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| ID | Type | Description | Link |
|---|---|---|---|
| 66-451-1-1 | Other Grant/Funding Number | Faculty of Medicine, Prince of Songkla University |
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The goal of this randomized clinical trial is to compare the effect of higher (10 mg per day) versus standard (1 mg per day) doses of zinc supplementation The main questions it aims to answer are:
After informed consent, the neonates enrolled were randomly allocated to two study groups: group A (higher dose of zinc sulfate 10 mg/day; each 1 mL contains 10 mg of elemental zinc; Pharmacy Division, Songklanagarind Hospital), and group B (standard dose of zinc sulfate 1 mg/day; each 1 mL contains 1 mg of elemental zinc; Pharmacy Division, Songklanagarind Hospital).
The zinc solution was available as a white powder in white opaque plastic container. When normal sterile water was added up to the indicator mark, it provided 60 mL of solution containing 10 mg/mL (osmolality 450 Osm/kg H2O) and 1 mg/mL (osmolality 45 Osm/kg H2O) of elemental zinc with similar color, taste and packing. The two doses of zinc preparations were provided in identical bottles and was labeled only zinc solution, hospital number and name-surname, without indication of group identity (A or B) or concentration by a neonatal registered pharmacist in the study center (only unblinded investigator who recorded the group allocation according to the randomization list in consecutive participant). This information was not available to the investigators during the data had been obtained, entered in the database, and analyzed by a blinded statistician.
After randomization, nurses blinded to the study aims administered the assigned preparation 1 mL via tuberculin syringe, once daily, 1 h after feeding. Zinc sulphate oral solution was prepared by the pharmaceutical compounding unit in the hospital. Each subject received a 60-mL bottle solution individually and continued the medication until finished, either at a concentration of 1 or 10 mg/mL, depending on the study group. The supplement was given again to subjects who vomited within 15 min after the administration. All episodes of vomiting were reported on the record form. Vomiting episodes within 15 min were recorded. The supplement assigned was discontinued at discharge or at 44 weeks' postmenstrual age whichever came first. Both groups received multivitamin products (1 mL/day) and iron supplement (2-3 mg/kg/day) as routine preterm care.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Higher dose of enteral zinc | Active Comparator | higher dose of zinc sulfate 10 mg/day; each 1 mL contains 10 mg of elemental zinc (osmolality 450 Osm/kg H2O). |
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| Standard dose of enteral zinc | Placebo Comparator | standard dose of zinc sulfate 1 mg/day; each 1 mL contains 1 mg of elemental zinc (osmolality 45 Osm/kg H2O). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Higher dose of enteral zinc | Dietary Supplement | Higher dose of zinc sulfate 10 mg/day; each 1 mL contains 10 mg of elemental zinc (osmolality 450 Osm/kg H2O). After randomization, nurses blinded to the study aims administered the assigned preparation 1 mL via tuberculin syringe, once daily, 1 hour after feeding. Zinc sulphate oral solution was prepared by the pharmaceutical compounding unit in the hospital. The supplement was given again to subjects who vomited within 15 minutes after the administration. All episodes of vomiting were reported on the record form. Vomiting episodes within 15 minutes were recorded. The supplement assigned was at discharge or at 44 weeks of postmenstrual age whichever came first. Both groups received multivitamin (MTV) products and iron supplement as routine preterm care. |
| Measure | Description | Time Frame |
|---|---|---|
| Weight velocity during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first) | Weight velocity was calculated during the beginning of study (time1 [T1], Weight1 [W1]) until the end of the time interval (time2 [T2], Weight [W2]). Weight gain (grams per kilogram per day) was calculated during the period using the 2-point average method [1000*(W2-W1)]/[(W2+W1)/2)*(T2-T1)]. Weight delta z-scores of were calculated weight z-scores at T2 minus weight z-scores at T1 from the Fenton's Growth Chart | during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first) |
| Length velocity during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first) | Length velocity was calculated during the beginning of study (time1 [T1], Length1 [L1]) until the end of the time interval (time2 [T2], Length [L2]). Length velocities (centimeters per kilogram per day) was calculated during the period using the 2-point average method [1000*(L2-L1)]/[(L2+L1)/2)*(T2-T1)] Length delta z-scores were calculated length z-scores at T2 minus length z-scores at T1 from the Fenton's Growth Chart | during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first) |
