Neonatal small intestinal motility' Motor responses to feeding in term and preterm infants C. L. Berseth, MD From the Department of Pediatrics, Mayo Clinic, Rochester, Minnesota
To explore the possibility that the intestinal motor response to feeding is intact even in infants with immature fasting patterns, we performed low-compliance, continuous-infusion manometry in 13 term and 23 preterm infants during the first postnatal week. Babies were fed a standard formula intraduodenally at 4 m l / k g / 2 hr by infusion pump. Small bowel motility responded to feeding; fasting patterns were replaced with long periods of persistent activity. During the infusion of formula, there was no significant difference in motor activity between preterm and term infants. Four characteristics of motor activity changed with feeding: motility index, the number of pressure peaks per 30-minute period, mean amplitude of pressure peaks, and duration of periods of quiescence. The number of pressure peaks per 30-minute period was the most sensitlve index of the motor response to feeding, and it was used to characterize the fed pattern response. The start and duration of the fed response were similar in both groups of infants. Thus, despite the presence of immaturity in fasting patterns, the intestine of the preterm infant responds appropriately to feeding. These data help explain why preterm infants usually tolerate antral feedings, and support their use. (J PEDIATR1990;117:777-82)
During fasting, term infants have interdigestive cycles of motility (the interdigestive motility cycle) containing periods that feature quiescence, nonpropagating activity, and then phasic propagative activity, called the migrating motor complex.l' 2 When given a feeding, term infants have a well-recognized motor response of persisting activity called the fed pattern. 2 In contrast to term infants, few preterm infants have MMCs during fasting l, 2; rather, their fasting motor activity consists of periods of quiescence and clustered nonpropagative activity. The characteristics of this clustered activity change significantly with gestational age, until the activity eventually evolves into the mature MMC.1 The presence of immature fasting motor activity in preterm 'infants suggests that there is functional impairment in the preterm infant's intestinal transit of enteral nutrients.
Supported by National Institutes of Health grant No. HD24558. Submitted for publication Feb. 15, 1990; accepted May t4, 1990. Reprint requests: C. L. Berseth, MD, Department of Pediatrics, Mayo Clinic, Rochester, MN 55905. 9/23/22306
However, all the babies in our previous studies tolerated enteral feedings without gastric residuals or abdominal distension. In fact the common practice of most newborn intensive care units is to provide some form of enteral nutrition to preterm infants. 3,4 The fact that babies tolerate MMC NICU
Migrating motor complex Newborn intensive care unit
these feedings suggests that their motor response to feedings is intact. The purpose of this study was to characterize and compare the intestinal motor response to feeding in preterm and term infants. METHODS
Subjects studied. All 36 babies who participated in this study were patients admitted consecutively to the NICU at St. Mary's Hospital. Thirteen were term (36 to 44 weeks of gestational age) and 23 were preterm infants, ranging from 27 to 35 weeks of gestational age. Term babies were admitted for pulmonary hypertension or congenital pneumonia; preterm babies were admitted for respiratory distress. All 777
778
Berseth
The Journal of Pediatrics November 1990
Infusion Proximal duodenum
iF
....
Mid duodenum
Distal duodenum
Proximal
] 50 mm Hg
jejunum
r~Tmio Fig. t. Sma•• intestina• m•t•r activity in term infant (4• weeks •fgestati•na• age) during fasting and pr•gressing thr•ugh initiation of milk infusion. Presence of MMC is followed by brief period of quiescence before feeding is initiated. Quiescence is replaced by persistent motor activity in all four leads shortly after feeding infusion is begun.
