Early diet of preterm infants and development of allergic or atopic disease: randomised prospective study.

OBJECTIVE--To study the effect of early diet on the development of allergic reactions in infants born preterm. DESIGN--Two randomised prospective trails. In trail A infants were randomly allocated banked donor milk or preterm formula as their sole diet or (separately randomised) as a supplement to their mother''s expressed breast milk. In trial B infants were allocated term or preterm formula. A blind follow up examination was done 18 months after the expected date of birth. SETTING--Neonatal units of hospitals in Cambridge, Ipswich, King''s Lynn, Norwich, and Sheffield. Outpatient follow up. PARTICIPANTS--777 Infants with a birth weight less than 1850 g born during 1982 to 1984. MAIN OUTCOME MEASURES--Development of eczema, allergic reactions to food or drugs, and asthma or wheezing by nine and 18 months after term. Whenever possible the observations were confirmed by rechallenge or clinical examination. RESULTS--At 18 months after term there was no difference in the incidence of allergic reactions between dietary groups in either trial. In the subgroup of infants with a family history of atopy, however, those in trial A who received preterm formula rather than human milk had a significantly greater risk of developing one or more allergic reactions (notably eczema) by 18 months (odds ratio 3.6; 95% confidence interval 1.4 to 9.1). CONCLUSIONS--Feeding neonates on formulas based on cows'' milk, including those with a high protein content, did not increase the overall risk of allergy. Nevertheless, in the subgroup with a family history of atopy early exposure to cows'' milk increased the risk of a wide range of allergic reactions, especially eczema.     

Effect of maternal dietary exclusion on breast fed infants with eczema: two controlled studies.

Thirty seven breast fed infants with eczema were studied to see whether changes in their mothers'' diets affected their skin condition. Nineteen mothers and babies took part in a double blind crossover trial of exclusion of egg and cows'' milk, and 18 took part in open exclusion of 11 foods followed by double blind challenge to those mothers whose infants seemed to respond. Babies were examined at the beginning and end of each dietary period, and the extent and severity of the rash were given a numerical score. The eczema improved in six infants when their mothers avoided egg and cows'' milk and worsened again when these were reintroduced. Two infants suffered gastrointestinal reactions after maternal ingestion of egg and cows'' milk, one developing colitis. Maternal dietary exclusion seems to benefit some breast fed babies with eczema.     

Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants.

OBJECTIVE--To examine the effects of maternal diet during lactation and the use of formula feeds on the development of atopic eczema in infants at risk. DESIGN--Mothers who planned to breast feed exclusively were randomly allocated to either a restricted diet (avoiding milk and other dairy products, eggs, fish, peanuts, and soybeans) or a diet without restrictions. Mothers who did not plan to breast feed were randomly allocated to using one of three formula feeds. SETTING--Child health centre in Canada. SUBJECTS--97 Mothers who chose to breast feed and 124 mothers who did not. INTERVENTIONS--Restricted diet for 49 mothers who breast fed. Casein hydrolysate formula, soy milk formula, or cows'' milk formula for infants not breast fed. MAIN OUTCOME MEASURE--Development of eczema in babies. RESULTS--Infants were followed up over 18 months and examined for eczema. Eczema was less common and milder in babies who were breast fed and whose mothers were on a restricted diet (11/49 (22%) v 21/48 (48%)). In infants fed casein hydrolysate, soy milk, or cows'' milk 9/43 (21%), 26/41 (63%), and 28/40 (70%), respectively, developed atopic eczema. CONCLUSIONS--In families with a history of atopic disease [corrected] mothers who breast feed should avoid common allergenic foods during lactation. If they choose not to breast feed a hydrolysate formula should be used.     

Metabolic acidosis and infant feeding.

