Cheng et al.1313. Cheng WD, Wold KJ, Bollinger LB, Ordiz MI, Shulman RJ, Maleta KM, et al. Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial. Am J Gastroenterol. 2019;114:671-8. |
214 |
12-23 months |
RCT |
16 weeks |
Lactoferrin and Lysozyme |
Significant change of L% over 8 weeks when compared to the control group (0.23% vs 0.14% P=0.04). But not sustained after 16 weeks of study (0.16% vs 0.11% P=0.17) |
After 16 weeks of intervention, there was no significant change in linear growth when compared to the control (0.028 mm/d and 0.030 mm/d respectively; P=0.12) l- |
|
Low |
Agapova et al.1616. Agapova SE, Stephenson KB, Divala O, Kaimila Y, Maleta KM, Thakwalakwa C, et al. Additional Common Bean in the Diet of Malawian Children Does Not Affect Linear Growth, but Reduces Intestinal Permeability. J Nutr. 2018;148:267-74. |
331 |
12-23 months |
RCT |
48 weeks |
Cowpea and common bean |
The dual sugar absorption test, measuring %L and L:M, were not significantly different between the intervention and control groups after 48 weeks. However, only the common bean group had a significant effect estimate on %L (-0.073396, SD 0.029887; P=0.0073) |
Change in LAZ score after 48 weeks of intervention was not significant compared to the control group. The changes in LAZ score was 0.14±0.49, -0.11±0.54 (P=0.67) and -0.07±0.51 (P=0.31) in the control, cowpea and common bean group respectively after 48 weeks |
The parameter was not studied |
Low |
Wessells et al.1010. Wessells KR, Hinnouho GM, Barffour MA, Arnold CD, Kounnavong S, Kewcharoenwong C, et al. Impact of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Plasma Biomarkers of Environmental Enteric Dysfunction among Rural Laotian Children: A Randomized Controlled Trial. Am J Trop Med Hyg. 2020;102:415-26. |
359 |
6-23 months |
RCT |
36 weeks |
Zinc and MNP |
The intervention after 36 weeks did not have a significant effect estimate on citrulline, kynurenine, tryptophan and KT ratio |
After 36 weeks, there was no significant difference of LAZ score between the intervention and control groups. The LAZ score at the end of the study were: preventive zinc group −1.93±0.97, micronutrient powder group −1.94±1.00, theraupetic zinc group −1.95±1.02 and control group −1.93±1.00 (P=0.58) obtained from parent trial (Balffour 2019) |
Citrulline, Kynurenine, Tryptophan and KT ratio was not associated with changes in LAZ score after 36 weeks |
Low |
Hinnouho et al1212. Hinnouho GM, Wessells KR, Barffour MA, Sayasone S, Arnold CD, Kounnavong S, et al. Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial. Am J Trop Med Hyg. 2020;103:1416-26. |
720 |
6-23 months |
RCT |
36 weeks |
Zinc and MNP |
The intervention had no significant impact on endline MPO, NEO and CAL after 36 weeks |
No data |
MPO, but not NEO and CAL, was associated with change in LAZ score after 16-20 weeks ((−0.029, (−0.054, −0.003); P= 0.027)). However, after 32-40 weeks of intervention, MPO, NEO and CAL were not associated with the change in LAZ score |
Low |
Bierut et al.2020. Bierut T, Duckworth L, Grabowsky M, Ordiz MI, Laury ML, Callaghan-Gillespie M, et al. The effect of bovine colostrum/egg supplementation compared with corn/soy flour in young Malawian children: a randomized, controlled clinical trial. Am J Clin Nutr. 2021;113:420-7. |
275 |
9 months |
RCT |
36 weeks |
Bovine Colostrum and Egg |
Using L%<0.20 as a cut-off for EED, after 36 months of intervention, the study found resolution of EED in 50% (10/20 subjects) of patients, while in the control group EED resolution was found in 13.3% (2/15 subjects) of patients (P<0.05) |
After 36 weeks of intervention, there was a significant difference of change in LAZ score between the intervention and control group (0.12 z-scores, P=0.0011). However, the study observed the two groups until 5 months post-intervention, and at that point the difference of change of LAZ score between the two groups was no longer significant. On the other hand, 5 months post intervention, the prevalence of stunting in the intervention group was significantly smaller (47 ((35)); RR 0.70; CI95%=0.52-0.94; P=0.018)) compared to the control group (62 ((49)) |
