RESUMEN
Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.
Asunto(s)
Densidad Ósea/genética , Estudio de Asociación del Genoma Completo , Adolescente , Factores de Edad , Animales , Niño , Preescolar , Sitios Genéticos , Humanos , Lactante , Recién Nacido , Ratones Noqueados , Polimorfismo de Nucleótido Simple/genética , Carácter Cuantitativo Heredable , Análisis de RegresiónRESUMEN
Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of â¼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n â¼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: ß = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.
Asunto(s)
Densidad Ósea/genética , Proteínas Portadoras/genética , Factores de Intercambio de Guanina Nucleótido/genética , Proteínas Wnt/genética , Adulto , Desarrollo Óseo , Huesos/fisiología , Niño , Estudios de Cohortes , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Estudios Longitudinales , Extremidad Inferior/crecimiento & desarrollo , Extremidad Inferior/fisiología , Masculino , Osteoporosis/epidemiología , Polimorfismo de Nucleótido Simple , Embarazo , Estudios Prospectivos , Cráneo/crecimiento & desarrollo , Cráneo/fisiología , Extremidad Superior/crecimiento & desarrollo , Extremidad Superior/fisiología , Adulto JovenRESUMEN
Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait.
Asunto(s)
Densidad Ósea/genética , Grupos Raciales/genética , Adulto , Alelos , Pueblo Asiatico/genética , Evolución Biológica , Población Negra/genética , Niño , Evolución Molecular , Femenino , Estudios de Asociación Genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Osteoporosis/genética , Polimorfismo de Nucleótido Simple , Selección Genética , Población Blanca/genéticaRESUMEN
FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
Asunto(s)
Proteínas en la Dieta/administración & dosificación , Ingestión de Energía/genética , Obesidad/etnología , Obesidad/genética , Polimorfismo de Nucleótido Simple , Proteínas/genética , Adulto , Negro o Afroamericano , Anciano , Alelos , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Pueblo Asiatico , Índice de Masa Corporal , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Obesidad/patología , Población BlancaRESUMEN
Breast-feeding has been associated with later bone health, but results from previous studies are inconsistent. We examined the associations of breast-feeding patterns and timing of introduction of solids with bone mass at the age of 6 years in a prospective cohort study among 4919 children. We collected information about duration and exclusiveness of breast-feeding and timing of introduction of any solids with postnatal questionnaires. A total body dual-energy X-ray absorptiometry scan was performed at 6 years of age, and bone mineral density (BMD), bone mineral content (BMC), area-adjusted BMC (aBMC) and bone area (BA) were analysed. Compared with children who were ever breast-fed, those never breast-fed had lower BMD (-4·62 mg/cm2; 95 % CI -8·28, -0·97), BMC (-8·08 g; 95 % CI -12·45, -3·71) and BA (-7·03 cm2; 95 % CI -12·55, -1·52) at 6 years of age. Among all breast-fed children, those who were breast-fed non-exclusively in the first 4 months had higher BMD (2·91 mg/cm2; 95 % CI 0·41, 5·41) and aBMC (3·97 g; 95 % CI 1·30, 6·64) and lower BA (-4·45 cm2; 95 % CI -8·28, -0·61) compared with children breast-fed exclusively for at least 4 months. Compared with introduction of solids between 4 and 5 months, introduction <4 months was associated with higher BMD and aBMC, whereas introduction between 5 and 6 months was associated with lower aBMC and higher BA. Additional adjustment for infant vitamin D supplementation did not change the results. In conclusion, results from the present study suggest that ever breast-feeding compared with never breast-feeding is associated with higher bone mass in 6-year-old children, but exclusive breast-feeding for 4 months or longer was not positively associated with bone outcomes.
