Susan P. Walker and Julie M. Meeks Gardner
contents
Abstract ... 164
Introduction ... 164
Linear Growth Retardation (Stunting) ... 165
Stunting and Cognitive Development ... 165
Longitudinal Studies of Stunting and Cognitive Development ... 165
Stunting and Social–Emotional Outcomes... 165
Impact of Supplementation on Development ... 167
Supplementation Trials with Undernourished Children ... 167
Supplementation Trials to Prevent Undernutrition in High-Risk Populations ... 168
Insufficient Breastfeeding ... 169
Iodine ... 170
Iodine Supplementation Studies ... 171
Peru ... 171
Ecuador ... 171
Zaire... 171
Papua New Guinea ... 171
China ... 171
Iron Deficiency Anemia ... 172
Follow-Up Studies of IDA ... 172
Studies of the Impact of Treatment on Development ... 172
Studies of the Benefits of Preventive Supplementation ... 173
AbstRAct
This chapter presents the evidence linking inadequate nutrition in children with poor developmental outcomes. Children are most likely to experience undernutri-tion in the early years, coinciding with the period of greatest brain development.
Chronic undernutrition can result in linear growth retardation or “stunting,” which affects about one third of children under 5 years in developing countries. There are other markers of poor nutrition, including deficiencies of micronutrients and insuf-ficient breastfeeding, that may also affect children’s development. There is very strong evidence that iodine deficiency causes cognitive deficits, leading to cretinism as well as less-devastating deficits in development. There is also strong evidence that chronic undernutrition leading to linear growth retardation and iron deficiency anemia have long-lasting effects on children’s cognitive development and behav-ior. There is an urgent need for strategies to reduce the numbers of children who become undernourished and the negative impact on children’s development as well as to strengthen efforts to prevent iodine deficiency in mothers and children. It also appears important that efforts are made to reduce iron deficiency anemia among women and children. Most studies suggest that breastfeeding is associated with a small benefit in IQ, but problems with the study designs and interpretation have not been fully addressed. Several other nutrients, such as zinc, vitamin A, and vitamin B12, may affect children’s development, but the evidence is inconsistent, and further research is needed.
IntRoductIon
The growth potential of young children is similar across different populations (WHO Multicentre Growth Reference Study Group 2006). Faltering in linear growth results from chronic undernutrition and high levels of infections (Waterlow 1992). Reduction in growth rates occurs early, sometimes beginning in utero, and is most common in the first 2 years of life. The first years are also the most critical period for child development; thus, children are most likely to experience undernutrition during the period when the brain is developing rapidly and can be affected by the quality of the environment, including nutrition.
Linear growth retardation or stunting is defined as height-for-age less than or equal to 2 standard deviations (SD) of reference values. One third of children under 5 in developing countries are stunted (UNICEF 2004), with as many as 50% of children stunted in some countries. Thus, the implications for the development of children in many countries are enormous. Children’s nutritional intake may be inad-equate in micronutrients as well as energy and protein. In this chapter, we describe
Zinc ... 173
Vitamin A ... 174
Vitamin B12... 174
Conclusions ... 175
References ... 175
the evidence linking undernutrition, defined in terms of linear growth retardation, with child development, and then the role of insufficient breastfeeding and specific micronutrients.
lIneAR gRowth RetARdAtIon (stuntIng) stuntinganD Cognitive DeveLoPment
Several studies have shown cross-sectional associations (height-for-age and devel-opment measured at the same time) between linear growth retardation and poor child development. These have been reviewed in detail (Grantham-McGregor et al.
2007) and are addressed briefly here. In young children, height-for-age is associated with poor development, for example, as shown in studies in Guatemala (Lasky et al.
1981), Jamaica (Powell and Grantham-McGregor 1985), and Kenya (Sigman et al.
