Association of specific microbiota taxa in the amniotic fluid at birth with severe acute and longer-term outcomes of very preterm infants: a prospective observational study | BMC Medicine

  • Gilbert J, Blaser MJ, Caporaso JG, Jansson J, Lynch SV, Knight R. Current understanding of the human microbiome. Nat Med. 2018;24:392–400.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016;375:2369–79.

    CAS 
    PubMed 

    Google Scholar 

  • de Vos WM, Tilg H, Van Hul M, Cani PD. Gut microbiome and health: mechanistic insights. Gut. 2022;71:1020–32.

    PubMed 

    Google Scholar 

  • Sanna S, van Zuydam NR, Mahajan A, Kurilshikov A, Vich Vila A, Võsa U, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat Genet. 2019;51:600–5.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dabke K, Hendrick G, Devkota S. The gut microbiome and metabolic syndrome. J Clin Invest. 2019;129:4050–7.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20:145–55.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Stiemsma LT, Michels KB. The role of the microbiome in the developmental origins of health and disease. Pediatrics. 2018;141: e20172437.

    PubMed 

    Google Scholar 

  • Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17:219–32.

    CAS 
    PubMed 

    Google Scholar 

  • Pattaroni C, Watzenboeck ML, Schneidegger S, Kieser S, Wong NC, Bernasconi E, et al. Early-life formation of the microbial and immunological environment of the human airways. Cell Host Microbe. 2018;24:857-865.e4.

    CAS 
    PubMed 

    Google Scholar 

  • Wu BG, Sulaiman I, Tsay J-CJ, Perez L, Franca B, Li Y, et al. Episodic aspiration with oral commensals induces a MyD88-dependent, pulmonary T-helper cell type 17 response that mitigates susceptibility to Streptococcus pneumoniae. Am J Respir Crit Care Med. 2021;203:1099–111.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cyr-Depauw C, Hurskainen M, Vadivel A, Mižíková I, Lesage F, Thébaud B. Characterization of the innate immune response in a novel murine model mimicking bronchopulmonary dysplasia. Pediatr Res. 2021;89:803–13.

    CAS 
    PubMed 

    Google Scholar 

  • Wallace B, Peisl A, Seedorf G, Nowlin T, Kim C, Bosco J, et al. Anti–sFlt-1 therapy preserves lung alveolar and vascular growth in antenatal models of bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2018;197:776–87.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dong Y, Rivetti S, Lingampally A, Tacke S, Kojonazarov B, Bellusci S, et al. Insights into the black box of intra-amniotic infection and its impact on the premature lung: from clinical and preclinical perspectives. Int J Mol Sci. 2022;23:9792.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • DeMauro SB. Neurodevelopmental outcomes of infants with bronchopulmonary dysplasia. Pediatr Pulmonol. 2021;56:3509–17.

    PubMed 

    Google Scholar 

  • Wang Y, Liu S, Lu M, Huang T, Huang L. Neurodevelopmental outcomes of preterm with necrotizing enterocolitis: a systematic review and meta-analysis. Eur J Pediatr. 2024;183:3147–58.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Stoll BJ, Hansen NI, Adams-Chapman I, Fanaroff AA, Hintz SR, Vohr B, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004;292:2357–65.

    CAS 
    PubMed 

    Google Scholar 

  • Diggikar S, Gurumoorthy P, Trif P, Mudura D, Nagesh NK, Galis R, et al. Retinopathy of prematurity and neurodevelopmental outcomes in preterm infants: a systematic review and meta-analysis. Front Pediatr. 2023;11:1055813.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Horbar JD, Greenberg LT, Buzas JS, Ehret DEY, Soll RF, Edwards EM. Trends in mortality and morbidities for infants born 24 to 28 weeks in the US: 1997–2021. Pediatrics. 2024;153: e2023064153.

    PubMed 

    Google Scholar 

  • Hong HK, Lee HJ, Ko JH, Park JH, Park JY, Choi CW, et al. Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity. J Neuroinflammation. 2014;11:87.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Young KC, Del Moral T, Claure N, Vanbuskirk S, Bancalari E. The association between early tracheal colonization and bronchopulmonary dysplasia. J Perinatol. 2005;25:403–7.

    PubMed 

    Google Scholar 

  • Lauer T, Behnke J, Oehmke F, Baecker J, Gentil K, Chakraborty T, et al. Bacterial colonization within the first six weeks of life and pulmonary outcome in preterm infants <1000 g. J Clin Med. 2020;9:2240.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Pammi M, Lal CV, Wagner BD, Mourani PM, Lohmann P, Luna RA, et al. Airway microbiome and development of bronchopulmonary dysplasia in preterm infants: a systematic review. J Pediatr. 2019;204:126-133.e2.

