深度水解蛋白配方奶治疗早产儿喂养不耐受的临床观察

目的:观察深度水解蛋白配方奶(eHF)治疗早产儿喂养不耐受及生长发育的疗效,与标准早产儿配方奶(SPF)及母乳喂养比较是否存在临床使用价值。方法:选取2014年4月至2015年9月我院收治的发生喂养不耐受且胎龄<34周的早产儿81例,随机分成三组: eHF组29例,予eHF喂养达全胃肠内营养后改SPF喂养;SPF组26例,予SPF喂养至出院;母乳组26例,坚持母乳喂养至出院,其中有9例因无法提供母乳退出该组,实际入组17例。记录患儿临床资料,比较三组之间喂养耐受性、宫外发育迟缓(EUGR)和新生儿坏死性小肠结肠炎(NEC)的发生情况。结果: eHF组与母乳组的胃残留次数、胃残留比比较差异无 统计学意义(P>0.05),但较SPF组均明显减少(P<0.05); eHF组与母乳组的肠内营养达基础热卡时间、达全胃肠道营养时间均明显短于SPF组(P<0.05),但eHF组与母乳组比较差异无统计学意义(P>0.05)。eHF组EUGR及NEC发生率与母乳组、SPF组比较差异无统计学意义(P>0.05)。结论:无充足母乳供应时,对喂养不耐受的早产儿予eHF喂养较SPF喂养耐受性更好,能更快达到全胃肠内喂养,且不会增加EUGR及NEC的发生率。     

Selenium status of Christchurch infants and the effect of diet.

OBJECT: New Zealanders, because of a soil deficiency, have a low intake of selenium. To determine the impact of this on the infant population in Christchurch. METHODS: we have measured red cell and plasma selenium and the selenoenzyme, glutathione peroxidase, in 70 infants less than 12 months old and related these to age and diet. RESULTS: the infant population as a whole had mean plasma levels of selenium and glutathione peroxidase of 33 micrograms/L and 97 U/L compared with adult values of 74 micrograms/L and 150 U/L. Infant red cell levels of 0.30 mu g selenium and 9.0 U glutathione peroxidase per g haemoglobin were similar to those in adults. The selenium status of most breast fed infants after birth remained similar to that of cord blood. Mean plasma selenium and glutathione peroxidase levels in formula fed infants were about half those of breast fed infants, and their red cell selenium was also significantly lower. These did not increase until solids were introduced into the diet. The status of the infants reflected their diet, with the concentration of selenium in formulae being 3.9-5.2 micrograms/mL compared with a mean of 13.4 micrograms/mL in breast milk. CONCLUSIONS: since infants in more replete selenium areas show a gradual rise in blood selenium parameters after birth, this study suggests that formula fed and some breast fed infants in Christchurch receive an inadequate selenium intake. Consideration should be given to supplementing infant formulae and perhaps also the diet of pregnant and/or breast feeding mothers.     

A comparative trial of casein or whey-predominant formulae in healthy infants

This study compared two infant formulae, one casein-predominant, Vitamilk and the other whey-predominant, Nurture. The nutritional components of Nurture were modified to be more similar to breast milk. This was a six week prospective double blind study of 100 healthy infants whose mothers had decided to bottle feed. The infants receiving Nurture showed significantly greater weight gain (p less than 0.005) and growth in head circumference (p less than 0.05) than those given Vitamilk. Analysis of the red cell membrane fatty acid profiles of the two groups showed significant differences which reflected the different fatty acids in the formulae. Nurture fed infants had significantly higher oleic and linoleic acid levels (p less than 0.001) and similar arachidonic acid levels to those fed Vitamilk. In both groups the concentrations of the essential fatty acids linoleic and linolenic were satisfactory. The blood urea concentrations were significantly lower (p less than 0.001) and the serum albumin concentrations significantly higher (p less than 0.01) in the infants fed Nurture. The formulae were well tolerated by all but seven infants. Four infants fed Vitamilk changed to a different formula because of constipation accompanied by sleeping problems, while three of those fed Nurture were changed, one for constipation and two with an atopic family history because of rashes and other symptoms. Constipation was significantly less frequent (p less than 0.01) in the infants receiving Nurture. While both formulae are satisfactory milk preparations for healthy infants, Nurture appeared to be superior.     

