adjunctive value of vitamin D3 in reducing rates of antenatal iron deficiency.


Assuntos
Anemia Ferropriva , Colecalciferol/uso terapêutico , Ferritinas/sangue , Hepcidinas/sangue , Inflamação , Complicações na Gravidez/sangue , Deficiência de Vitamina D/tratamento farmacológico , Adulto , Anemia Ferropriva/sangue , Anemia Ferropriva/complicações , Proteína C-Reativa/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Inflamação/sangue , Inflamação/complicações , Ferro/sangue , Estado Nutricional , Gravidez , Trimestres da Gravidez , Estações do Ano , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Adulto Jovem
6.
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.

7.
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.

8.
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.

9.
J Nutr ; 148(6): 959-966, 2018 Jun 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.

10.
Lancet ; 391(10132): 1830-1841, 2018 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-29673873

RESUMO

A woman who is healthy at the time of conception is more likely to have a successful pregnancy and a healthy child. We reviewed published evidence and present new data from low-income, middle-income, and high-income countries on the timing and importance of preconception health for subsequent maternal and child health. We describe the extent to which pregnancy is planned, and whether planning is linked to preconception health behaviours. Observational studies show strong links between health before pregnancy and maternal and child health outcomes, with consequences that can extend across generations, but awareness of these links is not widespread. Poor nutrition and obesity are rife among women of reproductive age, and differences between high-income and low-income countries have become less distinct, with typical diets falling far short of nutritional recommendations in both settings and especially among adolescents. Several studies show that micronutrient supplementation starting in pregnancy can correct important maternal nutrient deficiencies, but effects on child health outcomes are disappointing. Other interventions to improve diet during pregnancy have had little effect on maternal and newborn health outcomes. Comparatively few interventions have been made for preconception diet and lifestyle. Improvements in the measurement of pregnancy planning have quantified the degree of pregnancy planning and suggest that it is more common than previously recognised. Planning for pregnancy is associated with a mixed pattern of health behaviours before conception. We propose novel definitions of the preconception period relating to embryo development and actions at individual or population level. A sharper focus on intervention before conception is needed to improve maternal and child health and reduce the growing burden of non-communicable diseases. Alongside continued efforts to reduce smoking, alcohol consumption, and obesity in the population, we call for heightened awareness of preconception health, particularly regarding diet and nutrition. Importantly, health professionals should be alerted to ways of identifying women who are planning a pregnancy.


Assuntos
Comportamentos Relacionados com a Saúde , Estilo de Vida , Estado Nutricional , Cuidado Pré-Concepcional , Complicações na Gravidez/prevenção & controle , Feminino , Dieta Saudável , Humanos , Gravidez
11.
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 , Infecção/epidemiologia , Masculino , Mães , Obesidade/epidemiologia , Gravidez , Prevalência , Fatores de Risco , Ganho de Peso
12.
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
13.
Matern Child Nutr ; 13(4)2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-27896913

RESUMO

Experiences of nausea and/or vomiting in pregnancy (NVP) vary greatly, but the paucity of studies with pre-pregnancy dietary data mean that little is known about the effects of NVP on diet. Using an administered food frequency questionnaire, diet was assessed before pregnancy and at 11 and 34 weeks' gestation in 2270 participants in a UK birth cohort study (Southampton Women's Survey). Experience of NVP in early pregnancy was graded as none, mild, moderate, or severe. Participants reported their level of food consumption as more, the same, or less than before pregnancy. "Prudent" diet scores (derived using principal component analysis) were used to describe participants' diet quality before, in early and late pregnancy. In early pregnancy, 89% of women were nauseous, although most commonly, the NVP experienced was mild (48%) or moderate (30%); 11% had severe NVP. A total of 39% of women reported an increase in their level of food intake in early pregnancy; 34% reported a reduction. Increasing severity of nausea was associated with changes in intake of a range of foods, most notably reduced consumption of vegetables, tea/coffee, rice/pasta, breakfast cereals, beans/pulses and citrus fruits/fruit juices and increased consumption of white bread, and soft drinks. Increasing severity of nausea was also associated with decreasing prudent diet score from before to early pregnancy, such that women with severe nausea had prudent diet scores 0.29 SDs lower than those with no nausea (P < 0.001). However, this was transient as NVP was not related to change in diet quality from before to late pregnancy.