    PubMed 

    Google Scholar 

  • Lal CV, Kandasamy J, Dolma K, Ramani M, Kumar R, Wilson L, et al. Early airway microbial metagenomic and metabolomic signatures are associated with development of severe bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2018;315:L810–5.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Staude B, Gschwendtner S, Frodermann T, Oehmke F, Kohl T, Kublik S, et al. Microbial signatures in amniotic fluid at preterm birth and association with bronchopulmonary dysplasia. Respir Res. 2023;24:248.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Härtel C, Herting E, Humberg A, Hanke K, Mehler K, Keller T, et al. Association of administration of surfactant using less invasive methods with outcomes in extremely preterm infants less than 27 weeks of gestation. JAMA Netw Open. 2022;5: e2225810.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Dargaville PA, Kamlin COF, Orsini F, Wang X, De Paoli AG, Kanmaz Kutman HG, et al. Effect of minimally invasive surfactant therapy vs sham treatment on death or bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome. JAMA. 2021;326:1–10.

    PubMed Central 

    Google Scholar 

  • Schulman J, Stricof R, Stevens TP, Horgan M, Gase K, Holzman IR, et al. Statewide NICU central-line-associated bloodstream infection rates decline after bundles and checklists. Pediatrics. 2011;127:436–44.

    PubMed 

    Google Scholar 

  • Colaizy TT, Poindexter BB, McDonald SA, Bell EF, Carlo WA, Carlson SJ, et al. Neurodevelopmental outcomes of extremely preterm infants fed donor milk or preterm infant formula: a randomized clinical trial. JAMA. 2024;331:582–91.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Behnke J, Estreich V, Oehmke F, Zimmer K-P, Windhorst A, Ehrhardt H. Compatibility of rapid enteral feeding advances and noninvasive ventilation in preterm infants—an observational study. Pediatr Pulmonol. 2022;57:1117–26.

    PubMed 

    Google Scholar 

  • Voigt M, Schneider KTM, Jährig K. Analyse des Geburtengutes des Jahrgangs 1992 der Bundesrepublik Deutschland [Analysis of a 1992 birth sample in Germany. 1: New percentile values of the body weight of newborn infants]. Geburtshilfe Frauenheilkd. 1996;56:550–8.

    CAS 
    PubMed 

    Google Scholar 

  • Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723–9.

    CAS 
    PubMed 

    Google Scholar 

  • Wilkinson DJ, Andersen CC, Smith K, Holberton J. Pharyngeal pressure with high-flow nasal cannulae in premature infants. J Perinatol. 2008;28:42–7.

    CAS 
    PubMed 

    Google Scholar 

  • Walsh M, Engle W, Laptook A, Kazzi SNJ, Buchter S, Rasmussen M, et al. Oxygen delivery through nasal cannulae to preterm infants: can practice be improved? Pediatrics. 2005;116:857–61.

    PubMed 

    Google Scholar 

  • Deeg KH, Staudt F. von Rohden L [Classification of intracranial hemorrhage in premature infants]. Ultraschall Med. 1999;20:165–70.

    CAS 
    PubMed 

    Google Scholar 

  • Leistner R, Piening B, Gastmeier P, Geffers C, Schwab F. Nosocomial infections in very low birthweight infants in Germany: current data from the National Surveillance System NEO-KISS. Klin Padiatr. 2013;225:75–80.

    CAS 
    PubMed 

    Google Scholar 

  • Franz AR, Engel C, Bassler D, Rüdiger M, Thome UH, Maier RF, et al. Effects of liberal vs restrictive transfusion thresholds on survival and neurocognitive outcomes in extremely low-birth-weight infants: the ETTNO randomized clinical trial. JAMA. 2020;324:560–70.

    PubMed 

    Google Scholar 

  • Cheong JLY, Olsen JE, Lee KJ, Spittle AJ, Opie GF, Clark M, et al. Temporal trends in neurodevelopmental outcomes to 2 years after extremely preterm birth. JAMA Pediatr. 2021;175:1035–42.

    PubMed 

    Google Scholar 

  • Lueders T, Manefield M, Friedrich MW. Enhanced sensitivity of DNA- and rRNA-based stable isotope probing by fractionation and quantitative analysis of isopycnic centrifugation gradients. Environ Microbiol. 2004;6:73–8.

    CAS 
    PubMed 

    Google Scholar 

  • Nossa CW, Oberdorf WE, Yang L, Aas JA, Paster BJ, DeSantis TZ, et al. Design of 16S rRNA gene primers for 454 pyrosequencing of the human foregut microbiome. World J Gastroenterol. 2010;16:4135–44.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–6.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13:581–3.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rosenblad AJJ. Faraway: Extending the linear model with R: generalized linear, mixed effects and nonparametric regression models. Comput Stat. 2009;24:369–70.