1989). Many cross-sectional studies in school-aged children have also shown that being stunted is associated with poorer cognitive ability and lower school achieve-ment levels (Grantham-McGregor et al. 2007).
longitudinal studies of stunting and cognitive development
Several prospective cohort studies of the association of stunting in early child-hood (by age 2 or 3 years) with later cognitive functioning have been conducted (in longitudinal studies, stunting or height-for-age was assessed in early childhood and children remeasured after varying intervals). Details of the studies are given in Table 11.1. After controlling for social background covariates, stunting was associ-ated with deficits in IQ (Berkman et al. 2002, Walker et al. 2005), nonverbal intel-ligence (Martorell et al. 1992, Mendez & Adair 1999), and other cognitive domains (Walker et al. 2005). Follow-up in some cases continued to late adolescence (Walker et al. 2005) and adulthood (Martorell et al. 1992). Stunting is also associated with poor educational outcomes, such as fewer grades completed (Martorell et al. 1992) and increased dropout (Daniels and Adair 2004, Walker et al. 2005). Deficits in school achievement have also been found (Martorell et al. 1992, Chang et al. 2002, Walker et al. 2005).
Two cohorts from South Africa and Brazil were included in a recent analysis (Grantham-McGregor et al. 2007), and stunting was associated with reasoning abil-ity at age 7 years (South Africa) and school grades attained at age 18 years (Brazil).
Deficits were thus consistently found in all longitudinal studies investigating the effect of early childhood stunting. The magnitude of the difference between stunted and nonstunted children varied, but effects were generally moderate to large.
stuntinganD soCiaL–emotionaL outComes
In cross-sectional studies, underweight and stunted children were less happy and more apathetic and fussy (Meeks Gardner et al. 1999), and they showed lower levels of play and exploratory behavior (Graves 1976, 1978, Meeks Gardner et al. 1999) and more anxious attachment (Graves 1976, 1978, Valenzuela 1990). At school age, children malnourished during the first 2 years of life had attention deficits, more
tAble 11.1 linear growth Retardation and cognitive outcomes: Prospective cohort studies ReferencesampleoutcomescovariatesResults Berkmann et al. 2002Peru; random sample from periurban shanty town; 239 children followed from birth to 2 years old; 143 assessed at 9 years
IQ WISC-R at age 9 yearsPaternal education, school type, grade level, testerSeverely stunted in second year of life lower IQ (p = .011) than combined group (never stunted and not severely stunted) Martorell et al. 1992Guatemala; 4 villages; 243 subjects with height measurement at 3 years assessed at 18–26 years Reasoning ability, numeracy, literacy, general knowledge years at school
Village, maternal education, household wealthHeight at 3 years significantly correlated with schooling, literacy, knowledge, numeracy; correlated with reasoning ability in males only Mendez and Adair, 1999Philippines; birth cohort from randomly selected administrative units; 2131 children with cognition at 8 years and height at 2 years (69% of birth cohort)
Philippines nonverbal intelligence test at age 8 and 11 years Grade level, several social background variables, birth weight, maternal height, sex, dietary fat
Children stunted at age 2 years had significantly lower scores at 8 years; at 11 years, severely stunted had significantly lower scores but not those moderately stunted Daniels and Adair, 2004Same cohort as above; 1997–2191 children with schooling dataAge at enrollment, grade repetition, highest grade attained
Parity, maternal height, several social background variables
1 SD greater height for age at 2 years associated with reduced risks of late enrollment (boys 32%, girls 40%), grade repetition (boys 14%, girls 22%), and dropout in primary (boys 26%, girls 34%) or secondary school (boys 33%, girls 9%, n.s.) Walker et al, 2005Stunted and nonstunted children aged 9–24 months from poor neighborhoods in Kingston, Jamaica; 103 of 129 stunted followed up at 17 years, 64 of 84 nonstunted
IQ, reasoning ability, vocabulary, verbal analogies, memory, reading, math, school dropout Maternal verbal IQ, education, occupation, housing, and hunger at 17 years; home environment on enrollment Stunted participants had significant deficits compared to nonstunted in all tests except one memory test and more likely to drop out of school n.s., not significant; WISC-R, Wechsler Intelligence Scale for Children—Revised.
aggressive behavior, and poorer social relationships than classmates or neighbor-hood controls (Richardson et al. 1972, Galler and Ramsey 1989).