Most cows'' milk based formulae for infant feeding present a greater acid load to the infant than breast milk. To determine the effect of this difference the acid base state of 180 healthy term infants was measured on the sixth day of life and related to the type of feed. Those infants fed on cows'' milk formula (SMA) had a mean pH of 7-34 +/- 0-05 and a base deficit of 8-8 +/- 3-1, while those fed on breast milk had a mean pH of 7-38 +/- 0-05 and a base deficit of 5-6 +/- 3-1. The difference between the two groups of infants was significant for both these measurements. Metabolic acidosis was defined as a base deficit greater than 10 mmol/l. Seventy-four per cent of the 34 infants who were acidotic at six days were bottle-fed. There was a significant correlation between the pH of the feed and the degree of acidosis in the infant as measured by the base deficit. The findings suggest that when breast milk is not available a pH-adjusted milk formula would be desirable for preventing and treating neonatal metabolic acidosis.     

Effect of antigen load on development of milk antibodies in infants allergic to milk.

The phenomenon that large amounts of antigen, such as are absorbed during the neonatal period, suppress the IgE response while low-dose exposure enhances it was investigated by analysing the antibody responses of infants allergic to milk according to their degree of exposure to cows''-milk protein. IgG, IgA, and IgM milk-specific antibodies in these infants and in age-matched controls were measured by enzyme-linked immunosorbent assay. Milk-specific IgE and total IgE were also measured. Children allergic to milk who were breast fed and had had minimal exposure to cows'' milk had decreased titres of IgG, IgA, and IgM milk antibodies compared with infants allergic to milk who, before diagnosis, had been fed substantial volumes of cows'' milk. Conversely, the infants with minimal exposure to cows'' milk showed vastly increased total and milk-specific IgE antibodies compared with the milk-fed infants. These results support recent experimental evidence that appreciable amounts of allergen suppress rather than stimulate IgE production. These data may have important implications for dietary regimens in at-risk infants. The results also lend support for the role of IgE in immediate-type allergic reactions and suggest that various non-IgE immune mechanisms play a part in the aetiology of intolerance to cows''-milk protein in some children.     

Egg and cows' milk hypersensitivity in exclusively breast fed infants with eczema,and detection of egg protein in breast milk.

Forty nine eczematous infants who were still solely and exclusively breast fed and who had never received anything but breast milk were studied for evidence of sensitisation to foods. Thirty four similar infants without eczema formed a control group. The eczematous infants were divided into three groups according to clinical criteria: (1) definite atopic eczema; (2) possible atopic eczema; (3) atopic eczema unlikely. Twenty three infants showed cutaneous hypersensitivity to foods, usually egg and cows'' milk. Seven of 14 infants in group 1 and nine of 20 in group 2 were sensitised compared with four of 15 in group 3 and three of 34 controls (p less than 0.01). Ovalbumin was detected in breast milk from 14 of 19 mothers tested after ingestion of egg, the concentrations being the same for mothers feeding eczematous and normal infants. Breast fed babies developing eczema may be sensitised by foods eaten by their mothers.     

Continuous Intragastric Milk Feeds in Infants of Low Birth Weight

In a feeding trial 66 infants of low birth weight received continuous intragastric milk feeds from the fourth hour of life, starting with 60 ml/kg/24 hr and reaching a maximum of 300 ml/kg/24 hr on the ninth day. Each infant received only full-strength milk, which was either expressed human breast milk or SMA-S26 (a proprietary low-protein adapted cows'' milk) or half-cream Regal milk (partly-skimmed evaporated cows'' milk). For various reasons 10 babies had to be withdrawn, and the final assessment was made on the 56 who completed the trial successfully.Persistent vomiting was a problem in only four infants. In two of them the trial was continued after gastric lavage and in the other two vomiting stopped when the volume was reduced. Despite a careful search no evidence was found of aspiration of feeds in any infant. Continuous intragastric milk infusion was shown to be a safe method of feeding infants of low birth weight and SMA-S26 was almost as well tolerated as human milk. Because of the high-protein content of half-cream cows'' milk preparations and the resultant high plasma amino-acid levels when they are given in these large volumes they should be avoided for this type of feeding although they produce better weight gains in the first week of life.     

Influence of dietary nucleotides on plasma immunoglobulin levels and lymphocyte subsets of preterm infants.

