Early enteral feeding is the current standard protocol for preterm infants, as enteral nutrition has significant nutritional and non-nutritional benefits compared with parenteral nutrition [1]. To achieve enteral nutrition, the use of orogastric or nasogastric tubes is necessary for preterm infants born before 32 weeks of pregnancy because of underdeveloped suck-swallow-breath coordination [2]. However, even with gavage tubes enteral feeding is difficult for preterm infants, especially in addition to respiratory support.

Feeding-related cardiorespiratory symptoms are prevalent among preterm infants. Studies on feeding-associated cardiorespiratory events have identified suitable enteral feeding methods; however, no consensus has been reached on a feeding method for preterm infants with feeding-associated cardiorespiratory deterioration. As such, the feeding method for each patient is based on the judgment of the clinician.

In our center, slow infusion intermittent feeding (SIIF) was applied to reduce feeding-associated cardiorespiratory events, which consisted of 1 hour of feeding with an infusion pump followed by 2 hours of rest. This study aimed to determine whether SIIF could reduce cardiorespiratory deterioration during gavage feeding in preterm infants.

A total of 376 preterm infants with birth weights <1,500 g or gestational ages <32 weeks were born between January 2019 and March 2023. Among them, 34 patients whose feeding method was changed to SIIF were enrolled in this study. The study population demographics and clinical characteristics are presented in Table 1. The mean gestational age was 26.4±1.9 weeks and mean birth weight was 857.7±265.1 g. The mean postmenstrual age at the time of SIIF application was 30.1±1.9 weeks, and the duration of SIIF was 25.4±14.0 days. The mean postmenstrual age at the end of SIIF was 33.6±2.3 weeks.

To date, there is no consensus regarding the optimal feeding method for preterm infants with feeding-related cardiorespiratory deterioration. A Cochrane review and meta-analysis of randomized controlled trials found no significant differences in the duration of hospitalization, duration of parental feeding, weight gain, and incidence of NEC between continuous and bolus feeding in preterm infants with low birth weight [4,5].

Both intermittent and continuous bolus feeding have advantages and disadvantages. Bolus feeding is a physiological method that promotes the circadian rhythm of intestinal hormones and postprandial rhythms of ghrelin and insulin release in response to nutrition [6]. Recent studies comparing bolus feeding and continuous feeding in a newborn piglet model found that intermittent bolus feeding promotes greater lean growth and protein anabolism and enhances protein synthesis [7,8]. However, several investigators have demonstrated that 24-hour continuous feeding has several advantages over bolus feeding, especially in critically ill patients [9,10]. Previous studies have shown that continuous nutrient administration is associated with fewer gastrointestinal and respiratory complications [11,12]. In preterm infants, particularly in those with a much smaller gastric capacity, bolus feedingrelated feeding intolerance and pulmonary function impairment are obvious and have been described in several studies [2,13,14]. Blondheim et al. [2] compared the effects of intermittent and continuous feeding on the pulmonary function of very low birth weight infants and found a significant decrease in tidal volume, minute ventilation, and dynamic compliance after intermittent feeding. Furthermore, infants receiving noninvasive ventilation experience an unintended influx of air through the nasopharynx, leading to marked abdominal distention, known as continuous positive airway pressure (CPAP) belly syndrome [15]. Excessive swallowed air increases the intra-abdominal pressure, which requires an increase in CPAP pressure to alleviate, resulting in a vicious cycle [15]. In addition, a large volume of enteral feeding during noninvasive ventilator support exacerbates respiratory deterioration. D'Angelo et al. [16] found that with greater levels of abdominal distension in the supine position, both the electromechanical efficiency of the diaphragm and tidal volume declined in anesthetized rabbits. A recent meta-analysis of randomized controlled trials on continuous versus intermittent bolus feeding showed that more days of continuous feeding were needed to achieve full feeding, but there were no significant differences in feeding intolerance, duration of hospitalization, duration of parental feeding, weight gain, or proven NEC [4].

In the current study, we suggest a compromised method, SIIF, which can reduce the respiratory burden of preterm infants who require respiratory support during feeding and minimize the complications of 24-hour continuous feeding by providing a 3-hour interval between feedings. We found SIIF to significantly reduce feeding-associated cardiorespiratory events and respiratory support levels.

As cardiorespiratory events in preterm infants are affected by various factors, we attempted to monitor the acute effect of SIIF by comparing events 24 hours before and after the application of SIIF. We excluded infants with other factors that could affect cardiorespiratory events beyond the feeding modality, such as clinical or culture-proven sepsis, or those within 3 days of surgical treatment. A single researcher reviewed and analyzed every cardiorespiratory event detected by bedside cardiorespiratory monitors in all patients by reviewing the electronic medical records completed by the assigned nurses. After SIIF, 27 of 34 patients (79.6%) showed a decrease in the level of ventilator support or no change in the respiratory support modality, and all patients showed significantly decreased rates of feeding-related respiratory deterioration. The levels of respiratory support increased after SIIF in seven patients who were then weaned from ventilator support or were in the middle of the BPD aggravation period. Even though respiratory support increased, five of the seven patients showed a decrease in the number of cardiorespiratory events after SIIF.

This study had some limitations. First, the measurement of cardiorespiratory events relied entirely on alarms detected by the cardiorespiratory monitor; as such, events that recovered before the alarm activated may have been missed. In addition, there are no definite criteria for feeding-related alarms in preterm infants because the gastric emptying time may be longer depending on the gestational age and other conditions. In this study, events that occurred during or within 30 minutes after 1-hour of feeding were considered feeding-related cardiorespiratory events. Because this was a single-center retrospective study with a small sample size, multicenter, larger-sample studies are needed to further evaluate the effectiveness of SIIF. To clarify the effect of SIIF, a crossover study or comparison with a control group is also required. Finally, we focused only on the respiratory-related outcomes after SIIF. Further studies on SIIF-related gastrointestinal outcomes, such as the time to reach full enteral feeding, duration of gavage feeding, and symptoms associated with feeding intolerance, are also needed.

In conclusion, SIIF significantly reduced the frequency of feeding-related cardiorespiratory events in preterm infants requiring invasive and noninvasive respiratory support. Additionally, the degree of ventilator support significantly decreased after SIIF. Therefore, SIIF may be a therapeutic option for gavage feedingassociated cardiorespiratory deterioration in preterm infants in the NICU.