1932

Abstract

Prenatal screening using sequencing of circulating cell-free DNA has transformed obstetric care over the past decade and significantly reduced the number of invasive diagnostic procedures like amniocentesis for genetic disorders. Nonetheless, emergency care remains the only option for complications like preeclampsia and preterm birth, two of the most prevalent obstetrical syndromes. Advances in noninvasive prenatal testing expand the scope of precision medicine in obstetric care. In this review, we discuss advances, challenges, and possibilities toward the goal of providing proactive, personalized prenatal care. The highlighted advances focus mainly on cell-free nucleic acids; however, we also review research that uses signals from metabolomics, proteomics, intact cells, and the microbiome. We discuss ethical challenges in providing care. Finally, we look to future possibilities, including redefining disease taxonomy and moving from biomarker correlation to biological causation.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biodatasci-020722-094144
2023-08-10
2024-04-21
Loading full text...

Full text loading...

/deliver/fulltext/biodatasci/6/1/annurev-biodatasci-020722-094144.html?itemId=/content/journals/10.1146/annurev-biodatasci-020722-094144&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Chetty S, Garabedian MJ, Norton ME. 2013. Uptake of noninvasive prenatal testing (NIPT) in women following positive aneuploidy screening. Prenat. Diagn. 33:6542–46
    [Google Scholar]
  2. 2.
    Larion S, Warsof SL, Romary L, Mlynarczyk M, Peleg D, Abuhamad AZ. 2014. Uptake of noninvasive prenatal testing at a large academic referral center. Am. J. Obstet. Gynecol. 211:6651.e1–651.e7
    [Google Scholar]
  3. 3.
    Chan YM, Leung WC, Chan WP, Leung TY, Cheng YKY, Sahota DS. 2015. Women's uptake of non-invasive DNA testing following a high-risk screening test for trisomy 21 within a publicly funded healthcare system: findings from a retrospective review. Prenat. Diagn. 35:4342–47
    [Google Scholar]
  4. 4.
    Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C et al. 2014. DNA sequencing versus standard prenatal aneuploidy screening. N. Engl. J. Med. 370:9799–808
    [Google Scholar]
  5. 5.
    Petersen EE, Davis NL, Goodman D, Cox S, Mayes N et al. 2019. Vital signs: pregnancy-related deaths, United States, 2011–2015, and strategies for prevention, 13 states, 2013–2017. Morb. Mortal. Wkly. Rep. 68:18423–29
    [Google Scholar]
  6. 6.
    Liu L, Johnson HL, Cousens S, Perin J, Scott S et al. 2012. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 379:98322151–61
    [Google Scholar]
  7. 7.
    Inst. Med 2007. Preterm Birth: Causes, Consequences, and Prevention Washington, DC: Natl. Acad. Press
  8. 8.
    Lisonkova S, Joseph KS. 2013. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am. J. Obstet. Gynecol. 209:6544.e1–544.e12
    [Google Scholar]
  9. 9.
    Bianchi DW. 2021. Function follows form: gene expression and prenatal screening. Trends Mol. Med. 27:8725–27
    [Google Scholar]
  10. 10.
    Gray KJ, Hemberg M, Karumanchi SA. 2022. Cell-free RNA transcriptome and prediction of adverse pregnancy outcomes. Clin. Chem. 68:111358–60
    [Google Scholar]
  11. 11.
    Peterson LS, Stelzer IA, Tsai AS, Ghaemi MS, Han X et al. 2020. Multiomic immune clockworks of pregnancy. Semin. Immunopathol. 42:4397–412
    [Google Scholar]
  12. 12.
    Stevenson DK, Wong RJ, Aghaeepour N, Maric I, Angst MS et al. 2021. Towards personalized medicine in maternal and child health: integrating biologic and social determinants. Pediatr. Res. 89:2252–58
    [Google Scholar]
  13. 13.
    Moufarrej MN, Wong RJ, Shaw GM, Stevenson DK, Quake SR. 2020. Investigating pregnancy and its complications using circulating cell-free RNA in women's blood during gestation. Front. Pediatr. 8:605219
    [Google Scholar]
  14. 14.
    Tsao DS, Silas S, Landry BP, Itzep NP, Nguyen AB et al. 2019. A novel high-throughput molecular counting method with single base-pair resolution enables accurate single-gene NIPT. Sci. Rep. 9:14382
    [Google Scholar]
  15. 15.
