maternal and child undernutrition 1.pdf

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Maternal and Child Undernutrition 1

Maternal and child undernutrition: global and regional

exposures and health consequences

Robert E Black, Lindsay H Allen, Zulfiqar A Bhutta, Laura E Caulfield, Mercedes de Onis, Majid Ezzati, Colin Mathers, Juan Rivera, for the Maternal

and Child Undernutrition Study Group*

Maternal and child undernutrition is highly prevalent in low-income and middle-income countries, resulting insubstantial increases in mortality and overall disease burden. In this paper, we present new analyses to estimate theeffects of the risks related to measures of undernutrition, as well as to suboptimum breastfeeding practices onmortality and disease. We estimated that stunting, severe wasting, and intrauterine growth restriction together wereresponsible for 22 million deaths and 21% of disability-adjusted life-years (DALYs) for children younger than 5 years.

Deficiencies of vitamin A and zinc were estimated to be responsible for 06 million and 04 million deaths,respectively, and a combined 9% of global childhood DALYs. Iron and iodine deficiencies resulted in few child deaths,and combined were responsible for about 02% of global childhood DALYs. Iron deficiency as a risk factor for maternalmortality added 115 000 deaths and 04% of global total DALYs. Suboptimum breastfeeding was estimated to beresponsible for 14 million child deaths and 44 million DALYs (10% of DALYs in children younger than 5 years). In ananalysis that accounted for co-exposure of these nutrition-related factors, they were together responsible for about 35%of child deaths and 11% of the total global disease burden. The high mortality and disease burden resulting fromthese nutrition-related factors make a compelling case for the urgent implementation of interventions to reduce theiroccurrence or ameliorate their consequences.

IntroductionMaternal and child undernutrition remain pervasive anddamaging conditions in low-income and middle-income

countries. A framework developed by UNICEF recognisesthe basic and underlying causes of undernutrition,including the environmental, economic, andsociopolitical contextual factors, with poverty having acentral role (figure 1). Although addressing generaldeprivation and inequity would result in substantialreductions in undernutrition1 and should be a globalpriority, major reductions in undernutrition can also bemade through programmatic health and nutritioninterventions. This paper is the first in a Series of fivepapers that focus on the disease burden attributable toundernutrition and the interventions affecting householdfood availability and use, maternal and child care, andcontrol of infectious diseases. The first two papers

quantify the prevalence of maternal and childundernutrition and consider the short-term consequencesin terms of deaths and disease burden, as measured bydisability-adjusted life-years (DALYs). They also discussthe long-term educational and economic effects andassociations with adult chronic diseases, particularly ascountries go through the demographic, epidemiological,and nutritional transitions.26The third paper estimatesthe potential benefits of implementing health andnutrition interventions that current evidence indicatesare effective and applicable in low-income andmiddle-income countries. The final two papers considerthe current state of such interventions and how theycould be implemented fully through actions at nationaland global levels.

Undernutrition encompasses stunting, wasting, anddeficiencies of essential vitamins and minerals (col-lectively referred to as micronutrients) as one form of the

condition known as malnutrition, with obesity orover-consumption of specific nutrients as another form.The term hunger, which literally describes a feeling ofdiscomfort from not eating, has also been used to describe

Published Online

January 17, 2008

DOI:10.1016/S0140-

6736(07)61690-0

This is the first in a Seriesof five

papers about maternal and child

undernutrition

*Members listed at end of paper

Johns Hopkins Bloomberg

School of Public Health,

Baltimore, MD, USA

(Prof R E Black MD,

Prof L E Caulfield PhD); USDA,

ARS Western Human Nutrition

Research Center, Davis, CA, USA

(Prof L H Allen PhD);

Aga Khan University, Karachi,

Pakistan (Prof Z A Bhutta, MD);

World Health Organization,

Geneva, Switzerland

(M de Onis MD, C Mathers PhD);

Harvard School of Public

Health, Boston, MA, USA(M Ezzati PhD); and Mexico

National Institute of Public

Health, Cuernavaca, Mexico

(Prof J Rivera PhD)

Correspondence to:

Robert Black, Johns Hopkins

Bloomberg School of Public

Health, Baltimore, MD, USA

[email protected]

Key messages

Maternal and child undernutrition is the underlying cause

of 35 million deaths, 35%of the disease burden in

children younger than 5 years and 11% of total global

DALYs

The number of global deaths and DALYs in children less

than 5 years old attributed to stunting, severe wasting,

and intrauterine growth restriction constitutes the largest

percentage of any risk factor in this age group

Vitamin A and zinc deficiencies have by far the largest

remaining disease burden among the micronutrients

considered

Iodine and iron deficiencies have small disease burdens,

partly because of intervention programmes, but sustained

effort is needed to further reduce their burden

Suboptimum breastfeeding, especially non-exclusive

breastfeeding in the first 6 months of life, results in

14 million deaths and 10% of disease burden in children

younger than 5 years

Maternal short stature and iron deficiency anaemia

increase the risk of death of the mother at delivery,

accounting for at least 20% of maternal mortality


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undernutrition, especially in reference to food insecurity,

wherein people do not have physical and economicaccess to sufficient, safe, nutritious, and culturallyacceptable food to meet their dietary needs.7,8Undernutrition is an important determinant of maternaland child health.912

The Millennium Development Goals (MDGs) state asthe first goal to halve between 1990 and 2015 the proportionof people who suffer from hunger.7 One indicator tomonitor progress for this target is the proportion ofchildren who are underweightie, low weight comparedwith that expected for a well-nourished child of that ageand sex. This anthropometric indicator can indicatewasting (ie, low weight-for-height, indicating acute weightloss), or much more commonly, stunting (ie, low

height-for-age, indicating chronic restriction of a childspotential growth). Those two conditions can have differentdeterminants and respond to different interventions.13Therefore, consideration of wasting and stunting is moreuseful than consideration of underweight. This seriesprimarily uses these two indicators, but also presentsinformation on underweight because weight-for-age hasbeen used in previous analyses.911 Reduction of fetalgrowth restriction and micronutrient deficiencies is alsoessential to achieving the MDGs and deserves high priority,

even though there are no MDG indicators for these

conditions. This Series also examines the consequences oflow body-mass index and short stature in women.This paper consists mainly of new analyses of the

prevalence of nutritional conditions, risk factors, andconsequent disease burden; if this was not possible ornecessary, previously published results are presented.The burden of disease attributable to maternal and childundernutrition is presented for three world regionsAfrica, Asia, and Latin Americathat include primarilylow-income and middle-income countries; only 1% ofdeaths in children younger than 5 years occur outsidethese regions. UN regions and subregions (webtable 1)were used.

