A comparative study of a premature infant formula and preterm breast milk for low birthweight infants

Although the unique composition of preterm milk (PTM) has led to its increasing use in feeding of low birthweight (LBW) infants, controversy exists as to whether such milk adequately meets their requirements. This study compares the clinical tolerance and anthropometric, biochemical and haematological parameters of LBW infants fed exclusively with their own mother's PTM, a premature infant formula (Alprem; Nestlé Australia) and a mixture of PTM and Alprem. Of 90 enrolled LBW infants (1000-1750 g birthweight), 78 completed the feeding trial for a mean duration of 42 days. Twenty-eight babies were fed Alprem (Group A), 31 received a mixture of Alprem and PTM (Group B) and 18 received PTM (Group C). Babies in Groups A and B were smaller, less mature and more asphyxiated at birth than those in Group C. Weight gain from full enteral feeding was greater in Group A (18.1 g/kg per day) and Group B (17.6 g/kg per day) than in Group C (13.0 g/kg per day). Throughout the trial, weight gain in Groups A and B exceeded predicted intra-uterine growth rates, whereas that for Group C approximated the predicted intra-uterine growth rates. Growth rates of length and head circumference were also greatest in the Alprem-fed babies. Infants receiving PTM were supplemented with calcium, sodium, vitamins and energy, whereas the only three infants requiring mineral supplementation in the Alprem group were those receiving Frusemide therapy for chronic lung disease. Lower serum concentrations of phosphorus, iron, albumin and urea, and higher zinc and alkaline phosphatase concentrations were found in infants receiving PTM (P<0.05). Overall both PTM and Alprem were well tolerated with the four cases of necrotizing enterocolitis and five cases of transient gastrointestinal intolerance distributed equally among the groups. Alprem is a satisfactory alternative to PTM for the feeding of LBW infants as it provides adequate nutrition and supports a growth rate in excess of that in utero without stressing the infant's metabolic or excretory systems.     

Choice of formula and human milk supplement for preterm infants in Australia

Human milk (HM) is considered to be the optimal feed of choice for neonates, however, for preterm infants, HM fortifiers are often added to increase growth. If HM is unavailable, preterm formula is the next best option for preterm infants. Choosing which fortifier, if any, to use or which formula can be confusing. In this paper, the composition of milk feeds available in Australia and New Zealand is reviewed with the aim of assisting paediatricians to decide which feed is most appropriate for their patients.     

人乳与早产儿配方乳喂养对早产儿生长的Meta分析

目的对单纯人乳、强化人乳和早产儿配方乳喂养早产儿的生长进行评价。方法检索PubMed、ScienceDirect、EBSCOHost 、EMBASE 、OVID 、Cochrane图书 馆、维普中文科技期刊数据库和中国期刊全文数据库，并手工检索会议记录和专 题论文集等，收集关于单纯人乳、强化人乳与早产儿配方乳喂养早产儿的RCT研究 ，进行文献筛选和质量评价，采用RevMan 5.0.18软件进行Meta分析，计量资料采 用加权均数差（WMD）及其95％CI表示。无法进行合并分析的资料进行描述性分析 。结果共纳入7篇文献，文献质量评价5篇为B级，2篇为C级。Meta分析结果显示：① 对近期生长的影响：单纯人乳喂养组新生儿期体重增加速度（WMD＝-6.03，95％ CI：-9.58～-2.47，P=0.000 9）、身长增长速度（WMD＝-1.96，95％CI：-2.77 ～-1.16，P<0.000 01）及头围增长速度（WMD＝-2.04，95%CI：-3.71～-0.37， P=0.02）均显著慢于早产儿配方乳喂养组;强化人乳喂养组新生儿期体重、身长和 头围的增长速度与早产儿配方乳喂养组差异均无统计学意义。②对远期生长的影 响：单纯人乳喂养组与早产儿配方乳喂养组随访至9和18个月，以及7.5~8岁时的 体重、身长（高）和头围的差异均无统计学意义。结论现有证据提示，强化人乳喂养可促进早产儿生后近期内生长，单纯人乳和强 化人乳对早产儿远期生长的影响仍需进一步研究。     