    Zhang J, Li J, Saucier JB, Feng Y, Jiang Y et al. 2019. Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA. Nat. Med. 25:3439–47
    [Google Scholar]
  16. 16.
    Taglauer ES, Wilkins-Haug L, Bianchi DW. 2014. Review: cell-free fetal DNA in the maternal circulation as an indication of placental health and disease. Placenta 35:Suppl.S64–68
    [Google Scholar]
  17. 17.
    Maron JL, Johnson KL, Slonim D, Lai C-Q, Ramoni M et al. 2007. Gene expression analysis in pregnant women and their infants identifies unique fetal biomarkers that circulate in maternal blood. J. Clin. Investig. 117:103007–19
    [Google Scholar]
  18. 18.
    Koh W, Pan W, Gawad C, Fan HC, Kerchner GA et al. 2014. Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. PNAS 111:207361–66
    [Google Scholar]
  19. 19.
    Pan W, Ngo TTM, Camunas-Soler J, Song C-X, Kowarsky M et al. 2017. Simultaneously monitoring immune response and microbial infections during pregnancy through plasma cfRNA sequencing. Clin. Chem. 63:111695–704
    [Google Scholar]
  20. 20.
    Ngo TTM, Moufarrej MN, Rasmussen M-LH, Camunas-Soler J, Pan W et al. 2018. Noninvasive blood tests for fetal development predict gestational age and preterm delivery. Science 360:63931133–36
    [Google Scholar]
  21. 21.
    Munchel S, Rohrback S, Randise-Hinchliff C, Kinnings S, Deshmukh S et al. 2020. Circulating transcripts in maternal blood reflect a molecular signature of early-onset preeclampsia. Sci. Transl. Med. 12:550eaaz0131
    [Google Scholar]
  22. 22.
    Rasmussen M, Reddy M, Nolan R, Camunas-Soler J, Khodursky A et al. 2022. RNA profiles reveal signatures of future health and disease in pregnancy. Nature 601:7893422–27
    [Google Scholar]
  23. 23.
    Moufarrej MN, Vorperian SK, Wong RJ, Campos AA, Quaintance CC et al. 2022. Early prediction of preeclampsia in pregnancy with cell-free RNA. Nature 602:7898689–94
    [Google Scholar]
  24. 24.
    Stelzer IA, Ghaemi MS, Han X, Ando K, Hédou JJ et al. 2021. Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset. Sci. Transl. Med. 13:592eabd9898
    [Google Scholar]
  25. 25.
    Jain CV, Kadam L, van Dijk M, Kohan-Ghadr H-R, Kilburn BA et al. 2016. Fetal genome profiling at 5 weeks of gestation after noninvasive isolation of trophoblast cells from the endocervical canal. Sci. Transl. Med. 8:363363re4
    [Google Scholar]
  26. 26.
    Kølvraa S, Singh R, Normand EA, Qdaisat S, van den Veyver IB et al. 2016. Genome-wide copy number analysis on DNA from fetal cells isolated from the blood of pregnant women. Prenat. Diagn. 36:121127–34
    [Google Scholar]
  27. 27.
    Breman AM, Chow JC, U'Ren L, Normand EA, Qdaisat S et al. 2016. Evidence for feasibility of fetal trophoblastic cell-based noninvasive prenatal testing. Prenat. Diagn. 36:111009–19
    [Google Scholar]
  28. 28.
    Gao Y, Ruan L, Cao L, Lu G, Hong Q et al. 2022. Noninvasive isolation of transcervical trophoblast cells for fetal identification. J. Obstet. Gynaecol. Res. 48:71613–20
    [Google Scholar]
  29. 29.
    Phipps EA, Thadhani R, Benzing T, Karumanchi SA. 2019. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat. Rev. Nephrol. 15:5275–89
    [Google Scholar]
  30. 30.
    Burton GJ, Redman CW, Roberts JM, Moffett A. 2019. Pre-eclampsia: pathophysiology and clinical implications. BMJ 366:l2381
    [Google Scholar]
  31. 31.
    Pertile MD, Halks-Miller M, Flowers N, Barbacioru C, Kinnings SL et al. 2017. Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggest increased risk of feto-placental disease. Sci. Transl. Med. 9:405eaan1240
    [Google Scholar]
  32. 32.