Asunto(s)
Enfermedades Óseas Metabólicas/prevención & control , Lactancia Materna , Métodos de Alimentación , Alimentos Infantiles , Trastornos de la Nutrición del Lactante/prevención & control , Fenómenos Fisiológicos Nutricionales del Lactante , Osteogénesis , Densidad Ósea , Enfermedades Óseas Metabólicas/etiología , Niño , Desarrollo Infantil , Trastornos de la Nutrición del Niño/prevención & control , Efecto de Cohortes , Estudios de Cohortes , Métodos de Alimentación/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Trastornos de la Nutrición del Lactante/etiología , Trastornos de la Nutrición del Lactante/fisiopatología , Recién Nacido , Masculino , Países Bajos , Estudios ProspectivosRESUMEN
Maternal vitamin D status during pregnancy has been associated with infant birth and postnatal growth outcomes, but reported findings have been inconsistent, especially in relation to postnatal growth and adiposity outcomes. In a mother-offspring cohort in Singapore, maternal plasma vitamin D was measured between 26 and 28 weeks of gestation, and anthropometric measurements were obtained from singleton offspring during the first 2 years of life with 3-month follow-up intervals to examine birth, growth and adiposity outcomes. Associations were analysed using multivariable linear regression. Of a total of 910 mothers, 13·2 % were vitamin D deficient (<50 nmol/l) and 26·5 % were insufficient (50-75 nmol/l). After adjustment for potential confounders and multiple testing, no statistically significant associations were observed between maternal vitamin D status and any of the birth outcomes - small for gestational age (OR 1·00; 95 % CI 0·56, 1·79) and pre-term birth (OR 1·16; 95 % CI 0·64, 2·11) - growth outcomes - weight-for-age z-scores, length-for-age z-scores, circumferences of the head, abdomen and mid-arm at birth or postnatally - and adiposity outcomes - BMI, and skinfold thickness (triceps, biceps and subscapular) at birth or postnatally. Maternal vitamin D status in pregnancy did not influence infant birth outcomes, postnatal growth and adiposity outcomes in this cohort, perhaps due to the low prevalence (1·6 % of the cohort) of severe maternal vitamin D deficiency (defined as of <30·0 nmol/l) in our population.
Asunto(s)
Trastornos de la Nutrición del Lactante/etiología , Complicaciones del Embarazo/etiología , Segundo Trimestre del Embarazo/sangre , Deficiencia de Vitamina D/complicaciones , Vitamina D/sangre , Adiposidad , Antropometría , Pueblo Asiatico , Peso al Nacer , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Lactante , Trastornos de la Nutrición del Lactante/sangre , Recién Nacido de Bajo Peso/crecimiento & desarrollo , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Masculino , Fenómenos Fisiologicos Nutricionales Maternos , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/etnología , Resultado del Embarazo , Nacimiento Prematuro/etiología , Singapur , Deficiencia de Vitamina D/sangreRESUMEN
To identify genetic loci influencing bone accrual, we performed a genome-wide association scan for total-body bone mineral density (TB-BMD) variation in 2,660 children of different ethnicities. We discovered variants in 7q31.31 associated with BMD measurements, with the lowest P = 4.1 × 10(-11) observed for rs917727 with minor allele frequency of 0.37. We sought replication for all SNPs located ± 500 kb from rs917727 in 11,052 additional individuals from five independent studies including children and adults, together with de novo genotyping of rs3801387 (in perfect linkage disequilibrium (LD) with rs917727) in 1,014 mothers of children from the discovery cohort. The top signal mapping in the surroundings of WNT16 was replicated across studies with a meta-analysis P = 2.6 × 10(-31) and an effect size explaining between 0.6%-1.8% of TB-BMD variance. Conditional analyses on this signal revealed a secondary signal for total body BMD (P = 1.42 × 10(-10)) for rs4609139 and mapping to C7orf58. We also examined the genomic region for association with skull BMD to test if the associations were independent of skeletal loading. We identified two signals influencing skull BMD variation, including rs917727 (P = 1.9 × 10(-16)) and rs7801723 (P = 8.9 × 10(-28)), also mapping to C7orf58 (r(2) = 0.50 with rs4609139). Wnt16 knockout (KO) mice with reduced total body BMD and gene expression profiles in human bone biopsies support a role of C7orf58 and WNT16 on the BMD phenotypes observed at the human population level. In summary, we detected two independent signals influencing total body and skull BMD variation in children and adults, thus demonstrating the presence of allelic heterogeneity at the WNT16 locus. One of the skull BMD signals mapping to C7orf58 is mostly driven by children, suggesting temporal determination on peak bone mass acquisition. Our life-course approach postulates that these genetic effects influencing peak bone mass accrual may impact the risk of osteoporosis later in life.
