Effect of a Delayed Start to Oral Feeding on Feeding Performance and Physiological Responses in Preterm Infants: A Randomized Clinical Trial

Abstract

Background: 

The efficient and safe oral feeding of preterm infants, an essential criterion for hospital discharge, is affected by neurodevelopmental maturation. However, the timing of initiating oral feeding and its relation to maturation, feeding performance, and physiological responses are unclear.

Purpose: 

The aim of this study was to determine the effect of a 1-week delay in the initiation of oral feeding on feeding performance, transition time, weight gain, and cardiorespiratory responses in preterm infants.

Methods: 

In this randomized controlled trial, 40 infants with a gestational age at birth of less than 32 weeks were recruited. The control group (n = 18) began oral feeding when the infants were physiologically stable, whereas the experimental group (n = 22) began oral feeding 1 week later. Infant feeding performance, heart rate, and oxygen saturation were measured before, during, and after feeding on the first day of oral feeding and 3 days later. Daily weight gain was calculated by measuring body weight every morning, and transition time was calculated by counting the number of days from the initiation of oral feeding to the termination of tube feeding.

Results: 

There were no significant differences between the two groups in terms of feeding performance, weight gain, or postmenstrual age at the completion of full oral feeding. The transition time was significantly shorter in the experimental group than in the control group. More infants in the control group experienced episodes of oxygen desaturation during feeding than in the experimental group.

Conclusions/Implications for Practice: 

For infants with a postmenstrual age of greater than 32 weeks who are ready to initiate oral feeding, postponing oral bottle feeding for 1 week may be considered as an intervention to reduce physiological distress.

Introduction

Oral feeding is an essential criterion that preterm infants must achieve for hospital discharge (^{American Academy of Pediatrics Committee on Fetus and Newborn, 2008}). Therefore, successful transition to oral feeding is an important developmental milestone that is essential for growth and beneficial in mother–infant reunification (^{American Academy of Pediatrics Committee on Fetus and Newborn, 2008}; ^{Bertoncelli et al., 2012}; ^{Jadcherla et al., 2017}). Efficient and safe oral feeding requires the maturation of neurodevelopmental functions, including the regulation of behavioral states, the coordination of breathing with sucking and swallowing, and the stabilization of cardiorespiratory functions (^{Browne & Ross, 2011}). Functional sucking and swallowing occur in infants as early as 28–29 weeks of postmenstrual age (PMA; ^{Browne & Ross, 2011}; ^{Holloway, 2014}). At 32–34 weeks of PMA, physiologically stable infants exhibit early suck–swallow–breathe patterns and may be introduced to oral bottle feeding at 32–35 weeks of PMA (^{Browne & Ross, 2011}; ^{Gennattasio, Perri, Baranek, & Rohan, 2015}; ^{Holloway, 2014}).

The transition time from tube feeding to complete oral feeding for preterm infants who are born before the gestational age (GA) of 32 weeks and who start oral feeding at 32–34 weeks of PMA is 7–16 days (^{Hwang, Ma, Tseng, & Tsai, 2013}; ^{Pickler, Best, & Crosson, 2009}). Neurobehavioral readiness and ability to cope with the physiological stresses of oral feeding are crucial factors for successful oral feeding in preterm infants (^{Gennattasio et al., 2015}). Both premature development and severe disease exacerbate the difficulty of oral feeding in preterm infants (^{Hwang et al., 2013}; ^{Park, Knafl, Thoyre, & Brandon, 2015}; ^{Van Nostrand, Bennett, Coraglio, Guo, & Muraskas, 2015}). Therefore, bronchopulmonary dysplasia (BPD), characterized by immature lung functioning and extended oxygen dependency, is a critical factor influencing suck–swallow–breathe coordination and oral feeding milestones in preterm infants (^{da Costa et al., 2010}; ^{Mizuno et al., 2007}; ^{Van Nostrand et al., 2015}). Because of compromised ventilation and immature autonomic regulation, infants may experience problems such as desaturation, bradycardia, hypoxemia, and increased energy consumption when learning to feed orally (^{Holloway, 2014}; ^{Mizuno et al., 2007}). Although numerous researchers and clinical practitioners have emphasized that maturation is the determining factor for successful and safe oral feeding, it is also crucial to provide opportunities to practice feeding at an earlier age (^{Gennattasio et al., 2015}; ^{Pickler et al., 2009}; ^{Pickler, Reyna, Wetzel, & Lewis, 2015}). A recent randomized controlled trial on 86 infants showed that, when these infants were orally fed at a later PMA of 34 weeks at a maximum allowed daily feeding frequency, the PMA at which they completed full oral feeding and discharge did not differ from infants who were orally fed at an earlier PMA of 32 weeks (^{Pickler et al., 2015}). However, little is known regarding the differences in physiological responses of orally fed infants who have earlier and later PMAs (32 and 34 weeks, respectively). The timing for initiating oral feeding in preterm infants requires further evidence regarding feeding performance and physiological responses to support clinical decisions.

