Published online April 1, 2008
PEDIATRICS Vol. 121 No. 4 April 2008, pp. 766-776 (doi:10.1542/peds.2007-0054)
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ARTICLE

Growth and Nutrient Intakes of Human Milk–Fed Preterm Infants Provided With Extra Energy and Nutrients After Hospital Discharge

Deborah L. O'Connor, PhD, RDa,b,c, Sobia Khan, MSc, RDa,b,c, Karen Weishuhn, RDa,b,c, Jennifer Vaughan, RN, IBCLCa,c, Ann Jefferies, MDd,e, Douglas M. Campbell, MDd,f, Elizabeth Asztalos, MDd,g, Mark Feldman, MDd,h, Joanne Rovet, PhDd, Carol Westall, PhDi, Hilary Whyte, MDd,j on behalf of the Postdischarge Feeding Study Group

a Physiology and Experimental Medicine Program
b Department of Clinical Dietetics
j Department of Neonatology, Hospital for Sick Children, Toronto, Ontario, Canada
Departments of c Nutritional Sciences
d Pediatrics
i Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
e Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada
f Department of Pediatrics, St Michael's Hospital, Toronto, Ontario, Canada
g Department of Newborn and Developmental Pediatrics, Sunnybrook Hospital, Toronto, Ontario, Canada
h Department of Paediatrics, St Joseph's Health Centre, Toronto, Ontario, Canada


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVES. The purpose of this pilot study was to determine whether mixing a multinutrient fortifier to approximately one half of the human milk fed each day for a finite period after discharge improves the nutrient intake and growth of predominantly human milk–fed low birth weight infants. We also assessed the impact of this intervention on the exclusivity of human milk feeding.

METHODS. Human milk–fed (≥80% feeding per day) low birth weight (750–1800 g) infants (n = 39) were randomly assigned at hospital discharge to either a control or an intervention group. Infants in the control group were discharged from the hospital on unfortified human milk. Nutrient enrichment of human milk in the intervention group was achieved by mixing approximately one half of the human milk provided each day with a powdered multinutrient human milk fortifier for 12 weeks after discharge. Milk with added nutrients was estimated to contain ~80 kcal (336 kJ) and 2.2 g protein/100 mL plus other nutrients. Intensive lactation support was provided to both groups.

RESULTS. Infants in the intervention group were longer during the study period, and those born ≤1250 g had larger head circumferences than infants in the control group. There was a trend toward infants in the intervention group to be heavier at the end of the intervention compared with those in the control group. Mean protein, zinc, calcium, phosphorus, and vitamins A and D intakes were higher in the intervention group.

CONCLUSIONS. Results from this study suggest that adding a multinutrient fortifier to approximately one half of the milk provided to predominantly human milk–fed infants for 12 weeks after hospital discharge may be an effective strategy in addressing early discharge nutrient deficits and poor growth without unduly influencing human milk feeding when intensive lactation support is provided.

Key Words: low birth weight • premature infant • breastfeeding • human milk • growth

Abbreviations: LBW—low birth weight • GTA—greater Toronto area • CA—corrected age • SGA—small for gestational age • SAE—serious adverse event • VLBW—very low birth weight

In general, the earlier an infant is born before his or her expected term delivery date, the greater is their risk for morbidity and malnutrition.1,2 The reasons for undernutrition are widely known to clinicians and include that these low birth weight (LBW) infants are born with compromised nutrient reserves. Preterm infants often acquire nutrient deficits because initiation of parenteral nutrition and intralipids is frequently delayed; parenteral glucose and lipid solutions are poorly tolerated; and feedings are frequently withheld for clinical procedures, sepsis, or suspicion of necrotizing enterocolitis.3 Furthermore, comorbidities such as chronic lung disease limit the volume of feeding and/or route that nutrients are supplied, further complicating the provision of adequate nutrition.

Although more could be done to improve the nutritional status and growth of LBW infants during their initial hospitalization, it is becoming increasingly apparent that correction of acquired nutrient deficits is difficult to accomplish before discharge. In fact, many LBW infants leave the hospital with poorer nutritional status than when they started their postnatal life.3–8 For example, using weight-for-age centiles (<10th centile) as a crude indicator of nutritional status, Lemons et al6 demonstrated that whereas 22% of the 4500 VLBW infants who were born at 1 of the US Neonatal Network sites were at risk for undernutrition at birth, ~96% were so around the time of discharge. Furthermore, human milk–fed infants often accrue the greatest nutritional deficits by discharge.9 A plethora of review articles and position statements from authoritative bodies underscore the concern about the nutritional status of human milk–fed LBW infants after hospital discharge.2–4,10–13 In fact, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition recently recommended that human milk–fed preterm infants who are discharged from the hospital with subnormal weight for postconceptional age be routinely supplemented to provide an adequate nutrient supply.11 Despite the aforementioned concerns, recommendation, and the widely known advantages of human milk over formula feeding,14 no randomized, controlled trials have been conducted to ascertain whether multinutrient fortification of human milk after hospital would be beneficial. The objectives of this pilot study, then, were to determine whether mixing a multinutrient fortifier to approximately one half of mother's milk for 12 weeks after discharge would improve the nutrient intakes and growth of LBW (750–1800 g) infants. Because few data specific to the LBW infant exist suggesting what impact this intervention might have on human milk feeding, we also assessed the duration and exclusivity of human milk use.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Study Population
Primarily and exclusively human milk–fed infants and their mothers were enrolled between April 2004 and November 2005 from NICUs located in the greater Toronto area (GTA). These nurseries included Mount Sinai Hospital, Sunnybrook Hospital, The Credit Valley Hospital, St Joseph's Health Center, St Michael's Hospital, Scarborough Hospitals (Grace and General Divisions), Scarborough Centenary (Rouge Valley Health System), and Toronto East General Hospital. Singleton or twin infants (born <33 weeks’ gestational age and between 750 and 1800 g) who received ≥80% of their total feedings as human milk (fortified or unfortified) 3 days before hospital discharge were eligible to participate. Families agreed to feed their infants primarily human milk after hospital discharge and to supplement a predetermined volume of the human milk fed with a powdered multinutrient fortifier for 12 weeks if so randomly assigned. Infants with serious congenital or chromosomal anomalies that could affect growth were not eligible to participate. Other exclusion criteria were grade 3 or 4 periventricular or intraventricular hemorrhage, oral steroids within 14 days of randomization, severe asphyxia (hypoxia or ischemia characterized by an Apgar score of <5 at 5 minutes), and known maternal alcohol or drug abuse. Families were also ineligible when their principal residence was outside the GTA or when the mother was unable to communicate verbally in English. Last, infants were excluded from participation when any single feeding at hospital discharge needed to be nutrient enriched or concentrated to >24 kcal/fl oz (3800 kJ/L) or when >50% of the daily feeds required nutrient enrichment.

