There is currently insufficient evidence to determine whether feeding preterm infants in response to their own hunger cues is better than feeding set volumes of milk at pre-defined intervals. We identified seven small trials that examined this issue, but in general these were methodologically flawed and did not report on important clinical outcomes. Further randomised controlled trials are needed to address this question.
Various alternatives to a strict scheduled interval feeding regime for preterm infants have been described (Crosson 2004). These feeding strategies aim to respond to infant hunger cues and are particularly relevant to infants who are in the transition phase from gastric tube feeding to oral feeding (either breast, or bottle, or cup-feeding). At this stage (from about 32-34 weeks post-conceptional age), preterm infants are usually developing sustained alert activity and a coordinated suck-swallow-breathe pattern (Bu'lock 1990; Holditch-Davis 2003).
Crosson 2004 has
categorised these alternative feeding regimes as:
1. "Ad libitum feeding":
The enteral feed starts in response to the infant's hunger cues and ends when
the infant demonstrates satiation. The infant therefore determines the duration
and volume of intake.
2. "Demand feeding": The feed starts in response to the
infant's hunger cues but ends when a prescribed volume of intake is reached.
This strategy is more suited to infants who are receiving gastric tube feeds, or
who are fed orally from a bottle or cup. It is much more difficult to determine
when the target volume of intake has been reached in breast fed infants.
3.
"Semi-demand feeding": The infant's hunger cues are assessed at scheduled
intervals. If hunger cues are noted the infant is offered a feed. If the infant
is sleeping the assessment is delayed (usually by about 30 - 60 minutes). If
hunger cues are then noted the infant is offered a feed. If the infant remains
asleep then the infant is given a gavage fed. The volume of intake is
prescribed.
Ad libitum or demand/semi-demand feeding regimes may be considered a part of an integrated approach to providing "developmental care" for preterm infants. The Cochrane review of other related components of developmental care found some evidence that interventions such as minimising unnecessary exposure to external stimuli and clustering of care activities increases nutrient intake and rates of growth, and decreases the length of hospital stay (Symington 2003). Allowing preterm infants to dictate the timing and duration of enteral feeding may result in longer rest periods between some feeds, promote infant-determined sleep/wake patterns that reduce unnecessary energy expenditure, and increase the total nutrient intake and increase growth rates (McCain 2003). It is also possible that allowing the infant to determine the pattern of enteral feeding will help in the development of organised behaviour states and the earlier establishment of full oral feeding, a key criterion for hospital discharge for preterm infants (AAP 1998). There may be other benefits for the family and caregivers, principally allowing parents to feel more directly involved with their infant's care and increasing their confidence and ability to recognise and respond to their infant's needs during their hospital stay and beyond.
Potential adverse effects of an ad libitum or demand/semi-demand regime for feeding preterm infants are also recognised. These mainly relate to whether such a regime can guarantee metabolic stability, particularly normoglycaemia, in this clinically vulnerable group. Even at the point of discharge from hospital, some preterm infants are known to be susceptible to hypoglycaemia if a scheduled enteral feed is omitted or delayed (Hume 1999). There is concern that repeated or prolonged episodes of hypoglycaemia may impair longer term growth and development (Duvanel 1999). There may be more acute problems relating to gastro-intestinal immaturity such as feeding intolerance and a higher risk of aspiration of gastric contents into the lungs. There are also concerns that allowing unrestrained volumes of enteral intake may increase the risk of necrotising enterocolitis (Kennedy 2000).
If sufficient data were available, we planned to undertake additional
subgroup analyses of:
1. Trials where all participating infants were
enterally fed via gastric tubes (no oral feeding).
2. Trial where
participating infants were in transition from gastric tube to oral feeds.
3.
Trials where all participating infants were fed orally (no gastric tube
feeding).
4. Trials where all participating infants were exclusively fed from
the breast.
5. Trials where the infants' responses to non-nutritive sucking
were used to assess hunger.
6. Cluster randomised controlled trials.
Control:
Scheduled interval feeding: Feeds are given at scheduled
intervals without regard to the infant's sleep or hunger status. Orally fed
infants who are asleep are awakened to feed, or fed via an enteral feeding tube
if unable to be awoken sufficiently.
The infants in the comparison groups in each trial must have received the same type(s) of milk. Trials where the type of milk is a co-intervention were not eligible for inclusion (unless as part of a factorial design in the randomised controlled trial). Infant hunger cues included crying, quiet wakefulness, hand to mouth gestures, finger/fist sucking. Other hunger cues used by individual trialists were acceptable provided these had been defined in the trial protocol. Trials that used the response to non-nutritive sucking on a pacifier as a tool for assessing hunger in the intervention group were eligible for inclusion. However, we planned to interpret the findings of these trials with caution since the Cochrane review of non-nutritive sucking found evidence that this intervention shortens the transition from tube to bottle feeds, improves bottle feeding performance and behaviour, and is associated with a statistically significant decrease in length of hospital stay for preterm infants (Pinelli 2001). We did not specify a minimum trial duration as a primary eligibility criterion. However, we planned only to include growth data in meta-analyses from trials that allocated the intervention for a sufficient period (at least one week) to allow measurable effects on growth.
Secondary:
1. Age (postmenstrual age and days from birth) at
establishment of full oral feeding (independent of intra-gastric tube
feeding).
2. Nutrient intake during trial period: mean (and standard
deviation) volume of milk and intake of calories/protein per kilogram per
day.
3. Duration of breast feeding (time from start of trial until infant
stops receiving any human breast milk) and breast feeding prevalence (any and
fully) on discharge and at three and six months post term.
