Preventive effect of feeding high-risk infants a casein hydrolysate formula or an ultrafiltrated whey hydrolysate formula. A prospective, randomized, comparative clinical study

In a prospective study of a 1-year birth cohort of 158 high-risk infants the effect of feeding breastmilk, a casein hydrolysate (Nutramigen®) or a new ultrafiltrated whey hydrolysate (Profylac®) on the development of cow milk protein allergy/intolerance (CMPA/CMPI) was assessed and compared. All the infants had biparental or severe single atopic predisposition, the latter combined with cord blood IgE ≥ 0. 5 kU/L. At birth all infants were randomized to Nutramigen or Profylac, which was used when breastfeeding was insufficient or not possible during the first 6 months of life. During the same period this regimen was combined with avoidance of solid foods and cow milk protein. All mothers had unrestricted diets and were encouraged to do breastfeeding only. Moreover, avoidance of daily exposure to tobacco smoking, furred pets and dust-collecting materials in the the bedroom was advised. The infants were followed prospectively from birth to 18 months of age. All possible atopic symptoms were registered and controlled elimination/challenge studies were performed when symptoms suggested CMPA/CMPI. A total of 154 (97%) were followed up and 141 followed the diet strictly. Eighty-eight (62%) of the infants were breastfed for at least 6 months, 20 (14%) were breastfed exclusively, 59 and 62 had varying amounts of Nutramigen or Profylac respectively. CMPA/CMPI was diagnosed in 1/20, 1/59 and 3/62 in the breastfed, the Nutramigen and Profylac groups respectively, but 1 of the latter also had Nutramigen. None of the infants showed reactions against Nutramigen or Profylac. In 4 infants symptoms were provoked by breastmilk when the mother ingested cow milk and in 1 only by cow milk. The incidence of CMPA/CMPI among the infants who followed the dietary prevention programme was 3. 6% (5/141) which was a significant reduction compared to 20% (15/75) in an identically defined high-risk group without dietary preventive measures. None of the infants in the prevention group developed CMPA/CMPI after the age of 6 months. We conclude that feeding breastmilk, an extensively hydrolysed casein formula (Nutramigen) or an ultrafiltrated whey hydrolysate (Profylac) combined with avoidance of solid foods during the first 6 months of life in high-risk infants significantly reduced the cumulative incidence of CMPA/CMPI during the first 18 months of life. No difference was noted whether the infants were fed breastmilk, Nutramigen or Profylac and a diet period of 6 months seems sufficient. Both formulae were well tolerated and accepted by the infants.     

Whey protein hydrolysate formula for infants with gastrointestinal intolerance to cow milk and soy protein in infant formulas

Twenty-one infants less than 6 months of age with gastrointestinal symptoms of cow milk and/or soy protein-based infant formula intolerance (diarrhea in 14, hematochezia in 16, emesis in 8, failure to thrive in 4, and colic in 10) were treated clinically with a whey protein hydrolysate formula. Six patients improved when placed directly on the formula, and 15 remained asymptomatic or improved when given the whey hydrolysate formula following initial treatment with a casein hydrolysate or elemental formula. Eighteen had supporting evidence of an allergic basis for their symptoms, including a family history of allergies in 6, a clinical challenge with the offending formula in 1, laboratory tests consistent with atopy in 11, and/or rectal biopsy with histologic allergic features in 7. The whey hydrolysate formula may be an acceptable alternative to soy or casein hydrolysate formulas in most infants with gastrointestinal symptoms of cow milk and/or formula intolerance.     

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.     

Safety of a new, ultrafiltrated whey hydrolysate formula in children with cow milk allergy: a clinical investigation

