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ORIGINAL RESEARCH COMMUNICATION |
1 From the Research Institute of Child Nutrition, affiliated with the Rheinische Friedrich-Wilhelms-Universität, Bonn, Dortmund, Germany.
2 The analysis of data from the DONALD Study was funded by a research grant from the Long-range Research Initiative of the European Chemical Industry Council. The DONALD Study was funded by the Ministry of Science and Research of North Rhine Westphalia, Germany. Preparatory analyses regarding pubertal markers were also sponsored by a World Cancer Research grant (to NKD). 3 Reprints not available. Address correspondence to A Buyken, Nutrition and Health Unit, Research Institute of Child Nutrition, Heinstueck 11, 44225 Dortmund, Germany. E-mail: buyken{at}fke-do.de.
| ABSTRACT |
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Objective: The objective was to investigate whether body composition in the 2 y preceding the start of the pubertal growth spurt—a marker of puberty onset—is associated with the attainment of early and late pubertal markers in healthy German boys and girls.
Design: Multivariate-adjusted regression analyses were performed in 215 participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study for whom body mass index (BMI) and its components fat mass/height2 (FM/m2) and fat-free mass/height2 (FFM/m2) 1 and 2 y before the onset of the pubertal growth spurt (age at takeoff; ATO) and information on early life exposures were available. In addition, age at peak height velocity (APHV) and menarche were examined.
Results: Higher BMIs and FM/m2 z scores 1 and 2 y before ATO showed modest associations with chronological age at ATO among girls only (girls: P for = trend 0.05–0.1, adjusted for early life factors; boys: P = 0.2–0.6). FFM/m2 z scores were not related to age at ATO (P for trend = 0.5–0.8). Conversely, prepubertal BMI and FM/m2 more clearly predicted APHV and puberty duration (APHV minus ATO) in both sexes and age at menarche in girls (girls: adjusted P for trend <0.0001–0.03; boys: P = 0.01–0.046).
Conclusion: This longitudinal study suggests that prepubertal body composition in healthy boys and girls may not be critical for the initiation of the pubertal growth spurt but instead affects the progression of pubertal development, which results in earlier attainment of later pubertal stages.
| INTRODUCTION |
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To date, very few studies have prospectively analyzed the relevance of prepubertal body composition for the timing of puberty in boys (18–21). These studies, as well as those conducted in girls, have mostly addressed a relatively late stage of pubertal development (ie, onset of menarche in girls and age at peak height velocity (APHV) or voice break in boys) (3–14, 18–22). In addition, the prepubertal time window of 5–9 y of age analyzed may have actually encompassed the onset of early pubertal signs. Alternatively, alignment of age to one of the earliest pubertal markers could allow insights into the association between body composition at a biologically comparable definitively prepubertal stage and subsequent pubertal development.
Therefore, the aim of this study was to use the prospectively collected and frequent height measurements of both girls and boys from the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study to investigate whether chronological age at the initiation of puberty, as defined by the timing of the onset of the pubertal growth spurt (age at takeoff; ATO), was influenced by the level of BMI and the components of BMI, fat mass/height2 (FM/m2), and fat-free mass/height2 (FFM/m2) in the 2 preceding years, independently of early life factors. For comparative purposes with other studies, we also investigated whether body composition at this prepubertal stage was related to the chronological age at which later puberty markers (ie, PHV and menarche) occurred.
| SUBJECTS AND METHODS |
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3 visits in the first year, 2 in the second, and then once annually until early adulthood. During puberty, adolescents have also been asked to return for anthropometric measurements only at additional half-yearly intervals. The study was approved by the Ethics Committee of the University of Bonn, and all examinations are performed with parental consent.
Many DONALD participants have not yet reached adolescence. In addition, the ages of the children who were initially recruited into the DONALD Study were quite variable so that information on the first few years of life was not always available. Therefore, the number of children included in this analysis was derived as follows. Four hundred eleven term (37–42 wk gestation) singletons with a birth weight >2500 g had a minimum of both height measurements at 6 and 13 y and
5 measurements between these ages to allow estimation of ATO. The estimated ATO was considered plausible in 376 children (ie, it was between
5 and <13 y and in agreement with the visually inspected individual growth curve); 250 of these children also had information on rapid weight gain between birth and age 2 y. Finally, all children had to have complete information on breastfeeding and on maternal characteristics (BMI and educational status). Hence, the subcohort analyzed herein included 215 term singletons (49.8% female).
