Comparison of Physiological and Behavioral Responses to Fresh and Thawed Breastmilk in Premature Infants

Abstract

Background:

Breastmilk is usually frozen for premature infants when they are unable to feed orally. However, thawed breastmilk may have altered odor and taste from its original form. Few studies have investigated whether premature infants respond differently to fresh and thawed breastmilk. The purpose of this study was to examine the physiological and behavior responses of premature infants alternately fed fresh and thawed breastmilk.

Subjects and Methods:

An experimental, crossover study using random assignment was conducted. A convenience sample of 18 premature infants less than 37 weeks gestational age at birth with the capability of oral feeding was studied. The premature infants were fed with fresh and thawed breastmilk during two consecutive meals in a random order. Infants' heart rate and oxygen saturation levels were measured baseline and during feeding, as well as observed feeding cues during the feeding period.

Results:

Premature infants showed significant differences in heart rate when fed thawed, as opposed to fresh, breastmilk. Premature infants demonstrated more stress cues when fed thawed compared with fresh breastmilk (p=0.007). For infants with postmenstrual ages greater than 36 weeks gestation, feeding with thawed breastmilk showed more stress cues and greater effect on heart rate activity compared with fresh breastmilk (p<0.05).

Conclusions:

Older premature infants demonstrate more stress when fed with thawed breastmilk. Preterm infants should be directly breastfed or fed with nonfrozen breastmilk, when they show stress behaviors in being fed with thawed breastmilk.

Introduction

Breastmilk is the best source of nutrition for premature infants.¹ When a premature infant is unable to be fed orally or the mother has difficulties in breastfeeding, breastmilk is usually frozen and stored.² It is noteworthy that an issue with frozen breastmilk has been widely discussed on the Internet among mothers of infants. The issue is that the odors in thawed breastmilk are different from those of fresh breastmilk, and those odors are usually thought to be a feeding barrier to premature infants.³ Breastfeeding experts pointed out that even though there have been no proven harmful effects of off-flavor frozen-thawed breastmilk on infants, the off-flavor might influence infants' feeding.^4,5 Although an immature coordination of sucking– swallowing–breathing has been documented as the main reason for difficult feeding in premature infants,⁶ premature infants' feeding responses to thawed breastmilk rarely have been investigated.

The human interpretation and acceptance of food involve both physiological and psychological experiences. The perception of flavor is based on the integration of taste and smell receptors. Environmental stimuli from the touch, pain, and temperature of food are sensed and transmitted via the trigeminal nerve to the brain where the perception of food is formed.^7,8

The senses of smell and taste develop during fetal development. By the 11^th week of gestation, the morphology of the fetal olfactory bulb is similar to that in adulthood.⁹ At 28 weeks of gestation, the fetus is able to react to smell. Taste buds develop as early as 7–8 weeks of gestation and approach maturity by 13–15 weeks.¹⁰ Studies show that taste buds respond to chemical changes in amniotic fluid by 20 weeks.¹¹ The composition of a mother's food consumption can be transmitted into the amniotic fluid and can affect the infants' preference for certain foods after birth.^12,13 When sweet or bitter substances are injected into amniotic fluid, fetuses react with different swallowing reactions, preferring sweet substances.¹⁴

Studies have found that the altered odor of thawed breastmilk is the result of physical and chemical changes. The destruction of membranes enclosing the fat globules, during the process of freezing, results in an altered flavor.⁴ From the study of cow's milk, the altered flavor is believed to be related to the rancidification of fat.^15,16 The triacylglycerol in milk is catabolized by lipases into free fatty acids whose accumulation causes the rancid flavor. The unsaturated fatty acids may also be oxidized by radiation, oxidative reagents, or lipase and produce carboxylic acids, alcohols, aldehydes, and ketones, which create a bad taste.^2,17 A recent unpublished study found that the acid value of fat and the amount of free fatty acids of frozen-thawed breastmilk increased over storage time, which makes it more susceptible to becoming rancid (H.-Y.H., unpublished data, 2009).