    Steele MW, Breg WR. 1966. Chromosome analysis of human amniotic-fluid cells. Lancet 1:7434383–85
    [Google Scholar]
  33. 33.
    Bianchi DW, Chiu RWK. 2018. Sequencing of circulating cell-free DNA during pregnancy. N. Engl. J. Med. 379:5464–73
    [Google Scholar]
  34. 34.
    Gadsbøll K, Petersen OB, Gatinois V, Strange H, Jacobsson B et al. 2020. Current use of noninvasive prenatal testing in Europe, Australia and the USA: a graphical presentation. Acta Obstet. Gynecol. Scand. 99:6722–30
    [Google Scholar]
  35. 35.
    Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR. 2008. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. PNAS 105:4216266–71
    [Google Scholar]
  36. 36.
    Chiu RWK, Chan KCA, Gao Y, Lau VYM, Zheng W et al. 2008. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. PNAS 105:5120458–63
    [Google Scholar]
  37. 37.
    Cordier A-G, Fuchs F, Tassin M, Saada J, Letourneau A et al. 2016. Teaching invasive prenatal procedures: effectiveness of two simple simulators in training. Prenat. Diagn. 36:10905–10
    [Google Scholar]
  38. 38.
    Yaron Y. 2016. The implications of non-invasive prenatal testing failures: a review of an under-discussed phenomenon. Prenat. Diagn. 36:5391–96
    [Google Scholar]
  39. 39.
    Artieri CG, Haverty C, Evans EA, Goldberg JD, Haque IS et al. 2017. Noninvasive prenatal screening at low fetal fraction: comparing whole-genome sequencing and single-nucleotide polymorphism methods. Prenat. Diagn. 37:5482–90
    [Google Scholar]
  40. 40.
    Hui L, Bianchi DW. 2020. Fetal fraction and noninvasive prenatal testing: what clinicians need to know. Prenat. Diagn. 40:2155–63
    [Google Scholar]
  41. 41.
    Straver R, Sistermans EA, Reinders MJT. 2014. Introducing WISECONDOR for noninvasive prenatal diagnostics. Expert Rev. Mol. Diagn. 14:5513–15
    [Google Scholar]
  42. 42.
    Raman L, Dheedene A, De Smet M, Van Dorpe J, Menten B. 2019. WisecondorX: improved copy number detection for routine shallow whole-genome sequencing. Nucleic Acids Res 47:41605–14
    [Google Scholar]
  43. 43.
    Fan HC, Quake SR. 2010. Sensitivity of noninvasive prenatal detection of fetal aneuploidy from maternal plasma using shotgun sequencing is limited only by counting statistics. PLOS ONE 5:5e10439
    [Google Scholar]
  44. 44.
    Rose NC, Kaimal AJ, Dugoff L, Norton ME, Am. Coll. Obstet. Gynecol. Comm. Pract. Bull 2020. Screening for fetal chromosomal abnormalities: ACOG Practice Bulletin summary, number 226. Obstet. Gynecol. 136:4859–67
    [Google Scholar]
  45. 45.
    Lutgendorf MA, Stoll KA. 2015. Why 99% may not be as good as you think it is: limitations of screening for rare diseases. J. Matern. Fetal. Neonatal. Med. 29:71187–89
    [Google Scholar]
  46. 46.
    Gil MM, Galeva S, Jani J, Konstantinidou L, Akolekar R et al. 2019. Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of the fetal medicine foundation results and meta-analysis. Ultrasound Obstet. Gynecol. 53:6734–42
    [Google Scholar]
  47. 47.
    Gil MM, Accurti V, Santacruz B, Plana MN, Nicolaides KH. 2017. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet. Gynecol. 50:3302–14
    [Google Scholar]
  48. 48.
    Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC et al. 2015. Cell-free DNA analysis for noninvasive examination of trisomy. N. Engl. J. Med. 372:171589–97
    [Google Scholar]
  49. 49.
    Fajnzylber E, Hotz VJ, Sanders SG. 2010. An economic model of amniocentesis choice. Adv. Life Course Res. 15:111–26
    [Google Scholar]
  50. 50.
    Martin K, Iyengar S, Kalyan A, Lan C, Simon AL et al. 2018. Clinical experience with a single-nucleotide polymorphism-based non-invasive prenatal test for five clinically significant microdeletions. Clin. Genet. 93:2293–300
    [Google Scholar]
  51. 51.
