Childhood growth and development and DNA methylation age in mid-life

ABSTRACTBackgroundIn the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life.MethodsParticipants were from the Medical Research Council National Survey of Health and Development(n=1,376). Four DNAm age acceleration(AgeAccel) biomarkers were measured when participants were aged 53y:AgeAccelHannum, AgeAccelHorvath, AgeAccelLevine and AgeAccelGrim. Exposure variables included relative weight gain (standardised residuals from models of current weight z-score on current height, and previous weight and height z-scores) and linear growth (standardised residuals from models of current height z-score on previous height and weight z-scores) during infancy (0-2y, weight gain only), early childhood(2-4y), middle childhood(4-7y) and late childhood to adolescence(7- 15y), age at menarche and pubertal stage for men at 14-15y. The relationship between relative weight gain and linear growth and AgeAccel was investigated using conditional growth models. We replicated analyses from the late childhood to adolescence period and pubertal timing among 240 participants from The National Child and Development Study(NCDS).ResultsA 1 SD increase in relative weight gain in late childhood to adolescence was associated with 0.50y(95% CI:0.20,0.79) higher AgeAccelGrim. This was replicated in NCDS (0.57y(95%CI:-0.01, 1.16). A I SD increase in linear growth during early childhood was associated with lower AgeAccelLevine(−0.39y [95% CI:-0.74,-0.04) however we did not have the data to replicate this finding in NCDS. There was no strong evidence that relative weight gain and linear growth in childhood was associated with any other AgeAccel biomarker. There was no relationship between pubertal timing in men and AgeAccel biomarkers. Women who reached menarche ≥12y had 1.20y(95% CI:0.15,2.24) higher AgeAccelGrim on average than women who reached menarche <12y; however this was not replicated in NCDS.ConclusionsOur findings generally do not support an association between growth and AgeAccel biomarkers in mid-life. However, rapid weight gain during pubertal development, which we found to be related to older AgeAccelGrim and had previously been related to higher cardiovascular disease risk, warrants further investigation.

Download Full-text

Childhood growth and development and DNA methylation age in mid-life

Clinical Epigenetics ◽

10.1186/s13148-021-01138-x ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Jane Maddock ◽

Juan Castillo-Fernandez ◽

Andrew Wong ◽

George B. Ploubidis ◽

Diana Kuh ◽

...

Keyword(s):

Weight Gain ◽

Growth And Development ◽

Linear Growth ◽

Disease Risk ◽

Pubertal Timing ◽

Pubertal Development ◽

Cardiovascular Disease Risk ◽

Relative Weight ◽

Late Childhood ◽

Age At Menarche

Abstract Background In the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life. Methods Participants were from the Medical Research Council National Survey of Health and Development (n = 1376). Four DNAm age acceleration (AgeAccel) biomarkers were measured when participants were aged 53 years: AgeAccelHannum; AgeAccelHorvath; AgeAccelLevine; and AgeAccelGrim. Exposure variables included: relative weight gain (standardised residuals from models of current weight z-score on current height, and previous weight and height z-scores); and linear growth (standardised residuals from models of current height z-score on previous height and weight z-scores) during infancy (0–2 years, weight gain only), early childhood (2–4 years), middle childhood (4–7 years) and late childhood to adolescence (7–15 years); age at menarche; and pubertal stage for men at 14–15 years. The relationship between relative weight gain and linear growth and AgeAccel was investigated using conditional growth models. We replicated analyses from the late childhood to adolescence period and pubertal timing among 240 participants from The National Child and Development Study (NCDS). Results A 1SD increase in relative weight gain in late childhood to adolescence was associated with 0.50 years (95% CI 0.20, 0.79) higher AgeAccelGrim. Although the CI includes the null, the estimate was similar in NCDS [0.57 years (95% CI − 0.01, 1.16)] There was no strong evidence that relative weight gain and linear growth in childhood was associated with any other AgeAccel biomarker. There was no relationship between pubertal timing in men and AgeAccel biomarkers. Women who reached menarche ≥ 12 years had 1.20 years (95% CI 0.15, 2.24) higher AgeAccelGrim on average than women who reached menarche < 12 years; however, this was not replicated in NCDS and was not statistically significant after Bonferroni correction. Conclusions Our findings generally do not support an association between growth and AgeAccel biomarkers in mid-life. However, we found rapid weight gain during pubertal development, previously related to higher cardiovascular disease risk, to be associated with older AgeAccelGrim. Given this is an exploratory study, this finding requires replication.

