Effects of Different Doses, Forms, and Frequencies of Zinc Supplementation on Biomarkers of Iron and Zinc Status among Young Children in Dhaka, Bangladesh
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Participants
2.3. Interventions
2.4. Study Procedures
2.5. Laboratory Analysis Methods
2.6. Statistical Analyses
2.7. Ethical Considerations
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Standard MNP | HiZn LoFe Daily (n = 58) | HiZn LoFe Alternating (n = 57) | Zn Tablet Daily (n = 58) | Zn Tablet Intermittent (n = 59) | Placebo Control (n = 58) | |
---|---|---|---|---|---|---|
Child characteristics | ||||||
Age, months | 9.72 ± 0.82 | 9.83 ± 0.92 | 9.76 ± 0.83 | 9.70 ± 0.93 | 9.77 ± 0.82 | 9.86 ± 0.86 |
Male | 29 (50.0) | 29 (50.0) | 29 (50.9) | 29 (50.0) | 29 (49.2) | 29 (50.0) |
Breastfeeding | 58 (100) | 52 (89.7) | 54 (94.7) | 54 (93.1) | 57 (96.6) | 53 (91.4) |
Length-for-age Z-score | −1.08 ± 1.01 | −1.43 ± 1.00 | −1.16 ± 1.19 | −1.21 ± 1.06 | −1.22 ± 1.02 | −1.45 ± 1.12 |
Weight-for-age Z-score | −0.73 ± 1.02 | −1.39 ± 0.96 | −0.89 ± 1.07 | −0.91 ± 1.17 | −0.96 ± 0.93 | −1.29 ± 1.06 |
Weight-for-length-Z score | −0.17 ± 1.00 | −0.80 ± 0.88 | −0.32 ± 0.85 | −0.32 ± 1.06 | −0.39 ± 0.86 | −0.64 ± 0.92 |
MUAC, cm | 14.1 ± 0.96 | 13.6 ± 0.83 | 14.0 ± 0.94 | 14.1 ± 1.13 | 14.1 ± 0.90 | 13.7 ± 0.93 |
Child healthy at enrollment | 14 (24.1) | 15 (25.9) | 21 (36.8) | 11 (19.0) | 22 (37.3) | 15 (25.9) |
Maternal characteristics | ||||||
Age, years | 23.2 ± 5.35 | 24.8 ± 4.44 | 25.2 ± 6.17 | 25.4 ± 5.06 | 24.9 ± 5.39 | 24.4 ± 4.96 |
Currently married | 58 (100) | 58 (100) | 57 (100) | 58 (100) | 59 (100) | 58 (100) |
Occupation | ||||||
Housewife | 55 (94.8) | 56 (96.6) | 54 (94.7) | 55 (94.8) | 53 (89.8) | 54 (93.1) |
Work outside home | 2 (3.4) | 2 (3.4) | 3 (5.3) | 2 (3.4) | 6 (10.2) | 4 (6.9) |
Work from home | 1 (1.7) | 0 (0) | 0 (0) | 1 (1.7) | 0 (0) | 0 (0) |
Years of education completed | 6.83 ± 4.34 | 5.76 ± 3.81 | 6.60 ± 4.44 | 5.62 ± 3.65 | 7.07 ± 4.01 | 6.40 ± 3.80 |
Number of live births in lifetime | 1.72 ± 0.83 | 1.91 ± 0.88 | 1.88 ± 1.10 | 2.07 ± 1.06 | 1.63 ± 0.79 | 1.86 ± 1.08 |
Socioeconomic characteristics | ||||||
Number of people who sleep in the household | 4.47 ± 2.50 | 4.83 ± 1.68 | 4.58 ± 1.99 | 4.67 ± 1.77 | 4.42 ± 1.62 | 4.72 ± 1.70 |
Main source of drinking water | ||||||
