Essential fatty acids (EFA) are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LCPUFA). These fatty acids serve as specific precursors for eicosanoids that regulate numerous cell and organ functions. Results from animal and recent human studies support the essential nature of n-3 EFA in addition to the well-established role of n-6 EFA for human subjects, particularly in early life. The most significant effects relate to neural development and maturation of sensory systems. Recent studies using stable-isotope-labelled tracers demonstrate that even preterm infants are able to form arachidonic acid (AA) and docosahexaenoic acid (DHA), but that synthesis is extremely low. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation, and retinal and nervous system development. Regulation of gene expression by LCPUFA occurs at the transcriptional level and is mediated by nuclear transcription factors activated by fatty acids. These nuclear receptors are part of the steroid hormone receptor family. Two types of polyunsaturated fatty acid responsive transcription factors have been characterized, the peroxisome proliferator-activated receptor (PPAR) and the hepatic nuclear factor 4α. DHA also has significant effects on photoreceptor membranes involved in the signal transduction process, rhodopsin activation, and rod and cone development. Comprehensive clinical studies have shown that dietary supplementation with marine oil or single-cell oils, sources of LCPUFA, results in increased blood levels of DHA and AA, as well as an associated improvement in visual function in formula-fed premature infants to match that of human milk-fed infant. Recent clinical trials convincingly support LCPUFA supplementation of preterm infant formulations and possibly term formula to mimic human milk composition.

The present paper reviews the research of the authors and their colleagues over the past 20 years to provide improved nutritional and anthropometric guidelines for the assessment of lactational adequacy and for when the weaning process might be initiated. The nutritional guidelines are based on revised dietary energy requirements. The basic assumption is that since breast milk is a well-balanced food, if energy needs are satisfied so will those for essential nutrients. Energy requirements for young babies have been derived from the application of the doubly-labelled-water technique. This approach indicated that 460 kJ (110 kcal)/kg per d at 1 month and 397 and 355 kJ (95 and 85 kcal)/kg per d at 3 and 6 months respectively would be satisfactory for a nutrient content of high bioavailability. Translated into a breast-milk intake of 850 ml/d the latter would cover the dietary energy needs of the average child growing along the 50th centile until at least 4 months, but the typical child from many developing countries following the 25th centile until 6 months. The importance of revised growth reference values for infancy, equally crucial for assessing lactational adequacy, is also reviewed. In contrast with the shapes of earlier reference patterns, growth trajectories are different when babies are fed in accordance with modern paediatric advice. Mothers and health professionals using the older growth charts to assess the progress of a baby can be misled into assuming that the weaning process needs to be introduced sooner than necessary. Examples of this situation within the context of a developing country are provided.

The importance of cultural and behavioural factors in children’s nutrition, particularly with regard to feeding, has been recognized only recently. The combination of evidence regarding the importance of caregiving behaviour for good nutrition, and improved strategies for measuring behaviour have led to a renewed interest in care. The UNICEF conceptual framework suggests that care, in addition to food security and health care services, are critical for children’s survival, growth and development. The present paper focuses on the care practice of complementary feeding, specifically behavioural factors such as parental interaction patterns, feeding style and adaptation of feeding to the child’s motor abilities (self-feeding or feeding by others). Three kinds of feeding styles (Birch & Fisher, 1995) are identified: controlling; laissez-faire; responsive. Probable effects of each feeding style on nutrient intake are described. A number of studies of feeding behaviour have suggested that the laissez-faire style is most frequently observed among families and communities with a higher prevalence of malnourished children. Nutrition interventions that have been able to show significant effects on outcomes, such as the Hearth Model in Vietnam (Sternin et al. 1997), have usually incorporated behavioural components in their intervention. At this time, there have been no tests of the efficacy of behavioural interventions to improve feeding practices. Research is needed to understand behavioural factors in complementary feeding, and to identify and test intervention strategies designed to improve nutrient intake of young children. Finally, the paper concludes with a discussion of how nutrition programmes might change if care were incorporated.

