| Backgroud:Breast milk is the first choice for preterm infants because of its function of immune activity and infection protection.Well,exclusive breastfeeding is inadequate to maintain the growth of preterm infants and human milk fortifier(HMF)is essential.But the composition of breast milk varies among mothers and even within the same mother at various times,standard commercial fortification may not be appropriate for the growth of all preterm infants,so individualized fortification was proposed.There are two major methods of individualized fortification:"adjustable fortification" and "target fortification",both have their advantages and disadvantages.Objective:This study is to test the hypothesis that infants fed according to the new individualized fortification regimen have higher protein intakes and improved weight gain compared to infants fed according to current standard commercial fortification regimen.Methods:This is a prospective randomized control study.Infants with birth weight between 800g and 1800g,gestational age(GA)<34weeks,exclusive human milk feeding and without congenital malformation,metabolic disease or severe infection were eligible for this study.Preterm infants were enrolled into this study when enteral nutrition reached 60ml/kg/d and then randomized to individualized fortification group or standard fortification group.The individualized fortification regimen encompassed increasing or decreasing the amount of fortifier and adding supplemental protein based on periodic determinations of the protein concentration in human milk(PCHM)and body weight and blood urea nitrogen(BUN).T test or ?-square test had been used to compare the difference of nutrient intakes,growth rate,biochemical parameters and length of NICU stay between two groups.Linear regression was also used to explore the factors that associated with upgrading fortification.Results:Between September of 2012 and August of 2016,a total of 78 preterm infants were enrolled,but only 51 preterm infants finished the entire study.Individualized fortification group had 24 infants and standard fortification group had 27 infants.The GA was 30.4± 1.5 weeks,and the birth weight was 1375±240 g.?General conditions:There was no statistical difference on demographic characteristics between individualized group and standard group.?Parenteral nutrition:There was no difference on the intake of amino acids,fat or calories from parenteral nutrition when enrolled and during the whole study time.Enteral nutrition:most preterm infants started feeding with their own mother's milk mother from the very first day after birth(within 12 hours after birth).There was no difference between the two groups on the starting time of human milk fortification,the amount of breast milk started to fortify human milk,and the duration of human milk fortification.The time of enteral nutrition to reach 100kcal/kg.d and 120kcal/kg.d did not show significant difference between the two groups.?The composition of breast milk:there were no difference on the baseline levels of nutrient composition of preterm human milk:caloric density(61.2±11.3 kcal/100ml vs 57.3±6.7kcal/100ml,P=0.141),protein(1.8±0.3 g/100ml vs 1.6±0.3g/100ml,P=0.121),fat(3.1±1.3g/100ml vs 2.8±0.6g/100ml,P=0.346).With the progress of lactation,the protein content in milk decreased,while the changes of fat,carbohydrate and calories were not obvious.The fortification time of L0 level(11.6±6.5vs 21.1 ±9.3 days,P<0.001)demonstrated a statistically significant difference between the two groups,with much shorter time in individualized group.In the individualized fortification group,62.5%(15/24)preterm infants were fed with human milk fortified to L1 level,29.2%(7/24)to L2 fortification level,12.5%(3/24)to L3 fortification level,but there were still 12.5%(3/24)preterm infants were decreased to L-1 fortification level during study.In the individualized fortification group,Stratified analysis found that preterm infants less than 28 weeks GA were mainly fed with L0 and L1 fortification level.Upgrading fortification level(L1,L2,L3)demonstrated increased tendency with lactation,while preterm infants with GA greater than 28 weeks had more variable forfication levels and the upgrading tendency was less obvious than infants less than 28 weeks GA.The upgrading fortification duration in individulized fortification group was associated with birth weight,study duration and average protein level in human milk during study.?Protein calorie ratio:There was no significant difference between the mean protein calorie ratio from enteral nutrition from the first to the fourth week between the two groups,the same as the protein calorie ratio from both enteral and parenteral nutrition.During the study period the total intake of protein and calorie showed no difference between the two groups.?The weight gain velocity[16.7(15.3,18.6)vs 15.4(14.5,18.9)g/kg/d,P=0.540]between the two group of during hospitalization showed no significant difference,but the weight gain velocity in the third week in individualized fortification group was better than the standard group(20.8±7.9 vs 14.9±4.5 g/kg/d,P=0.022).The time to reach 2000g[27(18.0,40.0)d vs 28.0(23.8,37.0)d,P=0.399]also showed a shorter trend in individualized fortification group.?The metabolic indicators:the serum BUN(4.5±1.6 vs 3.9±2.0 mmol/L,P=0.235),prealbumin(88.5±18.1 vs 79.3±26.mg/L 1,P=0.158)and albumin level(33.1 ±3.9 g/L vs 32.1 ±2.8 g/L,P=0.267)in the first week showed no significant difference between the two groups.At the same time,the changes of the above metabolic indexes showed no difference between the two groups either.?Safety evaluation:the incidence of feeding intolerance,NEC and sepsis showed no significant difference between the two groups.Conclusion:Infants in individualized fortification group showed higher tendency of protein intake and weight gain,the weight gain velocity of individualized fortification group was much better than standard group in the third week of study.Larger scale clinical study should be carried out to prove this new individualized fortification regimen based both on human milk analysis and metabolic response of preterm infants.Precision medicine application in the area of nutrition,especially preterm infants