Fecal cholesterol excretion in preterm infants fed breast milk or formula with different cholesterol contents

In 44 very low-birth-weight infants, fecal cholesterol excretion was measured and in 29 other infants serum total cholesterol concentrations in response to different cholesterol intakes were studied. The infants received fortified breast milk (mean cholesterol content 15.3mg/dl) or were fed either a standard preterm formula (cholesterol content 5.5mg/dl) or the same formula but with a modified lipid composition (long chain polyunsaturated fatty acid concentration closely related to breast milk fat) and 30 mg of cholesterol/dl. In the group fed the high cholesterol formula, fecal cholesterol excretion was significantly higher (35.5mmol/kg/day) than in the groups fed breast milk or the standard formula (20.1 and 18.2mmol/kg/day). Cholesterol balance in the group fed the high cholesterol formula (21.8mg/kg/day) was significantly higher than in the group fed breast milk (+8.6mg/kg/day). In the infants fed the low cholesterol formula the balance was negative (-7.7 mg/ kg/day). Serum concentrations of total cholesterol were similar in the groups fed breast milk or the high cholesterol formula (3.47 and 3.51 mmol/1), but significantly higher than in the group fed the low cholesterol formula (3.15 mmol/1). The data suggest that preterm infants are able to regulate a higher cholesterol intake than during breast feeding by increasing fecal cholesterol excretion as well as decreasing endogenous synthesis.     

Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates

Aim: Protein hydrolysates have been introduced in preterm formulae, but it is not clear whether they are needed for the feeding of preterm infants. We designed a randomized, controlled trial to test the effects of a preterm formula with hydrolysed cow's milk proteins on short-term growth and urinary and plasma amino acids levels. Methods: Infants with a birthweight ≤1750 g and gestational age ≤34 wk fed a conventional preterm infant formula (formula B) or a hydrolysed formula (formula A). Weight was measured daily; length, head circumference, mid-arm circumference and total skinfold thickness were measured weekly. Blood and urine were analysed for amino acid concentrations at start, 14 and 28 d. Results: Twenty-one infants met the criteria for randomization. The daily feeding volumes were: formula A 172.8±5.6 vs formula B 170.1±2.8 ml/kg/d. Infants fed with formula A showed slower weight gain (17.4±3.4 vs 20.5±3.3 g/kg/d; p=0.045) and lower mean change in Z-scores for weight (-0.18±0.16 vs 0.00±0.09; p=0.009) and for head circumference (-0.06±0.13 vs 0.06±0.13; p=0.049). After 14 d, infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula B.

Conclusion: Our results support the hypothesis of less nutritional value of hydrolysed versus conventional preterm formulae. Higher renal excretion of essential amino acids may be one of the mechanisms involved. These findings must be confirmed by further studies with larger sample sizes and protein hydrolysates with different degrees of hydrolysis.     

A new breast milk supplement for preterm infants

Objective : To assess the effect of a new formula (Prenan), which contains n-3 and n-6 long-chain polyunsaturated fatty acids (LC PUFA) on the fatty acid profile of preterm infants.
Methodology : Plasma fatty acids were measured in 61 preterm infants at term by gas liquid chromatography. In 20 of these infants, paired samples were collected and changes in fatty acids with time analysed.
Results : Plasma docosahexaenoic acid (DHA) levels were higher in those who had been fed expressed breast milk (EBM) ±/or Prenan compared with those fed standard formula ± EBM, P <0.05. The plasma arachidonic acid (AA) levels of infants fed Prenan were not different to those fed EBM, both groups achieving higher levels than infants fed standard formula, P <0.05. Further, paired analysis demonstrated that DHA levels increased in infants changed from standard formula to Prenan to levels equal or higher than those of fully breast-fed infants ( P <0.01), whereas DHA levels remained unchanged with time in all other groups.
Conclusions : The fatty acid composition of Prenan enables preterm infants fed formula to have plasma DHA and AA levels similar to those of infants fed breast milk and consequently different to those of infants fed standard formula. Prenan is an appropriate supplement to breast milk for preterm infants in that it provides LC PUFA as well as additional phosphorus and protein without exposing the infant to intact cows milk protein.     