Experimental Design
The Human Ethics Committees at the Hospital for Sick Children and each of the aforementioned recruiting hospitals approved the study, which was conducted according to the policies and procedures of each institution and the Canadian Tri-council policy statement on ethical conduct of research involving human subjects.15 A computer-generated randomization schedule stratified for gender and birth weight group (≤1250 g, >1250 g) was prepared by 1 of the authors (Dr O'Connor), who was not involved in enrolling study participants. A separate randomization schedule was prepared for twins. For avoidance of biasing in-hospital feeding practices or which individuals were approached about the study, randomization assignments were placed in individually sealed envelopes that were opened the day before hospital discharge (study day 1).

Infants who were randomly assigned to the control group were discharged from the hospital on unfortified human milk (from breast or expressed), as is routine clinical practice in the GTA. For infants who were randomly assigned to the intervention group, our goal was to supply roughly half the volume of human milk as nutrient-enriched feedings after hospital discharge. Nutrient enrichment of human milk provided to infants in the intervention group was achieved by having caregivers mix a predetermined volume (150 mL x infant weight [kg]/2) of human milk (fresh or thawed) with a powdered multinutrient human milk fortifier (4 single-use packets [0.9 g each] per 100 mL of human milk; Table 1). Remaining feedings were to be provided as unfortified milk (from the breast or expressed). Using the milk intake data collected from term-corrected age (CA) breastfed preterm infants published by Wauben et al,16 we estimated that infants in this study would consume ~150 mL/kg per day around the time of hospital discharge. The exact volume (150 mL x infant weight [kg]/2) of nutrient-enriched feeding to be fed was determined by the study coordinator (Ms Vaughan) at discharge and recalculated at 4 and 8 weeks after discharge to accommodate changes in body weight. In combination with unfortified human milk feedings, the average daily energy and nutrient density provided to infants in the intervention group was predicted to be similar to those of infants who were fed commercially available nutrient-enriched formula designed for postdischarge feeding of preterm infants (eg, 22 kcal/fl oz [3100 kJ/L] and 18 g/L protein).2 Families could choose when during the day they wished to provide the nutrient-enriched feedings and whether they would use a bottle or supplemental nursing system.* Most families elected to use bottles. As is routine clinical practice in the GTA, infants in the control group were provided with vitamin drops consisting of vitamins A (1500 IU), D (400 IU), and C (30 mg) after discharge. For reduction of the possibility of inappropriately high intakes of fat soluble vitamins, infants who were randomly assigned to the intervention group were not provided with vitamins A and C and only 200 IU of vitamin D (ie, half the manufacturer recommended dosage of D-Vi-Sol [Mead Johnson Nutritionals, Ottawa, Ontario, Canada]). A daily iron supplement (15 mg/day) was prescribed for infants in both feeding groups.


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  		TABLE 1 Approximate Energy and Select Nutrient Composition of Mature Human Milk With and Without a Multinutrient Fortifier

 
An algorithm was created before study initiation to assess whether nutrient enrichment should be initiated for an infant in the control group who demonstrated poor growth. In general, when an infant's growth, as assessed by weight gain over >7-day period or 2 consecutive home visits, dropped by 2 percentile curves on the Infant Health and Development growth charts,17,18 a feeding intervention was initiated. The same was true when an infant demonstrated clinical signs (eg, low tone, lethargy) of poor intake and growth. It was at the discretion of the infant's pediatrician how nutrient enrichment was to be accomplished, but, in general, powdered postdischarge formula (eg, Similac Neosure) was added to human milk. The study coordinator, a certified lactation consultant, offered lactation support to mothers in both feeding groups. Mothers in both study groups were provided free of charge the vitamin/iron drops, feeding devices, and use of a double breast-expression electric breast pump (Purely Yours Breast Pump; Ameda, Mississauga, Ontario, Canada). Mothers in the intervention group were also provided the powdered human milk fortifier free of charge.