According to our clinical observations, choking, shortness of breath, hypoxia, and fatigue are common stress responses of healthy preterm infants who start oral feeding at 32 weeks of PMA. During the transition period from tube to oral feeding, the infants’ responses to feeding were variable, depending on their physiological stability and coordination of suck–swallow–breathe patterns. To some extent, the clinical decision to initiate oral feeding in preterm infants is still based on trial and error. The physiological distress that accompanies this process increases the risk of hypoxia and excessive energy consumption and creates a negative feeding experience in preterm infants. One study showed a positive correlation between a smooth feeding experience and favorable clinical outcomes in preterm infants (^{Pickler et al., 2009}). A follow-up study explored the maturation of feeding behavior in 26 healthy preterm infants from 32 to 36 weeks of PMA, showing that the sucking efficiency was better and the extent of oxygen desaturation was less at 33 weeks of PMA than at 32 weeks of PMA (^{Mizuno & Ueda, 2003}). Therefore, this study aimed to determine whether delaying the initiation of oral feeding for 1 week reduces physiological stress and improves feeding performance, transition time, weight gain, and cardiorespiratory responses in infants.

Methods

Design and Sample

A stratified randomized clinical trial was conducted to compare the outcomes of feeding performance, transition time, weight gain, and cardiorespiratory responses between two oral feeding groups of preterm infants. The study was approved by an institutional review board of a university hospital, and informed consent was obtained from the parents of all preterm infants before infant enrollment.

Eligible preterm infants with a GA of less than 32 weeks at birth who were enterally feeding, were without mechanical ventilation, and had been admitted to the neonatal intensive care unit of a hospital in southern Taiwan were recruited. Infants with congenital abnormalities, systemic infections, gastrointestinal diseases, Grade III intraventricular hemorrhages, or neurological disorders were excluded. Breastfeeding infants were also excluded. Before the experiment began, infants at 32 weeks of PMA were assessed by neonatologists and nurses to verify that they were sufficiently, physiologically stable for initiating oral feeding and that they expressed feeding cues. The indicators of physiological stability were composed of a respiratory rate of less than 60 breaths per minute, no apnea (defined as cessation of respiratory for more than 20 seconds), and no bradycardia (defined as heart rate [HR] of less than 100 beats per minute within a 3-day period; ^{McCain, 2003}). The feeding cue was showing a regular pattern of nonnutritive sucks (^{McCain, 2003}). Because of the lack of available evidence on transition time for calculating sample size, the sample size was estimated according to the observation of the first 10 infants enrolled (^{Sullivan, 2011}), whose effect size for transition time was 0.99, with a mean difference of 7.0 and a standard deviation of 7.01. According to the effect size, 18 infants in each group were determined as necessary to reach an 80% power with an alpha level of .05.

