Version July 2025
INTRODUCTION —
Spontaneous intestinal perforation (SIP; also referred to as isolated perforation or focal intestinal perforation [FIP]) of the newborn is a single intestinal perforation that is typically found at the terminal ileum [1-5].
SIP occurs primarily in preterm infants with very low birth weight (VLBW, birth weight <1500 g) and extremely low birth weight (ELBW, birth weight <1000 g). SIP is a separate clinical entity from necrotizing enterocolitis (NEC), the most severe gastrointestinal complication of preterm infants. This differentiation is important because of management considerations. (See 'Distinguishing between SIP and NEC' below.)
The epidemiology, clinical features, diagnosis, and management of SIP in neonates will be reviewed here.
The diagnosis, management, and pathology of NEC are discussed separately.
●(See "Neonatal necrotizing enterocolitis: Clinical features and diagnosis".)
●(See "Neonatal necrotizing enterocolitis: Management and prognosis".)
●(See "Neonatal necrotizing enterocolitis: Pathology and pathogenesis".)
EPIDEMIOLOGY —
SIP most commonly occurs in preterm very low birth weight (VLBW, BW <1500 g) and extremely low birth weight (ELBW, BW <1000 g) infants.
Incidence — In a study analyzing data from 658,001 neonates in the National Inpatient Sample (2002 to 2017), the reported incidence of SIP among VLBW infants was 1.6 percent [6]. The incidence of SIP increased with decreasing gestational age (GA), and 90 percent of SIP cases occurred in neonates ≤28 weeks GA. In a separate study analyzing data from >1.6 million neonates in the Pediatrix clinical database (1997 to 2020), the incidence of SIP among neonates born at 22 to 24 weeks GA was 3.9 percent [7]. In both studies, SIP was more common in male than female infants [6,7].
Risk factors
Preterm birth — Prematurity is the only well-established risk factor for SIP. The risk of SIP increases with decreasing GA [6,7].
Other risk factors — Other reported antenatal and postnatal risk factors are based upon limited data that include findings from case series [1,8-12]. It remains uncertain whether there is an association between SIP and the following factors.
●Antenatal
•Chorioamnionitis – Intraamniotic infection (chorioamnionitis) appears to be an risk factor for SIP. In one case-control study of 16 preterm infants with SIP, maternal intrapartum antibiotic therapy was more common among neonates with SIP compared with matched controls (93 versus 57 percent); confirmed maternal histologic chorioamnionitis was also more common in neonates with SIP (40 versus 12 percent) [8].
•Antenatal medications – Antenatal medications that have been reported to be associated with increased risk of SIP include glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and magnesium sulfate [7,10,13-17]. Although these studies have demonstrated a possible increased risk of SIP with antenatal glucocorticoid administration, it is important to recognize that the absolute risk is very small and is far outweighed by the well-established benefits of antenatal glucocorticoid for reducing respiratory morbidity. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery".)
●Postnatal
•Exposure to glucocorticoids – Early administration of postnatal glucocorticoids increases the risk of SIP [7,18-20]. This was best illustrated in a meta-analysis of four trials of prophylactic dexamethasone for the prevention of bronchopulmonary dysplasia in which VLBW infants treated with dexamethasone before 48 hours of life had an increased risk of SIP compared with controls (odds ratio [OR] 1.91, 95% CI 1.21-3.07) [18]. (See "Postnatal use of glucocorticoids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants", section on 'Adverse effects'.)
•Exposure to indomethacin – Some studies have found an association between postnatal use of indomethacin and SIP [7,14,16], whereas others have not [9,21,22]. (See "Patent ductus arteriosus (PDA) in preterm infants: Management and outcome", section on 'Indomethacin'.)
The risk of SIP in the setting of indomethacin use may be influenced by feeding status. In a retrospective cohort study of 4268 ELBW infants, indomethacin in combination with early feeding was associated with an increased risk of SIP, but early feeding alone was not associated with SIP [23].
•Others – Other reported postnatal risk factors include use of inotropic agents, severe intraventricular hemorrhage (grade III or higher), excessive early weight loss (>15 percent), and delayed onset of enteral feeding [7,24,25]. These risk factors likely are markers for severity of illness; they are unlikely to play a causative role.
Protective factors — Early enteral nutrition appears to be associated with a decreased incidence of SIP [26]. Components in breast milk, such as arginine and glutamine and polyunsaturated fatty acids in colostrum, have also been associated with protective effects [27].