Assuntos
Dieta , Ingestão de Alimentos , Náusea/epidemiologia , Complicações na Gravidez/epidemiologia , Vômito/epidemiologia , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Avaliação Nutricional , Gravidez , Primeiro Trimestre da Gravidez , Prevalência , Análise de Componente Principal
14.
J Clin Endocrinol Metab ; 101(12): 5012-5020, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27788053

RESUMO

CONTEXT: Current approaches to antenatal vitamin D supplementation do not account for interindividual differences in 25-hydroxyvitamin D (25(OH)D) response. OBJECTIVE: We assessed which maternal and environmental characteristics were associated with 25(OH)D after supplementation with cholecalciferol. DESIGN: Within-randomization-group analysis of participants in the Maternal Vitamin D Osteoporosis Study trial of vitamin D supplementation in pregnancy. SETTING: Hospital antenatal clinics. PARTICIPANTS: A total of 829 pregnant women (422 placebo, 407 cholecalciferol). At 14 and 34 weeks of gestation, maternal anthropometry, health, and lifestyle were assessed and 25(OH)D measured. Compliance was determined using pill counts at 19 and 34 weeks. INTERVENTIONS: 1000 IU/d of cholecalciferol or matched placebo from 14 weeks of gestation until delivery. MAIN OUTCOME MEASURE: 25(OH)D at 34 weeks, measured in a single batch (Diasorin Liaison). RESULTS: 25(OH)D at 34 weeks of gestation was higher in the women randomized to vitamin D (mean [SD], 67.7 [21.3] nmol/L) compared with placebo (43.1 [22.5] nmol/L; P < .001). In women randomized to cholecalciferol, higher pregnancy weight gain from 14 to 34 weeks of gestation (kg) (ß = -0.81 [95% confidence interval -1.39, -0.22]), lower compliance with study medication (%) (ß = -0.28 [-0.072, -0.48]), lower early pregnancy 25(OH)D (nmol/L) (ß = 0.28 [0.16, 0.40]), and delivery in the winter vs the summer (ß = -10.5 [-6.4, -14.6]) were independently associated with lower 25(OH)D at 34 weeks of gestation. CONCLUSIONS: Women who gained more weight during pregnancy had lower 25(OH)D in early pregnancy and delivered in winter achieved a lower 25(OH)D in late pregnancy when supplemented with 1000 IU/d cholecalciferol. Future studies should aim to determine appropriate doses to enable consistent repletion of 25(OH)D during pregnancy.


Assuntos
Colecalciferol/farmacologia , Avaliação de Resultados (Cuidados de Saúde) , Gravidez/sangue , Vitamina D/análogos & derivados , Vitaminas/farmacologia , Ganho de Peso , Adulto , Colecalciferol/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Gravidez/efeitos dos fármacos , Trimestres da Gravidez , Estações do Ano , Vitamina D/sangue , Vitaminas/administração & dosagem , Adulto Jovem
15.
Lancet Diabetes Endocrinol ; 4(5): 393-402, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26944421

