Michael Hermanussen

Knemometry in childhood: accuracy and standardization of a new technique of lower leg length measurement

Recently, a new anthropometric method of accurate lower leg length measurement (knemometry) was introduced. The present study was performed to investigate rigorously its strengths and weaknesses for auxological purposes, and to promote a standardized method of use. The data are based on 6 x 2200 single estimations of the lower leg length in 90 children of both sexes with normal, tall or short stature aged between 2.4 and 17.1 years. The overall technical error of this measurement was found to be 0.16 mm, which is reduced to 0.13 mm if the first estimation within each series of six is ignored. The following sources of systematic error could be detected: intra-daily variation, dependency on physical pressure put on or removed from the leg, vigorous physical activity prior to the measuring procedure, and a slow but significant correlation between day-to-day variation of lower leg length and body weight (r = 0.299, b = 0.372 mm/kg). There was no covariation with atmospheric parameters such as outside temperature, barometric pressure and others. After elimination of a linear trend from the individual growth curves, there was a remaining day-to-day variation of SD = 0.697 mm. This represents real changes of lower leg length and cannot be explained by the technical error of measurement which contributes to less than 10% of the total variation. Some of this day-to-day variation may be explained by non-linearity of growth. Knemometry appears to be a robust and precise new tool for the investigation of short term kinetics of longitudinal growth. Proposals for a standardized use of this technique are given.

KNEMOMETRIC MONITORING OF EARLY EFFECTS OF HUMAN GROWTH HORMONE ON LEG LENGTH IN CHILDREN WITH GROWTH HORMONE DEFICIENCY

The early effects of human growth hormone (hGH) were investigated by knemometry, a recently described technique of measuring lower leg length. In 14 growth hormone deficient children, the mean increase in the lower leg length was 0.47 +/- 0.10 (SE) mm within 24 h of a single intramuscular injection of 4 IU hGH. This increase occurred after about 80% of the single injections and was highly significant (p less than 0.01). 48 h after an injection, a slight but not significant reduction of the lower leg length was observed (-0.15 +/- 0.09 [SE]). These effects led to a marked zig-zag pattern of growth when hGH was given thrice weekly.

Can the Knemometer Shorten the Time for Growth Rate Assessment

Hermanussen, M., Geiger‐Benoit, K., Burmeister, J., and Sippell, W. G. (Endocrine Unit, Department of Paediatrics, Childrens Hospital, and Institute for Jnformatics and Practical Mathematics, University of Kiel, Kiel, West Germany. Acta Paediatr Scand [Suppl] 337:30, 1987.

Stature and stature distribution in recent West German and historic samples of Italian and Dutch conscripts

Based on the standard for the natural distribution of stature obtained from 11,851,168 West German conscripts (born in 1938–1971), stature and stature distribution were investigated in historic samples of Italian (born 1854–1963) and Dutch (drafts of 1863–1970) conscripts. Both stature and stature distribution in the historic Italian and Dutch samples showed a variety of characteristic deviations from the natural stature distribution of the modern populations, which strongly suggest that there are at least two developmental periods that are sensitive to socioeconomic events with regard to final stature. Environmental disasters during pregnancy and the first year of life lead to a ubiquitous reduction of mean stature in the total cohort affected. This is obvious in Italians born in 1945, who are 3.7 mm shorter than those born in 1944, and 7.9 mm shorter than those born in 1946. An even stronger suppression of final stature by more than 12 mm is obvious in Italians born in 1899 and 1900. Stature distribution, however, is influenced by environmental factors during adolescence. Particularly small persons become numerous during periods of war and economic depression. This is evident in the 19th century Dutch and Italian samples, and during the early 1920s. Changes in developmental tempo seem unlikely to cause these effects.

GH Deficient Children Receiving GH Replacement Do not Grow during Intermittent Infectious Illness

ABSTRACT. Five growth hormone deficient children, aged 5.3 to 12.6 yrs, were measured regularly once or twice weekly by knemometry, a novel and noninvasive technique of accurate lower leg length measurement. The total period of observation was 40 months in the 5 children. During this time all children received replacement therapy with extractive human pituitary growth hormone 12 IU/m2/week by daily S.C. injections. 11 intermittent infectious illnesses occurred within the observation period of 40 months. During the infectious diseases a significant decrease of the mean lower leg growth velocity down to ‐0.012 mm/day was observed. During the following convalescent period (14 days) mean lower leg growth velocity rose up to +0.107 mm/day (p< 0.001). Growth hormone substitution was not changed throughout the period of observation.

Does the thrifty phenotype result from chronic glutamate intoxication? A hypothesis.

