840 Am J Clin Nutr 2012;96:840–7. Printed in USA. Ó 2012 American Society for Nutrition
COMPLEMENTARY FEEDING AND STUNTING 841
foods or micronutrient supplements are recommended (9). These Sample size calculations were based on an effect size of 0.3 SD
products are typically less expensive but have the challenge of units in linear growth, and statistical power was set at 80% to
not being routinely available, especially in rural, resource-lim- detect a difference of 0.3 SD units in linear growth velocity from
ited settings, where access to and use of fortified commercial 6 to 18 mo of age between the 2 feeding groups by using a 2-tailed
products is often limited (10). Many education interventions to test and a 5% type 1 error rate. An assumed intracluster corre-
promote dietary diversification with locally available foods have lation coefficient of 0.05, adjustment for 20% attrition, and an
been undertaken and have shown promising results on growth allowance for cluster loss resulted in a requirement of 20 clusters
(12–14). To our knowledge, however, no efficacy trials of the and 600 subjects per treatment group (15).
effect of routine consumption of meats as a complementary food Randomization was performed at the community level,
have been reported. stratifying by site and stunting rate. Strata were created by
The broad goal of this study was to improve the growth, health, combining communities with similar stunting rates, as measured
and development of infants and young children in diverse low- in a pilot study (10), within each site, and a computer-generated
resource settings by improving the quality of complementary randomization algorithm assigned clusters at a 1:1 ratio within
feeding. We hypothesized that the daily provision of meat each stratum. For practical implementation reasons, neither the
compared with an equicaloric portion of a micronutrient-fortified study participants nor the study staff was masked to cluster
cereal as an early complementary food would result in greater treatment assignment. Geographic distance between clusters
linear growth velocity from 6 through 18 mo of age. Secondary minimized the risk of contamination of the intervention or com-
outcomes included dietary diversity, micronutrient status, neu- munication among study subjects in different clusters.
Intervention
SUBJECTS AND METHODS Subjects in the intervention clusters received a daily provision
of lyophilized beef (Mountain House Inc), equivalent to 30 g
Study design and setting
cooked meat/d from 6 through 11 mo of age and 45 g/d from 12
The details of the protocol for this trial were published through 18 mo of age. Subjects residing in clusters randomly
previously (15). Briefly, we applied a cluster randomized design assigned to the comparison group received a micronutrient-
to compare the effect of consumption of daily meat with that of fortified rice-soy cereal product (Nutrica), which was equicaloric
a micronutrient-fortified cereal, starting at 6 mo of age and to the daily meat portions: 70 and 105 kcal/d for the first and
continuing through 18 mo. The study was undertaken through second 6-mo periods, respectively. The levels of micronutrient
the Eunice Kennedy Shriver National Institute of Child Health fortification were based on recommendations from the literature
and Human Development–supported Global Network for (16). The specific comparison of the micronutrient content of the
Women’s and Children’s Health Research (GN)4. Participating 2 intervention foods was published previously (15); a graphic
GN sites were rural communities in the Democratic Republic comparison of selected aspects of the nutrient composition is
of Congo and Zambia, semirural communities in the Western presented in Figure 1. In addition, both groups received edu-
Highlands of Guatemala, and urban communities in Karachi, cational messages about complementary feeding: encourage
Pakistan. A total of 40 clusters, 5 in each study arm per site, were thickened feeds, offer complementary foods $3 times per day,
included. Cluster inclusion criteria included an estimated preva- and optimize variety of complementary foods. Messages re-
lence of stunting of $20%, based on pilot data obtained in the garding exclusive breastfeeding through 6 mo, hand washing,
same sites (10). and use of boiled water for food preparation were also empha-
sized. Compliance was monitored at weekly visits by counting
empty food packets and by mothers’ reports. Compliance for
Subjects each subject was calculated by dividing the number of days the
Inclusion criteria for individual subjects included infants aged subject ate the study food by the total number of days the subject
3–4 mo who were primarily or exclusively breastfed and whose was followed.
mothers intended to continue breastfeeding through at least the
first year of life. Individual exclusion criteria included use of
free or subsidized fortified complementary foods or infant for-
mula, multiple births, known congenital anomaly, and neuro-
logic deficit. Computer-generated lists of births within each
cluster were used to recruit and screen potential participants.
The subjects were assigned to the cluster in which they resided.
The protocol was approved by ethics boards located in the
countries where the studies were located, the partnering US
institutions, and RTI International, and the study was conducted
pursuant to these guidelines.
4
Abbreviations used: GN, Global Network for Women’s and Children’s
Health Research; LAZ, length-for-age z score; SES, socioeconomic status; FIGURE 1. Nutrient composition of the intervention foods per daily
WLZ, weight-for-length z score. portion for 6–12-mo-olds. B12, vitamin B-12; CHO, carbohydrate.
