Kathryn G. Dewey

Update on Technical Issues concerning Complementary Feeding of Young Children in Developing Countries and Implications for Intervention Programs

This paper provides an update to the 1998 WHO/UNICEF report on complementary feeding. New research findings are generally consistent with the guidelines in that report, but the adoption of new energy and micronutrient requirements for infants and young children will result in lower recommendations regarding minimum meal frequency and energy density of complementary foods, and will alter the list of “problem nutrients.” Without fortification, the densities of iron, zinc, and vitamin B6 in complementary foods are often inadequate, and the intake of other nutrients may also be low in some populations. Strategies for obtaining the needed amounts of problem nutrients, as well as optimizing breastmilk intake when other foods are added to the diet, are discussed. The impact of complementary feeding interventions on child growth has been variable, which calls attention to the need for more comprehensive programs. A six-step approach to planning, implementing, and evaluating such programs is recommended.

Differences in morbidity between breast-fed and formula-fed infants

To determine whether breast-feeding is protective against infection in relatively affluent populations, morbidity data were collected by weekly monitoring during the first 2 years of life from matched cohorts of infants who were either breast fed (BF) (N = 46) or formula fed (FF) (N = 41) until at least 12 months of age. Cohorts were matched for characteristics such as birth weight and parental socioeconomic status, and we controlled for use of day care in data analysis. Mean maternal educational level was high (16 years) in both groups. In the first year of life the incidence of diarrheal illness among BF infants was half that of FF infants; the percentage with any otitis media was 19% lower and with prolonged episodes (> 10 days) was 80% lower in BF compared with FF infants. There were no significant differences in rates of respiratory illness; nearly all cases were mild upper respiratory infections. Morbidity rates did not differ significantly between groups in the second year of life, but the mean duration of episodes of otitis media was longer in FF than BF infants (8.8 +/- 5.3 vs 5.9 +/- 3.5 days, respectively; p = 0.01). These results indicate that the reduction in morbidity associated with breast-feeding is of sufficient magnitude to be of public health significance.

Is Breastfeeding Protective Against Child Obesity

Recent studies suggest that breastfeeding reduces the risk of child obesity to a moderate extent. Of 11 studies that examined prevalence of overweight in children older than 3 years of age and that had a sample size of ≥ 100 per feeding group, 8 showed a lower risk of overweight in children who had been breastfed, after controlling for potential confounders. The 3 “negative” studies lacked information on the exclusivity of breastfeeding. A dose-response relationship with duration of breastfeeding was observed in some, but not all, of the “positive” studies. Possible mechanisms include learned self-regulation of energy intake, metabolic programming in early life, and residual confounding by parental attributes. If the association is causal, the effect of breastfeeding is probably small compared to other factors that influence child obesity, such as parental overweight. Nonetheless, it may be of public health significance considering the current epidemic of child overweight. J Hum Lact. 19(1):9-18.

Long‐term consequences of stunting in early life

This review summarizes the impact of stunting, highlights recent research findings, discusses policy and programme implications and identifies research priorities. There is growing evidence of the connections between slow growth in height early in life and impaired health and educational and economic performance later in life. Recent research findings, including follow-up of an intervention trial in Guatemala, indicate that stunting can have long-term effects on cognitive development, school achievement, economic productivity in adulthood and maternal reproductive outcomes. This evidence has contributed to the growing scientific consensus that tackling childhood stunting is a high priority for reducing the global burden of disease and for fostering economic development. Follow-up of randomized intervention trials is needed in other regions to add to the findings of the Guatemala trial. Further research is also needed to: understand the pathways by which prevention of stunting can have long-term effects; identify the pathways through which the non-genetic transmission of nutritional effects is mediated in future generations; and determine the impact of interventions focused on linear growth in early life on chronic disease risk in adulthood.

Effects of age of introduction of complementary foods on infant breast milk intake, total energy intake, and growth: a randomised intervention study in Honduras

In developing countries, the age at which breastfed infants are first given complementary foods is of public health importance because of the risk of diarrhoeal disease from contaminated weaning foods, and the potential risk of growth faltering if foods are inappropriately delayed. To evaluate whether there are any advantage of complementary feeding prior to 6 months, low-income primiparous mothers who had exclusively breastfed for 4 months were randomly assigned to one of 3 groups: continued exclusive breastfeeding to 6 months (EBF) (n = 50); introduction of complementary foods at 4 months with ad libitum nursing from 4-6 months (SF) (n = 47); and introduction of complementary foods at 4 months, with maintenance of baseline nursing frequency from 4-6 months (SF-M) (n = 44). Baby foods in jars were provided to the SF and SF-M groups from 4 to 6 months. Subjects were visited weekly and provided with lactation guidance; at 4, 5, and 6 months measurements were made of infant intake and breast milk composition. At 4 months, breast milk intake averaged 797 (139) g per day (no difference among groups). Between 4 and 6 months, breast milk intake was unchanged in EBF infants (+6) but decreased in the SF (-103), and SF-M (-62) groups (p < 0.001). Change in total energy intake (including solid foods) and infant weight and length gain did not differ significantly between groups. Weight and length gain from 4-6 months were comparable to those of breastfed infants in an affluent USA population. The results indicate that breastfed infants self-regulate their total energy intake when other foods are introduced. As a result, there is no advantage in introducing complementary foods before 6 months in this population, whereas there may be disadvantages if there is increased exposure to contaminated weaning foods.