PATHOLOGY AND PATHOGENESIS —
In most cases of SIP, there is a single isolated perforation. The typical location is the antimesenteric border of the terminal ileum, though perforation has also been reported in the jejunum and colon [1-5]. At the area of perforation, focal hemorrhagic necrosis with well-defined margins is observed in contrast to the ischemic and coagulative necrosis seen in necrotizing enterocolitis (NEC) [4,28]. In SIP, the bowel proximal and distal to the perforation appears normal (picture 1).
The etiology of SIP remains unknown. Several studies have explored a variety of different pathogenetic pathways.
●Thinning or absence of the muscularis propria at the perforation site has been reported in several cases [2,28-31], but it is unclear whether these changes are involved in the pathogenesis of SIP.
●A role for abnormal or delayed nitric oxide synthase (NOS) has been hypothesized based upon a single study of a NOS knock-out mouse model that demonstrated ileal perforation with exposure to indomethacin and/or dexamethasone [32].
●Changes in immunoregulatory pathways including angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia and oxidative stress, inflammation, and muscle contraction. Although, there is upregulation of these processes in SIP, it is milder in intestinal and plasma samples taken from patients with SIP versus those with necrotizing enterocolitis (NEC) [33,34].
CLINICAL MANIFESTATIONS
Age at presentation — SIP occurs in very low birth weight (VLBW) and extremely low birth weight (ELBW) preterm infants with a gestational age <27 weeks. In several case series of SIP, the median age at perforation was seven days with a range of 0 to 15 days [1,2,4,9,12,35,36]. In one large study, neonates with SIP presented earlier in the postnatal course compared with neonates with necrotizing enterocolitis (NEC) [9]. The median age at presentation was 7 days for neonates with SIP compared with 15 days for those with NEC. (See 'Distinguishing between SIP and NEC' below.)
Physical findings — Neonates with SIP present with an acute onset of abdominal distension. Abdominal distention usually occurs without the abdominal wall erythema, crepitus, and induration commonly seen in patients with NEC.
A black-bluish discoloration of the abdominal wall may be seen in SIP, and is not a finding that is typical of NEC (picture 2) [1,4,29,36-38]. The discoloration may extend into the groin and, in males, the scrotum.
Other associated findings may include tachycardia, hypotension, and signs of peritonitis. However, hemodynamic instability is less common in neonates with SIP than in those with NEC. (See 'Distinguishing between SIP and NEC' below.)
Associated infections — Concomitant bacterial or fungal bloodstream infections are common in neonates with SIP and this can be a major contributor to morbidity and mortality [1,2,8,36]. It is unknown whether the infections precede or are a result of bowel perforation. (See "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at less than 35 weeks gestation" and "Candida infections in neonates: Epidemiology, clinical manifestations, and diagnosis", section on 'Other organ involvement'.)
All neonates with SIP should have blood cultures obtained and should receive empiric antibiotic therapy. (See 'Initial medical management' below.)
Laboratory findings — The following laboratory findings are common in neonates with SIP. These are nonspecific findings and can be seen in many other neonatal conditions:
●Leukocytosis (white blood cell count >14,000/microL), which occurs in most infants with SIP [36,38].
●Serum alkaline phosphatase and bilirubin are often increased [38].
●Platelet count and hematocrit may be decreased [1].
●Hyperglycemia [39].
Lactic acidosis is uncommon, occurring in only approximately 10 percent of cases [39]. This contrasts with severe NEC, in which lactate levels are often elevated. Thus, the finding of intestinal perforation associated with hyperglycemia and normal lactate level is more suggestive of SIP than NEC. (See 'Distinguishing between SIP and NEC' below and "Neonatal necrotizing enterocolitis: Clinical features and diagnosis", section on 'Blood tests'.)
Radiographic findings — Abdominal radiographs demonstrating pneumoperitoneum support the diagnosis of SIP (image 1 and image 2). Images are performed in the supine position and either the supine cross-table lateral view or lateral decubitus position with the left side down to detect pneumoperitoneum (image 2). Radiographic findings that help to distinguish between NEC and SIP are discussed below. (See 'Distinguishing between SIP and NEC' below.)
If obtained, abdominal ultrasound may detect echogenic fluid collections in the peritoneal cavity, although this is more common in NEC [40].
DIAGNOSIS
●Presumptive diagnosis – A presumptive diagnosis of SIP is based upon the characteristic clinical and radiographic features in a preterm infant within the first 10 days after birth.
•Clinical findings include abdominal distension, often with the classical bluish discoloration of the abdominal wall in the absence of abdominal wall erythema (picture 2), crepitus, and induration. (See 'Physical findings' above.)
