Intestinal Perforation Associated With Perinatal Asphyxia and Anaemia

Field: Medicine (Health Sciences)

Perinatal asphyxia is frequently associated with multiorgan failure including a range of gastrointestinal (GI) injury from transient, altered intestinal motility to narcotising enterocolitis (NEC) (1,2). Isolated intestinal perforation without NEC has also been associated with perinatal asphyxia (3). Multicentre trials of therapeutic hypothermia (TH) for hypoxic ischemic encephalopathy (HIE) have not found an increased incidence of GI problems in neonates managed with hypothermia (1,2). We report 3 cases of isolated intestinal perforations for 13 years (2002–2014), among 586 (0.51%) neonates with HIE. All 3 neonates had significant perinatal asphyxia associated with anaemia at birth requiring early blood transfusion, raising the possibility that the addition of anaemic shock at birth may be a risk factor for the development of serious gut injury in neonates with perinatal asphyxia. Tables 1 and 2 provide detailed information on the 3 neonates; here we present the salient features of each case.TABLE 1: Baseline characteristics of the casesTABLE 2: Laboratory, imaging, and histopathology resultsCASE 1 A 32-week infant was pale and shocked at birth with initial haemoglobin of 71 g/L, following in utero bleeding from the umbilical cord immediately after amniocentesis. First blood transfusion was at 6 hours of age. She developed multiorgan failure, including moderate-severe HIE and acute renal failure necessitating peritoneal dialysis. She did not receive TH. On the fifth day, she developed abdominal distension with free peritoneal gas on x-ray. Laparotomy revealed 2 perforations in the terminal ileum without evidence of NEC; managed with a resection and an end-to-end anastomosis. Unfortunately, she died of multiorgan failure on day 28. CASE 2 A 40-week infant was pale, floppy and acidotic at birth, with initial haemoglobin of 89 g/L (due to ruptured vasa praevia) requiring an immediate blood transfusion. He had severe HIE necessitating TH. During the first week, he developed progressive renal failure requiring renal dialysis. Because of nonspecific signs of gut compromise the peritoneal dialysis catheters were placed via an exploratory laparotomy, which showed only a small area of terminal ileal necrosis and a perforation. An ileostomy was formed after an ileal resection. Subsequently his renal, gut, and neurological function improved. At 5 years of age, he has chronic renal failure and his neurodevelopment is progressing in the low average range. CASE 3 A 37-week twin was born very pale with Apgar of 0 until 30 minutes of age. There had been a massive antepartum haemorrhage thought to be due to a placental abruption. His cord haemoglobin was 89 g/L. He received an urgent blood transfusion as part of resuscitation. He developed severe HIE, requiring TH, and multiorgan failure. On day 7, an abdominal x-ray showed free peritoneal gas. At laparotomy, an isolated terminal ileal perforation was found without NEC. At 12 months of age his renal, gut, and neuro developmental functions were normal. His twin was also born without a heartbeat and required an urgent blood transfusion and full resuscitation; he was also cooled for moderate HIE but did not have any gut problems. DISCUSSION All of our cases had significant perinatal asphyxia and anaemic shock, with development of spontaneous ileal perforations and severe renal failure in 2 of the 3 neonates. The link between perinatal asphyxia, NEC, and intestinal perforations in neonates has been made previously (4). Prgomet et al (5) reports 3 infants with spontaneous GI perforation (non-NEC) associated with anaemia as a risk factor in these babies. The presence of significant acute anaemia theoretically adds a third insult, hypoxic anaemia, to ischemia and systemic hypoxemia and there is some evidence that this is less well tolerated compared with hypoxic hypoxia (6). Regional GI and renal blood flow has been shown to be significantly impaired in after asphyxiated term neonates in direct correlation to the degree of asphyxia. This is in keeping with the diving reflex, whereby in mild-to-moderate asphyxia, blood preferentially shunts to the brain, heart, and adrenals at the expense of less important areas for immediate survival, such as the splanchnic vascular bed (7). In keeping with this, all 3 perforations occurred in the known vascular watershed region of the terminal ileum. The benefits of TH in neonates with HIE have been well documented with relatively few minor side effects and in particular there is no evidence that TH places a neonate with HIE at increased risk of significant GI side effects (1,2). Because the incidence of significant GI injury in HIE is low, in our own study being 3/586 (0.51%), it is possible that much larger studies are, however, required to detect a significant difference in the rate of GI injury due to TH. The effect of TH on the gut in the subset of neonates with HIE and significant anaemia has not been specifically studied. We could not find any studies specifically reporting on the frequency of severe neonatal anaemia associated with perinatal asphyxia. Jacobs et al (1) in a Cochrane systematic review of TH in HIE, found that 51/379 (13.5%) infants who received standard care (not cooled) required a blood transfusion; the cause of the anaemia and timing of the transfusions were not specified. Feto-maternal haemorrhage associated with shock and perinatal asphyxia has been reported to be relatively uncommon, but carries a significant neonatal mortality and morbidity (8). The best outcome in our 3 cases was associated with early blood transfusion, when hemodynamic support was promptly provided to restore oxygen carrying capacity to the compromised vascular bed. Although blood transfusions have been implicated in gut injury in the neonate; further studies are needed in this setting to elucidate if blood transfusion itself could be the cause of significant GI injury. In summary, our experience indicates that significant anaemia with perinatal asphyxia could be a risk factor for bowel ischemia leading to intestinal perforation in neonates. Further studies are required to determine if acute anaemia is a significant additional risk factor for GI injury in the setting of HIE or whether blood transfusion for anaemia itself is problematic in the setting of HIE with whole body cooling. In the meantime, clinicians should be aware of this possible association when caring for neonates with HIE and anaemia.