Demographic Data, In-hospital Tolerance, and Morbidity
Family characteristics of enrolled infants were obtained from a personal interview with 1 or both parents. This included mother's gravidity and parity as well as parental age, height, ethnicity, and years of education. Each infant's weight and gestational age at birth, size at birth (ie, small for gestational age [SGA]or appropriate for gestational age), and in-hospital course were obtained from medical charts. The last included the number of days that parental nutrition was provided, days to reach full enteral feeds (100 kcal/kg per day [420 kJ/kg per day]), and days the infant received nothing by mouth after reaching full enteral feeds. Morbidity outcomes such as the number of infants with a confirmed case of necrotizing enterocolitis (more than Bell stage II), systemic infection (positive blood culture), or chronic lung disease before study day 1 were also recorded. Chronic lung disease was defined as the need for supplemental oxygen beyond 1 month chronological age or 36 weeks’ postconception.

The number of serious adverse events (SAEs) or unexpected adverse events was determined from study day 1 until 12 weeks after hospital discharge. An SAE was defined as any event that occurred during the clinical trial that resulted in death or was life-threatening or disabling, required hospital admission, or required intervention to prevent permanent impairment.

Growth
The weight, length, and head circumference of infants was determined according to standardized procedures by the study coordinator at study day 1 and at 4 (±3 days), 8 (±3 days), and 12 (±3 days) weeks after hospital discharge during home visits.19 Infants were weighed twice in the nude using a precision scale (±2 g; Medela BabyWeigh; Medela, Mississauga, Ontario). Recumbent length and head circumference were measured twice to the nearest 0.1 cm with a lengthboard (Ellard Instrumentation, Munroe, WA) and nonstretchable tape measure (InserTape, Ross Canada, Abbott Laboratories, Montreal, Quebec, Canada), respectively.

Enteral Intake
Dietary intake diaries were mailed to parents 3 days before each home visit (4, 8, and 12 weeks after discharge). Information collected in these diaries included intake of human milk consumed at the breast, unfortified expressed breast milk, nutrient-fortified human milk, formula, cow milk, and juice. Parents were taught to record their infant's fluid intake regardless of source (eg, breast milk, expressed milk, formula, other) using a previously validated and standardized test-weighing procedure.20 The test-weighing protocol required a caregiver to weigh infants before and after every feeding for 3 consecutive days before the 4-, 8-, and 12-weeks post-discharge home visit, using the Medela BabyWeigh scale, which was specifically designed for this purpose. The increase in weight after each feeding (in grams) provides an estimate of the amount of milk (in milliliters) consumed. Parents were instructed not to change the infant or add or remove blankets or clothing between the pre- and postfeeding weights. Use of vitamin and mineral drops was also recorded in the food diaries. Energy and select nutrient intakes (protein, calcium, phosphorus, zinc, iron, vitamin A, and vitamin D) were estimated using human milk composition values from the literature, manufacturer label claims for infant formulas and the powdered human milk fortifier, and the Canadian Nutrient File.21

To capture changes in human milk feeding frequency between 3-day food diaries, the study coordinator at the 4-, 8-, and 12-week postdischarge home visits asked mothers to estimate the number of times each day that her infant was fed since hospital discharge or the last visit and the number of these feeding that were provided as human milk. When the mother was no longer providing human milk, she was asked to recall the date when human milk feeding was discontinued.

Statistical Analysis
We estimated a priori that 34 infants who completed the feeding intervention of this pilot study would allow us to detect a 1-SD difference in the mean weight of infants in the 2 feeding groups at 12 weeks after hospital discharge with 80% power at an {alpha} level of .05. All data were analyzed using SAS 9.1 for Windows (SAS Institute, Cary, NC). All statistical tests were 2-tailed using an {alpha}-level of .05. Data were checked to ensure that they were normally distributed (PROC UNIVARIATE) and, as appropriate, transformed. Demographic data were analyzed using t tests for continuous variables and {chi}2 tests for categorical variables. Continuous outcome data collected at >1 time point were analyzed using mixed repeated-measures analysis of variance, which accommodates missing observations controlling for gender and birth weight strata (750–1250 g or 1251–1800 g [PROC MIXED]). Growth rates from study day 1 to 4 weeks, study day 1 to 8 weeks, and study day 1 to 12 weeks were individually analyzed using analysis of variance (PROC GLM) controlling for gender and birth weight strata. Volume of human milk consumed at the breast and the intake of fortified human milk were not normally distributed; hence, nonparametric pairwise comparisons were completed for these 2 variables at each time point (Wilcoxon rank-sum test).

Given that infants who are SGA account for 25% of the preterm population in some nurseries, we elected to include these infants in this study. However, preterm infants who are SGA often exhibit a different growth pattern than preterm infants who are appropriate for gestational age, so all statistical analyses were rerun excluding infants who were SGA to ensure that their inclusion did not influence the study findings.22 In these latter statistical analyses, 1 infant who developed hydrocephalus during the study in the intervention group was also excluded.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Study Sample
Families of 143 infants who were known to be primarily human milk fed were provided an information letter about the study. Of these infants, 51 did not meet the eligibility criteria and 53 refused to participate. Of the infants who met the eligibility criteria, 29 were excluded because their primary residence was outside the GTA and/or their mother decided to formula feed after hospital discharge. Mothers of 22 infants did not want to use bottles, a breast pump, or a human milk fortifier. Of the 53 eligible infants, the main reasons for refusing to participate were (1) the study was too much for them or they were busy with other children at home, (2) it was too far to travel to clinic visits planned for after the feeding intervention phase, and (3) they were already participating in other research studies (Fig 1).


Figure 1
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  		FIGURE 1 Study sample recruitment flow chart.

