Necrotizing By Randall W. Powell,
Enterocolitis
D. Lynn Dyess, Arnold Luterman, Mobile,
0 Over a 5-year period, 20 infants of multiple-gestation births (16 twin, 2 triplet) developed necrotizing enterocolitis (NEC) (15 infants) or suspected NEC (5 infants). During the same period, 532 infants of multiple gestations were admitted to our neonatal intensive care unit, yielding a NEC btcidence in this population of 3.6%. In two twin sets, both infants developed NEC or suspected NEC. and in three sets only the affected twin was transferred to our nursery. Five. infants required surgical intervention (25%) and three infants died (overall mortality, 15%). Fifteen siblings who did not develop NEC served as a control group. Analysis showed that the l-minute Apgar score was the most significant factor in predicting NEC (P < .0261 and need for surgical intervention (P -z 620). In this series, 62% of the infants with l-minute Apgar less than 6 developed NEC. whereas 31% with l-minute Apgar greater than 6 developed NEC. 0 16M by W.B. Saunders Company. INDEX WORDS: Necrotizing enterocolitis.
N
ECROTIZING enterocolitis (NEC) remains a leading cause of morbidity and mortality in neonatal intensive care units’ and represents the most common reason for exploratory celiotomy in newborn infants.’ The most common predisposing factor seems to be prematurity,3 but many series implicate a host of factors that seem to be predictive of developing NEC.‘v3 Multiple gestations typically involve premature delivery, and the incidence of NEC in multiple-gestation infants in series of infants with NEC ranges from 10% to 16%. lS4This report exa mines the perinatal factors in multiple-gestation infants developing NEC. MATERIALS
AND
in Multiple-Birth
METHODS
Infants
Neal P. Simon, and Max L. Ramenofsky
Alabama also compared to infants successfully treated medically (+NEC MRX) and to -NEC by independent f test. A similar comparison was made between first-born infants and their siblings. RESULTS
During the 5-year period reviewed, 532 infants of multiple gestations were admitted to the neonatal intensive care units. Fifteen infants were +NEC while five were ?NEC. Fifteen siblings who were -NEC were used as a contro4 group. In three twin sets, only the infant developing + NEC or ?NEC was transferred to our hospital. A summary of the three main groups and mean results of birth weight, gestational age, Apgar scores, age at first feeding, and ventilatory support time are shown in Table 1. When compared by unpaired t test, no significant difference existed between groups in regard to birth weight, gestational age, time of first feeding, ventilatory support, change in Apgar score, or birth rank. When comparing the Apgar scores in the three groups (independent variable t test), significant differences occurred between the ?NEC and -NEC groups in the l-minute score (P-L .029) and in the 5-minute score (P < .006). When the +NEC group was compared with the - NEC group, the 1-minute score approached significance (P < .068). When the +NEC and ?NEC groups were combined and compared with the - NEC group, the 1-minute score was highly significant as a predictor of developing NEC (P < .028). When comparison between infants with NEC requiring surgical intervention (+NEC OR) was made against +NEC MRX infants and -NEC infants, the only significant factor identified was again the lminute Apgar (Table 2). The P values were less than .OOl for the +NEC OR to -NEC groups, and less than .020 for the +NEC OR to +NEC MRX groups. When infants were grouped in relationship to their l-minute Apgar score, infants with a l-minute score less than 6 experienced an NEC incidence of 82%, whereas those at 6 or greater had an incidence of 3 1%.
