Contents

Introduction

Nutrition is a prerequisite of growth. This general biological principle is long known, and also applies to the human species from conception to adulthood. Severe maternal starvation is associated with smaller size already at birth – multiple historic birth weight data support this association, with data from the siege of Leningrad (Antonov 1947) and the Dutch hunger winter during World War II (Rooij et al. 2010). On the other side, maternal overweight and obesity are associated with larger neonatal weights. Table 1 exemplifies observations of the mid-19^th century (Gassner 1862). Yet, this association is deceptive. Growth is sensitive to food shortages and food excess (Brix et al. 2020; Li et al. 2017), but food is not the regulator of growth and final height in the proper sense. Neither tall stature nor short stature mirror food supply. Short stature is not a synonym of malnutrition (Scheffler and Hermanussen 2022b; Scheffler et al. 2019).

Growth is defined as increase in size over time. But whereas size is easily expressible in measures of length and volume, the commensurability of time is ambiguous. Physical time is measurable with clocks and calendars, but growth demands for an understanding of the pace of life (POL) (Dammhahn et al. 2018; Hermanussen and Meigen 2007; Réale et al. 2010). The POL differs between species and between individuals of the same species. The day length of the fruit fly differs in its meaning from the day length of the tortoise. Fruit fly and tortoise differ in POL, they live at different speed and differ in developmental tempo. So do humans. When most of the 6^th and 7^th grade school girls have started to exhibit the obvious signs of sexual maturity, most of their male classmates are still pre-pubertal. Even though girls and boys do not differ in calendar age, girls mature at faster pace than boys. Skeletal age (bone age (Greulich and Pyle 1959; Tanner et al. 1991)) that has become the gold standard for determining the state of maturity (Serinelli et al. 2011) clearly shows the differences between the sexes, and also the variation of maturity within the same sex (table 2). The same is true for dentition. Assessing the dental state is less accurate, but may serve as a radiation-free alternative for estimating the state of maturity in pre-pubertal children (Boeker et al. 2022; Almonaitiene et al. 2012; Lewis 1991).

The aim of this review is to highlight the association between nutrition and the developmental tempo. Excess food causes tempo acceleration. Food restriction delays tempo.

The binary concept of time tempo

An understanding of the binary concept of physical time and individual tempo is essential for the understanding of growth.

Tempo varies throughout life. Some people mature at slower, others at faster than average pace. Illness, stress, intermediate food shortage and other adverse environmental impacts, may lead to additional halts or periods of deceleration in the development of a child. In many cases, subsequent catch-up compensates for those halts: for a while, children may grow faster than normal. Yet, catch-up may not be complete. Periods of developmental delay may accumulate and in the long run decelerate an individual’s developmental pace. Tempo deceleration affects z-score patterns. Short developmental halts create short dips in the z-scores. Children who permanently mature at delayed or accelerated pace, show characteristic z-score patterns.

Children with delayed growth appear younger than documented in their passports, they are on average shorter and lighter than their classmates of the same age, and tend to grow at low z-scores for height and weight. At pubertal age their height and weight z-scores further decrease forming a V-shape trough, and thereafter rise to final size (Hermanussen 2010). Children with accelerated growth appear older, they are taller and heavier than their calendar age suggests. They tend to grow at high z-scores with a pubertal peak. Absolute height at a certain age depends on tempo, but height also depends on the prospective “true” size. “Truly” tall, but developmentally delayed children may appear normal in size, whereas a developmentally accelerated child may temporarily appear tall and mature early, but will finally end up normal in height (Llop-Viñolas et al. 2004). For better describing the “true” size in the sense of final outcome, the term amplitude has become established for many years. In analogy to the sine function – the sine value depends on both phase and amplitude – the term tempo refers to phase, that is the speed of development and to the state of maturity at a given calendar age; the term amplitude describes the maximum extension.

Tempo varies considerably among healthy individuals as reflected by the standard deviation of skeletal age in American children (Greulich and Pyle 1959) (table 2). It significantly contributes to the variation in momentary size. During adolescence, almost half of the height variance is due to tempo variation (Hermanussen and Meigen 2007). Thus, when talking about variation in growth velocity, we need to carefully consider calendar versus biological age, and to clearly distinguish between the aspects of amplitude and tempo of the growth process.

