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Necrotising Enterocolitis: epidemiology and imaging
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.ORCID iD: 0000-0001-5176-4949
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Necrotising enterocolitis (NEC) is a potentially devastating intestinal inflammation of multifactorial aetiology in premature or otherwise vulnerable neonates. Because of the broad spectrum of presentations, diagnosis and timing of surgical intervention may be challenging, and imaging needs to be an integrated part of management.

The first four studies included in this thesis used routinely collected, nationwide register data to describe the incidence of NEC in Sweden 1987‒2009, its variation with time, seasonality, space-time clustering, and associations with maternal, gestational, and perinatal factors, and the risk of intestinal failure in the aftermath of the disease.

Early infant survival increased dramatically during the study period. The incidence rate of NEC was 0.34 per 1,000 live births, rising from 0.26 per 1,000 live births in the first six years of the study period to 0.57 in the last five. The incidence rates in the lowest birth weights were 100‒160 times those of the entire birth cohort. Seasonal variation was found, as well as space-time clustering in association with delivery hospitals but not with maternal residential municipalities.

Comparing NEC cases with matched controls, some factors, positively associated with NEC, were isoimmunisation, fetal distress, caesarean section, persistent ductus arteriosus, cardiac and gastrointestinal malformations, and chromosomal abnormalities. Negative associations included maternal pre-eclampsia, maternal urinary infection, and premature rupture of the membranes. Intestinal failure occurred in 6% of NEC cases and 0.4% of controls, with the highest incidence towards the end of the study period.

The last study investigated current practices and perceptions of imaging in the management of NEC, as reported by involved specialists. There was great consensus on most issues. Areas in need of further study seem mainly related to imaging routines, the use of ultrasound, and indications for surgery.

Developing alongside the progress of neonatal care, NEC is a complex, multifactorial disease, with shifting patterns of predisposing and precipitating causes, and potentially serious long-term complications. The findings of seasonal variation, spacetime clustering, and negative associations with antenatal exposure to infectious agents, fit into the growing understanding of the central role of bacteria and immunological processes in normal maturation of the intestinal canal as well as in the pathogenesis of NEC. Imaging in the management of NEC may be developed through future studies combining multiple diagnostic parameters in relation to clinical outcome.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2017. , p. 97
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1586
National Category
Pediatrics Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:liu:diva-142375DOI: 10.3384/diss.diva-142375ISBN: 9789176854556 (print)OAI: oai:DiVA.org:liu-142375DiVA, id: diva2:1153383
Public defence
2017-11-24, Berzeliussalen, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2017-10-30 Created: 2017-10-30 Last updated: 2018-03-27Bibliographically approved
List of papers
1. Epidemiology and Trends of Necrotizing Enterocolitis in Sweden: 1987-2009
Open this publication in new window or tab >>Epidemiology and Trends of Necrotizing Enterocolitis in Sweden: 1987-2009
2013 (English)In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 132, no 2, p. E443-E451Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate temporal, seasonal, and geographic variations in the incidence of necrotizing enterocolitis (NEC) and its relation to early infant survival in the Swedish population and in subgroups based on gestational age, birth weight, and gender. less thanbrgreater than less thanbrgreater thanMETHODS: In the Swedish birth cohort of 1987 through 2009 all children with a diagnosis of NEC were identified in the National Patient Register, the Swedish Medical Birth Register, and the National Cause of Death Register. NEC incidence, early mortality, and seasonality were analyzed with descriptive statistics, Poisson regression, and auto regression. less thanbrgreater than less thanbrgreater thanRESULTS: The overall incidence of NEC was 3.4 in 10 000 live births, higher in boys than in girls (incidence rate ratio 1.22, 95% confidence interval 1.06-1.40, P = .005), with a peak in November and a trough in May, and increased with an average of similar to 5% a year during the study period. In most subgroups, except the most immature, an initial decrease was followed by a steady increase. Seven-day mortality decreased strongly in all subgroups over the entire study period (annual incidence rate ratio 0.96, 95% confidence interval 0.95-0.96, P andlt; .001). This was especially marked in the most premature and low birth weight infants. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: After an initial decrease, the incidence of NEC has increased in Sweden during the last decades. An association with the concurrent dramatically improved early survival seems likely.

Place, publisher, year, edition, pages
American Academy of Pediatrics, 2013
Keyword
necrotizing enterocolitis, premature infants, perinatal mortality, perinatal care, epidemiology, trends, seasonal variation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-98148 (URN)10.1542/peds.2012-3847 (DOI)000322957300017 ()
Note

Funding Agencies|County Council of Ostergotland||Futurum||Academy of Health Care||Jonkoping County Council, Jonkoping, Sweden||Medical Research Council of Southeast Sweden||

Available from: 2013-09-30 Created: 2013-09-30 Last updated: 2018-03-27
2. Population-based study showed that necrotising enterocolitis occurred in space-time clusters with a decreasing secular trend in Sweden
Open this publication in new window or tab >>Population-based study showed that necrotising enterocolitis occurred in space-time clusters with a decreasing secular trend in Sweden
Show others...
2017 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 7, p. 1097-1102Article in journal (Refereed) Published
Abstract [en]

Aim: This study investigated space-time clustering of neonatal necrotising enterocolitis over three decades. Methods: Space-time clustering analyses objects that are grouped by a specific place and time. The Knox test and Kulldorffs scan statistic were used to analyse space-time clusters in 808 children diagnosed with necrotising enterocolitis in a national cohort of 2 389 681 children born between 1987 and 2009 in Sweden. The municipality the mother lived in and the delivery hospital defined closeness in space and the time between when the cases were born - seven, 14 and 21 days - defined closeness in time. Results: The Knox test showed no indication of space-time clustering at the residential level, but clear indications at the hospital level in all the time windows: seven days (p = 0.026), 14 days (p = 0.010) and 21 days (p = 0.004). Significant clustering at the hospital level was found during 1987-1997, but not during 1998-2009. Kulldorffs scan statistic found seven significant clusters at the hospital level. Conclusion: Space-time clustering was found at the hospital but not residential level, suggesting a contagious environmental effect after delivery, but not in the prenatal period. The decrease in clustering over time may reflect improved routines to minimise the risk of contagion between patients receiving neonatal care.

