Effects of exclusive formula or breast milk feeding on oxidative stress in healthy preterm infants

Background

Compared to formula, breast milk is considered to have superior antioxidant properties and consequently may reduce the occurrence of a number of diseases of prematurity associated with oxidative stress.

Aims

To test whether the antioxidant properties of breast milk in healthy premature infants are different to those of formula milk by comparing vitamin E levels in milk and determining the excretion of malondialdehyde (MDA) in urine.

Methods

Vitamin E was measured in the breast milk of 20 mothers who had given birth prematurely. Urinary MDA was measured in 10 exclusively breast milk fed and 10 exclusively formula fed healthy preterm infants receiving no vitamin supplements. MDA was measured after derivatisation with 2,4‐dinitrophenylhydrazine and consecutive HPLC with UV detection.

Results

Urinary MDA concentrations were consistently very low (0.074±0.033 μM/mM Cr and 0.078±0.026 μM/mM Cr in breast and formula fed infants respectively) and not significantly different between healthy breast milk and formula fed infants. Both breast and formula milk contained satisfactory levels (0.3–3.0 mg/100 ml) of vitamin E.

Conclusion

Antioxidant properties of both breast milk and formulae are sufficient to prevent significant lipid peroxidation in healthy premature infants.     

Selenium status of preterm infants fed human milk, preterm formula, or selenium-supplemented preterm formula

The selenium status of 46 orally fed vitamin E-sufficient preterm infants (birth weight less than 1700 gm) was studied longitudinally for 3 weeks to determine the efficacy of selenium supplementation. Infants were fed either human milk (n = 21; 24 ng selenium/ml), preterm formula (n = 13; 7.8 ng selenium/ml), or preterm formula supplemented with sodium selenite (n = 12; 34.8 ng selenium/ml). Plasma and erythrocyte selenium and glutathione peroxidase activity and urinary and dietary selenium content were evaluated on study day 1 (day enteral feeds reached 100 kcal/kg/day) and weekly for 3 weeks. Throughout the study, selenium intakes of infants fed preterm formula plus sodium selenite were greater than those of infants fed human milk, which were greater than those of infants fed preterm formula (p less than 0.001). After 3 weeks no differences were observed among groups for plasma or erythrocyte selenium or glutathione peroxidase. Plasma selenium and glutathione peroxidase values within all groups were low compared with those reported for term infants fed human milk. Whereas urinary selenium levels of infants fed preterm formula plus sodium selenite were greater than those of infants fed preterm formula at weeks 1 and 2 (p less than 0.01), infants fed human milk and preterm formula had lower levels at week 3 than on study day 1 (p less than 0.05). We conclude that blood selenium measurements typically used to monitor selenium status do not reflect dietary selenium intakes of orally fed preterm infants.     

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.     

Plasma amino acids in small preterm infants fed on human milk or formula.

Plasma amino acids were measured in 35 preterm infants, of whom 11 weighed less than 1000 g and 24 weighed between 1000 g and 1500 g at the time of sampling. Repeat samples were obtained in 18 at least seven days later. Seventeen infants were fed with preterm formula milk and 18 with expressed maternal breast milk at one to two hourly intervals during the study period. Formula fed infants gained weight faster than those fed on breast milk but there was little difference in amino acid patterns. Infants fed on breast milk were more likely to have concentrations of essential amino acids below the mid trimester fetal range than formula fed infants, but few infants in either feeding group had values above the fetal range. Those that did were equally distributed between both groups. Only two samples approached toxic concentrations, both in the group fed breast milk. The ratio of branched chain to aromatic amino acids was higher in the group fed on formula after correction for post conceptional age, implying that liver maturation may be accelerated by formula feeding. No correlations were found between plasma amino acid concentrations and nitrogen retention or metabolisable energy 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.     