The discharge records of all multiple-gestation infants admitted to the neonatal intensive care units at the University of South Alabama Medical Center, a level III unit receiving patients from a 125-mile radius including southwestern Alabama, southeastern Mississippi, and the Florida panhandle, from 1981 to 1986 were reviewed. The full records of all infants developing NEC or suspected NEC and their siblings were reviewed and perinatal risk factors recorded, including maternal history, birth weight, l- and 5-minute Apgar scores, gestational age, need for ventilatory support, time of first feeding, and birth rank. The diagnosis of NEC was based on the common signs and symptoms, including increased gastric residuals, abdominal distention, occult or gross blood in the stools, and the radiologic findings of portal venous air or pneumotosis intestinalis. Suspect cases included clinical signs and symptoms but lacked radiologic confirmation. The risk factors of three main groups (infants developing NEC [ +NEC], infants suspected of having NEC[?NEC], and infants not developing NEC [ - NEC]) were analyzed by independent variable r tests. Twin and triplet sets in which one sibling developed NEC and the others did not were also analyzed by Fisher’s exact test, Risk factors of infants requiring surgical intervention (+NEC OR) were
From the University of South Alabama Medical Center and the University of South Alabama College of Medicine. Mobile. AL. Presented at the 21st Annual Meeting of the PaciJic Association of Pediatric Surgeons, Taipei, Taiwan, April I I-15. 1988. Date accepted: February 7.1989. Address reprint requests to Randall W. Powell, MD. Division of Pediatric Surgery, 2451 Fillingim St, Mobile. AL 36617. 8 1990 by W.B. Saunders Company. 0022-3468/90/2503-0011$03.00/0
Jounal of Pediatk SW~WY, Vol 25, No 3 (March), 1990: pp 319-321
319
320
POWELL ET AL Table 1. Clinical Features
+NEC (15)
1,614
31.7
?NEC (5) -NEC(15)
5.2
7.1
4.9
4.0
4.4
5.2
5.8
3.6
7.0
7.9
3.2
1.8
(28-35)
(760-2.360) 1,466
32.4
(890-2.500) 1,521
(30-39)
(9 1O-2.460)
(28-34)
31.1
In the eight twin sets and two triplet sets in which one sibling developed NEC and the other(s) did not, no significant difference could be found in birth weight, Apgar scores, age at first feeding, ventilatory support, or birth rank (Fisher’s exact test). DISCUSSION
Although many series address the question of predictive factors in developing NEC or determining the severity of the disease,1*c9 no single group of factors has yet been established. Although most series have used control groups, only one series has reported a comparison in multiple-gestation infants.” The use of the -NEC sibling allows a more controlled group, because many but not all prenatal and perinatal factors remain the same for these pairs of infants. Samm et al” examined 10 sets of twins and one set of triplets in which at least one infant developed NEC. In that study, the comparison was made between the first-born twin, all +NEC, and the matched sibling, three of 10 +NEC. Significant factors found by Samm et al” included birth rank, both Apgar scores, respiratory distress requiring oxygen therapy, resuscitation, and the age at first feeding. The investigators commented mainly on the birth-rank factor, and speculated that the earlier feeding in the first-born twin, also usually the less ill infant, may be the reason for their high incidence in the first-born infant.” Barnard et al’ also suggested that early feeding in premature infants, who seemed to be stable and have less significant risk factors, may lead to more severe bouts of NEC. The results of our series differ significantly from that of Samm et al in that birth rank was not a significant factor in the development of NEC. In our patients, eight first-born infants were + NEC or ?NEC, whereas 10 second-born developed the disease. In the two triplet
sets, the third-born infant developed NEC. When first-born infants were compared with their siblings, there was no significant difference found in birth weight, Apgar scores, age at first feeding, need for ventilatory support, or the development of NEC. When all infants were analyzed, the only significant factor in our series of infants was the l-minute Apgar score. This score was predictive as far as +NEC or ?NEC (P c .028) and was also predictive in regard to severity of disease. Infants developing +NEC OR had significantly lower l-minute Apgar scores than infants with +NEC MRX (P c .020) or -NEC infants (P c .OOl). When infants were divided into groups with a l-minute Apgar score of less than 6 or 6 and greater, 82% of the lower score group developed NEC whereas 3 1% of the higher score group developed the disease. The use of multiple-gestation siblings allows one to eliminate many factors related to the prenatal environment so that events occurring at and after birth can be studied. The unaffected sibling represents an excellent control group. The incidence of NEC might be expected to be reasonably high due to the increased incidence of prematurity in multiple gestations.” This study represents the second in the literature to specifically study this group of infants. The results differ from the study by Samm et al,” because only one significant factor was identified. However, the l-minute Apgar score was significant in predicting the development of NEC and in predicting the severity of disease. Four of the five infants requiring surgical intervention had l-minute Apgar scores of 4 or less, and the three infants who developed the disease had l-minute scores of 1, 1, and 4, respectively. The significance of the l-minute Apgar score seems to emphasize the role of hypoxia in the development of NEC. The clinical usefulness of this factor requires further
Table 2. Clinical Features-Suraerv Apssr
Gestational Age QWP
+NECOR
N
Birth
Weight (gl
bdcs)
l-Minute
S-Minute
Fii Feed hw)
Ventilatcq Support (days)
5
1,454
31.4
2.6
5.6
7.8
8.6
+ NEC MRX
16
1,618
32.1
5.9
6.9
4.2
2.3
-NEC
15
1,521
31.1
7.0
7.9
3.2
1.8
321
NEC IN MULTIPLE-BIRTH INFANTS
evaluation in larger series of multiple-gestation infants who develop NEC. Consideration may be given to feeding multiple-gestation infants, with an Apgar of less than 6, later in their course. These infants should be observed closely for any early signs of NEC, and
aggressive medical management instituted with the gastrointestinal tract put to rest with tube decompression and nutrition supplied parenterally. Attempts at early reinstitution of feeding or rapid advancement in feedings should be avoided.