•The radiographic finding that strongly supports the diagnosis of SIP (especially when observed in the context of the above clinical findings) is pneumoperitoneum without pneumatosis intestinalis or portal venous air (image 1 and image 2). (See 'Radiographic findings' above.)
●Definitive diagnoses – The diagnosis of SIP is confirmed by operative findings demonstrating an isolated bowel perforation in the setting of otherwise normal bowel (picture 1), and confirmed by histopathologic examination. However, as discussed below, most neonates with SIP can be managed without laparotomy. (See 'Surgical management' below.)
DISTINGUISHING BETWEEN SIP AND NEC —
The primary alternative diagnostic consideration for neonates with of SIP is necrotizing enterocolitis (NEC). There is considerable overlap between SIP and NEC [41]. However, since the optimal management of these two disorders may differ, it remains helpful to attempt to distinguish SIP from NEC.
Despite the overlap, the following common findings of SIP typically distinguish it from NEC [1,4,29,36,37,42,43]:
●SIP generally presents within the first week after birth whereas NEC typically presents at a later age (>7 days) after the neonate has started to feed.
●SIP has the characteristic physical finding of significant abdominal distention, often accompanied by a bluish discoloration (picture 2).
●Specific radiographic findings on abdominal radiographs that are diagnostic for NEC (eg, pneumatosis intestinalis, portal venous air, transient thickening of the intestinal wall, and fixed dilated small bowel loops) are absent in patients with SIP. Although pneumoperitoneum is a common supportive radiologic finding for SIP, occurring in approximately 30 to 50 percent of affected patients, it is not a distinguishing feature as it also frequently occurs in patients with NEC.
●Hemodynamic instability and lactic acidosis are uncommon in neonates with SIP. By contrast, neonates with NEC tend to appear more ill, may be unstable, and may require additional supportive care (eg, ventilatory or hemodynamic support).
These clinical features can usually make the distinction between SIP and NEC. Ultimately histopathologic examination of a surgical specimen is the most definitive way to make the distinction. Specific histopathological findings of SIP include isolated hemorrhagic necrosis as opposed to the more diffuse coagulative necrosis seen in NEC [4,28]. However, as discussed below, most neonates with SIP can be managed without obtaining a surgical specimen. (See 'Surgical management' below.)
MANAGEMENT
Initial medical management — Initial medical management of a neonate with suspected SIP is directed toward stabilization of the patient prior to surgical intervention and includes the following:
●Cessation of all feeds and enteral medications
●Nasogastric suction to decompress the abdomen
●Supportive care including fluid resuscitation and inotropic medications to correct hypotension
●Intravenous broad-spectrum antibiotics
These supportive measures, including the choice of antibiotic regimen, are generally the same as for neonates with necrotizing enterocolitis (NEC), as discussed in detail separately. (See "Neonatal necrotizing enterocolitis: Management and prognosis", section on 'Supportive care' and "Neonatal necrotizing enterocolitis: Management and prognosis", section on 'Antibiotic therapy'.)
Surgical management — Definitive treatment for SIP is surgical.
Choice of procedure — SIP can be managed with laparotomy or bedside primary peritoneal drainage (PPD) [4,29,44,45]. While laparotomy has historically been considered the definitive treatment for SIP, many pediatric surgeons, including the authors of this topic, now consider PPD to be the initial treatment of choice. If successful, PPD avoids laparotomy, general anesthesia, and the need for transport to the operating room for these very preterm and often unstable patients. Many patients with SIP who are managed with PPD recover without needing any further surgical intervention [45]. However, the choice of procedure varies depending on the resources and surgical expertise at the center.
The efficacy and safety of PPD were established in a multicenter randomized trial involving 213 extremely low birth weight (ELBW; <1000 g) infants with SIP who were randomly assigned to PPD or primary laparotomy [45]. The composite outcome of death or neurodevelopmental impairment (NDI) at 18 to 22 months corrected age occurred less commonly in the PPD group (63 versus 69 percent), but the difference did not achieve statistical significance (adjusted relative risk 0.90, 95% CI 0.76 to 1.05).
The results of this trial are consistent with previous observational data, including a multicenter, retrospective study of 171 infants with SIP [46-51]. In this report, infants managed with PPD (n = 110) and primary laparotomy (n = 61) had similar complication rates, time to resume feeds, length of hospital stay, and mortality [46].
An alternative procedure involving simple peritoneal needle aspiration has been described in a small case series from a single center in France [50]. However, we do not recommend this procedure until there are further studies confirming its efficacy and safety.