4. Milk
aspiration: consistent clinical history and chest x-ray findings
5.
Hypoglycaemia requiring treatment with unscheduled enteral supplement, or
intravenous fluids, or glucagon
6. Feed intolerance defined as a requirement
to cease enteral feeds and commence parenteral nutrition.
7. Necrotising
enterocolitis: at least two of the following features: Pneumatosis coli on
abdominal radiograph; abdominal distension or abdominal radiograph with gaseous
distension or frothy appearance of bowel lumen (or both); blood in stool;
lethargy, hypotonia, or apnea, or combination of these (Bell 1978).
8. Measures of
parental satisfaction using validated assessment tools.
9. Neurodevelopmental
outcomes at greater than 12 months corrected age measured using validated
assessment tools such as Bayley Scales of Infant Development, and
classifications of disability, including auditory and visual disability. The
composite outcome "severe neurodevelopmental disability" will be defined as any
one or combination of the following: non-ambulant cerebral palsy, developmental
delay (developmental quotient less than 70), auditory and visual impairment.
The search strategy used the following text words and MeSH terms: Infant, Newborn OR Infant, Premature OR Infant, Low Birth Weight, OR Premature Birth, OR preterm OR low birth weight OR LBW OR premature; AND Infant-Nutrition OR Milk, Human OR Feeding Behavior, OR Sucking Behavior, OR oral feeding OR demand feeding OR semi-demand feeding OR self-regulatory feeding OR ad libitum. We limited the search outputs with the relevant filters for clinical trials. We did not apply any language restriction.
We examined references in previous reviews and in studies identified as potentially relevant. We hand-searched the abstracts presented at the annual scientific meetings of the Society for Pediatric Research, the European Society for Pediatric Research since 1980 until 2004. Trials that had been reported only as abstracts were eligible for inclusion if sufficient information was available from the report, or from contact with the authors, to fulfil the inclusion criteria.
2. KT and WM used the criteria and standard methods of the Cochrane Neonatal Review Group to assess independently the methodological quality of the included trials in terms of allocation concealment, blinding of parents or caregivers and assessors to intervention, and completeness of assessment in all randomised individuals. We requested additional information from the trial author to clarify methodology and results.
3. KT and WM used a data collection form to aid extraction of relevant information and data from each included study. Each review author extracted the data separately, compared data, and resolved differences by discussion until consensus was achieved. If data from the trial reports were insufficient, we contacted the authors for further information.
4. We have presented outcomes for continuous data as (weighted) mean difference with 95% confidence interval. For categorical data, we planned to use relative risk, risk difference, and number needed to treat, with respective 95% confidence intervals.
5. For meta-analyses, we planned to estimate the treatment effects of individual trials and examine heterogeneity between trial results by inspecting the forest plots and quantifying the impact of heterogeneity using the I- squared statistic. If we detected statistical heterogeneity, we planned to explore the possible causes (for example, differences in study quality, participants, intervention regimens, or outcome assessments) using post hoc sub group analyses. We planned to use a fixed effects model for meta-analyses.
Population
All of the included studies were undertaken since 1980
by investigators attached to neonatal units in North America. The trials in
general were small. 417 infants in total participated. The participants in all
of the trials were clinically stable preterm infants who were fully enterally
fed and at transition from intragastric tube feeds to oral feeds (generally
between 32 and 36 weeks' postmenstrual age). Most of the trials specifically
excluded infants who were small for gestational age at birth and infants with
congenital anomalies, or gastrointestinal or neurological problems. The balance
of oral versus tube feeding at enrolment differed between trials. One trial
enrolled infants at the start of transition to oral feeding when infants were
mainly fed via an intragastric tube (McCain 2001). In the other
trials, infants were enrolled later in the transition phase when infants were
receiving most of their feeds orally. In five trials, intragastric feeding tubes
were removed when infants were allocated to the intervention group (Kansas 2004; Waber 1998; Collinge 1982; Pridham 1999; Pridham 2001).
Intervention
We classified four trials as comparing ad libitum
feeding with scheduled interval feeding (N = 294) (Collinge 1982; Kansas 2004; Pridham 1999; Pridham 2001). Ad libitum
feeding was generally described in the trial reports as allowing the infant to
feed orally in response to hunger cues such as crying, sucking on
fingers/pacifier, or rooting. Feeding was ceased only in response to satiation
cues such as sleep of failure to maintain sucking.
We classified three trials as comparisons of demand/semi-demand feeding with scheduled interval feeding (N = 123) (McCain 2001; Saunders 1991; Waber 1998). In two trials this meant that infants were fed in response to standard hunger cues (Saunders 1991; Waber 1998). If infants did not demonstrate these cues within five hours, infants were aroused to feed orally or given a prescribed volume of milk via an intra-gastric tube. In the other trial, the infant's readiness to feed was assessed every three hours by the response to non-nutritive sucking (McCain 2001). Oral feeds were stopped when the infant stopped sucking or fell asleep. If the minimum prescribed amount was not taken the infants received a prescribed volume via the intragastric tube.
Scheduled interval feeding was generally defined as regular feeding either
orally or via an intragastric feeding tube at three to four hourly intervals to
achieve an prescribed intake. The target volume of intake in the trials varied
from 100 to 160 millilitres per kilogram per day. In all of the trials the
infants in the intervention and control groups received the same type(s) of
milk. Most trial protocols permitted infants to receive either breast milk or
formula milk, or a mixture of these. One trial recruited only formula milk fed
infants (Saunders
1991).