The parameter was not studied |
Low |
Ryan et al.1111. Ryan KN, Stephenson KB, Trehan I, Shulman RJ, Thakwalakwa C, Murray E, et al. Zinc or Albendazole Attenuates the Progression of Environmental Enteropathy: A Randomized Controlled Trial. CGH. 2014;12:1507-1513.e1. |
222 |
12-36 months |
RCT |
48 days |
Zinc |
Change in L:M and the prevalence of subjects with L:M >0.30 was significantly lower in the zinc group compared to placebo (P<0.02 and P<0.04 respectively). However, there was no significant difference between groups for mannitol excretion after the intervention |
There was no significant change in length (cm) between groups after 48 days. The change in length was 1.1±0.9 in the zinc group and 1.1±1.6 in the placebo group |
The parameter was not studied |
Low |
Lin et al.1818. Lin A, Ali S, Arnold BF, Rahman MZ, Alauddin M, Grembi J, et al. Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Environmental Enteric Dysfunction in Young Children: A Cluster-randomized, Controlled Trial in Rural Bangladesh. Clin Infect Dis. 2020;70:738-47. |
1783 |
recruited since birth |
Cluster RCT |
18 months |
SQ-LNS |
NEO was lower in the intervention group at 3 months and 14 months. However, by 28 months there were no differences in NEO in between all groups |
Linear growth was an assessed parameter in the parent trial; however, the results are not yet published |
Association between Linear growth and EED was an assessed parameter in the parent trial, however, the results are not yet published |
Low |
|
|
|
|
|
|
At 3 and 14 months, there was no difference in MPO in between groups, however by 28 months, MPO was higher in the WASH group and nutrition group compared to controls |
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|
|
At 3 months, Lactulose was lower in all intervention groups compared to the control group. However, at 14 months there were no differences in all groups. And at 28 months, lactulose was higher in the WASH group compared to controls |
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|
At 3 months, mannitol was lower in all intervention groups compared to control groups. However, at 14 and s8 months, there were no difference in mannitol in all groups |
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|
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L:M at 3 months was no different in all groups. At 28 months, L:M was higher in all intervention groups compared to control group |
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|
There was no difference in AAT in all groups at 3, 14 and 28 months |
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|
|
Smith et al.1414. Smith HE, Ryan KN, Stephenson KB, Westcott C, Thakwalakwa C, Maleta K, et al. Multiple Micronutrient Supplementation Transiently Ameliorates Environmental Enteropathy in Malawian Children Aged 12-35 Months in a Randomized Controlled Clinical Trial. J Nutr. 2014;144:2059-65. |
230 |
12-35 months |
RCT |
24 weeks |
MNP and Fish Oil |
L:M after 24 weeks significantly improved from baseline in intervention groups and control group (P<0.05), however there was no significant difference between the intervention groups and the control group. In terms of L% excreted. there was no significant difference between groups after 24 weeks |
The parameter was not studied |
The parameter was not studied |
Low |
Gough et al.1717. Gough EK, Moulton LH, Mutasa K, Ntozini R, Stoltzfus RJ, Majo FD, et al. Effects of improved water, sanitation, and hygiene and improved complementary feeding on environmental enteric dysfunction in children in rural Zimbabwe: A cluster-randomized controlled trial. PLoS Negl Trop Dis. 2020;14:e0007963. |
1169 |
recruited since birth |
Cluster RCT |
18 months |
SQ-LNS |