We examined the effects of nucleotide supplementation to a preterm adapted milk formula on the lymphocyte subsets and plasma IgG, IgM and IgA levels in preterm infants for the first three months of life. Two groups of preterm infants received a milk formula or the same formula supplemented with CMP, AMP, UMP, GMP and IMP to mimic the concentration of acid-soluble nucleotides found in human milk. Blood samples were obtained at birth, 10 days, 20-30 days and 3 months of age. Preterm infants fed the nucleotide formula exhibited higher plasma levels of IgM in all postnatal study periods than neonates fed the standard formula; moreover, IgA was also higher at 3 months of age in nucleotide formula fed infants. No major differences were seen between groups for IgG levels and lymphocyte subsets. Thus, dietary nucleotides appear to exert actions on immature human neonate lymphocytes enhancing the in vivo production of Ig which may have a role in the defense capacity of neonates.     

Does early nutrition in infants born before term programme later blood pressure?

OBJECTIVES--To test whether nutrition early in infants'' development programmes later blood pressure and whether the reported relation between low birth weight and later high blood pressure is due to poor nutrition or growth before full term. DESIGN--Prospective randomisation of preterm infants to early diets differing greatly in nutrient content in four parallel multicentre trials, with blinded follow up 7.5-8 years later. SETTING--Neonatal units at Cambridge, Ipswich, King''s Lynn, Norwich, and Sheffield. SUBJECTS--758 children weighing under 1850 g at birth. MAIN OUTCOME MEASURE--Blood pressure at age of 7.5-8 years. RESULTS--There were major differences in nutrient intake from randomised diets (preterm formula v standard formula and preterm formula v donor breast milk; in each case with or without mother''s milk), but follow up showed no differences in later blood pressure. Individual subjects showed large variation in protein and energy intakes and in growth performance, including degrees of growth failure seldom seen in utero, but these factors were also unrelated to later blood pressure. CONCLUSION--Extremes of nutritional intake and growth performance in preterm infants do not programme later blood pressure at 7.5-8 years of age. These findings do not support the hypothesis that high blood pressure has early nutritional origins. We suggest that the long term rise in blood pressure reported in individuals who had low birthweight (at full term) is not, as previously speculated, due to poor fetal nutrition or growth as such.     

Breast Milk Substitute: A Bacteriological Study

The increased susceptibility of infants fed on cows'' milk preparations has been attributed, at least in part, to differences in the nature of the large-bowel content—owing to the acidity of the faeces and their high content of Lactobacillus bifidus. In an attempt to mimic these features of the breastfed infant in one who is fed artificially, a breast milk substitute was devised which resembles breast milk in several important ways. When this material was fed to newborn infants the faeces developed the characteristics of those of the breast-fed child.     

Associations of infant nutrition with insulin resistance measures in early adulthood: evidence from the Barry-Caerphilly Growth (BCG) study

Background

Previous studies suggest that over-nutrition in early infancy may programme long-term susceptibility to insulin resistance.

Objective

To assess the association of breast milk and quantity of infant formula and cows'' milk intake during infancy with insulin resistance measures in early adulthood.

Design

Long-term follow-up of the Barry Caerphilly Growth cohort, into which mothers and their offspring had originally been randomly assigned, between 1972–1974, to receive milk supplementation or not. Participants were the offspring, aged 23–27 years at follow-up (n = 679). Breastfeeding and formula/cows'' milk intake was recorded prospectively by nurses. The main outcomes were insulin sensitivity (ISI₀) and insulin secretion (CIR₃₀).

Results

573 (84%) individuals had valid glucose and insulin results and complete covariate information. There was little evidence of associations of breastfeeding versus any formula/cows'' milk feeding or of increasing quartiles of formula/cows'' milk consumption during infancy (<3 months) with any outcome measure in young adulthood. In fully adjusted models, the differences in outcomes between breastfeeding versus formula/cows'' milk feeding at 3 months were: fasting glucose (−0.07 mmol/l; 95% CI: −0.19, 0.05); fasting insulin (8.0%; −8.7, 27.6); ISI₀ (−6.1%; −11.3, 12.1) and CIR₃₀ (3.8%; −19.0, 32.8). There was also little evidence that increasing intakes of formula/cows'' milk at 3 months were associated with fasting glucose (increase per quartile of formula/cows'' milk intake = 0.00 mmol/l; −0.03, 0.03); fasting insulin (0.8%; −3.2, 5.1); ISI ₀ (−0.9%; −5.1, 3.5) and CIR₃₀ (−2.6%; −8.4, 3.6).