There has been no study exploring the effects of flavor of thawed breastmilk on feeding behavior and physiological responses among preterm infants. However, several studies have investigated the effects of varied flavor stimuli on full-term infants. Previous studies have indicated that sweet substances can elicit frequent sucking responses in both full-term and premature infants^18,19 and have analgesic effects to comfort infants undergoing intrusive procedures.²⁰ Compared with water, breastmilk induces more frequent sucking responses and increases volume intake.²¹

Previous studies have shown that full-term infants can express their taste by oral cavity movements and facial expressions. With a preferred taste, there are frequent oral movements such as licking, sucking, and chewing. Frowning, pouting, and moving the head to avert the source of the stimulus, which are stress cues, are related to less preferred tastes.^22,23 Autonomic nervous system changes such as changes in heart rate and respiration can represent infants' responses to various smells.^24–26 By observing stress cues and autonomic nervous system changes, timely and appropriate feeding interventions can be made.

The sensory organs for smell and taste develop before birth. These sensory developments may allow newborn infants to respond to different taste stimuli with a variety of oral movements, specific behavior, and facial expressions. The benefits of breastmilk to premature infants are well established; however, there is a need to consider the use of thawed breastmilk for premature infants in order to minimize their feeding stress.

The purpose of this pilot study was to compare the physiological and behavioral responses of premature infants fed with fresh and thawed breastmilk. This study's hypotheses are that premature infants' heart rate activity will be affected, their oxygen saturation levels will decrease, and they will display behaviors consistent with stress and dislike when fed thawed breastmilk, as compared with being fed fresh breastmilk.

Subjects and Methods

Protocol

An experimental, crossover design with random assignment was conducted from April 2009 to September 2009 at a tertiary-care medical center in southern Taiwan. The study was approved by the Institute Review Board, and written informed consent was obtained from the premature infants' parents. The premature infants were fed with fresh and thawed breastmilk for two consecutive meals prior to discharge from the Level II nursery.

Subjects

A convenience sample of 18 premature infants less than 37 weeks gestational age at birth with an appropriate capability of oral feeding was studied. The capability of oral feeding was assessed by both doctors and nurses, using the Neonatal Oral Motor Assessment Scale (NOMAS).²⁷ The three categories of oral feeding capability among premature infants determined by NOMAS are normal, disorganized, or dysfunctional oral sucking patterns. The normal oral sucking pattern refers to rhythmic and regular tongue and chin movements with sucking–swallowing–breathing coordination. A disorganized sucking refers to a lack of rhythm of total sucking activity. Dysfunctional sucking refers to a feeding interruption due to abnormal movements of the tongue and jaw. Because a dysfunctional oral sucking pattern would interrupt the observations of infants' stress behaviors, only those who had a normal or disorganized oral sucking pattern were eligible for the current pilot study.

Premature infants were excluded if they had the following conditions: dysfunctional oral motor movement classified by NOMAS, oropharyngeal abnormalities, grade III intraventricular hemorrhage, or congenital heart disease.

The premature infants were divided into two groups for subgroup analysis based on their weeks of postmenstrual age (postmenstrual age ≤36 weeks vs. postmenstrual age >36 weeks). Dividing the groups based on the 36-week postmenstrual age cutoff value was used because of the study of Raimbault et al.,²¹ which used 35 weeks of postmenstrual age to examine premature infants' odor responses to breastmilk.

Subject assignment

A two-period crossover design was used. Each subject was fed two consecutive meals with equal amounts of fresh and thawed breastmilk. The two consecutive meals were either fresh breastmilk first (fresh/thawed sequence; treatment schedule A) or thawed milk first (thawed/fresh sequence, treatment schedule B). To achieve a balanced number of schedule A and B treatments during study, a permuted block randomization was performed by the primary researcher (H.-Y.H.). Subjects were randomly assigned to treatment schedule A or B; our assignment method resulted in 10 subjects in treatment schedule A and eight subjects in treatment schedule B.

Handling of breastmilk

All of the breastmilk came from each premature infant's mother. Fresh breastmilk was defined as breastmilk that had been stored in a refrigerator at 4–7°C for less than 24 hours. Thawed breastmilk was defined as breastmilk that had been frozen in a refrigerator at −13°C for more than 5 days and was placed into a refrigerator to thaw for 24 hours before feeding. Both types of breastmilk were warmed before giving to premature infants. The minimum 5 days for the frozen period was determined through a panel discussion that involved five nurses as tasters for the flavor of thawed breastmilk. Each taster savored three samples of the thawed breastmilk that were frozen for 3, 5, or 10 days. Based on the tasting results, it was determined that the thawed breastmilk from the fifth day of freezing began to have an unpleasant flavor.