    Dar P, Jacobsson B, Clifton R, Egbert M, Malone F et al. 2022. Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome. Am. J. Obstet. Gynecol. 227:179.e1–79.e11
    [Google Scholar]
  52. 52.
    Lefkowitz RB, Tynan JA, Liu T, Wu Y, Mazloom AR et al. 2016. Clinical validation of a noninvasive prenatal test for genomewide detection of fetal copy number variants. Am. J. Obstet. Gynecol. 215:2227.e1–227.e16
    [Google Scholar]
  53. 53.
    Jacky L, Yurk D, Alvarado J, Leatham B, Schwartz J et al. 2021. Virtual-partition digital PCR for high-precision chromosomal counting applications. Anal. Chem. 93:5117020–29
    [Google Scholar]
  54. 54.
    Chandler NJ, Ahlfors H, Drury S, Mellis R, Hill M et al. 2020. Noninvasive prenatal diagnosis for cystic fibrosis: implementation, uptake, outcome, and implications. Clin. Chem. 66:1207–16
    [Google Scholar]
  55. 55.
    Camunas-Soler J, Lee H, Hudgins L, Hintz SR, Blumenfeld YJ et al. 2018. Noninvasive prenatal diagnosis of single-gene disorders by use of droplet digital PCR. Clin. Chem. 64:2336–45
    [Google Scholar]
  56. 56.
    Fan HC, Gu W, Wang J, Blumenfeld YJ, El-Sayed YY, Quake SR. 2012. Non-invasive prenatal measurement of the fetal genome. Nature 487:7407320–24
    [Google Scholar]
  57. 57.
    Kitzman JO, Snyder MW, Ventura M, Lewis AP, Qiu R et al. 2012. Noninvasive whole-genome sequencing of a human fetus. Sci. Transl. Med. 4:137137ra76
    [Google Scholar]
  58. 58.
    Verhoef TI, Hill M, Drury S, Mason S, Jenkins L et al. 2016. Non-invasive prenatal diagnosis (NIPD) for single gene disorders: cost analysis of NIPD and invasive testing pathways. Prenat. Diagn. 36:7636–42
    [Google Scholar]
  59. 59.
    Jenkins LA, Deans ZC, Lewis C, Allen S. 2018. Delivering an accredited non-invasive prenatal diagnosis service for monogenic disorders and recommendations for best practice. Prenat. Diagn. 38:144–51
    [Google Scholar]
  60. 60.
    Wapner RJ, Norton ME. 2021. An introduction: prenatal screening, diagnosis, and treatment of single gene disorders. Clin. Obstet. Gynecol. 64:4852–60
    [Google Scholar]
  61. 61.
    Chitty LS, Griffin DR, Meaney C, Barrett A, Khalil A et al. 2011. New aids for the non-invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell-free fetal DNA in maternal plasma. Ultrasound Obstet. Gynecol. 37:3283–89
    [Google Scholar]
  62. 62.
    Chitty LS, Khalil A, Barrett AN, Pajkrt E, Griffin DR, Cole TJ. 2013. Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA. Prenat. Diagn. 33:5416–23
    [Google Scholar]
  63. 63.
    Chitty LS, Mason S, Barrett AN, McKay F, Lench N et al. 2015. Non-invasive prenatal diagnosis of achondroplasia and thanatophoric dysplasia: next-generation sequencing allows for a safer, more accurate, and comprehensive approach. Prenat. Diagn. 35:7656–62
    [Google Scholar]
  64. 64.
    Hanson B, Scotchman E, Chitty LS, Chandler NJ. 2022. Non-invasive prenatal diagnosis (NIPD): how analysis of cell-free DNA in maternal plasma has changed prenatal diagnosis for monogenic disorders. Clin. Sci. 136:221615–29
    [Google Scholar]
  65. 65.
    Gu W, Koh W, Blumenfeld YJ, El-Sayed YY, Hudgins L et al. 2014. Noninvasive prenatal diagnosis in a fetus at risk for methylmalonic acidemia. Genet. Med. 16:7564–67
    [Google Scholar]
  66. 66.
    Parks M, Court S, Bowns B, Cleary S, Clokie S et al. 2017. Non-invasive prenatal diagnosis of spinal muscular atrophy by relative haplotype dosage. Eur. J. Hum. Genet. 25:4416–22
    [Google Scholar]
  67. 67.