Primary peritoneal drainage — PPD is the preferred initial procedure for infants with SIP at our centers.
●Procedure – PPD is performed at the bedside. Our practice is to use only a single drainage site, although other surgeons perform a counter incision in the left lower quadrant and thread the Penrose drain or vessel loop between the two incisions.
After the administration of intravenous pain medication, the abdomen is prepped with iodine solution, and local anesthesia is administered. A small transverse incision is made at McBurney's point (two-thirds of the distance from the umbilicus to the anterior superior iliac crest in the right lower quadrant). The layers of the abdominal wall are bluntly dissected to enter the peritoneal cavity. In many cases, there will be a rush of air followed by drainage of meconium.
Cultures are taken and a Penrose drain is gently threaded into the abdomen and secured. In some centers, the peritoneal cavity is irrigated with warm saline solution prior to the insertion of the Penrose drain, although there are no data to support this practice. Use of a small pigtail catheter instead of a Penrose drain has been reported in a small pilot study with encouraging results (less stool drainage, fewer transfusions, less time to refeeding, and no incisional hernias) [52]. These preliminary data support future study of the use of pigtail catheters for PPD.
●Drain removal – Once the drain is in place, drainage is monitored over the subsequent days. When there is no evidence of persistent intestinal or meconium drainage from the drain site, the drain is partially withdrawn daily until it is completely removed. It is not necessary to keep the drain in place until the infant is fed. After bowel function has returned (ie, once the neonate starts passing stools), a trial of feeding can be started or the patency of the gastrointestinal tract can be determined with a contrast study.
Many patients with SIP who are managed with PPD recover without needing any further surgical intervention. However, some neonates my still require laparotomy (eg, if there are ongoing signs of peritonitis and/or reaccumulation of pneumoperitoneum). (See 'Indications for laparotomy' below.)
Laparotomy — Laparotomy was traditionally considered the definitive treatment for SIP before practice shifted towards PPD [4,29,44]. (See 'Choice of procedure' above.)
Indications for laparotomy
●Primary laparotomy – At the authors’ centers, PPD is generally preferred over primary laparotomy for most neonates with SIP. However, as discussed above, other centers may perform primary laparotomy for initial management of SIP. (See 'Choice of procedure' above.)
●Laparotomy after PPD – Some neonates who have undergone PPD subsequently require laparotomy. Indications for laparotomy after PPD include [49]:
•Reaccumulation of free air after the drain is removed, indicating the perforated bowel did not seal.
•Ongoing sepsis, indicating a failure of the drain to control contamination and ongoing peritonitis.
•Fistula with persistent intestinal drainage that fails to close after several weeks of observation.
•Bowel obstruction, either due to adhesions or, more commonly, a stricture at the site of the perforation.
In the available studies, approximately 30 to 45 percent of neonates managed with PPD subsequently required laparotomy [45,46].
Procedure — Laparotomy typically involves bowel resection with either primary anastomosis or creation of an ostomy.
Postoperative care — Postoperative care for neonates who have undergone surgical treatment of SIP (either with PPD or laparotomy) includes the following:
●Ongoing supportive medical management, including parenteral nutrition and intravenous antibiotics. (See 'Initial medical management' above.)
●Monitoring output from the drain or ostomy. (See 'Primary peritoneal drainage' above.)
●Gradual introduction of enteral feeding – The timing of initiating enteral feeds depends on the postoperative course. Small enteral feeds to support gut integrity ("trophic feeds") are usually well tolerated. Enteral feeds can be increased once there is evidence of bowel function (ie, once the neonate is stooling or has ostomy output). Consultation with a dietitian can be helpful to assist with optimizing nutritional support and addressing complications of parenteral nutrition. (See "Parenteral nutrition in premature infants" and "Approach to enteral nutrition in the premature infant".)
●Ongoing pediatric surgical care is appropriate to ensure normal recovery and to address postoperative complications such as strictures, incisional hernias, and intestinal adhesions, which may lead to obstruction.
OUTCOME —
Preterm neonates with SIP are at increased risk of mortality and long-term neurodevelopmental impairment (NDI) compared with neonates without SIP of the same gestational age [6,7,53-57]. In the contemporary era, reported survival rates for neonates with SIP range from 60 to 90 percent [4-6,36,37,47,58,59]. The improvement in survival since the 1990s is likely due to advances in neonatal care including improved nutritional support. Outcomes for neonates with SIP are highly influenced by other comorbidities (eg, sepsis, bronchopulmonary dysplasia [BPD], intraventricular hemorrhage [IVH]).