Human milk supplementation for preterm infants

Nutrition support of the premature infant must be designed to compensate for metabolic and gastrointestinal immaturity, immunologic compromise, and associated medical conditions. The beneficial effects of human milk extend to the feeding of premature infants. However, nutritional concerns arise because the quantity of nutrients in human milk may not meet the great nutrient needs of the premature infant born weighing less than 1500 g. Human milk fortifiers are available to provide optimum nutrition. This review summarizes the benefits and limitations of human milk for the premature infant.     

Which milk for the preterm infant?

Abstract: The optimal diet for the low birthweight infant is one that supports a growth rate approximating that of the third trimester of intra-uterine life without imposing stress on the developing metabolic or excretory systems. Although preterm human milk does not meet the energy and nutrient needs of developing preterm infants, the benefits such as contributions to host defence and gastrointestinal trophic aspects, and the psychological benefits of maternal-infant bonding, make it the preferred diet.     

早产儿/低出生体重儿和足月儿配方粉对住院早产儿生长发育影响的多中心对照研究

目的研究不同组成成分的配方粉对胎龄<34周和（或）出生体重＜2 000 g的住院早产儿早期生长发育的影响,并对早产儿的喂养提出建议 。方法受试对象为上海市3家医院住院的胎龄＜34周或出生体重＜2 000 g的早产儿。分为两组,分别应用Ⅰ号（早产Ⅰ组）和Ⅱ号（早产Ⅱ组 ）配方粉进行喂养。研究采用严格的盲法,试验设计者不参与试验实施,数据整理者为独立的第3方人员,参与试验的医生和患儿家长对两种配 方粉的具体组成成分均不知情。Ⅰ号为适于早产儿的优博早产儿/低出生体重儿配方粉,Ⅱ号为足月儿或胎龄>34周早产儿的优博标准婴儿配方 粉。结果2007年7月至2008年6月,早产Ⅰ组117例,早产Ⅱ组106例进入分析。早产Ⅰ组体重、身长和头围的生长速度均显著快于早产Ⅱ组。试 验期间早产Ⅰ组和早产Ⅱ组的平均体重增加速度分别为12.6 g·kg-1·d-1 和10.6 g·kg-1·d-1（P＜0.001）,头围每周增长分别为0.86 cm 和0.80 cm（P＜0.05）,身长每周增长分别为0.73 cm和0.67 cm（P＜0.05）;按生理性体重下降恢复后计算,早产Ⅰ组和早产Ⅱ组的平均体重 增加速度分别为16.2 g·kg-1·d-1和14.1 g·kg-1·d-1（P＜0.001）,头围每周增长分别为0.96 cm和0.87 cm（P＜0.05）,身长增长分别为 1.08 cm和0.99 cm（P＜0.05）。早产Ⅰ组的宫外发育迟缓（EUGR）发生率（57.3％）低于早产Ⅱ组（72.5％）（P＜0.05）。结论在胎龄＜34 周或出生体重＜2 000 g的早产儿中,应用优博早产儿/低出生体重儿配方粉喂养对早产儿生长发育的影响明显优于优博标准婴儿配方粉,其体 重、身长和头围的生长速度都能够达到理想的宫内生长速度,也可明显降低EUGR的发生率。     

Comparison of the phospholipid classes in human milk in Japanese mothers of term and preterm infants