initially required ventilator support, but they had recovered from their illnesses at the tittle of study. All had been chosen by the attending neonatologist to begin enteral feedings. Babies with congenital anomalies and severe birth asphyxia were excluded. Of all infants eligible to participate in this study, only one family declined participation. By N I C U routine, all babies receiving ventilator support were initially supported by parenteral nutrition until umbilical arterial lines had been withdrawn on approximately postnatal day 5 to 10. No baby had received any enteral nutrition before this study. This study was approved by the Mayo Clinical Institutional Review Board, and all parents provided informed consent for their infants' participation in this study. Motility test. On the day of the study a motility-feeding tube was placed in the upper part of the small intestine. In the first 15 babies, tubes were placed during fluoroscopy and taped in place. Thereafter, nurses placed tubes orally, without radiologic guidance or sedation, in supine infants positioned with the right side down. The recording ports were perfused and activity was recorded as the tube was passed. As the ports were pushed from antrum to duodenum, the pressure-wave frequency changed from 3/min to 9 to 11/ minute. The final position of the tube was verified by the presence of a motor pattern characteristic of the upper part of the intestine (pressure waves occurring at 9 to 13 per minute). The average time required for tube placement was 30 minutes. The motility tube was made of polyvinyl extrusion tubing (Arndorfer Medical Specialties, Greendale, Wis.); it contained four manometric ports located 2.5 cm apart and a terminal feeding port 0.5 cm beyond the most distal motility port, and had an outer diameter of 3.7 mm. The recording lumina were connected to a modified neonatal perfusion system with transducers (model P23 LD, Spectramed Inc., Oxnard, Calif.) connected to a six-channel thermal oscillograph (Honeywell, Inc., Denver, Colo.). This previously validated neonatal motility unit was a low-
compliance, continuous-perfusion system that provided a continuous infusion at 0.01 ml/min/port at 10 psi air pressure. The pressure response rate, determined by the occlusion method of Dodds et al, 5 was 57 mm Hg/min. 2 Experimental design. Motility studies were performed in all babies during the first postnatal week before any enteral feedings had been given. Motility recordings were obtained for 4 to 6 hours during fasting. Infants were then fed Similac 20 formula (Ross Laboratories, Columbus, Ohio) at 4 ml/kg by continuous infusion for 2 hours into the feeding port in the distal duodenum. Motor activity was recorded during the 2-hour infusion and for an additional 2 hours after the feeding infusion, Data analysis. All recordings were analyzed in 30-minute intervals during the fasting, feeding, and postfeeding periods. During fasting, four types of activity were identified, as we have previously defined), 2 Phase I was defined as motor quiesence. Phase IlI was defined as regular phasic activity at a rate of nine per minute for more than 2 minutes and propagating over three or more ports. Phase III was considered to be equivalent to an MMC seen in adults. Phase II, which was interposed between phase 1 and phase IlI, included two forms of nonpropagating activity: (1) irregular activity and (2) regular phasic activity lasting 0.4 minute or longer that did not propagate over three or more ports. The latter activity was defined as "clusters." The motor response to food was defined as a visual change from the fasting pattern of quiescence and cluster activity to one of persisting activity lasting longer than 10 minutes in one or more leads (Fig. 1). Four calculations were used to characterize the presence of the fed response. First, a motility index was calculated as loge (Sum of amplitudes • Number of pressure peaks + 1). 6 Second, the amplitude of each episode of phase II activity was determined and a mean amplitude of all the activity calculated for each 30-minute period. Third, the number of pressure peaks of phase II ac-
Volume 117 Number 5
N e o n a t a l s m a l l intestinal m o t i l i t y
779
Infusion Antroduodenal junction
Proximal duodenum 9
Mid duodenum
50 mm Hg Distal duodenum
J i
1 rain
J
Fig. 2. Small intestinal motor activity in 32-week gestation preterm infant during fasting and progressing through initiation of milk infusion. Intermittent clusters and quiescence during fasting are present. After initiation of feedings, persisting activity develops in all four leads.