Patients with SIP appear to have a lower risk of mortality compared with patients with necrotizing enterocolitis (NEC), after adjusting for confounding factors [6,53-55]. However, both populations are at risk for long-term NDI [53,56,57]. (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors".)
In a study analyzing data from the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network database (2000-2005), rates of death or NDI for ELBW neonates with and without SIP or NEC were as follows [53]:
●Neonates with SIP – 61 percent survived to hospital discharge; only 37 percent of survivors were without NDI at 18 to 22 months
●Neonates with surgical NEC – 47 percent survived to hospital discharge; 43 percent of survivors were without NDI at 18 to 22 months
●Neonates without SIP or NEC – 78 percent survived to hospital discharge; 64 percent of survivors were without NDI at 18 to 22 months
After adjusting for potential confounders, neonates with SIP had a two-fold higher risk of death (adjusted odds ratio [aOR] 2.21, 95% CI 1.5-3.2) and NDI (aOR 2.17, 95% CI 1.4-3.2) compared with neonates without SIP or NEC.
In addition, neonates with SIP also appear to be at increased risk to develop retinopathy of prematurity, periventricular leukomalacia and other comorbidities (eg, sepsis) compared with those without SIP [42,53]. (See "Overview of short-term complications in preterm infants" and "Overview of the long-term complications of preterm birth" and "Retinopathy of prematurity (ROP): Risk factors, classification, and screening".)
SUMMARY AND RECOMMENDATIONS
●Definition and pathology – Spontaneous intestinal perforation (SIP) of the newborn is a single intestinal perforation typically found on the antimesenteric border of the terminal ileum. (See 'Pathology and pathogenesis' above.)
SIP is a separate clinical entity from necrotizing enterocolitis (NEC), the most severe gastrointestinal complication of preterm infants. (See "Neonatal necrotizing enterocolitis: Pathology and pathogenesis" and "Neonatal necrotizing enterocolitis: Clinical features and diagnosis".)
●Epidemiology – SIP occurs primarily in preterm infants. The risk increases with decreasing gestational age and birth weight. Among very low birth weight (VLBW; <1500 g) and extremely low birthweight (ELBW; <1000 g) neonates, the incidence is approximately 2 to 4 percent. Although preterm birth is the only well-established risk factor, other reported risk factors include chorioamnionitis, postnatal glucocorticoid therapy, and postnatal indomethacin therapy. (See 'Epidemiology' above.)
●Clinical manifestations – SIP generally presents within the first 10 days after birth with acute onset of abdominal distension. The classical physical finding is a black-bluish discoloration of the abdominal wall (picture 2). Other findings that are commonly seen in NEC (eg, abdominal wall erythema, crepitus, and induration) are usually absent in infants with SIP. (See 'Clinical manifestations' above.)
●Diagnosis – The diagnosis for SIP is based upon clinical presentation and physical findings consistent with SIP in the presence of pneumoperitoneum (image 1 and image 2) without other radiographic findings suggestive of NEC (ie, without pneumatosis intestinalis or portal venous air). (See 'Diagnosis' above.)
●Distinguishing between SIP and NEC – NEC is the main alternative diagnosis in the differential diagnosis of SIP. Distinguishing between the two disorders is usually based upon the clinical manifestations and abdominal radiographic findings, although there is considerable overlap between the two conditions. (See 'Distinguishing between SIP and NEC' above.)
●Management
•Initial medical management – The initial management for a neonate with SIP is directed towards stabilization of the patient. This includes discontinuing feeds and enteral medications, nasogastric suctioning, intravenous fluids, antibiotics, and, if needed, vasoactive medications to correct hypotension. The approach is similar to supportive care for neonates with NEC, as discussed separately. (See "Neonatal necrotizing enterocolitis: Management and prognosis", section on 'Medical management'.)
•Surgical management – Neonates with SIP require definitive surgical intervention. For most patients, we suggest primary peritoneal drainage (PPD) as the initial surgical intervention rather than primary laparotomy (Grade 2C). PPD appears to be equally effective, and it avoids general anesthesia and the need for transport to the operating room for these very preterm and often unstable patients. (See 'Surgical management' above.)
●Outcome – Preterm neonates with SIP are at increased risk of mortality and long-term neurodevelopmental impairment compared with neonates without SIP of the same gestational age. In the contemporary era, reported survival rates for neonates with SIP range from 60 to 90 percent. Outcomes for neonates with SIP are highly influenced by other comorbidities (eg, sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage). (See 'Outcome' above.)