Piped into dwelling | 52 (89.7) | 1 (1.7) | 47 (82.5) | 3 (5.2) | 3 (5.2) | |
Piped to yard/plot | 4 (6.9) | 33 (56.9) | 9 (15.8) | 33 (56.9) | 52 (88.1) | 36 (62.1) |
Public tap/stand pipe | 1 (1.7) | 18 (31.0) | 0 (0) | 19 (32.8) | 7 (11.9) | 15 (25.9) |
Tube well or borehole | 1 (1.7) | 4 (6.9) | 1 (1.8) | 3 (5.2) | 0 (0) | 3 (5.2) |
Other | 0 (0) | 2 (3.4) | 0 (0) | 0 (0) | 0 (0) | 1 (1.7) |
Flush toilet use | 57 (98.3) | 50 (86.2) | 57 (100) | 55 (94.8) | 59 (100) | 50 (86.2) |
Protected toilet use 3 | 7 (12.1) | 5 (8.6) | 8 (14.0) | 4 (6.9) | 7 (11.9) | 3 (5.2) |
Hygiene score 4 | 12.4 ± 2.38 | 12.9 ± 2.33 | 12.7 ± 2.29 | 12.9 ± 2.55 | 12.7 ± 2.19 | 12.5 ± 2.42 |
Asset score 5 | 5.02 ± 2.21 | 5.48 ± 2.09 | 5.49 ± 2.77 | 5.14 ± 2.38 | 5.59 ± 2.45 | 5.16 ± 2.38 |
Average monthly income for the entire household, BDT 6 | 18,078 ± 8443 | 13,853 ± 8325 | 22,000 ± 11,720 | 16,621 ± 12,421 | 18,864 ± 11,264 | 15,388 ± 9618 |
HFIAS classification 7 | ||||||
Food-secure | 44 (75.9) | 46 (79.3) | 46 (80.7) | 47 (81.0) | 41 (69.5) | 53 (91.4) |
Mildly food-insecure | 3 (5.2) | 2 (3.4) | 3 (5.3) | 2 (3.4) | 7 (11.9) | 0 (0) |
Moderately food-insecure | 6 (10.3) | 5 (8.6) | 1 (1.8) | 4 (6.9) | 3 (5.1) | 3 (5.2) |
Severely food-insecure | 5 (8.6) | 5 (8.6) | 7 (12.3) | 5 (8.6) | 8 (13.6) | 2 (3.4) |
Standard MNP | HiZn LoFe Daily | HiZn LoFe Alternating | Zn Tablet Daily | Zn Tablet Intermittent | Placebo Control | p Value | |
---|---|---|---|---|---|---|---|
Biomarker at enrollment | n = 58 | n = 58 | n = 57 | n = 58 | n = 59 | n = 57 | |
Serum zinc, ug/dL 3 | 70.0 ± 9.97 | 70.5 ± 10.09 | 67.8 ± 12.2 | 66.7 ± 12.8 | 70.2 ± 12.0 | 67.8 ± 14.4 | 0.40 |
Serum zinc < 65 ug/dL 3 | 15 (25.9) | 17 (29.3) | 24 (42.9) | 28 (48.3) | 15 (25.4) | 24 (42.1) | 0.03 |
Hemoglobin, g/dL 4 | 10.4 ± 1.16 | 10.3 ± 1.00 | 10.3 ± 1.12 | 10.3 ± 1.04 | 10.4 ± 1.19 | 10.3 ± 1.05 | 0.48 |
Hemoglobin < 11 g/dL 4 | 334 (69.4) | 345 (71.9) | 333 (69.2) | 357 (74.1) | 322 (66.9) | 347 (72.1) | 0.18 |
Adjusted ferritin, ug/L 5 | 6.26 ± 7.02 b | 10.9 ± 9.91 a | 6.05 ± 5.47 b | 9.87 ± 9.65 a,b | 7.69 ± 9.26 a,b | 9.15 ± 9.08 a,b | 0.007 |
Adjusted ferritin < 12 ug/L 5 | 38 (65.5) | 29 (50.0) | 43 (75.4) | 34 (58.6) | 35 (59.3) | 31 (54.4) | 0.10 |
sTfR, mg/L 6 | 12.2 ± 5.31 a,b | 9.71 ± 3.49 b | 10.4 ± 4.66 a,b | 11.1 ± 5.00 a,b | 10.5 ± 4.95 a,b | 12.4 ± 6.43 a | 0.03 |