Procedures

After the parents provided informed consent, infants who met the inclusion criteria were assessed for eligibility by neonatologists and nurses with more than 2 years of experience. The nurses and neonatologists were trained by the same researcher to ensure their understanding of the eligibility assessment. The infants were given pacifiers as a standard care practice for promoting sucking behavior and physiologic stability before 32 weeks of PMA (^{Foster, Psaila, & Patterson, 2016}). When the eligible infants were assessed as ready for oral feeding, they were randomized into the control or experimental group after being stratified by incidence of BPD, which was defined as a supplemental oxygen requirement lasting more than 28 days after birth (^{Bowen & Maxwell, 2014}). Randomization was performed by a researcher who was uninvolved in the study and who recorded the arrangement for each identification number in a sealed envelope. Oral feeding was initiated in the control group immediately if the infants passed the eligibility assessment. In the experimental group, oral feeding was initiated 7 days after the infants passed the eligibility assessment. Infants in the two groups were fed at 3-hour intervals by nurses with more than 2 years of experience. The outcomes of feeding performance and cardiorespiratory responses in each group were measured at two time points: the first oral feeding (Day 0) and 3 days later (Day 3). Bottle feedings on Days 0 and 3 were performed by a trained nurse with 10 years of experience in the neonatal intensive care unit, whereas the outcomes of feeding performance and physiological responses were measured by the research assistant. The oral feeding protocol for this study was based on the guideline developed by ^{McCain (2003)}. This gavage/oral feeding guideline is a semidemand feeding method that was established according to the neurodevelopment of behavior organization, suck–swallow–breathe patterns, and cardiorespiratory regulation in preterm infants. Before feeding, nonnutritive sucking was offered for 10 minutes, and behavioral state was assessed to identify feeding readiness (^{McCain, 2003}). If the oxygen saturation (SpO₂) decreased below 80% or no oral movement occurred during oral feeding, feeding was paused until the SpO₂ exceeded 90% and feeding readiness was exhibited. To avoid infant fatigue, a maximum 20-minute duration was allowed for oral feeding. The remaining prescribed milk was fed through a preplaced orogastric tube after oral feeding. Daily weight gain was recorded until the infants were no longer dependent on tube feeding (Figure 1).

Figure 1.: Flow diagram of the participant allocation procedure.

Measurements

The indicators for feeding performance were total intake, feeding duration, and feeding efficiency (^{Lau & Schanler, 2000}). Total intake was defined as the percentage of the volume fed by bottle to the total volume of milk that was prescribed for each feeding. Cotton tissues were weighed before and after each oral feeding using an electronic scale (JADEVER JKD-250; Jadever Scale Co. Ltd., New Taipei City, Taiwan), with an error of ± 0.01 g to account for seepage, which was later deducted. Feeding duration, which was defined as the oral feeding time minus rest and burp times, was recorded by a trained research assistant. Feeding efficiency was calculated as the volume of oral feeding per unit of time (milliliters per minute) for each feeding session. Total feeding amount was defined as the total volume (milliliters) fed by bottle and orogastric tube.

Cardiorespiratory responses observed during oral feeding were HR and SpO₂. HR and SpO₂ were measured using an electrocardiographic monitor (Biopac ECG100A; BIOPAC Systems Inc., Goleta, CA, USA) and a pulse oximeter (Biopac OXY100C; BIOPAC Systems Inc., Goleta, CA, USA), which were attached to the infant’s foot. Continuous measurements of HR and SpO₂ were recorded using a computerized data acquisition system (Biopac MP100; BIOPAC Systems Inc., Goleta, CA, USA) 10 minutes before, during, and 10 minutes after each oral feeding. Motion artifacts were excluded during data coding. The frequency of desaturation episodes, which was defined as declines in SpO₂ to less than 90% for longer than 20 seconds, was determined through visual examination (^{Chang, Anderson, Dowling, & Lin, 2002}).

Infant body weight was measured using an electronic scale (Digital Baby Scale DS-200; Taiwan) at 8:30 A.M. every day. Daily weight gain was recorded until the infant was weaned from tube feeding. The transition time was calculated as the number of days from the initiation of oral feeding to the termination of tube feeding, which occurred when all of the prescribed volumes were fed orally without tube feeding assistance in 24 hours (^{McCain, 2003}).