Prevalence and consequencesMaternal short stature and low body-mass index inpregnancy and lactationMaternal undernutrition, including chronic energy andmicronutrient deficiencies, is prevalent in many regions,especially in south-central Asia, where in some countriesmore than 10% of women aged 1549 years are shorterthan 145 cm (webtable 2). Maternal undernutritionie,body-mass index of less than 185 kg/mrangesfrom 10% to 19% in most countries. A serious problem ofmaternal undernutrition is evident in most countries insub-Saharan Africa, south-central and southeastern Asia,and in Yemen, where more than 20% of women have abody-mass index of less than 185 kg/m. With aprevalence of low body-mass index around 40% inwomen, the situation can be considered critical in India,Bangladesh, and Eritrea. Maternal short stature and lowbody-mass index have independent adverse effects onpregnancy outcomes.

The nutritional status of a woman before and duringpregnancy is important for a healthy pregnancyoutcome.14,15 Maternal short stature is a risk factor forcaesarean delivery, largely related to cephalopelvicdisproportion. A meta-analysis of epidemiological studiesfound a 60% (95% CI 5070) increased need for assisteddelivery among women in the lowest quartile of stature(146 cm to 157 cm, depending on the region) compared

with women in the highest quartile.16If operative deliveryto ensure a healthy birth is not available to women whoneed it, both mother and baby are at risk.17 Even ifoperative delivery is accessible, affordable, and safe,anaesthesia and laparotomy increase the risk of maternalmorbidity.18 Low maternal body-mass index does notseem to increase the risk of pregnancy complications andassisted delivery.16Rather, there seems to be a synergisticpositive effect of short stature and higher maternalbody-mass index on increasing these complications.19,20

Low maternal body-mass index is associated withintrauterine growth restriction.11 Previous analysesestimated the disease burden of low maternal body-massindex as a risk factor for perinatal conditions,11whereasthe estimates presented in this paper consider intrauterine

Long-term consequences:

Adult size, intellectual ability,

economic productivity,reproductive performance,metabolic and cardiovascular disease

Short-term consequences:

Mortality, morbidity, disability

Inadequate care

Income poverty:employment, self-employment,

dwelling, assets, remittances,pensions, transfers etc

Lack of capital: financial, human,physical, social, and natural

Social, economic,and political context

Unhealthy householdenvironment and lack

of health services

Household foodinsecurity

Inadequate dietary intake Disease Immediatecauses

Basiccauses

Underlyingcauses

Maternal and childundernutrition

Figure 1:Framework of the relations between poverty, food insecurity, and other underlying and immediatecauses to maternal and child undernutrition and its short-term and long-term consequences

See Onlinefor webtable 1



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growth restriction to be the risk factor for neonatalconditions. Additional work is needed to quantify therelative effects of low maternal body-mass index, extentof weight gain in pregnancy, and maternal micronutrientdeficiencies on the occurrence and severity of intrauterinegrowth restriction.

Maternal undernutrition has little effect on thevolume or composition of breast milk unlessmalnutrition is severe. The concentration of somemicronutrients (vitamin A, iodine, thiamin, riboflavin,pyridoxine, and cobalamin) in breast milk is dependenton maternal status and intake, so the risk of infantdepletion is increased by maternal deficiency.21 Thisfactor is most evident in the case of vitamin A, wherethe content in breast milk is the main determinant ofinfant status because stores are low at birth. Maternal

supplementation with these micronutrients increasesthe amount secreted in breast milk, which can improveinfant status.

Childhood underweight, stunting, and wastingThe prevalences of underweight, stunting, and wastingworldwide and for UN regions are based on analysisof 388 national surveys from 139 countries, applyingcomparable methods, including use of the new WHOChild Growth Standards.2226 In 2005, 20% of childrenyounger than 5 years in low-income and middle-incomecountries had a weight-for-age Z score of less than 2(table 1). The prevalences were highest in south-centralAsia and eastern Africa where 33% and 28%, respectively,were underweight.

For all developing countries, an estimated 32%(178 million) of children younger than 5 years had aheight-for-age Z score of less than 2 in 2005 (table 1).22,23Eastern and middle Africa have the highest prevalenceestimates in UN subregions with 50% and 42%,respectively; the largest number of children affected bystunting, 74 million, live in south-central Asia.

Of the 40 countries with a child stunting prevalenceof 40% or more, 23 are in Africa, 16 in Asia, and one inLatin America; and of the 52 countries with prevalence ofless than 20%, 17 are in Latin America and the Caribbean,16 in Asia, 11 in Europe, and four each in Africa and

Children


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Oceania (figure 2). Including only countries with astunting prevalence of 20% or more, 36 countries accountfor 90% of all stunted children worldwide (webtable 3).These countries will be the focus of estimations of theeffects of interventions on disease burden.2821 of thesecountries are in Africa and, although fewer countries arein Asia (13), they account for 61% of the total stuntedchildren because of their large populations. India, withan estimated prevalence of 51%, has more than 61 millionstunted children, 34% of the global total; however, theprevalence varies substantially by state within India(figure 3). Within countries the prevalence of stunting isgenerally highest for the poorest segments of thepopulation (panel 1, figure 4).29

The global estimate of wasting (weight-for-heightZ score of less than 2) is 10% (55 million children).South-central Asia is estimated to have the highestprevalence (16%) and numbers affected (29 million). Thesame regional pattern is seen for severe wasting(weight-for-height Z score of less than 3), often used asa criterion for therapeutic feeding interventions, with aprevalence of 35% or 19 million children (table 1). Thehighest percentages of children with severe wasting areseen in south-central Asia and middle Africa. Of the36 countries with 90% of stunted children, the prevalence

of severe wasting varies from 01% to 12% (webtable 4).For the disease burden estimations, it is important to

know the extent of overlap of the populations of childrenyounger than 5 years who are stunted (height-for-ageZ score


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identifying children who are stunted will not capture mostof those with severe wasting. Furthermore, stunting andsevere wasting are not necessarily associated on ageographical or ecological basisie, countries with a

similar stunting prevalence can have a several-fold

difference in the prevalence of severe wasting.