REFERENCES 1. Kliegman RM, Walsh MC: Neonatal necrotizing enterocolitis: Pathogenesis, classification, and spectrum of illness. Curr Probl Pediatr 17:218-288, 1987 2. Koslcske AM: Surgery of necrotizing enterocolitis. World J Surg 9:277-284,1985 3. Walsh MC, Kliegman RM: Necrotizing enterocolitis: Treatment based on staging criteria. Pediatr Clin North Am 33:179-201, 1986 4. Yu VYH, Tudehope PI: Neonatal necrotizing enterocolitis: 2. Perinatal risk factors. Med J Aust 1:688-693, 1977 5. Kliegman RM, Hack M, Jones P, et al: Epidemiologic study of necrotizing enterocolitis among low-birth-weight infants: Absence of identifiable risk factors.-J Pediatr, 100~440-444, 1982 6. Cikrit D, Mastandrea J, West KW, et al: Necrotizing entero-
colitis: Factors affecting mortality in 101 surgical cases. Surgery 96:648-655, 1984 7. Cikrit D, Mastandrea J, Grosfeld JL, et al: Significance of portal vein air in necrotizing enterocolitis: Analysis of 53 cases. J Pediatr Surg 20:425-430,198s 8. Barnard JA, Cotton RB, Lutin W: Necrotizing enterocolitis: Variables associated with the severity of disease. Am J Dis Child 139~375-377, 1985 9. McCormack CJ, Emmens RW, Putnam TC: Evaluation of factors in high risk neonatal necrotizing enterocolitis. J Pediatr Surg 22:488-491,1987 10. Samm M, Curtis-Cohen M, Keller M, et al: Necrotizing enterocolitis in infants of multiple gestation. Am J Dis Child 140:937-939, 1986
Enterocolitis
D. Lynn Dyess, Arnold Luterman, Mobile,
0 Over a 5-year period, 20 infants of multiple-gestation births (16 twin, 2 triplet) developed necrotizing enterocolitis (NEC) (15 infants) or suspected NEC (5 infants). During the same period, 532 infants of multiple gestations were admitted to our neonatal intensive care unit, yielding a NEC btcidence in this population of 3.6%. In two twin sets, both infants developed NEC or suspected NEC. and in three sets only the affected twin was transferred to our nursery. Five. infants required surgical intervention (25%) and three infants died (overall mortality, 15%). Fifteen siblings who did not develop NEC served as a control group. Analysis showed that the l-minute Apgar score was the most significant factor in predicting NEC (P < .0261 and need for surgical intervention (P -z 620). In this series, 62% of the infants with l-minute Apgar less than 6 developed NEC. whereas 31% with l-minute Apgar greater than 6 developed NEC. 0 16M by W.B. Saunders Company. INDEX WORDS: Necrotizing enterocolitis.
N
ECROTIZING enterocolitis (NEC) remains a leading cause of morbidity and mortality in neonatal intensive care units’ and represents the most common reason for exploratory celiotomy in newborn infants.’ The most common predisposing factor seems to be prematurity,3 but many series implicate a host of factors that seem to be predictive of developing NEC.‘v3 Multiple gestations typically involve premature delivery, and the incidence of NEC in multiple-gestation infants in series of infants with NEC ranges from 10% to 16%. lS4This report exa mines the perinatal factors in multiple-gestation infants developing NEC. MATERIALS
AND
in Multiple-Birth
METHODS
Infants
Neal P. Simon, and Max L. Ramenofsky
Alabama also compared to infants successfully treated medically (+NEC MRX) and to -NEC by independent f test. A similar comparison was made between first-born infants and their siblings. RESULTS
During the 5-year period reviewed, 532 infants of multiple gestations were admitted to the neonatal intensive care units. Fifteen infants were +NEC while five were ?NEC. Fifteen siblings who were -NEC were used as a contro4 group. In three twin sets, only the infant developing + NEC or ?NEC was transferred to our hospital. A summary of the three main groups and mean results of birth weight, gestational age, Apgar scores, age at first feeding, and ventilatory support time are shown in Table 1. When compared by unpaired t test, no significant difference existed between groups in regard to birth weight, gestational age, time of first feeding, ventilatory support, change in Apgar score, or birth rank. When comparing the Apgar scores in the three groups (independent variable t test), significant differences occurred between the ?NEC and -NEC groups in the l-minute score (P-L .029) and in the 5-minute score (P < .006). When the +NEC group was compared with the - NEC group, the 1-minute score approached significance (P < .068). When the +NEC and ?NEC groups were combined and compared with the - NEC group, the 1-minute score was highly significant as a predictor of developing NEC (P < .028). When comparison between infants with NEC requiring surgical intervention (+NEC OR) was made against +NEC MRX infants and -NEC infants, the only significant factor identified was again the lminute Apgar (Table 2). The P values were less than .OOl for the +NEC OR to -NEC groups, and less than .020 for the +NEC OR to +NEC MRX groups. When infants were grouped in relationship to their l-minute Apgar score, infants with a l-minute score less than 6 experienced an NEC incidence of 82%, whereas those at 6 or greater had an incidence of 3 1%.