sTfR 6 > 8.3 mg/L 6 | 45 (77.6) | 38 (65.5) | 33 (57.9) | 40 (69.0) | 33 (55.9) | 41 (71.9) | 0.12 |
Adjusted BIS, mg/kg body weight 6,7 | −3.69 ± 5.15 b | −0.93 ± 3.98 a | −3.24 ± 4.23 a,b | −1.69 ± 4.44 a,b | −2.38 ± 5.54 a,b | −2.33 ± 4.63 a,b | 0.02 |
Adjusted BIS < 0 6,7 | 43 (74.1) | 30 (51.7) | 42 (73.7) | 34 (58.6) | 36 (61.0) | 34 (59.6) | 0.09 |
Iron deficiency anemia | 34 (58.6) | 25 (43.1) | 30 (52.6) | 32 (55.2) | 26 (44.1) | 24 (42.1) | 0.33 |
RBP, umol/L 6 | 1.08 ± 0.22 a,b | 0.98 ± 0.23 b | 1.14 ± 0.23 a | 0.96 ± 0.30 b | 1.12 ± 0.25 a | 0.95 ± 0.28 b | <0.0001 |
RBP < 0.81 umol/L 6 | 4 (6.9) a,b | 10 (17.2) a,b | 2 (3.5) a | 14 (24.1) a,b | 4 (6.8) a,b | 16 (28.1) b | 0.001 |
CRP, mg/L 6 | 0.23 ± 0.46 | 0.23 ± 0.41 | 0.22 ± 0.38 | 0.32 ± 0.63 | 0.14 ± 0.25 | 0.21 ± 0.43 | 0.31 |
CRP> 5 mg/L 6 | 5 (8.6) | 4 (6.9) | 2 (3.5) | 5 (8.6) | 2 (3.4) | 6 (10.5) | 0.61 |
AGP, g/L 6 | 0.68 ± 0.30 | 0.62 ± 0.33 | 0.66 ± 0.30 | 0.67 ± 0.38 | 0.614 ± 0.27 | 0.604 ± 0.33 | 0.66 |
AGP > 1 g/L 6 | 9 (15.5) | 13 (22.4) | 11 (19.3) | 14 (24.1) | 7 (11.9) | 9 (15.8) | 0.53 |
Biomarker at 24 week visit | n = 50 | n = 51 | n = 49 | n = 53 | n = 48 | n = 54 | |
Serum zinc, ug/dL 7 | 71.2 ± 2.38 c,d | 80.7 ± 2.56 b,c | 81.3 ± 2.60 a,b | 92.5 ± 2.86 a | 66.7 ± 2.28 d | 73.7 ± 2.22 b–d | <0.0001 |
Serum zinc < 65 ug/dL | 9 (18.0) a,b | 6 (12.2) a,b | 7 (14.3) a,b | 3 (5.8) a | 17 (35.4) b | 18 (32.7) b | 0.0003 |
Hemoglobin, g/dL 3 | 11.0 ± 0.05 a | 10.7 ± 0.05 b | 10.7 ± 0.05 b | 10.2 ± 0.05 c | 10.21 ± 0.0 c | 10.2 ± 0.05 c | <0.0001 |
Hemoglobin < 11 g/dL | 203 (45.9) a | 247 (54.8) a,b | 264 (60.4) b | 324 (73.8) c | 303 (69.5) c | 340 (75.2) c | <0.0001 |
Adjusted ferritin, ug/L 4 | 14.4 ± 2.01 a | 10.8 ± 1.42 a | 10.9 ± 1.44 a | 5.10 ± 0.65 b | 5.09 ± 0.73 b | 5.68 ± 0.72 b | <0.0001 |
Adjusted ferritin < 12 ug/L | 23 (46.0) a | 22 (43.1) a | 23 (46.9) a,b | 42 (79.2) c | 36 (75.0) b,c | 46 (83.6) c | <0.0001 |
sTfR6, mg/L | 7.72 ± 0.2 d | 10.0 ± 0.56 b–d | 9.95 ± 0.56 c,d | 12.9 ± 0.62 a | 12.3 ± 0.68 a,b | 12.2 ± 0.60 a–c | <0.0001 |
sTfR6 > 8.3 mg/L | 19 (38.0) a | 28 (54.9) a | 31 (63.3) a–c | 45 (84.9) c | 28 (58.3) a,b | 45 (81.8) b,c | <0.0001 |
Adjusted BIS, mg/kg body weight 6,7 | 0.78 ± 0.60 a | −0.95 ± 0.56 a | −0.87 ± 0.57 a | −4.73 ± 0.55 b | −4.40 ± 0.61 b | −4.04 ± 0.54 b | <0.0001 |
Adjusted BIS < 0 mg/kg body weight 6,7 | 20 (40.0) a | 24 (47.1) a | 27 (55.1) a | 44 (83.0) b | 33 (68.8) a,b | 47 (85.5) b | <0.0001 |