Conclusions

We found no evidence that increasing consumption of formula/cows'' milk in early infancy was associated with insulin resistance in young adulthood.     

Improvement of Expressed Breast Milk in Mothers of Preterm Infants by Recording Breast Milk Pumping Diaries in a Neonatal Center in China

Objectives

Because inadequate expression of human milk (EBM) in mothers of hospitalized infants were noticed in a neonatal center of our hospital, family education program was carried out to increase the EBM.

Methods

A breast milk pumping diary was introduced to the mothers with preterm infant(s) admitted in the NICU. The ratios of EBM (days of EBM to NICU/hospitalized days), breast milk feeding (BMF) (days of infants fed with exclusive human milk/hospitalized days), mixed feeding (MF) (days of infants fed with partial breast milk and partial formula/hospitalized days), and formula feeding (FF) (days of infants fed with preterm formula/hospitalized days) were evaluated.

Results

During January to April, 2014, the ratios of EBM to the NICU, BMF, MF and FF were 28.11%, 6.6%, 32.8% and 60.6%, respectively. After the introduction of breast milk pumping diary to the mothers from May 2014, the ratio of EBM to the NICU increased significantly to 53.3% (p<0.01) within the following eight months. Both the ratios of BMF and MF also rose to 23.8% and MF 55.3%, respectively. Consequently, the ratio of FF was reduced to 20.9%. Exclusive breast milk feeding also significantly reduce the duration of nil per oral (NPO) of the very low birth weight infants during hospital stay as compared to those fed with mixed feeding and formula feeding.

Conclusion

The introduction of a breast milk pumping diary was associated with a significant increase in the intake of EBM of the hospitalized preterm newborns.     

Prevalence of anemia among James Bay Cree infants of northern Quebec

BACKGROUND: Anemia is common among First Nation infants in Canada, often as a result of iron deficiency, which places them at risk for psychomotor impairment. Prevalence data are unavailable, and the risk factors are unknown. This study assessed the prevalence of anemia and associated risk factors among 9-month-old Cree infants in northern Quebec. METHODS: Between January 1995 and October 1998, 6 of 9 Cree villages in the James Bay region adopted a screening protocol for anemia in 9-month-old infants. Cross-sectional data were obtained from medical charts. The data for babies of very low birth weight and those with fever or infection were excluded. Among the 386 babies whose hemoglobin concentration was known, the type of milk consumed at the time of screening was known for 354. Associations between hemoglobin concentration and mean cell volume at 9 months, and milk type and weight gain since birth were analysed. RESULTS: The mean hemoglobin concentration of the 386 infants was 114.1 (standard deviation [SD] 10.6) g/L. The prevalence of anemia was 31.9% (95% confidence interval [CI] 27.2%-36.7%) with a hemoglobin cutoff value of 110 g/L, 17.6% 95% CI 13.9%-21.7%) with a cutoff value of 105 g/L, and 7.8% (95% CI 5.3%-10.9%) with a cutoff value of 100 g/L. Babies exclusively fed formula at 9 months had a higher mean hemoglobin concentration (118.5 [SD 9.9] g/L) than those exclusively fed breast milk (109.9 [SD 10.0] g/L), cow''s milk (112.5 [SD 10.1] g/L) or more than one type of milk (112.0 [SD 10.8] g/L) (p < 0.05). Compared with formula, the odds ratio (OR) for anemia was 7.9 (95% CI 3.4-18.2) for breast milk, 5.0 (95% CI 2.0-12.7) for cow''s milk and 5.2 (95% CI 1.9-14.6) for mixed milks. Infants fed formula and those fed cow''s milk had significantly greater weight gains since birth, by 724 g and 624 g respectively, than breast-fed infants (p < 0.05). When milk type was controlled for, weight gain since birth was significantly associated with the presence of microcytic erythrocytes (OR comparing highest tertile of weight gain to lowest tertile 2.9, 95% CI 1.2-6.6). INTERPRETATION: Iron-deficiency anemia is highly prevalent among James Bay Cree infants. Measures to increase iron intake are required.     