The Jamaican follow-up study of stunted children provided the most informa-tion on possible long-term social-emoinforma-tional effects of childhood growth retar-dation. Children stunted in early childhood had more conduct disorder at age 11 years (Chang et al. 2002) and were more inhibited and less attentive in a test ses-sion than nonstunted children (Fernald and Grantham-McGregor 1998). At 17 years, stunted participants reported more symptoms of anxiety and depression and lower self-esteem than participants who were never stunted. Parents of the stunted group reported more problems with hyperactive behavior than parents of nonstunted par-ticipants (Walker et al. 2007).
imPaCtof suPPLementationon DeveLoPment
If undernutrition contributes to poor child development, then interventions to improve nutrition in undernourished children or reduce undernutrition in children at high risk of growth retardation would be one approach to reducing the cognitive and behavioral consequences. A number of randomized trials have been reported in which food supplements were given in an attempt to improve children’s nutritional status and development.
supplementation trials with undernourished children Indonesia
In Indonesia, 20 day care centers on tea plantations were randomized to treatment or no treatment (75 supplemented, 38 control children aged 6–20 months). Snacks were provided 6 days a week for 90 days. Supplementation benefited motor but not mental development when measured at the end of intervention (Husaini et al. 1991). Sixty-six supplemented children and 36 controls were remeasured at age 9 years. Benefits were found for one of four cognitive tests only in children who were less than 18 months at the beginning of the intervention. No differences were found in arithmetic or verbal comprehension (Pollitt et al. 1997).
Indonesia
Two cohorts of nutritionally at-risk children were enrolled from 24 day care centers in Indonesia. One cohort comprised 53 children aged 12 months and the other 83 children aged 18 months. Children were randomized to energy plus micronutrients, skimmed milk plus micronutrients, or skimmed milk only. The supplement was provided 6 days a week for 1 year. In the 12-month cohort, children who received the energy intervention had benefits to motor and mental development, increased vocalizations, longer duration of play, and decreased fussing but no differences in sociability. There were no significant benefits to the 18-month cohort (Pollitt and Schurch 2000).
Jamaica
There were 129 stunted children aged 9 to 24 months who were identified by house-to-house survey of poor neighborhoods in Kingston, Jamaica. Children were
randomized to (1) supplementation, (2) psychosocial stimulation with weekly home visits, (3) supplement and stimulation, or (4) control. Interventions were provided for 2 years. Stimulation and supplementation benefited the children’s developmental levels (Grantham-McGregor et al. 1991) and had additive but not interactive effects.
There were no benefits of supplementation to child exploration or affect assessed after 6 months of intervention (Meeks Gardner et al. 1999). Children were reassessed at 7 to 8 years, and small benefits of supplementation on a range of educational and cognitive tests were seen but no significant differences on any one test (Grantham-McGregor et al. 1997). No benefits from supplementation were detected at 11 or 17 years to cognitive functioning or behavior (Chang et al. 2002, Walker et al. 2005, 2006).
supplementation trials to Prevent undernutrition in high-Risk Populations Guatemala
Four villages in Guatemala were randomized to high-energy and protein supplement (atole) or low-energy supplement. Supplements were provided ad libitum twice daily at centers for pregnant and lactating women and children up to age 7 years. Atole benefited motor but not mental development at 24 months and perceptual organiza-tion and verbal skills at age 4 and 5 years but not 3 and 6 years (Pollitt et al. 1993).
Children of lower socioeconomic status benefited the most. Children of participants supplemented with atole in pregnancy who were supplemented through at least age 2 years performed significantly better on 4 of 6 psychoeducational tests and on 2of 7 information processing tests at age 13–19 years (Pollitt et al. 1993). In a subsample of children at age 6 to 8 years, those who received higher levels of supplementation from birth to 2 years were more socially involved, happier and more angry, and less anxious (Barrett et al. 1982).
