Time of Onset of Necrotizing Enterocolitis and Focal Perforation in Preterm Infants: Impact on Clinical, Surgical, and Histological Features

Abstract

Objective: There is no gold standard test for diagnosis of necrotizing enterocolitis (NEC). Timing of onset is used in some definitions and studies in an attempt to separate NEC from focal intestinal perforation (FIP) with 14 days used as a cutoff. In a large, detailed data set we aimed to compare NEC and FIP in preterm infants born <32 weeks gestation, presenting before 14 days of life in comparison to cases presenting later.Design: Infants with NEC or FIP when parents had consented to enrollment in an observational and sample collection study were included from 2009 to 2019. Clinical, surgical, histological, and outcome data were extracted and reviewed by each author independently.Patients/Episodes: In 785 infants, 174 episodes of NEC or FIP were identified of which 73 (42%) occurred before 14 days, including 54 laparotomies and 19 episodes of medically managed NEC (“early”). There were 56 laparotomies and 45 episodes of medically managed NEC presenting on or after 14 days age (“late”).Results: In early cases, 41% of laparotomies were for NEC (22 cases) and 59% for FIP (32 cases), and in late cases, 91% of laparotomies (51 cases) were for NEC and 9% (five cases) were for FIP. NEC presenting early was more likely to present with an initial septic presentation rather than discrete abdominal pathology and less likely to have clear pneumatosis. Early cases did not otherwise differ clinically, surgically, or histologically or in outcomes compared with later cases. FIP features did not differ by age at presentation.Conclusions: Although most FIP occurred early, 14% occurred later, whereas almost one third (29%) of NEC cases (surgical and medical) presented early. Infant demographics and surgical and histological findings of early- and late-presenting disease did not differ, suggesting that early and late cases are not necessarily different subtypes of the same disease although a common pathway of different pathogenesis cannot be excluded. Timing of onset does not accurately distinguish NEC from FIP, and caution should be exercised in including timing of onset in diagnostic criteria.

Neurologic Consequences of Neonatal Necrotizing Enterocolitis

“…Over 90% of NEC cases occur in VLBW newborns (<1,500 g) born before 32 weeks of gestation, with a 5-fold increase for those infants born before 28 weeks [16, 17]. NEC appears to present earlier in less premature infants, occurring on average 7 days postnatally in that cohort, compared with a mean of 32 days in lower weight, lower gestational age newborns, with a peak incidence at 32 weeks postmenstrual age [18]. This bimodal age of NEC occurrence is significant, as neonates presenting early experience a lower rate of respiratory distress, a less common occurrence of patent ductus arteriosus requiring treatment, a less frequent need for steroids, and a shorter amount of time on the ventilator [18].…”

“…NEC appears to present earlier in less premature infants, occurring on average 7 days postnatally in that cohort, compared with a mean of 32 days in lower weight, lower gestational age newborns, with a peak incidence at 32 weeks postmenstrual age [18]. This bimodal age of NEC occurrence is significant, as neonates presenting early experience a lower rate of respiratory distress, a less common occurrence of patent ductus arteriosus requiring treatment, a less frequent need for steroids, and a shorter amount of time on the ventilator [18]. The timeframe of NEC presentation contrasts with that of spontaneous intestinal perforation (SIP), which occurs between 0 and 3 days in the less premature and 7–10 days in those infants born more preterm [19].…”

Association between prognostic factors and the clinical deterioration of preterm neonates with necrotizing enterocolitis

“…The cut-off value of age at onset, CRP, leukocyte count, and platelet count was analyzed by receiver operating characteristics (ROC) curves. According to a previous study, we assumed the cut-off level for late-onset NEC in preterm infants was ≥ 14 days 9 .…”

Imaging manifestations of neonatal necrotizing enterocolitis to predict timing of surgery

“…Inclusion criteria 1) Meet the revised Bell's NEC II or III clinical diagnostic criteria 7 , and the X-ray features suggests of NEC, including pneumatosis, portal venous gas, gasless abdomen, or fixed dilated loops. 8 2) Complete clinical case records were necessary which included onset time, weight, metabolic disorder indicators, abdominal x-rays, abdominal ultrasound, and surgical records.…”