International Journal of Oral Implantology & Clinical Research

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VOLUME 2 , ISSUE 2 ( May-August, 2011 ) > List of Articles

CLINICAL RESEARCH

Histologic and Clinical Evaluation of a Bioactive Calcium Phosphosilicate Bone Graft Material in Postextraction Alveolar Sockets

Aron Gonshor, Stephen A Saroff, Charles R Anderegg, Frederic PC Joachim, Jacques A Charon, Srinivas Katta

Citation Information : Gonshor A, Saroff SA, Anderegg CR, Joachim FP, Charon JA, Katta S. Histologic and Clinical Evaluation of a Bioactive Calcium Phosphosilicate Bone Graft Material in Postextraction Alveolar Sockets. Int J Oral Implantol Clin Res 2011; 2 (2):79-84.

DOI: 10.5005/jp-journals-10012-1040

License: CC BY-ND 4.0

Published Online: 01-04-2015

Copyright Statement:  Copyright © 2011; The Author(s).


Abstract

Background: Long-term success of dental implants has been demonstrated when placed simultaneously with or after a socket grafting procedure. Although optimal bone formation can be from 6 to 9 months or longer with grafting materials other than autogenous bone, there is the avoidance of potentially hazardous harvesting autogenous bone. Methods: This study evaluated bone formation following grafting of 22 postextraction alveolar sockets with a bioactive calcium phosphosilicate putty (CPS putty) graft material. Results: At 5 to 6 months postgrafting, there was bone regeneration showing both normal clinical attributes and radiographic trabecular appearance. Histomorphometric analysis revealed average vital bone content of 48.2 ± 6.8% to residual graft content of 2.4 ± 1.4% for the 22 sockets in the study, at an average healing period of 5.4 ± 1.5 months. Conclusions: The high percentage of vital bone content after a relatively short healing phase, suggests that CPS putty can be a reliable choice for osseous regeneration in cases of crest preservation and implant related surgeries.