    Lo YMD, Chan KCA, Sun H, Chen EZ, Jiang P et al. 2010. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci. Transl. Med. 2:6161ra91
    [Google Scholar]
  68. 68.
    Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR. 2010. Analysis of the size distributions of fetal and maternal cell-free DNA by paired-end sequencing. Clin. Chem. 56:81279–86
    [Google Scholar]
  69. 69.
    Yu SCY, Jiang P, Peng W, Cheng SH, Cheung YTT et al. 2021. Single-molecule sequencing reveals a large population of long cell-free DNA molecules in maternal plasma. PNAS 118:50e2114937118
    [Google Scholar]
  70. 70.
    Zipursky A, Hull A, White FD, Israels LG. 1959. Fœtal erythrocytes in the maternal circulation. Lancet 273:7070451–52
    [Google Scholar]
  71. 71.
    Walknowska J, Conte FA, Grumbach MM. 1969. Practical and theoretical implications of fetal-maternal lymphocyte transfer. Lancet 1:76061119–22
    [Google Scholar]
  72. 72.
    Herzenberg LA, Bianchi DW, Schröder J, Cann HM, Iverson GM. 1979. Fetal cells in the blood of pregnant women: detection and enrichment by fluorescence-activated cell sorting. PNAS 76:31453–55
    [Google Scholar]
  73. 73.
    Bianchi DW, Simpson JL, Jackson LG, Elias S, Holzgreve W et al. 2002. Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. Prenat. Diagn. 22:7609–15
    [Google Scholar]
  74. 74.
    Huang L, Ma F, Chapman A, Lu S, Xie XS. 2015. Single-cell whole-genome amplification and sequencing: methodology and applications. Annu. Rev. Genom. Hum. Genet. 16:79–102
    [Google Scholar]
  75. 75.
    Fu Y, Zhang F, Zhang X, Yin J, Du M et al. 2019. High-throughput single-cell whole-genome amplification through centrifugal emulsification and EMDA. Commun. Biol. 2:147
    [Google Scholar]
  76. 76.
    Biezuner T, Raz O, Amir S, Milo L, Adar R et al. 2021. Comparison of seven single cell whole genome amplification commercial kits using targeted sequencing. Sci. Rep. 11:17171
    [Google Scholar]
  77. 77.
    Moser G, Drewlo S, Huppertz B, Armant DR. 2018. Trophoblast retrieval and isolation from the cervix: origins of cervical trophoblasts and their potential value for risk assessment of ongoing pregnancies. Hum. Reprod. Update 24:4484–96
    [Google Scholar]
  78. 78.
    Bailey-Hytholt CM, Sayeed S, Kraus M, Joseph R, Shukla A, Tripathi A. 2019. A rapid method for label-free enrichment of rare trophoblast cells from cervical samples. Sci. Rep. 9:12115
    [Google Scholar]
  79. 79.
    Huang C-E, Ma G-C, Jou H-J, Lin W-H, Lee D-J et al. 2017. Noninvasive prenatal diagnosis of fetal aneuploidy by circulating fetal nucleated red blood cells and extravillous trophoblasts using silicon-based nanostructured microfluidics. Mol. Cytogenet. 10:44
    [Google Scholar]
  80. 80.
    Vossaert L, Wang Q, Salman R, McCombs AK, Patel V et al. 2019. Validation studies for single circulating trophoblast genetic testing as a form of noninvasive prenatal diagnosis. Am. J. Hum. Genet. 105:61262–73
    [Google Scholar]
  81. 81.
    Scott F, Menezes M, Smet ME, Carey K, Hardy T et al. 2022. Influence of fibroids on cell-free DNA screening accuracy. Ultrasound Obstet. Gynecol. 59:1114–19
    [Google Scholar]
  82. 82.
    Bianchi DW. 2018. Cherchez la femme: Maternal incidental findings can explain discordant prenatal cell-free DNA sequencing results. Genet. Med. 20:9910–17
    [Google Scholar]
  83. 83.
    Turriff AE, Annunziata CM, Bianchi DW. 2022. Prenatal DNA sequencing for fetal aneuploidy also detects maternal cancer: importance of timely workup and management in pregnant women. J. Clin. Oncol. 40:222398–401
    [Google Scholar]
  84. 84.