All of the data were collected and managed by the research assistant, who was trained by the corresponding author for 4 months on preterm-infant feeding and on the use of the measurement system. There was a 90% consistency of artifact checking in the computerized data acquisition system between the research assistant and the corresponding author.

Data Analysis

The data of outcome indicators were normally distributed. Therefore, an independent t test was employed to determine the differences between the two groups in terms of infant characteristics, feeding performance parameters, and cardiorespiratory responses. The Mann–Whitney U test was conducted to assess differences in daily weight gain, PMA at the completion of oral feeding, and transition time between the two groups for infants with and without BPD. The Fisher exact test was used to compare the number of desaturation episodes between the two groups before, during, and after feeding. An alpha level of .05 (two-tailed) was set for significance. SPSS software for Windows (Version 17.0; SPSS Inc., Chicago, IL, USA) was employed to analyze the data.

Results

Forty preterm infants (22 in the experimental group and 18 in the control group) were enrolled in this study. No significant differences were identified between the two groups in terms of the infant characteristics of GA, birth weight, and weight on the first day of oral feeding. Although preterm infants in the experimental group started oral feeding 1 week later than those in the control group, the infants in both groups were completely weaned from tube feeding at the same PMA (36.3 ± 1.6 vs. 36.2 ± 1.7 days, t = 0.20, p > .05) because of a shorter transition time in the experimental group (12.7 ± 6.7 vs. 18.1 ± 7.1 days, t = 2.30, p = .03). No difference between the two groups was observed in terms of daily weight gain (21.5 ± 8.7 vs. 22.8 ± 6.3 days, t = 0.49, p > .05; Table 1).

TABLE 1.: Infant Characteristics and Transition Times (N = 40)

The duration until infants were considered ready to feed orally after birth was 26.4 ± 14.9 days (range = 5–56 days) in infants without BPD and 59.1 ± 10.8 days (range = 45–95 days) in infants with BPD. Among the infants with or without BPD, there was no difference in daily weight gain or PMA at the completion of oral feeding between the experimental and control groups. However, the results of the Mann–Whitney U test showed that infants without BPD had a shorter transition time in the experimental group (n = 11) than those in the control group (n = 10; 9.8 ± 4.5 vs. 18.7 ± 8.7 days, p = .02). No significant difference in transition time was identified between the experimental (n = 11) and control (n = 8) groups among infants with BPD (15.2 ± 7.5 vs. 17.3 ± 4.6 days).

Regarding feeding performance, no difference was found in terms of the total intake, feeding duration, or feeding efficiency between the two groups at the two time points that were measured (Table 2). The total feeding amount for the experimental group on Day 0 was significantly higher than that of the control group (16.9 ± 12.0 vs. 10.1 ± 6.8 ml, t = 2.12, p = .04). Table 2 presents the increases in the total feeding amount, total intake, and feeding efficiency of the two groups.

TABLE 2.: Comparison of Feeding Performance and Cardiorespiratory Responses (N = 40)

The infants in both groups had similar HRs at 10 minutes before oral feeding on Days 0 and 3. For both groups, the HR increased during feeding and returned to the baseline level 10 minutes after feeding (159 ± 15 vs. 168 ± 10 beats per minute, t = 2.09, p = .04). However, on Day 3, the HR of the infants in the experimental group during feeding was significantly lower than that of the control group. The magnitude of the increase in HR during feeding for the experimental group on Day 3 was not greater than that observed on Day 0. The SpO₂ of both groups measured at both time points showed a minor reduction from the baseline during the feeding process but returned to the baseline after feeding (Table 2).

The SpO₂ decrease in the control group was greater than that in the experimental group during feeding on Day 3, although no significant difference was observed (Table 2). Infants in both groups experienced episodes of oxygen desaturation during the two measurements (Table 3). On Day 0, more infants in the control group experienced episodes of desaturation before (p = .002) and during (p < .001) feeding than their experimental group peers. Moreover, on Day 3, more infants in the control group experienced episodes of desaturation during feeding than their experimental group peers (p = .004).