Abstract The thrifty phenotype hypothesis proposes that the epidemiological associations between poor fetal and infant growth and the subsequent development of the metabolic syndrome, result from the effects of poor nutrition in early life. The present review however, considers an opposite explanation. We hypothesize that fetal over-nutrition plays a major role in the development of the metabolic syndrome. We found evidence that the thrifty phenotype may be the consequence of fetal hyperglutamatemia. Maternal glutamate (GLU) reaches the fetal circulation, as part of the materno-fetal glutamine-glutamate exchange. Glutamine is absorbed from the maternal circulation, and deaminated for nitrogen utilization, resulting in a fetal production of GLU. GLU is extracted as it returns to the placenta. When the umbilical plasma flow is low, GLU may be trapped in the fetal circulation, and reaches neurotoxic levels. Administering GLU to newborn rodents completely destructs arcuate nucleus neurons, and results in permanently elevated plasma leptin levels that fail to adequately counter-regulate food intake. Chronic fetal exposure to elevated levels of GLU may be caused by chronic maternal over-nutrition or by reduced umbilical plasma flow. We strongly suggest abandoning the flavoring agent monosodium glutamate and reconsidering the recommended daily allowances of protein and amino acids during pregnancy.

Modeling determinants of growth: evidence for a community-based target in height?

Background:Human growth is traditionally envisaged as a target-seeking process regulated by genes, nutrition, health, and the state of an individual’s social and economic environment; it is believed that under optimal physical conditions, an individual will achieve his or her full genetic potential.Methods:Using a panel data set on individual height increments, we suggest a statistical modeling approach that characterizes growth as first-order trend stationary and allows for controlling individual growth tempo via observable measures of individual maturity. A Bayesian framework and corresponding Markov-chain Monte Carlo techniques allowing for a conceptually stringent treatment of missing values are adapted for parameter estimation.Results:The model provides evidence for the adjustment of the individual growth rate toward average height of the population.Conclusion:The increase in adult body height during the past 150 y has been explained by the steady improvement of living conditions that are now being considered to have reached an optimum in Western societies. The current investigation questions the notion that the traditional concept in the understanding of this target-seeking process is sufficient. We consider an additional regulator that possibly points at community-based target seeking in growth.

Statistical agreement and cost–benefit: Comparison of methods for constructing growth reference charts

Abstract Background: Growth reference charts are important tools for adequate paediatric decisions. Aim: In view of the workload required to construct empirical growth reference charts we debate practicable and less demanding alternatives and took the recent national 2000–2002 Lithuanian growth charts as an example. Two options appeared reasonable: (1) applying international WHO child growth standards and WHO growth reference data for 5–19 years that are recommended for global use; or (2) replacing the costly empirical method of deriving national growth references by more convenient low-cost statistics, e.g. the method of generating synthetic references for the Lithuanian population. Methods: We analysed the degree of agreement between the 2000–2002 Lithuanian growth charts, and the international WHO child growth standards and WHO growth reference data for 5–19 years and synthetic references for the Lithuanian population using the Bland–Altman method. Results: Synthetically generated references for the Lithuanian population slightly surpassed the national Lithuanian reference for body height (males +0.3 (SD 0.9) cm; females +0.2 (SD 0.6) cm) particularly at young age, which may be regarded clinically irrelevant. WHO international child growth standards and the WHO growth reference data for 5–19 years, however, failed to match the Lithuanian references as they underestimated mean height in boys by –2.8 (SD 1.4) cm and in girls by –2.9 (SD 1.1) cm, with extremely discrepant estimates of more than –6 cm occurring in several adolescent cohorts. Conclusions: The analysis revitalizes the debate on clinically relevant and at the same time practicable but less demanding alternatives for constructing growth reference charts, and for economic reasons, strongly suggests replacing the traditional empirical methods by synthetic growth references.

Children do not grow continuously but in spurts

The description of the human growth pattern in limited largely to the traditional vocabulary of “linear growth rates,” i.e., height or length increments divided by certain time intervals such as months or years. These studies have been performed using conventional techniques of body length or stature measurement with a technical error of approximately 1.5 mm. During the last 10 years, measurements of lower leg length (knemometry) have been performed with a significantly lower technical error (0.09–0.16 mm). Repeated determinations of lower leg length at short intervals are now feasible, and evidence indicates that “short term growth” is a phenomenon that includes both length increment and decrement. At measurement intervals of exactly 1 week, growth appears periodic showing marked spurts that alternate with intervals of decreased growth velocity with a peak‐to‐peak distance of 30–55 days (mini growth spurts). These spurts have significant clinical importance and can be used as predictive criteria for successful growth promotion in growth hormone therapy of short stature. Lower leg length measurements at 24‐hour intervals provide evidence for the existence of circaseptan periodicity.

The association between birth order and adult stature

First-borns are smaller than later-borns at birth. We investigated adult stature of families with three or more adult children, aged between 20 and 70 (mean 32) years. There was no significant correlation between size of the family and final adult stature of the siblings. We found a mean height reduction of first-borns compared to the mean of all sibs of -1.2 cm (P less than 0.02 using conventional analysis of variance, P less than 0.05 using nonparametric prediction configural frequency analysis). Males tend to increase in height with increasing birth order, whereas females do not beyond the second-born. These observations could not be explained by decreasing age of later-born sibs, nor by periods of malnutrition immediately after the war (1945-1948). Thus, we conclude that birth order is a factor that contributes significantly to the variance of adult height within sibships.