Both types of breastmilk were warmed to 40°C and gently shaken to achieve a homogeneous mixture prior to feeding. Subjects were fed by the researcher (H.-Y.H.), in a semireclined position with the infant's neck supported, using a single-hole (0.7–0.8 mm in diameter) nipple. No stimulation was allowed 5 minutes before, during the feeding, and 5 minutes after feeding. If bradycardia (heart rate<100 beats/minute) or desaturation (saturation of peripheral O₂ [SpO₂]<85%) occurred, feeding was suspended until heart rate and oxygen saturation returned to baseline. Premature infants were not force-fed. After feeding, infants were burped and placed in a supine position at 30°. The infants' heart rate and oxygen saturation were measured 5 minutes before, during, and 5 minutes after feeding. The feeding cues of infants were observed and videotaped during the feeding period.

Measurements

Physiological responses of premature infants

Indicators of physiological responses to feeding included heart rate and SpO₂. Heart rate was measured by an electrocardiograph (model ECG 100B; Biopac System Inc., Goleta, CA). SpO₂ was measured by a noninvasive pulse oximeter (model OXY100A; Biopac System Inc.) with an error of 1.7±1.2%. The pulse oximeter sensor was placed on the same foot during each feeding. The MP100 was used for continuous recording of heart rate and SpO₂. Data that contained motion artifacts were excluded during data analysis. The premature infants' feeding cues, heart rate, and SpO₂ were measured by the primary researcher.

The mean values of heart rate and SpO₂ baseline and during feeding were calculated. Changes in heart rate and SpO₂ reflect infants' responses to environmental stimuli. Recording the changes provided additional information to measure infants' feeding responses. A heart rate event change was defined as an heart rate increase or decrease greater than 2 SD from baseline. An SpO₂ event change was defined as an SpO₂ amplitude decrease greater than 2 SD from baseline.²⁸ Any events when the SpO₂ decreased to less than 90% were specifically noted.

Behavioral responses of premature infants

The Preterm Feeding Cues Coding System (PFCCS) developed in 2005 by C.H. Lin (National Cheng Kung University Hospital, Tainan, Taiwan; personal communication) was used to measure infants' behavioral responses to feeding. The PFCCS classifies 23 feeding responses into hunger cues, self-regulatory cues, stress cues, and satiety cues. The System has a high content and face validity with an intra-observer reliability of 87–91% and inter-observer reliability of 76–82% (C.H. Lin, personal communication). As the purpose of the current study was to determine whether infants respond differently to the fresh and thawed breastmilk, only the measurements of self-regulatory and stress cues were used. Self-regulation cues include seven responses, and stress cues consist of 12 responses (Table 1). The current study only assessed 11 stress cues. Discoloration around mouth was not included because the evaluation of perioral color was difficult because of the angle of the videotape.

Table 1.

Behavioral Response of Premature Infants

Cues	Item
Self-regulation cues (7 items)	Overflow of milk; closed mouth; pushed-out nipple; intermittent sucking; frowning or painful expression; temporary cessation of sucking; yawning
Stress cues (12 items)	Vomiting/retching; coughing/choking; change in sleep state; crying; pulling up the chin; arching back; shortness of breath; incomplete swallow; making noises; continuous burping; body twisting/flushing; discoloring around mouth^a

This item was not included in the current study.

In total, 36 videos were recorded. Each video was assigned a serial number that could not to be recognized as to the types of milk being fed. The videotapes of the 36 feedings were transferred to computer software (Observer version 7.0, 2001; Noldus Information Technology, Wageningen, The Netherlands) for coding and documentation of feeding cues. Responses in the videos were coded by the primary researcher (H.-Y.Y.), who was not blinded to the types of milk being fed. Each feeding cue observed was counted as a single event response. Even if a response lasted longer than 5 seconds, it was still only counted as a single event.