Download Full-text

Relative Weight Gain Through Age 4 Years Is Associated with Increased Adiposity, and Higher Blood Pressure and Insulinemia at 4–5 Years of Age in Mexican Children

Journal of Nutrition ◽

10.1093/jn/nxy068 ◽

2018 ◽

Vol 148 (7) ◽

pp. 1135-1143 ◽

Cited By ~ 4

Author(s):

Ivonne Ramirez-Silva ◽

Juan A Rivera ◽

Belem Trejo-Valdivia ◽

Aryeh D Stein ◽

Reynaldo Martorell ◽

...

Keyword(s):

Blood Pressure ◽

Weight Gain ◽

Cardiometabolic Risk ◽

Relative Weight ◽

Risk Markers ◽

Z Score ◽

Mexican Children ◽

Unit Increase ◽

Z Scores ◽

Cardiometabolic Risk Markers

AbstractBackgroundRapid early weight gain has been associated with increased risk of obesity and cardiometabolic alterations, but evidence in low and middle-income countries is inconclusive.ObjectiveWe evaluated the relation between relative weight gain from 1 to 48 mo with adiposity and cardiometabolic risk factors at 4–5 y of age, and determined if adiposity is a mediator for cardiometabolic alterations.MethodsWe studied 428 Mexican children with anthropometric and blood pressure (BP) information from birth to 5 y of age from POSGRAD (Prenatal Omega-3 fatty acid Supplementation and child GRowth And Development), of whom 334 provided measures of adiposity and cardiometabolic risk markers at 4 y. We estimated relative weight gain by means of conditional weight-for-height z scores for the age intervals 1–6, 6–12, 12–24, and 24–48 mo. Associations between relative weight gain and adiposity and cardiometabolic risk markers (lipid profile, triglycerides, insulin, glucose, and BP) were analyzed by multivariate multiple linear models and path analysis.ResultsA 1-unit increase in conditional weight-for-height z score within each age interval was positively associated with adiposity at 5 y, with coefficients of 0.43–0.89 for body mass index (BMI) z score, 1.08–3.65 mm for sum of skinfolds, and 1.21–3.87 cm for abdominal circumference (all P < 0.01). Positive associations were documented from ages 6 to 48 mo with systolic BP (coefficient ranges: 1.19–1.78 mm Hg; all P < 0.05) and from ages 12 to 48 mo with diastolic BP (1.28–0.94 mm Hg; P < 0.05) at 5 y. Conditional weight-for-height z scores at 12–24 and 24–48 mo of age were more strongly associated with adiposity and BP relative to younger ages. A unit increase in conditional weight-for-height z scores from 12 to 24 mo was associated with 14% higher insulin levels (P < 0.05) at 4 y. Path analyses documented that the associations of conditional weight gain with BP were mediated by BMI and sum of skinfolds.ConclusionRelative weight gain at most periods during the first 4 y of life was associated with greater adiposity and higher systolic and diastolic BP at 5 y. These associations with BP were mediated by adiposity. Relative weight gain from 12 to 24 mo was associated with increased serum insulin concentrations at 4 y, but there were no associations with lipid profiles or glucose concentration.

Download Full-text

Racial and Ethnic Disparities in Early Childhood Obesity

10.1542/9781610022781-racial ◽

2018 ◽

pp. 58-72

Author(s):

Inyang A. Isong ◽

Sowmya R. Rao ◽

Marie-Abèle Bind ◽

Mauricio Avendaño ◽

Ichiro Kawachi ◽

...

Keyword(s):

Risk Factors ◽

Early Childhood ◽

Weight Gain ◽

Childhood Obesity ◽

Ethnic Disparities ◽

Z Score ◽

Z Scores ◽

Obesity Risk Factors ◽

Early Childhood Obesity ◽

Infant Weight Gain

OBJECTIVES The prevalence of childhood obesity is significantly higher among racial and/or ethnic minority children in the United States. It is unclear to what extent well-established obesity risk factors in infancy and preschool explain these disparities. Our objective was to decompose racial and/or ethnic disparities in children’s weight status according to contributing socioeconomic and behavioral risk factors. METHODS We used nationally representative data from ~10 700 children in the Early Childhood Longitudinal Study Birth Cohort who were followed from age 9 months through kindergarten entry. We assessed the contribution of socioeconomic factors and maternal, infancy, and early childhood obesity risk factors to racial and/or ethnic disparities in children’s BMI z scores by using Blinder-Oaxaca decomposition analyses. RESULTS The prevalence of risk factors varied significantly by race and/or ethnicity. African American children had the highest prevalence of risk factors, whereas Asian children had the lowest prevalence. The major contributor to the BMI z score gap was the rate of infant weight gain during the first 9 months of life, which was a strong predictor of BMI z score at kindergarten entry. The rate of infant weight gain accounted for between 14.9% and 70.5% of explained disparities between white children and their racial and/or ethnic minority peers. Gaps in socioeconomic status were another important contributor that explained disparities, especially those between white and Hispanic children. Early childhood risk factors, such as fruit and vegetable consumption and television viewing, played less important roles in explaining racial and/or ethnic differences in children’s BMI z scores. CONCLUSIONS Differences in rapid infant weight gain contribute substantially to racial and/or ethnic disparities in obesity during early childhood. Interventions implemented early in life to target this risk factor could help curb widening racial and/or ethnic disparities in early childhood obesity.