 
For the remaining 39 infants, 20 were randomly assigned to the control group and 19 to the intervention group. We had sufficient data on 34 infants at 12 weeks after discharge to conduct an intention-to-treat analysis. There were 5 withdrawals in the study: 3 in the control group before study day 1 because of insufficient milk supply and 2 in the intervention group after study day 1 but before the 4-week home visit because of a sick infant and an overwhelmed mother who chose to withdraw from the study.

Infant and Family Demographics
Most baseline infant and family demographics, including infant weight, length, and head circumference, at study day 1 did not differ statistically between the 2 feeding groups (Table 2). There was a trend toward older gestational age at birth (29.8 ± 1.7 weeks) in the control versus intervention group (28.9 ± 1.2 weeks; P = .06) and fewer male infants in the control (11 of 20) versus intervention group (14 of 19; P = .07). The potential impact of these trends on outcomes was addressed by including the randomization strata (birth weight and gender) in all of the statistical analyses.


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  		TABLE 2 Neonatal Characteristics of the Study Population of Preterm Infants

 
Infants and their families were primarily white, and parents were well educated (Table 3). Domperidone (Motilium; Loudwater, High Wycombe, United Kingdom), a galactagogue prescribed as part of usual clinical practice in the GTA, was used by a significant number of women in both feeding groups (control: n = 12; intervention: n = 14) after hospital discharge.23


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  		TABLE 3 Family Characteristicsa

 
Growth
By the end of the study period, infants in the intervention group tended to be heavier (P = .07), and during the study period they were longer (P = .02) than infants in the control group (Table 4). Among infants who were ≤1250 g, those in the intervention group had a larger mean head circumference than those in the control group (P = .0009). The adjusted mean head circumferences of infants who were ≤1250 g in the control group were 32.5 ± 0.4, 34.7 ± 0.4, 36.6 ± 0.4, and 38.0 ± 0.4 cm at study day 1 and at 4, 8, and 12 weeks after discharge, respectively. Likewise, the adjusted mean head circumferences of infants who were ≤1250 g in the intervention group were 34.0 ± 0.3, 37.0 ± 0.3, 39.0 ± 0.3, and 40.6 ± 0.3 cm at study day 1 and at 4, 8, and 12 weeks after discharge, respectively. No difference in mean head circumference existed between feeding groups for infants born >1250 g.


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  		TABLE 4 Weight, Length and Head Circumference Measurements from Study Day 1 to 12 Weeks After Hospital Discharge

 
The aforementioned statistical analyses included all infants as randomly assigned (intention-to-treat) including 2 infants in the control group who were fed human milk that contained powdered discharge formula to increase the nutrient concentration of the human milk fed to address slow growth. All statistical analyses controlled for gender and birth weight strata (750–1250 g or 1251–1800 g). Re-analysis of these growth data without the infants who were SGA (n = 3) and a child who developed hydrocephalus after randomization did not appreciably change the results for length and head circumference, but the trend for a difference in weight between the 2 feeding groups disappeared.

A statistically significant difference was found between feeding groups among infants ≤1250 g in length gains (cm/wk) between study day 1 and 12 weeks after discharge (P = .009). There was a trend toward infants in the intervention group having more rapid head circumference gains versus the control group from study day 1 to 8 weeks after discharge (P = .09). This difference in head circumference gain was highly significant for infants born ≤1250 g up to 4 weeks after discharge (P < .0001). No differences in weight gains were observed between the feeding groups at any interval after discharge. When study day 1 anthropometrics (weight length or head circumference as appropriate) were added as a covariate to the statistical models, the results for length did not change, but a statistically significant difference in head circumference gain between feeding groups was observed from study day 1 to 12 weeks after discharge for infants born ≤1250 g (P = .03). There was a trend toward infants in the intervention group having greater weight gains to 4 weeks after discharge compared with infants in the control group (P = .05). These observed differences in length and head circumference gains early after hospital discharge are consistent with previous observations that infants are at greatest nutritional risk at this time.9,24 Re-analysis of the aforementioned growth gains without the infants who were SGA and a child who developed hydrocephalus after randomization did not appreciably change the results, and, if anything, P values were strengthened.

Enteral Intake
Most infants consumed at least 1 human milk feeding per day at the 12-week postdischarge visit; only 1 infant in the control group and a set of twins in the intervention group did not. Likewise, the percentage of daily feedings provided as human milk at the 4-, 8-, and 12-week postdischarge home visits did not differ between the control (81 ± 37%, 71 ± 40%, and 71 ± 38%) and intervention (82 ± 27%, 93 ± 10%, and 88 ± 15%) groups. Furthermore, the total volume of human milk consumed (all sources) did not differ between feeding groups (Table 5). As planned, approximately half of the total human milk consumed each day in the intervention group had human milk fortifier added. None of the aforementioned enteral intake results differed when the infants who were SGA and the infant with hydrocephalus were removed from the statistical analyses.


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  		TABLE 5 Intake Volumes (mL/kg per D) by Feeding Type at 4, 8, and 12 Weeks After Hospital Discharge

 
The mean volume of feedings (mL/kg per day) from any source (human milk + formula + other) was greater in the control than the intervention group at the 4-, 8-, and 12-week home visits (P = .02). Except for energy and iron intake, mean nutrient intakes of infants in the intervention group were greater than that of infants in the control group (Table 6). Because the iron content of both human milk and the human milk fortifier used in this study was low, the primary source of iron came from iron drops. These results did not change appreciably when the statistical analyses were rerun without the infants who were SGA and the infant with hydrocephalus; however, the difference in protein intake was no longer statistically significant (P = .06). The nutrient intakes of study infants were also compared with the recommended intakes for postdischarge feeding of preterm infants published by the Canadian Paediatric Society.25 Mean energy, protein, zinc, and iron intakes generally were just at or below recommended levels for both feeding groups (Table 6). Mean vitamin D and calcium intakes generally exceeded the recommended levels in the intervention but not in the control group.


