® cRscm* Bic! sar (SCM Wee Effect of Oral Zinc Supplementation on The Growth of Preterm Infants Risma Kerina Kaban san PICU NICU Update Ancella Marsha M Jauri Neonatology Division Child Health Department Faculty of Medicine University of Indonesia Dr. Cipto Mangunkusumo Hospital INDONESIAN PICU NICU UPDATE - 2020/2021Background + Micronutrients fulfillment often neglected * Most micronutrients are provided by dietary sources (human or formula milk) + However, some trace minerals are not adequately supplied with readily available parenteral preparations * To avoid deficiency, some additional micronutrients (including Zinc) has to be supplemented for preterm infants, or those patients with high nutrient losses maf tain a. 2010417 on es 00 orBie ‘* Zinc * One of the most abundant elements within cells ~ 95% of zinc is within the cells + Zinc (Zn) contributes to many vital physiologic process: * Catalytic > enzymatic function + Regulatory > gene expression + Structural > hormonal and protein integrity + Metabolism of energy, proteins, carbohydrates, lipids and nucleic acids (leet a eaReven VN pr 200 fing Am nt. 201 1282) as, ta ated 209 WeeCesc The Role of Zinc in Cell Growth and Development Numerous cellular processes that require zinc: Cellular Cellapoptosis Cell growth | membrane integrity Cell ell proliferation | differentiationRole of Zinc in Organ Systems Sse amine nical insulin secretion ae _ al absorption® Gescm Fetal Zinc Metabolism weeks 4 8 12 16 20 8 2 36 40 most zinc accretion begi Zinc transfer from maternal > fetus 1.5 mg/Kg/day Mostly stored in (60% on 3 semester) ee feral lives | Fetal zinc concentrations are maintained 1 and bones© Gens Neonatal Zinc Metabolism Atbirth, the placental Zn supply is abruptly terminated Absorbed in smalll intestine | and large intestine, mostly in the proximal gut | Sa Factors 1 risk of deficiency + Low body stores (prematurity, low maternal zinc) 1 1 1 1 1 ' + Low intake : 1 t 1 ' In the absence of adequate supplementation, serum zine concentrations | rapidly during the first months of life + Increased endogenous losses (fecal and urine) “ern ta arts 218072) ann tid 2Zinc in Breastmilk * Zinc content in human milk varies considerably (0.7 to 1.6 mg/L) and declines with time * Zn in colostrum : 8-12 mg/L *Znin human milk at 7 days of life: 3-6 mg/L + Rapidly | at 1 month of life 21-3 mg/L * Maternal zinc intake or status > minor effect on breastmilk concentrations “ern ea acts 2015 72 ars eta eae 20 Ree© Gan Zinc in Formula Milk + Formula milk concentration of zinc is 1.5-6 mg/L + Zn concentration in formula > human milk + However, net absorption is higher in human milk (60% vs. 20%) + Preterm infant consuming 180 mL/kg per day of supplemented human milk would receive only 0.5-1 mg/kg per day of zinc “erin 6 ta tans 205 066742). Senge et htt eae© Gsew The influence of other nutrients on Zinc metabolism Improve Zinc absorption: + Protein + Medium-chain triglycerides + Vitamin A Reduce Zinc absorption: + Casein + Calcium, Iron, Magnesium + Folic acidNormal Serum Zinc Levels Infants: * Zinc deficiency :<55 ug/dh * Normal concentration :>70 ug/dL. In preterm infants > serum zinc levels rapidly \) during the first month of life + Serum zinc levels measured in cord blood at birth are higher in preterm compared with at term neonates * At PCA 40 weeks, may be lower in preterm neonates compared with term neonates No consensus as to when to monitor concentrations be ert end and ution bub 207 et PCA Post Conceptionl Age trina ens 23® Crscm* ne Zinc levels in neonatal cord blood at birth by gestational age and birth weight Mean Values + Gestational age at Birth weight, ‘i Reference Neonates Standard Deviation birth, weeks rams tva/aty Perveen etal, ete 24-28 116 + 45 2002 n 29-33, 94419 9 34-37 89415 et aa-42 8749 Galinier eta, 53 26-31 160 +27 2005 76 31-33 137230 66 33-34 125523 53 34-37 128 +18 262 237 3234.2 358 12320 Tsuzukiet a, 14 3642 2388 + 465 89414 2013 30 3941 3043 + 321 26416 esi tt bets 2945 os ee ea aeZinc Requirements Stable growing preterm infant : 1-2.5 mg/kg/d Extremely low birth weight infants _: up to 3 mg/kg/d. Subse covane att of Steet Rss: 0175.4 NS: C0077Crscm* Zinc Deficiency * Subclinical zinc deficiency in preterm infants: 25% to > 50% + No data indicate at what plasma level of zinc contributes to clinical manifestation of zinc deficiency * Severe zinc deficiency ~> Typical clinical manifestations sub acon atts Stent Revie. 