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。     

母乳及配方奶喂养对NICU早产儿的影响

目的分析母乳喂养对不同出生胎龄早产儿的重要性。方法 639例出生胎龄28~(+3)~36~(+6)周的早产儿中单纯母乳喂养组(亲乳母乳喂养,未添加强化剂)237例,以及单纯配方奶(液态早产奶)喂养组402例。比较喂养方式对体重增长,白蛋白(ALB)、碱性磷酸酶(ALP)水平,以及喂养不耐受发生率、坏死性小肠结肠炎(NEC)、早产儿视网膜病(ROP)等并发症发生率的影响。结果与配方奶喂养相比,母乳喂养的出生胎龄28~30周早产儿日体重增长较快,喂养不耐受、NEC患病率较低,碱性磷酸酶较高,白蛋白较低,差异有统计学意义(P0.05);贫血、ROP、BPD、院内感染患病率及住院时间的差异均无统计学意义(P0.05)。出生胎龄31~33周的早产儿母乳喂养组较配方奶组日体重增长快,喂养不耐受率低,住院时间短,碱性磷酸酶高,差异均具有统计学意义(P0.05);两组间NEC、贫血、ROP、BPD、院内感染的发生率及白蛋白的差异无统计学意义(P0.05)。出生胎龄34~36周早产儿不同喂养方式组的各项指标差异均无统计学意义(P0.05)。结论母乳喂养对出生胎龄28~33周早产儿体重的增长,喂养不耐受率的降低,住院时间的缩短以及NEC发生率的减低有重要意义。     

采集母乳与母乳库母乳喂养对早产儿生长发育的影响

采集母乳与母乳库母乳可以作为早产儿在无法获得直接母乳喂养时可选择的一种喂养方式.目前文献提示,单纯以采集母乳与母乳库母乳喂养的早产儿生后短期内生长要慢于早产儿配方乳喂养,对早产儿远期生长的影响尚不明确;但采集母乳与母乳库母乳喂养可供给早产儿一定量的人乳特有成分,有利于早产儿神经发育,并减少坏死性小肠结肠炎、喂养不耐受等喂养相关并发症的发生.采集母乳与母乳库母乳的临床广泛应用还面临一些亟待解决的问题,将来的研究应更多关注于对早产儿远期生长发育的影响.     

Influence of breast versus formula milk on physiological gastroesophageal reflux in healthy, newborn infants.

The effect of milk type on physiological, gastroesophageal reflux (GER) was studied in 37 breast-fed and 37 formula-fed, healthy, term neonates aged 2-8 days. The neonates were randomly selected from the public maternity ward and studied for 4 h after their morning milk feed. GER was recorded by a pH microelectrode placed 6 cm above the gastroesophageal junction and analyzed in the third and fourth postprandial hours. Sleep state was accurately defined from the electroencephalogram, electrooculogram, electromyogram, breathing, and behavioral observations. Movement was recorded from a piezo-electric transducer. In active sleep, the breast-fed neonates demonstrated GER episodes of significantly shorter duration than the formula-fed neonates. The means and 95% confidence intervals (CI) were 3.0 (1.6,5.2) compared with 8.3 (5.0,13.3) min/h of active sleep respectively (p less than 0.05). This could not be explained by greater milk volume or increased movement before or during reflux in formula-fed neonates. However, the lower median pH values for GER in breast-fed neonates, 2.0 versus 2.5, were significantly different (p less than 0.05). This difference may reflect more rapid gastric emptying. The lower esophageal pH is more likely to stimulate peristalsis and thus limit the duration of reflux (shorter episodes), in the breast-fed neonates.     

Essential fatty acids in full term infants fed breast milk or formula.

To determine the biochemical effects of the fatty acid composition of plasma lipids, two groups of 10 healthy full term infants who were either exclusively breast fed or received a formula with similar contents of linoleic and alpha linolenic acids, but without long chain polyunsaturated (LCP) fatty acids, were studied prospectively. Plasma phospholipid, triglyceride, and sterol ester fatty acids were determined at the age of 2, 4, and 8 weeks by high resolution capillary gas chromatography. Breast fed infants maintained stable LCP fatty acid concentrations throughout the study. Formula fed infants had significantly lower median values of arachidonic acid (AA) at the ages of 2 (6.9 v 9.5% wt/wt) and 4 weeks (5.9 v 7.9%) and docosahexaenoic acid (DHA) at the ages of 4 (1.1 v 1.7%) and 8 weeks (1.0 v 1.7%) in plasma phospholipids. Median AA values in triglycerides were also significantly lower in the infants receiving formula at the ages of 2 (0.4 v 0.6%) and 4 weeks (0.3 v 0.6%). It is concluded that formula fed full term infants are unable to match the omega-3 and omega-6 LCP status of breast fed full term infants until at least two months after birth.     