Anthropometric measures
DONALD Study participants are measured at each visit according to standard procedures (24). They are dressed in underwear only and are barefoot. The trained nurses who conduct the measurements undergo an annual quality-control check during which inter- and intraobserver agreements are carefully monitored. Recumbent length in children aged <2 y is measured to the nearest 0.1 cm with a Harpenden (Holtain, Crymych, United Kingdom) stadiometer. From the age of 2 y onward, standing height is measured to the nearest 0.1 cm using a digital stadiometer. Weight is measured to the nearest 0.1 kg with an electronic scale (753 E; Seca, Hamburg, Germany). Skinfold thicknesses are measured from the age of 6 mo onward on the right side of the body to the nearest 0.1 mm with a Holtain caliper.
At the time of their child's admission to the study, parents are interviewed by the study pediatrician and weighed and measured by the study nurses using the same equipment as for children from age 2 y onward. Information on birth weight, length, and head circumference at birth as well as gestational age is abstracted from the Mutterpass, a standardized document given to all pregnant women in Germany.
Anthropometric calculations
For the present analysis, we used those anthropometric measurements obtained as closely as possible to the 2 y before estimated ATO. Because not all participants had anthropometric measurements for all scheduled visits, these missing data were linearly imputed by using measurements before and afterward (maximum gap between 2 measurements was 1.5 y). The measurements closest to the ATO and 1 and 2 y before the ATO were then set to time = 0, –1, and –2, respectively. For each BMI, sex- and age-independent SD scores (SDS) were calculated by using the German reference curves (25). Percentage body fat (BF%) was calculated by using the Slaughter equations for prepubertal children (26). BF%, however, has recently been criticized to incorrectly reflect body-size-adjusted adiposity (27). Instead, it has been suggested to adjust FM for fat-free proxies of body size such as height (27). However, in the present study, the outcome ATO (and APHV) was itself derived from height measurements (see below). Because adjustments for height in multivariate analyses would hence be inappropriate, the components of BMI, FM/m2 (FM = weight x BF%), and FFM/m2 (FFM = weight – fat mass) as previously introduced by Maynard et al (28) were used as additional measures of body composition. Subsequently, z scores of BMI-SDS, log-transformed FM/m2, and FFM/m2 were obtained by internal standardization to the sample in this analysis (mean = 0, SD = 1; by chronological age and sex).
Puberty variables
All original height measurements were analyzed by using the parametric Preece and Baines model 1 (PB1) (29). The parameters of each child's growth curve were estimated by a nonlinear regression model (PROC NLIN in SAS; SAS Institute Inc, Cary, NC). The PB1 was fitted on various sex-specific age ranges of the height-for-age data, beginning with age 2 y, to determine the optimal range for our data. ATO was defined as the age at minimal height velocity (zero acceleration) at the onset of the pubertal growth spurt (30). Best fit was determined by 1) graphical inspection of each child's individual growth curve, 2) a comparison of the residual SDs (random error had to be smaller than the expected measurement error for height), and 3) considering the plausibility and distribution of the pubertal variables estimated. On the basis of these 3 criteria the following age ranges were selected: all measurements from age 5 y onward for girls and from age 6 y onward for boys. The PB1 model also produced estimates of velocity at takeoff (VTO), APHV, and PHV. From these, we calculated the duration of the pubertal growth spurt (APHV – ATO), which in this article is termed "puberty duration."
Two other puberty variables were considered in this analysis for the sake of comparability with other studies: age at Tanner stage 2 for either breast or penis development in girls (n = 75) and boys (n = 66), respectively, and age at menarche in girls only (n = 87). Tanner stage is visually assessed by one of the DONALD Study doctors at each visit after attainment of school age. After the age of 8 y, girls are also regularly asked whether menarche has already occurred, and if so, in which month and year.
Early life factors
Birth weight was considered as both a continuous and as a categorical variable (ie, in those infants who weighed
2500 g but <3000 g compared with those who weighed
3000 g at birth). Other birth variables included gestational age, birth year, being firstborn (yes/no), and breastfeeding status (defined as those who had been fully breastfed for
2 wk). Growth patterns in infancy and early childhood were assessed by using rapid weight gain, which was defined as an increase in weight SDS >0.67 between birth and 24 mo (31) according to the German reference values (25). The following parental characteristics were also considered: maternal overweight status (BMI
25), high maternal educational status (
12 y of schooling), maternal age at birth, and smoking in the household (yes/no).