The inter-individual variability of tempo and its sensitivity to nutrition has caused much confusion. Overfeeding causes mild developmental acceleration. For many years child obesity has been related with tall stature, and was even specifically termed as “Adiposogigantismus” in German literature (Joppich et al. 1975). Meanwhile, the spurious association between food excess and tempo acceleration has been recognized well (Brix et al. 2020; Li et al. 2017). Nowadays, nobody would propagate to treat tall stature by means of diet anymore, but this is much less obvious in the case of short stature and food restriction.

The clinical audience is still wedded to the idea that short stature, called stunting, is caused by malnutritional (Scheffler and Hermanussen 2022b; Scheffler et al. 2019; Hermanussen et al. 2019; Scheffler and Hermanussen 2022a). Also, among the nutrition community, there is “…convergence on the use of length‐for‐age as the indicator of choice in monitoring the long‐term impact of chronic nutritional deficiency” (Lartey 2015). Food restriction delays tempo. Schlesinger (1919) wrote: “The difficult living conditions in the last years of the war [World War I] might even more often cause the delay of the increase in growth during puberty,“ and: “The whole growth disturbance described here is also to be regarded as a simple inhibition; the growth type, the growth curve, did not undergo any significant change in its form, apart from the occasionally observed slight delay of the puberty drive, the onset of puberty increase”. The fact of inhibition of the longitudinal growth of children during the last years of the war is of more scientific interest than practical importance for the above-mentioned reason of the expected reparative capacity; it is an indication of the intensity of the general malnutrition of children. Schlesinger considered the “whole growth disturbance” as a “simple inhibition” that does not affect the form of the growth curve. He also mentioned “expected reparative capacity”, that is catch-up growth in modern terminology.

Catch-up growth

The term catch-up growth (Wit et al. 2013) insinuates catch-up in amplitude. But this is not the case. Catch-up growth describes the compensatory and transitory tempo acceleration following a preceding deceleration in tempo. Catch-up in “growth” is in fact catch-up in tempo. Catch-up growth is cause-specific and characterized by height velocity above the limits of normal for a certain age. It follows a removal of previous biological or psychosocial growth-inhibiting conditions and may occur already within a few days. Catch-up growth is an immediate dynamic physical response and a sensitive indicator of preceding developmental malfunction (Scheffler et al. 2021; Scheffler et al. 2020).

The historic perspective

The sensitivity of tempo is not restricted to nutrition. Tempo is sensitive to a broad spectrum of social, economic, political, and emotional (SEPE) factors (Bogin 2021a; Bogin 2021b). Historic growth data obtained in boarding school boys in 18^th century Germany (Komlos et al. 1992) illustrate the social and political impact on developmental tempo. Adolescents of high aristocratic background are not only taller, but they enter puberty some two years earlier than their non-aristocratic classmates. In the second half of the 19th century, Kotelmann (1879) studied male students of a Latin school in Hamburg. The boys increased in height velocity from 2.17cm per year in the 9th to 10th year of age to a maximum of 7.46 cm in the 15th to 16th year of age, i.e. they experienced their adolescent growth spurt some 2-3 years later than modern boys. Similarly, late adolescent growth was repeatedly reported throughout the second half of the 19^th century and also in the rural areas in the first half of the 20^th century. Further evidence for the sensitivity of tempo to environmental stimuli was provided by studies of menarcheal age. First menstrual bleedings occurred at a surprising 4–5 year delay in the mid-19^th century compared with modern European girls. We assume that social networking and the collective inhibition of sexuality in the 19^th century bourgeoisie was responsible for this “collective social amenorrhea” that, by far, exceeded the delay in growth and physical development of the girls (Hermanussen et al. 2012).