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  		TABLE 6 Daily Energy and Select Nutrient Intake at 4, 8, and 12 Weeks After Hospital Discharge

 
For confirmation that intakes of vitamin A and D remained within a safe intake range among infants who were consuming nutrient-enriched human milk, intakes were compared with adverse effect levels as published by the Institute of Medicine Dietary Reference Intakes for term-born infants.26,27 This comparison demonstrated that mean vitamin D intakes (diet + vitamin and mineral drops) remained below the no observed adverse effect level of 1800 IU/day for infants 0 to 12 months.26 Likewise, mean vitamin A remained below the lowest observed adverse effect level of 6000 µg/day preformed vitamin A for infants who are younger than 1 year.27

Serious Adverse Events
Only 1 infant who was randomly assigned to the intervention group had an SAE, which consisted of 2 hospital admissions as a result of gastroesophageal disease. He was withdrawn soon after study day 1 at the request of his parents. This infant had not yet received the study human milk fortifier after hospital discharge.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Growth
Data from this pilot study suggest that LBW (<1800 g) infants who were fed human milk that contained extra nutrients for 12 weeks after hospital discharge were longer during the study period (P = .02), and those born ≤1250 g had larger head circumferences than infants who were sent home on human milk alone (P = .0009). There was a trend toward infants in the intervention group to be heavier at the end of the study period (5535 ± 766 g) compared with those in the control group (5042 ± 967 g; P = .07). All statistical models controlled for gender and birth weight strata (750–1250 g or 1251–1800 g). As far as we are aware, this is the first randomized, controlled trial conducted to evaluate the impact of adding energy and multiple nutrients to human milk fed to LBW infants after discharge.

The growth results for human milk–fed infants reported herein are consistent with observations of higher growth among LBW infants fed nutrient-enriched as opposed to a standard term formula after hospital discharge in most24,28–35 but not all studies.36,37 For example, Carver et al24 reported that infants (born <1800 g) who were fed a nutrient-enriched postdischarge formula (eg, 22 kcal/fl oz [3100 kJ/L], 19 g/L protein) weighed more and gained more weight until 2 months’ CA and were longer at 3 months’ CA compared with infants who were fed a standard term formula (20 kcal/fl oz [2800 kJ/L], 14 g/L protein). As was the case with human milk–fed infants in this study, infants in the study by Carver et al who had birth weights ≤1250 g and were fed nutrient-enriched feedings had larger head circumferences than LBW infants who were fed a standard term formula after hospital discharge.

Although published comparisons of infants who were fed standard term versus nutrient-enriched formula after hospital discharge differed considerably in experimental design, growth differences between feeding regimens most consistently occurred within the first few weeks of hospital discharge and among very low birth weight (VLBW) infants.11,24,32,38 This likely reflects the time frame and population at highest risk for malnutrition and that feeding strategies designed for term-born infants are probably insufficient to address nutrient deficits for VLBW formula-fed infants early after discharge. We know from our previous work with a large cohort of LBW preterm infants (n = 463) that human milk–fed infants may, in fact, be at increased nutritional risk at hospital discharge compared with their formula-fed counterparts.9

Estimated Energy and Nutrient Intakes
The estimated energy intakes (kcal/kg per day [kJ/kg per day]) of infants in our study did not differ between feeding groups, suggesting that human milk–fed LBW infants are able to compensate to some degree for the energy and/or nutrient density of their feeding. These observations are consistent with previously published comparisons among LBW infants who were fed standard term or nutrient-enriched formula after hospital discharge in which no differences in energy intake were observed.24,28,31 Furthermore, these data are consistent with that of a well-controlled study in which term-born infants exhibited an early capacity to upregulate intake in response to the energy density of formula provided.39 Although energy intakes of infants in both feeding groups in this study were generally just at or below those recommended, they are consistent with those reported by others who used a test-weighing procedure to measure human milk intake or weighed feeding bottles to estimate formula intake.16,29,31

Mean intakes of protein, calcium, phosphorus, vitamin A, vitamin D, and zinc differed between infants who were fed human milk that contained extra nutrients and those who were fed human milk alone. These data suggest that although infants fed human milk alone may be able to upregulate their intake to match the energy intake of infants in the intervention group, they were unable to compensate for the disproportionate concentration of several nutrients. Given that the intakes of protein, calcium, and zinc not only differed between feeding groups but also were consumed below recommended levels in the control group, we speculate that these nutrients in particular may be responsible, in part, for our observations of improved length and head circumference gains (cm/wk) among infants ≤1250 g in the intervention group immediately after hospital discharge. The lack of difference in weight gains (g/kg per day) may reflect the lack of a difference in energy intake.

Our intake data are consistent with the results from studies that demonstrated improved protein, vitamin D, calcium, phosphorus, and zinc intakes among infants who consumed nutrient-enriched formula compared with those who consumed standard term formula or human milk alone after hospital discharge.24,28–31,35 Lucas et al39 suggested that the higher calcium and phosphorus intakes among infants who consumed nutrient-enriched formula may have contributed to the observed increase in linear growth up to 9 months’ CA in their study. Brunton et al29 attributed the greater linear growth velocity and lean body mass accretion among infants who had bronchopulmonary dysplasia and were fed nutrient-enriched formula to higher protein and zinc intakes. Finally Wauben et al16 speculated that the higher percentage of body fat among LBW infants who were fed human milk after hospital discharge compared with infant formula (by parental choice) may have been attributable to lower calcium, phosphorus, and protein intakes.