tivity was counted for each 30-minute period. Finally, the duration of quiescence activity, measured in minutes per hour per lead, was calculated. Of the four calculations, the number of pressure peaks per 30-minute period appeared to be the most sensitive index of a change in the fed pattern, and it was used to characterize the fed pattern further. The number of peaks per 30-minute period was calculated for the three 30-minute periods before the feeding and for each of eight 30-minute intervals after the initiation of the feeding. The fed pattern was defined as the presence of pressure peaks per 30-minute period that exceeded 2 SD of the mean value of the fasting period. This definition of the presence of the fed pattern was used to identify the 30-minute interval in which it first appeared. Characteristics of motor activity were compared between preterm and term infants by unpaired t tests. Characteristics of motor activity were compared between fasting and feeding infusion by paired t tests. For these comparisons, data obtained 1 hour after the initiation of the milk infusion were used as feeding data to ensure that the majority of babies had established a fed pattern response. RESULTS Qualitative results. During fasting, all term infants had interdigestive cycles containing phases I, II, and III. Preterm infants had quiescence and nonpropagating activity. All infants had frequent cluster activity. The start of the fed pattern in term infants disrupted the interdigestive cycle (Fig. 1). In preterm infants the fed pattern disrupted the randomly occurring pattern of quiescence and nonpropagating activity (Fig. 2). Because feedings were given by slow infusion, infants rarely responded immediately to the initiation of feeding. Most had a transition period of 30 to 60 minutes when fasting patterns persisted, but three infants (two preterm and one term) had M M C s during this transition period. N o infant displayed
T a b l e I. Characteristics of fasting motor activity and characteristics of fed responses in term and preterm infants Term (n = 13)
Fasting Motility index 13.4 _+ 0.2 Clusters Duration (min/ 26.2 +_ 2.7 hr/lead) Mean duration 2.2 +_ 0.2 per cluster (rain) Frequency (No./ 21.2 -- 2.4 hr/lead) Quiescence Duration (min/ 17.9 +_ 1.8 hr/lead) Mean duration per 1.0 +_ 0.2 episode (min) Frequency (No. 21.2 _+ 2.4 of episodes/ hr/lead) Milk infusion Time of start of fed pattern (rain) --
To explore the possibility that the intestinal motor response to feeding is intact even in infants with immature fasting patterns, we performed low-compliance, continuous-infusion manometry in 13 term and 23 preterm infants during the first postnatal week. Babies were fed a standard formula intraduodenally at 4 m l / k g / 2 hr by infusion pump. Small bowel motility responded to feeding; fasting patterns were replaced with long periods of persistent activity. During the infusion of formula, there was no significant difference in motor activity between preterm and term infants. Four characteristics of motor activity changed with feeding: motility index, the number of pressure peaks per 30-minute period, mean amplitude of pressure peaks, and duration of periods of quiescence. The number of pressure peaks per 30-minute period was the most sensitlve index of the motor response to feeding, and it was used to characterize the fed pattern response. The start and duration of the fed response were similar in both groups of infants. Thus, despite the presence of immaturity in fasting patterns, the intestine of the preterm infant responds appropriately to feeding. These data help explain why preterm infants usually tolerate antral feedings, and support their use. (J PEDIATR1990;117:777-82)
During fasting, term infants have interdigestive cycles of motility (the interdigestive motility cycle) containing periods that feature quiescence, nonpropagating activity, and then phasic propagative activity, called the migrating motor complex.l' 2 When given a feeding, term infants have a well-recognized motor response of persisting activity called the fed pattern. 2 In contrast to term infants, few preterm infants have MMCs during fasting l, 2; rather, their fasting motor activity consists of periods of quiescence and clustered nonpropagative activity. The characteristics of this clustered activity change significantly with gestational age, until the activity eventually evolves into the mature MMC.1 The presence of immature fasting motor activity in preterm 'infants suggests that there is functional impairment in the preterm infant's intestinal transit of enteral nutrients.