Place, publisher, year, edition, pages
WILEY, 2017
Keyword
Cluster analysis; Necrotising enterocolitis; Neonatal care; Precipitating contagion; Preterm infant
National Category
Pediatrics
Identifiers
urn:nbn:se:liu:diva-139608 (URN)10.1111/apa.13851 (DOI)000405216700022 ()28349558 (PubMedID)
Note

Funding Agencies|Swedish government; county councils

Available from: 2017-08-16 Created: 2017-08-16 Last updated: 2018-03-27
3. Maternal, fetal and perinatal factors associated with necrotizing enterocolitis in Sweden: A national case-control study
Open this publication in new window or tab >>Maternal, fetal and perinatal factors associated with necrotizing enterocolitis in Sweden: A national case-control study
2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, PLoS ONE, ISSN 1932-6203, Vol. 13, no 3, article id e0194352Article in journal (Refereed) Published
Abstract [en]

Objective

To analyze associations of maternal, fetal, gestational, and perinatal factors with necrotizing enterocolitis in a matched case-control study based on routinely collected, nationwide register data.

Study design

All infants born in 1987 through 2009 with a diagnosis of necrotizing enterocolitis in any of the Swedish national health care registers were identified. For each case up to 6 controls, matched for birth year and gestational age, were selected. The resulting study population consisted of 720 cases and 3,567 controls. Information on socioeconomic data about the mother, maternal morbidity, pregnancy related diagnoses, perinatal diagnoses of the infant, and procedures in the perinatal period, was obtained for all cases and controls and analyzed with univariable and multivariable logistic regressions for the whole study population as well as for subgroups according to gestational age.

Results

In the study population as a whole, we found independent positive associations with necrotizing enterocolitis for isoimmunization, fetal distress, cesarean section, neonatal bacterial infection including sepsis, erythrocyte transfusion, persistent ductus arteriosus, cardiac malformation, gastrointestinal malformation, and chromosomal abnormality. Negative associations were found for maternal weight, preeclampsia, maternal urinary infection, premature rupture of the membranes, and birthweight. Different patterns of associations were seen in the subgroups of different gestational age.

Conclusion

With some interesting exceptions, especially in negative associations, the results of this large, population based study, are in keeping with earlier studies. Although restrained by the limitations of register data, the findings mirror conceivable pathophysiological processes and underline that NEC is a multifactorial disease.

Place, publisher, year, edition, pages
San Francisco, United States: Public Library of Science, 2018
National Category
Pediatrics
Identifiers
urn:nbn:se:liu:diva-146093 (URN)10.1371/journal.pone.0194352 (DOI)000428168400016 ()29570713 (PubMedID)2-s2.0-85044427061 (Scopus ID)
Note

Funding agencies: Region Ostergotland, Sweden [LiO-107641]; Medical Research Council of Southeast Sweden [FORSS-77481]; Futurum - the Academy of Health Care, Jonkoping County Council, Jonkoping, Sweden; Region Ostergotland [LIO-130291, LIO-204581, LIO-280451, LIO-361481, L

Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-05-14Bibliographically approved
4. The role of imaging in the management of necrotising enterocolitis: a multispecialist survey and a review of the literature
Open this publication in new window or tab >>The role of imaging in the management of necrotising enterocolitis: a multispecialist survey and a review of the literature
2018 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, p. 1-11Article in journal (Refereed) Epub ahead of print
Abstract [en]

Objectives

To investigate current practices and perceptions of imaging in necrotising enterocolitis (NEC) according to involved specialists, put them in the context of current literature, and identify needs for further investigation.

Methods

Two hundred two neonatologists, paediatric surgeons, and radiologists answered a web-based questionnaire about imaging in NEC at their hospitals. The results were descriptively analysed, using proportion estimates with 95% confidence intervals.

Results

There was over 90% agreement on the value of imaging for confirmation of the diagnosis, surveillance, and guidance in decisions on surgery as well as on abdominal radiography as the first-choice modality and the most important radiographic signs. More variation was observed regarding some indications for surgery and the use of some ultrasonographic signs. Fifty-eight per cent stated that ultrasound was used for NEC at their hospital. Examination frequency, often once daily or more but with considerable variations, and projections used in AR were usually decided individually rather than according to fixed schedules. Predicting the need of surgery was regarded more important than formal staging.

Conclusion

Despite great agreement on the purposes of imaging in NEC and the most important radiographic signs of the disease, there was considerable diversity in routines, especially regarding examination frequency and the use of ultrasound. Apart from continuing validation of ultrasound, important objectives for future studies include definition of the supplementary roles of both imaging modalities in relation to other diagnostic parameters and evaluation of various imaging routines in relation to timing of surgery, complications, and mortality rate.

Place, publisher, year, edition, pages
Springer, 2018
Keyword
Enterocolitis, necrotising, Abdominal radiography, Ultrasonography, Surveys and questionnaires, Professional practice
National Category
Pediatrics
Identifiers
urn:nbn:se:liu:diva-146094 (URN)10.1007/s00330-018-5362-x (DOI)
Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-03-27

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