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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 (\u226537\u2009weeks 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\u20137.8). 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\u20134.6). 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\u201310.3), 2 were admitted with proven GBS sepsis (OR 66.6, 95% CI 7.3\u2013963.7), 6 were admitted and had chorioamnionitis (inflammation of the foetal membranes) (OR 5.3, 95% CI 2.0\u201313.4), and 5 were admitted and had funisitis (inflammation of the umbilical cord) (OR 6.7, 95% CI 12.5\u201317.7). Foetal cytokine storm (two or more pro-inflammatory cytokines &gt;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\u201360.8). Overall, ~1 in 200 term births had GBS detected in the placenta, which was associated with infant NNU admission and morbidity.<\/jats:p>","DOI":"10.1038\/s41564-023-01528-2","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T17:02:32Z","timestamp":1701277352000},"page":"2338-2348","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and foetal pro-inflammatory cytokines in term infants"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7178-8921","authenticated-orcid":false,"given":"Francesca","family":"Gaccioli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1255-2641","authenticated-orcid":false,"given":"Katie","family":"Stephens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0799-1105","authenticated-orcid":false,"given":"Ulla","family":"Sovio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Jessop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary S.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3556-065X","authenticated-orcid":false,"given":"Susanne","family":"Lager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6142-4443","authenticated-orcid":false,"given":"Emma","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus C.","family":"de Goffau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty","family":"Le Doare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1718-2782","authenticated-orcid":false,"given":"Sharon J.","family":"Peacock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-5958","authenticated-orcid":false,"given":"Julian","family":"Parkhill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2936-4890","authenticated-orcid":false,"given":"D. Stephen","family":"Charnock-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2124-0997","authenticated-orcid":false,"given":"Gordon C. S.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"1528_CR1","doi-asserted-by":"publisher","unstructured":"Prevention of group B streptococcal early-onset disease in newborns: ACOG committee opinion, number 797. Obstet. Gynecol. https:\/\/doi.org\/10.1097\/AOG.0000000000003668 (2020).","DOI":"10.1097\/AOG.0000000000003668"},{"key":"1528_CR2","doi-asserted-by":"publisher","first-page":"S100","DOI":"10.1093\/cid\/cix658","volume":"65","author":"NJ Russell","year":"2017","unstructured":"Russell, N. J. et al. Maternal colonization with group B Streptococcus and serotype distribution worldwide: systematic review and meta-analyses. Clin. Infect. Dis. 65, S100\u2013S111 (2017).","journal-title":"Clin. Infect. Dis."},{"key":"1528_CR3","doi-asserted-by":"publisher","first-page":"S152","DOI":"10.1093\/cid\/cix655","volume":"65","author":"NJ Russell","year":"2017","unstructured":"Russell, N. J. et al. Risk of early-onset neonatal group B streptococcal disease with maternal colonization worldwide: systematic review and meta-analyses. Clin. Infect. Dis. 65, S152\u2013S159 (2017).","journal-title":"Clin. Infect. Dis."},{"key":"1528_CR4","doi-asserted-by":"publisher","first-page":"e807","DOI":"10.1016\/S2214-109X(22)00093-6","volume":"10","author":"BP Goncalves","year":"2022","unstructured":"Goncalves, B. P. et al. Group B Streptococcus infection during pregnancy and infancy: estimates of regional and global burden. Lancet Glob. Health 10, e807\u2013e819 (2022).","journal-title":"Lancet Glob. 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Y. et al. Sampling and definitions of placental lesions: Amsterdam placental workshop group consensus statement. Arch. Pathol. Lab Med 140, 698\u2013713 (2016).","journal-title":"Arch. Pathol. Lab Med"},{"key":"1528_CR8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3389\/fped.2018.00027","volume":"6","author":"KA Patras","year":"2018","unstructured":"Patras, K. A. & Nizet, V. Group B streptococcal maternal colonization and neonatal disease: molecular mechanisms and preventative approaches. Front. Pediatr. 6, 27 (2018).","journal-title":"Front. Pediatr."