Figure 2  Height z-score pattern of the Swiss boy #197 (see Figure 1). Through line: Z-score pattern based on calendar age. The significant distortion of this z-score pattern with its characteristic adolescent trough coincides with the delay in bone age maturation. Rectangles: Z-score pattern based on RUS (radius, ulnar, small bones) bone age (Tanner et al. 1991). This pattern adjusts for tempo and lacks the adolescent trough as it refers to skeletal maturity

Pace of life (POL)

The POL (Dammhahn et al. 2018; Réale et al. 2010) as reflected in the concept of tempo in human growth is not restricted to early development. Factors that affect tempo tend to persist throughout life. Caloric restriction as one of the most obvious modulators of developmental tempo can extend mean and maximal lifespan. This was first shown in rats (McCay et al. 1935), and thereafter in many other species. The studies contributed essential pieces of knowledge for our understanding of the mechanisms of ageing (McDonald and Ramsey 2010). Thompson et al. showed that humans who grow fastest have the highest hazard of death, and the shortest life expectancy.

These data question modern notions of “optima” and “maxima” in nutrition and height. We appreciate superabundant choices of food in supermarkets and tall and fast-growing children, but we must be increasingly cautious when linking maxima and optima. There is increasing evidence that optimum nutrition rather propends to what we may call “mild caloric restriction”. The association between tempo and life expectancy on the one side – the latter being one of the most frequently used health status indicators (Health status - life expectancy at birth - OECD Data 2022) – and nutritional supply on the other side, suggests modesty in our recommendations and warrens serious contemplation when linking shortness in stature and any necessity of nutrition interventions.

Both tempo and amplitude are dynamic physical responses to environmental circumstances. The wide margin within which both parameters can vary suggests that life-history trade-offs and the plasticity of tempo and amplitude have been most advantageous traits in the bio-cultural evolution of our species.

Many years ago, Jim Tanner [personal communication 1988] borrowed a picture from the world of music: tempo does not change the number of notes or harmonies within a particular piece of music. Yet, it makes an essential difference whether you play this piece of music largo, adagio, or presto.

The effect of tempo on z-score patterns

It has become common practice to depict anthropometric variables on centile curves, or to transform the raw measurement values into z-scores (standard deviation scores, SDS), and thereby relating individual measurements to a reference population of the same sex and the same calendar age (Cole and Green 1992). Z-scores are most appropriate for describing patterns of human growth.

Z-scores depict both amplitude and tempo. But whereas taller than average amplitude results in positive, and smaller than average amplitude in negative z-scores, variations in tempo result in the distortion of the z-score pattern. Children who develop at delayed pace with late onset pubertal growth show an adolescent trough in their z-score pattern (Figure 1, center row), children who develop at faster than average pace temporarily increase in z-scores with an adolescent peak (Figure 1, bottom row).

Figure 3 LOWESS-fitted curves applied to semi-longitudinal data on growth collected between 1951 and 2006 in rural Gambian males. Height-for-age z scores were calculated against the UK 1990 reference. The slightly higher lines in adulthood are the post-1970 data (Prentice et al. 2013). The height-for-age z-score pattern resembles the pattern in Figure 2 suggesting tempo delay of the Gambian male population (reprinted with kind permission of Oxford University Press, November 30th 2020).

Allometry

There is not one tempo for the whole body. Allometry describes the growth of body parts and organ systems at different pace, resulting in changes of proportions. Even the sequence of organ maturation may vary within the body. The maturation of the endocrine system may uncouple from the tempo at which the skeletal maturation proceeds as illustrated in growth studies of girls adopted from orphanages in India or Bangladesh into high-income Scandinavian households (Teilmann et al. 2006; Kuzawa and Bragg 2012). Proos (2009) reported that adopted Indian girls tended to start pubertal development already at age 11.6 (range of 7.3 –14.6) years which was much earlier than Swedish (13.0 years) and wealthy Indian girls (12.4 –12.9 years). The degree to which maturation was sped up in these girls depended on their age of adoption: girls adopted at older ages who spent more time in less favorable conditions, entered puberty earliest upon environmental improvement (Proos et al. 1991). The premature onset of the endocrine regulation seriously interfered with skeletal maturation, and impaired the adolescent growth component. The adolescent growth spurt, though normal in duration and magnitude, was on average 1.5 years earlier, started at shorter height, with final height being reduced to 154 cm. 8% of the adopted Indian girls remained 145 cm or shorter. Several studies from India (Datta Banik 2022b) and Mexico (Datta Banik 2022a) refer to the effect of nutrition and unfavorable living conditions on relative leg length and body proportion.