Colombia
High-risk families in Bogota, Columbia, were randomized to receive supplementa-tion for varying periods: from pregnancy to infants aged 6 months (n = 57), infants aged 6 to 36 months (n = 60), from pregnancy to infants aged 36 months (n = 57), or control (n = 54). At 4 and 8 months, supplemented infants showed less apathy.
At 36 months, supplement benefited developmental levels in those supplemented from pregnancy through 36 months (Waber et al. 1981). Benefits for the two groups supplemented for shorter periods were inconsistent. At follow-up at age 5 to 8 years, supplementation benefited scores on reading readiness but not arithmetic or basic knowledge; however, these results have only been reported in a conference abstract.
These studies provide consistent evidence that food-based supplements that pro-vide additional energy and protein (and varying amounts of micronutrients) have concurrent benefits for child development. Limited or no benefits were found after supplementation ended in two studies in which supplementation was given to under-nourished children. The most substantial benefits to later development have been found in the study conducted in Guatemala among participants whose mothers were supplemented in pregnancy and who were supplemented at least until age 2 years.
In summary, early childhood linear growth retardation is associated with poor development in childhood and with later cognitive deficits and poorer educational outcomes. Undernutrition is also associated with altered behavior in early childhood.
Information on later behavior suggests problems with attention, social relationships, and psychological functioning. The benefits demonstrated in food supplementation trials provide further evidence that childhood undernutrition contributes to under-achievement among children in developing countries. There is an urgent need for strategies to reduce the numbers of children who become undernourished and the impact on children’s development.
InsuffIcIent bReAstfeedIng
Breastfeeding provides several important benefits to both mothers and their infants, especially in terms of reduced infectious diseases and mortality (World Health Organization [WHO], 2003). However, the benefits of breastfeeding to children’s development are much less clear. Such benefits could result from direct effects of the nutrients in breast milk, especially the fatty acid composition, or there may be indirect benefits from improved growth or immune response or from the closer mother-child interactions associated with breastfeeding (Grantham-McGregor et al. 1999).
The question has been widely investigated in over 50 studies, a number of reviews, and a meta-analysis. Many studies reported short or long-term benefits to psychomotor development with breastfeeding. The meta-analysis included 11 studies (Anderson et al. 1999), and the results indicated that breastfeeding was associated with significantly higher cognitive scores than formula feeding (3.16 points adjusted for covariates). This benefit was greater among preterm infants (5.18 points) com-pared with term infants (2.26 points). The IQ advantage increased with duration of breastfeeding, reaching a maximum at 4–6 months. However, a later review (Rey 2003) pointed out a number of flaws within the 11 included studies, suggesting that the conclusions were probably not valid. Other studies have not found a relationship between breastfeeding and development after adjustment for confounders (Clark et al. 2006).
In one systematic review (Jain et al. 2002), although 27 (68%) of the 40 stud-ies concluded that breastfeeding promotes intelligence, methodological flaws were found in most of the studies. Only 2 were high-quality studies of full-term infants.
One concluded that breastfeeding had a significant beneficial effect (Johnson et al.
1996), while the other did not (Wigg et al. 1998); thus, the reviewers cautioned read-ers attempting to interpret the results.
One of the major problems with the studies is that many have not adjusted for important covariates. In general, mothers in developed countries who choose to breastfeed and are successful at it have a number of other advantages that are likely to lead to better developmental outcomes among their children. These include higher socioeconomic status, better education, greater intelligence, less depression, and enhanced home environments. Most studies of breastfeeding and development have been carried out in developed countries where breastfeeding is highly confounded
with socioeconomic status (Grantham-McGregor et al. 1999). Two reports from developing countries suggest a complicated relationship between development and breastfeeding. In Chile, exclusive breastfeeding for under 2 months or more than 8 months was associated with poorer mental and motor outcomes at 5½ years (Clark et al. 2006). Another report from Honduras indicated that infants who were exclu-sively breastfed for 6 months crawled sooner and were more likely to be walking at 12 months compared with infants exclusively breastfed for 4 months when additional high-quality, complementary foods were also offered (Dewey et al. 2001). These studies require replication before firm conclusions are drawn.