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  1. Klinge B, Hultin M, Berglundh T. Peri-implantitis. Dental Clinics of North America 2005;49:661-76.
  2. Lekovic V, Kenney E, Weinlaender M, Han T, Klokkeveld P, Nedic M. A bone regeneration approach to alveolar ridge maintenance following tooth extraction: Report of 10 cases. J Perodontol 1997;68:563-70.
  3. Anderegg CR, Alexander DC, Freidman M. A bioactive glass particulate in the treatment of molar furcation invasions. Journal of periodontology 1999;70:384-87.
  4. Hench LL, West JK. Biological applications of bioactive glasses. Life Chem Rep 1996;13:187-241.
  5. Hench LL. Bioceramics: Material characteristics versus in vivo behavior 1988.
  6. Gross U, Strunz V. The interface of various glasses and glass ceramics with a bony implantation bed. Journal of Biomedical Materials Research 1985;19:251-71.
  7. Hench LL, Splinter RJ, Allen WC, Greenlee TK. Bonding mechanisms at the interface of ceramic prosthetic materials. Journal of Biomedical Materials Research 1971;5:117-41.
  8. Zhong JP, LaTorre GP, Hench LL. The kinetics of bioactive ceramics: (Part VII). Binding of collagen to hydroxyapatite and bioactive glass. In: Anderson OH, Yli-Urpo (Eds): Oxford: Butterworth-Heinemann 1994.
  9. Price N, Bendall S, Frondoza C, Jinnah R, DS H. Human osteoblast-like cells (MG63) proliferate on a bioactive glass surface. J Biomed Mater Res 1997;37:394-400.
  10. Wilson J, Low SB. Bioactive ceramics for periodontal treatment: Comparative studies in the Patus monkey. Journal of Applied Biomaterials 1992;3:123-29.
  11. Cancian DC, Hochuli-Vieira E, Marcantonio RA, Garcia JIR. Utilization of autogenous bone, bioactive glasses, and calcium phosphate cement in surgical mandibular bone defects in Cebus apella monkeys. The International Journal of Oral and Maxillofacial Implants 2004;19:73-79.
  12. Wilson J, Pigott GH, Schoen FJ, Hench LL. Toxicology and biocompatibility of bioglasses. Journal of Biomedical Materials Research 1981;15:805-17.
  13. Donath K, Breuner G. A method for the study of undecalcified bones and teeth with attached soft tissues. Journal of Oral Pathology and Medicine 1982;11:318-26.
  14. Rohrer MD, Schubert CC. The cutting-grinding technique for histologic preparation of undecalcified bone and bone-anchored implants: Improvements in instrumentation and procedures. Oral Surgery, Oral Medicine, Oral Pathology 1992;74:73-78.
  15. Watzek G, Ulm C, Haas R. Anatomic and physiologic fundamentals of sinus floor augmentation. In: Jensen O (Ed). The sinus bone graft. Chicago: Quintessance 1992:35-37.
  16. Hench LL, Polak JM, Xynos ID, Buttery LDK. Bioactive materials to control cell cycle. Materials Research Innovations 2000;3:313-23.
  17. Ogino M, Ohuchi F, Hench LL. Compositional dependence of the formation of calcium phosphate films on bioglass. Journal of Biomedical Materials Research 1980;14:55-64.
  18. Oonishi H, Hench LL, Wilson J, Sugihara F, Tsuji E, Matsuura M, et al. Quantitative comparison of bone growth behavior in granules of BioglassÆ, AW glass-ceramic, and hydroxyapatite. Journal of Biomedical Materials Research Part A 2000;51: 37-46.
  19. Hench LL, Polak JM. A genetic basis for design of biomaterials for in situ tissue regeneration. Key Engineering Materials 2008;377:151-66.
  20. Xynos ID, Edgar AJ, Buttery LDK, Hench LL, Polak JM. Geneexpression profiling of human osteoblasts following treatment with the ionic products of BioglassÆ 45S5 dissolution. Journal of Biomedical Materials Research Part A 2001;55:151-57.
  21. OrÈfice R, Hench L, Brennan A. Evaluation of the interactions between collagen and the surface of a bioactive glass during in vitro test. Journal of Biomedical Materials Research (Part A) 2009;90:114-20.
  22. Bombonato Prado KF, Bellesini LS, Junta CM, Marques MM, Passos GA, Rosa AL. Microarray based gene expression analysis of human osteoblasts in response to different biomaterials. Journal of Biomedical Materials Research (Part A) 2009;88: 401-08.
  23. Carinci F, Palmieri A, Martinelli M, Perrotti V, Piattelli A, Brunelli G, et al. Genetic portrait of osteoblast-like cells cultured on PerioGlas 2007.