Statistical methods
For description of the sample characteristics, 3 ATO groups were created by using the sex-specific distribution of ATO: early onset (<25th percentile), middle onset (
25th percentile and
75th percentile), and late onset (>75th percentile). Differences in characteristics between ATO groups were tested by using Kruskal-Wallis tests for continuous variables and chi-square tests for categorical variables.
Least-squares regression analyses were used to analyze the association of body composition with pubertal variables. Trend testing was performed with ATO as a continuous outcome and z scores of BMI, FM/m2, or FFM/m2 as continuous influencing variables. Furthermore, the distributions of BMI, FM/m2, or FFM/m2 z scores at 1 or 2 y before ATO were grouped to represent 3 sex-specific categories of body composition: low (<25th percentile), normal (
25th percentile and
75th percentile), and high (>75th percentile). In multivariate analysis, ATO was adjusted for potentially confounding early-life exposures. Each variable was initially considered separately, and those variables that had their own independent significant fixed effect in the basic models were included in the multivariate analyses. The adjusted means were the least-squares means predicted by the model when the other variables were held at their mean values. Similarly, multivariable models were constructed for APHV, puberty duration, and age at menarche. Finally, tracking of body composition from 1 y before ATO to APHV was analyzed by comparing the proportion of boys and girls grouped into the 3 categories of BMI, FM/m2, or FFM/m2 z scores described above. A
value of
0.2 was selected to indicate the existence of poor tracking,
0.4 for moderate tracking,
0.6 for good tracking, and
0.8 for excellent tracking (32).
Because it has been suggested that the association between body composition and timing of puberty may differ between girls and boys (1), tests for sex interactions were performed. The association of the categories of BMI and FFM/m2 with the chronological age at ATO was found to differ between boys and girls at 2 y before ATO (test for interaction: P = 0.02 and P = 0.1, respectively, in the full model), but not at 1 y before ATO (test for interaction: P = 0.14 and P = 0.4, respectively, in the full model). However, sex differences were also observed for associations of BMI with later puberty markers (test for interaction: P = 0.1 for associations between categories of BMI). Thus, all analyses were stratified by sex. A P value <0.05 was considered statistically significant. All statistical analyses were carried out by using SAS version 8.2 (SAS Institute Inc).
| RESULTS |
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2 wk than boys with later puberty onset.
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: 0.68 and 0.71, respectively, indicated good tracking). For categories of FM/m2 and FFM/ m2 z scores, moderate tracking between 1 y before ATO and APHV was observed in girls (weighted kappa: 0.58 and 0.58, respectively) and in boys (weighted
: 0.60 and 0.41, respectively). | DISCUSSION |
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This study was the first to analyze the body composition of both boys and girls at a comparable biological age before puberty onset for associations with many pubertal markers and hence allows us to disentangle potential prepubertal influences on earlier and later pubertal development. Previous studies investigating childhood body composition at different chronological ages for its association with later pubertal markers have been criticized because the age range investigated may still have encompassed the earliest pubertal developments (14). The present study overcomes this potential shortcoming by using body composition 1 and 2 y before the onset of the pubertal growth spurt—one of the earliest puberty markers.
Our finding that prepubertal body composition is associated with later puberty markers is in line with previous studies showing similar associations with childhood body composition at 5–9 y of age (3, 4, 6–8, 10–13, 18–21). Despite only investigating later puberty markers, these studies have commonly been interpreted to suggest that higher levels of body fat before puberty predispose to an earlier puberty onset (1, 12, 18, 19). However, the present study suggests only a weak association between prepubertal body composition and initiation of the pubertal growth spurt. Instead, children with higher prepubertal BMI or FM/m2 values appeared to proceed more rapidly to PHV or menarche. Recent studies have provided new evidence of the obligatory role of hypothalamic kisspeptin in initiating puberty by disinhibiting the pulsatility of gonadotropin releasing hormone (33). It may well be that kisspeptin continues to be involved in the coordination between metabolic status and the reproductive axis, thus also influencing the rate of pubertal progression (34). Kisspeptin expression in turn may be regulated by adiposity signals such as leptin (35, 36), insulin (36), and the hunger hormone ghrelin (37). Because BMI and fatness clearly tracked from 1 y before ATO to APHV, it is conceivable that the relevance of prepubertal body composition for puberty duration seen in this study may at least be partly a consequence of the continuous prepubertal and peripubertal flux of endocrine signals from the periphery (eg, leptin and insulin) to the hypothalamus.