Iron deficiency anemia | 14 (28.0) a | 17 (33.3) a,b | 15 (30.6) a–c | 32 (61.5) a–c | 26 (54.2) b,c | 39 (70.9) c | <0.0001 |
RBP, umol/L 6 | 0.93 ± 0.04 a,b | 1.09 ± 0.04 a | 0.91 ± 0.04 a,b | 0.97 ± 0.04 a,b | 0.84 ± 0.04 b | 1.02 ± 0.04 a,b | 0.008 |
RBP < 0.81 umol/L 6 | 8 (16.0) | 4 (7.8) | 8 (16.3) | 8 (15.1) | 12 (25.0) | 6 (10.9) | 0.20 |
CRP, mg/L 6 | 0.37 ± 0.15 | 0.17 ± 0.06 | 0.60 ± 0.23 | 0.17 ± 0.06 | 0.46 ± 0.19 | 0.32 ± 0.12 | 0.28 |
CRP > 5 mg/L 6 | 6 (12.0) | 7 (13.7) | 8 (16.3) | 8 (15.1) | 9 (18.8) | 10 (18.2) | 0.94 |
AGP, g/L 6 | 0.60 ± 0.06 b | 0.69 ± 0.06 a,b | 0.83 ± 0.07 a | 0.64 ± 0.05 a,b | 0.67 ± 0.06 a,b | 0.76 ± 0.06 a,b | 0.03 |
AGP > 1 g/L 6 | 10 (20.0) a,b | 11 (21.6) a,b | 20 (40.8) b | 7 (13.2) a | 15 (31.3) a,b | 13 (23.6) a,b | 0.04 |
Variable | Effect Modifier (X) | Standard MNP | HiZn LoFe Daily | HiZn LoFe Alternating | Zn Tablet Daily | Zn Tablet Intermittent | Placebo Control | Group by X p-Value | Group within X p-Value |
---|---|---|---|---|---|---|---|---|---|
Adj. ferritin at 24 weeks, ug/L 3 | Baseline adj. ferritin at 10th %ile 3 | 7.04 ± 1.29 a | 4.22 ± 0.96 a,b | 4.39 ± 0.81 a,b | 2.14 ± 0.48 b,c | 1.37 ± 0.25 c | 3.10 ± 0.66 a–c | 0.004 | <0.0001 |
Baseline adj. ferritin at 90th %ile 3 | 23.6 ± 4.71 a,b | 24.4 ± 4.31 a | 23.5 ± 5.36 a–c | 11.1 ± 1.84 b,c | 17.1 ± 3.19 a–c | 10.4 ± 1.78 c | 0.0002 | ||
Lowest tertile of consumption | 7.61 ± 1.90 | 6.66 ± 1.61 | 9.56 ± 2.0 | 5.63 ± 1.48 | 6.27 ± 1.68 | 5.79 ± 1.31 | 0.01 | 0.62 | |
Mid tertile of consumption | 11.8 ± 2.61 a | 12.02 ± 2.08 a | 10.2 ± 2.06 a | 5.51 ± 0.93 a | 5.48 ± 1.04 a | 6.48 ± 1.17 a | 0.0003 | ||
Highest tertile of consumption | 22.0 ± 3.89 a | 12.3 ± 2.44 a | 12.8 ± 2.55 a | 4.19 ± 0.83 b | 4.24 ± 0.85 b | 4.85 ± 0.89 b | <0.0001 | ||
Adj. ferritin < 12 ug/L at 24 weeks 3 | Baseline adj. ferritin at 10th %ile 3 | 63.5 ± 10.3 a | 88.9 ± 7.75 a | 83.7 ± 8.64 a,b | 99.9 ± 0.15 b | 98.8 ± 1.65 a,b | 98.9 ± 1.56 a,b | 0.03 | 0.004 |
Baseline adj. ferritin at 90th %ile 3 | 25.9 ± 10.0 a,b | 13.6 ± 7.01 a | 5.73 ± 4.92 a | 46.0 ± 13.4 a,b | 37.4 ± 14.5 a,b | 64.3 ± 11.02 b | 0.001 | ||
sTfR at 24 weeks, mg/L 3,4 | Baseline sTfR at 10th %ile 3 | 6.99 ± 0.65 a,b | 6.86 ± 0.59 b | 7.19 ± 0.63 a,b | 9.39 ± 0.68 a | 7.83 ± 0.63 a,b | 9.28 ± 0.68 a | <0.0001 | 0.007 |