RESUMO

BACKGROUND: Maternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation. METHODS: The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial that recruited pregnant women from three study sites in the UK (Southampton, Oxford, and Sheffield). Eligible participants were older than 18 years, with a singleton pregnancy, gestation of less than 17 weeks, and a serum 25-hydroxyvitamin D (25[OH]D) concentration of 25-100 nmol/L at 10-17 weeks' gestation. P'articipants were randomly assigned (1:1), in randomly permuted blocks of ten, to either cholecalciferol 1000 IU/day or matched placebo, taken orally, from 14 weeks' gestation (or as soon as possible before 17 weeks' gestation if recruited later) until delivery. Participants and the research team were masked to treatment allocation. The primary outcome was neonatal whole-body BMC, assessed within 2 weeks of birth by dual-energy x-ray absorptiometry (DXA), analysed in all randomly assigned neonates who had a usable DXA scan. Safety outcomes were assessed in all randomly assigned participants. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN 82927713, and the European Clinical Trials Database, EudraCT 2007-001716-23. FINDINGS: Between Oct 10, 2008, and Feb 11, 2014, we randomly assigned 569 pregnant women to placebo and 565 to cholecalciferol 1000 IU/day. 370 (65%) neonates in the placebo group and 367 (65%) neonates in the cholecalciferol group had a usable DXA scan and were analysed for the primary endpoint. Neonatal whole-body BMC of infants born to mothers assigned to cholecalciferol 1000 IU/day did not significantly differ from that of infants born to mothers assigned to placebo (61·6 g [95% CI 60·3-62·8] vs 60·5 g [59·3-61·7], respectively; p=0·21). We noted no significant differences in safety outcomes, apart from a greater proportion of women in the placebo group with severe post-partum haemorrhage than those in the cholecalciferol group (96 [17%] of 569 mothers in the placebo group vs 65 [12%] of 565 mothers in the cholecalciferol group; p=0·01). No adverse events were deemed to be treatment related. INTERPRETATION: Supplementation of women with cholecalciferol 1000 IU/day during pregnancy did not lead to increased offspring whole-body BMC compared with placebo, but did show that 1000 IU of cholecalciferol daily is sufficient to ensure that most pregnant women are vitamin D replete, and it is safe. These findings support current approaches to vitamin D supplementation in pregnancy. Results of the ongoing MAVIDOS childhood follow-up study are awaited. FUNDING: Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Recém-Nascido , Fenômenos Fisiológicos da Nutrição Pré-Natal , Vitamina D/administração & dosagem , Adulto , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Gravidez , Estações do Ano
16.
PLoS One ; 10(12): e0143653, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26657885

RESUMO

INTRODUCTION: Maternal environment and lifestyle factors may modify placental function to match the mother's capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content) on a selection of metabolic and amino acid transporter genes and their associations with fetal growth. METHODS: RNA was extracted from 102 term Southampton Women's Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR. RESULTS: Increased placental LAT2 (p = 0.01), y+LAT2 (p = 0.03), aspartate aminotransferase 2 (p = 0.02) and decreased aspartate aminotransferase 1 (p = 0.04) mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01), ASCT1 (p = 0.03), mitochondrial branched chain aminotransferase (p = 0.02) and glutamine synthetase (p = 0.05) was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05) associated with higher maternal diet quality (prudent dietary pattern) pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05) and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01) associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01). Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001). CONCLUSION: A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking, physical activity and diet raises the possibility that their effects are mediated in part through alterations in placental function. The observed changes in placental gene expression in relation to modifiable maternal factors are important as they could form part of interventions aimed at maintaining a healthy lifestyle for the mother and for optimal fetal development.


Assuntos
Sistemas de Transporte de Aminoácidos/genética , Aminoácidos/metabolismo , Placenta/fisiologia , Adulto , Sistemas de Transporte de Aminoácidos/metabolismo , Aminoácidos/genética , Transporte Biológico , Dieta , Exercício , Feminino , Expressão Gênica , Interação Gene-Ambiente , Humanos , Estilo de Vida , Placenta/metabolismo , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fumar
17.
Am J Clin Nutr ; 102(5): 1081-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26399867