Background: Phospholipids (PLs) play an essential role in the growth and brain development of infants. Aim: To investigate PL composition in human milk (HM), including lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine (PC) and sphingomyelin (SM), from healthy Japanese mothers. Analyses were performed on colostrum, transitional milk and mature milk from mothers of preterm and term infants. Methods: HM samples were collected from mothers of 15 term infants (term group) and of 19 preterm infants (preterm group). PL composition was determined by two-dimensional thin-layer chromatography in conjunction with phosphorus analysis. Results: In both groups, the PL content (% of total lipid) of mature milk was significantly lower than in colostrum. SM and PC were the main PLs in HM, but in the preterm group, the percentage of SM in mature milk was significantly higher and PC in mature milk was significantly lower than in the term group.

Conclusion: The transition from colostrum to mature milk leads to an increase in SM and a decrease in PC in the HM of preterm infants, along with a decrease in PL content. This is the first report to demonstrate the differences in PL composition in HM between mothers of preterm and term infants.     

Plasma amino acid and protein concentrations in infants fed human milk or a whey protein hydrolysate formula during the first month of life

The aim of the study was to compare growth parameters, biochemical indices of protein metabolism and plasma amino acid concentrations in infants fed either human milk ( n = 12) or a whey protein hydrolysate formula ( n = 13) during the first month of life. Growth and gain in skin fold thickness were similar in both groups whereas serum protein concentration was significantly decreased (57.4 ± 3.9 versus 61.2 ± 2.9 g/l) in the infants fed the whey hydrolysate formula. The discrepancies between the plasma amino acid pattern of the whey hydrolysate formula group and that of the human milk group lessened during the first month. Nevertheless, at a mean age of 33 days the plasma threonine concentration remained twice as high and the plasma tyrosine, phenylalanine and proline concentrations were Significantly lower in the whey hydrolysate formula group than in the human milk group. Thus, compared with breast-fed infants, growth and most of the biological indices of protein metabolism were satisfactory in infants fed during the first month of life on a whey protein hydrolysate formula. Nevertheless, the decrease in total plasma protein concentration needs to be confirmed in a larger cohort of infants. In addition, further research is necessary to investigate the possible ways of reducing the hyperthreoninemia and preventing other plasma amino acid disturbances since it would be desirable to obtain plasma amino acid levels similar to those of breast-fed infants.     

Fatty acid balance studies in preterm infants fed formula milk containing long-chain polyunsaturated fatty acids (LCP) II

A milk formula (Prematil-LCP) containing long-chain polyunsaturated fatty acids (LCP) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants. A double-blind randomized controlled trial was performed comparing fatty acid absorption from Prematil-LCP (n = 10) and standard Prematil (n = 10). Formula-fed preterm infants underwent 3 d fat balances (once full enteral feeds were established) along with a parallel human milk fed group (n = 11). Plasma samples were taken on the last day. Median total fat excretion (absorption, %) was 2.34 g kg (82.0), 2.64 g kg (82.9) and 1.65 g kg (87.8) with Prematil, Prematil-LCP and human milk feeding, respectively. This reflected differences in the excretion and absorption of long-chain saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was higher in infants fed human milk than in those fed Prematil-LCP, particularly for n -6 LCP (p <0:01). Nevertheless, excreted LCP equated to <30% dietary intake, with Prematil-LCP feeding. Plasma lipid fatty acid composition reflected differences in dietary LCP intake.     

