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      Global incidence of Necrotizing Enterocolitis: a systematic review and Meta-analysis

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          Abstract

          Background

          Necrotizing Enterocolitis (NEC) is a major cause of morbidity and mortality in the Neonatal Intensive Care Unit (NICU), yet the global incidence of NEC has not been systematically evaluated. We conducted a systematic review and meta-analysis of cohort studies reporting the incidence of NEC in infants with Very Low Birth Weight (VLBW).

          Methods

          The databases searched included PubMed, MEDLINE, the Cochrane Library, EMBASE and grey literature. Eligible studies were cohort or population-based studies of newborns including registry data reporting incidence of NEC. Incidence were pooled using Random Effect Models (REM), in the presence of substantial heterogeneity. Additional, bias adjusted Quality Effect Models (QEM) were used to get sensitivity estimates. Subgroup analysis and meta-regression were used to explore the sources of heterogeneity. Funnel plots as appropriate for ratio measures were used to assess publication bias.

          Results

          A systematic and comprehensive search of databases identified 27 cohort studies reporting the incidence of NEC. The number of neonate included in these studies was 574,692. Of this 39,965 developed NEC. There were substantial heterogeneity between studies (I 2 = 100%). The pooled estimate of NEC based on REM was 7.0% (95% CI: 6.0–8.0%). QEM based estimate (6.0%; 95% CI: 4.0–9.0%) were also similar. Funnel plots showed no evidence of publication bias. Although, NEC estimates are similar across various regions, some variation between high and low income countries were noted. Meta regression findings showed a statistically significant increase of NEC over time, quantified by the publication year.

          Conclusion

          Seven out of 100 of all VLBW infants in NICU are likely to develop NEC. However, there were considerable heterogeneity between studies. High quality studies assessing incidence of NEC along with associated risk factors are warranted.

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          Most cited references21

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          Necrotising enterocolitis hospitalisations among neonates in the United States.

          Robert Holman, Barbara Stoll, Aaron T. Curns … (2006)
          The objective of this study was to estimate the rate and describe the epidemiology of necrotising enterocolitis (NEC) among neonates (infants <1 month of age) hospitalised in the United States. Hospital discharge records for neonates with an NEC diagnosis and an in-hospital death or routine discharge were selected for analysis from the 2000 Kids' Inpatient Database. An estimated 4463 (SE = 219) hospitalisations associated with NEC occurred among neonates in the United States during the year 2000, resulting in a hospitalisation rate of 109.9 [95% CI 97.2, 122.6] per 100 000 livebirths. The rate of NEC hospitalisations was highest among non-Hispanic Black neonates. The median hospital length of stay was 49 days. The in-hospital fatality rate was 15.2% (SE = 1.0%). Neonates who underwent a surgical procedure during hospitalisation were more likely to have a longer length of stay and to die than were those who did not have surgical intervention. Low-birthweight (LBW) neonates with NEC were more likely than LBW neonates hospitalised with other diagnoses to be very LBW (VLBW), non-Hispanic Black and male. In addition, compared with LBW neonates hospitalised with other diagnoses, LBW neonates with NEC had higher hospital charges and longer lengths of stay, and were more likely to die during hospitalisation. This study provides the first national estimate of the rate of hospitalisation for NEC among neonates in the United States. During 2000, there was one NEC hospitalisation per 1000 livebirths, with approximately 1 in 7 NEC hospitalisations ending in death. NEC accounts for substantial morbidity; thus, the development of prevention strategies and effective therapies continues to be an important issue.
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            The NICHD neonatal research network: changes in practice and outcomes during the first 15 years.