Asunto(s)
Alelos , Densidad Ósea/genética , Estudio de Asociación del Genoma Completo , Osteoporosis/genética , Proteínas Wnt/genética , Adulto , Factores de Edad , Animales , Densidad Ósea/fisiología , Niño , Preescolar , Femenino , Perfilación de la Expresión Génica , Frecuencia de los Genes , Heterogeneidad Genética , Humanos , Masculino , Ratones , Fenotipo , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Cráneo/fisiologíaRESUMEN
BACKGROUND: Overweight has its origins largely in early life. We aimed to identify the most important parental, fetal, and infant risk factors of preschool overweight. METHODS: In a prospective cohort study, among 3,610 Caucasian preschool children, we assessed the associations of 34 putative parental, fetal, and infant factors with overweight risk. RESULTS: Higher maternal BMI, paternal BMI, and birth weight were associated with higher risk of preschool overweight (odds ratio (OR): 1.23, 95% confidence interval (CI): 1.10, 1.39; OR: 1.35, 95% CI: 1.19, 1.53; and OR: 2.71, 95% CI: 2.27, 3.25, respectively, per SD increase). The same model identified low household income (OR: 1.74, 95% CI: 1.24, 2.45), being female (OR: 1.55, 95% CI: 1.20, 2.01), and experiencing third-trimester accelerated growth (OR: 1.73, 95% CI: 1.24, 2.40) or postnatal accelerated growth (OR: 6.39, 95% CI: 4.54, 8.99) as risk factors for preschool overweight. Higher polyunsaturated fat intake at 14 mo was associated with a lower risk of preschool overweight (OR: 0.77, 95% CI: 0.62, 0.96 per SD). CONCLUSION: Parental anthropometrics and household income, fetal and infant accelerated growth, and infant dietary fat intake are the major risk factors for the development of preschool overweight. Further studies need to explore whether these risk factors could be potential targets for preventive interventions.
Asunto(s)
Peso al Nacer/fisiología , Índice de Masa Corporal , Desarrollo Fetal/fisiología , Fenómenos Fisiologicos Nutricionales Maternos/fisiología , Sobrepeso/epidemiología , Sobrepeso/etiología , Antropometría , Preescolar , Estudios de Cohortes , Padre , Femenino , Humanos , Modelos Logísticos , Masculino , Madres , Países Bajos/epidemiología , Oportunidad Relativa , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Factores Socioeconómicos , Encuestas y Cuestionarios , Población BlancaRESUMEN
Suboptimal maternal dietary intake during pregnancy might lead to fetal cardiovascular adaptations and higher blood pressure in the offspring. The aim of the present study was to investigate the associations of maternal first-trimester dietary intake with blood pressure in children at the age of 6 years. We assessed first-trimester maternal daily dietary intake by a FFQ and measured folate, homocysteine and vitamin B12 concentrations in the blood, in a population-based prospective cohort study among 2863 mothers and children. Childhood systolic and diastolic blood pressure was measured using a validated automatic sphygmomanometer. First-trimester maternal daily intake of energy, fat, protein and carbohydrate was not associated with childhood blood pressure. Furthermore, maternal intake of micronutrients was not associated with childhood blood pressure. Also, higher maternal vitamin B12 concentrations were associated with a higher diastolic blood pressure (0·31 mmHg per standard deviation increase in vitamin B12 (95% CI 0·06, 0·56)). After taking into account multiple testing, none of the associations was statistically significant. Maternal first-trimester folate and homocysteine concentrations were not associated with childhood blood pressure. The results from the present study suggest that maternal Fe intake and vitamin B12 concentrations during the first trimester of pregnancy might affect childhood blood pressure, although the effect estimates were small and were not significant after correction for multiple testing. Further studies are needed to replicate these findings, to elucidate the underlying mechanisms and to assess whether these differences in blood pressure persist in later life.