How much energy does the breast fed infant consume and expend?

Energy intake in breast fed infants is uncertain. The doubly labelled water method was used to measure, simultaneously and non-invasively, energy expenditure, energy intake, milk volume intake, energy deposition, and the energy content of breast milk in 12 "free living" breast fed babies at 5 and 11 weeks of age. The validity of this new approach was assessed in a parallel study in 12 formula fed infants. The babies who were exclusively breast fed expended 1.28 and 1.68 MJ/day at five and 11 weeks and had intakes of 1.81 and 2.22 MJ/day; these intakes were associated with normal growth but were well below those recommended previously. At five and 11 weeks the calculated energy content of breast milk was 0.24 and 0.25 MJ/100 ml, which is substantially lower than that commonly reported in milk obtained unphysiologically by expression of the breast. These data cast doubt on the widely used published standards for infant feeding.     

The excretion of dothiepin and its primary metabolites in breast milk.

1. The excretion of dothiepin, nordothiepin, dothiepin-S-oxide and nordothiepin-S-oxide into breast milk was studied in eight women. Exposure to drug was measured in five of their infants, and possible drug-related effects were assessed in all eight infants. 2. Using pre-feed milk samples mean (+/- s.e. mean) milk:plasma (M:P) ratios were 0.78 +/- 0.12, 0.85 +/- 0.16, 1.18 +/- 0.29 and 1.86 +/- 0.29 for dothiepin, nordothiepin, dothiepin-S-oxide and nordothiepin-S-oxide, respectively. In post-feed milk samples, the mean M:P ratio for dothiepin (1.59 +/- 0.32) was significantly greater (P less than 0.05) but M:P ratios for the metabolites were similar. 3. Mean total calculated infant daily doses, (in dothiepin equivalents and as a percent of the maternal dose) were 0.58% for dothiepin, 0.23% for nordothiepin, 2.47% for dothiepin-S-oxide, and 1.17% for nordothiepin-S-oxide. 4. Plasma samples were obtained from five infants. In one, both dothiepin and nordothiepin were below their minimum quantifiable levels (2 micrograms l-1) while in four others both dothiepin-S-oxide and nordothiepin-S-oxide were below their minimum quantifiable levels (10 micrograms l-1). No adverse effects were found in any of the eight infants. 5. Use of dothiepin by depressed mothers is unlikely to be a significant hazard to their breast-feeding infants.     

Valproic acid in breast milk: how much is really there?

Valproic acid (VPA) concentrations were measured by a sensitive and highly specific gas chromatographic/mass spectrometric assay in breast milk from 16 patients treated with VPA during 17 lactation periods. The range of VPA levels in 36 breast milk samples was 0.4-3.9 micrograms/ml (mean 1.9 +/- 1.2 microgram/ml). During the investigations of breast milk it was found that the concentration of total VPA in breast milk was not much higher than that of unbound VPA. These findings agree with clinical observations of infants fed with milk from VPA-treated mothers.     

早产儿母乳喂养中应用母乳强化剂的可行性分析

目的:探讨早产儿母乳喂养中应用母乳强化剂的可行性。方法:出生胎龄<34周、出生体重<2000g的200例早产儿分为强化母乳组(试验组)和早产院内配方奶组(对照组)各100例,试验组开始用早产母乳喂养,当喂养量达到100ml/(kg·d)时开始添加母乳强化剂;对照组全部用早产院内配方奶喂养。对两组的体格生长速度、合并症进行比较。结果:试验组和对照组的早产儿体重、身长、头围的增长速度非常相近,两组早产儿喂养不耐受、坏死性小肠结肠炎、院内感染的发生率无统计学意义(P>0.05)。结论:母乳喂养中应用母乳强化剂进行喂养下的早产儿住院期间体格生长速度、合并症发生率与早产配方奶喂养的早产儿相似。     

Characterization of the penetration of garenoxacin into the breast milk of lactating women