Strontium-89 and Strontium-90 Levels in Breast Milk and in Mineral-Supplement Preparations

Strontium-90, strontium-89 and S.U. values were determined in human milk before and after the resumption of atmospheric nuclear testings in 1961, and the levels were compared to cows'' milk values reported during the same time. S.U.⁹⁰ levels in human milk were approximately one-fifth of those found in cows'' milk. Assuming an average dietary intake of 11-13 S.U.⁹⁰ during the period tested, the mean strontium/calcium ratio of 1.78 found in human milk represents an Observed Ratio milk-diet of approximately 0.14-0.16. Although strontium-89 was present in cows'' milk already in September 1961, it did not appear in human milk until November 1961. It seems, therefore, that there was a two-month lag period between the appearance of fresh fallout in cows'' milk and human milk. Calcium-supplement mineral preparations used by pregnant and lactating women were tested to find their strontium-89, strontium-90 and S.U. levels, because strontium isotopes, if present in these products, will be transferred to the fetus and to breast-fed infants. The compounds tested had S.U.⁹⁰ levels of 0.13-2.62; in none of the preparations was Sr⁸⁹ present.     

Feeding Overstrength Cows' Milk to Babies

The dangers of overstrength milk feeds have been emphasized in several reports during the last two years. They may even be a factor in unexpected death in infants. Samples of prepared dried milk feeds were obtained from 302 mothers who brought their 5- to 8-week-old infants to a special follow-up clinic. Determination of the sodium content of the milk indicated that 57% of the feeds were significantly overstrength. There is an urgent need to improve mothers'' knowledge of the importance of preparing dried cows'' milk infant feeds correctly.     

深度水解蛋白配方奶在不同体重早产儿喂养中的临床效果观察

目的:评估深度水解配方奶(eHPF)在不同体重早产儿早期喂养中临床应用效果。方法:选取2017年9月至2018年12月出生的早产儿,分为极低出生体重儿组(体重1000-1500g之间)62例和低出生体重儿(体重1500-2000g之间)100例,每组再随机分为两组,分别予以深度水解蛋白奶(eHPF)和早产儿配方奶(SPF)喂养。极低出生体重儿组于12小时后开始微量喂养,低出生体重儿12小时内适量喂养;极低出生体重儿组深度水解蛋白奶喂养2周后改早产儿奶喂养,低出生体重儿组深度水解蛋白奶1周后改早产儿奶喂养。比较深度水解蛋白奶在不同体重早产儿早期喂养中的临床应用效果,不同体重早产儿恢复出生体重时间、每日体重增长速度、胃管留置时间、完全肠内喂养天数、住院天数、喂养不耐受发生率、宫外发育迟缓发生率及尿素氮、碱性磷酸酶指标。结果:深度水解蛋白喂养组极低出生体重儿/低出生体重儿恢复出生体重天数、完全肠道喂养天数、胃管留置时间、住院天数较早产儿奶喂养组明显缩短(P0.05),每天体重增长优于早产儿组,喂养不耐受、宫外发育迟缓发生率明显低于早产儿组(P0.05),尿素氮、碱性磷酸酶无统计学差异(P0.05)。结论:深度水解蛋白奶用于不同体重早产儿早期喂养效果明显优于早产儿配方奶,其更有助于早产儿的生长发育。     