Supported by National Institutes of Health grant No. HD24558. Submitted for publication Feb. 15, 1990; accepted May t4, 1990. Reprint requests: C. L. Berseth, MD, Department of Pediatrics, Mayo Clinic, Rochester, MN 55905. 9/23/22306
However, all the babies in our previous studies tolerated enteral feedings without gastric residuals or abdominal distension. In fact the common practice of most newborn intensive care units is to provide some form of enteral nutrition to preterm infants. 3,4 The fact that babies tolerate MMC NICU
Migrating motor complex Newborn intensive care unit
these feedings suggests that their motor response to feedings is intact. The purpose of this study was to characterize and compare the intestinal motor response to feeding in preterm and term infants. METHODS
Subjects studied. All 36 babies who participated in this study were patients admitted consecutively to the NICU at St. Mary's Hospital. Thirteen were term (36 to 44 weeks of gestational age) and 23 were preterm infants, ranging from 27 to 35 weeks of gestational age. Term babies were admitted for pulmonary hypertension or congenital pneumonia; preterm babies were admitted for respiratory distress. All 777
778
Berseth
The Journal of Pediatrics November 1990
Infusion Proximal duodenum
iF
....
Mid duodenum
Distal duodenum
Proximal
] 50 mm Hg
jejunum
r~Tmio Fig. t. Sma•• intestina• m•t•r activity in term infant (4• weeks •fgestati•na• age) during fasting and pr•gressing thr•ugh initiation of milk infusion. Presence of MMC is followed by brief period of quiescence before feeding is initiated. Quiescence is replaced by persistent motor activity in all four leads shortly after feeding infusion is begun.
initially required ventilator support, but they had recovered from their illnesses at the tittle of study. All had been chosen by the attending neonatologist to begin enteral feedings. Babies with congenital anomalies and severe birth asphyxia were excluded. Of all infants eligible to participate in this study, only one family declined participation. By N I C U routine, all babies receiving ventilator support were initially supported by parenteral nutrition until umbilical arterial lines had been withdrawn on approximately postnatal day 5 to 10. No baby had received any enteral nutrition before this study. This study was approved by the Mayo Clinical Institutional Review Board, and all parents provided informed consent for their infants' participation in this study. Motility test. On the day of the study a motility-feeding tube was placed in the upper part of the small intestine. In the first 15 babies, tubes were placed during fluoroscopy and taped in place. Thereafter, nurses placed tubes orally, without radiologic guidance or sedation, in supine infants positioned with the right side down. The recording ports were perfused and activity was recorded as the tube was passed. As the ports were pushed from antrum to duodenum, the pressure-wave frequency changed from 3/min to 9 to 11/ minute. The final position of the tube was verified by the presence of a motor pattern characteristic of the upper part of the intestine (pressure waves occurring at 9 to 13 per minute). The average time required for tube placement was 30 minutes. The motility tube was made of polyvinyl extrusion tubing (Arndorfer Medical Specialties, Greendale, Wis.); it contained four manometric ports located 2.5 cm apart and a terminal feeding port 0.5 cm beyond the most distal motility port, and had an outer diameter of 3.7 mm. The recording lumina were connected to a modified neonatal perfusion system with transducers (model P23 LD, Spectramed Inc., Oxnard, Calif.) connected to a six-channel thermal oscillograph (Honeywell, Inc., Denver, Colo.). This previously validated neonatal motility unit was a low-