The primary objective of this study was to characterize the extent of excretion of garenoxacin, a novel des-F(6)-quinolone antimicrobial, into the breast milk of lactating women. A secondary objective was to determine the time after dose administration that garenoxacin was no longer detected in breast milk so as to define when a mother may resume breastfeeding if it was interrupted for garenoxacin administration. Six healthy, lactating women (age [mean +/- SD]: 32 +/- 6 years; weight: 68.3 +/- 19.8 kg; body mass index: 26 +/- 5 kg/m(2)) who had completed weaning their infants were administered a single 600-mg oral dose of garenoxacin. Plasma samples were collected predose and repeatedly up to 72 hours postdose. Breast milk was collected predose and for 6- to 12-hour intervals repeatedly up to 120 hours postdose. Breast milk/plasma concentration ratios for garenoxacin ranged from 0.35 to 0.44 up to 24 hours postdose, and the mean peak breast milk concentration was 3.0 microg/mL (0- to 6-h collection interval). Overall, garenoxacin exposure in breast milk was minimal, with a mean of 0.07% of the administered dose recovered within 120 hours. Indeed, garenoxacin was undetectable in the breast milk of a majority of subjects within 84 hours of dosing. As such, an infant nursing from a mother who had received a single 600-mg oral dose of garenoxacin could theoretically be exposed to 0.42 mg of garenoxacin (0.105 mg/kg/day for a 4-kg infant over the period of 5 days of nursing). If extrapolated to a 14-day course of garenoxacin 600 mg once daily, total exposure would be approximately 5.88 mg. These findings indicate that, like other quinolone antimicrobials, garenoxacin is secreted in breast milk.     

1144例婴儿喂养方式与疾病的关系

目的 探讨不同喂养方式对婴儿疾病的影响，进一步促进母乳喂养。方法 对1144例4个月内住院婴儿喂养方式与疾病的关系进行临床分析。结果 健康婴儿母乳喂养率高于疾病婴儿的母乳喂养率；母乳喂养较人工喂养儿的病程短；喂养方式与城乡、婴儿性别关系不大。结论 婴儿喂养方式与患病及病程密切相关，提高母乳喂养率能减少疾病，缩短病程。     

Disopyramide and its N-monodesalkyl metabolite in breast milk.

The plasma and breast milk were sampled from a woman who was breastfeeding whilst taking disopyramide (200 mg three times daily). Paired samples taken on the fifth to eighth day of treatment showed that disopyramide was present in breast milk in a similar concentration to plasma (mean +/- s.d. milk; plasma ratio 0.9 +/- 0.17). The estimated dose likely to be ingested by an infant is less than 2 mg kg-1 day-1. The active N-monodesalkyl metabolite of disopyramide (NMD) although present in plasma in much smaller concentrations than the parent compound, was excreted in breast milk (mean +/- s.d. milk: plasma ratio 5.6 +/2.9) in concentrations similar to those of disopyramide. The pharmacological and toxicological properties of the disopyramide metabolite need to be considered when assessing likely effects on the infant. No adverse effects were noted in the infant in this case. Maternal plasma and breast milk were sampled again along with infant plasma after 28 days. Disopyramide and NMD were undetectable in the infant's serum. No evidence was found to indicate that the concentrations of disopyramide or NMD in breast milk might be sufficient to pose a definite risk to the infant. Whenever disopyramide is prescribed in a breast feeding mother, close observation of the baby and measurement of both disopyramide and its active metabolite NMD in breast milk or infant plasma is recommended, pending further investigation.     

Citalopram and demethylcitalopram in human milk; distribution, excretion and effects in breast fed infants