Vitamin E status in preterm infants fed human milk or infant formula

Vitamin E status was assessed in 36 infants with birth weights less than 1500 gm who were assigned randomly to receive one of three sources of nutrition: milk obtained from mothers of preterm infants (preterm milk), mature human milk, or infant formula. Infants in each dietary group were further assigned randomly to receive iron supplementation (2 mg/kg/day) beginning at 2 weeks or to receive no iron supplementation. All infants received a standard multivitamin, providing 4.1 mg alpha-tocopherol daily. Serum vitamin E concentrations at 6 weeks were significantly related both to type of milk (P less than 0.0001) and to iron supplementation (P less than 0.05). Infants fed preterm milk had significantly higher serum vitamin E levels than did infants fed mature human milk, and both groups had significantly higher levels than did those fed formula. Ratios of serum vitamin E/total lipid were also significantly greater for infants fed human milks than for those fed formula. The addition of iron to all three diets resulted in significantly lower serum vitamin E levels at 6 weeks (P less than 0.05); however, only in the group fed formula was there evidence of vitamin E deficiency. Preterm milk with routine multivitamin supplementation uniformly resulted in vitamin E sufficiency in VLBW infants whether or not iron was administered.     

Randomized, double-blind comparison of growth in infants receiving goat milk formula versus cow milk infant formula

OBJECTIVE: To compare growth of infants fed goat milk infant formula (GMF) or cow milk infant formula (CMF) and to compare tolerability and safety of the two formulas. METHODS: The study was conducted in Auckland, New Zealand. This was a double-blind randomized controlled trial. Newborn term infants were randomized within 72 h of birth to GMF or CMF. Milk formula powder in single serve sachets were reconstituted and fed to infants from trial commencement until age 168 days. No other formula given from randomization until age 168 days. Infant weight, length and head circumference were measured at birth and age 14, 28, 56, 84, 112, 140 and 168 days. Bowel motion frequency and consistency, sleeping and crying patterns and adverse events were also measured. RESULTS: Seventy-two infants were randomized, 36 each to GMF or CMF, with 62 infants completing the intervention. At enrollment the average weight of infants in the GMF group (mean +/- SD) was 3.33 +/- 0.43 kg and in the CMF group 3.43 +/- 0.47 kg; and at study completion 8.07 +/- 0.90 kg (GMF) and 7.87 +/- 0.99 kg (CMF). The difference in average weight gain over the study period for the GMF group versus the CMF group was not significant (+309 g; 95% CI = -49 to +668, P = 0.09). Median daily bowel motion frequency was greater in the GMF group than the CMF group (2.4 vs 1.7, P = 0.01). There were no group differences in bowel motion consistency, duration of crying, ease of settling, or frequency of adverse events. CONCLUSION: Growth of infants fed GMF is not different to that of infants-fed CMF.     

Selenium content of human milk,cow's milk and cow's milk infant formulas

The selenium content of human milk, cow's milk and cow's milk infant formula were estimated by instrumental neutron activation analysis. The highest values were found in 3 samples of human colostrum (524–865×10^-9 g/g dry weight). There was a significant decrease with increasing time post partum. Mature human milk exhibited a selenium content of 230±79×10^-9 g/g dry weight.The selenium content of 45 samples of cow's milk from the north-western area of Germany was 200±39×10^-9 g/g dry weight. While there was no significant difference between the values of mature human milk and of cow's milk, cow's milk infant formula exhibited significantly (P<0.01) lower values than human milk. The average selenium content of 107 samples of 10 different commercially available fluid and powdered cow's milk infant formulas (range: 18–171×10^-9 g/g dry weight) amounted to about only one third of that in mature human milk.With support of the Deutsche Forschungsgemeinschaft     

Longitudinal changes in milk composition of mothers delivering preterm and term infants

The concentrations of protein nitrogen (PN), non-protein nitrogen (NPN), energy, fat, sodium (Na), calcium (Ca), phosphorus (P), magnesium (Mg), and zinc (Zn) were determined in human milk from mothers giving birth to full-term (n = 13) and preterm infants (n = 8). Milk samples were collected under controlled conditions at two-week intervals for 12 weeks postpartum. Statistically significant differences in PN, Ca, and P concentrations were detected between the milk from mothers of preterm and term infants. The mean PN concentration in the preterm milk was statistically higher than that of term milk (198 vs. 164 mg N/dl), in contrast to the lower mean Ca (220 vs. 261 mg/1) and P (125 vs. 153 mg/1) concentrations detected in the preterm milk. No other differences in mean nutrient concentration were observed between the two groups. Concentrations of PN, NPN, Na, P, and Zn decreased over time. The concentration of Mg increased slightly. The content of fat, energy, and Ca did not change.     