The purpose of this study was to determine whether a new ultrafiltrated whey hydrolysate infant formula, Profylac®, could be administered safely to children with cow milk protein allergy/intolerance. Profylac has a stated molecular weight of < 8 kD and at least 30, 000 times reduced antigenicity which is controlled by a combination of ELISA-techniques and immunochemical methods. The study comprised 66 children with cow milk protein allergy/intolerance diagnosed by controlled elimination/ challenge procedures. The children were aged 1 month-14. 5 years, median 1% years and 15 were below 1 year. Thirty-five of these children had proven IgE-mediated reactions (cow milk protein allergy). Sixty-one of the children had at least two different symptoms and 31 had concomitant allergies to other foods and/or inhalants. All 66 children underwent and tolerated open, controlled challenges with Profylac. A total of 64 children continued having Profylac daily for at least 3 months and 58 for at least 6 months after challenge. Nine of the children older than 1 year did not like the taste and only had Profylac in minor amounts. No side effects were registered. Fifteen of the infants were below 1 year of age, and this group was compared with an age matched group of 16 infants challenged with and fed an extensively hydrolysed casein hydrolysate, Nutramigen®. All the infants in these two groups accepted and tolerated Profylac and Nutramigen, respectively, and no side effects were registered. Among the 35 patients with IgE-mediated reactions 6% (2/35) had positive skin prick tests and 11% (3/28) had specific IgE class 2 against Profylac, 2 of the latter before intake of Profylac. None of the patients with non-IgE-mediated reactions had a positive skin prick test or specific IgE against Profylac. The study provides 95% confidence that this product is tolerated by at least 95% of children with cow milk protein allergy/intolerance and by 90% with IgE-mediated reactions. We conclude, that this ultrafiltrated whey hydrolysate is generally safe to feed to children with verified adverse reactions to cow milk protein, including children with IgE-mediated reactions. The taste of the product was widely accepted, also by older children.     

极低出生体重儿母乳喂养与配方乳喂养的比较

目的探讨极低出生体重儿在进行母乳喂养、早产儿配方乳喂养条件下黄疸消退、体重增长、耐受全胃肠营养的时间及常见并发症的区别。方法对2002年10月至2005年4月我科收治的111例极低出生体重儿提供母乳喂养的39例,另72例采用早产儿配方乳喂养,观察两组在黄疸消退日龄、回升到出生体重日龄、过渡到全胃肠道营养日龄、住院天数等的差别,并比较两组在喂养不耐受、新生儿坏死性小肠结肠炎、酸中毒的发生率方面的不同。结果两组过渡到全胃肠道营养日龄的差异有统计学意义(t=15.06,P<0.01);两组在喂养不耐受和酸中毒发生率的差异也有统计学意义(χ2分别为4.203和4.811,P<0.05);黄疸消退日龄、回升到出生体重日龄差异两组无统计学意义(t值分别为0.70和0.27,P>0.05);新生儿坏死性小肠结肠炎发生率的两组差异也无统计学意义(χ2=0.01,P>0.05)。结论在极低出生体重儿应积极进行母乳喂养,这对于早日过渡到全胃肠道营养、减少喂养不耐受发生率、缩短住院天数、降低酸中毒发生率均有积极作用。     

极低出生体重儿母乳喂养与配方乳喂养的比较

目的 探讨极低出生体重儿在进行母乳喂养、早产儿配方乳喂养条件下黄疸消退、体重增长、耐受全胃肠营养的时间及常见并发症的区别.方法 对2002年10月至2005年4月我科收治的111例极低出生体重儿提供母乳喂养的39例,另72例采用早产儿配方乳喂养,观察两组在黄疸消退日龄、回升到出生体重日龄、过渡到全胃肠道营养日龄、住院天数等的差别,并比较两组在喂养不耐受、新生儿坏死性小肠结肠炎、酸中毒的发生率方面的不同.结果 两组过渡到全胃肠道营养日龄的差异有统计学意义（t=15.06,P＜0.01）;两组在喂养不耐受和酸中毒发生率的差异也有统计学意义（χ2分别为4.203和4.811,P＜0.05）;黄疸消退日龄、回升到出生体重日龄差异两组无统计学意义（t值分别为0.70和0.27, P＞0.05）;新生儿坏死性小肠结肠炎发生率的两组差异也无统计学意义（χ^2=0.01,P＞0.05）.结论 在极低出生体重儿应积极进行母乳喂养,这对于早日过渡到全胃肠道营养、减少喂养不耐受发生率、缩短住院天数、降低酸中毒发生率均有积极作用.     