Download Full-text

Dental Caries Severity and Nutritional Status of Nigerian Preschool Children

JDR Clinical & Translational Research ◽

10.1177/23800844211002108 ◽

2021 ◽

pp. 238008442110021

Author(s):

O.O. Olatosi ◽

A.A. Alade ◽

T. Naicker ◽

T. Busch ◽

A. Oyapero ◽

...

Keyword(s):

Early Childhood ◽

Dental Caries ◽

Nutritional Status ◽

Early Childhood Caries ◽

Z Score ◽

Cross Sectional ◽

Risk Of Death ◽

Malnourished Children ◽

Z Scores ◽

Childhood Caries

Introduction: Malnutrition in children is one of the most prevalent global health challenges, and malnourished children have a higher risk of death from childhood diseases. Early childhood caries (ECC) is the most common chronic disease of childhood. Complications from ECC such as pain, loss of tooth/teeth, and infection can undermine a child’s nutrition and growth. Aim: This study aims to evaluate the severity of decay, missing, and filled tooth (dmft) by nutritional status using the z scores of the anthropometric measurements: height for age (HFA), weight for age (WFA), weight for height (WFH), and body mass index for age (BMIA) among children with ECC in Nigeria. Study Design: This is a cross-sectional study conducted in 5 local government areas (LGAs) in Lagos State, Nigeria. A multistage sampling technique was used. Results: A total of 273 cases of ECC were included in the analyses (mean age 4.19 ± 0.96 y). Overall, the mean dmft was 3.04 ± 2.28, and most (96%) were accounted for by untreated decay. The distribution of dmft within the different z score categories of BMIA (<–3 = severely wasted, –2 to –3 = wasted, –2 to +2 = normal, +2 to +3 = overweight and >+3 = obese) showed the highest dmft scores among the combined severely wasted and wasted groups, lowest among children with normal z scores, and intermediate in the overweight and obese groups. There was a significant negative correlation between BMIA z score, WFH z score, and dmft ( r = −0.181, P < 0.05 and r = −0.143, P < 0.05, respectively). However, the correlations between HFA z score, WFA z score, and dmft were positive but not significant ( r = 0.048, P = 0.44 and r = 0.022, P = 0.77, respectively). Conclusion: Our study showed an increased severity of dental caries among severely wasted or wasted children with ECC compared to those of normal or overweight. Knowledge Transfer Statement: The results from this study will raise awareness among clinicians and policy makers on the need for a primary prevention program for early childhood caries in countries with high burden of malnutrition and limited resources. Also, it will help draw the attention of clinicians to the caries status of malnourished children that can be managed to improve the nutritional outcomes.

Download Full-text

The Effect of Phosphate Supplementation on Linear Growth in Children with X-Linked Hypophosphatemia

PEDIATRICS ◽

10.1542/peds.94.4.478 ◽

1994 ◽

Vol 94 (4) ◽

pp. 478-481

Author(s):

Mouin G. Seikaly ◽

Richard H. Browne ◽

Michel Baum

Keyword(s):

Vitamin D ◽

Standard Deviation ◽

Linear Growth ◽

Standard Deviation Score ◽

Initial Therapy ◽

Current Therapy ◽

Height Standard Deviation Score ◽

Z Score ◽

Z Scores ◽

Phosphate Supplementation

Background. X-linked hypophosphatemia is the most common inherited cause of rickets. Current therapy for this disorder includes vitamin D and phosphate supplementation; however, phosphate therapy has been associated with nephrocalcinosis. The purpose of this study is to evaluate the effect of oral phosphate therapy on growth in patients with X-linked hypophosphatemia treated with either calcitriol or dihydrotachysterol (vitamin D). Methods. We retrospectively evaluated the prepubertal growth of 36 children with X-linked hypophosphatemia. The height standard deviation score (Z-score) of patients initially treated with vitamin D alone and the Z-scores of patients treated with vitamin D and phosphate therapy were compared. In addition, the growth of patients treated with vitamin D was compared with that of patients treated with vitamin D and phosphate from the outset of therapy. Results. Patients treated with vitamin D alone for 5.36 ± 2.18 years had an improvement in Z-score from -3.18 ± 1.10 to -2.49 ± 0.66 SDS, ,P < .05. Adding phosphate therapy for patients initially treated with vitamin D alone for 4.83 ± 2.99 years did not further improve Z-score (-2.49 ±0.66 vs -2.35 ± 0.83). Initial therapy with vitamin D and phosphate for 4.33 ± 2.19 years also improved Z-score, (-2.84 ± 1.02 vs -1.98 ± 0.82, P < .05). The change in Z-score was similar to the group treated with vitamin D alone compared with the group treated initially with vitamin D and phosphate (0.65 ± 0.54 vs 0.85 ± 0.65, respectively). Conclusion. These data demonstrate that both vitamin D alone and in combination with phosphate improved linear growth. Adding oral phosphate for children initially treated with vitamin D alone did not improve Z-score. Initial therapy with vitamin D and vitamin D plus phosphate produced similar changes in linear growth.