    Bianchi DW, Chudova D, Sehnert AJ, Bhatt S, Murray K et al. 2015. Noninvasive prenatal testing and incidental detection of occult maternal malignancies. JAMA 314:2162–69
    [Google Scholar]
  85. 85.
    Dharajiya NG, Grosu DS, Farkas DH, McCullough RM, Almasri E et al. 2018. Incidental detection of maternal neoplasia in noninvasive prenatal testing. Clin. Chem. 64:2329–35
    [Google Scholar]
  86. 86.
    van der Meij KRM, Sistermans EA, Macville MVE, Stevens SJC, Bax CJ et al. 2019. TRIDENT-2: national implementation of genome-wide non-invasive prenatal testing as a first-tier screening test in the Netherlands. Am. J. Hum. Genet. 105:61091–101
    [Google Scholar]
  87. 87.
    Ji X, Li J, Huang Y, Sung P-L, Yuan Y et al. 2019. Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests. Genet. Med. 21:102293–302
    [Google Scholar]
  88. 88.
    Lenaerts L, Brison N, Maggen C, Vancoillie L, Che H et al. 2021. Comprehensive genome-wide analysis of routine non-invasive test data allows cancer prediction: a single-center retrospective analysis of over 85,000 pregnancies. eClinicalMedicine 35:100856
    [Google Scholar]
  89. 89.
    Heesterbeek CJ, Aukema SM, Galjaard R-JH, Boon EMJ, Srebniak MI et al. 2022. Noninvasive prenatal test results indicative of maternal malignancies: a nationwide genetic and clinical follow-up study. J. Clin. Oncol. 40:222426–35
    [Google Scholar]
  90. 90.
    Benn P, Plon SE, Bianchi DW. 2019. Current controversies in prenatal diagnosis 2: NIPT results suggesting maternal cancer should always be disclosed. Prenat. Diagn. 39:5339–43
    [Google Scholar]
  91. 91.
    Linthorst J, Welkers MRA, Sistermans EA. 2023. Clinically relevant DNA viruses in pregnancy. Prenat. Diagn. 43:4457–66
    [Google Scholar]
  92. 92.
    De Vlaminck I, Khush KK, Strehl C, Kohli B, Luikart H et al. 2013. Temporal response of the human virome to immunosuppression and antiviral therapy. Cell 155:51178–87
    [Google Scholar]
  93. 93.
    De Vlaminck I, Martin L, Kertesz M, Patel K, Kowarsky M et al. 2015. Noninvasive monitoring of infection and rejection after lung transplantation. PNAS 112:4313336–41
    [Google Scholar]
  94. 94.
    Kowarsky M, Camunas-Soler J, Kertesz M, De Vlaminck I, Koh W et al. 2017. Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA. PNAS 114:369623–28
    [Google Scholar]
  95. 95.
    Yu J, Diaz JD, Goldstein SC, Patel RD, Varela JC et al. 2021. Impact of next-generation sequencing cell-free pathogen DNA test on antimicrobial management in adults with hematological malignancies and transplant recipients with suspected infections. Transplant. Cell. Ther. 27:6500.e1–500.e6
    [Google Scholar]
  96. 96.
    Shishido AA, Noe M, Saharia K, Luethy P. 2022. Clinical impact of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay on treatment decisions: a single-center retrospective study. BMC Infect. Dis. 22:372
    [Google Scholar]
  97. 97.
    Linthorst J, Baksi MMM, Welkers MRA, Sistermans EA. 2023. The cell-free DNA virome of 108,349 Dutch pregnant women. Prenat. Diagn. 43:4448–56
    [Google Scholar]
  98. 98.
    Chesnais V, Ott A, Chaplais E, Gabillard S, Pallares D et al. 2018. Using massively parallel shotgun sequencing of maternal plasmatic cell-free DNA for cytomegalovirus DNA detection during pregnancy: a proof of concept study. Sci. Rep. 8:4321
    [Google Scholar]
  99. 99.
    Liu S, Huang S, Chen F, Zhao L, Yuan Y et al. 2018. Genomic analyses from non-invasive prenatal testing reveal genetic associations, patterns of viral infections, and Chinese population history. Cell 175:2347–59.e14
    [Google Scholar]
  100. 100.
