All you ever wanted to know about infant formulas (but were afraid to ask)

The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and health care professionals) will experiment with the infant formula available and often attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.     

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.     

Colic in breast-milk-fed infants: treatment by temporary substitution of neocate infant formula

Infant colic is a common problem characterized by excessive crying and fussing. We examined whether colic symptoms of exclusively breast-milk-fed infants would be improved by temporary substitution of Neocate, an amino acid-based infant formula, for breast milk. Six infants with colic were studied using Barr-type infant behavior diaries for a 3-5 d baseline period while they continued exclusive breast-milk-feeding, followed by a 4-8 d intervention period of exclusive Neocate feeding. All infants showed improvement in distressed behavior during intervention; five of the six improved within 1-2 d. For the period after 1 d of Neocate feeding, the total recorded crying and fussing time was reduced by an average of 42%, representing a decrease of 1.0 to 3.1 h daily. A significant difference was found between cry and fuss time at baseline versus during exclusive Neocate use. Concurrent with Neocate intervention, mothers strictly avoided all milk and dairy products. After colic symptoms improved, infants were reintroduced to breast milk, which was reasonably well tolerated in four of the six infants. Two infants had rapid recurrences of crying and fussing upon return to breastfeeding and required an additional period of Neocate feedings before subsequent reintroduction to breastfeeding. All infants exhibited colic symptoms when directly or indirectly challenged with bovine IgG (BGG), suggesting that BGG may play an etiologic role in colic. We propose that a brief intervention with Neocate, coupled with strict maternal avoidance of milk and dairy products under direct supervision of a lactation consultant, may be an effective treatment for colic in some breast-milk-fed infants.     

Treatment of infant colic with amino acid-based infant formula: a preliminary study

Infant colic, a common disorder of infancy, is characterized by excessive crying and fussing. In this preliminary study we examined whether Neocate, an amino acid-based formula, would be accepted by formula-fed infants with colic, 3-7 wk of age, and whether Neocate would improve their symptoms. Six infants with colic were studied using Barr-type infant behavior diaries for 3-6 d on their current formula and then for 5-17 d on Neocate exclusively. All infants tolerated Neocate well and all improved, usually within 1-2 d. The total time spent crying and fussing was reduced by an average of 45%, representing a decrease of 1.0 to 5.2 h daily. After colic symptoms improved, infants were challenged with oral doses of 75 mg of bovine IgG at a 1 mg/ml concentration in order to assess its potential role in colic. Bovine IgG challenges resulted in increased crying and fussing behavior, suggesting that this protein may be etiologically important.     

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.     

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.     

Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention:A prospective, randomized study

The aim of this study was to compare the allergy‐preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High‐risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five‐hundred and ninety‐five high‐risk infants were identified. High‐risk infants were defined as having bi‐parental atopy, or a single atopic first‐degree relative combined with cord blood immunoglobulin E (IgE) ≥ 0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast‐feed exclusively. If breast‐feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products, and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk‐based formula were given when needed. All infants were followed‐up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to non‐compliance. Of 478 infants who completed the study, 232 were exclusively breast‐fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast‐fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast‐feeding was high; only eight (2%) children were not breast‐fed at all. The three formula groups were identical in regard to duration of breast‐feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental‐reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p = 0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast‐fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7% (four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p = 0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency of atopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.     

Scientific rationale and benefits of nucleotide supplementation of infant formula

The present review examines the role of dietary nucleotides in infants, and the scientific rationale and benefits of nucleotide supplementation of infant formula. The immunoprotective benefits of human milk, the biology of human milk nucleotides, and the immunological and gastrointestinal effects of dietary nucleotides in animal studies and in vitro experiments are examined. Clinical studies are reviewed, especially those examining the efficacy of nucleotide-supplemented infant formula in enhancing immunity and reducing the risk of sepsis. The presence of human milk cells, and a variety of immunoactive and trophic components of human milk, can explain the reduced incidence of sepsis in breastfed term and preterm infants. Nucleotides, believed to play an immunomodulatory role, are found in lower concentrations in infant formula. Animal studies have shown that dietary nucleotides enhance a number of immune responses and the growth, differentiation and repair of the gut. Several clinical studies have reported beneficial effects of nucleotide supplementation on gut microflora, diarrhoea and immune function, and one study has reported better catch-up growth in term infants with severe intrauterine growth retardation. More basic research studying the metabolism of nucleotides in neonates is encouraged. Additional randomized controlled trials are necessary to demonstrate the clinical benefits of nucleotide supplementation of infant formula, as it cannot be presumed that nucleotides produce the same benefits for the infant as human milk. Studies are especially necessary in high-risk neonatal situations, such as extreme prematurity, significant suboptimal nutrient intake before and after birth, and recovery from gut injury.     

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.     

Enterobacter sakazakii and other bacteria in powdered infant milk formula

Recently there has been considerable concern related to the presence of bacteria, in particular Enterobacter sakazakii, in powdered infant formula milk. This paper considers the bacteria in these products at point of sale, with reference to current microbiological testing and the need for good hygienic practice in their subsequent preparation before feeding. The ingestion of raised numbers of E. sakazakii resulting from temperature abuse after reconstitution is highlighted as well as the uncertain routes of E. sakazakii product contamination.     