Oligosaccharides from feces of preterm infants fed on breast milk

Nine neutral and five acidic oligosaccharides were isolated from feces of a preterm (30th postmenstrual week) blood group A nonsecretor infant fed on pooled breast milk. Structural analyses were carried out using sugar and methylation analyses, fast atom bombardment mass spectrometry, and 1H NMR. The acidic oligosaccharides are well-known components of human milk. The neutral oligosaccharides are characteristic of nonsecretor milk. Surprisingly, no secretor gene-dependent oligosaccharides were present in the feces. Another preterm (27th postmenstrual week) blood group A, secretor infant fed on pooled breast milk showed the same fecal oligosaccharide pattern as above during the first week after birth, despite being a secretor individual. Also notable was the absence of blood group A-active oligosaccharides in this sample. Another sample of feces collected 8 weeks later from the latter infant contained the expected blood group A-active oligosaccharides. Furthermore, free sialic acid was present at the cost of the sialyl oligosaccharides seen earlier. Thus, infants born prematurely do not show the same degree of development of oligosaccharide metabolism as their more mature counterparts.     

Induction of histamine release and desensitization in human leukocytes. Effect of anaphylatoxin.

Hog anaphylatoxin (AT) in concentrations from 0.5 to 5 mug/ml gives a dose-dependent histamine release from human leukocytes. Concentration of 100 mug/ml AT give the same high histamine release as 5 mug/ml. This is in contrast to the histamine release obtained with anti-IgE or allergen, which give low histamine release with high doses. The histamine release obtained with AT is completed in 20 sec and the reaction is temperature- and calcium-dependent. Treatment of cells with AT in the presence or absence of calcium makes them insensitive to another challenge with AT. Such treated cells are fully responsive, however, to challenge with anti-IgE if the pretreatment has been performed in the absence of calcium. This, together with the calcium- and temperature-dependence indicates that the AT-induced histamine release is nontoxic. Treatment of cells with AT in the presence of calcium induces, besides histamine release, decrease in sensitivity to anti-IgE, indicating that both AT and anti-IgE release histamine from the same cells. We discuss to what extent AT and cell-bound Ig share intracellular mechanisms for induction of histamine release.     

Antimicrobial Protein and Peptide Concentrations and Activity in Human Breast Milk Consumed by Preterm Infants at Risk of Late-Onset Neonatal Sepsis

ObjectiveWe investigated the levels and antimicrobial activity of antimicrobial proteins and peptides (AMPs) in breast milk consumed by preterm infants, and whether deficiencies of these factors were associated with late-onset neonatal sepsis (LOS), a bacterial infection that frequently occurs in preterm infants in the neonatal period.ResultsLevels of most AMPs and antibacterial activity in preterm breast milk were higher at day 7 than at day 21. Lactoferrin was the only AMP that limited pathogen growth >50% when added to formula at a concentration equivalent to that present in breast milk. Levels of AMPs were similar in the breast milk fed to infants with and without LOS, however, infants who developed LOS consumed significantly less breast milk and lower doses of milk AMPs than those who were free from LOS.ConclusionsThe concentrations of lactoferrin and defensins in preterm breast milk have antimicrobial activity against common neonatal pathogens.     

Effect of two doses of docosahexaenoic acid (DHA) in the diet of preterm infants on infant fatty acid status: results from the DINO trial

Formula supplemented with docosahexaenoic acid (DHA) improves retinal function of preterm infants but the optimal dose is unknown. In a randomized controlled trial we examined the effect of increasing the DHA concentration of human milk and formula on circulating fatty acids of preterm infants. Infants born <33 weeks gestation were fed high-DHA milk (1% total fat as DHA) or standard-DHA milk (0.2-0.3% DHA) until reaching their estimated due date (EDD). Milk arachidonic acid (AA) concentration was approximately 0.5% for both groups. At EDD, erythrocyte membrane phospholipid DHA was elevated in the high-DHA group compared with standard-DHA (mean+/-SD, high-DHA 6.8+/-1.2, standard-DHA 5.2+/-0.7, p<0.0005) but AA was lower (high-DHA 14.9+/-1.3, standard-DHA 16.0+/-1.2, p<0.0005). Feeding preterm infants human milk and formula with 1% DHA raises but does not saturate erythrocyte phospholipids with DHA. Milk exceeding 1% DHA may be required to increase DHA status to levels seen in term infants.