Baseline sTfR at 90th %ile 3 | 10.6 ± 0.87 c | 15.3 ± 1.47 b,c | 15.1 ± 1.14 b,c | 19.2 ± 1.37 a,b | 23.2 ± 1.52 a | 17.3 ± 0.98 b | <0.0001 | ||
BIS (mg/kg body weight) 4,5 | Baseline body iron at 10th %ile | −1.81 ± 0.88 a | −5.41 ± 1.15 a–c | −4.44 ± 0.91 a,b | −8.98 ± 1.08 c,d | −10.9 ± 0.89 d | −7.23 ± 0.96 b–d | 0.0002 | <0.0001 |
Baseline body iron at 90th %ile | 3.48 ± 0.89 a,b | 4.07 ± 0.81 a | 3.83 ± 0.97 a,b | −0.15 ± 0.74 c | 2.62 ± 0.83 a–c | 0.75 ± 0.82 b,c | 0.0002 | ||
Lowest tertile of consumption | −0.84 ± 1.15 | −2.24 ± 1.12 | 0.21 ± 0.98 | −2.51 ± 1.21 | −2.75 ± 1.24 | −2.46 ± 1.05 | 0.007 | 0.32 | |
Mid tertile of consumption | 1.02 ± 1.02 a | 0.29 ± 0.80 a | 0.49 ± 0.93 a | −3.46 ± 0.78 b | −2.47 ± 0.87 a,b | −2.62 ± 0.83 a,b | <0.0001 | ||
Highest tertile of consumption | 3.20 ± 0.81 a | 0.89 ± 0.91 a | 0.23 ± 0.92 a,b | −5.90 ± 0.91 c | −4.70 ± 0.93 c | −3.06 ± 0.84 b,c | <0.0001 | ||
BIS < 0 4,5 | Baseline BIS at 10th %ile | 42.9 ± 11.2 a | 88.9 ± 7.92 a,b | 85.2 ± 9.14 a,b | 99.8 ± 0.37 b | 99.6 ± 0.83 b | 97.4 ± 2.77 a,b | 0.0291 | 0.0004 |
Baseline body iron at 90th %ile | 17.5 ± 8.25 a,b | 12.0 ± 6.33 a | 6.50 ± 5.04 a | 46.3 ± 11.6 b | 15.3 ± 9.40 a,b | 42.8 ± 11.9 a,b | 0.01 |
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Islam, M.M.; Black, R.E.; Krebs, N.F.; Westcott, J.; Long, J.M.; Islam, K.M.; Peerson, J.M.; Sthity, R.A.; Khandaker, A.M.; Hasan, M.; et al. Effects of Different Doses, Forms, and Frequencies of Zinc Supplementation on Biomarkers of Iron and Zinc Status among Young Children in Dhaka, Bangladesh. Nutrients 2022, 14, 5334. https://doi.org/10.3390/nu14245334
Islam MM, Black RE, Krebs NF, Westcott J, Long JM, Islam KM, Peerson JM, Sthity RA, Khandaker AM, Hasan M, et al. Effects of Different Doses, Forms, and Frequencies of Zinc Supplementation on Biomarkers of Iron and Zinc Status among Young Children in Dhaka, Bangladesh. Nutrients. 2022; 14(24):5334. https://doi.org/10.3390/nu14245334
Chicago/Turabian StyleIslam, M. Munirul, Robert E. Black, Nancy F. Krebs, Jamie Westcott, Julie M. Long, Kazi M. Islam, Janet M. Peerson, Rahvia Alam Sthity, Afsana Mim Khandaker, Mehedi Hasan, and et al. 2022. "Effects of Different Doses, Forms, and Frequencies of Zinc Supplementation on Biomarkers of Iron and Zinc Status among Young Children in Dhaka, Bangladesh" Nutrients 14, no. 24: 5334. https://doi.org/10.3390/nu14245334