Our systematic literature search found 521 articles. Of these, 11 articles reporting on 748 infants met eligibility criteria and were included in our final analysis (Fig. 1) [13,14,15,16,17,18,19,20,21,22,23]. The characteristics of the included studies are summarized in Table 1. The gestational age range of the infants was 23 to 41 weeks. Two of the studies were prospective cohorts, six were retrospective cohorts and three were case series. Bowel US was performed as part of routine evaluation for NEC in five studies, while the remaining six studies performed bowel US selectively per clinical discretion. In seven studies, bowel US was performed in infants with suspected NEC (Bell’s stage ≥1), while in four studies bowel US was performed on infants with definite NEC (Bell’s stage ≥2). The outcome of surgery or death was evaluated in seven studies, while four studies evaluated the outcome of surgical management only.
Table 1 Characteristics of included studies on ultrasound of necrotizing enterocolitis (NEC) Quality assessment
Quality assessment of the included studies is summarized in Table 2. All studies scored 6 to 7 out of a possible 9 on the Newcastle-Ottawa Scale, indicating fair to good quality studies. The criterion most studies scored poorly on was “comparability,” which examines for adjustment of important confounders in the analysis.
Table 2 Quality assessment of selected studies Pooled analyses
Thirteen bowel US findings were evaluated by at least three studies and were included in the meta-analysis. Included studies did not have any missing or unclear data that required contacting study authors. Decreased bowel perfusion, peritoneal calcification, increased superior mesenteric artery flow, and reduced inflation of the intestine were each evaluated only once and were excluded. Decreased peristalsis and ascites (unspecified if simple or complex) were evaluated twice and were also excluded. One study [19] evaluated decreased or absent peristalsis together, while another study [21] assessed complex ascites and focal fluid collections together (both studies were also excluded from further analysis). Studies that investigated the association of bowel US findings with surgery alone were analyzed separately from studies that investigated the combined outcome of surgery or death. Bowel US findings associated with poor outcomes in NEC are summarized in Table 3, while bowel US findings not associated with poor outcomes in NEC are summarized in Table 4. Forest plots summarizing the association of various bowel US findings with surgery or death are also provided in the supplement (Online Resource 2–14).
Table 3 Bowel US findings associated with surgery or death in necrotizing enterocolitis Table 4 Bowel US findings not associated with surgery or death in necrotizing enterocolitis Portal venous gas, pneumatosis intestinalis and free air
Portal venous gas and pneumatosis intestinalis were evaluated in 11 and 10 studies, respectively, while free air was evaluated in six studies. Pooled analysis showed that portal venous gas was not associated with either surgery (OR 1.94, 95% CI 0.99–3.77) or the combined outcome of surgery or death (OR 2.98, 95% CI 0.84–10.60). Pneumatosis was also not associated with surgery or death (OR 2.07, 95% CI 0.85–5.05) but was associated with surgery (OR 2.23, 95% CI 1.01–4.92). As expected, free air was found to be strongly associated with surgery or death (OR 9.63, 95% CI 1.65–56.32) in pooled analysis.
Bowel wall: thickening, thinning, and echogenicity
Bowel wall thickening was evaluated in nine studies, while bowel wall thinning was included in seven studies. The cutoff measurements used for bowel wall thickening and thinning were 2.6 mm and 1.0 mm, respectively, although two studies [21, 22] did not provide clear definitions. Pooled analysis revealed that bowel wall thickening, but not bowel wall thinning, was associated with increased risk for surgery (bowel wall thickening: OR 4.74, 95% CI 2.53–8.89 and bowel wall thinning: OR 3.01, 95% CI 0.88–10.27). When looking at studies that investigated surgery or death, pooled analysis showed both bowel wall thickening and thinning were associated with this combined outcome (bowel wall thickening: OR 3.86, 95% CI 2.43–6.14 and bowel wall thinning: OR 7.11, 95% CI 1.56–32.29). An increase in bowel wall echogenicity, which was defined as an increase in mural echogenicity with loss of hypoechogenic muscle layer [9], was assessed in three studies and found to be associated with an increased risk for surgery or death (OR 8.58, 95% CI 3.42–21.53).
Peristalsis
Five studies looked at absent peristalsis in NEC. No studies specified whether absent peristalsis was localized or generalized throughout the bowel. One study [21] evaluated its association with surgery and was excluded from further analysis. The remaining four studies evaluated surgery or death as a combined outcome and found it to be associated with absent peristalsis on bowel US (OR 10.68, 95% CI 1.65–69.02).
Bowel perfusion
Five studies assessed the association of increased bowel perfusion using color Doppler with NEC outcomes, although increased perfusion was variably defined. Two studies [15, 20] objectively defined increased perfusion as having more than nine dots of color Doppler signal per square centimeter; another two studies [16, 23] used more subjective criteria based on patterns of flow and one study [18] did not provide a clear definition for increased perfusion. No studies evaluated bowel perfusion using Doppler waveforms. Only one study [18] investigated increased perfusion with outcome of surgery and was excluded from further analysis. The remaining four studies investigated the combined outcome of surgery or death. Pooled analysis of these four studies showed that increase in bowel perfusion was not associated with surgery or death in NEC (OR 2.60, 95% CI 0.61–11.13). Absent perfusion was assessed in four studies. Of these, we pooled analysis from the three studies that assessed the outcome of surgery or death. In contrast to increased perfusion, we found that absent perfusion was associated with the combined outcome of surgery or death (OR 6.99, 95% CI 2.06–23.76).
Abdominal fluid: simple ascites, complex ascites, and focal fluid collections
Seven studies investigated the association of simple ascites with outcomes in NEC – two studies looked at surgery alone, while five studies looked at surgery or death. Pooled analysis showed that simple ascites was not associated with either surgery alone (OR 0.46, 95% CI 0.03–6.97) or surgery or death (OR 0.54, 95% CI 0.12–2.47). Of the four studies that evaluated complex ascites, only three studies that assessed surgery or death were pooled for analysis. In contrast to simple ascites, complex ascites was found to be associated with surgery or death (OR 11.28, 95% CI 4.23–30.04). Six studies assessed the association of focal fluid collection with outcomes in NEC. One study [18] evaluated for the outcome of surgery, while the remaining five studies evaluated for the combined outcome of surgery or death. Pooled analysis from these five studies showed that focal fluid collection was associated with surgery or death (OR 17.92, 95% CI 3.11–103.31).
Intestinal dilation
Intestinal dilation was not clearly defined by the three studies that assessed its association with surgery or death. Nevertheless, its presence was found to be associated with an increased risk for surgery or death (OR 3.50, 95% CI 1.81–6.75).