    Google Scholar 

  • Gallacher D, Mitchell E, Alber D, Wach R, Klein N, Marchesi JR, et al. Dissimilarity of the gut–lung axis and dysbiosis of the lower airways in ventilated preterm infants. Eur Respir J. 2020;55:1901909.

  • Takahashi Y, Takahashi T, Usuda H, Carter S, Fee EL, Furfaro L, et al. Pharmacological blockade of the interleukin-1 receptor suppressed Escherichia coli lipopolysaccharide-induced neuroinflammation in preterm fetal sheep. Am J Obstet Gynecol MFM. 2023;5: 101124.

    CAS 
    PubMed 

    Google Scholar 

  • Tremblay S, Miloudi K, Chaychi S, Favret S, Binet F, Polosa A, et al. Systemic inflammation perturbs developmental retinal angiogenesis and neuroretinal function. Invest Ophthalmol Vis Sci. 2013;54:8125–39.

    CAS 
    PubMed 

    Google Scholar 

  • Sentenac M, Benhammou V, Aden U, Ancel P-Y, Bakker LA, Bakoy H, et al. Maternal education and cognitive development in 15 European very-preterm birth cohorts from the RECAP Preterm platform. Int J Epidemiol. 2022;50:1824–39.

    PubMed 

    Google Scholar 

  • Seppänen A-V, Draper ES, Petrou S, Barros H, Andronis L, Kim SW, et al. Follow-up after very preterm birth in Europe. Arch Dis Child Fetal Neonatal Ed. 2022;107:113–4.

    PubMed 

    Google Scholar 

  • Ehrhardt H, Aubert AM, Ådén U, Draper ES, Gudmundsdottir A, Varendi H, et al. Apgar score and neurodevelopmental outcomes at age 5 years in infants born extremely preterm. JAMA Netw Open. 2023;6: e2332413.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Cnattingius S, Johansson S, Razaz N. Apgar score and risk of neonatal death among preterm infants. N Engl J Med. 2020;383:49–57.

    PubMed 

    Google Scholar 

  • Shah PS, Norman M, Rusconi F, Kusuda S, Reichman B, Battin M, et al. Five-minute Apgar score and outcomes in neonates of 24–28 weeks’ gestation. Arch Dis Child Fetal Neonatal Ed. 2022;107:437–46.

    PubMed 

    Google Scholar 

  • Salmon F, Kayem G, Maisonneuve E, Foix-L’Hélias L, Benhammou V, Kaminski M, et al. Clinical chorioamnionitis and neurodevelopment at 5 years of age in children born preterm: the EPIPAGE-2 cohort study. J Pediatr. 2024;267.

  • Glaser K, Jensen EA, Wright CJ. Prevention of inflammatory disorders in the preterm neonate: an update with a special focus on bronchopulmonary dysplasia. Neonatology. 2024;121:636–45.

    PubMed 

    Google Scholar 

  • Mukhopadhyay S, Puopolo KM, Hansen NI, Lorch SA, DeMauro SB, Greenberg RG, et al. Impact of early-onset sepsis and antibiotic use on death or survival with neurodevelopmental impairment at 2 years of age among extremely preterm infants. J Pediatr. 2020;221:39-46.e5.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Behnke J, Dippel CM, Choi Y, Rekers L, Schmidt A, Lauer T, et al. Oxygen toxicity to the immature lung—part ii: the unmet clinical need for causal therapy. Int J Mol Sci. 2021;22:10694.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pruski P, Correia GDS, Lewis HV, Capuccini K, Inglese P, Chan D, et al. Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth. Nat Commun. 2021;12:5967.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Polglase GR, Dalton RGB, Nitsos I, Knox CL, Pillow JJ, Jobe AH, et al. Pulmonary vascular and alveolar development in preterm lambs chronically colonized with Ureaplasma parvum. Am J Physiol Lung Cell Mol Physiol. 2010;299:L232-241.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kallapur SG, Kramer BW, Knox CL, Berry CA, Collins JJP, Kemp MW, et al. Chronic fetal exposure to Ureaplasma parvum suppresses innate immune responses in sheep. J Immunol. 2011;187:2688–95.

    CAS 
    PubMed 

    Google Scholar 

  • Staude B, Misselwitz B, Louwen F, Rochwalsky U, Oehmke F, Köhler S, et al. Characteristics and rates of preterm births during the COVID-19 pandemic in Germany. JAMA Netw Open. 2024;7: e2432438.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Hammond JD, Kielt MJ, Conroy S, Lingappan K, Austin ED, Eldredge LC, et al. Exploring the association of male sex with adverse outcomes in severe bronchopulmonary dysplasia: a retrospective, multicenter cohort study. Chest. 2024;165:610–20.

    PubMed 

    Google Scholar 

  • Blaser MJ, Devkota S, McCoy KD, Relman DA, Yassour M, Young VB. Lessons learned from the prenatal microbiome controversy. Microbiome. 2021;9:8.