Although failure to thrive (FTT) is generally thought to be a nutritional problem, dietary intake in children with FTT has been little researched. We describe two community-based studies of dietary intake and eating behaviour in FTT. The first study of ninety-seven children with FTT identified by population screening found that only a minority of case children were associated with neglect, organic illness or deprivation, even though dietary information suggested an underlying nutritional cause in the majority. Limited case-control data suggested significantly delayed weaning and less liking for food in general among the case children. The second study found diminished appetite, delayed progression onto solid foods and fewer foods eaten by forty-four children referred with FTT compared with forty-five controls, but was unable to detect a significant difference in energy intake, even allowing for varying body composition and other confounding variables. This study also revealed the bias introduced by recruiting case children by referral rather than screening, and that despite rigorous matching procedures the controls were not representative of the general population. These studies suggest a wide range of differences in eating behaviour and feeding patterns between children with FTT and controls, but suggest that measurements of nutrient totals may not be robust. Studies of FTT based on referred children can be misleading, as can comparison with controls, unless allowance can be made for important confounding social variables.

The literature on the long-term effects of nutritional deficiencies in early life is reviewed. The severity and duration of the deficiency, the stage of the children’s development, the biological condition of the children and the socio-cultural context may all modify the effect. There is substantial evidence that reduced breast-feeding, small-for-gestational-age birth weight, Fe and I deficiency, and protein-energy malnutrition (PEM) are associated with long-term deficits in cognition and school achievement. However, all these conditions are associated with poverty and poor health, which may account for the association. It is difficult to establish that the long-term relationship is causal, as it requires a randomized treatment trial with long-term follow-up. Such studies are only available for I deficiency in utero and early childhood PEM. Results from these studies indicate that I deficiency has a long-term effect and PEM probably has a long-term effect.

Several factors have been found recently to have a significant impact on newborn bone mineral content (BMC) and developing fetal bone. Recently we showed that maternal vitamin D deficiency may affect fetal bone mineralization. Korean winter-born newborn infants had extremely low serum 25-hydroxyvitamin D (25-OHD), high serum cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker), and markedly lower (8 %) total body BMC than summer-born newborn infants. Infant total body BMC was positively correlated with cord serum 25-OHD and inversely correlated with ICTP, which was also negatively correlated with vitamin D status. In three separate studies on North American neonates we found markedly lower (8–12 %) BMC in summer newborn infants compared with winter newborn infants, the opposite of the findings for Korean neonates. The major reason for the conflicting BMC results might be the markedly different maternal vitamin D status of the North American and Korean subjects. Recently, we found evidence of decreased bone formation rates in infants who were small-for-gestational age (SGA) compared with infants who were appropriate-for-gestational age; we reported reduced BMC, cord serum osteocalcin (a marker of bone formation) and 1,25-dihydroxyvitamin D (the active metabolite of vitamin D), but no alterations in indices of fetal bone collagen metabolism. In theory, reduced utero-placental blood flow in SGA infants may result in reduced transplacental mineral supply and reduced fetal bone formation. Infants of diabetic mothers (IDM) have low BMC at birth, and infant BMC correlated inversely with poor control of diabetes in the mother, specifically first trimester maternal mean capillary blood glucose concentration, implying that factors early in pregnancy might have an effect on fetal BMC. The low BMC in IDM may be related to the decreased transplacental mineral transfer. Cord serum ICTP concentrations were higher in IDM than in control subjects, implying increased intrauterine bone resorption. BMC is consistently increased with increasing body weight and length in infants. Race and gender differences in BMC appear in early life, but not at birth. Ethanol consumption and smoking by the mother during pregnancy affect fetal skeletal development.

Retinoic acid (RA) is the bioactive metabolite of vitamin A (retinol) which acts on cells to establish or change the pattern of gene activity. Retinol is converted to RA by the action of two types of enzyme, retinol dehydrogenases and retinal dehydrogenases. In the nucleus RA acts as a ligand to activate two families of transcription factors, the RA receptors (RAR) and the retinoid X receptors (RXR) which heterodimerize and bind to the upstream sequences of RA-responsive genes. Thus, in addition to the well-established experimental paradigm of depriving animals of vitamin A to determine the role of RA in embryonic and post-embryonic development, molecular biology has provided us with two additional methodologies: knockout the enzymes or the RAR and RXR in the mouse embryo. The distribution of the enzymes and receptors, and recent experiments to determine the endogenous distribution of RA in the embryo are described here, as well as the effects on the embryo of knocking out the enzymes and receptors. In addition, recent studies using the classical vitamin A-deprivation technique are described, as they have provided novel insights into the regions of the embryo which crucially require RA, and the gene pathways involved in their development. Finally, the post-embryonic or regenerating systems in which RA plays a part are described, i.e. the regenerating limb, lung regeneration, hair cell regeneration in the ear and spinal cord regeneration in the adult.