20ci, Pa Prevalens dan Faktor Risiko Terjadinya Hino- meu + zincemia Bayi Berat Lahir Rendah Res Koreksi Mendekati Cukup Bulan 63 babies (Ga=25.34 ‘BW = 600-1850gram) Hypozincemia No Hypozincemia Bat 7% (n=18) eee) 67% with 2% symptoms; Growth disorder No Amnon sat ota even i kor alata poems BLE Sa Peat 202© G@scm Zinc Deficiency and Neonatal Complications * Dermatitis + Most common clinical feature of zinc deficiency + Respond quickly to soral zinc supplementation (~ 1 week) * Unexplainable dermatologic manifestation > evaluate zinc status Trin ge ants 2015 467wie 4 Ose, ..Zinc Deficiency * Growth Retardation + 4 weight gain > zinc requirements 4 > VU serum zinc levels, + 4 enzyme activity and protein synthesis > growth + Preterm infant not growing well despite adequate intake > consider zinc deficiency + Necrotizing Enterocolitis + Zinc modulates the expression of inflammatory cytokines in the intestine + Zinc deficiency worsens damage due to the reduced enzymatic antioxidant activities Tern tal Mtns 201 412) sub tea coor tte of teat hes, 20179 at COT.® Crscm* me, ‘* ..Zinc Deficiency * Neurologic Damage + Zinc regulates the expression of neurotrophic factors > apoptosis and “P neuronal regeneration * Zinc > modulation of vascular tone at the cerebral level * Bronchopulmonary Dysplasia * Zinc epithelial development + Repair tissue damage, protects against infection + Modulates inflammatory response in respiratory system eng a bts 2908 ee etal Coane Dette Senate ess 21,3 A No COOL* Zinc rucial element of the immune response + Zinc stabilizes the membranes of immune cells, regulates apoptosis, diapedesis and recruitment of immune cells * Retinopathy of Prematurity * Zinc = most abundant trace metal in the retina * Crucial antioxidant in retina sen ets aes 201 070) Sub catone tbe srtnatc ests 2017.9 Ht Na COLIN, ose aera]Zinc balance in fetal and neonatal lifeZinc Supplementation * Preterm infants : negative zinc balance within the first 4-8 weeks of life, unless supplemented * Only 60% of parenterally infused zinc is retained + Recommended dose: * Parenteral »: 0.4-0.5 mg/Kg/day (preterm) 0.25 mg/Kg/day (term) * Enteral : 4-5 mg/Kg/day me ta cn ay. 2080617)Zinc Supplementation Recommendation ESPGHAN Zn should be provided with PN at a dose of 400-500 jig/kg/d in preterm infants, 250 .g/kg/d in infants from term to 3 months, 100 ugikg per day for infants from 3 to 12 months and 50 y.g/kg/ din children >12 months of age, up to a maximum of 5 mg/d for routine supplementation. (LoE 4, RG 0, strong recommendation, strong consensus) Zn status (serum Zn, alkaline phosphatase) should be periodically monitored in patients on long-term PN and more often in those with high gastrointestinal fluid output (usually jeostomy losses), who may have significantly higher Zn requirements. (LoE 3, RG 0, strong recommendation, strong consensus) Ooms, ta ESPGHAWFESPENESPR euitine on pete PN en andre minerals© Geen aie 4 wee, Enteral Supplementation of Zinc Institution / Researcher “The American Academy of Pediatrics Committee on nutrition ESPGNN, Committee on hutrtion preterm Lira etal Hambidge etal ifn et at Farghall eta. Year of Publication 1985 1987 1998 2006 2013 zon 2015 Neonatal Population all a 1500 -<2500 5 aw < 10008 ‘BW 1000-20008 ‘BW 2000-3500 Human mi Formula mil 15008 13006, 06 ma/ ke / day 0,7~4,4 ma/ ke / day ‘Sma/ day 2,4 may ef day el kel day 1.0m@/ ke day 2,3-2,ma/eg/day 118-24ma/eg/day 0me/ har 0m@/ har© Gscut Zinc Could be Provided From | Parenteral | nutrition i | support Formulas designed re for premature infants FHMF eos Human containing zine Milk 8 remy manent 2015 e012 Specific products© Gan —_ Bszanon Farex } Effect of Oral Zine Supplementation on the Growth of Preterm Infants, uss, MAK Cuan ASK! SHE MK HSMM 50) Pvalue Group 1(n=50) Weight (@) Baseline 1730.44 4407 632823217 039 Astfolow-up 2343.845403, 2060.2 + 396.3, 1500 g, > 28 weeks GA, no congenital malformations or evidence of considerable illness + Zinc dose: 10 mg/day vs. placebo for 6 months * Conclusion: early start of oral zinc supplementation in low-birth-weight neonates assists catch-up growth tXfaahl cs OX Mad eS 205M 5308,[OFiginal RaEaTEN EEG et te) eh 34855 INH a Cais Sajith 3S Razin Nazarall Control (n=50) ) Pvalue ‘Mean +SD Mean +S Weight (ke) ‘At birth 2.184030 2.054029 0.003 3 months follow-up 4414057 5.212065, Length (em) ‘birth 49.001097 4gsis125 0.003, 3 months follow-up 53524092 57.41 +093 Head Circumference (em) A birth 32654052 32.50.2055 0599 3 months follow-up 38854083, 38524054 + Subjects: 100 LBW infants (BW < 2500 grams) + Zinc dose: 10 mg of elemental zinc daly for 3 months. + Conclusion: Zinc supplementation in LBW infants was found to be effective to enhance the growth and decrease morbidity and mortality. reer® Cescm* ie Effect of Oral Zinc Supplementation on The Growth of Preterm Infants + Subjects was taken from 4 hospitals in Jakarta : Cipto Mangunkusumo Hospital, Harapan, 7 kita Woman and Children Hospital, Bunda Hospital Menteng and Fat mawati Hospi + Subjects: 166 infants born at 28-32 weeks GA + Supplementation dose: 10 mg/day + Starting fom day 3.0r when enteral feeding» 20 mi/hg/day ‘+ Until discharged from the hospital or PMA 40 weeks Serum Zinc Levels (ue/dl) Pvalue sect ZineGroup Placebo Group Before supplementation «79942668 © 74.75428.79 0.271 0.702 (05) ‘After supplementation ——-75.27424.79 —57.09818.77 277116Bie “* ... The Growth of Preterm Infants Zine Supp Placebo Morbi Pvalue 195% "Y(w7) (0:76) 1370 BPD 7 2 0.199 (0.523-3.5890 0136 nec 2 7 079 (0.017.214 op : 1 os o9st wa 7 7 0.959 (0304-2978) Dermatitis -... The Growth of Preterm Infants Zine Placebo a ‘Mean Difference (n=25) 25) (85% cH Growth velocity (/Ke/day) 9.068452 701648 0073 1.74 (0.054355) 0.008 Length diference em) on010 58 0.794041 090993817 eee an ace HS 0661048 ©0847 0.015(-0.140.17) (em) Conclusion: Preterm infants supplemented with 10 mg/day of zinc shows better growth velocity in body weight, but not statistically significant in body length and head circumference.wie ‘-e MSM. * POPULATION/ CONDITION In infants < 37 weeks gestation or < 2500 grams Any enteral zinc supplementation Sees (formulation, regimen, or dose ) Cee ed Compared to without supplementation or placebo oo ia Tatinitiipentl ikem mortality © TYPE OF STUDY Randomized Control Trial (RCT) or quasi- RCT y ¥ vBie ‘* Cochrane Library Cre oul Peano Co) Staub Evers, Aske Author's Conclusion: Enteral supplementation of zinc in preterm infants compared to no supplementation or placebo may moderately decrease mortality and probably improve short-term weight gain and linear growth, but may have little or no effect on common morbidities of prematurity. There are no data to assess the effect of zinc supplementation on long- term neurodevelopment. tal enter plaertatn for ewerSummary * Enteral supplementation of zinc in preterm infants + May moderately decrease mortality + Improve short-term weight gain and linear growth *Zinc status should be evaluated in every infants showing signs of growth retardation or unexplainable skin rashes,longterm parenteral nutrition, high output intestinal fluid + Normal serum zinc levels in infants: > 70 mcg/dL + Recommended zinc supplementation dose ranges from 5-10 mg/day