  24. Waltimo T, Brunner TJ, Vollenweider M, Stark WJ, Zehnder M. Antimicrobial effect of nanometric bioactive glass 45S5. Journal of dental research 2007;86:754-57.
  25. Gubler M, Brunner TJ, Zehnder M, Waltimo T, Sener B, Stark WJ. Do bioactive glasses convey a disinfecting mechanism beyond a mere increase in pH? International Endodontic Journal 2008;41:670-78.
  26. Leatherman BD, Dornhoffer JL. Bioactive glass ceramic particles as an alternative for mastoid obliteration: Results in an animal model. Otology and Neurotology 2002;23:657-60.
  27. Froum SJ, Weinberg MA, Tarnow D. Comparison of bioactive glass synthetic bone graft particles and open debridement in the treatment of human periodontal defects: A clinical study. Journal of periodontology 1998;69:698-709.
  28. Mengel R, Soffner M, Flores-de-Jacoby L. Bioabsorbable membrane and bioactive glass in the treatment of intrabony defects in patients with generalized aggressive periodontitis: Results of a 12-month clinical and radiological study. Journal of Periodontology 2003;74:899-908.
  29. Galindo Moreno P, Avila G, Fern·ndez Barbero JE, Mesa F, O’Valle Ravassa F, Wang HL. Clinical and histologic comparison of two different composite grafts for sinus augmentation: A pilot clinical trial. Clinical Oral Implants Research 2008;19:755-59.
  30. Misch CE. Diagnostic cast, peri-implant proshodontics, treatment prosthesis, and surgical templates. In: Misch CE (Ed). Contemporary Implant Dentistry (2nd ed). St Louis: Mosby 1999;143-44.
  31. Abdel-Latif HH, Hobkirk JA, Kelleway JP. Functional mandibular deformation in edentulous subjects treated with dental implants. Int J Prosthodont 2000;13:513-19.
  32. Arenal AA, Lasheras FS, Fernández EM, González I. A jaw model for the study of the mandibular flexure taking into account the anisotropy of the bone. Mathematical and Computer Modelling 2009;50:695-704.
  33. Chen DC, Lai YL, Chi LY, Lee SY. Contributing factors of mandibular deformation during mouth opening. J Dent 2000;28:583-88.
  34. Jiang T, AI M. In vivo mandibular elastic deformation during clenching on pivots. J Oral Rehabil 2002;29:201-08.
  35. Paez CY, Barco T, Roushdy S, Andres C. Split-frame implant prosthesis designed to compensate for mandibular flexure: A clinical report. J Prosthet Dent 2003;89:341-43.
  36. Zarone F, Apicella A, Nicolais L, Aversa R, Sorrentino R. Mandibular flexure and stress build-up in mandibular full-arch fixed prostheses supported by osseointegrated implants. Clin Oral Impl Res 2003;14:103-14.
  37. Vollmer D, Meyer U, Joos U, Vegh A, Piffko J. Experimental and finite element study of a human mandible. J Craniomaxillofac Surg 2000;28:91-96.
  38. Shinkai RSA, Canabarro SA, Schmidt CS, Sartori EA. Reliability of a digital mandibular flexure measurement. J Appl Oral Sci 2004;12:358-62.
  39. Canabarro SA, Shinkai RSA. Medial mandibular flexure and maximum occlusal force in dentate adults. Int J Prosthodont 2000;19:177-82.
  40. Misch CE. The completely edentulous mandible: Treatment plan for fixed restoration. In: Misch CE (ed). Contemporary Implant Dentistry (3rd ed). St Louis: Mosby 2008;316-17.
  41. Abrahamsson I, Berglundh T. The mucosal barrier following the abutment dis/reconnection: An experimental study in dogs. J Clin Perioodntol 1997;24:568-72.
  42. Albreketsson T, Isidor F. Consensus report of session 4. In Lang NP, Karring T (Eds). Proceedings of 1st European Workshop of Periodontology London Quintessence Publishing 1994; 365-69.
  43. Becker W, Becker BE, Newman MG. Clinical and microbiologic findings that may contribute to dental implant failure. Int J Oral Maxillofac Implants 1990;5:31-38.
  44. Lindquist LW, Rockler B, Carlsson GE. Bone resorption around fixtures in edentulous patients treated with mandibular fixed tissue integrated prosthesis. J Prosthet Dent 1988;59:59-63.
  45. Levignac J. Losteolyse periimplantaire, periimplantose, periimplantite. Rev Fr Odontostomatol 1965;12:1251-60.
  46. Rams TE, Link CC. Microbiology of the failing dental implants in humans: Electron microscopic observations. J Oral Implantol 1983;11:93-100.