    Tong X, Yu X, Du Y, Su F, Liu Y et al. 2022. Peripheral blood microbiome analysis via noninvasive prenatal testing reveals the complexity of circulating microbial cell-free DNA. Microbiol. Spectr. 10:3e0041422
    [Google Scholar]
  101. 101.
    Burnham P, Gomez-Lopez N, Heyang M, Cheng AP, Lenz JS et al. 2020. Separating the signal from the noise in metagenomic cell-free DNA sequencing. Microbiome 8:18
    [Google Scholar]
  102. 102.
    Gaccioli F, Lager S, de Goffau MC, Sovio U, Dopierala J et al. 2020. Fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes the mother to pre-eclampsia. Nat. Microbiol. 5:7901–8
    [Google Scholar]
  103. 103.
    Miura H, Kawamura Y, Ohye T, Hattori F, Kozawa K et al. 2021. Inherited chromosomally integrated human herpesvirus 6 is a risk factor for spontaneous abortion. J. Infect. Dis. 223:101717–23
    [Google Scholar]
  104. 104.
    UNFPA (U.N. Popul. Fund), WHO (World Health Organ.), UNICEF (U.N. Child. Fund), World Bank Group, U.N. Popul. Div 2019. Trends in Maternal Mortality 2000 to 2017: Estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division: Executive Summary Geneva: WHO
  105. 105.
    Duley L. 2009. The global impact of pre-eclampsia and eclampsia. Semin. Perinatol. 33:3130–37
    [Google Scholar]
  106. 106.
    Jeyabalan A. 2013. Epidemiology of preeclampsia: impact of obesity. Nutr. Rev. 71:Suppl. 1S18–25
    [Google Scholar]
  107. 107.
    Moffett A, Shreeve N. 2022. Local immune recognition of trophoblast in early human pregnancy: controversies and questions. Nat. Rev. Immunol. 23:222–35
    [Google Scholar]
  108. 108.
    Roberge S, Nicolaides K, Demers S, Hyett J, Chaillet N, Bujold E. 2017. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am. J. Obstet. Gynecol. 216:2110–20.e6
    [Google Scholar]
  109. 109.
    Marić I, Contrepois K, Moufarrej MN, Stelzer IA, Feyaerts D et al. 2022. Early prediction and longitudinal modeling of preeclampsia from multiomics. Patterns 3:12100655
    [Google Scholar]
  110. 110.
    Smith GCS. 2010. First-trimester determination of complications of late pregnancy. JAMA 303:6561–62
    [Google Scholar]
  111. 111.
    Chappell LC, Cluver CA, Kingdom J, Tong S. 2021. Pre-eclampsia. Lancet 398:10297341–54
    [Google Scholar]
  112. 112.
    Han X, Ghaemi MS, Ando K, Peterson LS, Ganio EA et al. 2019. Differential dynamics of the maternal immune system in healthy pregnancy and preeclampsia. Front. Immunol. 10:1305
    [Google Scholar]
  113. 113.
    Vorperian SK, Moufarrej MN Tabula Sapiens Consort. , Quake SR. 2022. Cell types of origin of the cell-free transcriptome. Nat. Biotechnol. 40:6855–61
    [Google Scholar]
  114. 114.
    Camunas-Soler J, Gee EPS, Reddy M, Mi JD, Thao M et al. 2022. Predictive RNA profiles for early and very early spontaneous preterm birth. Am. J. Obstet. Gynecol. 227:172.e1–72.e16
    [Google Scholar]
  115. 115.
    Aghaeepour N, Ganio EA, Mcilwain D, Tsai AS, Tingle M et al. 2017. An immune clock of human pregnancy. Sci. Immunol. 2:15aan2946
    [Google Scholar]
  116. 116.
    Gudnadottir U, Debelius JW, Du J, Hugerth LW, Danielsson H et al. 2022. The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis. Sci. Rep. 12:7926
    [Google Scholar]
  117. 117.
    Bayar E, Bennett PR, Chan D, Sykes L, MacIntyre DA. 2020. The pregnancy microbiome and preterm birth. Semin. Immunopathol. 42:4487–99
    [Google Scholar]
  118. 118.
    Fettweis JM, Serrano MG, Brooks JP, Edwards DJ, Girerd PH et al. 2019. The vaginal microbiome and preterm birth. Nat. Med. 25:61012–21
    [Google Scholar]
  119. 119.