Outcomes
Most trials assessed only short
term outcomes, principally volume and calorie intake and growth parameters
(usually weight) during the study period. The duration of study period was less
than seven days in six of the trials. In the other trial the intervention was
continued until the infants were assessed as being ready for discharge home, on
average ten days (Kansas
2004).
Excluded studies
We excluded three studies (Anderson 1990; Chang 2004; Horton 1952). The reasons
for exclusion are listed in the table, Characteristics of excluded studies. Anderson 1990 assessed the
effect of a range of nipples for bottle feeding and for non-nutritive sucking
but did not specifically assess ad libitum or demand/semi-demand feeding versus
scheduled interval feeding. Chang 2004 described a
randomised crossover study in which 11 preterm infants were randomly allocated
to receive ad libitum feeds for 48 hours followed by scheduled interval feeds
for 48 hours, or vice versa. Because this study design does not allow the
collection of meaningful data on growth and time to hospital discharge, the
primary outcomes of this review, the trial was not considered eligible for
inclusion. Horton 1952
reported a case series of low birth weight infants who received demand oral
feeds.
PRIMARY OUTCOMES
Outcome 01.01: Growth (four trials
reported data)
(a) Kansas 2004 reported that
the rate of weight gain was statistically significantly lower in the study
group: 8.6 (SD 5.3) grams per kilogram per day in the study group versus 11.9
(SD 6.1) grams per kilogram per day in the control group: Mean difference -3.30
(95% confidence interval -6.2 to -0.4) grams per kilogram per day (table01_01).
However, there was not a statistically significant difference in the weight at
discharge between the groups: 2167 (SD 258) grams in the study group versus 2035
(SD 304) grams in the control group: Mean difference 132 (95% confidence
interval -11.7 to 275.7) grams. Collinge 1982 reported
that the mean weight gain per day in the three-day study period did not differ
significantly between the groups (11.2 grams versus 14.6 grams; standard
deviations not reported). We have contacted the trial investigators to seek
these additional data. Both Pridham 1999 and Pridham 2001 reported that
there was no a statistically significant difference in the rate of weight gain
(grams per kilogram per day) during the five days study period. These data were
presented in graphs and applied only to the enrolled infants who were not
discharged home before completing the pre-specified five days study period. Data
are not available for infants discharged home before completing the five days
study period (personal communication from the principal investigator).
None of the trials collected data on linear growth, head circumference growth, or changes in skinfold thickness during the trial period.
(b) None of the trials collected any data on longer term growth parameters.
Outcome 01.02: Postmenstrual age and/or chronological age (days
from birth) to discharge to home from hospital (four trials reported
data)
Kansas 2004
reported that there was not a statistically significant difference in age (days
from birth) to discharge to home from hospital: 45 (SD 22) days in the
intervention group versus 42 (SD 18) days in the control group: Mean difference
3.0 (95% confidence interval -7.3 to 13.3) days after birth. Collinge 1982 did not
report age at discharge but did state that there was a statistically
significantly difference in the number of days from study enrolment until
infants were ready for hospital discharge: 2.7 days in the intervention group
versus 8.9 days in the control group. Standard deviations were not reported. We
have contacted the trial investigators to seek these data. Pridham 1999 and Pridham 2001 did not report
age at hospital discharge but did state that there was not a statistically
significant difference in the duration of hospital stay following randomisation.
We have contacted the trial investigators to seek additional data.
SECONDARY OUTCOMES
Outcome 01.03: Age at establishment of full
oral feeds (two trials reported data)
Kansas 2004 reported a
statistically significant difference in the time taken to achieve full oral
feeding after trial entry: 0.9 (SD 0.3) days in the intervention group versus
3.1 (SD 2.4) days in the control group: mean difference -2.2 (95% confidence
interval -3.1 to -1.3) days. Collinge 1982 reported
that the intervention group achieved establishment of full oral feeds
independent of tube feeding earlier than the control group but did not comment
on statistical significance or provide data to assess statistical significance.
We have contacted the trial investigators to seek these additional data. Pridham 1999 and Pridham 2001 did not
evaluate age at establishment of full oral feeds as all participating infants
were receiving full oral feeds at enrolment.
Outcome 01.04: Nutrient intake during trial period (four trials reported
data)
Kansas 2004
reported that the daily volume of intake and the daily caloric intake during the
study period for those infants who were not breast fed (since it was not
possible to measure nutrient intake of breast feeding infants). Volume and
calorie intake were statistically significantly lower in the study group (N =
19) than the control group (N = 22):
(i) Volume: 129 (SD 23) millilitres per
kilogram per day in the intervention group versus 152 (SD 35) millilitres per
kilogram per day in the control group: mean difference -23.0 (95% confidence
interval -40.9 to -5.1) millilitres per kilogram per day.
(ii) Calories: 93 (SD 17) calories per kilogram per day in the intervention
group versus 113 (SD 24) calories per kilogram per day in the control group:
mean difference -20.0 (95% confidence interval -32.6 to -7.4) calories per
kilogram per day.