As we extensively describe elsewhere, there are a number of approaches that could be used to provide extra nutrients to human milk–fed infants after discharge, each with its own set of strengths and limitations.2 One advantage of using a powdered human milk fortifier is that it minimizes the dilution of human milk. Limitations of using a powdered human milk fortifier include that they are not sterile and that these products were never designed or studied for use after hospital discharge. Unless carefully planned, using a powdered human milk fortifier to nutrient-enrich human milk after hospital discharge could result in inappropriately high intakes of certain nutrients, such as iron, vitamin A, and vitamin D. It is very important to note that different human milk fortifiers vary considerably in their nutrient content and are not interchangeable. To address some of the potential shortcomings of using the human milk fortifier that was used in this study (Similac Human Milk Fortifier), we altered the type and quantity of vitamin and mineral drops typically provided to human milk–fed LBW infants at discharge. Because the human milk fortifier that was used in this study was low in iron, infants were provided with iron drops (15 mg/day elemental iron) after hospital discharge, regardless of their feeding assignment. Instead of providing drops that contained vitamins A, D (400 IU), and C as we did in the control group, infants in the intervention group were given half the dosage of vitamin D (200 IU) and no vitamins A and C. Nutrient intakes from all sources in the intervention group were well below the lowest observed adverse effect level for vitamin A (6000 µg/day) and iron (40 mg/day) and below the no observed adverse effect level for vitamin D (1800 IU/day).26,27 Although the aforementioned adverse effect level cutoffs were established for healthy term-born infants, these data do suggest that adding this particular powdered human milk fortifier to approximately half of expressed human milk for a finite period of time after hospital discharge can be done in such a manner so as not to provide inappropriately high levels of select nutrients.

Impact of the Intervention on Human Milk Feeding
During the feeding intervention, we saw no differences between groups with respect to the number of infants who were being human milk fed, the total volume of human milk provided each day, or the percentage of daily feedings provided as human milk. At 12 weeks after discharge, 71 ± 38% and 88 ± 15.4% of daily feedings in the control and intervention groups, respectively, were provided as human milk. The percentage of infants who were still being fed human milk 12 weeks after discharge in this study is much higher than that reported in the literature and is likely because they were predominantly human milk fed at discharge and because of the significant amount of lactation support that they received at home.41–44

Clinical Application
We acknowledge that there our limitations with this study that need to be considered before applying it to practice. First, this is a pilot study and, hence, the sample size was small. Second, mothers in this study had access to an unusually high level of lactation support after hospital discharge: a lactation consultant, breast pumps, scales to measure milk intake, and the galactagogue domperidone to stimulate milk production. Confirmation of the findings reported herein in larger studies with lactation support levels more typically available are warranted. Given competing priorities of families at hospital discharge and the resultant low rate of willingness to participate in research studies, future studies require multicenter collaboration. In addition to the short-term growth and nutrient intake outcomes reported herein, the success or failure of this feeding intervention needs to include evaluation of longer term human milk feeding and developmental and body composition outcomes. Finally, whereas in this study the volume of human milk was directly assessed, literature values were used to estimate the energy and nutrient content of breast milk; therefore, ascribing a specific nutrient intake level to precise growth outcomes needs to be done with caution.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Results from this pilot study suggest that adding a multinutrient fortifier to approximately half of the milk that was fed to predominantly human milk–fed infants for 12 weeks after hospital discharge may be an effective strategy in addressing early discharge nutrient deficits and poor growth without unduly influencing human milk feeding when intensive lactation support is provided. In addition to the short-term growth and nutrient intake outcomes reported herein, future larger studies to evaluate the success or failure of this feeding intervention need to include an assessment of human milk feeding rates at 1 year and longer term developmental and body composition outcomes.


   ACKNOWLEDGMENTS
 
This study was supported by the Institute of Musculoskeletal Health and Arthritis, Canadian Institute of Health Research. Ms Khan and Ms Weishuhn received graduate student stipends from the Canadian Institute of Health Research Training Program in Clinical Nutrition Research.

The Postdischarge Feeding Study Group also included Kirsten Kotsopoulos (Mount Sinai Hospital), Kirsten McFadden and Pauline Darling (St Michael's Hospital), Andrea Nash (Sunnybrook Hospital), Debby Arts-Rodas (St Joseph's Health Care), Sandra Gabriele and Jaimie MacKinnon (Credit Valley Hospital), Peter Azzopardi (Scarborough Hospitals), and Jelena Popovic (Toronto East General).

We grateful to all of the families who participated in this study and especially thank the dietitians, nurses, and physicians who assisted with study recruitment at each site. We also thank Abbott Nutrition (Montreal, Quebec, Canada) and Mead Johnson Nutritionals (Ottawa, Ontario, Canada) for providing, at our request, the human milk fortifier and many of the disposable supplies used to collect and store human milk in this study.


   FOOTNOTES
 
Accepted Aug 27, 2007.

Address correspondence to Deborah L. O'Connor, PhD, RD, Room 8511C, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. E-mail: deborah_l.o'connor{at}sickkids.ca

* Usually made up of a plastic container serving as a reservoir for supplemental milk and a capillary tube extending from the reservoir and placed adjacent to the mother's nipple. Back

The authors have indicated they have no financial relationships relevant to this article to disclose.

