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Maternal, fetal and perinatal factors associated with necrotizing enterocolitis in Sweden: A national case-control study
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
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
Department of Pediatrics, Institution of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery, Ryhov County Hospital, Jönköping, Sweden .
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. Vol. 13, no 3, article id e0194352
National Category
Pediatrics
Identifiers
URN: urn:nbn:se:liu:diva-146093DOI: 10.1371/journal.pone.0194352ISI: 000428168400016PubMedID: 29570713Scopus ID: 2-s2.0-85044427061OAI: oai:DiVA.org:liu-146093DiVA, id: diva2:1193589
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
In thesis
1. Necrotising Enterocolitis: epidemiology and imaging
Open this publication in new window or tab >>Necrotising Enterocolitis: epidemiology and imaging
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:nbn:se:liu:diva-142375 (URN)10.3384/diss.diva-142375 (DOI)9789176854556 (ISBN)
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: 2019-10-28Bibliographically approved

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Ahle, MargaretaDrott, PederAndersson, Roland E.

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