I is required for the synthesis of thyroid hormones. These hormones, in turn, are required for brain development, which occurs during fetal and early postnatal life. The present paper reviews the impact of I deficiency (1) on thyroid function during pregnancy and in the neonate, and (2) on the intellectual development of infants and children. All extents of I deficiency (based on I intake (μg/d); mild 50–99, moderate 20–49, severe > 20) affect the thyroid function of the mother and neonate, and the mental development of the child. The damage increases with the extent of the deficiency, with overt endemic cretinism as the severest consequence. This syndrome combines irreversible mental retardation, neurological damage and thyroid failure. Maternal hypothyroxinaemia during early pregnancy is a key factor in the development of the neurological damage in the cretin. Se deficiency superimposed on I deficiency partly prevents the neurological damage, but precipitates severe hypothyroidism in cretins. I deficiency results in a global loss of 10–15 intellectual quotient points at a population level, and constitutes the world’s greatest single cause of preventable brain damage and mental retardation.

Insufficient polyamine intake could play a role in the induction of sensitization to dietary allergens. This proposal is based essentially on investigations made in sucking rats and in children. In sucking rats it has been established that oral administration of spermine can induce all the modifications occurring in the digestive tract at weaning. In the intestine events occur in two phases. The early event consists of desquamation of the epithelium resulting from an activation of apoptosis. The late event appears to involve an hormonal cascade in which adrenocorticotropic hormone, cytokines, bombesin and corticosterone are included. Observations in human subjects show that: (1) the spermine and spermidine concentrations are generally lower in infant formulas than in human breast milk. Mothers seem consistently to have relatively high or relatively low concentrations of spermine and spermidine in their milk. These individual variations may be due to diet, lifestyle or genetic background; (2) the probability of developing allergy can reach 80 % if the mean spermine concentration in the milk is lower than 2 nmol/ml milk. It is approximately 0 % if the mean spermine concentration is higher than 13 nmol/ml milk; (3) preliminary results show that the intestinal permeability to macromolecules differs in premature babies when they are fed on breast milk compared with infant formulas (J Senterre, J Rigo, G Forget, G Dandrifosse and N Romain, unpublished results). This difference does not seem to be present when powdered milk is supplemented with polyamines at the concentration found in breast milk; (4) spermine increases proliferation and differentiation of lymphocytes isolated from the tonsils of children.

The period of growth and development between birth and weaning is crucial for the long-term well-being of the organism. Protein deposition is very rapid, is achieved with a high nutritional efficiency, and is accompanied by marked differences in the growth rates of individual tissues and a series of maturational processes. These important aspects of development occur while the neonate is consuming a single and highly-specific food source, milk. Surprisingly, although there is a clear relationship between the nutrient density of milk and the growth rate of its recipient, this relationship does not apply to the overall amino acid composition of mixed milk proteins. Some amino acids, notably glycine and arginine, are supplied in milk in quantities that are much less than the needs of the neonate. The milk-fed neonate is therefore capable of carrying out a tightly-regulated transfer of N from amino acids in excess to those that are deficient. The rapid growth of the neonate is supported by a high rate of tissue protein synthesis. This process appears to be activated by the consumption of the first meals of colostrum. Recent research has identified that skeletal muscle and the brain are specifically responsive to an unidentified factor in colostrum. Following the initial anabolic response the rate of protein synthesis in some tissues, notably muscle, falls from birth to weaning. This decrease reflects a progressively smaller anabolic response to nutrient intake, which not only involves an overall fall in the capacity for protein synthesis, but also in responses to insulin and amino acids. The study of growth and protein metabolism, and their regulation in the neonate is not only important for pediatrics, but may provide important pointers to more general aspects of regulation that could be applied to the nutrition of the mature animal.