AIMS: To characterize milk/plasma (M/P) ratio and infant dose, for citalopram and demethylcitalopram, in breast-feeding women taking citalopram for the treatment of depression, and to determine the plasma concentration and effects of these drugs in their infants. METHODS: Seven women (mean age 30.6 years) taking citalopram (median dose 0.36 mg kg(-1) day(-1)) and their infants (mean age 4.1 months) were studied. Citalopram and demethylcitalopram in plasma and milk were measured by high-performance liquid chromatography over a 24 h dose interval. Infant exposure was estimated (two separate methods) as the product of milk production rate and drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. RESULTS: Mean M/PAUC values of 1.8 (range 1.2-3) and 1.8 (range 1.0-2.5) were calculated for citalopram and demethylcitalopram, respectively. The mean maximum concentrations of citalopram and demethylcitalopram in milk were 154 (95% CI, 102-207) microg l(-1) and 50 (23-77) microg l(-1). Depending on the method of calculation, mean infant exposure was 3.2 or 3.7% for citalopram and 1.2 or 1.4% for demethylcitalopram. Citalopram (2.0, 2.3 and 2.3 microg l(-1)) was detected in three of the seven infants. Demethylcitalopram (2.2 and 2.2 microg l(-1) was detected in plasma from two of the same infants. No adverse effects were seen in the infants, all were within appropriate percentile limits for weight and all had normal Denver developmental quotients. CONCLUSIONS: The mean combined dose of citalopram and demethylcitalopram (4.4-5.1% as citalopram equivalents) transmitted to infants via breast milk is below the 10% notional level of concern. Plasma concentrations of these drugs in the infants were very low or absent and there were no adverse effects. These data support the safety of the use of citalopram in breast feeding women. Nevertheless, each decision to breast feed should always be made as an individual risk:benefit analysis.     

The content of some trace elements in infant milk foods and supplements available in New Zealand.

The concentrations of iron, copper, zinc, manganese, nickel, cadmium and lead are reported for milk foods and supplements offered to infants before the introduction of mixed feeding. Levels of most of the trace elements in samples of breast milk and homogenised cows' milk were within the ranges reported overseas. Most of the milk products should supply adequate amounts of iron, copper, manganese and nickel to the young infant although zinc intakes may be marginal. Concentrations of cadmium and lead were well below the maximum values permitted by law.     

Excretion of chloroquine and desethylchloroquine in human milk

The excretion of chloroquine and the major metabolite, desethylchloroquine, in breast milk was investigated in eleven lactating mothers following a single oral dose of chloroquine (600 mg base). The average milk to plasma concentration ratio at the 24th hour was 6.6 +/- 2.4 for chloroquine and 1.5 +/- 0.6 for desethylchloroquine in five of the volunteers. In five other volunteers the elimination half-life of chloroquine in milk was 8.8 +/- 4.7 days which was longer than that in saliva (3.9 +/- 1.0 days) from the same volunteers. The maximum daily dose of the drug that the infant can receive from breastfeeding was about 0.7% of the maternal start dose of the drug in malaria chemotherapy. It is, therefore, suggested that it is safe for mothers to breastfeed their infants when undergoing treatment for malaria with chloroquine.     

Antidepressants and breast-feeding: a review of the literature

For every antidepressant so far investigated in the breast milk of mothers prescribed these medications, findings indicate that some amount of drug will be excreted into the breast milk. Nursing infants will be exposed to some, usually a very low, amount of drug and drug metabolites. Levels of drug exposure to infants for the many antidepressants available are examined, discussing milk to plasma drug concentration ratios and the infant dose as a percentage of the maternal dose. Drug concentrations in infant plasma and adverse effects of drug exposures to infants are reviewed. Factors influencing the decision on whether to breast or bottle feed an infant nursed by a mother taking antidepressants are discussed, concluding that the decision needs to be made on an individual basis. The lactating mother, in consultation with her doctor, should be in a position to make an informed decision on whether or not to breast feed. Under certain circumstances the decision to bottle feed may be wise, but more commonly the advantages of breast-feeding will outweigh the very low risk of an adverse event from drug exposure to the infant.     