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.     

深度水解乳清蛋白配方奶粉改善婴儿湿疹的临床观察

目的了解深度水解乳清蛋白配方奶粉改善小婴儿头面部湿疹的作用。方法采用随机对照开放研究,将配方奶粉喂养或以配方奶粉喂养为主的头面部湿疹婴儿随机分为治疗组和对照组。所有入选婴儿均针对湿疹进行基础治疗,同时治疗组婴儿的配方奶粉改换为深度水解乳清蛋白配方奶粉,而对照组婴儿仍为普通配方奶粉。评价并记录就诊当日,治疗第7、14、28天时的婴儿皮损情况。结果治疗第14天,治疗组婴儿的湿疹EASI 4级评分、疗效指数、治疗显效率和痊愈率均高于对照组,差异有统计学意义(P均<0.05);第28天,治疗组婴儿湿疹痊愈后复发率明显低于对照组,差异有统计学意义(P<0.05)。结论深度水解乳清蛋白配方奶粉能有效改善部分婴儿湿疹。[临床儿科杂志,2012,30(5):438-441]     

Normal early infant behaviour patterns

As part of a wider study, infant behaviour was reviewed prospectively, using a 24 h diary completed by the mother. Infants' sleep, awake, fussing, crying and feeding behaviour were recorded at 1,2,4,6 and 8 weeks. Completed records were obtained from 21 infants. As expected most time was spent asleep, with a mean of 16.2 h at 1 week and 15.5 h at 8 weeks. Most sleeping occurred between midnight and 4 a.m. even by week 1 and there was a progressive fall in the average duration of feeding during that time interval over the 8 week period. Fussing and crying were mostly noted between 4 and 8 p.m. with an additional peak between 8 a.m. and noon, the latter disappearing by week 4. There was also a progressive drop in both the average feeding and fussing/crying times by week 8, reflecting increased settled and awake periods. It is against a background of normal early infant behaviour patterns that one can evaluate interventions aimed at altering such behaviour and dealing with the vexed problem of 'colic'.     

水解蛋白配方与婴幼儿牛奶过敏的预防和治疗

食物过敏是婴幼儿最早出现的过敏问题,牛奶是婴幼儿最常见的过敏食物。牛奶过敏的临床表现多种多样,可涉及皮肤、呼吸道、消化道等多器官多系统。母乳喂养是过敏高风险婴儿的首选喂养方式,但对不能进行母乳喂养的婴儿应选择适当的低敏配方奶,水解蛋白是获得低敏配方的最好方法。根据水解的程度,水解蛋白配方分为适度水解蛋白配方和完全水解蛋白配方。完全水解配方被推荐用于牛乳蛋白过敏婴儿的治疗,适度水解配方通常推荐用于特应质高风险婴儿的初级干预。     

Comprehensiveness of infant formula and bottle feeding resources: A review of information from Australian healthcare organisations

The use of infant formula is widespread internationally. In Australia, 55% of infants receive formula before 6 months of age, with higher rates among disadvantaged communities. Infant formula use can contribute to childhood overweight and obesity, through formula composition and feeding behaviours, such as adding cereal to bottles and parental feeding style. While information abounds to promote and support breastfeeding, formula‐feeding parents report a paucity of advice and support; many rely on formula packaging for information. This study systematically searched and reviewed online resources for infant formula and bottle feeding from Australian governments, health services, hospitals, and not‐for‐profit parenting organisations. A comprehensive search strategy located 74 current resources, mostly for parents. Researchers evaluated the resources against best practice criteria derived from Australian government and UNICEF guidelines on six topics. They assessed how comprehensively the resources addressed each topic and whether the resources provided all the information necessary for parents to understand each topic. The mean ‘comprehensiveness’ rating for topics across all resources was 54.36%. However, some topics were addressed more fully than others. Information on ‘discussing infant formula with health workers’ and on ‘preparing infant formula’ was more frequently accurate and comprehensive. However, there was much less comprehensive information on ‘using infant formula’, including amounts of formula to feed, use of bottle teats, appropriate bottle‐feeding practice and responsiveness to infant satiety cues. Over half the resources were written at an acceptable reading level.     

Post-discharge nutrition for the preterm infant

Newly designed, 'enriched,' formulas are now available for the formula feeding premature infant after hospital discharge. These new formulations add to the array of milks from which to choose when the discharge of the premature infant is approaching. However, the data to support optimal or reference nutrient intakes to use for the premature infant in the post-discharge are lacking. Breastfeeding should be encouraged as its beneficial effects may be related to the duration in which it is fed. Infants at risk for growth failure in the post-discharge period, such as infants unable to consume ad libitum intakes of milk, and who already have growth faltering or abnormal nutritional indices, may benefit for the addition of enriched formula. This review summarizes the recent data and comments on recommendations on post-discharge nutrition for premature infants.