Conclusion

Nutrition is a prerequisite, but not a regulator of growth in the sense of final outcome in height or weight (amplitude). Nutrition influences the developmental tempo. Excess food causes acceleration, food restriction delays tempo. Tempo acceleration makes children mature at faster pace, and makes them temporarily appear taller than their age mates. Delay in tempo makes children appear short, but it is temporary shortness. Narrowing the view on calendar age leads to the delusion that it is the food that regulates growth. Yet this is deceptive. Tempo reflects the pace of life (POL), and is a dynamic physical response to a broad spectrum also of stressful social, economic, political, and emotional (SEPE) factors. Slowing down tempo e.g. by mild starvation retards the pace of life and thereby, can even extend life expectancy. Tempo is organ specific. Different organ systems grow and mature at different pace.

Appendix

Figure 1  Z-scores for height (centiles for height on the right margins) of nine exemplarily chosen boys of the Swiss longitudinal growth study (Prader et al. 1989) aged 2 to 19 years. Numbers refer to the original numbering of the studied children. APHV indicates age at peak height velocity. Left column: three tall boys, center column: three average height boys, right column: three short boys. Top row: Z-score patterns of children who grow at average tempo (APHV 13.4 to 14.4 years) tend to be horizontal. Center row: Z-score patterns of delayed children (APHV 14.8 to 15.8 years) show an adolescent trough. Bottom row: Z-score patterns of accelerated children (APHV 11.9 to 12.5 years) show an adolescent peak.

References

Almonaitiene, R./Balciuniene, I./Tutkuviene, J. (2012). Standards for permanent teeth emergence time and sequence in Lithuanian children, residents of Vilnius city. Stomatologija 14 (3), 93–100.

Antonov, A. N. (1947). Children born during the siege of Leningrad in 1942. The Journal of Pediatrics 30 (3), 250–259. https://doi.org/10.1016/s0022-3476(47)80160-x.

Boeker, S./Hermanussen, M./Scheffler, C. (2022). Dental age is an independent marker of biological age. Human Biology and Public Health 3. https://doi.org/10.52905/hbph2021.3.24.

Bogin, B. (2021a). Patterns of human growth. Cambridge, Cambridge University Press.

Bogin, B. (2021b). Social-Economic-Political-Emotional (SEPE) factors regulate human growth. Human Biology and Public Health 1. https://doi.org/10.52905/hbph.v1.10.

Brix, N./Ernst, A./Lauridsen, L. L. B./Parner, E. T./Arah, O. A./Olsen, J./Henriksen, T. B./Ramlau-Hansena, C. H. (2020). Childhood overweight and obesity and timing of puberty in boys and girls: cohort and sibling-matched analyses. International Journal of Epidemiology 49 (3), 834–844. https://doi.org/10.1093/ije/dyaa056.

Cole, T. J./Green, P. J. (1992). Smothing reference centile curves: The LMS Method and penalized likelihood. Statistics in Medicine 11, 1305–1319.

Dammhahn, M./Dingemanse, N. J./Niemelä, P. T./Réale, D. (2018). Pace-of-life syndromes: a framework for the adaptive integration of behaviour, physiology and life history. Behavioral Ecology and Sociobiology 72 (3). https://doi.org/10.1007/s00265-018-2473-y.

Datta Banik, S. (2022a). Association of early menarche with elevated BMI, lower body height and relative leg length among 14- to 16-year-old post-menarcheal girls from a Maya community in Yucatan, Mexico. Anthropological Review 85 (1), 85–100. https://doi.org/10.18778/1898-6773.85.1.06.

Datta Banik, S. (2022b). Inter-relationships between percentage body fat, relative subischial leg length and body mass index among adolescents and adults from the Limbu community of Darjeeling, West Bengal. Journal of Biosocial Science 54 (1), 124–134. https://doi.org/10.1017/S0021932020000723.