Four videos were randomly selected from the total 36 samples for evaluating the reliability of observation. Intra-observer agreement of the four videos was 90% on feeding cues. Inter-observer reliability was examined by calculating the agreement between the researcher and a trained research assistant. The research assistant was familiar with the PFCCS and blinded to the types of milk being fed. The researcher and the research assistant viewed and coded the four videos independently. The average agreement for the feeding cues was 83%. The high agreement between the two coders could decrease a possible bias in coding that came from the primary researcher who was not blinded to the types of milk being fed.

Feeding performance

The feeding performance was measured with feeding time and feeding efficiency.²⁹ The feeding time was calculated from the time when the bottle nipple was inserted into each infant's mouth to the time the ordered volume of breastmilk was finished. Any time for burping infants was deducted from the feeding time. Feeding efficiency was defined as the oral intake volume divided by the feeding time in seconds (volume/second).

Statistical analysis

SPSS version 15.0 for Windows XP (SPSS, Inc., Chicago, IL) was used to manage data and perform statistical analysis. Wilcoxon matched-pairs signed rank test was used to compare heart rate, SpO₂, and feeding cues of premature infants during feeding with fresh and thawed breastmilk.

Results

Characteristics of the sample

The postmenstrual age of premature infants at the time of data collection was 36.9 weeks (range=34.6–41.0, SD=1.79). Of the 18 premature infants studied, one was diagnosed with chronic lung disease, and two required oxygen support when fed. Those three infants had a stable physical condition and appropriate oral capability assessed by NOMAS when they participated in the study (Table 2). Thawed breastmilk was frozen for a mean of 26.2 days (range, 6–98; SD=24.62).

Table 2.

Characteristics of Premature Infants (n=18)

Variable	Value	Minimum	Maximum
Gestational age (weeks)	30.2±2.49	25.4	34.1
Postmenstrual age at data collection (weeks)	36.9±1.79	34.6	41.0
Body weight (g)
At birth	1,290±320	770	1,810
Body weight at data collection	2,048±297	1588	2774
Boy	10 (55.6)
Small for gestational age	2 (11.1)
Supplemental oxygen
Before feeding	1 (5.6)
During feeding	2 (11.1)

Data are mean±SD values or number (%), as shown.

Physiological responses

Table 3 presents the comparisons of physiological responses to fresh breastmilk and thawed breastmilk. None of the heart rate parameters (baseline, during feeding, and total changed events) differed significantly between the two types of breastmilk given. Similarly, none of the SpO₂ parameters (baseline, during feeding, decreased events, and events of SpO₂<90%) differed significantly between the two types of breastmilk given.

Table 3.

Comparisons of Physiological Responses of Premature Infants Fed with Fresh and Thawed Breastmilk (n=18)

	Mean±SD
Variable	Fresh breastmilk	Thawed breastmilk	Z^a	p value
Total sample (n=18)
Heart rate
Baseline (beats/minute)	161±15	157±16	−1.33	0.184
During feeding (beats/minute)	164±9	163±12	−0.98	0.327
Total changed events	15.2±13.4	21.6±20.7	−1.73	0.084
Increased events	5.8±8.0	8.9±15.2	−1.04	0.300
Decreased events	9.4±10.3	12.7±12.9	−0.90	0.368
SpO₂
Baseline (%)	97.1±1.1	96.1±2.7	−1.63	0.102
During feeding (%)	95.4±1.8	94.7±2.6	−0.76	0.446
Decreased events	12.2±8.3	10.4±8.6	0.83	0.407
Events of SpO₂ <90% events	5.7±6.1	7.0±7.5	−0.98	0.329
PMA ≤36 weeks (n=8)
Heart rate
Total changed events	18.5±16.6	21.6±17.7	−0.280	0.779
Increased events	8.4±10.0	8.4±14.2	−0.511	0.610
Decreased events	10.1±10.7	13.3±12.5	−0.421	0.674
SpO₂
Decreased events	13.3±6.8	11.5±10.9	−0.280	0.779
SpO₂ events <90%	6.75±6.1	7.3±4.9	−0.339	0.734
PMA >36 weeks (n=10)
Heart rate
Total changed events	12.6±10.3	21.6±23.8	−2.312	0.021
Increased events	3.8±5.8	9.3±16.6	−1.068	0.285
Decreased events	8.8±10.5	12.3±13.8	−1.009	0.313
SpO₂
Decreased events	11.4±9.6	9.5±6.9	−1.126	0.260
SpO₂ events <90%	4.8±6.2	6.8±9.3	−1.018	0.309

Wilcoxon matched-pairs signed ranks test.