    Wylie KM, Wylie TN, Cahill AG, Macones GA, Tuuli MG, Stout MJ. 2018. The vaginal eukaryotic DNA virome and preterm birth. Am. J. Obstet. Gynecol. 219:2189.e1–189.e12
    [Google Scholar]
  120. 120.
    Flaviani F, Hezelgrave NL, Kanno T, Prosdocimi EM, Chin-Smith E et al. 2021. Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort. JCI Insight 6:16e149257
    [Google Scholar]
  121. 121.
    Ghaemi MS, DiGiulio DB, Contrepois K, Callahan B, Ngo TTM et al. 2019. Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy. Bioinformatics 35:95–103
    [Google Scholar]
  122. 122.
    Larson MH, Pan W, Kim HJ, Mauntz RE, Stuart SM et al. 2021. A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection. Nat. Commun. 12:2357
    [Google Scholar]
  123. 123.
    Johnston M, Warton C, Pertile MD, Taylor-Sands M, Delatycki MB et al. 2022. Ethical issues associated with prenatal screening using non-invasive prenatal testing for sex chromosome aneuploidy. Prenat. Diagn. 43:2226–34
    [Google Scholar]
  124. 124.
    Ravitsky V, Roy M-C, Haidar H, Henneman L, Marshall J et al. 2021. The emergence and global spread of noninvasive prenatal testing. Annu. Rev. Genom. Hum. Genet. 22:309–38
    [Google Scholar]
  125. 125.
    Dondorp WJ, Page-Christiaens GCML, de Wert GMWR. 2016. Genomic futures of prenatal screening: ethical reflection. Clin. Genet. 89:5531–38
    [Google Scholar]
  126. 126.
    Minear MA, Alessi S, Allyse M, Michie M, Chandrasekharan S. 2015. Noninvasive prenatal genetic testing: current and emerging ethical, legal, and social issues. Annu. Rev. Genom. Hum. Genet. 16:369–98
    [Google Scholar]
  127. 127.
    Ibarra A, Zhuang J, Zhao Y, Salathia NS, Huang V et al. 2020. Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing. Nat. Commun. 11:400
    [Google Scholar]
  128. 128.
    Toden S, Zhuang J, Acosta AD, Karns AP, Salathia NS et al. 2020. Noninvasive characterization of Alzheimer's disease by circulating, cell-free messenger RNA next-generation sequencing. Sci. Adv. 6:50eabb1654
    [Google Scholar]
  129. 129.
    Chalasani N, Toden S, Sninsky JJ, Rava RP, Braun JV et al. 2021. Noninvasive stratification of nonalcoholic fatty liver disease by whole transcriptome cell-free mRNA characterization. Am. J. Physiol. Gastrointest. Liver Physiol. 320:4G439–49
    [Google Scholar]
  130. 130.
    Cristiano S, Leal A, Phallen J, Fiksel J, Adleff V et al. 2019. Genome-wide cell-free DNA fragmentation in patients with cancer. Nature 570:7761385–89
    [Google Scholar]
  131. 131.
    Liu Y. 2022. At the dawn: cell-free DNA fragmentomics and gene regulation. Br. J. Cancer 126:3379–90
    [Google Scholar]
  132. 132.
    Schlee M, Hartmann G. 2016. Discriminating self from non-self in nucleic acid sensing. Nat. Rev. Immunol. 16:9566–80
    [Google Scholar]
  133. 133.
    Rizzuto G, Brooks JF, Tuomivaara ST, McIntyre TI, Ma S et al. 2022. Establishment of fetomaternal tolerance through glycan-mediated B cell suppression. Nature 603:7901497–502
    [Google Scholar]
  134. 134.
    Erickson JJ, Archer-Hartmann S, Yarawsky AE, Miller JLC, Seveau S et al. 2022. Pregnancy enables antibody protection against intracellular infection. Nature 606:7915769–75
    [Google Scholar]
  135. 135.
    Flynn RA, Pedram K, Malaker SA, Batista PJ, Smith BAH et al. 2021. Small RNAs are modified with N-glycans and displayed on the surface of living cells. Cell 184:123109–24.e22
    [Google Scholar]
/content/journals/10.1146/annurev-biodatasci-020722-094144
Loading
/content/journals/10.1146/annurev-biodatasci-020722-094144
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error