  47. Mombelli A, Van Oosten MAC, Lang NP. The microbiota associated with successful or failing osseointegrated titanium implants. Oral Microbiol Immunol 1987;2:145-51.
  48. Mombelli A. Prevention and therapy of peri-implantitis infections. In: Lang NP, Karring T, Lindhe J (Eds). Proceedings of 3rd European Workshop on Periodontology: Implant Dentistry. Berlin: Quintessence Publishing Co 1999:281-303.
  49. Lindhe J, Meyle J. Peri-implant diseases: Consensus report of the sixth European Workshop on Periodontolgy. J Clin Periodontol 2008;35(S-8):282-85.
  50. Tarnow D, Elian N, Fletcher P, et al. Vertical distance from the crest of bone to the height of the interproximal papilla between adjacent implants. J Periodontol 2003;74:1785-88.
  51. Ericsson J, Persson LG. Different types of implant-associated reactions in periodontal soft tissues. J Clin Periodont 1995; 22:255-61.
  52. Steinebrunner L, Wolfart S. In vitro evaluation of bacterial leakage along the implant of different implant abutment interface of different implant systems. Int J Oral Maxillofac Implants 2005;20:875-81.
  53. Engelke W, Decco OA. In vitro evaluation of horizontal implant micromovement in bone specimen with contact endoscopy. Implant Dent 2004;13:88-94.
  54. Hermann J, Buser D, Schenk RK, Schoolfield JD. Influence of the size of the microgap on crestal bone changes around titanium implants: A histometric evaluation of unloaded non-submerged implants in canine mandible. J Periodontol 2001;72:1372-83.
  55. Hermann JS, Buser D, Schenk RK, et al. Crestal bone changes around titanium implants: A histometric evaluation of unloaded non-submerged and submerged implants in the canine mandible. J Peridontol 2000;71:1412-24.
  56. Wohrle PS. Nobel perfect esthetic scalloped implant: Rationale for a new design. Clin Implant Dent Relat Res 2003;5:64-73.
  57. Nentwig GH. Ankylos implant system: Concept and clinical application. J Oral Implantol 2004;30:171-77.
  58. Gardener D. Maintaining crestal bone around dental implants: Literature review and clinical technique. Dentistry Today 2006.
  59. Tonetti MS, Sanz M. Consensus report of session B. In: Lang N, Karring T, Lindhe J. Proceedings of the 3rd European Workshop on Periodontology and Implant Dentistry. Berlin: Quintessence 1999:185-88.
  60. Huang MT, Ho CT, Wang ZY, Ferraro T, Lou YR, Stauber K, Ma W, Georgiadis C, Laskin JD, Conney AH. Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Res. 1994 Feb;54(3):701-708.
  61. Bernardes WA, Lucarini R, Tozatti MG, Souza MG, Silva ML, Filho AA, Martins CH, Crotti AE, Pauletti PM, Groppo M, et al. Antimicrobial activity of tosmarinus officinalis against oral pathogens: relevance of carnosic acid and carnosol. Chem Biodivers 2010 Jul;7(7):1835-1840.
  62. Parolia A, Thomas MS, Kundabala M, Mohan M. Propolis and its potential uses in oral health. Int J Med Sci 2010 Jul;2(7): 210-215.
  63. Oncag O, Cogulu D, Uzel A, Sorkun K. Efficacy of propolis as an intracanal medicament against Enerococcus faecalis. Gen Dent 2006 Sep-Oct:54(5):319-322.
  64. Martin MP, Pileggi R. A quantitative analysis of propolis: a promising new storage media following avulsion. Dent Traumatol 2004 Apr:20(2):85-89.
  65. Carbajal D, Casaco A, Arruzazabala L, Gonzalez R, Tolon Z. Pharmacological study of Cymbopogon citratus leaves. J Ethnopharmacol 1989 Feb;25(1):103-107.
  66. Sanches NR, Cortez DAG, Schiavini MS, Nakamura CV, Filho BPD. An evaluation of antibacterial activities of Psidium guajava. Braz Arch Biol Technol 2005 May;48(3):4229-4230.
  67. Sanda KA, Grema HA, Geidam YA, Bukar-Kolo YM. Pharmacological aspects of Psidium guajava: an update. Int J Pharmacol 2011 May;7:316-324.
  68. Menezes SM, Cordeiro LN, Viana GS. Punica grantum (pomegranate) extract is active against dental plaque. J Herb Pharmacother 2006;6(2):79-92.
  69. Vasconcelos LC, Sampaio FC, Sampaio MC, Pereira Mdo S, Higino JS, Peixoto MH. Minimum inhibitory concentration of adherence of punica granatum linn (pomegranate) gel against S. mutans, S. mitis and C albicans. Braz Dent J 2006;17(3): 223-227.
  70. Prasad D, Kunnaiah R. Punica granatum: a review on its potential role in treating periodontal disease. J Indian Soc Periodontol 2014 Jul;18(4):428-432.