Bioavailability of cadmium from infant diets in newborn rats

Infants are exposed to higher levels of cadmium (Cd) from infant and follow-on formulas than from breast milk. We studied the bioavailability of 109CdCl2 from cows' milk formula, soy formula, wheat/oat/milk formula, wholemeal/milk formula and water in 11-day-old rat pups. The pups received a single oral dose of one diet labelled with 109Cd, 0.1 or 0.3 mg Cd/kg body weight. After 2 or 24 h or 4, 9 or 12 days the fractional retention of 109Cd in the whole body, in segments of rinsed small intestine and in tissue was measured in a gamma counter. Pups receiving 109Cd in water or cows' milk formula had the highest mean whole-body retention. It ranged from 67% of the dose in the water group to 52% in the wholemeal/milk formula group 4 days after dosing. The retention of 109Cd in the rinsed small intestine was significantly higher in the water group and the cows' milk formula group than in the cereal-based formula groups at 24 h and 4 days after dosing. It was still high in all groups on day 9, ranging from 26 to 11%. Initially most of the 109Cd was retained in the duodenum but by day 4 it had moved further down into the jejunum. In the liver, the highest and lowest retention on day 4 was 16%, and 3 per thousand of the dose in the water group and wholemeal/milk formula group, respectively. In the kidney, 109Cd was still increasing 12 days after exposure in all groups. Whole-body retention and tissue levels were higher than previously reported in adult animals. The lower bioavailability of 109Cd from the cereal-based formulas compared to water and cows milk formula on the longer survival times is most likely explained by Cd binding to dietary fibre and phytic acid in the cereal-based formulas reducing the intestinal binding and decreasing the bioavailability of Cd. The high retention of 109Cd in the small intestine, leading to a prolonged absorption period, emphasizes the importance of extending studies on neonatal Cd absorption over a long time period in order to detect for example, endpoints, accumulation of Cd in the kidney.     

Vitamin A status of term and preterm infants delivered at Harare Central Hospital and fed exclusively on breast milk

OBJECTIVE: To investigate the vitamin A status of pregnant mothers, lactating mothers, preterm and term infants who were being fed exclusively on breast milk. DESIGN: Systematic/cross sectional. SETTING: Vitamin A research laboratory, animal science research laboratory, University of Zimbabwe, and Harare Central Hospital. SUBJECTS: 105 pregnant mothers attending the antenatal clinic at Harare Central Hospital for a routine check up were recruited for the study. Two groups of infants: those born at term and those with gestational age < or = 36 weeks. MAIN OUTCOME MEASURES: Serum retinol levels of infants/mothers pairs. Breast milk retinol levels. RESULT: The serum retinol levels for the infants were similar irrespective of age with a mean of 26.15 +/- 9.78 microg/dl. There was no statistically significant difference. The mean serum retinol levels of infants and mothers were significantly different, (p = 0.001). With mother/infant ratio of serum retinol concentration of 1.7:1. Maternal serum retinol levels correlated positively with infant serum retinol levels, r = 0.728. Forty four percent of the preterm and 17% of the term infants had serum retinol levels < 20 microg/dl, indicating deficiency, 2 and only 20% of the infants had retinol levels > 40 microg/dl. CONCLUSION: The majority of infants might be at risk of vitamin A deficiency. Increased intake of vitamin A in pregnant women is necessary, and direct vitamin A supplementation of infants should be considered.     

Transfer of carisoprodol to breast milk

There is no published information on the transfer of the centrally acting muscle relaxant carisoprodol and its active metabolite meprobamate into breast milk. The objective of this study was to quantify the excretion of carisoprodol and meprobamate in human milk and estimate the dose received by breast-fed infants. The concentrations of carisoprodol and meprobamate were measured in breast milk on 4 consecutive days at steady-state conditions in one woman using carisoprodol 2100 mg/d. The average milk concentrations were 0.9 microg/mL for carisoprodol and 11.6 microg/mL for meprobamate. Based on the milk concentrations measured, the absolute dose ingested by an exclusively breast-fed infant could be estimated at 1.9 mg/kg per day, and the relative dose would be 4.1% of the weight-adjusted maternal dose. No adverse effects were observed in the infant, but the infant was partly fed with formula because of insufficient maternal milk production. Thus, the authors consider that at least during prolonged use, lactation is generally inadvisable until more clinical data are available.     