Asunto(s)
Presión Sanguínea , Dieta , Fenómenos Fisiologicos Nutricionales Maternos , Niño , Estudios de Cohortes , Suplementos Dietéticos/análisis , Femenino , Ácido Fólico/sangre , Ácido Fólico/química , Homocisteína/sangre , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Masculino , Micronutrientes/análisis , Países Bajos , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Vitamina B 12/sangreRESUMEN
Maternal fish consumption during pregnancy has been suggested to affect birth outcomes. Previous studies mainly focused on birth outcomes and did not study fetal growth during pregnancy. In a prospective cohort study from early pregnancy onwards in The Netherlands, we assessed the associations of first-trimester maternal total-fish, lean-fish, fatty-fish and shellfish consumption with fetal growth characteristics in the second and third trimesters, growth characteristics at birth and the risks of neonatal complications, including pre-term birth, low birth weight and small for gestational age. In total, 3380 mothers completed a 293-item semi-quantitative FFQ to obtain information about fish consumption during the first trimester of pregnancy. Head circumference, femur length and fetal weight were estimated in the second and third trimesters by ultrasound. Information about birth anthropometrics and neonatal complications was available from hospital and midwife registries. Maternal older age, higher educational level, folic acid supplement use, alcohol use and not smoking were associated with higher fish consumption (P < 0·01). After adjustment, we observed no consistent associations of maternal total-fish consumption or specific consumption of lean fish, fatty fish or shellfish with fetal growth characteristics in the second and third trimesters and at birth. Likewise, total-fish consumption or specific consumption of any type of fish was not consistently associated with the risks of neonatal complications. These findings suggest that in a population with a relatively low fish intake, consumption of lean fish, fatty fish or shellfish in the first trimester is not associated with fetal growth or the risks of neonatal complications.
Asunto(s)
Dieta , Desarrollo Fetal , Recién Nacido de Bajo Peso , Nacimiento Prematuro/etiología , Fenómenos Fisiologicos de la Nutrición Prenatal , Alimentos Marinos , Adolescente , Adulto , Factores de Edad , Grasas de la Dieta/administración & dosificación , Escolaridad , Femenino , Desarrollo Fetal/efectos de los fármacos , Peso Fetal , Ácido Fólico/administración & dosificación , Edad Gestacional , Humanos , Recién Nacido , Persona de Mediana Edad , Países Bajos , Embarazo , Estudios Prospectivos , Fumar , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits.
Asunto(s)
Proteínas Portadoras/genética , Pleiotropía Genética , Estudio de Asociación del Genoma Completo/métodos , Metaanálisis como Asunto , Desarrollo Musculoesquelético/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Peso Corporal , Densidad Ósea , Niño , Femenino , Expresión Génica , Humanos , Masculino , Análisis Multivariante , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo/genéticaRESUMEN
Bone strength, a key determinant of fracture risk, has been shown to display clear sexual dimorphism after puberty. We sought to determine whether sex differences in bone mass and hip bone geometry as an index of strength exist in school-age prepubertal children and the degree to which the differences are independent of body size and lean mass. We studied 3514 children whose whole-body and hip scans were measured using the same densitometer (GE-Lunar iDXA) at a mean age of 6.2 years. Hip dual-energy X-ray absorptiometry (DXA) scans underwent hip structural analyses (HSA) with derivation of bone strength indices. Sex differences in these parameters were assessed by regression models adjusted for age, height, ethnicity, weight, and lean mass fraction (LMF). Whole-body bone mineral density (BMD) and bone mineral content (BMC) levels were 1.3% and 4.3% higher in girls after adjustment by LMF. Independent of LMF, boys had 1.5% shorter femurs, 1.9% and 2.2% narrower shaft and femoral neck with 1.6% to 3.4% thicker cortices than girls. Consequent with this geometry configuration, girls observed 6.6% higher stresses in the medial femoral neck than boys. When considering LMF, the sexual differences on the derived bone strength indices were attenuated, suggesting that differences in muscle loads may reflect an innate disadvantage in bone strength in girls, as consequence of their lower muscular acquisition. In summary, we show that bone sexual dimorphism is already present at 6 years of age, with boys having stronger bones than girls, the relation of which is influenced by body composition and likely attributable to differential adaptation to mechanical loading. Our results support the view that early life interventions (ie, increased physical activity) targeted during the pre- and peripubertal stages may be of high importance, particularly in girls, because before puberty onset, muscle mass is strongly associated with bone density and geometry in children. © 2015 American Society for Bone and Mineral Research.