Collinge 1982 reported
that during the three-days study period the infants allocated to demand feeding
received "significantly" less feeds per day (5.1 in the study group versus 7.8
in the control group) and a "significantly" less number of gavage feeds per day
(0.1 in the study group versus 4.6 in the control group). The total average milk
intake did not differ between the groups (154.9 millilitres per kilogram per day
in the study group versus 154.4 millilitres per kilogram per day in the control
group). Standard deviations were not reported for these outcomes. We have
contacted the trial investigators to seek these additional data. Pridham 1999 and Pridham 2001 both reported
that caloric intake was lower in the ad libitum group than the control group
during the five days study period. The reports do not state whether this
difference was statistically significant. The mean daily calorie intake data
were presented in graphs and applied only to the enrolled infants were not
discharged home before completing the pre-specified five days study period. We
could not extract the data for statistical analyses. However, the graphs
illustrate that the standard errors for intervention and control groups for each
daily mean calorie intake in each of the trials overlapped suggesting that
differences were not statistically significant. We have contacted the authors
for clarification.
Duration of breast-feeding: Not reported in any of the included studies.
Milk aspiration: Not reported in any of the included studies.
Hypoglycaemia: Not reported in any of the included studies.
Feed intolerance: Not reported in any of the included studies.
Necrotising enterocolitis: Not reported in any of the included studies.
Measures of parental satisfaction: Not reported in any of the included studies.
Neurodevelopmental outcomes: Not reported in any of the included studies.
Comparison 02: Demand/semi-demand feeding versus scheduled interval
feeding (three trials: McCain 2001;Saunders 1991; Waber 1998)
PRIMARY OUTCOMES
Outcome 02.01: Growth (three trials reported
data)
(a) McCain
2001reported that there was not a statistically significant difference in
the rate of weight gain during two phases of the study period: (i)
Gavage-to-oral feeding phase (average duration 5 days in the intervention group
versus 10 days in the control group: see below): 23.5 (SD 8.9) grams per day in
the intervention group versus 26.3 (SD 8.3) grams per day in the control group,
(ii) First 48 hours of exclusive oral feeding phase: 31.9 grams (SD 13.3) per
day in the intervention group versus 33.5 (SD 13.4) grams per day in the control
group. Saunders 1991
reported that there was not a statistically significant difference in the rate
of weight gain (grams per day) during the six days study period. These data were
presented in graphs only. Waber 1998 reported that the
average daily weight gain in the intervention group was 26.4 grams versus 34.1
grams in the control group. The authors did not state whether this difference
was statistically significant. Standard deviations were not reported.
None of the trials provided data on linear growth, head circumference growth, or changes in skinfold thickness during the trial period.
(b) None of the trials reported any data on longer term growth parameters.
Outcome 02.02: Postmenstrual age and/or chronological age (days from
birth) to discharge to home from hospital (three trials reported data)
McCain 2001 reported that
the post-menstrual age at discharge was statistically significantly lower in
infants in the intervention group (34.0 weeks; SD 0.8 weeks) compared to control
infants (33.4 weeks; SD 0.9 weeks): mean difference -0.6 (95% confidence
interval -0.97 to -0.23) weeks. Saunders 1991 did not
report age at hospital discharge but did state that there was not a
statistically significant difference in the duration of hospital stay following
randomisation: 7.2 days in the intervention group versus 8.4 days in the control
group. Standard deviations were not reported. Further data are no longer
available from the principal investigator. Waber 1998 reported that the
duration of hospital stay was 31 days in the intervention group versus 33 days
in the control group. The authors did not state whether this difference was
statistically significant. Standard deviations were not reported. We have sought
further data from the trial authors.
SECONDARY OUTCOMES
Outcome 02.03: Age at establishment of full
oral feeds (one trial reported data)
McCain 2001 reported a
statistically significant difference in the number of days from trial entry to
establishment of full oral feeds: 5.0 (SD 4.2) days in the intervention group
versus 10.0 (SD 3.1) days in the control group: mean difference -5.0 (95%
confidence interval -6.6 to -3.4) days (table02_03). Neither Saunders 1991 nor Waber 1998 collected data on
age at establishment of oral feeding.
Outcomes 02.04 and 02.05: Nutrient intake during trial period (two trials
reported data)
McCain
2001 reported that there was not a statistically significant difference in
volume of milk intake during two phases of the study period: (i) Gavage-to-oral
feeding phase (average duration 5 days in the intervention group versus 10 days
in the control group): 259 (SD 44) millilitres per day in the intervention group
versus 262 (SD 40) millilitres per day in the control group, (ii) First 48 hours
of exclusive oral feeding phase: 287 (SD 43) millilitres per day in the
intervention group versus 289 (SD 43) millilitres per day in the control group
(outcome 02.04). McCain
2001 reported that the average daily intake of calories was statistically
significantly higher in the intervention group during the two phases of the
study period: (i) Gavage-to-oral feeding phase (average duration 5 days in the
intervention group versus 10 days in the control group): 122 (SD 10) calories
per kilogram body weight per day in the intervention group versus 188 (SD 7)
calories per kilogram body weight per day in the control group: mean difference
4.0 (95% confidence interval 0.2 to 7.8) calories per kilogram body weight per
day, (ii) First 48 hours of exclusive oral feeding phase: 126 (SD 14) calories
per kilogram body weight per day in the intervention group versus 119 (SD 10)
calories per kilogram body weight per day in the control group: mean difference
7.0 (95% confidence interval 1.7 to 12.3) calories per kilogram body weight per
day (outcome 02.05). Waber
1998 reported that (i) the average calorie intake was 88.7 kilocalories per
kilogram per day in the intervention group versus 115.6 kilocalories per
kilogram per day in the control group, (ii) the average protein intake was 2.5
grams per kilogram per day in the intervention group versus 3.4 grams per
kilogram per day in the control group, and (iii) the average fluid intake was
119.1 millilitres per kilogram per day in the intervention group versus 146.8
millilitres per kilogram per day in the control group. The authors did not state
whether any of these differences were statistically significant. Standard
deviations were not reported and are not available from the trial authors. Saunders 1991 did not
collect data on nutrient intake (personal communication from principal
investigator).