31

Eight data sets from low-income countries (Ghana,Guinea Bissau, Senegal, the Philippines, Nepal, Pakistan,India, and Bangladesh)3238 were used for analysis ofdisease risks associated with childhood undernutrition.These data were from specific study populations, butwere broadly representative of these countries andlow-income countries in general. Children were groupedby Z score as less than 3, 3 to less than 2, 2 to lessthan 1, and 1 or more for each of these indices.Generalised linear mixed models were used to estimatethe risk of all-cause mortality, as well as of death due todiarrhoea, pneumonia, malaria, and measles for each ofthe groups with Z scores less than 1. The estimated

odds ratios were then adjusted for confounding due tosocioeconomic factors that affect mortality through otherpathways, such as non-nutritional determinants ofinfection or access to better clinical care. The adjustmentused data sets with robust measurement of socioeconomicstatus from Nepal36,37 and Honduras39 and showed thatodds ratios were attenuated by 10% and 20%, respectively.On the basis of these results, 15% attenuation was appliedto the odds ratios calculated with the generalised linearmixed models for underweight, stunting, and wasting.The odds ratios derived for cause-specific mortality werealso used for diarrhoea, pneumonia, and malariamorbidity.

The risk of death increases with descending Z scoresfor underweight, stunting, or wasting (table 2). Theincreased risks are all significant for the below 3 category,as are many in the other two categories.


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Term low-birthweight

Babies born at term (ie, who have completed 37 weeks ofgestation), but of low birthweight (


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effect of vitamin A on malaria morbidity,61but another did

not;

62

thus, this effect is not included in our estimates. Anincreased risk of maternal mortality due to vitamin Adeficiency was not included because results from trials inNepal63 and Bangladesh64 are inconsistent, leading to anon-significant pooled estimate.

Zinc deficiencyThe International Zinc Nutrition Consultative Group hasproposed a method for assessment of the populationsrisk of zinc deficiency based on indirect indicatorsie,the prevalence of stunting, one of the clinicalmanifestations of zinc deficiency, and the adequacy ofabsorbable zinc in the food supply at the country level.65,66

The populations risk of zinc deficiency was estimated

for the 178 countries for which information is availablefrom the UN Food and Agriculture Organization. Thelatest prevalence of stunting for 131 countries wasobtained from the WHO Global Database on ChildGrowth and Malnutrition.24Data from other sources wereused to classify 35 additional countries by stuntingprevalence. Each country was classified into threecategories of risk of zinc deficiency on the basis of thecombination of stunting prevalence and adequacy of zincin the food supply.65,66 Countries at high risk of zincdeficiency are those with a stunting prevalence of morethan 20% and estimated prevalence of inadequate zincintake of more than 25%; countries at low risk of zincdeficiency are those with stunting prevalence of lessthan 10% and inadequate zinc intake of less than 15%;countries at medium risk of zinc deficiency are thosewith all other combinations of the categories of stuntingprevalence and adequacy of zinc in the food supply. Allthe trials of zinc supplementation included in the diseaseburden risk estimates were done in countries classifiedas having medium-high zinc deficiency. The nationalprevalence of zinc deficiency is high in south Asia, mostof sub-Saharan Africa, and parts of Central and SouthAmerica (figure 6). In countries classified as having zincdeficiency, all children were considered to be at risk.

Zinc deficiency in children results in increased risk ofdiarrhoea, pneumonia, and malaria, as evidenced by

many randomised placebo-controlled trials done invarious populations in all regions of the world.6771 Therelative risk of deficiency for outcomes in the at-riskpopulations can be calculated by inverting the reductionin morbidity and mortality seen in the trials of zincsupplementation. The pooled relative risk for morbidityassociated with zinc deficiency is 109 (95% CI 101118)for diarrhoea, 125 (109143) for pneumonia, and 156(129189) for malaria.72,73For mortality in infants aged159 months the relative risk is estimated to be 127(096163) for diarrhoea, 118 (090154) forpneumonia, and 111 (094130) for malaria, based on ameta-analysis (S Sazawal, unpublished) of randomisedcontrolled trials in Bangladesh,74Nepal,71and Zanzibar.69These values were used in the estimates of disease

burden for the age group 659 months because this agegroup has a more consistent benefit in supplementationtrials than infants younger than 6 months.

Iron deficiency anaemiaAccording to a WHO review of nationally representativesurveys from 1993 to 2005, 42% of pregnant women and47% of preschool children worldwide have anaemia.75Forthese analyses, 60% of this anaemia was assumed to bedue to iron deficiency in non-malaria areas and 50% inmalaria areas.76

The major cause of iron deficiency anaemia is lowconsumption of meat, fish, or poultry, especially in poorpeople (panel 1).77In young children the peak prevalenceof iron deficiency anaemia occurs around 18 months ofage and then falls as iron requirements decline and ironintake is increased through complementary foods.Women of childbearing age are at high risk for negativeiron balance because of blood loss during menstruationand the substantial iron demands of pregnancy.

Previous analyses examined the relation betweenanaemia in pregnancy and risk of maternal mortality.12An odds ratio of 08 (95% CI 070091) for maternalmortality was found for a 10 g/L increase in mean

haemoglobin in late pregnancy. These analyses alsoassessed the effects of anaemia on child cognition: thecombined analysis of the five available trials found 173(95% CI 104241) lower IQ points per 10 g/L decreasein haemoglobin.12 A separate meta-analysis of ironsupplementation trials an overall benefit of 12 IQ points,in children receiving iron, but there was no effect inchildren younger than 27 months.78

Iodine deficiencyThe prevalence of sequelae of iodine deficiency, such asgoitre, congenital hypothyroidism, and developmentaldisability, have been estimated and assigned disabilityweights to calculate disease burden.79More recently theprevalence of iodine deficiency has been measured by an

No data

Low

Medium

High

Figure 6: National risk of zinc deficiency in children under 5 years


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indicator of low urinary iodine concentration; however,the rates of resulting sequelae have not been linked tothis new exposure measure. Thus, previously usedmethods have been retained for the analysis in this paper.Iodine deficiency has adverse effects on both pregnancyoutcome and child development. Even mild, subclinicalmaternal iodine deficiency during pregnancy impairsmotor and mental development of the fetus and increasesrisk of miscarriage and fetal growth restriction. Maternalsupplementation with iodine in more severe deficiencyimproves pregnancy outcomes especially if done by thesecond trimester, and improves neurological andcognitive development of the infant.80 There areinsufficient data on benefits to pregnancy outcomes frominterventions when deficiency is mild.81 Breast milkiodine content is very low in areas of endemic iodinedeficiency, exacerbating depletion in infants andincreasing their risk of impaired development. Ameta-analysis showed that populations with chronicdeficiency have a 135 point reduction in IQ.82

Folic acid, vitamin B12, and other micronutrientdeficienciesOther micronutrient deficiencies of concern in maternal

and child health include calcium, iodine, the B vitamins(especially folic acid and vitamin B12), and vitamin D.Calcium deficiency is recognised as the main cause ofrickets in Africa and some parts of tropical Asia, andincreasingly in other parts of the world.83 Anestimated 3580% of children in countries such as Turkey,India, Egypt, China, Libya, and Lebanon are vitamin Ddeficient (serum 25[OH]D


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predominant breastfeeding, and not breastfeeding had

very high relative risks. In infants aged 623 monthsthere was a statistically raised risk of not breastfeedingfor all-cause mortality and diarrhoea incidence, but therewas no significant raised risk for other outcomes.

