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Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and foetal pro-inflammatory cytokines in term infants.

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Peer-reviewed

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Authors

Gaccioli, Francesca  ORCID logo  https://orcid.org/0000-0001-7178-8921
Jessop, Flora 
Wong, Hilary S 

Abstract

Streptococcus agalactiae (Group B Streptococcus; GBS) is a common cause of sepsis in neonates. Previous work detected GBS DNA in the placenta in ~5% of women before the onset of labour, but the clinical significance of this finding is unknown. Here we re-analysed this dataset as a case control study of neonatal unit (NNU) admission. Of 436 infants born at term (≥37 weeks of gestation), 7/30 with placental GBS and 34/406 without placental GBS were admitted to the NNU (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.3-7.8). We then performed a validation study using non-overlapping subjects from the same cohort. This included a further 239 cases of term NNU admission and 686 term controls: 16/36 with placental GBS and 223/889 without GBS were admitted to the NNU (OR 2.4, 95% CI 1.2-4.6). Of the 36 infants with placental GBS, 10 were admitted to the NNU with evidence of probable but culture-negative sepsis (OR 4.8, 95% CI 2.2-10.3), 2 were admitted with proven GBS sepsis (OR 66.6, 95% CI 7.3-963.7), 6 were admitted and had chorioamnionitis (inflammation of the foetal membranes) (OR 5.3, 95% CI 2.0-13.4), and 5 were admitted and had funisitis (inflammation of the umbilical cord) (OR 6.7, 95% CI 12.5-17.7). Foetal cytokine storm (two or more pro-inflammatory cytokines >10 times median control levels in umbilical cord blood) was present in 36% of infants with placental GBS DNA and 4% of cases where the placenta was negative (OR 14.2, 95% CI 3.6-60.8). Overall, ~1 in 200 term births had GBS detected in the placenta, which was associated with infant NNU admission and morbidity.

Description

Acknowledgements: The work was funded by the Medical Research Council (United Kingdom; MR/K021133/1) and supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (Women’s Health theme). K.S. is funded by the Cambridge Wellcome Trust PhD Programme for Health Professionals. We thank L. Bibby, S. Ranawaka, K. Holmes, J. Gill, R. Millar, L. Sánchez Busó, J. Warner and K. Vickers for technical assistance during the study. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.


Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272


Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440

Keywords

Infant, Newborn, Humans, Pregnancy, Infant, Female, Placenta, Streptococcus agalactiae, Case-Control Studies, Streptococcal Infections, Inflammation, Sepsis

Journal Title

Nat Microbiol

Conference Name

Journal ISSN

2058-5276
2058-5276

Volume Title

8

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/K021133/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
The work was funded by the Medical Research Council (United Kingdom; MR/K021133/1) and supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (Women’s Health theme). KS is funded by the Cambridge Wellcome Trust PhD Programme for Health Professionals.