    PubMed 
    PubMed Central 

    Google Scholar 

  • de Goffau MC, Lager S, Sovio U, Gaccioli F, Cook E, Peacock SJ, et al. Human placenta has no microbiome but can contain potential pathogens. Nature. 2019;572:329–34.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Yamamoto T, Nomiyama M, Oshima Y, Ono T, Kozuma Y, Nakura Y, et al. Prenatal exposure to intra-amniotic infection with Ureaplasma species increases the prevalence of bronchopulmonary dysplasia. J Matern Fetal Neonatal Med. 2024;37:2320670.

    PubMed 

    Google Scholar 

  • Kusanovic JP, Jung E, Romero R, Mittal Green P, Nhan-Chang C-L, Vaisbuch E, et al. Characterization of amniotic fluid sludge in preterm and term gestations. J Matern Fetal Neonatal Med. 2022;35:9770–9.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hosang L, Canals RC, van der Flier FJ, Hollensteiner J, Daniel R, Flügel A, et al. The lung microbiome regulates brain autoimmunity. Nature. 2022;603:138–44.

    CAS 
    PubMed 

    Google Scholar 

  • Argaw-Denboba A, Schmidt TSB, Di Giacomo M, Ranjan B, Devendran S, Mastrorilli E, et al. Paternal microbiome perturbations impact offspring fitness. Nature. 2024;629:652–9.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Staude B, Oehmke F, Lauer T, Behnke J, Göpel W, Schloter M, et al. The microbiome and preterm birth: a change in paradigm with profound implications for pathophysiologic concepts and novel therapeutic strategies. Biomed Res Int. 2018;2018:7218187.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Romero R, Miranda J, Chaemsaithong P, Chaiworapongsa T, Kusanovic JP, Dong Z, et al. Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2015;28:1394–409.

    CAS 
    PubMed 

    Google Scholar 

  • Xiang Q, Yan X, Shi X, Huang Y, Li L, Zhong J, et al. Prolonged premature rupture of membranes with increased risk of infection is associated with gut accumulation of Pseudomonas from the environment. Comput Struct Biotechnol J. 2024;23:2851–60.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dos Anjos Borges LG, Pastuschek J, Heimann Y, Dawczynski K, PEONS study group, Schleußner E, et al. Vaginal and neonatal microbiota in pregnant women with preterm premature rupture of membranes and consecutive early onset neonatal sepsis. BMC Med. 2023;21:92.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu Y, Ma J, Li X, Zhao H, Ai Q, Zhang L, et al. No microorganism was detected in amniotic fluid of healthy pregnancies from the second trimester to the delivery. Microbiome. 2025;13:20.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Croxen MA, Finlay BB. Molecular mechanisms of Escherichia coli pathogenicity. Nat Rev Microbiol. 2010;8:26–38.

    CAS 
    PubMed 

    Google Scholar 

  • Wang Y, Florez ID, Morgan RL, Foroutan F, Chang Y, Crandon HN, et al. Probiotics, prebiotics, lactoferrin, and combination products for prevention of mortality and morbidity in preterm infants: a systematic review and network meta-analysis. JAMA Pediatr. 2023;177:1158–67.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Yu CW, Popovic MM, Dhoot AS, Arjmand P, Muni RH, Tehrani NN, et al. Demographic risk factors of retinopathy of prematurity: a systematic review of population-based studies. Neonatology. 2022;119:151–63.

    PubMed 

    Google Scholar 

  • Been JV, Rours IG, Kornelisse RF, Jonkers F, de Krijger RR, Zimmermann LJ. Chorioamnionitis alters the response to surfactant in preterm infants. J Pediatr. 2010;156:10-15.e1.

    CAS 
    PubMed 

    Google Scholar 

  • Levesque BM, Kalish LA, Winston AB, Parad RB, Hernandez-Diaz S, Phillips M, et al. Low urine vascular endothelial growth factor levels are associated with mechanical ventilation, bronchopulmonary dysplasia and retinopathy of prematurity. Neonatology. 2013;104:56–64.

    CAS 
    PubMed 

    Google Scholar 

  • Wang L-W, Lin Y-C, Wang S-T, Huang C-C. Identifying risk factors shared by bronchopulmonary dysplasia, severe retinopathy, and cystic periventricular leukomalacia in very preterm infants for targeted intervention. Neonatology. 2018;114:17–24.

    PubMed 

    Google Scholar 

  • Hellström A, Ley D, Hansen-Pupp I, Hallberg B, Ramenghi LA, Löfqvist C, et al. Role of insulinlike growth factor 1 in fetal development and in the early postnatal life of premature infants. Am J Perinatol. 2016;33:1067–71.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Continue Reading