Complementary feedingEven with optimum breastfeeding children will becomestunted if they do not receive an adequate quantity andquality of complementary foods after 6 months of age.Most incident stunting (and wasting outside of faminesituations) happens in the first 2 years of life when childrenhave a high demand for nutrients and there are limitationsin the quality and quantity of their diets, especially after theperiod of exclusive breastfeeding.95This age group (younger

than 2 years) also has a high rate of infectious diseasessuch as diarrhoea that adversely affect growth andnutritional status. A study that quantified the relativeeffects of poor complementary diet and infectious diseaseson reduced growth found that they were of roughly equalimportance in one setting in rural Bangladesh,96but thisresult might vary in other settings. Suboptimumcomplementary feeding is clearly a determinant ofstunting, and improvements in most settings need to focuson both feeding frequency and energy density, and ensurean adequate quality diet, including sufficientmicronutrients.97There is a clear disparity in dietary quality,as indicated by the lower consumption of animal sourcefoods by poor children (panel 1).

Information derived from efficacy trials that attemptedto improve complementary feeding through nutritioneducation, food supplementation, or both, can provide aperspective on the importance of suboptimumcomplementary feeding as a determinant of stunting.The effects on linear growth seem to be best withinterventions that use specific educational messageseg, on consumption of animal-source foods emphasiseenergy density of the diet, and, in areas with foodinsecurity or low consumption of sources ofmicronutrients, provide food supplements withmicronutrient fortification.98,99

Contribution of infectious diseases to stunting andintrauterine growth restrictionInfectious diseases are important determinants ofstunting.100Although there can be contributions to growthfaltering from respiratory illnesses101 or malaria,102 therole of diarrhoea seems to be particularly important,103106perhaps because of its association with malabsorption ofnutrients, as well as anorexia and catabolism.107

To quantify the contribution of diarrhoea to theoccurrence of stunting, data sets from Bangladesh (1),104Brazil (2),103,108 Guinea-Bissau (2),109111 Ghana (1),112,113 andPeru (3)105,114,115were analysed. Data were pooled to estimatethe effects of diarrhoeal incidence on the odds of stuntingat 24 months of age. All were longitudinal studies thatenrolled children at or near birth and followed them with

regular anthropometric measurements and daily recordsof diarrhoeal surveillance. Because children weremeasured at different ages, the measurement ofheight-for-age Z score at the oldest date in the intervalbetween 18 and 24 months of age was accepted as theZ score at 24 months. Logistic regression was used tomodel the stunting at 24 months as a function of diarrhoealincidence. Children were only included if they contributedat least 250 days of follow-up, up to the date when theoutcome was measured. The effect of diarrhoeal incidenceon stunting did not differ by study (p=0409; likelihoodratio test), allowing us to pool across studies (webfigure).By contrast, our analysis required study-specific interceptsand study-specific gender effects. The odds of stuntingincreased multiplicatively with each episode of diarrhoea.The adjusted odds of stunting at 24 months of ageincreased by a factor of 105 (odds ratio 105, 95% CI103107) with each episode of diarrhoea in the first24 months. The magnitude of this effect was not affectedwhen the children who were stunted in the first 6 monthsof life were excluded.

Malaria in pregnancy is associated with intrauterinegrowth restriction which increases the risk of death ininfancy.116Infection at the end of pregnancy seems to be

particularly harmful.117

Global and regional disease burden fromundernutritionThe global burden of disease projectThe global burden of disease project reports mortalityand burden of disease for 136 comprehensive categoriesof specific diseases and injuries, and their sequelae.54Theburden of disease measures the gap between the currenthealth of a population and an ideal situation whereeveryone in the population lives into old age in full health,in DALYs. DALYs combine years of life lost due topremature death and years of life lived with disabilities(YLD) into one indicator allowing assessment of the totalloss of health from different causes. One DALY can be

0

Afr ica Asia L atin Americ a

and the Caribbean

10

20

30

40

50

60

70

80

90

100


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regarded as roughly 1 lost year of so-called healthy life.

Methods and data for estimating mortality and DALYs inthe global burden of disease project are describedelsewhere.54

WHO has made an incremental revision of the globalburden of disease for 2004, which included updatingmortality and causes of death, and revising YLD estimatesfor selected causes if new data were available. Estimatesof child deaths by cause have been revised to take intoaccount new estimates of the total numbers of neonatal,infant, and child deaths for 2004,118 updatedcountry-specific estimates of deaths in children youngerthan 5 years by cause based on models developed by theWHO Child Epidemiology Reference Group,119,120 andupdated UNAIDS and WHO estimates for HIV/AIDS,

tuberculosis, and vaccine-preventable child deaths.121,122YLD estimates for protein-energy malnutrition have beenupdated to take into account latest WHO estimates ofstunting and wasting according to the new WHO

standards,23 and YLD estimates for iron deficiency

anaemia have been updated using the most recent datafrom the WHO Global Database on Anaemia.123 Allestimates of death and disease burden attributable toundernutrition in this analysis are for the year 2004.

The 136 diseases and injuries in the global burden ofdisease project follow the rules of the internationalclassification of disease (ICD) system. The ICD considersfour groups of nutritional deficiencies, and their sequelae,as possible direct causes of death: protein-energymalnutrition, iron deficiency anaemia, vitamin Adeficiency, and iodine deficiency. For this reason,estimates were made of the number of deaths andamount of disability that could be directly attributed tothese conditions. As described above, in addition to these

direct deaths, undernourished children are at anincreased risk of illness and death from many infectiousdiseases, also included in the global burden of diseasecategories. Indeed, substantially more children die as aresult of the synergy between infectious diseases andundernutrition than from the direct sequelae of thenutritional conditions themselves.11 Like the ICD, globalburden of disease also includes low birthweight as adirect cause of death; nearly all of these deaths indeveloping countries are due to preterm births, notintrauterine growth restriction among births at term.119

Estimating deaths and burden of disease attributable tonutritional risk factorsTo estimate the number of deaths from various infectiousdiseases attributable to different forms of undernutrition,the methods of the comparative risk assessment projectwere used.124,125In brief, for each risk factor and for each ofthe diseases that are affected by it, population attributablefractions were computed using the following equation,which is for a risk factor with n levels of exposure.Population attributable fractions estimate the proportionalreduction in mortality that would be seen if risk factorexposure had been reduced to an alternative (counterfactual)distribution that would result in the lowest population risk,irrespective of whether currently attainable in practice.This optimum exposure, referred to as the theoretical-

minimum-risk exposure distribution, results in estimatesof deaths and disease burden that could be avoided if alllevels of suboptimum nutrition were addressed, in aconsistent and comparable way across risk factors.