Gassner, U. K. (1862). Über die Veränderungen des Körpergewichts bei Schwangeren, Gebärenden und Wöchnerinnen. Monatsschrift für Geburtskunde und Frauenkrankheiten 19, 1–68.

Greulich, W. W./Pyle, Sarah I. (1959). Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. Stanford, California, Stanford University Press.

Hermanussen, M. (2010). Auxology: an update. Hormone Research in Paediatrics 74 (3), 153–164. https://doi.org/10.1159/000317440.

Hermanussen, M./Bogin, B./Scheffler, C. (2019). The impact of social identity and social dominance on the regulation of human growth: a viewpoint. Acta Paediatrica 108 (12), 2132–2134. https://doi.org/10.1111/apa.14970.

Hermanussen, M./Lehmann, A./Scheffler, C. (2012). Psychosocial pressure and menarche: a review of historic evidence for social amenorrhea. Obstetrical & Gynecological Survey 67 (4), 237–241. https://doi.org/10.1097/OGX.0b013e31824c94ad.

Hermanussen, M./Meigen, C. (2007). Phase variation in child and adolescent growth. The International Journal of Biostatistics 3 (1), Article 9. https://doi.org/10.2202/1557-4679.1045.

Joppich, G./Asperger, H./Feer, E. (Eds.) (1975). Lehrbuch der Kinderheilkunde. 23rd ed. Stuttgart, Fischer.

Komlos, J./Tanner, J. M./Davies, P. S./Cole, T. (1992). The growth of boys in the Stuttgart Carlschule, 1771-93. Annals of Human Biology 19 (2), 139–152. https://doi.org/10.1080/03014469200002022.

Kotelmann, L. (1879). Die Körperverhältnisse der Gelehrtenschüler des Johanneums in Hamburg: Ein statistischer Beitrag zur Schulhygiene. Zeitschrift des Königlich Preussischen Statistischen Bureaus.

Kuzawa, C. W./Bragg, J. M. (2012). Plasticity in human life history strategy. Current Anthropology 53 (S6), S369-S382. https://doi.org/10.1086/667410.

Lartey, A. (2015). What would it take to prevent stunted growth in children in sub-Saharan Africa? The Proceedings of the Nutrition Society 74 (4), 449–453. https://doi.org/10.1017/S0029665115001688.

Lewis, A. B. (1991). Comparisons between dental and skeletal ages. Angle Orthodontist 61 (87-92). https://doi.org/10.1043/0003-3219(1991)061<0087:CBDASA>2.0.CO;2.

Li, W./Liu, Q./Deng, X./Chen, Y./Liu, S./Story, M. (2017). Association between obesity and puberty timing: a systematic review and meta-analysis. International Journal of Environmental Research and Public Health 14 (10). https://doi.org/10.3390/ijerph14101266.

Llop-Viñolas, D./Vizmanos, B./Closa Monasterolo, R./Escribano Subías, J./Fernández-Ballart, J. D./Martí-Henneberg, C. (2004). Onset of puberty at eight years of age in girls determines a specific tempo of puberty but does not affect adult height. Acta Paediatrica 93 (7), 874–879. https://doi.org/10.1111/j.1651-2227.2004.tb02683.x.

McCay, C. M./Crowell, Mary F./Maynard, L. A. (1935). The effect of retarded growth upon the length of life span and upon the ultimate body size. The Journal of Nutrition 10 (1), 63–79. https://doi.org/10.1093/jn/10.1.63.

McDonald, R. B./Ramsey, J. J. (2010). Honoring Clive McCay and 75 years of calorie restriction research. The Journal of Nutrition 140 (7), 1205–1210. https://doi.org/10.3945/jn.110.122804.

OECD (2022). Health status - life expectancy at birth - OECD Data. Available online at https://data.oecd.org/healthstat/life-expectancy-at-birth.htm (accessed 5/24/2022).

Prader, A./Largo, R. H./Molinari, L./Issler, C. (1989). Physical growth of Swiss children from birth to 20 years of age. First Zurich longitudinal study of growth and development. Helvetica Paediatrica Acta. Supplementum 52, 1–125.