            James Walsh, Avroy A Fanaroff, Maureen Hack (2003)
            The National Institute of Child Health and Human Development (NICHD) Neonatal Research Network was founded in 1986 to perform trials that, because of their size and complexity, were beyond the scope of a single center and required the expertise and resources of many collaborating centers. This report briefly documents changes in mortality, selected morbidities, and therapies amongst Network centers. The Network registry incorporating perinatal and neonatal data on all infants with a birth weight 501-1500 g cared for at participating centers served as the database. Mortality and selected morbidities were compared for 3 time periods, 1987/1988, (7 centers 1,765 infants, presurfactant); 1993/1994 (12 centers, 4,593 infants, postsurfactant and moderate antenatal corticosteroid utilization); and 1999/2000 (15 centers, 5,848 infants, postsurfactant and widespread corticosteroid use). Detailed outcomes for infants with birth weights between 501 and 800 g, and gestational ages of 23 to 25 weeks are also presented because they dramatically document the changes over time. Mortality for the entire cohort decreased from 23% in 1987/1988 to 17% in 1993/1994 and 14% in 1999/2000. Between 1987/1988 and 1999/2000 mortality prior to discharge, decreased from 66% to 45% for infants weighing 501-750 g; from 34% to 12% for birth weight between 751 to 1000 g, and from 13% to 7% for infants between 1001 and 1500 g. Mortality was higher in boys. Survival free of major morbidity (chronic lung disease/bronchopulmonary dysplasia, necrotizing enterocolitis or grade III/IV intraventricular hemorrhage) did not change significantly over time. Since the inception of the Network, multiple births have increased from 18% to 26%; deliveries by Cesarean section from 47% to 57%, and antenatal corticosteroid use increased from 16% to 79%. Surfactant, which was not used prior to 1990, is now given to 57% of the infants, including 87% with birth weights between 501 and 750 g. There have been significant decreases in the incidence of grade III-IV intraventricular hemorrhage from 18% in 1987/1988 to about 11% since 1993/1994, and periventricular leukomalacia from 8% to 3%. However, other morbidities, including necrotizing enterocolitis, patent ductus arteriosus, and late onset sepsis, have not changed substantially. Advances in perinatal care within NICHD Network centers have resulted in marked improvements in survival. Further advances are required to increase survival free of neonatal morbidity or neurodevelopmental impairment.
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              Epidemiology of neonatal necrotising enterocolitis: a population-based study.

              Timothy Dye, Gustavo Rico-Llanos, J Kendig … (2002)
              We examined the birthweight-, gender- and race-specific incidence as well as the biodemographic and clinical correlates of necrotising enterocolitis (NEC) in a well-defined six-county perinatal region in upstate New York. We conducted a retrospective, 8-year population-based survey to identify all cases of proven NEC (modified Bell stage II and above) in the area's regional neonatal intensive care unit (NICU). The denominator used to calculate the incidence was obtained from the Statewide Planning Research Cooperative System. Incidence was expressed as cases per 1000 live births. A total of 85 documented cases of proven NEC was identified in a six-county perinatal region that experienced 117 892 live births during the 8-year period. The average annual incidence was 0.72 cases per 1000 live births [95% CI 0.57, 0.87 per 1000 live births]. The highest incidence of NEC occurred among infants weighing 750-1000 g at birth and declined with increasing birthweight. The urban county had a 1.53 times higher risk of NEC than rural counties [95% CI 0.9, 2.6]. The overall incidence of NEC for non-Hispanic blacks was significantly greater than that for non- Hispanic whites (2.2 vs. 0.5 cases per 1000 live births, P = 0.00). The differences remained statistically significant even after correction for birthweight. Most cases (93%) in this series were preterm (gestational age <37 weeks). Only two patients were never fed before the diagnosis of NEC was confirmed. Positive blood cultures were documented in 27% of the cases with a predominance of Gram-negative enteric micro-organisms. NEC remains an important health problem especially for preterm infants and the non-Hispanic black population.
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                Author and article information

                Contributors
                Lukman Thalib:
                ORCID: http://orcid.org/0000-0002-1211-6495
                Lthalib@qu.edu.qa
                Journal
                Journal ID (nlm-ta): BMC Pediatr
                Journal ID (iso-abbrev): BMC Pediatr
                Title: BMC Pediatrics
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2431
                Publication date (Electronic): 13 July 2020
                Publication date PMC-release: 13 July 2020
                Publication date Collection: 2020
                Volume: 20
                Electronic Location Identifier: 344
                Affiliations
                [1 ]GRID grid.412603.2, ISNI 0000 0004 0634 1084, Department of Public Health, College of Health Sciences, QU Health, , Qatar University, ; Doha, Qatar
                [2 ]GRID grid.413548.f, ISNI 0000 0004 0571 546X, HMC Medical Cooperation, ; Doha, Qatar
                [3 ]Sidra Medicine, Doha, Qatar
                Author information
                http://orcid.org/0000-0002-1211-6495
                Article
                Publisher ID: 2231
                DOI: 10.1186/s12887-020-02231-5
                PMC ID: 7359006
                PubMed ID: 32660457
                SO-VID: f3a0921b-7887-4f4a-9de2-a02e45925396
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 16 February 2020
                Date accepted : 30 June 2020
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Pediatrics
                Keywords: necrotizing enterocolitis,incidence,systematic review,meta-analysis
                Data availability:
                ScienceOpen disciplines: Pediatrics
                Keywords: necrotizing enterocolitis, incidence, systematic review, meta-analysis

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