The discharge records of all multiple-gestation infants admitted to the neonatal intensive care units at the University of South Alabama Medical Center, a level III unit receiving patients from a 125-mile radius including southwestern Alabama, southeastern Mississippi, and the Florida panhandle, from 1981 to 1986 were reviewed. The full records of all infants developing NEC or suspected NEC and their siblings were reviewed and perinatal risk factors recorded, including maternal history, birth weight, l- and 5-minute Apgar scores, gestational age, need for ventilatory support, time of first feeding, and birth rank. The diagnosis of NEC was based on the common signs and symptoms, including increased gastric residuals, abdominal distention, occult or gross blood in the stools, and the radiologic findings of portal venous air or pneumotosis intestinalis. Suspect cases included clinical signs and symptoms but lacked radiologic confirmation. The risk factors of three main groups (infants developing NEC [ +NEC], infants suspected of having NEC[?NEC], and infants not developing NEC [ - NEC]) were analyzed by independent variable r tests. Twin and triplet sets in which one sibling developed NEC and the others did not were also analyzed by Fisher’s exact test, Risk factors of infants requiring surgical intervention (+NEC OR) were
From the University of South Alabama Medical Center and the University of South Alabama College of Medicine. Mobile. AL. Presented at the 21st Annual Meeting of the PaciJic Association of Pediatric Surgeons, Taipei, Taiwan, April I I-15. 1988. Date accepted: February 7.1989. Address reprint requests to Randall W. Powell, MD. Division of Pediatric Surgery, 2451 Fillingim St, Mobile. AL 36617. 8 1990 by W.B. Saunders Company. 0022-3468/90/2503-0011$03.00/0
Jounal of Pediatk SW~WY, Vol 25, No 3 (March), 1990: pp 319-321
319
320
POWELL ET AL Table 1. Clinical Features
+NEC (15)
1,614
31.7
?NEC (5) -NEC(15)
5.2
7.1
4.9
4.0
4.4
5.2
5.8
3.6
7.0
7.9
3.2
1.8
(28-35)
(760-2.360) 1,466
32.4
(890-2.500) 1,521
(30-39)
(9 1O-2.460)
(28-34)
31.1
In the eight twin sets and two triplet sets in which one sibling developed NEC and the other(s) did not, no significant difference could be found in birth weight, Apgar scores, age at first feeding, ventilatory support, or birth rank (Fisher’s exact test). DISCUSSION
Although many series address the question of predictive factors in developing NEC or determining the severity of the disease,1*c9 no single group of factors has yet been established. Although most series have used control groups, only one series has reported a comparison in multiple-gestation infants.” The use of the -NEC sibling allows a more controlled group, because many but not all prenatal and perinatal factors remain the same for these pairs of infants. Samm et al” examined 10 sets of twins and one set of triplets in which at least one infant developed NEC. In that study, the comparison was made between the first-born twin, all +NEC, and the matched sibling, three of 10 +NEC. Significant factors found by Samm et al” included birth rank, both Apgar scores, respiratory distress requiring oxygen therapy, resuscitation, and the age at first feeding. The investigators commented mainly on the birth-rank factor, and speculated that the earlier feeding in the first-born twin, also usually the less ill infant, may be the reason for their high incidence in the first-born infant.” Barnard et al’ also suggested that early feeding in premature infants, who seemed to be stable and have less significant risk factors, may lead to more severe bouts of NEC. The results of our series differ significantly from that of Samm et al in that birth rank was not a significant factor in the development of NEC. In our patients, eight first-born infants were + NEC or ?NEC, whereas 10 second-born developed the disease. In the two triplet