配方奶添加半乳糖-低聚糖对婴儿肠道微生态调节作用的研究

目的观察婴儿配方奶(Frisolac Advanced)添加半乳糖-低聚糖,对婴儿肠道微生态和肠道内发酵的影响,并与母乳和原有配方奶(Frisolac H)比较其功能特点。方法选取华东、华南地区2个城市的4家医院,选择足月健康新生儿,随机分配进入已添加半乳糖-低聚糖2.4g/L的配方喂养组(Frisolac Advanced)/未添加低聚糖的配方喂养组(Frisolac H),并选择纯母乳喂养为参考对照。共371个健康足月儿参与此项目。我们邀请所有参与的婴儿在满3个月时入院,采样检测大便中肠道微生态(双歧杆菌、乳酸杆菌、大肠杆菌)和短链脂肪酸(乙酸),测定大便pH值,并记录婴儿体格生长、大便性状与机体抵抗力。结果在婴儿满3个月时,Frisolac Advanced配方喂养组和纯母乳喂养组肠道益生菌(双歧杆菌、乳酸杆菌)数量均显著高于Frisolac H配方喂养组,Frisolac Ad-vanced配方喂养组和纯母乳喂养组之间差异无显著性;各组间肠道大肠杆菌数量差异无显著性。与原有配方(Frisolac H)比较,配方添加半乳糖-低聚糖2.4g/L可显著提高大便短链脂肪酸(乙酸)含量,降低大便pH值,改善大便性状,提高大便次数,增加大便体积。配方添加半乳糖-低聚糖2.4g/L喂养婴儿,未见明显肠道不良反应(哭闹,溢奶,呕吐)。结论婴儿配方奶添加半乳糖-低聚糖2.4g/L,可部分模拟母乳功能,调整肠道微生态,提高肠道益生菌数量,促进肠道内营养物质酵解产生短链脂肪酸,并改善大便性状。     

Defective humoral and cellular immune functions associated with veno-occlusive disease of the liver

We describe veno-occlusive disease of the liver associated with humoral and cellular immune defects in two siblings. Another child, with aplastic anemia, died before the age of 1 year. No consanguinity was found in the family. Both infants had lymphopenia and hypogammaglobulinemia; the surviving infant has defective in vitro immunoglobulin production after stimulation of lymphocytes with pokeweed mitogen, increased proportions of OKT8 positive cells, defective proliferative responses to phytomitogens, and decreased help for immunoglobulin production. A therapeutic trial with cimetidine, an H2 receptor antagonist, has not changed the immunologic status of the surviving child.     

建立母乳喂养1、2和3月时生长速率曲线——基于母乳与配方粉喂养的多中心随机对照试验

目的建立1~2月龄健康婴儿母乳喂养1、2和3月时的生长速率百分位曲线,为评价生长发育提供更全面的参考。方法采用多中心RCT方案,6个研究现场儿童保健科体检的胎龄37周、1~2月龄、性别不限、自动放弃母乳喂养的婴儿为配方粉组(按随机化原则分配至配方粉1亚组和配方粉2亚组),在相同研究现场与配方粉组单号性别、体重匹配的胎龄37周、1~2月龄、坚持母乳喂养的婴儿进入母乳组。主要观察指标为入组1、2和3月时身长、体重和头围的生长速率,月生长速率=[(本次随访的测量值-上次随访的测量值)/(本次实际随访时间-上次实际随访时间)天〗×30。次要观察指标:(1)入组1、2和3月时的大便形状和次数,根据婴儿家长手机拍摄新鲜大便照片按Bristol大便形状7分型图判断便型;(2)研究期间发生的不良事件。生长速率和便次、便型采用全分析集(FAS)分析,不良反应采用安全集(SS)分析。应用LMS软件,以偏度-中位数-变异系数(LMS)法表现入组1、2和3月时身长、体重和头围的生长速率的百分位数。结果 2016年5月6日至2016年10月30日征集到符合本研究纳入和排除标准的(SS集)配方粉组152名和母乳组72名,2组分别有24名和3名退出,FAS集分别为128名和69名。2组性别、入组时日龄、身长、体重、胎龄和生产方式差异无统计意义。(1)母乳组喂养1、2和3月时身长增长速率(厘米/月)分别为3.1±1.4、3.0±0.8和2.7±0.6,呈逐月下降趋势;体重增长速率(克/月)分别为951±371、824±278和749±219,呈逐月下降趋势;头围增长速率(厘米/月)分别为1.5±0.7、1.4±0.5和1.3±0.3,下降趋势缓慢。(2)在喂养1、2和3月时,配方粉组与母乳组身长、体重和头围增长速率差异均无统计学意义,亦呈逐月下降趋势。(3)入组时及喂养1、2和3月时,配方粉组大便次数和形状与母乳组差异有统计学意义。(4)224名(SS集)婴儿均未发生与配方粉或母乳喂养有直接关系的不良反应事件。结论 1~2月健康婴儿母乳喂养1、2和3月时身长、体重增长速率呈逐月下降趋势,头围增长速率下降趋势较身长和体重缓慢。配方粉喂养生长速率趋势同母乳。     