Duration of breast-feeding: Not reported in any of the included studies.
Milk aspiration: Not reported in any of the included studies.
Hypoglycaemia: Not reported in any of the included studies.
Feed intolerance: Not reported in any of the included studies.
Necrotising enterocolitis: Not reported in any of the included studies.
Measures of parental satisfaction: Not reported in any of the included studies.
Neurodevelopmental outcomes: Not reported in any of the included studies.
Subgroup analyses:
1. Trials where all participating infants were
enterally fed via gastric tubes (no oral feeding): None of the trials belonged
to this subgroup.
2. Trial where participating infants were in transition
from gastric tube to oral feeds: All of the trials belonged to this
subgroup
3. Trials where all participating infants were fed orally (no
gastric tube feeding): None of the trials belonged to this subgroup.
4.
Trials where all participating infants were exclusively fed from the breast:
None of the trials belonged to this subgroup.
5. Trials where the infants'
responses to non-nutritive sucking were used to assess hunger. One trial
belonged to this subgroup (McCain 2001). See above for
trial description and findings.
6. Cluster randomised controlled trials: We
did not identify any cluster randomised controlled
trials.
Meta-analyses:
Meta-analyses were not undertaken
because of insufficient data. We have contacted the relevant investigators to
determine if these data are available. If so, we will include these in a future
update of this review.
The primary outcomes for this review were growth rates and age at hospital discharge. Most of the trials did not report statistically significant differences in growth rates for infants fed ad libitum or demand/semi-demand compared to infants fed at scheduled intervals. However, the duration of the intervention and the duration of data collection and follow up (less than five days) in these trials is not likely to have allowed detection of measurable effects on growth. Only one trial assessed growth for longer than one week (on average for about 10 days). This study found that the rate of weight gain was lower in the ad libitum fed infants (Kansas 2004). The clinical significance of this finding is unclear as the trial did not find a statistically significant difference in the weight nor the age at discharge. Two of the included trials reported that infants fed ad libitum or demand/semi-demand were discharged home several days earlier than infants in the scheduled interval feeding group (Collinge 1982; McCain 2001). The other trials did not confirm this finding. Additionally, since McCain 2001 used non-nutritive sucking on a pacifier to assess readiness to feed, the finding in that trial of a shortened time to hospital discharge should be interpreted cautiously. Evidence exists that non-nutritive sucking shortens reduces the length of hospital stay for preterm infants (Pinelli 2001).
With regard to secondary outcomes, three of the included trials reported that ad libitum or demand/semi-demand feeding shortened the duration of the transition phase from tube to full oral feeds. The relevance of this finding is unclear, as most trials enrolled infants when they were already mainly fed orally (at which point intragastric feeding tubes were removed from infants in the intervention group). Only one of the trials recruited infants at the start of transition to oral feeding phase (McCain 2001). However, as discussed above, the findings from this trial should be interpreted cautiously because of the possibility that non-nutritive sucking itself shortens the transition from tube to oral feeds for preterm infants (Pinelli 2001).
One trial reported that nutrient intake was lower during the study period for those infants fed ad libitum, consistent with the finding that infants fed ad libitum had lower rates of weight gain (Kansas 2004). Paradoxically, the infants fed ad libitum also had less variance in the quantity of nutrient intake. This may be due to variation in the prescribed volume of intake in the scheduled interval feeding group- from 110 to 150 millilitres per kilogram per day depending on postnatal age at enrolment. Conversely, the trial that assessed the effect of demand/semi-demand feeding using the infant's response to non-nutritive sucking to assess readiness to feed reported that infants in the intervention group had a greater intake of calories during the study period (McCain 2001). The clinical significance of this marginal difference (about four to seven calories per kilogram per day) is unclear. None of the other trials reported that ad libitum or demand/semi-demand feeding affected nutrient intake but in general the data reported are not sufficient to assess statistical significance and differences in study design limited the validity of data synthesis.
| Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
| Collinge 1982 | Blinding of randomisation: can't tell Blinding of intervention: no Complete follow-up: yes Blinding of outcome measurement: can't tell |
36 preterm infants, birth weight less than 2500 grams and appropriate for gestational age. Infants were recruited when they weighed at least 1800 grams and were fully enterally fed and receiving at least one feed per day by gavage via an intra-gastric feeding tube. Breast milk fed and formula milk fed infants (or mixed) participated in the trial. Formula fed infants received either standard calorie milk or calorie and protein enriched ("low birth weight") formula milk, or both. There is no indication in the report that the choice of type of formula milk was associated with the feeding regime allocation. Infants with severe gastrointestinal or neurological problems were not eligible to participate. | Intervention (N=18): "Ad libitum" feeding, defined in the trial report
as "allowing the infant to feed as frequently as (s)he wishes, and to take
as much as desired at each feeding". Infants were fed (orally or via a
gastric feeding tube) in response to crying, sucking on fingers/pacifier,
activity and rooting. The trial report does not state which satiation cues
were assessed. Control (N= 18) received prescribed volumes of milk (up to 160 ml/kg/day) either orally or via a feeding-tube at three to four hourly intervals. |
Volume of intake, and calorie-intake during trial period. Total number of feeds per day, and number of feeds given via gastric feeding tube per day. Time from randomisation to discharge from hospital. |
Setting: Montreal Children's Hospital, Canada. 1981-1982.