PAF=population attributable fractions. RRi=relativerisk of disease or mortality for the ithexposure category.Pi=proportion of children/women of child-bearing agein the ith exposure category. P

i

=proportion ofchildren/women of child-bearing age in the ithexposure

Panel 2:Specific assumptions for calculating the population

attributable fraction for multiple nutritional risks

The hazardous effects of one risk are not mediated

through other risks

This assumption might not hold for zinc deficiency because

some of its hazardous effects are mediated through reducing

growth. On the basis of the effects of zinc supplementation on

linear growth,127

and the model used to estimate interventioneffects,28it is estimated that around 46% of the excess risk for

zinc deficiency is mediated through stunting. There would be

no mediation via stunting for vitamin A deficiency128or iron

deficiency,129because of their lack of effects on growth.

The proportional risks for one risk do not depend on

exposure to other risks

This assumption seems to be valid in that there has been no

effect modification found in factorial design trials of

vitamin A, zinc supplementation, or both,130,131and no

difference in effect of vitamin A supplementation by baseline

nutritional status by various anthropometric measures.37,132

Likewise, no significant differences have been seen with the

effects of zinc supplementation on infectious diseasemorbidity in children with better or worse nutritional status.133

Exposures to these risks are uncorrelated

The data from the cohort studies used to estimate odds ratios

show that there was a small positive correlation between

severe wasting and stunting (the prevalences of severe

wasting in children with height-for-ageZscores below and

above 2 were 47% and 29%, respectively). There was also a

positive correlation between stunting and zinc deficiency, but

this is accounted for in the mediated effect mentioned above.

Correlation was not incorporated in the calculations, which

results in a slight underestimation of the combined effects,

but previous sensitivity analyses have shown that the

underestimation is small for these risks.126

PAF=P

iRR

iP

iRR

i

PiRR

ii=1

n

i=1 i=1

nn


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category in alternative/counterfactual exposure

scenarios.n=number of exposure categories.Deaths and disease burden associated withprotein-energy malnutrition (an ICD condition), and itsdirect sequelae as estimated in global burden of disease,54were added to the burden associated with underweight.In estimating the disease burden for stunting andwasting it is appropriate to add the direct protein-energymalnutrition burden to only one; it was added to wasting(or severe wasting) because this condition is mostconsistent with mortality from severe acute malnutrition,even though YLDs for chronic effects were attributed toboth stunting and wasting.

The nutritional status measuresunderweight,stunting, and wastingwere treated as risk factors whose

exposures and relative risks applied to all children in theage group 159 months, and intrauterine growthrestriction-low birthweight only for the first month of life.The analyses for vitamin A and zinc deficiencies andsuboptimum breastfeeding, for which either exposure orincreased risk were age-dependent, had to be done for agegroups other than all children under 5 or neonatal, thetwo groups that are readily available from global burdenof disease databases. The division of cause-specific deathsbetween 4 weeks and 59 months by age (eg, for the interval15 months, 611 months, 1223 months) were from datafor total (all-cause) deaths by month of age estimatedusing demographic techniques from complete birthhistories in demographic and health surveys.

Exposures and relative risks for the calculation ofinfectious disease deaths and burden fromnutrition-related risk factors were largely newly derived,as described in this paper; however, the estimation of thedirect sequelae was done using previous methods withthe results updated to 2004. A summary of the source ofthe inputs is provided in webtable 7.

Cause-specific deaths can be caused by multiple riskfactors acting simultaneously, and hence can be preventedby intervention on each of the risks. For example, somedeaths from diarrhoea could be prevented by removingexposure to stunting, zinc deficiency, vitamin A deficiency,or suboptimum breastfeeding. Such deaths are attributable

to all four risks when considered individually. As a resultof multi-causality, the population attributable fractions formultiple risk factors that affect the same disease outcomeoverlap and cannot be combined by simple addition;rather their combined effect is generally less than thecrude sum of individual ones, because some deaths areattributed to multiple exposures.126 Under specificassumptions (panel 2), the combined (joint) populationattributable fraction that avoids double-counting can beestimated from those of individual risks.126

Deaths and burden of disease attributable to nutritionalrisk factorsOf the nutritional status measures for children,underweight was responsible for the largest disease burden

(table 5). The burden due to severe wasting from infectiousdiseases is modest compared with the other measures,largely because most children with non-optimum weightfor height have a Z score of 1 to 3 and substantially fewerhave a score less than 3. The burden associated with alllevels of wasting was slightly less than that of stunting.

Stunting, severe wasting, and intrauterine growthrestriction-low birthweight together were responsible for21 million deaths (21% of worldwide deaths in childrenunder 5) and 910 million DALYs (21% of global DALYsfor children under 5; 7% of global total DALYs). Of theUN subregions, the disease burden attributed to theseanthropometric measures is highest in south-centralAsia (webtable 8), where India alone has 06 million

deaths and 246 million DALYs attributed to stunting,severe wasting, and intrauterine growth restriction-lowbirthweight. The undernutrition burden is also high ineastern, middle and western Africa; these subregions,which together have an under-5 population of 111 million(93% of India), 11 million deaths, and 423 millionDALYs, showing higher relative and absolute effectsamong African children.

Among the deficiencies of vitamins and mineralsexamined, the largest disease burdens were attributed tovitamin A and zinc deficiencies (table 6). Vitamin Adeficiency in newborn babies, infants, and childrenresulted in about 6% of under-5 deaths, 5% of under-5DALYs, and 17% of total DALYs. Zinc deficiency resultedin about 4% of under-5 deaths and DALYs and 1% of total

Deaths Percentage of

deaths in childrenunder 5 years

Disease burden

(1000 DALYs)

Percentage of

DALYs in childrenunder 5 years

Underweight* 1 957 530 190 81 358 187

Stunting 1 491 188 145 54 912 126

Wasting* 1 505 236 146 64 566 148

Severe wasting* 449 160 44 25 929 60

Intrauterine growth restriction-

low birthweight

337 047 33 13 536 31

Total of stunting, severe wasting,

and intrauterine growth

restriction-low birthweight

2 184 973 214 90 962 212

*Deaths (138 739) and DALYs (14 486 400) directly attributed to protein energy malnutrition included Included in

wasting. Total takes into account the joint distribution of stunting and severe wasting.