早产儿和低出生体重儿使用捐赠母乳与配方奶喂养的荟萃分析

目的探讨不同喂养对新生儿坏死性小肠结肠炎(NEC)发病率的影响,并分析其对新生儿生长发育的不同作用。方法应用Donor human milk、formula milk、premature、low birth weight等关键词检索Pubmed、EMBASE、Ovid、the Cochrane Library和中国生物医学文献数据库发表的文章,并同时检索相关参考文献,对资料进行Meta分析。结果不同国家的7项研究共16篇文献被纳入此研究。共纳入病例1012例,其中单纯使用捐赠母乳或配方奶者669例,同时进行母乳喂养者343例,荟萃分析发现应用捐赠母乳可降低NEC的发病风险,合并的相对风险度RR=0.34,95%CI(0.16～0.71)。但是其对早产儿和低出生体重儿生长发育的作用弱于配方奶。结论捐赠母乳应该得推广,从而在降低NEC和胃肠不耐受的同时使早产儿和低出生体重儿更快地成长。     

早产儿和低出生体重儿使用捐赠母乳与配方奶喂养的荟萃分析

目的 探讨不同喂养对新生儿坏死性小肠结肠炎(NEC)发病率的影响,并分析其对新生儿生长发育的不同作用.方法 应用Donor human milk、formula milk、premature、low birth weight等关键词检索Pubmed、EMBASE、Ovid、the Cochrane Library和中国生物医学文献数据库发表的文章,并同时检索相关参考文献,对资料进行Meta分析.结果 不同国家的7项研究共16篇文献被纳入此研究.共纳入病例1012例,其中单纯使用捐赠母乳或配方奶者669例,同时进行母乳喂养者343例,荟萃分析发现应用捐赠母乳可降低NEC的发病风险,合并的相对风险度RR:0.34,95%CI(0.16～0.71).但是其对早产儿和低出生体重儿生长发育的作用弱于配方奶.结论 捐赠母乳应该得推广,从而在降低NEC和胃肠不耐受的同时使早产儿和低出生体重儿更快地成长.     

Nutrient balance studies in premature infants fed premature formula or fortified preterm human milk

This report compares fat, nitrogen, calcium, phosphorus, zinc, and copper absorption and retention data from 13 nutritional balance studies performed in 12 appropriate-for-gestational-age premature infants with birth weights less than or equal to 1,600 g fed a proprietary premature formula or their own mother's preterm human milk (PTHM) fortified with a powdered protein-mineral supplement. At the time of each balance study, each infant had a stable condition, was tolerating feedings, and was gaining weight steadily. Stool and urine were collected separately; doses of carmine red given 72 h apart were used to define dietary intake and the stool and urine collections. The balance studies were performed at an average age of 36 postnatal days. Both diets were found to support weight gain and nutrient retention at similar rates. Balance studies (n = 7) with premature formula demonstrated a weight gain of 16.8 +/- 5.2 g/kg/day, with a net fat absorption of 6.36 +/- 0.97 g/kg/day, net nitrogen retention of 427.9 +/- 47.1 mg/kg/day, net calcium retention of 95.0 +/- 14.1 mg/kg/day, net phosphorus retention of 56.7 +/- 5.9 mg/kg/day, net zinc retention of 208 +/- 903 micrograms/kg/day, and net copper retention of 26.4 +/- 30.8 micrograms/kg/day (mean +/- SD). Comparison balance studies (n = 6) with fortified PTHM demonstrated a weight gain of 17.2 +/- 7.1 g/kg/day, net fat absorption of 5.60 +/- 1.55 g/kg/day, net nitrogen retention of 366.0 +/- 84.0 mg/kg/day, net calcium retention of 82.2 +/- 10.8 mg/kg/day, net phosphorus retention of 58.6 +/- 5.9 mg/kg/day, net zinc retention of 685 +/- 363 micrograms/kg/day, and net copper retention of 67.3 +/- 37.2 micrograms/kg/day. These rates of weight gain and of fat, nitrogen, zinc, and copper retention approximate those of the third trimester of intrauterine life; only calcium and phosphorus retention approached the lower range of estimated in utero accretion.     

Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis

OBJECTIVES: To compare the effect of donor breast milk with infant formula in preterm infants. Separate comparisons with formula were made for donor breast milk that was: (1) given as a sole diet; (2) given as a supplement to mother's own breast milk; and (3) fortified with macronutrients and micronutrients. The main outcomes were death, necrotising enterocolitis (NEC), infection, growth and development. DATA SOURCES: Electronic databases-Cochrane, CENTRAL, MEDLINE, EMBASE, CINAHL, and HMIC: DH. REVIEW METHODS: Systematic review and meta-analysis of trials and observational studies of preterm or low birthweight infants. RESULTS: Seven studies (including five randomised controlled trials), all from the 1970s and 1980s, fulfilled the inclusion criteria. All studies compared the effect of sole donor breast milk with formula (combined n = 471). One of these also compared the effect of donor breast milk with formula given as a supplement to mother's own milk (n = 343). No studies examined fortified donor breast milk. A meta-analysis based on three studies found a lower risk of NEC in infants receiving donor breast milk compared with formula (combined RR 0.21, 95% CI 0.06 to 0.76). Donor breast milk was associated with slower growth in the early postnatal period, but its long-term effect is unclear. CONCLUSION: Donor breast milk is associated with a lower risk of NEC and slower growth in the early postnatal period, but the quality of the evidence is limited. Further research is needed to confirm these findings and measure the effect of fortified or supplemented donor breast milk.     

Growth and biochemical response of premature infants fed pooled preterm milk or special formula

This study compared growth of a group of very low birth weight infants fed a formula specifically developed for such infants (Formula) with another group fed expressed breast milk (EBM). The Formula contained 2.4 g/dl of protein (lactalbumin:casein ratio, 60:40); 4.1 g/dl of fat (40% medium-chain triglycerides); 8.8 g/dl of carbohydrates; and 81 kcal/dl, with more calcium, phosphorus, and electrolytes than are in human milk. Premature babies with birth weights between 1,200 and 1,500 g and gestational age less than 36 weeks were eligible for the study and were fed either pooled EBM or Formula until they reached a weight of 1,800 g. Twenty infants fed EBM and 19 infants fed Formula completed the trial. Weight gain was faster in the Formula-fed infants after a caloric intake of 100 kcal/kg/day was achieved (Formula 27.7 g/day vs. EBM 17.2 g/day; p less than 0.001). Time to reach 1,800 g was 27 days for the Formula group and 39 days for those on EBM (p less than 0.001). Increments in head circumference and skinfold thickness were also greater in the Formula-fed group. Laboratory studies in the two groups of infants showed higher alkaline phosphatase levels, which were not due to vitamin D deficiency, in the EBM-fed infants.     

Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula

At present, not much is known about the absorption and metabolism of human milk (HM) oligosaccharides in term and preterm infants. We investigated the renal excretion of lactose and complex oligosaccharides in preterm infants fed HM ( n = 9, mean actual body weight 2290 g) or a cow's milk-based infant formula ( n = 9, mean actual body weight 2470 g). We found that the renal excretion of lactose in HM-fed infants was slightly lower than in formula-fed infants (14.0 ± 7.4 versus 20.4 ± 8.7 mg kg^-1 day^-1, mean ± SD). The excretion of neutral sugars deriving from oligosaccharides was similar in HM-fed and formula-fed infants (3.8 ± 2.1 versus 2.9 ± 0.9mgkg^-1 day^1-); the difference between means was not statistically significant. The separation and characterization of oligosaccharides by high-pH anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) and subsequent analysis by fast atom bombardment-mass spectrometry (FAB-MS) revealed a more complex pattern in HM-fed infants compared to the formula-fed group. Lactose-derived oligosaccharides characteristic for HM (e.g lacto- N -tetraose, and lacto- N -fucopentaoses I and II) were excreted in HM-fed but not in formula-fed infants. These results indicate that nutrition has a significant impact on the oligosaccharide composition in urine of preterm infants.