compliance, continuous-perfusion system that provided a continuous infusion at 0.01 ml/min/port at 10 psi air pressure. The pressure response rate, determined by the occlusion method of Dodds et al, 5 was 57 mm Hg/min. 2 Experimental design. Motility studies were performed in all babies during the first postnatal week before any enteral feedings had been given. Motility recordings were obtained for 4 to 6 hours during fasting. Infants were then fed Similac 20 formula (Ross Laboratories, Columbus, Ohio) at 4 ml/kg by continuous infusion for 2 hours into the feeding port in the distal duodenum. Motor activity was recorded during the 2-hour infusion and for an additional 2 hours after the feeding infusion, Data analysis. All recordings were analyzed in 30-minute intervals during the fasting, feeding, and postfeeding periods. During fasting, four types of activity were identified, as we have previously defined), 2 Phase I was defined as motor quiesence. Phase IlI was defined as regular phasic activity at a rate of nine per minute for more than 2 minutes and propagating over three or more ports. Phase III was considered to be equivalent to an MMC seen in adults. Phase II, which was interposed between phase 1 and phase IlI, included two forms of nonpropagating activity: (1) irregular activity and (2) regular phasic activity lasting 0.4 minute or longer that did not propagate over three or more ports. The latter activity was defined as "clusters." The motor response to food was defined as a visual change from the fasting pattern of quiescence and cluster activity to one of persisting activity lasting longer than 10 minutes in one or more leads (Fig. 1). Four calculations were used to characterize the presence of the fed response. First, a motility index was calculated as loge (Sum of amplitudes • Number of pressure peaks + 1). 6 Second, the amplitude of each episode of phase II activity was determined and a mean amplitude of all the activity calculated for each 30-minute period. Third, the number of pressure peaks of phase II ac-
Volume 117 Number 5
N e o n a t a l s m a l l intestinal m o t i l i t y
779
Infusion Antroduodenal junction
Proximal duodenum 9
Mid duodenum
50 mm Hg Distal duodenum
J i
1 rain
J
Fig. 2. Small intestinal motor activity in 32-week gestation preterm infant during fasting and progressing through initiation of milk infusion. Intermittent clusters and quiescence during fasting are present. After initiation of feedings, persisting activity develops in all four leads.
tivity was counted for each 30-minute period. Finally, the duration of quiescence activity, measured in minutes per hour per lead, was calculated. Of the four calculations, the number of pressure peaks per 30-minute period appeared to be the most sensitive index of a change in the fed pattern, and it was used to characterize the fed pattern further. The number of peaks per 30-minute period was calculated for the three 30-minute periods before the feeding and for each of eight 30-minute intervals after the initiation of the feeding. The fed pattern was defined as the presence of pressure peaks per 30-minute period that exceeded 2 SD of the mean value of the fasting period. This definition of the presence of the fed pattern was used to identify the 30-minute interval in which it first appeared. Characteristics of motor activity were compared between preterm and term infants by unpaired t tests. Characteristics of motor activity were compared between fasting and feeding infusion by paired t tests. For these comparisons, data obtained 1 hour after the initiation of the milk infusion were used as feeding data to ensure that the majority of babies had established a fed pattern response. RESULTS Qualitative results. During fasting, all term infants had interdigestive cycles containing phases I, II, and III. Preterm infants had quiescence and nonpropagating activity. All infants had frequent cluster activity. The start of the fed pattern in term infants disrupted the interdigestive cycle (Fig. 1). In preterm infants the fed pattern disrupted the randomly occurring pattern of quiescence and nonpropagating activity (Fig. 2). Because feedings were given by slow infusion, infants rarely responded immediately to the initiation of feeding. Most had a transition period of 30 to 60 minutes when fasting patterns persisted, but three infants (two preterm and one term) had M M C s during this transition period. N o infant displayed
T a b l e I. Characteristics of fasting motor activity and characteristics of fed responses in term and preterm infants Term (n = 13)
Fasting Motility index 13.4 _+ 0.2 Clusters Duration (min/ 26.2 +_ 2.7 hr/lead) Mean duration 2.2 +_ 0.2 per cluster (rain) Frequency (No./ 21.2 -- 2.4 hr/lead) Quiescence Duration (min/ 17.9 +_ 1.8 hr/lead) Mean duration per 1.0 +_ 0.2 episode (min) Frequency (No. 21.2 _+ 2.4 of episodes/ hr/lead) Milk infusion Time of start of fed pattern (rain) --