This trial has been registered at www.clinicaltrials.gov (identifier NCT00413985).


What's Known on This Subject

Although more could be done to improve the nutritional status of low birth weight (LBW) infants during their initial hospitalization, it is apparent that correction of acquired nutrient-deficits for many very LBW infants is difficult to accomplish before discharge.

 

What This Study Adds

Adding a multi-nutrient fortifier to ~half of the milk provided to predominantly human milk-fed infants for 12 weeks after discharge may be an effective strategy in addressing early discharge nutrient-deficits without unduly influencing human milk feeding when lactation support is provided.

 


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Ehrenkranz RA, Younes N, Lemons JA, et al. Longitudinal growth of hospitalized very low birth weight infants. Pediatrics. 1999;104 (2 pt 1):280 –289[Abstract/Free Full Text]
  2. O'Connor DL, Merko S, Brennan J. Human milk feeding of very low birth weight infants during initial hospitalization and after discharge. Nutr Today. 2004;39 (3):102 –111[CrossRef]
  3. Griffin IJ. Postdischarge nutrition for high risk neonates. Clin Perinatol. 2002;29 (2):327 –344[CrossRef][Web of Science][Medline]
  4. Carlson SE. Feeding after discharge: growth, development and long-term effects. In: Tsang RC, Uauy R, Koletzko B, Zlotkin SH, eds. Nutrition of the Preterm Infant: Scientific Basis and Practical Guidelines. 2nd ed. Cincinnati, OH: Digital Educational Publishing, Inc; 2005:357–381
  5. Embleton NE, Pang N, Cooke RJ. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics. 2001;107 (2):270 –273[Abstract/Free Full Text]
  6. Lemons JA, Bauer CR, Oh W, et al. Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996. Pediatrics. 2001;107 (1). Available at: www.pediatrics.org/cgi/content/full/107/1/e1
  7. Lucas A. Nutrition, growth and development of postdischarge preterm infants. In: Silverman E, ed. Posthospital Nutrition in the Preterm Infant. Columbus, OH: Ross Products Division, Abbott Laboratories; 1996:81–89
  8. Merko S, Shah PS, Wong KY, et al. Nutrient intakes and growth of very preterm infants born <28 weeks gestation [abstract]. Can J Diet Pract Res. 2002;63 (2 Suppl):105
  9. O'Connor DL, Jacobs J, Hall R, et al. Growth and development of premature infants fed predominantly human milk, predominantly premature infant formula, or a combination of human milk and premature formula. J Pediatr Gastroenterol Nutr. 2003;37 (4):437 –446[Web of Science][Medline]
  10. American Academy of Pediatrics. Nutritional needs of the preterm infant. In: Klienman R, ed. Pediatric Nutrition Handbook. 5th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2004:23–54
  11. Aggett PJ, Agostoni C, Axelsson I, et al. Feeding preterm infants after hospital discharge: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2006;42 (5):596 –603[CrossRef][Web of Science][Medline]
  12. Greer FR. Feeding the preterm infant after hospital discharge. Pediatr Ann. 2001;30 (11):658 –665[Web of Science][Medline]
  13. Schanler RJ. Post-discharge nutrition for the preterm infant. Acta Paediatr Suppl. 2005;94 (449):68 –73[CrossRef][Medline]
  14. Gartner LM, Morton J, Lawrence RA, et al. Breastfeeding and the use of human milk. Pediatrics. 2005;115 (2):496 –506[Abstract/Free Full Text]
  15. Canadian Institute of Health Research, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada. Tri-council Policy Statement: Ethical Conduct for Research Involving Humans. Ottawa, Ontario, Canada: Public Works and Government Services; 1998
  16. Wauben IP, Atkinson SA, Shah JK, Paes B. Growth and body composition of preterm infants: influence of nutrient fortification of mother's milk in hospital and breastfeeding post-hospital discharge. Acta Paediatr. 1998;87 (7):780 –785[CrossRef][Web of Science][Medline]
  17. Casey PH, Kraemer HC, Bernbaum J, et al. Growth patterns of low birth weight preterm infants: a longitudinal analysis of a large, varied sample. J Pediatr. 1990;117 (2 pt 1):298 –307[CrossRef][Web of Science][Medline]
  18. Casey PH, Kraemer HC, Bernbaum J, Yogman MW, Sells JC. Growth status and growth rates of a varied sample of low birth weight, preterm infants: a longitudinal cohort from birth to three years of age. J Pediatr. 1991;119 (4):599 –605[CrossRef][Web of Science][Medline]
  19. Gibson R, ed. Principles of Nutritional Assessment. 2nd ed. New York, NY: Oxford University Press; 2005
  20. Woolridge M, Butte N, Dewey K, et al. Methods for the measurement of milk volume intake of the breast-fed infant. In: Jensen G, Neville MC, eds. Human Milk: Milk Components and Methodologies. New York, NY: Plenum Publishing Corp; 1985:5–21
  21. Health Canada. Food Program. Canadian nutrient file, 2001. Available at: www.hc-sc.gc.ca/food-ailment/ns-sc/nr-rn/surveillance/cnf-fcen/e_cnf_downloads.html. Accessed February 8, 2008
  22. Anderson D. Nutritional implications of premature birth, birth weight and gestational age classification. In: Groh-Wargo S, ed. Nutritional Care for High-Risk Newborns. 3rd ed. Chicago, IL: Precept Press, Inc; 2000:3–10