Download Full-text

Early growth and changes in blood pressure during adult life

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174415007886 ◽

2015 ◽

Vol 7 (3) ◽

pp. 306-313 ◽

Cited By ~ 1

Author(s):

S. Sandboge ◽

C. Osmond ◽

E. Kajantie ◽

J. G Eriksson

Keyword(s):

Blood Pressure ◽

Weight Gain ◽

Systolic Blood Pressure ◽

Linear Growth ◽

Growth Models ◽

Relative Weight ◽

Adult Life ◽

Birth Cohort Study ◽

Inverse Association ◽

Childhood Growth

Previous studies suggest that the inverse association between birth weight and adult blood pressure amplifies with age. Rapid childhood growth has also been linked to hypertension. The objective of this study was to determine whether the association between childhood growth and adult blood pressure amplifies with age. The study comprised 574 women and 462 men from the Helsinki Birth Cohort Study who attended a clinical study in 2001–2004 and a follow-up in 2006–2008. Mean age at the clinic visits was 61.5 and 66.4 years, respectively. Blood pressure was measured at both occasions. Conditional growth models were used to assess relative weight gain and linear growth. We studied the associations between conditional growth and blood pressure as well as the presence of hypertension. Relative weight gain and linear growth between ages 2 and 11 years were inversely associated with systolic blood pressure at mean age 66.4 years, after adjustment for sex, blood pressure at mean age 61.5 years, as well as other covariates. A one s.d. increase in linear growth between 2 and 11 years was associated with an OR of 0.61 for hypertension at mean age 66.4 years. Contrary to previous studies, we have shown an inverse association between childhood growth and adult blood pressure. There were, however, no associations between childhood growth and systolic blood pressure at mean age 61.5 years indicating that the beneficial effects of a more rapid than expected childhood growth might become more apparent with increasing age.

Download Full-text

Early Weight Gain, Linear Growth, and Mid-Childhood Blood Pressure

Hypertension ◽

10.1161/hypertensionaha.115.06635 ◽

2016 ◽

Vol 67 (2) ◽

pp. 301-308 ◽

Cited By ~ 47

Author(s):

Wei Perng ◽

Sheryl L. Rifas-Shiman ◽

Michael S. Kramer ◽

Line K. Haugaard ◽

Emily Oken ◽

...

Keyword(s):

Blood Pressure ◽

Body Mass Index ◽

Weight Gain ◽

Systolic Blood Pressure ◽

Body Mass ◽

Early Life ◽

Linear Growth ◽

Birth Size ◽

Z Score ◽

Score Gain

In recent years, the prevalence of hypertension and prehypertension increased markedly among children and adolescents, highlighting the importance of identifying determinants of elevated blood pressure early in life. Low birth weight and rapid early childhood weight gain are associated with higher future blood pressure. However, few studies have examined the timing of postnatal weight gain in relation to later blood pressure, and little is known regarding the contribution of linear growth. We studied 957 participants in Project Viva, an ongoing US prebirth cohort. We examined the relations of gains in body mass index z-score and length/height z-score during 4 early life age intervals (birth to 6 months, 6 months to 1 year, 1 to 2 years, and 2 to 3 years) with blood pressure during mid-childhood (6–10 years) and evaluated whether these relations differed by birth size. After accounting for confounders, each additional z-score gain in body mass index during birth to 6 months and 2 to 3 years was associated with 0.81 (0.15, 1.46) and 1.61 (0.33, 2.89) mm Hg higher systolic blood pressure, respectively. Length/height gain was unrelated to mid-childhood blood pressure, and there was no evidence of effect modification by birth size for body mass index or length/height z-score gain. Our findings suggest that more rapid gain in body mass index during the first 6 postnatal months and in the preschool years may lead to higher systolic blood pressure in mid-childhood, regardless of size at birth. Strategies to reduce accrual of excess adiposity during early life may reduce mid-childhood blood pressure, which may also impact adult blood pressure and cardiovascular health.

Download Full-text