We have contacted the trial investigators to seek further information on methodology and results. |
B |
| Kansas 2004 | Blinding of randomisation: yes Blinding of intervention: no Complete follow-up: yes Blinding of outcome measurement: no |
59 preterm infants (born before 33 weeks' gestational age) who were able to take at least half of their enteral feeds orally from a nipple (either bottle or breast). | Intervention (N= 29): "Ad libitum" feeding: At randomisation, enteral
feeding tubes were removed and infants were then fed ad libitum (no
maximum or minimum feeding volume or interval) via a nipple in response to
hunger and satiation cues. Control (N= 30) scheduled interval feeding with gavage feeding if infant did not ingest prescribed volume from nipple. |
Days (from birth) to discharge to home from hospital. Daily weight gain, and weight at discharge. Days (from randomisation) to full nipple feeding. Average daily volume/calorie intake. |
Setting: duPont Hospital for Children, Philadelphia, USA.
2003. Reported in abstract form only. Further information on methodology kindly provided by trial investigators. |
A |
| McCain 2001 | Blinding of randomisation: yes Blinding of intervention: no Complete follow-up: yes Blinding of outcome measurement: no |
81 preterm infants of postmenstrual age between 32 to 34 weeks who were fully enterally-fed. Infants with severe periventricular haemorrhage, congenital anomalies, or gastrointestinal or neurological problems were not eligible to participate. Infants were fed fortified human milk or commercial formula at 105 to 130 kcal/kg/day per nursery standard of care. The infants had indwelling nasogastric tubes until they reached full oral feeding. | Intervention group (N=40): Semi-demand feeding- infants received 10
minutes of non-nutritive sucking every three hours to assess wakefulness
and behavioural state. Infants who were wakeful were offered an oral feed.
If the infant was not sufficiently awake, he/she was left to sleep a
further 30 minutes and the process was repeated. If the infant continued
to sleep at that stage, (s)he was given a gavage feed of the full
prescribed volume. Feeds were stopped when the infant stopped sucking or
fell asleep or demonstrated clinically instability. If the minimum
prescribed amount was not taken the infants were supplemented by
gavage. Control infants (N=41) received prescribed volumes of milk either orally or via a feeding-tube at three hourly interval. Feeding duration was restricted to a maximum of 30 minutes. One infant in the control group was transferred to another hospital after completing the study protocol. The "age at discharge home" is not known. |
Time taken from start of study to achieve full oral feeding, and rate of weight gain (grams per day) during transition from enteral tube to oral feeds. | Setting: Neonatal units affiliated to University of Cincinnati, Ohio,
USA, late 1990s. Randomisation method: pre-prepared random sequence unknown to investigators (personal communication from principal investigator). |
A |
| Pridham 1999 | Blinding of randomisation: yes Blinding of intervention: no Complete follow-up: no Blinding of outcome measurement: no |
150 infants less than 35 weeks' gestational age at birth and appropriate weight for gestational age were enrolled and randomised. Infants were enrolled in the trial when taking at least 80% of enteral feeds directly from a nipple (either breast or bottle), at which point tube feeding was ceased and all feeds were offered by nipple. Most infants received standard formula milk. As part of a factorial trial design, some infants were randomly allocated to receive calorie-enriched formula milk. | Intervention (N= 94): "Ad libitum" initiated response to infant hunger
cues and terminated in response to infant satiation. Control (N= 56): Prescribed feeding at 4 hourly intervals. |
Weight change and volume-and calorie-intake during the study period (5 days). | Setting: Level III neonatal unit in Wisconsin, USA. 1992- 1994.
Failure to complete full 5 days study period: 69 of the 150 (46%) enrolled infants were discharged home before completing the 5 days study period and no outcome data were presented for these infants. Further information on methodology kindly provided by trial investigators. |
A |
| Pridham 2001 | Blinding of randomisation: yes Blinding of intervention: no Complete follow-up: no Blinding of outcome measurement: no |
49 infants less than 35 weeks' gestational age at birth and appropriate weight for gestational age. Infants were enrolled in the trial when taking at least 80% of enteral feeds directly from a nipple (either breast or bottle), at which point tube feeding was ceased and all feeds were offered by nipple. Most participating infants received breast milk. | Intervention (N= 25): "Ad libitum" initiated in response to infant
hunger cues and terminated in response to infant satiation. Control (N= 24): Prescribed feeding at 3 hourly intervals. |
Weight change and volume-and calorie-intake during the study period (5 days). | Setting: Level III neonatal unit in Wisconsin, USA. 1990- 1993.
Failure to complete full 5 days study period: 23 of the 49 (47%) enrolled infants were discharged home before completing the 5 days study period and no outcome data were presented for these infants. Further information on methodology kindly provided by trial investigators. |
A |
| Saunders 1991 | Blinding of randomisation: yes Blinding of intervention: no Complete follow-up: no Blinding of outcome measurement: no |
29 preterm infants (born before 37 completed weeks' gestation), without major neurological or gastrointestinal disorders. Infants were enrolled when their weight was greater than 1550 grams and they were fully enterally fed with formula milk. | Intervention (N= 15): "Demand" fed in response to hunger cues (crying,
finger/fist sucking, rooting, persistently "unsettled" following a nappy
change or re-positioning). Five hours limit between feeds.