PMA, postmenstrual age; SpO₂, saturation of peripheral O₂.

When grouping premature infants based on postmenstrual age, results revealed that infants with a postmenstrual age greater than 36 weeks had more heart rate event changes when they were fed thawed breastmilk compared with fresh breastmilk (21.6±23.8 vs. 12.6±10.3; Z=2.31, p=0.021).

Feeding cues

The premature infants had a significantly higher number of stress cues when fed thawed breastmilk compared with when fed fresh breastmilk (p=0.007). No difference was observed in self-regulatory cues and total number of feeding cues.

When the premature infants were grouped by their postmenstrual age, results revealed that infants with a postmenstrual age greater than 36 weeks (n=10) had a significantly higher number of stress cues when fed with thawed breastmilk compared with fresh breastmilk (4.2±3.8 vs. 1.7±1.7; Z=−2.27, p=0.023). However, in the infants with postmenstrual age ≤36 weeks gestation, no significant differences in self-regulatory and stress cues were found between the two types of breastmilk given (Table 4).

Table 4.

Comparisons of Feeding Cues and Feeding Performance of Infants Fed with Fresh and Thawed Breastmilk

	Mean±SD number of cues
	Fresh breastmilk	Thawed breastmilk	Z^a	p value
Total sample (n=18)
Self-regulation cues	28.8±17.4	34.8±21.0	−1.35	0.178
Stress cues	1.9±2.0	4.2±3.6	−2.68	0.007
Total cues^b	30.8±17.9	39.0±22.9	−1.33	0.185
PMA ≤36 weeks (n=8)
Self-regulation cues	24.1±11.5	33.6±24.1	−0.93	0.352
Stress cues	2.3±2.5	4.3±3.7	−1.12	0.263
Total cues^b	26.4±11.3	37.9±26.4	−0.93	0.352
PMA >36 weeks (n=10)
Self-regulation cues	32.6±20.8	35.70±19.54	−0.83	0.406
Stress cues	1.7±1.7	4.2±3.8	−2.27	0.023
Total cues^b	34.3±21.8	39.9±21.0	−0.97	0.333
Feeding performance (n=18)
Feeding efficiency (mL/second)	0.08±0.04	0.07±0.05	−0.45	0.653
Total feeding time (seconds)	1,163±673	1,274±771	−0.697^c	0.506
Oral feeding time (seconds)	813±362	820±373	−0.092^c	0.506

Wilcoxon matched-pairs signed rank test.

Self-regulation cues+stress cues.

Paired t tests.

There were no differences in feeding time and feeding efficiency in premature infants fed with the two types of breastmilk (Table 4). The sequence in which the two milk types were given did not influence the physiological or behavioral responses to feeding.

Discussion

Premature infants demonstrated more stress cues when fed with thawed breastmilk, particularly for premature infants older than 36 weeks of postmenstrual age. There were no overall significant differences in heart rate or SpO₂ when premature infants were fed with thawed breastmilk compared with fresh breastmilk. However, feeding with thawed breastmilk caused more heart rate change events and stress cues, but only for the premature infants with a postmenstrual age greater than 36 weeks.

The results of this study revealed that substantial physical responses and feeding stress to thawed breastmilk only are evident for premature infants older than 36 weeks of postmenstrual age, not for premature infants less than 36 weeks of postmenstrual age. The findings may be explained by the maturity of olfactory sensory organs. According to Mennella and Beauchamp,³⁰ fetal sensory systems such as smell and taste are well developed at 32–34 weeks of gestation. The sense of smell plays a larger role than the sense of taste in the perception of flavor. The sense of taste can only differentiate sour, sweet, bitter, salty, and savory, while the sense of smell is capable of distinguishing thousands of odors. Moreover, a physical stable condition also determines the premature infants' responses to taste and smell.³¹

Similarly, a previous study also suggests that premature neonates at 35 weeks postmenstrual age are able to respond to maternal milk odor.²¹ While premature infants increase in developmental maturity, their sensory organs become increasingly sensitive to stimuli. This is likely why the older premature infants in this study were able to detect the altered flavor of the thawed breastmilk.