There was no consistent evidence that the intervention interacted with any biomarker in this study |
The parameter was not studied |
The parameter was not studied |
Low |
|
|
|
|
|
|
Stool biomarkers of inflammation decreased at the end of the study, MPO was consistent from months 1-6 7518 ng/mL (95%CI:7014-8059) then rapidly declined to 2825ng/mL (95%CI:2669-2991) at 18 months. NEO increased in the first six months (from 980 nmol/L (95%CI:908-1057) to 1283 nmol/L (95%CI:1230-1337)) then decreased at 18 months to 383 nmol/L (95%CI:362-407) |
|
|
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|
|
Intestinal damage biomarkers had no discernible pattern. Stool REG-1β increased in the first 12 months from 40.6μg/mL (95%CI:36.4-45.1) to 154.6 μg/mL (95%CI:145.5-164.2) then decreased to 132.9μg/mL (95%CI:123.1-143.6). Plasma citrulline increased from 2744 ng/mL (95%CI:2658-2834) at month 6 to 3150 ng/mL (95%CI:3075-3227) by 12 months. I-FABP had a U-shaped pattern, starting with a decline in the first 6 months from 1031 pg/mL (95%CI:993-1021) to 913 pg/mL (95%CI:892-934, then increased to 1198 pg/mL (95%CI:1160-1237) at 18 months |
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Intestinal permeability biomarkers overall decreased during the 18 month follow-up, showed by AAT from 0.47 mg/mL (95%CI:0.44-0.51) to 0.24 mg/mL (95%CI:0.22-0.25) at 18 months and urinary LM ratio declined from 0.84 (95%CI:0.71-0.8) at 6 months to 0.49 (95%CI:0.43,0.53) at 18 month |
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Plasma systemic inflammation markers showed opposite patterns, where CRP steadily increased rom 0.63mg/L (95%CI:0.55-0.71) to 1.28mg/L (95%CI:1.14-1.43) in 18 months, KTR declined from 64.8 (95%CI: 62.2,67.6) at 1 month to 44.9 (95%CI: 43.6,46.3) between 6-12 months |
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Marker of microbial translocation, Soluble CD14 increased from 769,192 pg/mL (95%CI: 741,069-798,383) to 1,334,175 pg/mL (95%CI: 1,292,950-1,3767,16) in 18 months |
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Meanwhile IGF-1 decreased from 27.1 ng/mL (26.0-28.2) to 17.9 ng/mL at 12 months (17.4-18.5) |
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Vilander et al.2121. Vilander AC, Hess A, Abdo Z, Ibrahim H, Doumbia L, Douyon S, et al. A Randomized Controlled Trial of Dietary Rice Bran Intake on Microbiota Diversity, Enteric Dysfunction, and Fecal Secretory IgA in Malian and Nicaraguan Infants. J Nutr. 2022;152:1792-800. |
95 |
6 months |
RCT |
6 months |
Rice bran |
There was no significant difference of total fecal sIgA between rice bran and control groups after intervention. Total fecal sIgA is significantly correlated with NEO, AAT, CAL and MPO over a 6 month period of study. Malian rice bran groups observed significantly decreased EED scores compared to control group, but this was not observed in the Nicaragua rice-bran group. NEO, AAT, CAL and MPO were not correlated with EED scores |
The parameter was not studied |
The parameter was not studied |
Low |
Stephenson et al.1515. Stephenson KB, Agapova SE, Divala O, Kaimila Y, Maleta KM, Thakwalakwa C, et al. Complementary feeding with cowpea reduces growth faltering in rural Malawian infants: a blind, randomized controlled clinical trial. Am J Clin Nutr. 2017;106:1500-7. |
291 |
6 months |
RCT |
6 months |
Cowpea and common bean |
After 6 months of intervention, there was no significant difference of L:M, Lactulose excretion and mannitol secretion compared to the control group |
The cowpea group observed a significant decrease in LAZ score ((-0.14±0.52 (111); P=0.048) compared to common bean and placebo in the first 3 months of the study. However no significant change of LAZ score was observed in all groups after 6 months of intervention. At the end of the study, the change of LAZ score was -0.13±0.68 (103), -0.17±0.66 (106), -0.14±0.60 (98) for cowpea, common bean and the control group respectively (P>0.05) |
The parameter was not studied |
Low |