TABLE 3.: Infants Experiencing Episodes of Oxygen Desaturation

Discussion

The results of this study indicate that the delayed start of oral feeding in preterm infants shorten the transition time and reduce physiological stress during this critical period. Furthermore, the delayed start had no effect on feeding performance parameters, PMA upon completing oral feeding, or weight gain. These findings are consistent with those of a study that compared the effect of maturation and practice factors on the transition time of bottle feeding in preterm infants (^{Pickler et al., 2015}), finding that the age at which the preterm infants achieved complete oral feeding was not affected by the time at which they started oral feeding (^{Pickler et al., 2015}). Preterm infants with low GA and PMA at the first oral feeding have a longer transition to the oral feeding process (^{Park et al., 2015}; ^{White-Traut et al., 2013}). Rhythmic sucking and swallowing, which are necessary for complete oral feeding, are closely associated with the maturation of neuromuscular functions; however, feeding practice has no association with the maturation of these functions (^{Browne & Ross, 2011}). In addition, a recent clinical trial showed that the PMAs of infants who had completed full oral feeding were the same, irrespective of whether preterm infants had received swallowing and sucking exercises (^{Lau & Smith, 2012}). Although oral stimulation may improve the feeding performance of preterm infants who experience feeding difficulties after their initial oral feeding, feeding practice does not accelerate the maturation timeline of feeding competence (^{Hwang et al., 2010}; ^{Lau & Smith, 2012}). The higher total feeding amount in the delayed-start oral feeding group on Day 0 may have been caused by the greater nutritional needs and the better mature gastrointestinal tract functions of the experimental group infants, who were 1 week older than their counterparts at that time. Therefore, the indicators for feeding performance, including total intake of oral feeding, feeding duration, and feeding efficiency, were the same for the two groups in our study. Confirming the findings of a previous study (^{Pickler et al., 2015}), this study also revealed that infants with a delayed start in oral feeding achieved full oral feeding at the same PMA and had the same weight gain as infants who started oral feeding 1 week earlier. These findings indicate that a 1-week delay in starting oral feeding does not negatively affect preterm infant feeding performance and growth during the transition time.

Moreover, the delayed-start oral feeding infants exhibited fewer oxygen desaturation episodes and steadier HRs during the feeding process. Some nonexperimental descriptive studies have shown that, after exhibiting oral feeding readiness, preterm infants should be provided a maximal number of opportunities for oral feeding as learning experiences for neurological maturation as well as be helped to achieve earlier full oral feeding (^{Pickler et al., 2009}; ^{Tubbs-Cooley, Pickler, & Meinzen-Derr, 2015}). Physiological stability at the time of feeding is the determinant criterion for oral feeding readiness (^{Tubbs-Cooley et al., 2015}). Safe oral feeding requires mature sucking, swallowing, and respiration as well as coordination among the muscles that are involved in these functions (^{Rommel et al., 2011}). The sucking pattern of preterm infants at 33–34 weeks of PMA resembles that of term infants, involving rhythmic alternation of suction and expression, which are the principal motor components of nutritive sucking (^{Amaizu, Shulman, Schanler, & Lau, 2008}). However, with the maturation of respiratory control, the pharyngoesophageal function of infants before 32 weeks of PMA is still weaker than at 33–36 weeks of PMA (^{Lorch, Srinivasan, & Escobar, 2011}; ^{Rommel et al., 2011}). During feeding, preterm infants tend to continue to breathe during swallowing and/or exhibit prolonged inhibition of respiration, leading to apnea. These phenomena disrupt the complex coordination among sucking, swallowing, and breathing functions (^{Vice & Gewolb, 2008}). The immature respiratory control of preterm infants has been shown to reduce respiratory rate and functional residual capacity, resulting in apnea, decreased ventilation, lower tidal volume, and insufficient oxygen supply (^{Mathew, 1988}). Insufficient oxygen supply during feeding increases the requirement for supplemental oxygen and is related to necrotizing enteritis (^{Lorch et al., 2011}). The increased workload in sucking–swallowing and the process of nutrient intake have been shown to increase HR during feeding (^{Suiter & Ruark-McMurtrey, 2007}). In addition, increased HR has been shown to indicate increased oxygen consumption (^{Goldfield, Richardson, Lee, & Margetts, 2006}). Therefore, preterm infants may exhibit reduced desaturation as well as cardiorespiratory regulation that is more secure if oral feeding is delayed to 1 week after the age of oral feeding readiness.