Asunto(s)
Estatura/fisiología , Tamaño Corporal/fisiología , Densidad Ósea/fisiología , Desarrollo Infantil/fisiología , Cuello Femoral/metabolismo , Caracteres Sexuales , Absorciometría de Fotón , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
Low birth weight is associated with lower bone accrual in children and peak bone mass in adults. We assessed how different patterns of longitudinal fetal and early childhood growth influence bone properties at school age. In 5431 children participating in a population-based prospective cohort study, we measured fetal growth by ultrasound at 20 and 30 weeks gestation, and childhood growth at birth, 1, 2, 3, and 4 years of age. We analyzed these growth measurements in relation to total body (less head) BMD measured by DXA at age 6. We used conditional growth modeling; a technique which takes into account correlation between repeatedly measured growth measures. Our results showed that estimated fetal weight gain, femur length growth between 20 and 30 weeks of gestation, femur length growth between 30 weeks and birth, as well as all height and weight growth measurements from birth to 4 years of age were all positively associated with BMC, bone area (BA), and BMD (all p < 0.01). Fetal femur length growth between 30 weeks and birth was positively associated with BMC and BA (both p < 0.001), but not with BMD. Overall, childhood growth measurements exerted a larger influence on bone measures than fetal growth measures. The strongest effect estimate was observed during the first year of life. Children born small (<10th percentile) for gestational age (SGA) had lower BMC and BA, but not BMD, than children born appropriate for gestational age (AGA), whereas children born large (>90th percentile) for gestational age (LGA) had higher BMC and BA (all p < 0.001). These differences were no longer present in children showing subsequent accelerated and decelerated infant growth, respectively. We conclude that both fetal and childhood growth patterns are associated with bone mineral accrual, showing the strongest effect estimates in infancy. Compensatory infant growth counteracts the adverse consequences of fetal growth restriction on bone development.
Asunto(s)
Densidad Ósea , Desarrollo Óseo , Desarrollo Infantil , Fémur/crecimiento & desarrollo , Desarrollo Fetal , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Adulto , Niño , Preescolar , Femenino , Fémur/metabolismo , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional/metabolismo , Masculino , EmbarazoRESUMEN
CONTEXT: Higher infant growth rates are associated with an increased risk of obesity in later life. OBJECTIVE: We examined the associations of longitudinally measured fetal and infant growth patterns with total and abdominal fat distribution in childhood. DESIGN, SETTING, AND PARTICIPANTS: We performed a population-based prospective cohort study among 6464 children. We measured growth characteristics in the second and third trimesters of pregnancy, at birth, and at 6, 12, and 24 months. MAIN OUTCOME MEASURES: Body mass index, fat mass index (body fat mass/height(2)), lean mass index (body lean mass/height(2)), android/gynoid fat ratio measured by dual-energy x-ray absorptiometry, and sc and preperitoneal abdominal fat measured by ultrasound at the median age of 6.0 years (90% range, 5.7-7.4). RESULTS: We observed that weight gain in the second and third trimesters of fetal life and in early, mid, and late infancy were independently and positively associated with childhood body mass index (P < .05). Only infant weight gain was associated with higher fat mass index, android/gynoid fat ratio, and abdominal fat in childhood (P < .05). Children with both fetal and infant growth acceleration had the highest childhood body mass index, fat mass index, and sc abdominal fat, whereas children with fetal growth deceleration and infant growth acceleration had the highest value for android/gynoid fat ratio and the lowest value for lean mass index (P < .05). CONCLUSIONS: Growth in both fetal life and infancy affects childhood body mass index, whereas only infant growth directly affects measured total body and abdominal fat. Fetal growth deceleration followed by infant growth acceleration may lead to an adverse body fat distribution in childhood.