Multiple causes of asphyxia in infants at high risk for sudden infant death.

A wide range of clinical findings was present in 58 near-miss sudden infant death syndrome (SIDS) infants and 6 surviving twins of SIDS siblings. Specific investigations included: studies of gastro-oesophageal reflux and aspiration (24-hour oesophageal pH recordings, barium swallow, radionuclide ''milk-scan''); polygraphic studies of breathing, reflux, and sleep state; studies of upper airways disease (lateral airways radiography and endoscopy); detection of seizure activity by electroencephalography; evaluation of thiamine status by erythrocyte transketolase activity of venous blood. Thiamine deficiency was found in 12 of 43 tested infants; 5 of the deficient infants had a familial history of SIDS. Many potential mechanisms for asphyxia were found: idiopathic central apnoea (7 infants), tracheal obstruction from minimal tracheomalacia or aberrant innominate artery (4 infants), temporal lobe or generalised seizures (6 infants), gastro-oesophageal reflux (55 infants) with intrapulmonary aspiration (11 infants). The high incidence, severity, and timing of reflux were new findings. Reflux occurred in active and indeterminate sleep, but not in quiet sleep. The depression of respiratory reflexes by active sleep stresses the vulnerability to asphyxia. Two factors suggest that near-miss episodes are related to SIDS: the similar age distribution but earlier occurrence of near-miss episodes compared with age at death of SIDS infants, and the subsequent sudden death of 2 infants whose necropsies were consistent with SIDS.     

Stability of vitamin and mineral concentrations of a low-birth-weight infant formula during continuous enteral feeding

The stability of several vitamins and minerals of a new formula for premature infants, Similac Special Care, was examined following passage through a simulated continuous infusion apparatus designed to duplicate that used for continuous enteral feeding in infants. The concentrations of calcium, iron, zinc, copper, magnesium, vitamin A, vitamin C, and vitamin E were measured before and after infusion at rates appropriate for delivering 120 calories/kg to infants weighing 733 and 1,000 g. Following passage through this apparatus, significant reductions were noted for calcium (44-54%), iron (23-34%), and zinc (18-32%). Concentrations of copper, magnesium, and vitamins A, C, and E remained stable. When another formula commonly used for premature infants, Similac 24LBW, was subjected to similar analysis, the concentrations of all vitamins and minerals studied remained stable. Our study demonstrates that infants fed Similac Special Care by continuous infusion may not receive the quantity of calcium, iron, and zinc implied by the product label.     

腹泻期去乳糖奶粉辅助治疗婴儿急性腹泻的疗效观察

目的：探讨腹泻期去乳糖配方奶粉对婴儿急性腹泻病的辅助治疗作用。方法：采用严格的双盲、随机、对照等效性试验。120例婴儿急性腹泻病例被随机分为二组：去乳糖奶粉喂养组（去乳糖组）和常规奶粉喂养组（常规组），每组60例。两组均给予常规药物和口服补液治疗。观察1周后两组的治疗效果。结果：去乳糖组腹泻的治愈率及总有效率分别为58.3%和96.7%；常规组治愈率及总有效率分别为8.3%和85.0%，两组疗效的差异有显著性意义（P<0.05）。去乳糖组腹泻缓解天数为（3.17±1.04）d，明显低于常规组的（5.25±1.58）d （P<0.05）。治疗后去乳糖组大便菌群紊乱发生率亦低于常规组（P<0.05）。两组均无明显的不良事件发生。结论：去乳糖奶粉联合腹泻常规治疗方案治疗婴儿腹泻病能明显缩短病程，提高治疗效果。［中国当代儿科杂志，2009，11（7）：532-536］