RESUMO

BACKGROUND: The role of maternal 25-hydroxyvitamin D [25(OH)D] in fetal development is uncertain, and findings of observational studies have been inconsistent. Most studies have assessed 25(OH)D only one time during pregnancy, but to our knowledge, the tracking of an individual's 25(OH)D during pregnancy has not been assessed previously. OBJECTIVE: We determined the tracking of serum 25(OH)D from early to late pregnancy and factors that influence this. DESIGN: The Southampton Women's Survey is a prospective mother-offspring birth-cohort study. Lifestyle, diet, and 25(OH)D status were assessed at 11 and 34 wk of gestation. A Fourier transformation was used to model the seasonal variation in 25(OH)D for early and late pregnancy separately, and the difference between the measured and seasonally modeled 25(OH)D was calculated to generate a season-corrected 25(OH)D. Tracking was assessed with the use of the Pearson correlation coefficient, and multivariate linear regression was used to determine factors associated with the change in season-corrected 25(OH)D. RESULTS: A total of 1753 women had 25(OH)D measured in both early and late pregnancy. There was a moderate correlation between season-corrected 25(OH)D measurements at 11 and 34 wk of gestation (r = 0.53, P < 0.0001; n = 1753). Vitamin D supplementation was the strongest predictor of tracking; in comparison with women who never used supplements, the discontinuation of supplementation after 11 wk was associated with a reduction in season-corrected 25(OH)D (ß = -7.3 nmol/L; P < 0.001), whereas the commencement (ß = 12.6 nmol/L; P < 0.001) or continuation (ß = 6.6 nmol/L; P < 0.001) of supplementation was associated with increases in season-corrected 25(OH)D. Higher pregnancy weight gain was associated with a reduction in season-corrected 25(OH)D (ß = -0.4 nmol · L(-1) · kg(-1); P = 0.015), whereas greater physical activity (ß = 0.4 nmol/L per h/wk; P = 0.011) was associated with increases. CONCLUSIONS: There is a moderate tracking of 25(OH)D status through pregnancy; factors such as vitamin D supplementation, weight gain, and physical activity are associated with changes in season-corrected 25(OH)D from early to late gestation. These findings have implications for study designs and analyses and approaches to intervention studies and clinical care.


Assuntos
Suplementos Nutricionais , Fenômenos Fisiológicos da Nutrição Materna , Modelos Biológicos , Estado Nutricional , Complicações na Gravidez/prevenção & controle , Deficiência de Vitamina D/prevenção & controle , Vitamina D/uso terapêutico , 25-Hidroxivitamina D 2/sangue , Adulto , Calcifediol/sangue , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Análise de Fourier , Humanos , Estudos Longitudinais , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Manutenção da Gravidez , Estudos Prospectivos , Risco , Estações do Ano , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Adulto Jovem
18.
Bone ; 75: 105-10, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25703480

RESUMO

BACKGROUND: Studies in childhood suggest that both body composition and early postnatal growth are associated with bone mineral density (BMD). However, little is known of the relationships between longitudinal changes in fat (FM) and lean mass (LM) and bone development in pre-pubertal children. We therefore investigated these associations in a population-based mother-offspring cohort, the Southampton Women's Survey. METHODS: Total FM and LM were assessed at birth and 6-7 years of age by dual-energy x-ray absorptiometry (DXA). At 6-7 years, total cross-sectional area (CSA) and trabecular volumetric BMD (vBMD) at the 4% site (metaphysis) of the tibia was assessed using peripheral quantitative computed tomography [pQCT (Stratec XCT-2000)]. Total CSA, cortical CSA, cortical vBMD and strength-strain index (SSI) were measured at the 38% site (diaphysis). FM, LM and bone parameters were adjusted for age and sex and standardised to create within-cohort z-scores. Change in LM (ΔLM) or FM (ΔFM) was represented by change in z-score from birth to 7 years old and conditioned on the birth measurement. Linear regression was used to explore the associations between ΔLM or ΔFM and standardised pQCT outcomes, before and after mutual adjustment and for linear growth. The ß-coefficient represents SD change in outcome per unit SD change in predictor. RESULTS: DXA at birth, in addition to both DXA and pQCT scans at 6-7 years, were available for 200 children (48.5% male). ΔLM adjusted for ΔFM was positively associated with tibial total CSA at both the 4% (ß=0.57SD/SD, p<0.001) and 38% sites (ß=0.53SD/SD, p<0.001), cortical CSA (ß=0.48SD/SD, p<0.001) and trabecular vBMD (ß=0.30SD/SD, p<0.001), but not with cortical vBMD. These relationships persisted after adjustment for linear growth. In contrast, ΔFM adjusted for ΔLM was only associated with 38% total and cortical CSA, which became non-significant after adjustment for linear growth. CONCLUSION: In this study, gain in childhood LM was positively associated with bone size and trabecular vBMD at 6-7 years of age. In contrast, no relationships between change in FM and bone were observed, suggesting that muscle growth, rather than accrual of fat mass, may be a more important determinant of childhood bone development.