The substrate demands of lactation must be met by increased dietary intake or by mobilization of nutrients from tissues. The capacity of animals to rely on stored nutrients depends to a large extent on body size; large animals have greater stores, relative to the demands of lactation, than do small animals. The substrate demands of lactation depend on the composition and amount of milk produced. Animals that fast or feed little during lactation are expected to produce milks low in sugar but high in fat, in order to minimize needs for gluconeogenesis while sustaining energy transfers to the young. The patterns of nutrient transfer are reviewed for four taxonomic groups that fast during part of or throughout lactation: sea lions and fur seals (Carnivora: Otariidae), bears (Carnivora: Ursidae), true seals (Carnivora: Phocidae) and baleen whales (Cetacea: Mysticeti). All these groups produce low-sugar high-fat milks, although the length of lactation, rate of milk production and growth of the young are variable. Milk protein concentrations also tend to be low, if considered in relation to milk energy content. Maternal reserves are heavily exploited for milk production in these taxa. The amounts of lipid transferred to the young represent about one-fifth to one-third of maternal lipid stores; the relative amount of the gross energy of the body transferred in the milk is similar. Some seals and bears also transfer up to 16–18 % of the maternal body protein via milk. Reliance on maternal reserves has allowed some large mammals to give birth and lactate at sites and times far removed from food resources.

Appropriate nutrient partitioning between the maternal body and gravid uterus is essential for optimum fetal growth and neonatal survival, and in adult sheep nutrient partitioning during pregnancy generally favours the conceptus at the expense of the dam. However, recent studies using an overnourished adolescent sheep model demonstrate that the hierarchy of nutrient partitioning during pregnancy can be dramatically altered in young growing females. Overnourishing the adolescent dams to promote rapid maternal growth throughout pregnancy results in a major restriction in placental mass and leads to a significant decrease in birth weight relative to moderately-fed adolescents of equivalent gynaecological age. High maternal feed intakes are also associated with an increased incidence of non-infectious spontaneous abortion, a reduction in gestation length and colostrum production, and a higher incidence of neonatal mortality. The present paper examines the putative role of a variety of endocrine regulators of nutrient partitioning in this unusual model system, where the dam is overnourished while the stunted placenta restricts nutrient supply to the fetus. The central role of nutritionally-mediated alterations in placental growth and development in setting the subsequent pattern of nutrient partitioning between the maternal body, placenta and fetus is examined, and critical periods of sensitivity to alterations in maternal nutritional status are defined. Finally, the consequences of this form of inappropriate nutrient partitioning on the growth and development of the fetus and neonate are described with particular emphasis on the reproductive axis.

Empirical evidence suggests that prolonged underfeeding of protein to late-pregnant dry cows can have modest negative carry-over effects on milk volume and/or protein yield during early lactation, and may also cause increased incidence of metabolic diseases associated with fatty liver. However, assessment of requirements is hampered by lack of information on relationships between dietary intake of crude protein (N × 6·25) and metabolizable protein supply during late pregnancy, and by incomplete understanding of the quantitative metabolism of amino acids in maternal and conceptus tissues. Inability of the postparturient cow to consume sufficient protein to meet mammary and extra-mammary amino acid requirements, including a significant demand for hepatic gluconeogenesis, necessitates a substantial, albeit transient, mobilization of tissue protein during the first 2 weeks of lactation. Ultimately, much of this mobilized protein appears to be derived from peripheral tissues, especially skeletal muscle and, to a lesser extent, skin, through suppression of tissue protein synthesis, and possibly increased proteolysis. In the shorter term, soon after calving, it is likely that amino acids required for hepatic glucose synthesis are diverted from high rates of synthesis of splanchnic tissue and export proteins, including serum albumin. The prevailing endocrine milieu of the periparturient cow, including major reductions in plasma levels of insulin and insulin-like growth factor-I, together with insulin resistance in peripheral tissues, must permissively facilitate, if not actively promote, net mobilization of amino acids from these tissues.

Changes in the amount and metabolism of adipose tissue (AT) occur in underfed ruminants, and are amplified during lactation, or in fat animals. The fat depot of the tail of some ovine breeds seems to play a particular role in adaptation to undernutrition; this role could be linked to its smaller adipocytes and high sensitivity to the lipolytic effect of catecholamines. Glucocorticoids and growth hormone probably interact to induce teleophoretic changes in the AT responses to adenosine and catecholamines during lactation. Fat mobilization in dry ewes is related both to body fatness and to energy balance. The in vivo β-adrenergic lipolytic potential is primarily related to energy balance, whereas basal postprandial plasma non-esterified fatty acids (NEFA) are related to body fatness, and preprandial plasma NEFA is the best predictor of the actual body lipid loss. Several mechanisms seem to be aimed at avoiding excessive fat mobilization and/or insuring a return to the body fatness homeostatic set point. As well as providing the underfed animal with fatty acids as oxidative fuels, AT acts as an endocrine gland. The yield of leptin by ruminant AT is positively related to body fatness, decreased by underfeeding, β-adrenergic stimulation and short day length, and increased by insulin and glucocorticoids. This finding suggests that the leptin chronic (or acute) decrease in lean (or underfed respectively) ruminants is, as in rodents, a signal for endocrine, metabolic and behavioural adaptations aimed at restoring homeostasis.

