summarises the review of published data and our new analyses, restricted to anthropometric indicators of undernutrition (panel 2
). We provide strong evidence that adequate nutrition in utero and in the first 2 years of life is essential for formation of human capital. Undernourished children are more likely to become short adults, to have lower educational achievement, and to give birth to smaller infants. Undernutrition is also associated with lower economic status in adulthood. At present our cohorts are too young to assess the association between undernutrition and life expectancy, but in view of the direct association between longevity and schooling,159
such an association will probably become apparent in the long term. Because of the major importance of nutrition for human capital, the amount of research on this issue is remarkably small. Areas in which further research is particularly needed are listed in panel 3
Summary of the evidence, particularly from low-income and middle-income settings, on the associations between maternal and child undernutrition and adult exposures
Panel 2. What this paper does not cover
This paper addresses maternal and child undernutrition through the use of anthropometric indicators. There are other dimensions of undernutrition that are equally important. These include micronutrient deficiencies—eg, iodine, iron, vitamin A, and calcium—which might lead to long-term consequences. An earlier Lancet
Series addressed the long-term consequences of iodine and zinc deficiency on intellectual development,156
and these deficiencies were incorporated in the estimates of burden of diseases included in the first paper in this Series.1
Breastfeeding can also have long-term health consequences. A recent series of systematic reviews addressed its association with body-mass index, blood pressure, diabetes and related indicators, blood lipids, and schooling.86
Two important studies on the effects of short exposures to malnutrition during famines in Europe—the Dutch famine157,158
and Leningrad siege studies—were cited only when evidence from low-income and middle-income countries was very scarce. Although these investigations provide unique information about crucial periods when undernutrition is likely to have lasting effects, they were deemed not to be representative of the situation in such countries when undernutrition acts throughout longer time periods including pregnancy, infancy, and childhood.
Panel 3. Areas for future research
• Association between rapid weight and length gain at different age intervals in infancy and childhood with human capital and outcomes related to chronic disease, to define the age after which rapid growth should be avoided
• Long-term effects of weight gain in late childhood stratified in previously stunted and non-stunted children, and for children with and without intrauterine growth restriction
• Long-term effects of micronutrient deficiencies in childhood
• Association between undernutrition and long-term changes in immune function, blood lipids, osteoporosis, and mental illness
• Improved quantification of the economic effect of undernutrition on adult productivity
• Interactions between genes and environmental factors in long-term outcomes
The effect of undernutrition spans at least three generations, as suggested by the small but significant association between grandmother's height and birthweight of children born to women from the five cohorts. Because of their fairly small magnitude, intergenerational effects do not preclude achievement of progress by acting only on the present generation.
The results of outcomes related to chronic disease were not so straightforward (). Adult body-mass index seems to be strongly affected by the childhood indices related to weight, and to a lesser extent by height-for-age. Because body-mass index includes fat and lean mass, its associations with early weight and height might have different biological implications. Glucose concentrations were not associated with any of the exposures, but it should be noted that participants in the five cohorts are fairly young and that a post-glucose-load concentration was available in only one cohort. In high-income countries, the association of lower birthweight with raised glucose concentration is seen mainly with post-glucose-load values. Systolic and diastolic blood pressure were positively associated with childhood weight and height, and to a lesser extent to body-mass-index-for-age, but these associations were small and their clinical relevance is questionable. Taken together, our results show weaker associations between size at birth or in infancy with outcomes related to chronic disease than do those arising from cohorts in developed countries. In addition to the young age of our cohorts, other factors might have a role, including the fact that the causes of low birthweight are different and there is less catch-up growth compared with developed settings, and that some of our cohorts were not undergoing the nutrition transition.
We analysed five long running prospective cohorts in low-income and middle-income countries in a similar way. The consistency of most results is remarkable, considering that study sites are located in South and Central America, sub-Saharan Africa, and south and east Asia. Because analyses were defined a priori, our results are not affected by publication bias.
