ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 12, No. 3 Copyright 1982, Institute for Clinical Science, Inc.
Necrotizing Enterocolitis of the NewbornLAURENCE E. BRISKI, M.D.,* VOLLRAD VON BERG,
and JAMES J. HUMES, M.D.*Departments of *Pathology and f Surgery,
St. John Hospital, Detroit, MI 48236
ABSTRACTThe clinical presentation, diagnostic features, therapeutic measures, and
results of treatm ent of 29 infants with the firmly established diagnosis of necrotizing enterocolitis are reviewed. A cohort of control patients are studied in an attempt to identify risk factors which may predispose infants to develope this serious complication of the newborn period. The incidence of necrotizing enterocolitis in our series is 1.2 per 1000 live births, similar to that reported by other investigators. The prognosis is particularly grave in infants of very low birth weight and among those who exhibit radiographic evidence of portal venous air or who develop disseminated intravascular coagulation.
IntroductionSince its original description in 1891
by Genersich,6 necrotizing enterocolitis (NEC) has gained recognition as a serious and frequently fatal disorder affecting newborn infants. The first comprehensive reports on NEC appeared in 1965 from Babies Hospital, New York10 with the first significant surgical experience recorded from that same institution in 1967.15 With the advent of neonatology and the institution of neonatal intensive care units, NEC has come to the forefront among problems afflicting young infants, as evidenced by the plethora of articles appearing in the pediatric and surgical literature by the mid-1970s.
The purpose of this paper is to describe our experience with the diagnosis, clinical manifestations, management, and outcome of NEC, the pathogenesis of which is poorly understood. In order to gain insight into the etiology and obtain information about possible predisposing factors, clinical data from affected infants and from a control group are compared.Patients and Methods
St. John Hospital is a 550 bed acute care hospital, with a 26 unit neonatal intensive care facility serving northeast Detroit and its neighboring suburbs. From January, 1975 through December, 1980,2,861 neonates were admitted to our intensive care unit. All charts with a discharge diagnosis
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NECROTIZING EN TEROCOLITIS O F TH E NEW BORN 187of necrotizing enterocolitis during this study period were reviewed. A case was accepted as NEC if there was (1) pathologic conformation of NEC from surgical or autopsy specimens, or (2) radiographic evidence of pneumatosis intestinalis and one or more of the following: (a) abdominal distention, (b) vomiting or regurgitation, (c) guaiac positive or grossly bloody stools. Forty charts were reviewed and utilizing the previously mentioned criteria, 29 cases were accepted as NEC. It should be emphasized that the 11 patients rejected for the purpose of this study have shown all or part of the clinical picture of NEC, but they failed to demonstrate roentgen evidence of pneumatosis intestinalis. This group represents an important and significant num ber of infants in whom the diagnosis was suspected and medical therapy instituted before the full blown syndrome developed. However, without more objective evidence of NEC, it is difficult to assess accurately these patients; therefore, they were omitted from this review.
A control group was developed by selecting infants admitted to our neonatal intensive care unit (NICU), in whom the diagnosis of NEC was never entertained, within one month of each patient with NEC, providing their birthweight was within 75 grams of the patient under study. This created a control group comparable in weight, gestational age, and sex to the study group and obviated any changes in the nursery or house staff environment. Wherever possible, two controls were selected for each patient w ith NEC. However, in some instances only one control could be found, resulting in a control group of 44 patients.12
ResultsP a t i e n t P o p u l a t i o n
There were 19 males and 10 females with NEC among the 2,861 infants, repre
j 3000 O h co 2800 U E3 2 2600O' ~ 2400 2 2 0 0
1800 1600 1400 1200
800 600 400 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44
GESTATIONAL AGE (weeks)
Definite necrotizing enterocolitis Suspect necrotizing enterocolitis
F i g u r e 1. A g e -w e ig h t re la t io n s h ip o f in fa n ts w ith n e c ro tiz in g e n te ro c o l it is .
senting 1.0 percent of the total admissions to our NICU during the half-decade from 1975 through 1980. During the same period, there were 9,916 live births at St. John Hospital, including 12 of the patients with NEC, yielding an incidence of1.2 cases per 1000 live births. This is identical to the projected annual incidence in the U.S. based on an informal survey of 31 neonatal intensive care units in the U.S. and Canada from 1975 through 1977.
Twenty-four patients (82.8 percent) were "born prematurely (less than 38 weeks gestation) and were of low birthweight; only five infants weighed more
F ig u r e 2. A ge a t o n s e t o f n e c ro tiz in g e n te ro c o l it is .