Table 5:Global deaths and disease burden measured in disability-adjusted life-years (DALYs) in children

under 5 years of age attributed to nutritional status measures in 2004

Deaths Percentage of deaths in

children under 5 years

Disease burden

(1000 DALYs)

Percentage of DALYs in

children under 5 years

Vitamin A deficiency 667 771 65 22 668 53

Zinc deficiency 453 207 44 16 342 38

Iron deficiency 20 854 02 2 156 05

Iodine deficiency 3 619 003 2 614 06

Table 6:Global deaths and disability-adjusted life-years (DALYs) in children under 5 years of age

attributed to micronutrient deficiencies in 2004




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DALYs. The regional patterns for disease burden

attributed to vitamin A and zinc deficiencies are similar.The highest burden for each is in South-central Asia,followed by several subregions of Africa (webtable 9).

Iron deficiency resulted in a relatively small number ofunder-5 deaths and DALYs (table 6). This burden is directlyattributed to the sequelae of iron deficiency anaemia inchildren including cognitive impairment.76 In addition,iron deficiency anaemia in pregnancy is considered a riskfactor for maternal mortality; 115 000 deaths per year frommaternal causes, resulting in 34 million DALYs, havebeen attributed to this risk factor.12 Iodine deficiencyresults in a very small number of deaths, which isattributed to an excess risk of death with congenitalhypothyroidism, and a modest number of DALYs that

primarily result from multiple sequelae from iodinedeficiency, including cognitive and motor impairment andhearing loss.79

In an analysis taking into account the joint distributionof nutritional status risk factors (intrauterine growthrestriction, stunting, severe wasting, and deficiencies ofvitamin A or zinc) and the fact that some of the effect ofzinc deficiency is mediated through stunting, it isestimated that there were 28 million child deaths(28% of under-5 deaths) and 1140 million DALYs (27% ofunder-5 DALYs) attributable to these forms of childhoodundernutrition. This constitutes 85% of the total globaldisease burden.

There was a large disease burden attributed tosuboptimum breastfeeding, including 14 million deaths(12% of under-5 deaths) and 435 million DALYs, whichis 10% of global under-5 DALYs and 3% of total DALYs.Most of the attributable deaths (106 million) and DALYs(370 million) were due to non-exclusive breastfeeding inthe first 6 months of life, accounting for 77% and 85%,respectively, of deaths and DALYs attributed tosuboptimum breastfeeding. Again the highest diseaseburden estimates are for south-central Asia and severalsub-regions of Africa (webtable 10). This risk factor wascombined with anthropometric status and deficiencies ofvitamin A and zinc in an analysis allowing for co-exposureand avoiding double counting of disease burden. If one

assumes that the risks of suboptimum breastfeeding andother nutritional factors are independent, the combinedmortality effects of all risk factors were 36 million childdeaths (35% of under-5 deaths) and 1405 million DALYs(35% of under-5 DALYs); this is 10% of the total globaldisease burden. These estimates change only slightly ifthe burden of disease directly attributed to iron andiodine deficiencies are added. These results are robust toassumptions about some of the effects of suboptimumbreastfeeding being mediated through other nutritionalexposures. For example, if 25% of the hazardous effectsof suboptimum breastfeeding are mediated throughother nutritional risks, the total number of attributablechild deaths is reduced to 35 million, still about35% deaths and DALYs in this age group. Adding the

maternal deaths and DALYs due to iron deficiency

anaemia increases the total global disease burdenattributed to undernutrition to 11%.

DiscussionThe attribution of more than a third of child deaths andmore than 10% of total global disease burden to maternaland child undernutrition demonstrates the importance ofthese prevalent risk factors. The 21% of global deaths andDALYs in children younger than 5 years old attributed tostunting, severe wasting, and intrauterine growthrestriction-low birthweight, largely because of theirsynergistic relationship with infectious diseases, constitutesthe largest percentage for any risk factor in this agegroup.125

The estimated total burden attributed to the com-bination of underweight and intrauterine growthrestriction-low birthweight is about the sameie, 22% ofdeaths, and disease burden in children younger than 5yearsas the burden attributed to stunting, severewasting, and intrauterine growth restriction-lowbirthweight. This result is lower than our previousestimate that indicated that 35% of child deaths could beattributed to childhood underweight and maternal lowbody-mass index operating through intrauterine growthrestriction to affect low birthweight.11 There are severalreasons for this difference. The new estimates were donefor a different base year (2004 vs 2000) with modestreductions in overall child mortality and in some majorcauses of death, such as diarrhoea, malaria, and measles,that are affected by the nutritional risk factors. Further,there have been declining trends in the prevalence ofstunting in most regions.134More importantly the currentestimates used the new WHO growth standards for allnutritional status prevalence and mortality and morbidityrisk estimates. These factors, along with the use ofdifferent data sets for much of the risk analysis, resultedin somewhat lower relative risks of mortality than inprevious analyses,10,11especially for children with Zscoresbetween 1 and 2. Thus, some of the difference inestimated disease burden is due to changes in methods,but it also is likely to indicate progress in preventing and

managing undernutrition and reducing some importantcauses of death.

The methods used in these analyses indicate severaladvances from those used previously.11,12,56,73 Most of therisk relations were re-examined, as were the exposuredefinitions and prevalences, with the most currentevidence. The latest information on total and cause-specificchild mortality was used. The new WHO growth standardswere used for all analyses. Importantly, the prevalence ofstunting is about 15% higher with the new standards thanwith the previous growth reference.135 The attributabledeaths and DALYs were estimated for intrauterine growthrestriction, stunting, and severe wasting, separately andtogether, as well as for all wasting and underweight.Co-exposures were considered, and the resulting estimate




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for the anthropometric and micronutrient factors, as well

as suboptimum breastfeeding, provides a total diseaseburden without double counting that results from simpleaddition of the burdens from individual factors.