While being underweight or stunted is recognized as an important risk factor for increased prevalence and severity of infection and high mortality rates, there is increasing evidence for an independent role for micronutrient deficiency. Improving vitamin A status reduces mortality among older infants and young children and reduces pregnancy-related mortality; it also reduces the prevalence of severe illness and clinic attendance among children. Improving Zn status reduces morbidity from diarrhoeal and respiratory infection. Treatment of established infection with vitamin A is effective in measles-associated complications, but is not as useful in the majority of diarrhoeal or respiratory syndromes. Zn supplements, however, have significant benefit on the clinical outcome of diarrhoeal and respiratory infections. Concerns that Fe supplements might increase morbidity if given in malarious populations appear to be decreasing, in the light of new studies on Fe supplements showing improved haemoglobin without an increase in morbidity. Breast-feeding, well known to protect against diarrhoea, is also important in protecting against respiratory infection, especially in the young infant. Transmission of human immunodeficiency virus (HIV) in breast milk is recognized, but new data showing reduced transmission in infants who receive exclusive breast-feeding rather than mixed feeding reinforces the importance of promoting this practice in areas where environmental contamination precludes the safe use of other infant feeding regimens. The presence of subclinical mastitis, now recognized to occur in approximately 20 % of mothers in several developing countries, has been shown to increase the concentration of HIV in breast milk. Preliminary findings suggest that the prevalence of subclinical mastitis is reduced by dietary supplements containing antioxidants. Governments and international agencies now have a strong scientific basis to be much more active and innovative in the introduction of focused nutrition interventions especially micronutrients, for the control of infection.

Poor growth performance during infancy and early childhood is a frequent fact of life in most developing countries. Work in The Gambia has demonstrated that more than 43 % of observed growth faltering during the first 15 months of life can be explained by the presence of a mucosal enteropathy in the small intestine. Within communities the illness is very common: in the area investigated more than 95 % of infants above 8 months of age were affected, and on average they suffered a growth-limiting enteropathy for more than 75 % of their first year of life. Two mechanisms of weight loss have been defined. First, partial villus atrophy reduces absorption and digestion of lactose and probably other nutrients. Second, and more importantly, damage to the mucosal barrier allows translocation of macromolecules into the mucosa and blood, triggering both local and systemic immune and inflammatory mechanisms. Given the severity of the enteropathy it is not surprising that infants fail to grow at a normal rate. Recent findings suggest that these lesions continue throughout childhood and into adulthood. Thus, a persistence of chronic, local and systemic inflammation throughout childhood may be responsible for continued poor growth during this period. Although the nature of the enteropathy and the mechanisms of growth failure have been defined, the factors involved in the initiation and persistence of the intestinal lesion remain uncertain, making clinical management difficult. More work is clearly required to elucidate these factors and to define interventions to prevent or treat the enteropathy.

The nutritional condition of children with human immunodeficiency virus (HIV) infection continues to be a problem both in developed and developing countries. HIV-infected children grow below normal standards in both height and weight when compared with HIV-exposed non-infected children. These patterns persist over time. It is possible that acute infectious episodes and increased HIV viral burden contribute to decrements in all growth variables. Potential aetiologies for abnormal growth include inadequate dietary intake, gastrointestinal malabsorption, increased energy utilization and psycho-social problems. It is likely that all these factors contribute to the growth problems of these children to some extent. With the development of protease inhibitor anti-retroviral therapy and highly-active anti-retroviral treatment regimens, children with HIV infection in developed countries are living longer with a chronic illness. New nutritional problems have arisen with the development of the fat redistribution syndrome or lipodystrophy. Emerging problems are now being recognized, with the development of insulin resistance and truncal obesity which may potentially lead to premature cardiovascular disease.