188 B R IS K I, V O N B E R G , A N D H U M E ST A B L E I
Percent of Patients Statistical NEC Controls Significance
Complication (n=29) (n=44) (p)
Rupture of membranes > 24 hours
34.5 22.7 NS
Breech delivery 10.3 20.4 NSCesarian section 17.2 13.6 NSPlacenta praevia 6.9 11.4 NSAbruptio placenta 6.9 11.4 NSBirth asphyxia 48.3 52.3 NSApgar < 7 at 48.3 56.8 NS
NEC = Necrotizing enterocolitis NS = Not significant
than 2,500 grams (figure 1). This did not differ significantly from the control group. The mean age at onset of NEC was 7.3 days (range 1 to 37), with nearly two- thirds occurring during the first week of life (figure 2).
P e r i n a t a l C o m p l i c a t i o n sThe incidence of perinatal complica
tions was high; in only six patients was the delivery and immediate postpartum pe-
T A B L E II
Percent of Patients Statistical NEC Controls Significance
Complication (n=29) (n=44) (P)
RDS 79.3 90.9 NSHeadbox < 40 per 41.3 40.9 NScent FIO2Keadbox > 40 per 17.2 22.7 NScent FIO2CPAP 24.1 20.5 NSVentilator 18.2 15.9 NS
Apnea 44.8 40.9 NSPatent ductuc 37.9 20.5 NS
arteriosusExchange trans 6.9 2.3 NS
fusionUAC 48.3 36.4 NS
Above renal 42.9 43.7 NSartery
Enteric feedings 79.3 78.1 NS
NEC = Necrotizing enterocolitis RDS = Respiratory distress syndrome NS = Not significantCPAP - Continuous positive airway pressure UAC = Umbilical artery catheterization
riod recorded as normal. Birth asphyxia, requiring bagging and resuscitation in the delivery room, occurred in 14 patients (48.3 percent). Low apgar ratings were also recorded in 14 patients, 11 of whom required immediate resuscitation. Premature rupture of membranes more than 24 hrs prior to delivery occurred in 10 patients (34.5 percent). Other complications included a relatively high percentage of Cesarean sections (17.2 percent), breech deliveries (10.3 percent), placenta praevia (6.9 percent), and abruptio placenta (6.9 percent). However, when compared to the control group, no signficant difference was recorded among these perinatal risk factors (table I).P o s t n a t a l C o m p l i c a t i o n s
Postnatal complications were commonly encountered (table II). Respiratory distress syndrome of sufficient severity to require various degrees of ventilatory support and recurrent apnea occurred with similar frequency in both groups. Although the incidence of patent ductus arteriosus (37.9 percent) and umbilical artery catheterization (48.3 percent) was greater in the NEC group as compared to the control group (20.5 percent and 36.4 percent, respectively), this difference was not statistically significant (p > 0.05). Twenty-three patients (79.3 percent) were receiving oral feedings until the onset of NEC. On the same day of life that symptoms developed, 78.1 percent of the age weight matched control group were also receiving oral feedings. Most of the infants in both groups were fed 20 calories per ounce of standard commercial formula averaging 12 ml per kg every three hours.C l i n i c a l P i c t u r e
The disease was characterized by a pattern of poor feeding, recurrent apnea, and lethargy, associated frequently with abdominal distention and occult blood loss from the gastrointestinal tract in an infant apparently recovering from a stressful
N E C R O T IZ IN G E N T E R O C O L IT IS O F T H E N E W B O R N 189perinatal period (table III). Clinical signs of perforation with or w ithout peritonitis, sepsis, and disseminated intravascular coagulation (DIC) developed in infants with advanced disease (table IV).
Routine antemortum cultures of the stool were performed in all patients and were consistently negative for pathogens. Blood cultures were positive in 11 infants (37.9 percent) with Klebsiella pneumoniae recorded in five, E. coli in three, Enterobacter cloace in one, Streptococcus bovis in one, and Micrococcus in one. However, in no instance did septicemia precede the onset of abdominal symptoms in patients with NEC. Peritoneal fluid cultures had a similar distribution of organisms. The DIC occurred in seven patients, as evidenced by worsening anemia, thrombocytopenia, prolonged prothrombin time, and partial thromboplastin time. This event had ominous portent as six of the infants expired.R o e n t g e n F i n d i n g s
In order o