Asunto(s)
Grasa Abdominal/crecimiento & desarrollo , Distribución de la Grasa Corporal , Desarrollo Infantil , Desarrollo Fetal , Adulto , Índice de Masa Corporal , Niño , Preescolar , Femenino , Humanos , Recién Nacido , Países Bajos/epidemiología , Embarazo , Aumento de Peso , Adulto JovenRESUMEN
BACKGROUND: Breastfeeding may have a protective effect on the development of obesity in later life. Not much is known about the effects of infant feeding on more-specific fat measures. OBJECTIVE: We examined associations of breastfeeding duration and exclusiveness and age at the introduction of solid foods with general and abdominal fat outcomes in children. DESIGN: We performed a population-based, prospective cohort study in 5063 children. Information about infant feeding was obtained by using questionnaires. At the median age of 6.0 y (95% range: 5.7 y, 6.8 y), we measured childhood anthropometric measures, total fat mass and the android:gynoid fat ratio by using dual-energy X-ray absorptiometry, and preperitoneal abdominal fat by using ultrasound. RESULTS: We observed that, in the models adjusted for child age, sex, and height only, a shorter breastfeeding duration, nonexclusive breastfeeding, and younger age at the introduction of solid foods were associated with higher childhood general and abdominal fat measures (P-trend < 0.05) but not with higher childhood body mass index. The introduction of solid foods at a younger age but not breastfeeding duration or exclusivity was associated with higher risk of overweight or obesity (OR: 2.05; 95% CI: 1.41, 2.90). After adjustment for family-based sociodemographic, maternal lifestyle, and childhood factors, the introduction of solid food between 4 and 4.9 mo of age was associated with higher risks of overweight or obesity, but the overall trend was not significant. CONCLUSIONS: Associations of infant breastfeeding and age at the introduction of solid foods with general and abdominal fat outcomes are explained by sociodemographic and lifestyle-related factors. Whether infant dietary composition affects specific fat outcomes at older ages should be further studied.
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Tejido Adiposo/patología , Adiposidad , Lactancia Materna , Alimentos Infantiles , Fenómenos Fisiológicos Nutricionales del Lactante , Obesidad/epidemiología , Sobrepeso/epidemiología , Grasa Abdominal/crecimiento & desarrollo , Grasa Abdominal/patología , Adipogénesis , Tejido Adiposo/crecimiento & desarrollo , Niño , Desarrollo Infantil , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Países Bajos/epidemiología , Obesidad/patología , Sobrepeso/patología , Estudios Prospectivos , Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants. OBJECTIVE: We assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel of European birth cohort studies. DESIGN: The study sample of 151,880 mother-child pairs was derived from 19 population-based European birth cohort studies. Individual data from cohorts were pooled and harmonized. Adjusted cohort-specific effect estimates were combined by using a random- and fixed-effects meta-analysis. RESULTS: Women who ate fish >1 time/wk during pregnancy had lower risk of preterm birth than did women who rarely ate fish (≤ 1 time/wk); the adjusted RR of fish intake >1 but <3 times/wk was 0.87 (95% CI: 0.82, 0.92), and for intake ≥ 3 times/wk, the adjusted RR was 0.89 (95% CI: 0.84, 0.96). Women with a higher intake of fish during pregnancy gave birth to neonates with a higher birth weight by 8.9 g (95% CI: 3.3, 14.6 g) for >1 but <3 times/wk and 15.2 g (95% CI: 8.9, 21.5 g) for ≥ 3 times/wk independent of gestational age. The association was greater in smokers and in overweight or obese women. Findings were consistent across cohorts. CONCLUSION: This large, international study indicates that moderate fish intake during pregnancy is associated with lower risk of preterm birth and a small but significant increase in birth weight.