In this study, both the modest associations of prepubertal body composition with the start of the pubertal growth spurt and the stronger associations with later pubertal markers were seen independently of early life factors. In our view, this suggests that early life factors (15) and prepubertal body composition operate largely independently to influence puberty; thus, infancy and prepuberty are 2 critical periods during which the timing of pubertal events could be influenced. The potential to intervene may, however, be limited by a common genetic background regulating pubertal timing as well as growth during infancy and childhood (21).
It has been suggested that the link between body fat and timing of puberty may differ between girls and boys (1). In this study, the associations of prepubertal body composition with later pubertal markers were seen in both girls and boys. For boys, 3 recent prospective studies have also shown that those with higher childhood BMIs experience PHV (20, 21) and voice break (19) at an earlier age. Taken together, these data and our data provide evidence that prepubertal body composition in boys is related to later pubertal markers in a similar way as in girls, which largely refutes previous suggestions of an opposite association in boys (38, 39).
Nonetheless, the modest association of prepubertal body composition with the initiation of puberty, ie, the start of the pubertal growth spurt, was primarily seen in girls (test for interactions: see Subjects and Methods). Furthermore, our study suggested that, among girls, APHV and age at menarche were somewhat more consistently related to FM/m2 than to BMI (tests for interaction: see Subjects and Methods). These findings may be attributable, at least in part, to the fact that, in comparison with boys, girls have a lower muscle mass (as indicated by 24-h creatinine excretion) per kilogram body weight (40) and a higher FM (41) already during childhood. Interestingly, in both girls and boys, higher lean mass (FFM/m2) values before the pubertal growth spurt were—although unrelated to the timing of early or late pubertal marker—associated with a shorter duration of puberty. This indicates a potential relevance of muscle mass for puberty.
The main strength of our study was its use of very detailed anthropometric data from early childhood until adolescence on a comparably large sample of both boys and girls. These data allowed the determination of both the initiation and the maximal growth spurt as indicators of somatic maturation. Alternatively, Tanner stages are commonly used to determine the initiation of puberty. However, these factors are difficult to assess and have been criticized as being subjective with considerable interobserver variability (42). The estimated values of ATO and APHV in our study are in accordance with values reported from other European studies (18, 20, 21) and showed an acceptable consistency with other pubertal markers assessed in the DONALD Study. Additional strengths of our study included our ability to control for the potential confounding effect of early life factors, particularly for rapid weight gain in the first 2 y of life, and the fact that we could investigate prepubertal BMI and its components FM/m2 and FFM/m2.
The main limitation of this study was the fact that the components FM/m2 and FFM/m2 were estimated from skinfold-thickness measurements, which are known to be more susceptible to measurement error than specialized research-based techniques, such as dual-energy X-ray absorptiometry, and may underestimate body fatness (43). However, intra- and interobserver variability are notably reduced when measurements are conducted by trained personnel, as was the case in our study (23). In addition, in the prepubertal DONALD participants, strong associations were observed between FFM estimated from skinfold-thickness measurements and independent measures of muscularity such as creatinine excretion, grip force, and forearm muscle area as assessed by peripheral quantitative computed tomography analysis (44). Finally, the elaborate design of the DONALD Study results in a select population with high educational attainment and socioeconomic status. Thus, our study does not include a large percentage of overweight "at risk" children. However, nonrepresentativeness is less relevant for the present longitudinal analyses of physiologic processes and will likely result in underestimation rather than overestimation of the true associations.
In conclusion, the present study does not suggest that prepubertal body composition is critical for the timing of puberty initiation, at least among healthy free-living boys and girls. Instead, higher prepubertal BMI or FM/m2 values may influence how quickly both girls and boys progress through puberty and result in an earlier attainment of later pubertal stages.
| ACKNOWLEDGMENTS |
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The authors responsibilities were as follows—AEB and TR: conceived the project; AEB: conducted the statistical analyses and drafted the manuscript; and AEB, NK-D, and TR: contributed to the interpretation of the data and revision of the manuscript. None of the authors had any personal or financial conflicts of interest.
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