The randomization of the infants was stratified by BPD, which is an important factor influencing oral feeding in preterm infants (^{Mizuno et al., 2007}; ^{Van Nostrand et al., 2015}). This study showed that the delayed start of oral feeding in infants with BPD may not affect transition time, as compared with that of infants with BPD in the control group. However, the infants without BPD had a significantly shorter transition time than those with BPD in the experimental group. This finding may be attributable to the underlying pathogenesis of BPD, particularly the possibilities of delayed pulmonary maturation and feeding competence, which are related to this condition (^{da Costa et al., 2010}). However, because of the small sample size of infants with BPD, additional studies on the effects of BPD on delayed oral feeding in preterm infants are required to address their special circumstances.

Clinically, it is tempting to start orally feeding preterm infants earlier rather than later because of the potential negative effects of tube feeding such as oral hypersensitivity, crying, refusal to feed, and esophageal and/or pharyngeal inflammation as well as because successful oral feeding is a criterion for discharge from the hospital (^{Thomas, 2007}). However, this study showed that infants with a delayed start to oral bottle feeding had the same PMA at the time of completion as those infants whose start had not been delayed because of a reduced transition time. Although the adverse effects of tube feeding were not assessed, for preterm infants older than 32 weeks of PMA who were ready to initiate oral feeding, a 1-week delay in the start of oral bottle feeding did not prolong the overall duration of tube feeding. Furthermore, infants with a delayed start to oral bottle feeding experienced less physiological stress than their counterparts in the control group. HRs during feeding in both groups fell within acceptable parameters, although the control group had significantly higher mean HR values than the experimental group. A rise in HR leads to increased energy expenditure (^{Goldfield et al., 2006}). Whether the cumulative effect of increased energy expenditure during feeding across the transitional period had an adverse effect on preterm infants is unknown. A shorter transition time and a lower physiological burden may create a pleasurable oral feeding experience for preterm infants and may lead to a more favorable clinical outcome. In addition, the manpower costs of feeding infants and resolving oxygen desaturation complications may be reduced.

Several limitations affected this study. First, the small sample size of the subgroups in infants with BPD limits the generalizability of results to other populations. Second, the nurses (including the trained nurse who provided oral feeding) and parents were not blinded to the intervention allocation. Whether there is a performance bias is unknown. Third, the effect of desaturation before feeding on the relationship between desaturation during feeding and the delayed start of oral feeding is unknown and should be investigated in the future. Finally, this study was limited to infants who were bottle-fed and physiologically stable at a PMA of more than 32 weeks. Whether the effect of a delayed start to oral feeding is similar in breastfeeding infants or in infants of different PMAs or physical conditions is unknown. Because the suck–swallow–breathe coordination and SpO₂ differ between the processes of breastfeeding and bottle feeding (^{Gutierrez & Theodorou, 2012}), we do not know whether delayed oral feeding in breastfeeding will yield the same results as in bottle feeding. Further research on breastfeeding infants and on infants with different PMAs and physical conditions than those explored herein is needed.

Conclusions

This study shows that the delayed initiation of oral feeding in physiologically stable preterm infants shortens the transition time without increasing the overall duration of tube feeding and may reduce the cardiorespiratory burden during the transition time. Therefore, the start of oral feeding in preterm infants with a PMA of more than 32 weeks who are ready to initiate oral feeding may be delayed for 1 week to reduce physiological distress and to achieve the same clinical outcome as that achieved without a delay in oral feeding.