Initial Laparotomy Versus Peritoneal Drainage in Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial

Abstract

Objective: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP).

Summary background data: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown.

Methods: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches.

Results: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage [adjusted relative risk (aRR) 1.0; 95% confidence interval (CI): 0.87-1.14]. A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (P = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR 0.81; 95% CI: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%.

Conclusions: There was no overall difference in death or NDI rates at 18 to 22 months corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment.

Figure 1

Participant flow

Figure 2. Posterior distribution of the effect of initial surgical treatment (Initial Laparotomy vs. Initial Drainage) on Death or Neurodevelopmental Impairment (NDI) at 18–22 months corrected age.

Posterior probability distributions of the adjusted risk ratio and risk difference (Initial Laparotomy minus Initial Drainage) derived by combining a prior distribution with trial results. The dashed blue line plots a neutral prior distribution centered at a risk ratio of 1.0, indicating that a priori an equal number of infants would be expected to benefit by either laparotomy or drainage. Light blue shaded areas indicate the posterior probability of reduced death or disability with initial laparotomy (benefit). Dark blue shaded areas indicate the posterior probability of increased death or disability with initial laparotomy (harm). The total area under each probability density curve equals 1. Among infants with a preoperative diagnosis of NEC (a and c), light blue areas indicate a 97% probability that death or NDI in infants treated with Laparotomy is less likely than in infants treated with initial drainage (benefit). Among infants with a pre-operative diagnosis of IP (b and d), the dark blue areas indicate the probability of death or disability among infants treated with Laparotomy is higher than for infants treated with Initial Drainage (harm).