A neurological mechanism of smell sensation can be applied to explain the physiological changes and stress cues to thawed breastmilk among premature infants. Food smell in the mouth can reach the nasal cavity via the back of the throat. The neurological mechanism of smell receptors stimulating the brain explains why premature infants respond with different physiological and behavioral actions when fed thawed breastmilk.^32,33 The smell of buccal contents, enhanced by the action of swallowing, is referred to as retronasal olfaction. The smell stimulates receptors in the nasal cavity and is carried via the olfactory tract to the olfactory center of the pyriform cortex. The neurological impulses are further projected to the bottom of orbitofrontal cortex through the thalamus, where flavor is perceived and differentiated. In addition, smell receptors also project to the hypothalamus, amygdala, and hippocampus, which explains the emotional, motivational, and physiological responses caused by smell.^32,33 Previous studies have indicated the postmenstrual age and severity of illness can affect the sensory threshold of premature infants.³⁴ The learning experience of feeding and familiarity with the flavor of breastmilk can also contribute to the physiological and behavioral reactions of the premature infants to smell and taste stimulus.³⁵

For premature infants older than 36 weeks of postmenstrual age, substantial heart rate event changes are discovered when these infants are fed with thawed breastmilk. These changes in heart rate (both increases and decreases) can be explained by the gustatory-vagal hypothesis postulated by Porges and Lipsitt.³⁶ They emphasized that sucking–swallowing–breathing coordination and heart rate are controlled by the nucleus ambiguous in the brain. Therefore, when stimulated by smell and taste, premature infants may increase their sucking frequency and in turn inhibit vagal activity, resulting in an increased heart rate to meet the energy requirements of the digestive system.^37,38 Conversely, an unpleasant smell can stimulate vagal nerve activity, which may induce apnea, hypotension, and bradycardia. In addition, a strong stimulus leads to apnea and bradycardia, whereas a mild stimulus induces either fast or deeper breathing with tachycardia.³⁹

The findings of the current study demonstrate that thawed breastmilk elicits more negative physiological responses and stress cues in older premature infants. To avoid the physiological and feeding stresses induced by the rancid flavor from thawed breastmilk, older preterm infants should be provided with fresh breastmilk when they resist frozen-thawed breastmilk. To prevent stress behavior during feeding, fresh breastmilk administration to premature infants should be a priority. Neonatal nurseries need to change their traditional service rule for frozen breastmilk from “first in, first out” to “last in, first out.” However, if thawed breastmilk is given instead of fresh breastmilk, the unpleasant odor of thawed breastmilk should be considered. The unpleasant odor of thawed breastmilk results from lipolysis of fat, which increases the acid value of the milk (H.-Y.H., unpublished data, 2009). To inhibit enzyme activity of lipase and reduce rancidification, a heat treatment has been suggested in the process of freezing breastmilk.^40,41 The heat treatment means breastmilk is frozen at −20°C after undergoing a 62°C heat treatment. This procedure has been demonstrated to decline the levels of free fatty acids in the milk.⁴² Nurses may suggest the method of heat treatment to mothers with premature infants for decreasing the rancid off-flavor of thawed milk. Furthermore, caregivers should pay attention to the uncoordinated feeding patterns occurring among older premature infants. It is possible that the uncoordinated feeding responses are the results of retro-olfactory stimulation caused by the different odor of thawed breastmilk and not a developmental problem with the premature infant.

This study shows that preterm infants at a postmenstrual age close to full-term infants adversely react to thawed breastmilk given to them, compared with fresh breastmilk. The effects of frozen breastmilk on full-term infants' physiologic and behavioral responses require further investigation. In addition, further studies are required to explore physiological responses and stress cues when premature infants are fed with heat-treated breastmilk that is then frozen to see if the problem with frozen breastmilk is mitigated.