Other problems with the studies included variation in the definitions of breast-feeding (e.g., definitions depending on the duration and exclusivity of breastbreast-feeding), small sample sizes in some studies, and observers were not always blind to the par-ticipants’ status (Drane and Loggeman 2000).
Despite the problems with the studies, some reviewers have argued that the con-sistency of the findings suggest that a small benefit to cognition from breastfeeding is likely (e.g., Grantham-McGregor et al. 1999, American Academy of Pediatrics 2005). Uauy and Peirano (1999) concluded that while high-quality scientific research should be demanded before accepting findings, the suggestive positive results should be taken into account for policy recommendations. The additional 2 to 5 IQ points would be a small difference for individuals but may be of great importance at a population level.
IodIne
Iodine deficiency can lead to cretinism and irreversible mental retardation (Black 2003b) and is the most common preventable cause of mental retardation. A global program to reduce iodine deficiency primarily through salt iodization has had sub-stantial success; nonetheless, iodine deficiency continues to threaten the develop-ment of children in many parts of the world.
Iodine is a constituent of the thyroid hormones thyroxine and triiodothyronine, which influence the development of the central nervous system (Pharoah and Connolly 1995). Maternal iodine deficiency during pregnancy affects brain development in utero (Hetzel and Mano 1989), and deficiency in infancy and early childhood may also affect development.
In addition to the most serious effects of cretinism, iodine deficiency in the sub-clinical range can also affect mental development. Studies comparing children living in iodine-deficient areas with those living in iodine-sufficient areas have generally shown children in iodine-deficient regions to have lower cognitive development and school achievement. In a 1994 meta-analysis of 18 studies, IQ scores averaged 13.5 points lower in iodine-deficient groups (Bleichrodt and Born 1994). A second meta-analysis of 37 studies reported a very similar deficit of 12.5 IQ points (Qian et al.
2005). However, communities with iodine-deficient soil are often more isolated and poorer. In a study adjusting for possible confounding factors, subclinical prenatal iodine deficiency remained associated with poor infant development (Choudhury and Gorman 2003).
ioDine suPPLementation stuDies
Peru
Children of mothers from three iodine-deficient villages in Peru supplemented in preg-nancy had higher developmental levels compared with unsupplemented controls from the same villages (Pretell et al. 1972). However, the difference was not significant.
ecuador
Pregnant women in one iodine-deficient village in Ecuador were treated with iodized oil either during months 4 to 7 of pregnancy (group 1) or before conception (group 2). Compared with control children from an untreated village, children in group 2 had higher IQ scores, but there were no differences between group 1 and controls (Ramirez et al. 1969). In a second study, a greater percentage of children of mothers treated before the sixth month of pregnancy had normal developmental levels than was the case in children of untreated mothers (Ramirez et al. 1972).
zaire
Pregnant women in an area of severe iodine deficiency in Zaire were randomized to either iodized oil or a vitamin placebo on average at the 28th week of pregnancy (Thilly et al. 1980). Infants of treated mothers had significantly higher developmen-tal levels than infants of placebo-treated mothers.
Papua new guinea
In a double-blind randomized controlled trial in 16 villages in Papua New Guinea, iodine treatment in pregnancy led to a significant reduction in cretinism (Pharoah et al. 1971). Children in 5 of the villages were followed up in later studies. Children whose mothers received iodized oil had better cognitive and fine motor skills than control children (Connolly et al. 1979).
china
Treatment in China was given to pregnant women, infants, and children aged 1 to 3 years. Scores of the 1- to 3-year-old children prior to treatment were used as control values. At age 2 years, children whose mothers received iodine during the first or second trimester of pregnancy had higher developmental scores than the controls (Cao et al. 1994). In another trial, children whose mothers received iodine in early
Treatment in China was given to pregnant women, infants, and children aged 1 to 3 years. Scores of the 1- to 3-year-old children prior to treatment were used as control values. At age 2 years, children whose mothers received iodine during the first or second trimester of pregnancy had higher developmental scores than the controls (Cao et al. 1994). In another trial, children whose mothers received iodine in early