Control (N=14): Prescribed feeding of set volumes at 3 hourly intervals to achieve at least 120 ml/kg/day intake. Infants in either group who failed to take adequate amounts orally for
two consecutive feeds were fed a prescribed volume (to achieve a daily
intake of 120 ml/kg/day) via an intra-gastic feeding tube for the next
feed. |
Volume of milk ingested and rate of weight gain during the 6 days trial period. Length of hospitalisation. | Setting: Level III neonatal unit at the Women's Hospital, Greensbora,
North Carolina, USA. Three infants were withdrawn from the study, one for withdrawal of parental consent, one because of infection, and one because of hypoglycaemia. It is not stated which feeding group these infants had been randomly allocated to. We received further information on methodology and results from the trial investigator. |
A |
| Waber 1998 | Blinding of randomisation: no Blinding of intervention: no Complete follow-up: no Blinding of outcome measurement: no |
13 preterm infants born before 34 weeks' gestation, and appropriate for gestational age. Weight greater than 1500 grams, post-conceptional age greater than 32 weeks at time of enrollment and fully enterally fed. | Intervention (N=5): "Demand"; oral feeding (intra-gastric tubes
removed) in response to hunger cues (crying, finger/hand/pacifier sucking,
rooting, "unsettled"). The feeds were regarded as complete and ceased in
response to infant satiation cues (refusal to suck and sleep). If infant
did not demonstrate hunger cues within five hours of a previous feed, then
infant gently aroused to a "feeding alert state". Control (N=5): Prescribed feeding of set volumes at 3-4 hourly intervals to achieve intake of 140 to 150 ml/kg/day. |
Growth: average weight gain during trial period. Average volume of intake, and calorie and protein intake during trial period. No standard deviations given. |
Setting: The Children's Regional Hospital, Camden, New Jersey, USA.
Method of randomisation: "Coin-toss" for alternate infants, with allocation to opposite group for subsequently-enrolled infant. 10 of 13 enrolled infants completed the trial, but the reasons for withdrawal/drop-out were not stated. We contacted the trial investigators to seek further information on methodology and results. |
C |
| Study | Reason for exclusion |
| Anderson 1990 | This trial assessed the effect of a range of nipples for bottle feeding and for non-nutritive sucking but did not specifically assess ad libitum or demand/semi-demand feeding versus scheduled interval feeding. This study was reported only as book chapter. |
| Chang 2004 | This is a two period crossover study comparing ad libitum feeding with
3 hourly scheduled interval feeding. Because this study design does not
allow the collection of meaningful data on growth and time to hospital
discharge, the primary outcomes of this review, the trial was not
considered eligible for inclusion. |
| Horton 1952 | This is an observational study of demand feeding in low birth weight infants. |
Collinge JM, Bradley K, Perks C, Rezny A, Topping P. Demand vs. scheduled feedings for premature infants. Journal of Obstetric, gynecologic, and Neonatal Nursing 1982;11:362-7.
Kansas 2004 {published data only}
Kansas KL, Mackley AB, Desai S, Leef KH, Paul DA, Stefano JL. Self-regulation of feeding in the premature infant; a randomised trial of ad lib vs. scheduled feedings. Pediatric Research 2004;55:2493 (abstract).
McCain 2001 {published data only}
* McCain GC, Gartside PS, Greenberg JM, Lott JW. A feeding protocol for healthy preterm infants that shortens time to oral feeding. Journal of Pediatrics 2001;139:374-9.
McCain GC, Gartside PS. Behavioral responses of preterm infants to a standard-care and semi-demand feeding protocol. Newborn and Infant Nursing Reviews 2002;2:187–93.
Pridham 1999 {published data only}
Pridham K, Kosorok MR, Greer F, Carey P, Kayata S, Sondel S. The effects of prescribed versus ad libitum feedings and formula caloric density on premature infant dietary intake and weight gain. Nursing Research 1999;48:86-93.
Pridham 2001 {published data only}
Pridham KF, Kosorok MR, Greer F, Kayata S, Bhattacharya A, Grunwald P. Comparison of caloric intake and weight outcomes of an ad lib feeding regimen for preterm infants in two nurseries. Journal of Advanced Nursing 2001;35:751-9.
Saunders 1991 {published data only}
Saunders RB, Friedman CB, Stramoski PR. Feeding preterm infants. Schedule or demand? Journal of Obstetric, Gynecologic, and Neonatal Nursing 1991;20:212-8.
Waber 1998 {published data only}
Waber B, Hubler EG, Padden ML. A comparison of outcomes in demand versus schedule formula-fed prematute infants. Nutrition in Clinical Practice 1998;13:132-5.
Anderson GC, Behnke M, Gill NE, Conlon M, Measel CP, McDonie TE. Self-regulatory gavage-to-bottle feeding for preterm infants: Effects of behavioral state, energy expenditure, and weight gain. In: Funk SG, Tornquist EM, Champayne MT, Coop LA, Wiese RA, editor(s). Key aspects of recovery: Nutrition, rest, and mobility. New York: Springer, 1990:83-97.
Chang 2004 {published data only}
Chang SR, Chen KH. Demand feeding for healthy premature newborns: a randomized crossover study. Journal of the Formosan Medical Association 2004;103:112-7.
Horton 1952 {published data only}
Horton FH, Lubchenco LO, Gordon HH. Self-regulatory feeding in a premature nursery. Yale Journal of Biology and Medicine 1952;24:263-72.
* indicates the primary reference for the study
American Academy of Pediatrics, Committee on Fetus and Newborn. Hospital discharge of the high-risk neonate-proposed guidelines. Pediatrics 1998;102:411-7.
Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Annals of Surgery 1978;187:1-7.