  23. da Silva OP, Knoppert DC. Domperidone for lactating women. CMAJ. 2004;171 (7):725 –726[Free Full Text]
  24. Carver JD, Wu PY, Hall RT, et al. Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge. Pediatrics. 2001;107 (4):683 –689[Abstract/Free Full Text]
  25. Nutrition Committee of the Canadian Paediatric Society. Nutrient needs and feeding of premature infants. CMAJ. 1995;152 (11):1765 –1781[Abstract]
  26. Institute of Medicine. Vitamin D. In: Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. Washington, DC: National Academy Press; 1997:250–287
  27. Institute of Medicine. Vitamin A. In: Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium and Zinc. Washington, DC: National Academy Press; 2001:82–161
  28. Atkinson S. Randomized trial of feeding nutrient-enriched vs standard formula to premature infants during the first year of life [abstract]. Pediatr Res. 1999;45 (Suppl):276A
  29. Brunton JA, Saigal S, Atkinson SA. Growth and body composition in infants with bronchopulmonary dysplasia up to 3 months corrected age: a randomized trial of a high-energy nutrient-enriched formula fed after hospital discharge. J Pediatr. 1998;133 (3):340 –345[CrossRef][Web of Science][Medline]
  30. Chan GM. Growth and bone mineral status of discharged very low birth weight infants fed different formulas or human milk. J Pediatr. 1993;123 (3):439 –443[CrossRef][Web of Science][Medline]
  31. Cooke RJ, Griffin IJ, McCormick K, et al. Feeding preterm infants after hospital discharge: effect of dietary manipulation on nutrient intake and growth. Pediatr Res. 1998;43 (3):355 –360[Web of Science][Medline]
  32. Lucas A, Fewtrell MS, Morley R, et al. Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants. Pediatrics. 2001;108 (3):703 –711[Abstract/Free Full Text]
  33. Wheeler RE, Hall RT. Feeding of premature infant formula after hospital discharge of infants weighing less than 1800 grams at birth. J Perinatol. 1996;16 (2 pt 1):111 –116[Medline]
  34. Worrell LA, Thorp JW, Tucker R, et al. The effects of the introduction of a high-nutrient transitional formula on growth and development of very-low-birth-weight infants. J Perinatol. 2002;22 (2):112 –119[CrossRef][Medline]
  35. Lapillonne A, Salle BL, Glorieux FH, Claris O. Bone mineralization and growth are enhanced in preterm infants fed an isocaloric, nutrient-enriched preterm formula through term. Am J Clin Nutr. 2004;80 (6):1595 –1603[Abstract/Free Full Text]
  36. De Curtis M, Pieltain C, Rigo J. Body composition in preterm infants fed standard term or enriched formula after hospital discharge. Eur J Nutr. 2002;41 (4):177 –182[CrossRef][Web of Science][Medline]
  37. Koo WW, Hockman EM. Posthospital discharge feeding for preterm infants: effects of standard compared with enriched milk formula on growth, bone mass, and body composition. Am J Clin Nutr. 2006;84 (6):1357 –1364[Abstract/Free Full Text]
  38. Cooke RJ, Embleton ND, Griffin IJ, Wells JC, McCormick KP. Feeding preterm infants after hospital discharge: growth and development at 18 months of age. Pediatr Res. 2001;49 (5):719 –722[Web of Science][Medline]
  39. Fomon SJ, Filmer LJ Jr, Thomas LN, Anderson TA, Nelson SE. Influence of formula concentration on caloric intake and growth of normal infants. Acta Paediatr Scand. 1975;64 (2):172 –181[Web of Science][Medline]
  40. Lucas A, Bishop NJ, King FJ, Cole TJ. Randomised trial of nutrition for preterm infants after discharge. Arch Dis Child. 1992;67 (3):324 –327[Abstract/Free Full Text]
  41. Callen J, Pinelli J. A review of the literature examining the benefits and challenges, incidence and duration, and barriers to breastfeeding in preterm infants. Adv Neonatal Care. 2005;5 (2):72 –88, quiz 89–92[CrossRef][Medline]
  42. Furman L, Minich N, Hack M. Correlates of lactation in mothers of very low birth weight infants. Pediatrics. 2002;109 (4). Available at: www.pediatrics.org/cgi/content/full/109/4/e57
  43. Kaufman KJ, Hall LA. Influences of the social network on choice and duration of breast-feeding in mothers of preterm infants. Res Nurs Health. 1989;12 (3):149 –159[Web of Science][Medline]
  44. Pinelli J, Atkinson SA, Saigal S. Randomized trial of breastfeeding support in very low-birth-weight infants. Arch Pediatr Adolesc Med. 2001;155 (5):548 –553[Abstract/Free Full Text]
  45. Institute of Medicine. Vitamin E. In: Dietary Reference Intakes For Vitamin C, Vitamin E, Selenium and Carotenoids. Washington, DC: National Academy Press; 2000:186–283
  46. Atkinson S. Effects of gestational stage at delivery on human milk components. In: Jensen R, ed. Handbook of Milk Composition. San Diego, CA: Academic Press; 1995:222–237
  47. Klein CJ. Nutrient requirements for preterm infant formulas. J Nutr. 2002;132 (6 Suppl 1):1395S –1577S[Abstract/Free Full Text]
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S. Groh-Wargo and A. Sapsford
Enteral Nutrition Support of the Preterm Infant in the Neonatal Intensive Care Unit
Nutr Clin Pract, June 1, 2009; 24(3): 363 - 376.
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