Asunto(s)
Desarrollo Fetal , Peces , Contaminación de Alimentos , Fenómenos Fisiologicos Nutricionales Maternos , Nacimiento Prematuro/prevención & control , Alimentos Marinos/efectos adversos , Contaminantes Químicos del Agua/toxicidad , Animales , Peso al Nacer/efectos de los fármacos , Estudios de Cohortes , Europa (Continente)/epidemiología , Femenino , Desarrollo Fetal/efectos de los fármacos , Promoción de la Salud , Humanos , Estudios Longitudinales , Política Nutricional , Embarazo , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Estudios Prospectivos , RiesgoRESUMEN
BACKGROUND: Maternal diet during pregnancy has been suggested to influence bone health in later life. OBJECTIVE: We assessed the association of maternal first-trimester dietary intake during pregnancy with childhood bone mass. DESIGN: In a prospective cohort study in 2819 mothers and their children, we measured first-trimester daily energy, protein, fat, carbohydrate, calcium, phosphorus, and magnesium intakes by using a food-frequency questionnaire and homocysteine, folate, and vitamin B-12 concentrations in venous blood. We measured childhood total body bone mass by using dual-energy X-ray absorptiometry at the median age of 6.0 y. RESULTS: Higher first-trimester maternal protein, calcium, and phosphorus intakes and vitamin B-12 concentrations were associated with higher childhood bone mass, whereas carbohydrate intake and homocysteine concentrations were associated with lower childhood bone mass (all P-trend < 0.01). Maternal fat, magnesium intake, and folate concentrations were not associated with childhood bone mass. In the fully adjusted regression model that included all dietary factors significantly associated with childhood bone mass, maternal phosphorus intake and homocysteine concentrations most-strongly predicted childhood bone mineral content (BMC) [ß = 2.8 (95% CI: 1.1, 4.5) and ß = -1.8 (95% CI: -3.6, 0.1) g per SD increase, respectively], whereas maternal protein intake and vitamin B-12 concentrations most strongly predicted BMC adjusted for bone area [ß = 2.1 (95% CI: 0.7, 3.5) and ß = 1.8 (95% CI: 0.4, 3.2) g per SD increase, respectively]. CONCLUSION: Maternal first-trimester dietary factors are associated with childhood bone mass, suggesting that fetal nutritional exposures may permanently influence bone development.
Asunto(s)
Densidad Ósea/fisiología , Dieta , Fenómenos Fisiologicos Nutricionales Maternos , Primer Trimestre del Embarazo , Absorciometría de Fotón , Adulto , Calcio de la Dieta/administración & dosificación , Calcio de la Dieta/sangre , Niño , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/sangre , Homocisteína/administración & dosificación , Homocisteína/sangre , Humanos , Estilo de Vida , Magnesio/administración & dosificación , Magnesio/sangre , Masculino , Fósforo Dietético/administración & dosificación , Fósforo Dietético/sangre , Embarazo , Estudios Prospectivos , Factores Socioeconómicos , Encuestas y Cuestionarios , Vitamina B 12/administración & dosificación , Vitamina B 12/sangreRESUMEN
BACKGROUND: Maternal cow-milk consumption may increase birth weight. Previous studies did not assess the association of maternal milk consumption with trimester-specific fetal growth. OBJECTIVE: The objective was to assess associations of first-trimester maternal milk consumption with fetal growth characteristics in different trimesters and the risk of neonatal complications. DESIGN: In total, 3405 mothers participating in a prospective cohort study completed a 293-item semiquantitative food-frequency questionnaire to obtain information about dairy consumption during the first trimester of pregnancy. Fetal head circumference, femur length, and weight were estimated in the second and third trimesters by ultrasonography. RESULTS: Maternal milk consumption of >3 glasses/d was associated with greater fetal weight gain in the third trimester of pregnancy, which led to an 88-g (95% CI: 39, 135 g) higher birth weight than that with milk consumption of 0 to 1 glass/d. In addition, head circumference tended to be 2.3 cm (95% CI: -0.0, 4.6 cm) larger when mothers consumed >3 glasses/d. Maternal milk consumption was not associated with length growth. Maternal protein intake (P for trend = 0.01), but not fat or carbohydrate intake, from dairy products was associated with higher birth weight. This association appeared to be limited to milk (P for trend < 0.01), whereas protein intake from nondairy food or cheese was not associated with birth weight. CONCLUSIONS: Maternal milk consumption is associated with greater fetal weight gain. The association seems to be due to milk protein, or milk components closely associated with protein, rather than to the fat or carbohydrate fraction of milk.