Bu'lock F, Woolridge MW, Baum JD. Development of co-ordination of sucking, swallowing and breathing: ultrasound study of term and preterm infants. Developmental Medicine and Child Neurology 1990;32:669-78.
Crosson DD, Pickler RH. An integrated review of the literature on demand feedings for preterm infants. Advances in Neonatal Care 2004;4:216-25.
Duvanel CB, Fawer CL, Cotting J, Hohlfeld P, Matthieu JM. Long-term effects of neonatal hypoglycemia on brain growth and psychomotor development in small-for-gestational-age preterm infants. Journal of Pediatrics 1999;134:492-8.
Fomon SJ, Filer LJ, Thomas LN, Rogers RR, Procksch AM. Relationship between formula concentration and rate of growth of normal infants. Journal of Nutrition 1969;98:241-54.
Fomon SJ, Filer LJ, Thomas LN, Anderson TA, Nelson SE. Influence of formula concentration on caloric intake and growth of normal infants. Acta Paediatrica Scandinavica 1975;64:172-81.
Holditch-Davis D, Brandon DH, Schwartz T. Development of behaviors in preterm infants: relation to sleeping and waking. Nursing Research 2003;52:307-17.
Hume R, McGeechan A, Burchell A. Failure to detect preterm infants at risk of hypoglycemia before discharge. Journal of Pediatrics 1999;134:499-502.
Kennedy KA, Tyson JE, Chamnanvanakij S. Rapid versus slow rate of advancement of feedings for promoting growth and preventing necrotizing enterocolitis in parenterally fed low-birth-weight infants. In: The Cochrane Database of Systematic Reviews, Issue 2, 2000.
McCain GC. An evidence-based guideline for introducing oral feeding to healthy preterm infants. Neonatal Network 2003;22:45-50.
Pinelli J, Symington A. Non-nutritive sucking for promoting physiologic stability and nutrition in preterm infants. In: The Cochrane Database of Systematic Reviews, Issue 3, 2001.
Ross ES, JV Brown JV. Developmental progression of feeding skills: an approach to supporting feeding in preterm infants. Seminars in Neonatology 2002;7:469-75.
Siddell EP, Froman RD. A national survey of neonatal intensive-care units: criteria used to determine readiness for oral feedings. Journal of Obstetric, Gynecologic, and Neonatal Nursing 1994;23:783-9.
Symington A, Pinelli J. Developmental care for promoting development and preventing morbidity in preterm infants. In: The Cochrane Database of Systematic Reviews, Issue 4, 2003.
Tyson JE, Lasky RE, Mize CE, Richards CJ, Blair SN, Whyte R et al. Growth, metabolic response, and development in very-low-birth-weight infants fed banked human milk or enriched formula. I. Neonatal findings. Journal of Pediatrics 1983;103:95-104.
| Comparison or outcome | Studies | Participants | Statistical method | Effect size |
|---|---|---|---|---|
| 01 Ad libitum feeding versus scheduled interval feeding | ||||
| 01 Growth: weight change during study period (grams per kilogram per day) | 1 | 59 | WMD (fixed), 95% CI | -3.30 [-6.21, -0.39] |
| 02 Age at discharge (days) | 1 | 59 | WMD (fixed), 95% CI | 3.00 [-7.28, 13.28] |
| 03 Time to establishment of full oral feeds (after trial entry) | 1 | 59 | WMD (fixed), 95% CI | -2.20 [-3.07, -1.33] |
| 04 Nutrient intake during trial period (non breast fed infants only) | WMD (fixed), 95% CI | Subtotals only | ||
| 02 Demand/semi-demand feeding versus scheduled interval feeding | ||||
| 01 Growth: weight gain during study period (grams per day) | 2 | 162 | WMD (fixed), 95% CI | -2.45 [-5.60, 0.70] |
| 02 Postmenstrual age at discharge (weeks) | WMD (fixed), 95% CI | Subtotals only | ||
| 03 Time to establishment of full oral feeds (days after trial entry) | 1 | 81 | WMD (fixed), 95% CI | -5.00 [-6.61, -3.39] |
| 04 Volume of intake during the trial period (millilitres per day) | WMD (fixed), 95% CI | No total | ||
| 05 Calorie intake during the trial period (per kilogram per day) | WMD (fixed), 95% CI | No total | ||
01.01 Growth: weight change during study period (grams per kilogram per day)
01.03 Time to establishment of full oral feeds (after trial entry)
01.04 Nutrient intake during trial period (non breast fed infants only)
01.04.01 Volume of milk (millilitres per kilogram per day)
01.04.02 Calorie intake (kilocalories per kilogram per day)
02 Demand/semi-demand feeding versus scheduled interval feeding
02.01 Growth: weight gain during study period (grams per day)
02.01.01 Gavage to oral feeding transition phase
02.01.02 Exclusive oral feeding phase (first 48 hours)
02.02 Postmenstrual age at discharge (weeks)
02.03 Time to establishment of full oral feeds (days after trial entry)
02.04 Volume of intake during the trial period (millilitres per day)
02.04.01 Gavage to oral feeding transition phase
02.04.02 Exclusive oral feeding phase (first 48 hours)
02.05 Calorie intake during the trial period (per kilogram per day)
02.05.01 Gavage to oral feeding transition phase
02.05.02 Exclusive oral feeding phase (first 48 hours)
| This review is published as a Cochrane review in The
Cochrane Library, Issue 3, 2006 (see http://www.thecochranelibrary.com for
information). Cochrane reviews are regularly updated as new evidence
emerges and in response to feedback. The Cochrane Library shoud be
consulted for the most recent version of the
review. |