There were substantial increases in the coefficients after adjustment for adult body-mass index and height. In earlier analyses related to the Barker hypothesis, adjustment for present size was a standard procedure, but this practice has been challenged.84
Our reviews of studies from low-income and middle-income countries on lipid profiles, diabetes, blood pressure, and cardiovascular disease showed that the negative effects of undernutrition often only become apparent—or at least were strengthened—after such adjustment. If an early weight and present weight or body-mass index are included in the same regression equation, the coefficient associated with the early weight measure will become negative whenever weight gain is positively associated with the outcome. For example, a negative association with birthweight that becomes apparent only when adult body-mass index is included in the statistical model does not suggest that low birthweight itself is a risk factor; in fact, postnatal excessive weight gain might have a large role.70,84,95,119
For the outcomes for which no new data are presented, there is insufficient evidence linking undernutrition to long-term changes in immune function or blood lipids, or in indicators related to osteoporosis. Birthweight is positively associated with lung function, and there is some evidence that undernutrition might contribute to mental illness. By contrast with these findings (ie, showing detrimental effects of undernutrition), studies suggest a positive association between birthweight and the incidence of some cancers.
A recent symposium160
addressed the contrasting perspectives of auxology and biomedicine—“poor growth is poor health”—and evolutionary biology and anthropology—“poor growth is adaptive”. The evidence for the biomedical stance is overwhelming and recognised by the symposium participants, but the two approaches are not incompatible. In response to poor nutrient availability at the cellular level, vital functions are preserved, linear growth is stopped, and muscle and fat can be metabolised for continued function. Thus poor growth can be a survival strategy. However, the evidence that growth failure has a huge cost is overwhelming: compared with people who grow well, there is increased susceptibility to infections and greater mortality1
and losses in human capital in survivors. A population of stunted people will indeed have lower nutritional requirements than will a population with unrestricted growth, which might be seen as an adaptation; however, such a population will be less likely to be competitive in the modern world because of reduced human capital.
Rapid weight gain is especially relevant in low-income and middle-income countries that are undergoing rapid transition and facing an epidemic of overweight and obesity. The long-term effects of early undernutrition might be compounded by the adoption of diets and lifestyles of developed countries.134
A baby of low birthweight, who is stunted and underweight in infancy and gains weight rapidly in childhood and adult life, can represent a worst-case scenario for cardiovascular and metabolic disease.10,134,161,162
However, rapid weight gain in infancy is associated with lower morbidity and mortality in low-income and middle-income settings,1,163
and as shown above, bodysize at 2 years of age is clearly associated with enhanced human capital. Although these are sufficient reasons for strong efforts in the prevention of undernutrition, attention should also be given to preventing excessive weight gain after infancy.
To design evidence-based policies, the potential hazards of rapid weight gain in different age ranges should be established. There is growing evidence that a high birthweight64
and weight gain in infancy lead primarily to accumulation of lean body mass, whereas gaining weight later in childhood is more likely to result in accumulation of fat mass.9,22,65,164
A recent meta-analysis centred on studies from high-income countries concluded that “there is insufficient evidence to recommend prevention of adult disease through strategies to alter infant growth.”95
Therefore, present evidence does not accord with limiting weight gain in the first year of life, and suggests that rapid weight gain becomes hazardous only later in childhood. Further research is needed to establish the exact age when rapid weight gain does more harm than good.
The first article in this Series proposed stunting as a better overall indicator of undernutrition than underweight.1
In countries undergoing the nutrition transition, monitoring length-for-age and weight-for-length in young children has been argued to be more appropriate than monitoring weight-for-age,165
because weight gain can reflect children becoming taller, fatter, or both. Our findings support this argument. Height-for-age at 2 years was more closely related to outcomes for human capital than birthweight, weight-for-age, or body-mass-index-for-age. Body-mass-index-for-age was not an important predictor of human capital, although it is highly predictive of adult body-mass index. Countries undergoing the nutrition transition should consider the advantages of assessing height-for-age and body-mass-index-for-age, in view of their different predictive values.
Because of the observational nature of our analyses, the possibility of residual confounding cannot be ruled out. However, that adjustment for confounders, including socioeconomic indicators, made little difference to estimates of effect size is reassuring. In the one trial included in our analysis, exposure to a nutritious supplement during pregnancy and early childhood, compared with exposure to low-energy supplement, led to greater adult height, schooling (women only), improved scores on tests of intelligence and reading, greater income, and better growth of the next generation.31,38,48,57,166,167
Our results strongly suggest that undernutrition leads to long-term impairment. This evidence, combined with the well-known short-term effects of undernutrition, is sufficient for giving the prevention of undernutrition high priority in national health, education, and economic agendas in low-income and middle-income countries.45,168
At the same time as investments are made against undernutrition, middle-income countries undergoing the nutrition transition should also address the negative consequences of rapid weight gain, especially in later childhood.