The feeding performance of the premature infants in the current study did not show obvious decline when they were fed thawed-frozen breastmilk, but their stress cues were significantly discovered. It is possible that premature infants are likely to have a weaker sucking effort to synchronize their breathing and swallowing when fed thawed breastmilk. A comparison of sucking pressure and rhythm between feeding thawed and fresh breastmilk could be examined in future studies.

A limitation of the current study is the small sample size. With a small trial, this preliminary study was prone to a Type 2 error, which reduces the ability to detect a significant difference in physiological responses when feeding thawed or fresh breastmilk. This means we probably underestimated the extent of the effect. It is likely a greater problem than we demonstrated in this study.

Conclusions

The results of this study highlight the physiological and behavioral responses among premature infants who are fed with thawed breastmilk. Maturity affects the response of premature infants who are greater than 36 weeks postmenstrual age to thawed breastmilk, as indicated by more stress cues and heart rate event changes being evident. In order to provide a pleasant oral feeding experience for premature infants, fresh breastmilk is clearly the better option over thawed breastmilk.

Footnotes

Acknowledgments

This study was founded by CHENG-HSING Medical Foundation.

Disclosure Statement

No competing financial interests exist.

References

Sears

, Sears

et al. The Premature Baby Book: Everything You Need to Know About Your Premature Baby from Birth to Age One. Little Brown: New York, 2004.

Jensen

. Handbook of Milk Composition. Academic Press: San Diego, CA, 1995.

Kellymom. My Expressed Breast Milk Doesn't Smell Fresh. What Can I Do? www.kellymom.com/bf/pumping/lipase-expressedmilk.html. 2009 January 15.

Lawrence

. Breastfeeding: A Guide for the Medical Profession. Mosby: St. Louis, 1994.

Jensen

. Lipids in breast milk. Lipids, 1999; 34:1243–1271.

McCain

. An evidence-based guideline for introducing oral feeding to healthy preterm infants. Neonatal Netw, 2003; 22:45–50.

Beverly

, Coeart , Gary

et al. Development of taste and smell in the neonate. Polin

, Abman

. Fetal and Neonatal Physiology. Saunders/Elsevier: Philadelphia, 2004; 1819–1827.

Parker

. The Encyclopedic Atlas of the Human Body: A Visual Guide to the Human Body. Global Book: Lane Cove, Australia, 2004.

Gesteland

, Yancey

, Farbman

. Development of olfactory receptor neuron selectivity in the rat fetus. Neuroscience, 1982; 7:3127–3136.

10.

Miller

. Deglutition. Physiol Rev, 1982; 62:129–184.

11.

Mistretta

, Bradley

. Taste responses in sheep medulla: Changes during development. Science, 1978; 202:535–537.

12.

Mennella

. Mother's milk: A medium for early flavor experiences. J Hum Lact, 1995; 11:39–45.

13.

Greer

. Nutrition support of the premature infant. Baker

, Baker

, Davis

. Pediatric Nutrition Support. Jones and Bartlett: Sudbury, MA, 2007; 383–393.

14.

Mistretta

, Bradley

. Taste and swallowing in utero. Br Med Bull, 1975; 31:80–84.

15.

Harding

. Milk Quality. Blackie Academic & Professional: London, 1995.

16.

Novak

, Junqueira

, Dias

et al. Sensorial analysis of expressed human milk and its microbial load. J Pediatr, 2008; 84:181–184.

17.

Deeth

. Lipoprotein lipase and lipolysis in milk. Int Dairy J, 2006; 16:555–562.

18.

Crook

. Neonatal sucking: Effects of quantity of the response-contingent fluid upon sucking rhythm and heart rate. J Exp Child Psychol, 1976; 21:539–548.

19.

Maone

, Mattes

, Bernbaum

et al. A new method for delivering a taste without fluids to preterm and term infants. Dev Psychobiol, 1990; 23:179–191.

20.

Ramenghi

, Wood

, Griffith

et al. Reduction of pain response in premature infants using intraoral sucrose. Arch Dis Child Fetal Neonatal Ed, 1996; 74:F126–F128.

21.

Raimbault

, Saliba

, Porter

. The effect of the odour of mother's milk on breastfeeding behaviour of premature neonates. Acta Paediatr, 2007; 96:368–371.