842 KREBS ET AL
Outcome assessments and primary and secondary outcomes by using generalized es-
Study assessments were conducted by trained staff different timating equation extensions of logistic models (for binary
from the intervention teams; standardized assessments were measures) and linear models (for continuous measures) to ac-
conducted when participating infants were 6, 9, 12, and 18 mo of count for the correlation of subjects induced by the cluster
age. Assessments included anthropometric measurements, the randomization with control for GN site. Analogous generalized
Infant and Child Feeding Index and its components (17, 18), estimating equation models compared outcomes between the
Bayley Scales of Infant Development at 18 mo, and biochemical treatment arms, adjusting for potential confounders; covariates
indexes of micronutrient status at 18 mo, which were determined included both subject level and community level (as above). An
in a convenience subsample of w300 subjects per group (60% of additional post hoc analysis was performed to examine the effect
total subjects), with approximately equal numbers of subjects of meat consumption on linear growth velocity over time by
sampled from each site (15). Hemoglobin concentrations, obtained modeling longitudinal growth data from 6 to 18 mo by using
via finger stick, were obtained from 63–77% of subjects at 3 of the linear mixed models. Data were analyzed by using SAS statis-
4 sites. Because of a protocol deviation, measurements of hemo- tical software (SAS Inc) and are presented as means 6 SDs and
globin were not obtained from subjects at the Pakistani site. 95% CIs unless otherwise indicated.
Length
LAZ
6 mo 21.44 6 1.333 (21.55, 21.32) 21.32 6 1.39 (21.44, 21.21) 0.233
9 mo 21.49 6 1.39 (21.61, 21.37) 21.43 6 1.43 (21.55, 21.31) 0.542
12 mo 21.70 6 1.39 (21.82, 21.58) 21.68 6 1.31 (21.80, 21.57) 0.745
18 mo 22.04 6 1.33 (22.16, 21.93) 21.89 6 1.42 (22.01, 21.77) 0.126
Stunting rate (LAZ ,2) [n (%)]
6 mo 181 (34) (30, 38) 177 (33) (29, 37) 0.713
9 mo 184 (35) (31, 39) 179 (34) (30, 38) 0.676
12 mo 222 (42) (38, 46) 212 (40) (36, 44) 0.510
18 mo 273 (51) (47, 56) 239 (45) (41, 49) 0.080
Weight
Weight-for-age z score
Although iron status was significantly more favorable for the groups, with approximately two-thirds of the hemoglobin mea-
cereal group, both anemia and iron-deficiency rates for both surements from the African sites (171 and 178 for Democratic
groups at 18 mo were notably lower than worldwide prevalence Republic of Congo and Zambia, respectively), compares very
estimates and suggest a benefit of both food interventions on iron favorably with WHO anemia prevalence estimates of 67.6% for
status. In particular, the anemia rate of ,25% for both of the Africa (27). Data for iron deficiency are much more limited, but
TABLE 4
Biomarkers of micronutrient status at 18 mo of age by group
Meat Cereal
Hemoglobin (g/dL)2 287 11.5 6 1.5 (11.3, 11.7) 267 11.7 6 1.3 (11.5, 11.8) 0.189
Ferritin (ng/mL) 290 27.6 6 27.6 (24.4, 30.8) 261 38.2 6 44.2 (32.8, 43.6) 0.002
Tranferrin receptor (mg/L) 335 13.7 6 6.9 (12.9, 14.4) 301 12.1 6 4.7 (11.5, 12.6) 0.001
Zinc (mg/dL) 291 63.2 6 12.3 (61.9, 64.5) 262 62.2 6 12.4 (60.8, 63.6) 0.429
Vitamin B-12 (pg/mL) 312 221 6 103 (210, 233) 285 222 6 123 (207, 236) 0.762
1
Type 3 generalized estimating equation analysis.
2
Measurements not obtained at the Pakistani site.
846 KREBS ET AL
the prevalence is typically much higher than for iron deficiency AT, CLB, OP, RLG, EC, and WAC: participated in the design and imple-
anemia. The rates of low ferritin observed for both groups in this mentation of the study, the intervention, and the evaluation procedures; and
study are much lower than prevalence estimates for such settings MK, NG, TDH, and EMM: participated in the study design, data manage-
ment, and statistical analysis. The remaining authors participated in the de-
(28) and are comparable with observed outcomes after home-
sign and implementation of the study. All authors read and approved the
fortification interventions with micronutrient powders (29, 30). manuscript. None of the authors had any conflicts of interest.
Although the heme iron in meat would be expected to be highly
bioavailable, the absorption would have needed to be w50%
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