Growth Characteristics of Breast-Fed Compared to Formula-Fed Infants

In affluent populations, breast-fed infants generally exhibit a different pattern of growth than formula-fed infants. The average weight gain of the former is lower than that of the latter, even after complementary foods are introduced. In some studies, the length gain is also lower among breast-fed infants, whereas in others there is no significant difference in linear growth between feeding groups. Growth in head circumference does not differ by feeding mode. Because of the difference in weight gain, breast-fed infants are generally leaner than formula-fed infants by 12 months of age. Breast-fed infants appear to self-regulate their energy intake at a lower level than consumed by formula-fed infants and have a lower metabolic rate. Evidence to date suggests that there are no apparent adverse consequences associated with the lower intake and slower weight gain of breast-fed infants: compared to formula-fed infants, they do not differ in activity level, and they experience less illness and appear to have enhanced cognitive development. The reasons for differences in growth patterns by feeding mode require further research.

Nutrition and brain development in early life

Presented here is an overview of the pathway from early nutrient deficiency to long-term brain function, cognition, and productivity, focusing on research from low- and middle-income countries. Animal models have demonstrated the importance of adequate nutrition for the neurodevelopmental processes that occur rapidly during pregnancy and infancy, such as neuron proliferation and myelination. However, several factors influence whether nutrient deficiencies during this period cause permanent cognitive deficits in human populations, including the childs interaction with the environment, the timing and degree of nutrient deficiency, and the possibility of recovery. These factors should be taken into account in the design and interpretation of future research. Certain types of nutritional deficiency clearly impair brain development, including severe acute malnutrition, chronic undernutrition, iron deficiency, and iodine deficiency. While strategies such as salt iodization and micronutrient powders have been shown to improve these conditions, direct evidence of their impact on brain development is scarce. Other strategies also require further research, including supplementation with iron and other micronutrients, essential fatty acids, and fortified food supplements during pregnancy and infancy.

Effect of timing of umbilical cord clamping on iron status in Mexican infants: a randomised controlled trial

BACKGROUND Delayed clamping of the umbilical cord increases the infants iron endowment at birth and haemoglobin concentration at 2 months of age. We aimed to assess whether a 2-minute delay in the clamping of the umbilical cord of normal-weight, full-term infants improved iron and haematological status up to 6 months of age. METHODS 476 mother-infant pairs were recruited at a large obstetrics hospital in Mexico City, Mexico, randomly assigned to delayed clamping (2 min after delivery of the infants shoulders) or early clamping (around 10 s after delivery), and followed up until 6 months postpartum. Primary outcomes were infant haematological status and iron status at 6 months of age, and analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00298051. FINDINGS 358 (75%) mother-infant pairs completed the trial. At 6 months of age, infants who had delayed clamping had significantly higher mean corpuscular volume (81.0 fL vs 79.5 fL 95% CI -2.5 to -0.6, p=0.001), ferritin (50.7 mug/L vs 34.4 mug/L 95% CI -30.7 to -1.9, p=0.0002), and total body iron. The effect of delayed clamping was significantly greater for infants born to mothers with low ferritin at delivery, breastfed infants not receiving iron-fortified milk or formula, and infants born with birthweight between 2500 g and 3000 g. A cord clamping delay of 2 minutes increased 6-month iron stores by about 27-47 mg. INTERPRETATION Delay in cord clamping of 2 minutes could help prevent iron deficiency from developing before 6 months of age, when iron-fortified complementary foods could be introduced.

Infant feeding policies in maternity wards and their effect on breast-feeding success : an analytical overview

OBJECTIVES The purpose of this review is to examine the plausibility of a causal relationship between maternity ward practices and lactation success. METHODS Studies were located with MEDLINE, from our personal files, and by contacting researchers working in this field. Of the 65 studies originally reviewed, 18 met our inclusion criteria (i.e., hospital-based intervention, experimental design with randomization procedures, or quasi-experimental design with adequate documentation). RESULTS Meta-analysis indicated that commercial discharge packs had an adverse effect on lactation performance. The impact of early mother-infant contact on lactation success was unclear. Rooming-in and breast-feeding guidance in a rooming-in context had a beneficial impact on breast-feeding among primiparae. Breast-feeding on demand was positively associated with lactation success. In-hospital formula supplementation of 48 mL per day was not associated with poor breast-feeding performance. CONCLUSIONS Hospital-based breast-feeding interventions can have a beneficial effect on lactation success, particularly among primiparous women.

Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children

Microbiota and infant development Malnutrition in children is a persistent challenge that is not always remedied by improvements in nutrition. This is because a characteristic community of gut microbes seems to mediate some of the pathology. Human gut microbes can be transplanted effectively into germ-free mice to recapitulate their associated phenotypes. Using this model, Blanton et al. found that the microbiota of healthy children relieved the harmful effects on growth caused by the microbiota of malnourished children. In infant mammals, chronic undernutrition results in growth hormone resistance and stunting. In mice, Schwarzer et al. showed that strains of Lactobacillus plantarum in the gut microbiota sustained growth hormone activity via signaling pathways in the liver, thus overcoming growth hormone resistance. Together these studies reveal that specific beneficial microbes could potentially be exploited to resolve undernutrition syndromes. Science, this issue p. 10.1126/science.aad3311, p. 854 Microbes from healthy children protect mice from the detrimental effects of the microbiota of malnourished infants. INTRODUCTION As we come to appreciate how our microbial communities (microbiota) assemble following birth, there is an opportunity to determine how this facet of our developmental biology relates to the healthy or impaired growth of infants and children. Childhood undernutrition is a devastating global health problem whose long-term sequelae, including stunting, neurodevelopmental abnormalities, and immune dysfunction, remain largely refractory to current therapeutic interventions. RATIONALE To test the hypothesis that perturbations in the normal development of the gut microbiota are causally related to undernutrition, we first applied random forests (RF), a machine learning method, to bacterial 16S ribosomal RNA data sets generated from fecal samples that were collected serially from healthy Malawian infants and children during their first 3 postnatal years. Age-discriminatory bacterial taxa were identified with distinctive time-dependent changes in their relative abundances; they were used to construct a sparse RF-derived model describing a program of normal postnatal gut microbiota development that is shared across biologically unrelated individuals. A metric based on this model (microbiota-for-age Z-score) was used to define the state of development (maturation) of fecal microbiota from infants and children with varying degrees of undernutrition. Fecal samples obtained from 6- and 18-month-old children with healthy growth patterns or with varying degrees of undernutrition were transplanted into young germ-free mice that were fed a representative Malawian diet. The recipient animals’ rate of lean body mass gain was characterized by serial quantitative magnetic resonance, their metabolic phenotypes were determined by targeted mass spectrometry, and their femoral bone morphologic features were delineated by microcomputed tomography. RESULTS Undernourished children in the Malawian birth cohort that we studied have immature gut microbiota. Unlike microbiota from healthy children, immature microbiota transmit impaired growth, altered bone morphology, and metabolic abnormalities in the muscle, liver, and brain to recipient gnotobiotic mice. The representation of several age-discriminatory taxa in the transplanted microbiota harbored by recipient animals correlated with their growth rates. Microbiota from 6-month-old infants produced greater effects on growth than did microbiota from 18-month-old children, although in each age bin, the growth effects produced by a healthy donor’s community were greater than those produced by an undernourished donor’s community. Cohousing coprophagic mice shortly after they received microbiota from healthy or severely stunted and underweight 6-month-old infants resulted in the invasion of age- and growth-discriminatory taxa from the former into the latter microbiota in the recipient animals, with associated prevention of growth impairments. Introducing cultured members from this group of invasive species ameliorated growth and metabolic abnormalities in recipients of microbiota from undernourished donors. CONCLUSION These preclinical findings provide evidence that gut microbiota immaturity is causally related to childhood undernutrition. The age- and growth-discriminatory taxa that we identified should help direct studies of the effects of host and environmental factors on gut microbial community development, and they represent therapeutic targets for repairing or preventing gut microbiota immaturity. Preclinical evidence that gut microbiota immaturity is causally related to childhood undernutrition. (A) A model of normal gut microbial community development in Malawian infants and children, based on the relative abundances of 25 bacterial taxa that provide a microbial signature defining the “age,” or state of maturation, of an individual’s (fecal) microbiota. (Hierarchical clusterings of operational taxonomic units are indicated on the left.) (B) Fecal samples from healthy (H) or stunted and underweight (Un) infants and children were transplanted into separate groups of young germ-free mice that were fed a Malawian diet. The immature microbiota of Un donors transmitted impaired growth phenotypes to the mice