Clinical Characteristics of Necrotizing Enterocolitis Diagnosed by Independent Adjudication of Abdominal Radiographs, Laparotomy, or Autopsy in Preterm Infants in the “Connection Trial”

Josef Neu; Rachana Singh; Mihaela Demetrian; Jaime Flores-Torres; Mark Hudak; John A. Zupancic; Anders Kronström; Jonas Rastad; Staffan Strömberg; Marcus Thuresson; The “Connection Study” Group

doi:10.1055/s-0044-1788275

American Journal of Perinatology, Table of Contents

CC BY-NC-ND 4.0 · Am J Perinatol 2025; 42(02): 268-280
DOI: 10.1055/s-0044-1788275

Original Article

Clinical Characteristics of Necrotizing Enterocolitis Diagnosed by Independent Adjudication of Abdominal Radiographs, Laparotomy, or Autopsy in Preterm Infants in the “Connection Trial”

Authors

Josef Neu

¹Department of Pediatrics, UF Health Shands Children's Hospital, Gainesville, Florida
Rachana Singh

²Department of Pediatrics, Tuft's Children's Hospital, Tuft's University School of Medicine, Boston, Massachusetts
Mihaela Demetrian

³Department of Neonatology, Spitalul Clinic Filantropia, Bucharest, Romania
Jaime Flores-Torres

⁴Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida
Mark Hudak

⁵Department of Pediatrics, University of Florida College of Medicine, Jacksonville, Florida
John A. Zupancic

⁶Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Anders Kronström

⁷Infant Bacterial Therapeutics, Stockholm, Sweden
Jonas Rastad

⁷Infant Bacterial Therapeutics, Stockholm, Sweden
Staffan Strömberg

⁷Infant Bacterial Therapeutics, Stockholm, Sweden
Marcus Thuresson

⁷Infant Bacterial Therapeutics, Stockholm, Sweden

The “Connection Study” Group

Abstract

Objective Necrotizing enterocolitis (NEC) classically is diagnosed by radiographic demonstration of pneumatosis intestinalis/portal venous gas (PI/PVG). This study examines clinical characteristics of NEC confirmed by independent evaluation of abdominal radiographs, taken for clinical signs of NEC, or by pathologic findings at laparotomy or autopsy (confirmed NEC [cNEC]).

Study Design The investigated cohort included 1,382 extremely low birth weight (BW) infants (BW range: 500–1,000 g) with median 27 weeks (range: 23–32) gestational age (GA) at birth. They were randomized into the placebo-controlled “Connection Trial” of the new biological drug candidate IBP-9414 with cNEC as one primary endpoint.

Results Total 119 infants (8.6%) had cNEC diagnosed at median 14 days of age by confirming PI/PVG at X-ray adjudication (n = 111) and/or by surgery/autopsy (n = 21). Sixteen percent of cNEC cases died. Adverse events of NEC were reported in 8.5% of infants and 4.1% had NEC diagnosed by radiology and surgery/autopsy at the participating centers. Regression analyses showed that the risk of cNEC decreased by 11 to 30% for every 100-g increment in BW and single-week increment in GA and associated cNEC with odds ratios (ORs) > 2.0 for gastrointestinal (GI) perforation and obstruction, hypotension, hypokalemia, hypophosphatemia, and death. Comparing risks of cNEC in infants below and above 750-g BW showed higher ORs (2.7–4.3) for GI perforation, hypotension, hypokalemia, and renal complications in the smaller infants, whereas the bigger infants had higher ORs (1.9–3.2) for serious non-GI events, late-onset sepsis (LOS), and death. Predictors of cNEC (hazard ratio, HR > 1.5) included serious non-GI events (mainly infections), hyponatremia, and hyperglycemia, whereas the HR was 0.52 for intravenous antibiotics. After cNEC diagnosis, there were higher rates of GI perforation and obstruction, hypotension, hypokalemia, and LOS.

Conclusion Independent adjudication of abdominal radiographs increased radiological recognition of NEC and proved to be feasible in a multicenter study setting as well as able to diagnose clinically relevant NEC.

Key Points

Independent adjudication of abdominal radiographs in ELBW infants increased NEC recognition.
Risk of NEC decreased by 11 to 30% with every 100-g increment in BW and GA week.
In infants with BW 750 to 1,000 g, the risk of death from NEC was almost twice that in infants with BW 500 to 749 g
Infants with NEC received antibiotics during one-third and parenteral nutrition during half of the first 7 postnatal weeks.

Keywords

ELBW infants - abdominal radiography - necrotizing enterocolitis - clinical associations - risk factors

Full Text

References

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