These estimations using a risk factor method show that449 000 child deaths can be attributed to severe wasting.Estimates by others136have ranged up to 17 million deathsusing a methodology based on actual mortality rates instudies done an average 18 years (maximum 25 years)ago, when overall child mortality rates were much higherthan today. The case fatality rates implied by these twocalculations would be 2% versus 9%. True case-fatalityrates for all cases of severe wasting identified in across-sectional population survey are unknown, but arealmost certainly lower than these of severely malnourished

children presenting to hospitals or feeding centres inemergency settings. Futhermore, over time case fatalityrates have decreased because of better treatment. Sincethe prevalence of HIV infection has increased in somepopulations, some of the deaths reported to have beendue to protein-energy malnutrition in civil registrationsystems could actually have been due to AIDS, but themagnitude of this possible misclassification is unknown.Finally, direct application of case fatality (versusproportional risk) overlooks the fact that some of theexposed children would have non-zero risk of deathregardless of their severe wasting status. Irrespective ofwhether the true number of deaths attributable to severewasting is closer to a half million or to 15 million a year,therapeutic feeding interventions are important com-ponents of nutrition programmes in settings wheresevere wasting is common.

Deficiencies of vitamin A and zinc were confirmed tobe important risk factors in terms of their effects on totalchild mortality. The current estimate of disease burdendue to vitamin A deficiency is similar to previousestimates despite increases in the population coveragewith vitamin A supplementation, because of inclusion ofrisk in the 05 month age group for the first time. Inother words, the true decline in the burden in childrenabove 6 months of age has been numerically compensatedby the finding that vitamin A is important in an even

younger age group. That the estimates of disease burdendue to zinc deficiency are about 40% lower thanpreviously reported73is because of the lower relative risksbased on analysis of additional studies.72 TheWHO/UNICEF recommendation that zinc be usedalong with oral rehydration therapy for all childhooddiarrhoea is just beginning to be implemented in manycountries, and preventive use of zinc supplementationor fortification is uncommon. The high residual burdenof those micronutrient deficiencies indicates thatinterventions need to be expanded, especially insouth-central Asia and Africa.

Iodine and iron deficiencies currently result in onlysmall disease burdens. For iodine deficiency, there hasbeen substantial success with promotion of the use of

iodised salt; this and other interventions should be

continued to prevent resurgence of the related diseaseburden. For iron deficiency the disease burden inchildren is relatively small, accounting for only 05% ofunder-5 DALYs, despite inclusion in the calculations oflife-long developmental disability in 20% of children whohave ever had severe anaemia.76 This postulatedpermanent disability has not been seen in all studies andits existence might need to be reconsidered in thefuture.137 Nevertheless, children with iron deficiencyanaemia should be treated to prevent any possible currentand future adverse effects. Iron deficiency anaemia is animportant contributor to maternal mortality, increasingthe risk of dying with blood loss during delivery.12

Suboptimum breastfeeding has large mortality

consequences worldwide, similar to those of stunting.The estimate reported here is the same (14 milliondeaths) as a previous estimate using a differentcategorisation of breastfeeding practices (combiningpartial and predominant breastfeeding) and differentmortality risks.94,138 The timing of initiation ofbreastfeeding was not considered in these estimates.There is epidemiological evidence to suggest thatbeginning breastfeeding within the first day post partumwould have additional benefit with regard to mortalityeven in exclusively breastfed infants, reaffirmingrecommendations to begin breastfeeding immediatelyafter delivery.89More than three quarters of the burdenattributed to suboptimum breastfeeding is due tonon-exclusive breastfeeding in the first 6 months of lifewhen even provision of water or teas leads to an increasedrisk of death. These estimates do not consider the adverseeffect of transmission of HIV in breast milk. Recentevidence indicates that conditions in which breast milksubstitutes are recommended for babies of HIV-positivemothers are rarely met, and there is a net benefit ofbreastfeeding in terms of HIV-free survival even inpopulations with a high prevalence of HIV infection. 139141Exclusive breastfeeding results in lower rates of HIVtransmission than partial breastfeeding with ratesof 1%142,143and 4%140being reported from studies in Africa.With around 2 million babies born to HIV-positive

mothers every year,144 these transmission rates wouldresult in 20 00080 000 HIV-infected infants in the first6 months of life. Antiretroviral treatment for pregnant orlactating women will substantially reduce these resultinginfections, and such treatment is increasing in Africa.144Because HIV transmission continues with partialbreastfeeding after the first 6 months of life,145 earlybreastfeeding cessation has been considered an option.Evidence is still incomplete; however, a recent trial foundno difference in HIV-free survival at 24 months of age inchildren who were randomly assigned to abrupt weaningat 4 months of age or continued breastfeeding.146

Inadequate complementary feeding contributes tostunting as do infectious diseases, especially repeatedepisodes without adequate case management. These


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exposures, which are arguably the key determinants of

stunting, were not modelled as risk factors in this paper.However, the effects on stunting and related diseaseburden of interventions to improve complementaryfeeding and to reduce diarrhoea incidence are calculatedin a subsequent paper in the Series.28Results presentedhere on the effects of diarrhoea on the risk of stunting areincorporated in these calculations of intervention effects,but other infectious diseases and perhaps asymptomaticinfections are also likely to contribute to stunting.

The nutrition-related risk factors individually result inlarge disease burdens, but often coexist both in individualsand in populations. Stunting and severe wasting inchildren 159 months of age are largely uncorrelated, andthe estimation of the joint effects of these two risk factors

resulted in a slightly smaller total disease burden thansimply adding their effects because even in the absence ofstatistical correlation, some children would be exposed toboth conditions. Intrauterine growth restriction-lowbirthweight was considered for these estimations to affectonly infants younger than 1 month, but in reality couldaffect later ages. Vitamin A, zinc, iron, and iodinedeficiencies and the anthropometric measures as riskfactors are largely uncorrelated, but there is still overlap intheir risk because there is multicausality, such as diarrhoeafor vitamin A, zinc, and stunting. In addition to simplemulticausality, about half of the effect of zinc deficiency ismediated through stunting; the rest is a more direct effecton morbidity and mortality, probably as a result of reducedimmune function.147 The risk related to suboptimumbreastfeeding might in part be due to micronutrientdeficiencies resulting from inadequate dietary intake, butis also due to avoidance of infection. Calculating thecombined effects of suboptimum breastfeeding and theother nutrition-related risk factors found that, even afteraccounting for overlapping effects from multicausality ofdiarrhoea and pneumonia, about half of the diseaseburden attributable to suboptimum breastfeeding wasadded to the other risk factors. Therefore, even if all other

Panel 3:Research needs

Development of methods to assess nutritional status and

its determinants

Prevalence of deficiencies of vitamin A, zinc, iron, and

iodine in subnational populations

Consequences of nutritional deficiencies for mortality

from HIV/AIDS, malaria, and other important infectious

diseases

Consequences of nutritional deficiencies for immune

competence, brain development, cognitive ability, and

other possible effects

Overlap of micronutrients and their joint effects on

mortality and morbidity

Development of international fetal and newborn growth

standards

nutritional risks were addressed, a substantial number of

child deaths would still require interventions related tobreastfeeding practices.Additional research will be important for improving

understanding of the distribution of nutritional de-ficiencies in populations and their risk relations. Somespecific research topics are listed in panel 3. Despite theremaining research needs, these results, which showthe high prevalence of various forms of maternal andchild undernutrition and their health consequences,present a compelling justification for implementationof effective nutrition-related interventions. The potentialeffects of these interventions are considered in the thirdpaper in this Series, with particular attention to theircontribution to achievement of MDG 1 with reduced

undernutrition and also MDGs 4 and 5 regarding childand maternal mortality.