should also be emphasized.Objectives To evaluate the nutritional status of extremely low birth weight infants and the progress in nutritional support policies during last decade in China.Methods Retrospectively analyzed the enteral and parental nutritional support data,growth velocity and complications of extremely low birth weight infants during hospitalization in the neonatal intensive care unit(NICU)from 2005 to 2014.Results The eighteen extremely low birth weight infants admitted to NICU from 2005 to 2009 were defined as previous 5 years group(group pre5)and the 40 counterparts admitted from 2010 to 2014 were defined as latest 5 years group(group late5).There was no statistical difference between group pre5 and group late5 when comparing the gestational age(28.6± 1.9w vs 28.1 ±2.0w,p=0.461),birth weight(881.1 ± 80.9g vs 850.6± 118.6g,p=0.327)and head circumference(25.2±0.9cm vs 24.8 ± 1.4cm,p=0.241),Incidence of SGA(33.3%vs 35%,p=0.902)and EUGR ratio at discharge(77.8%vs 52.5%,p=0.069)was similar.When compared with group pre5,infants in group late5 had larger amount of initial enteral feeding(2.4ml/kg/d vs 4.4ml/kg/d,p=0.014)and feeding volume at the end of the first week(12.2 ±9.5ml/kg/d vs 19.8±16.0ml/kg/d,p=0.036).Similarly,the starting dose of amino acids in parenteral nutrition(1.0g/kg/d vs 2.0g/kg/d,p<0.001),maximal dose of amino acids(3.5g/kg/d vs 4.0g/kg/d,p<0.001),total calories at the end of the first week(71.1±15.2kcal/kg/d vs 82.6±12.6kcal/kg/d,p=0.004)and the second week(92.3±17.9kcal/kg/d vs 103.7±19.8kcal/kg/d,p=0.041),the weight gain velocity from birth to discharge(16.9±2.8g/kg/d vs 18.7±2.9g/kg/d,p=0.031),weight at 34 week of corrected gestatinal age(1494±286g vs1682±368g,p=0.041)and change of Z scores for weight(?Z)[-1.2(-1.6,-0.8)vs-0.6(-1.0,-0.4),p=0.004]all had statistical differences between the two groups,with better outcomes in group late5.However,the duration of parenteral nutrition,the total amount of amino acids,the ratio of protein to calories from the first to the fourth week,the time to full enteral feeding,length of hospital stay were similar between two groups.Ten cases of infants in group pre5 were breastfed,accounting for 61.1%,and four of them were fortified with human milk fortifier(HMF)(fortified rate was 22%).Breastfeeding cases in group late5 was 32(80%),exclusive breastfeeding with human milk fortifier was 23 cases(fortified rate was 57.5%).The time to initiate HMF was at 30.2±13.2 days,and human milk amount was 89.9±34.5ml/kg,fortified duration was 32.8±15.7 days.Conclusions The nutritional support strategy for extremely low birth weight infant in China has improved during the past ten years.We can see the initial amount of enteral feeding and the feeding volume of the first week had increased dramatically.The starting dose and maximal dose of amino acids in parenteral nutrition also increased.Human milk and human milk fortification of preterm infants was preferred as routine.Above nutritional management accelerated the weight gain velocity of extremely low birth weight infants without obvious side effects.Objectives The incidence of preterm related complications and extrauterin growth restriction were high among extremely low birth weight infants.Early and positive nutritional support of preterm infants had provided opportunity for catch-up growth.In recent years,the progress on the nutritional support strategy also achieved better gowth results.So the objective of this study was to explore the catch up growth pattern of ELBW infants during hospitalization and after discharge and provide data for future study on long-term prognosis of preterm infants.Methods Retrospectively analyzed the clinical data of ELBW infants in part two,including the general condition at birth and nutritional support strategy during hospitalization.Calculate the Z score for weight,length and head circumference both at birth and discharge.Evaluate the growth data at corrected age(CA)of term(3 7?42 weeks),0?3 months,4?6 months,7?12 months,13?24 months,especially the retardation rate.Student t test,non-parametric test or x-square test had been used to compare the difference between groups.Results From 2005 to 2014,a total of 50 ELBW infants were followed up for over 6 months with 30 males and 20 females.Gestational age was 28 ±2.5 weeks,weight was 861.7± 104.9 grams,average length was 34.3±2.1cm and head circumference was 24.9±1.3 cm.The incidence of SGA was 32%at birth.Parenteral nutrition lasted an average of 48±17 days.During hospitalization,80%(40/50)of preterm infants were exclusively or partially breastfed,with human milk fortification rate of 56%(28/50).Weight at discharge was 2285.4±401.2g,length 42.8±3.9 cm and head circumference 32.3±3.2 cm.EUGR incidence at discharge was 60%.The average weight gain velocity was 17.9±2.8g/kg/d during hospitalization.Z scores for weight,length and head circumference at discharge were lower than that at birth.The period with the lowest growth retardation rate was 0?3 months of CA,which was respectively 20%,26%and 22%by weight,length and head circumference.By the time 24 months of CA,the rate of growth retardation showed a little increase.These infants were divided into groups according to SGA or not,the gestational age at birth(<28 weeks and>28 weeks),birth weight(?750g and>750g)and the period at birth(2004?2009 and 2010?2014),and the growth retardation rates were compared between groups at 6 and 24 months of CA.The SGA group and>28 weeks group had higher growth retardation rate at 6 months of CA.By the time of 24 months of CA,growth retardation rate(by head circumference)was higher in the group with birth weight<750g.The BMI and its Z score were among the normal range for preterm infants at 6 month and 24 month of CA.Conclusion ELBW infants showed high rate of intra-uterine growth retardation and even higher rates of extra-uterine growth retardation.With more aggressive and positive nutritional support recent years,the majority of preterm infants accomplished catch up growth by 3 months of CA,while the BMI of these catch-up growth infants had normal BMI.ELBW infants who were SGA at birth or with birth weight<750g may be more prone to show growth retardation. |
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