Assuntos
Composição Corporal , Desenvolvimento Ósseo/fisiologia , Tíbia/diagnóstico por imagem , Tíbia/crescimento & desenvolvimento , Absorciometria de Fóton , Tecido Adiposo , Densidade Óssea , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Tomografia Computadorizada por Raios X
19.
Am J Clin Nutr ; 101(2): 368-75, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25646335

RESUMO

BACKGROUND: Early life may be a "critical period" when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects. OBJECTIVE: The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey). DESIGN: Five risk factors were defined: maternal obesity [prepregnant body mass index (BMI; in kg/m(2)) >30], excess gestational weight gain (Institute of Medicine, 2009), smoking during pregnancy, low maternal vitamin D status (<64 nmol/L), and short duration of breastfeeding (none or <1 mo). Obesity outcomes examined when the children were aged 4 and 6 y were BMI, dual-energy X-ray absorptiometry-assessed fat mass, overweight, or obesity (International Obesity Task Force). Data were available for 991 mother-child pairs, with children born between 1998 and 2003. RESULTS: Of the children, 148 (15%) had no early-life risk factors, 330 (33%) had 1, 296 (30%) had 2, 160 (16%) had 3, and 57 (6%) had 4 or 5. At both 4 and 6 y, there were positive graded associations between number of early-life risk factors and each obesity outcome (all P < 0.001). After taking account of confounders, the relative risk of being overweight or obese for children who had 4 or 5 risk factors was 3.99 (95% CI: 1.83, 8.67) at 4 y and 4.65 (95% CI: 2.29, 9.43) at 6 y compared with children who had none (both P < 0.001). CONCLUSIONS: Having a greater number of early-life risk factors was associated with large differences in adiposity and risk of overweight and obesity in later childhood. These findings suggest that early intervention to change these modifiable risk factors could make a significant contribution to the prevention of childhood obesity.


Assuntos
Sobrepeso/epidemiologia , Obesidade Pediátrica/epidemiologia , Absorciometria de Fóton , Adulto , Composição Corporal , Índice de Massa Corporal , Aleitamento Materno , Criança , Pré-Escolar , Feminino , Humanos , Modelos Lineares , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Gravidez , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Vitamina D/administração & dosagem , Vitamina D/sangue , Ganho de Peso
20.
BMJ Open ; 4(7): e005412, 2014 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-24993768

RESUMO

OBJECTIVES: To assess whether changes in measures of fat distribution and body size during early life are associated with blood pressure at 36 months of age. DESIGN: Analysis of data collected from a prospective cohort study. SETTING: Community-based investigation in Southampton, UK. PARTICIPANTS: 761 children with valid blood pressure measurements, born to women participating in the Southampton Women's Survey. PRIMARY AND SECONDARY OUTCOME MEASURES: Anthropometric measurements were collected at 0, 6, 12, 24 and 36 months and conditional changes between the time points calculated. Blood pressure was measured at 36 months. Factors possibly influencing the blood pressure were assessed using linear regression. All independent variables of interest and confounding variables were included in stepwise multiple regression to identify the model that best predicted blood pressure at 36 months. RESULTS: Greater conditional gains in abdominal circumference (AC) between 0-6 and 24-36 months were associated with higher systolic and diastolic blood pressures at 36 months (p<0.001). Subscapular skinfold and height gains were weakly associated with higher blood pressures, while greater weight gains between 0-6, 12-24 and 24-36 months were more strongly associated, but the dominant influences were AC gains, particularly from 0-6 to 24-36 months. Thus one SD score increases in AC between 0-6 and 24-36 months were associated with 1.59 mm Hg (95% CI 0.97 to 2.21) and 1.84 mm Hg (1.24 to 2.46) higher systolic blood pressures, respectively, and 1.04 mm Hg (0.57 to 1.51) and 1.02 mm Hg (0.56, 1.48) higher diastolic pressures, respectively. CONCLUSIONS: Conditional gains in abdominal circumference, particularly within 6 months of birth and in the year preceding measurement, were more positively associated with blood pressure at 36 months than gains in other anthropometric measures. Above-average AC gains in early childhood may contribute to adult hypertension and increased cardiovascular disease risk.


Assuntos
Abdome/anatomia & histologia , Pressão Sanguínea , Ganho de Peso , Pesos e Medidas Corporais , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos
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