Transfer of the antidepressant mirtazapine into breast milk

AIMS: To investigate the transfer of mirtazapine and desmethylmirtazapine into milk and to calculate dose to the infant via milk. METHODS: Plasma and milk samples were obtained from eight breast-feeding women who were taking a median dose of 38 mg mirtazapine per day. Milk/plasma ratio (M/P) and infant doses were estimated by standard methods. The infants were examined clinically and in four infants blood was taken for analysis. RESULTS: Mean (95% confidence interval) relative infant doses for mirtazapine and desmethylmirtazapine (n = 8) were 1.5% (0.8, 2.2) and 0.4% (0.2, 0.6) respectively. The mean M/P (area under curve n = 4, single or paired samples n = 3) was 1.1 (0.7,1.5) for mirtazapine and 0.6 (0.5, 0.7) for desmethylmirtazapine. No adverse effects were seen. Mirtazapine was detected (1.5 microg l(-1)) in only one of four infants tested. CONCLUSION: We suggest that mirtazapine use by lactating women is safe for the breast-fed infant. Nevertheless, each decision to breast feed should always be made on the basis of an individual risk/benefit analysis.     

早产儿出院后配方奶喂养有营养不良高危因素早产儿的疗效

目的观察早产儿出院后配方奶对具有营养不良高危因素的早产儿出院后喂养的效果。方法采用前瞻性研究,以2005年九省市中国儿童生长标准为对照,对具有营养不良高危因素的100例早产儿出院后采用早产儿出院后配方奶喂养,定期进行生长发育检测,当生长参数(头围、身高、体重)均达到相当月龄生长曲线第25百分位者即转换婴儿配方奶或者母乳,探索喂养时间的长短。矫正年龄1岁时,以头围、身高、体重作为评判指标,将生长指标≤P10(生长曲线第10百分位)定义为宫外生长发育迟缓,分别记录其发生率;应用贝利婴幼儿发展量表评估其智力发展指数与运动发展指数。结果本组病例中无退出病例,最短的喂养时间为4个月即转换奶粉,最长的喂养时间是12个月才转换奶粉,大部分为喂养7～11个月即转换奶粉,其中以喂养10月转换奶粉者为最多,为32例。矫正年龄1岁时以头围、身高、体重作为评判指标,宫外生长发育迟缓分别为3%、2%、2%,智力发展指数平均为(92.26±9.84),运动发展指数为(90.04±8.84)。结论早产儿出院后配方奶对具有营养不良高危因素的早产儿出院后喂养的效果较好,大部分喂养7～11个月即能够帮助其实现追赶性生长,矫正年龄1岁体格发育与神经系统发育大致正常。     

Hydromorphone transfer into breast milk after intranasal administration

STUDY OBJECTIVES: To determine the distribution of hydromorphone into breast milk and the potential exposure of the suckling infant, and whether the distribution of hydromorphone into milk can be predicted accurately by a passive diffusion model. DESIGN: Single-dose, pharmacokinetic study. SETTING: University clinical research unit. PATIENTS: Eight lactating, nonsmoking, healthy women aged 24-32 years. INTERVENTION: Hydromorphone HCl 2 mg was given intranasally to the women to characterize its pharmacokinetics and extent of its transfer into breast milk. MEASUREMENTS AND MAIN RESULTS: Plasma and milk samples were analyzed using liquid chromatography with tandem mass spectrometry detection. The milk:plasma ratio (M:P) was calculated as the total area under the concentration-time curve (AUC) of the milk divided by the total AUC of the plasma. Predicted in vitro M:P ratios were calculated using a diffusion model. Protein binding in milk and plasma, partitioning into milk fat (whole milk:skim milk ratios), as well as pH partitioning between plasma and milk were incorporated in the model. Protein binding was determined by equilibrium dialysis. Protein binding was minimal in both milk and plasma, with unbound fractions of 1 and 0.84, respectively There was little partitioning into milk fat, as demonstrated by the whole milk:skim milk ratio of 0.98. The observed and predicted M:P ratios +/- SD for hydromorphone were 2.57 +/- 0.47 and 1.11 +/- 0.28, respectively. The 95% confidence interval for the observed M:P ratio overlapped the confidence interval of the predicted M:P ratio, a finding that supports a role for both passive diffusion and active transport as mechanisms of hydromorphone transfer into milk. CONCLUSION: Hydromorphone distributes rapidly from plasma into breast milk; however, the drug does not partition into fat. The suckling infant would receive approximately 0.67% of the maternal dose of hydromorphone (adjusted for body weight). As this is a limited exposure, further studies are needed to determine any potential impact to an infant who is fed breast milk from a mother treated with hydromorphone.