},{"key":"1528_CR9","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/S1473-3099(18)30555-3","volume":"19","author":"CP O\u2019Sullivan","year":"2019","unstructured":"O\u2019Sullivan, C. P. et al. Group B streptococcal disease in UK and Irish infants younger than 90 days, 2014\u201315: a prospective surveillance study. Lancet Infect. Dis. 19, 83\u201390 (2019).","journal-title":"Lancet Infect. 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Safety and immunogenicity of a novel hexavalent group B streptococcus conjugate vaccine in healthy, non-pregnant adults: a phase 1\/2, randomised, placebo-controlled, observer-blinded, dose-escalation trial. Lancet Infect. Dis. 21, 263\u2013274 (2021).","journal-title":"Lancet Infect. Dis."},{"key":"1528_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-021-01184-w","volume":"10","author":"I Moreno","year":"2022","unstructured":"Moreno, I. et al. Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Microbiome 10, 1 (2022).","journal-title":"Microbiome"},{"key":"1528_CR17","unstructured":"Clinical guidance [CG62]. Antenatal care for uncomplicated pregnancies. National Institute for Health and Care https:\/\/www.nice.org.uk\/guidance\/ng201 (2016)."},{"key":"1528_CR18","doi-asserted-by":"publisher","first-page":"732756","DOI":"10.3389\/fimmu.2021.732756","volume":"12","author":"A Roberts","year":"2021","unstructured":"Roberts, A. et al. A recent update on advanced molecular diagnostic techniques for COVID-19 pandemic: an overview. Front. Immunol. 12, 732756 (2021).","journal-title":"Front. Immunol."},{"key":"1528_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2393-8-51","volume":"8","author":"D Pasupathy","year":"2008","unstructured":"Pasupathy, D. et al. Study protocol. A prospective cohort study of unselected primiparous women: the pregnancy outcome prediction study. BMC Pregnancy Childbirth 8, 51 (2008).","journal-title":"BMC Pregnancy Childbirth"},{"key":"1528_CR20","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1016\/j.placenta.2016.10.011","volume":"59","author":"F Gaccioli","year":"2017","unstructured":"Gaccioli, F., Lager, S., Sovio, U., Charnock-Jones, D. S. & Smith, G. C. S. The pregnancy outcome prediction (POP) study: investigating the relationship between serial prenatal ultrasonography, biomarkers, placental phenotype and adverse pregnancy outcomes. Placenta 59, S17\u2013S25 (2017).","journal-title":"Placenta"},{"key":"1528_CR21","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1002\/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E","volume":"17","author":"RG Newcombe","year":"1998","unstructured":"Newcombe, R. G. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat. Med. 17, 857\u2013872 (1998).","journal-title":"Stat. 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Res."}],"container-title":["Nature Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41564-023-01528-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41564-023-01528-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41564-023-01528-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T18:07:14Z","timestamp":1701281234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41564-023-01528-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,29]]},"references-count":22,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1528"],"URL":"https:\/\/doi.org\/10.1038\/s41564-023-01528-2","relation":{},"ISSN":["2058-5276"],"issn-type":[{"value":"2058-5276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,29]]},"assertion":[{"value":"23 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"G.C.S.S. and D.S.C.-J. receive research funding from Pfizer Bacterial Vaccines for studies on the relationship between placental GBS DNA and maternal circulating levels of GBS antibodies. Cambridge Enterprise (United Kingdom) has filed a patent relating to the primers and probe used in the nested PCR\u2013qPCR assay described in this paper with F.G., M.C.d.G., D.S.C.-J. and G.C.S.S. as the named inventors. The competing interests outside the area of the submitted work are as follows: J.P. reports grants from Pfizer and personal fees from Next Gen Diagnostics LLC; S.J.P. reports personal fees from Specific and personal fees from Next Gen Diagnostics; G.C.S.S. and D.S.C.-J. report grants from GlaxoSmithKline Research and Development Limited, grants and non-financial support from Roche Diagnostics Ltd and non-financial support from Illumina Inc; G.C.S.S. reports personal fees from GlaxoSmithKline Research and Development Limited; K.L.D. is an adviser for Pfizer, Minervax and GSK for GBS vaccines; and K.S., U.S., F.J., H.S.W., S.L. and E.C. declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}