Prentice, A. M./Ward, K. A./Goldberg, G. R./Jarjou, L. M./Moore, S. E./Fulford, A. J./Prentice, A. (2013). Critical windows for nutritional interventions against stunting. The American Journal of Clinical Nutrition 97 (5), 911–918. https://doi.org/10.3945/ajcn.112.052332.

Proos, L. A./Hofvander, Y./Tuvemo, T. (1991). Menarcheal age and growth pattern of Indian girls adopted in Sweden. II. Catch-up growth and final height. Indian Journal of Pediatrics 58 (1), 105–114. https://doi.org/10.1007/BF02810420.

Proos, Lemm A. (2009). Growth & development of Indian children adopted in Sweden. The Indian Journal of Medical Research 130 (5), 646–650.

Réale, D./Garant, D./Humphries, M. M./Bergeron, P./Careau, V./Montiglio, P.-O. (2010). Personality and the emergence of the pace-of-life syndrome concept at the population level. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 365 (1560), 4051–4063. https://doi.org/10.1098/rstb.2010.0208.

Rooij, S. R. de/Wouters, H./Yonker, J. E./Painter, R. C./Roseboom, T. J. (2010). Prenatal undernutrition and cognitive function in late adulthood. Proceedings of the National Academy of Sciences of the United States of America 107 (39), 16881–16886. https://doi.org/10.1073/pnas.1009459107.

Scheffler, C./Bogin, B./Hermanussen, M. (2021). Catch-up growth is a better indicator of undernutrition than thresholds for stunting. Public Health Nutrition 24 (1), 52–61. https://doi.org/10.1017/S1368980020003067.

Scheffler, C./Hermanussen, M. (2022a). Stunting is the natural condition of human height. American Journal of Human Biology 34 (5), e23693. https://doi.org/10.1002/ajhb.23693.

Scheffler, C./Hermanussen, M. (2022b). What tells us stunting. Human Biology and Public Health (2).

Scheffler, C./Hermanussen, M./Bogin, B./Liana, D. S./Taolin, F./Cempaka, P. M. V. P./Irawan, M./Ibbibah, L. F./Mappapa, N. K./Payong, M. K. E./Homalessy, A. V./Takalapeta, A./Apriyanti, S./Manoeroe, M. G./Dupe, F. R./Ratri, R. R. K./Touw, S. Y./K, P. V./Murtani, B. J./Nunuhitu, R./Puspitasari, R./Riandra, I. K./Liwan, A. S./Amandari, P./Permatasari, A. A. I./Julia, M./Batubara, J./Pulungan, A. (2019). Stunting is not a synonym of malnutrition. European Journal of Clinical Nutrition. https://doi.org/10.1038/s41430-019-0439-4.

Scheffler, C./Hermanussen, M./Rogol, A. (2020). Stunting: historical lessons that catch-up growth tells us for mapping growth restoration. Archives of Disease in Childhood. https://doi.org/10.1136/archdischild-2020-319240.

Schlesinger, E. (1919). Wachstum, Gewicht und Konstitution der Kinder und der heranwachsenden Jugend während des Krieges. Zeitschrift für Kinderheilkunde 22, 80–123.

Serinelli, S./Panetta, V./Pasqualetti, P./Marchetti, D. (2011). Accuracy of three age determination X-ray methods on the left hand-wrist: a systematic review and meta-analysis. Legal Medicine (Tokyo, Japan) 13 (3), 120–133. https://doi.org/10.1016/j.legalmed.2011.01.004.

Tanner, J. M./Whitehouse, R. H./Marshall, W. A./Healy, M.J.R./Goldstein, H. (1991). Assessment of skeletal maturity and prediction of adult height (TW2 method). 2nd ed. London, Academic Press.

Teilmann, G./Pedersen, C. B./Skakkebaek, N. E./Jensen, T. K. (2006). Increased risk of precocious puberty in internationally adopted children in Denmark. Pediatrics 118 (2), e391-9. https://doi.org/10.1542/peds.2005-2939.

Wit, C. C. de/Sas, Theo C. J./Wit, J. M./Cutfield, W. S. (2013). Patterns of catch-up growth. The Journal of Pediatrics 162 (2), 415–420. https://doi.org/10.1016/j.jpeds.2012.10.014.