22.

Rosenstein

, Oster

. Differential facial responses to four basic tastes in newborns. Child Dev, 1988; 59:1555–1568.

23.

Zhang

, Li

. Taste development in Chinese newborn. World J Pediatr, 2007; 3:203–208.

24.

Van Reempts

, Wouters

, De Cock

et al. Stress responses to tilting and odor stimulus in preterm neonates after intrauterine conditions associated with chronic stress. Physiol Behav, 1997; 61:419–424.

25.

Soussignan

, Schaal

, Marlier

et al. Facial and autonomic responses to biological and artificial olfactory stimuli in human neonates: Re-examining early hedonic discrimination of odors. Physiol Behav, 1997; 62:745–758.

26.

Soussignan

, Schaal

, Marlier

. Olfactory alliesthesia in human neonates: Prandial state and stimulus familiarity modulate facial and autonomic responses to milk odors. Dev Psychobiol, 1999; 35:3–14.

27.

Case-Smith

, Cooper

, Scala

. Feeding efficiency of premature neonates. Am J Occup Ther, 1989; 43:245–250.

28.

Harrison

, Berbaum

, Stem

et al. Use of individualized versus standard criteria to identify abnormal levels of heart rate or oxygen saturation in preterm infants. J Nurs Meas, 2001; 9:181–200.

29.

Lau

, Schanler

. Oral feeding in premature infants: Advantage of a self-paced milk flow. Acta Paediatr, 2000; 89:453–459.

30.

Mennella

, Beauchamp

. Early flavor experiences: Research update. Nutr Rev, 1998; 56:205–211.

31.

Schaal

, Hummel

, Soussignan

. Olfaction in the fetal and premature infant: Functional status and clinical implications. Clin Perinatol, 2004; 31:261–285.

32.

Brand

. Olfactory/trigeminal interactions in nasal chemoreception. Neurosci Biobehav Rev, 2006; 30:908–917.

33.

Browne

. Chemosensory development in the fetus and newborn. Newborn Infant Nurs Rev, 2008; 8:180–186.

34.

Sarnat

. Olfactory reflexes in the newborn infant. J Pediatr, 1978; 92:624–626.

35.

Porter

, Raimbault

, Henrot

et al. Responses of pre-term Infants to the odour of mother's milk. Hurst

, Beynon

, Roberts

. et al. Chemical Signals in Vertebrates 11. Springer, New York, 2007; 337–342. www.springerlink.com/content/pmj288005647w80m/. 2009 November 13.

36.

Porges

, Lipsitt

. Neonatal responsively to gustatory stimulation: The gustatory-vagal hypothesis. Infant Behav Dev, 1993; 16:487–494.

37.

Porges

. Cardiac vagal tone: A physiological index of stress. Neurosci Biobehav Rev, 1995; 19:225–233.

38.

Sahni

, Schulze

, Kashyap

et al. Maturational changes in heart rate and heart rate variability in low birth weight infants. Dev Psychobiol, 2000; 37:73–81.

39.

Daly

, Angell-James

. The diving response and its possible clinical implications. Ann Intern Med, 1979; 1:12–19.

40.

Scanlan

, Bather

, Day

. Contribution of free fatty acids to the flavor of rancid milk. J Dairy Sci, 1965; 48:1582.

41.

Hernell

, Olivecrona

. Human milk lipases. I. Serum-stimulated lipase. J Lipid Res, 1974; 15:367.

42.

Slutzah

, Codipilly

, Potak

et al. Refrigerator storage of expressed human milk in the neonatal intensive care unit. J Pediatr, 2009; 155:336–340.

Comparison of Physiological and Behavioral Responses to Fresh and Thawed Breastmilk in Premature Infants—A Preliminary Study

Abstract

Abstract

Background:

Subjects and Methods:

Results:

Conclusions:

Introduction

Subjects and Methods

Protocol

Subjects

Subject assignment

Handling of breastmilk

Measurements

Physiological responses of premature infants

Behavioral responses of premature infants

Feeding performance

Statistical analysis

Results

Characteristics of the sample

Physiological responses

Feeding cues

Discussion

Conclusions

Footnotes

Acknowledgments

Disclosure Statement

References