sets, the third-born infant developed NEC. When first-born infants were compared with their siblings, there was no significant difference found in birth weight, Apgar scores, age at first feeding, need for ventilatory support, or the development of NEC. When all infants were analyzed, the only significant factor in our series of infants was the l-minute Apgar score. This score was predictive as far as +NEC or ?NEC (P c .028) and was also predictive in regard to severity of disease. Infants developing +NEC OR had significantly lower l-minute Apgar scores than infants with +NEC MRX (P c .020) or -NEC infants (P c .OOl). When infants were divided into groups with a l-minute Apgar score of less than 6 or 6 and greater, 82% of the lower score group developed NEC whereas 3 1% of the higher score group developed the disease. The use of multiple-gestation siblings allows one to eliminate many factors related to the prenatal environment so that events occurring at and after birth can be studied. The unaffected sibling represents an excellent control group. The incidence of NEC might be expected to be reasonably high due to the increased incidence of prematurity in multiple gestations.” This study represents the second in the literature to specifically study this group of infants. The results differ from the study by Samm et al,” because only one significant factor was identified. However, the l-minute Apgar score was significant in predicting the development of NEC and in predicting the severity of disease. Four of the five infants requiring surgical intervention had l-minute Apgar scores of 4 or less, and the three infants who developed the disease had l-minute scores of 1, 1, and 4, respectively. The significance of the l-minute Apgar score seems to emphasize the role of hypoxia in the development of NEC. The clinical usefulness of this factor requires further
Table 2. Clinical Features-Suraerv Apssr
Gestational Age QWP
+NECOR
N
Birth
Weight (gl
bdcs)
l-Minute
S-Minute
Fii Feed hw)
Ventilatcq Support (days)
5
1,454
31.4
2.6
5.6
7.8
8.6
+ NEC MRX
16
1,618
32.1
5.9
6.9
4.2
2.3
-NEC
15
1,521
31.1
7.0
7.9
3.2
1.8
321
NEC IN MULTIPLE-BIRTH INFANTS
evaluation in larger series of multiple-gestation infants who develop NEC. Consideration may be given to feeding multiple-gestation infants, with an Apgar of less than 6, later in their course. These infants should be observed closely for any early signs of NEC, and
aggressive medical management instituted with the gastrointestinal tract put to rest with tube decompression and nutrition supplied parenterally. Attempts at early reinstitution of feeding or rapid advancement in feedings should be avoided.
REFERENCES 1. Kliegman RM, Walsh MC: Neonatal necrotizing enterocolitis: Pathogenesis, classification, and spectrum of illness. Curr Probl Pediatr 17:218-288, 1987 2. Koslcske AM: Surgery of necrotizing enterocolitis. World J Surg 9:277-284,1985 3. Walsh MC, Kliegman RM: Necrotizing enterocolitis: Treatment based on staging criteria. Pediatr Clin North Am 33:179-201, 1986 4. Yu VYH, Tudehope PI: Neonatal necrotizing enterocolitis: 2. Perinatal risk factors. Med J Aust 1:688-693, 1977 5. Kliegman RM, Hack M, Jones P, et al: Epidemiologic study of necrotizing enterocolitis among low-birth-weight infants: Absence of identifiable risk factors.-J Pediatr, 100~440-444, 1982 6. Cikrit D, Mastandrea J, West KW, et al: Necrotizing entero-
colitis: Factors affecting mortality in 101 surgical cases. Surgery 96:648-655, 1984 7. Cikrit D, Mastandrea J, Grosfeld JL, et al: Significance of portal vein air in necrotizing enterocolitis: Analysis of 53 cases. J Pediatr Surg 20:425-430,198s 8. Barnard JA, Cotton RB, Lutin W: Necrotizing enterocolitis: Variables associated with the severity of disease. Am J Dis Child 139~375-377, 1985 9. McCormack CJ, Emmens RW, Putnam TC: Evaluation of factors in high risk neonatal necrotizing enterocolitis. J Pediatr Surg 22:488-491,1987 10. Samm M, Curtis-Cohen M, Keller M, et al: Necrotizing enterocolitis in infants of multiple gestation. Am J Dis Child 140:937-939, 1986