| Head circumference (HC) velocity during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first) | HC velocity was calculated during the beginning of study (time1 [T1], HC1) until the end of the time interval (time2 [T2], HC2). HC velocities (centimeters per kilogram per day) was calculated during the period using the 2-point average method [1000*(HC2-HC1)]/[(HC2+HC1)/2)*(T2-T1)] HC delta z-scores were calculated HC z-scores at T2 minus HC z-scores at T1 from the Fenton's Growth Chart |
| Measure | Description | Time Frame |
|---|---|---|
| Growth at 24 months postnatal age (PNA) | Growth [at 24 months PNA, 20-24 months corrected age]) was assessed by corrected age | At 24 months PNA (20-24 months corrected age) |
| Neurodevelopment at 24 months postnatal age (PNA) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anucha Thatrimontrichai, MD | Contact | +66 954300690 | tanucha@medicine.psu.ac.th | |
| Boonwiroj Jitwilertrat, MD | Contact | +66 914953851 | Boonwiroj@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Anucha Thatrimontrichai, MD | Prince of Songkla University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Songklanagarind Hospital, Prince of Songkla University | Recruiting | Hat Yai | Changwat Songkhla | 90110 | Thailand |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37939725 | Background | Sahin S, Sari FN, Bidev D, Bozkurt O, Dizdar EA, Oguz SS. Zinc Supplementation in Very Low Birth Weight Infants: A Randomized Controlled Trial. Am J Perinatol. 2024 May;41(S 01):e3107-e3114. doi: 10.1055/s-0043-1776762. Epub 2023 Nov 8. | |
| 21546443 | Background | Ram Kumar TV, Ramji S. Effect of zinc supplementation on growth in very low birth weight infants. J Trop Pediatr. 2012 Feb;58(1):50-4. doi: 10.1093/tropej/fmr036. Epub 2011 May 5. |
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There is not a plan to make IPD available.
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| ID | Term |
|---|---|
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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The study design was approved by the ethics committee of our Center. Written informed consent was obtained from the parents of the infants enrolled in the study. Stratification was performed based on birthweight [BW] (401-999 or 1,000-1,499 or 1,500-1800 grams) and small for gestational age (yes or no). Participants were randomly allocated (1:1) to one of two treatments (higher or standard doses of zinc supplement). The allocation sequence was performed via computer generation, with permuted block and kept as consecutive numbers by statistician. Allocation concealment was ensured by using identical, opaque, and sealed envelopes.
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The two doses of zinc preparations were provided in identical bottles without indication of group identity or content by a neonatal registered pharmacist (assigned participants to interventions, only unblinded investigator) in the study center. A dedicated nurse (enrolled participants, obtained informed consent, monitored intervention, and recorded data), registered nurses and attending neonatologists (did routine neonatal care), statistician (generated the allocation sequence), and dedicated clinical psychologist were blinded the allocation groups.
|
| Standard dose of enteral zinc | Dietary Supplement | Standard dose of zinc sulfate 1 mg/day; each 1 mL contains 1 mg of elemental zinc (osmolality 45 Osm/kg H2O). After randomization, nurses blinded to the study aims administered the assigned preparation 1 mL via tuberculin syringe, once daily, 1 hour after feeding. Zinc sulphate oral solution was prepared by the pharmaceutical compounding unit in the hospital. The supplement was given again to subjects who vomited within 15 minutes after the administration. All episodes of vomiting were reported on the record form. Vomiting episodes within 15 minutes were recorded. The supplement assigned was discontinued at discharge or at 44 weeks of postmenstrual age whichever came first. Both groups received multivitamin (MTV) products and iron supplement as routine preterm care. |
|
| during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first) |
Neurodevelopmental outcomes (Bayley-III tests, were evaluated by only dedicated clinical psychologists at 24 months PNA [20-24 months corrected age]) were assessed by corrected age
| At 24 months PNA (20-24 months corrected age) |
| 24025633 | Background | Terrin G, Berni Canani R, Passariello A, Messina F, Conti MG, Caoci S, Smaldore A, Bertino E, De Curtis M. Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country. Am J Clin Nutr. 2013 Dec;98(6):1468-74. doi: 10.3945/ajcn.112.054478. Epub 2013 Sep 11. |
| D000091642 | Urogenital Diseases |