Serum total and free tryptophan levels in term infants fed cow's milk formula or human milk

We found no significant differences in mean total and free tryptophan concentrations in sera of healthy, full-term infants fed cow's milk formula and healthy, full-term infants who were breast-fed. Serum tryptophan concentrations were measured 1 h after feeding when the infants were 2 and 6 days of age. In this study cow's milk formula compared favourably with human milk as primary nutrition for full-term infants, despite a two-to-three fold higher level of free tryptophan in human colostrum.     

A metabolic balance study in term infants fed lactose-containing or lactose-free formula

Lactose-free (L-) formulas are recommended for infants with conditions affecting lactose digestion. Cows' milk protein-based formulas containing other carbohydrate sources are most often used for such infants. This study compared fat absorption and absorption and retention of nitrogen, calcium, phosphorus, and magnesium in term infants fed either a L- or standard lactose-containing (L+) bovine milk protein-based formula. Data from three single-centre, double-blind, randomized, parallel-group metabolic balance studies were combined. After a 4-7-d equilibration period on either L- or L+ formula, a 72-h balance study was performed. Twenty infants received L- and 21 received L+ formula. Besides the L- group having a higher percentage of males (65%) and the L+ group a higher percentage of females (52.4%), other baseline measurements were similar. The majority of nutrient balance data was similar between the two groups. Exceptions were relative nitrogen absorption, calcium intake and calcium retention, magnesium retention, and faecal phosphorus excretion, all of which were significantly higher in the L- group. Vitamin D supplementation did not significantly affect either calcium or phosphorus data. This new L- formula provided similar nutrients and is a suitable alternative to a L+ formula in term infants requiring L- feedings.     

Evaluation of full-term infants fed an evaporated milk formula

The objective of this prospective, cohort study was to compare the nutritional status of full-term infants who were fed human milk (BF, n = 29). formula (FF, n = 30) or evaporated milk formulae (EM, n = 30) for at least 3 months. Infants were seen at enrollment, 3 and 6 months, at which times a blood sample, diet record and anthropometric data were collected. Infants in the EM group received solids earlier (12 ± 5 weeks) than did FF infants (15 ± 4 weeks), and both were earlier than BF infants (19 ± 4 weeks). Only 26% of the EM fed group received iron supplements as ferrous sulphate drops. Seven BF, 12 FF and 20 EM had abnormal ferritin values (<10ngml^-1) at 6 months. Copper intake was lower in the EM infants at 3 and 6 months. However, plasma copper and erythrocyte copper zinc superoxide dismutase (ZnCuSOD) levels did not differ between groups. Selenium intake was lower in the EM group (5 ± 1 and 10 ± 5 μg d^-1; 3 and 6 months) than in the FF infants (13 ± 4 and 19 ± 7 μgd^-1; 3 and 6 months). Erythrocyte SeGHSPx levels in EM infants were lower at 6 months (EM, 33.2 ± 3.4; FF, 35.2 ± 3.9; BF, 36.1 ± S.SmUmgHb^-1). Thiamin intake (0.99 ± 0.08 and 1.24 ± 0.32; 3 and 6 months, mg 1000 kcal^-1) was higher in the FF group than in EM infants (0.38 ± 0.39 and 0.66 ± 0.38; 3 and 6 months). There were more (13%) abnormal thiamin assays in the EM group at 6 months than in the BF and FF infants (0%). In conclusion, infants fed evaporated milk formula receive adequate copper but may not receive enough thiamin or selenium. Unless supplemented from birth with medicinal iron, intakes of iron will be inadequate.