Contributors

RB conceptualised and coordinated the analyses and preparation of thepaper. Primary responsibility for specific topics were as follows: LHA,maternal undernutrition and consequences of selected micronutrientdeficiencies; ZB, complementary feeding; LEC, analysis of intrauterinegrowth restriction-low birthweight and childhood undernutrition risksfor mortality; MdO, stunting, wasting and low birthweight prevalence bycountry and region; ME, analysis of risk factor attributable mortality anddisease burden; CM, update of country, regional, and globaldisease-specific mortality and burden of disease for 2004; and JR,exposure to zinc deficiency by country. All authors contributed to thefinal paper.

Other contributors

Analyses of national surveys for prevalence of underweight, stunting andwasting based on new WHO Child Growth Standards: Monika Blssner,Yang Hong, Allen Shoemaker (WHO, Switzerland). Provision ofestimates of prevalence of breastfeeding status: Ana Betrn, Jeremy Lauer,(WHO, Switzerland). Review of relative risks of suboptimumbreastfeeding: Ai Koyanagi, Sunil Sazawal (Johns Hopkins BloombergSchool of Public Health, USA). Provision of panel 1 (equity gaps in regardto stunting and dietary diversity): Satoru Shimokawa (Cornell University,USA), Cesar Victora (University of Pelotas, Brazil). Provision of data foranalysis of mortality risks related to anthropometric indicators:Keith West, Luke Mullany, Parul Christian, Larry Moulton, James Tielsch(Johns Hopkins Bloomberg School of Public Health, USA), Linda Adair(University of North Carolina School of Public Health, USA), Kre Mlbak(Statens Serum Institut, Denmark), Zulfiqar A Bhutta (Aga KhanUniversity, Pakistan), A M Menezes (University of Pelotas, Brazil),Michel Garenne (Institute Pasteur, France), Shams El Arifeen(International Centre for Diarrhoeal Diseases Research, Bangladesh),M Andersen (University of Copenhagen, Denmark). Provision of data foranalysis of socioeconomic confounding: Saul S Morris (London School ofHygiene and Tropical Medicine, United Kingdom), Keith West (JohnsHopkins Bloomberg School of Public Health, USA). Review of risk relatedto maternal body-mass index: Anju Aggarwal (Johns Hopkins BloombergSchool of Public Health, USA). Provision of data on vitamin Asupplementation coverage: Nita Dalmiya (UNICEF, USA). Assistance inclassifying countries as vitamin A deficient: Keith West (Johns HopkinsBloomberg School of Public Health, USA). Analysis of the contribution ofdiarrhoea to stunting: William Checkley, Gillian Buckley (Johns HopkinsBloomberg School of Public Health, USA). Analyses of mortality andburden of disease attributable to nutrition risk factors: Rodrigo Dias(Harvard University Initiative for Global Health, USA). Analyses of agepatterns of deaths in children younger than 5 years: Kenneth Hill,Thomas Laakso (Harvard University Initiative for Global Health, USA).Analyses of contribution of undernutrition to mortality by cause at birthand during childhood, confounding by socioeconomic factors and ofcorrelation between stunting and wasting: Ping Chen, Carmen Carrillo(Johns Hopkins Bloomberg School of Public Health, USA).


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Maternal and Child Undernutrition Study Group

Series steering committeeRobert E Black (Johns Hopkins Bloomberg

School of Public Health, USA), Zulfiqar A Bhutta (Aga Khan University,Pakistan), Jennifer Bryce (Johns Hopkins Bloomberg School of PublicHealth, USA), Saul S Morris (London School of Hygiene and TropicalMedicine, UK), Cesar G Victora (Federal University of Pelotas, Brazil).Other membersLinda Adair (University of North Carolina, USA),Tahmeed Ahmad (ICDDR,B, Bangladesh), Lindsay H Allen (USDA ARSWestern Human Nutrition Research Center, USA), Laura E Caulfield(Johns Hopkins Bloomberg School of Public Health),Bruce Cogill(UNICEF, USA), Denise Coitinho (WHO, Switzerland), Simon Cousens(London School of Hygiene and Tropical Medicine, UK), Ian Darnton-Hill(UNICEF, USA), Mercedes de Onis (WHO, Switzerland); Kathryn Dewey(University of California, Davis, USA), Majid Ezzati (Harvard School ofPublic Health, USA), Caroline Fall (University of Southhampton, UK),Elsa Giugliani (Federal University of Rio Grande de Sul, Brazil),Batool A Haider (Aga Khan University, Pakistan), Pedro Hallal (FederalUniversity of Pelotas, Brazil), Betty Kirkwood (London School of Hygieneand Tropical Medicine, UK), Reynaldo Martorell (Emory University,

Rollins School of Public Health, USA), Colin Mathers (WHO,Switzerland), David Pelletier (Cornell University, USA),Per Pinstrup-Andersen (Cornell University, USA), Linda Richter (HumanSciences Research Council, South Africa), Juan A Rivera (Mexico NationalInstitute of Public Health), Harshpal Singh Sachdev (Sitaram BhartiaInstitute of Science and Research, India), Meera Shekar (World Bank,USA), Ricardo Uauy (Institute of Nutrition, Chile).

Conflict of interest statement

We declare that we have no conflict of interest. As corresponding author,R Black states that he had full access to all data and final responsibility tosubmit for publication.

Acknowledgments

Funding for the preparation of the Series was provided by the Bill &Melinda Gates Foundation. Meetings were hosted by the UNICEFInnocenti Research Centre and the Rockefeller Foundation BellagioConference Center. The sponsors had no role in the analysis and

interpretation of the evidence nor in writing the report and the decisionto submit for publication. We thank Barbara Ewing and Mary Rybczynskifor administrative assistance with the Series.

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