  71. Sauvaire Y, Petit P, Baissac Y, Ribes G. Chemistry and pharmacology of fenugreek. In: Herbs, botanicals and teas. Mazza G, Oomah BD, editors. Lancaster, Pennsylvania: Technomic Pub. Co; 2000. p. 107-129.
  72. Acharya SN, Basu SK, Thomas JE. Methods for the improvement of plant medicinal properties with particular reference to fenugreek (Trigonella foenum-graecum L.). In: Acharya SN, Thomas JE, editors. Advances in medicinal plant research. Kerala, India: Research Signpost; 2007b p. 491-412.
  73. Al-Habori M, Raman A. Pharmacological properties in fenugreek. - In: Petropoulos GA, editor. The genus trigonella. 1st ed. London and New York: Taylor and Francis 2002. p. 163-182.
  74. Saini P, Al-Shibani N, Sun J, Zhang W, Song F, Gregson KS, Windsor LJ. Effects of calendula officinalis on human gingival fibroblasts. Homeopathy 2012 Apr;101(2):92-98.
  75. Khairnar MS, Pawar B, Marawar PPA. Evaluation of calendula officinalis as an anti-plaque and anti-gingivitis agent. J Indian Soc Periodontol 2013 Nov-Dec;17(6):741-747.
  76. Chakraborthy GS. Antimicrobial activity of leaf extract of calendula officinalis Linn. J Herb Med Toxicol 2008 Jun;2(2):65–66.
  77. Zilda CG, Claudia MR, Sandra RF. Antifungal activity of the essential oil from calendula officinalis L growing in Brazil. Braz J Microbiol 2008;39(1):61-63.
  78. Bussadori SK, Castro LC, Galvão AC. Papain gel: a new chemo-mechanical caries removal agent. J Clin Pediatr Dent 2005 Winter;30(2):115-119.
  79. Bertassoni LE, Marshall GW. Papain-gel degrades intact nonmineralized type I collagen fibrils. Scanning 2009 Nov- Dec;31(6):253-258.
  80. Moon SE, Kim HY, Cha JD. Synergistic effect between clove oil and its major compounds and antibiotics against oral bacteria. Arch Oral Biol 2011 Sep;56(9):907-916.
  81. Pinto E, Vale-Silva L, Cavaleiro C, Salgueiro L. Antifungal activity of the clove essential oil from Syzygium aromaticumon, candida, aspergillus and dermatophyte species. J Med Microbiol 2009 Nov;58(Pt 11):1454-1462.
  82. Olajide OA, Makinde JM, Awe SO. Evaluation of the pharmacological properties of nutmeg oil in rats and mice. Pharma Biol 2000;38(5):385-390.
  83. Thanoon SZ, Al-Refai AS, Kamal A. Antibacterial effect and healing potential of nutmeg oil for chemically induced oral ulcerations in rabbits. Zanco J Med Sci 2013;17(2): 393-399.
  84. Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril 2001;75:305-09.
  85. Sammour A, Bijan MM, Tan SL, Tulandi T. Prospective randomised trial comparing the effects of letrazole (LE) and clomiphene citrate (CC) on follicular development, endometrial thickness and pregnancy rate in patients undergoing superovulation prior to intrauterine insemination (IUI). Fertil Steril 2001;76(Suppl 1):S110.
  86. Mitwally MF, Casper RF. Single-dose administration of an aromatase inhibitor for ovarian stimulation. Fertil Steril 2005;83:229-31.
  87. Fisher SA, Reid RL, Van Vugt DA, Casper RF. A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women. Fertil Steril 2002;78:280-85.
  88. Fatemi HM, Kalibianakis E, Tournaye H, Camus M, Van Steirteghem AC, Devroey P. Clomiphene citrate vs letrozole for ovarian stimulation: A pilot study. Reprod Biomed Online 2003;7:543-46.
  89. Hu Y, Cortvrindt R, Smitz J. Effects of aromatase inhibition on in vitro follicle and oocyte development analyzed by early preantral mouse follicle culture. Mol Reprod Dev 2002;61: 549-59.
  90. Shetty G, Krishnamurthy H, Krishnamurthy HN, Bhatnagar S, Moudgal NR. Effect of estrogen deprivation on the reproductive physiology of male and female primates. J Steroid Biochem Mol Biol 1997;61:157-66.
  91. Mitwally MF, Casper RF. Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility. Hum Reprod 2003;18:1588-97.
  92. Mitwally MF, Casper RF. Aromatase inhibition improves ovarian response to follicle-stimulating hormone in poor responders. Fertil Steril 2002;77:776-80.
  93. Goswami SK, Das T, Chattopadhyay R, Sawhney V, Kumar J, Chaudhury K, Chakravarty BN, Kabir SN. A randomized single blind controlled trial of letrozole as a low-cost IVF protocol in women with poor ovarian response: A preliminary report. Hum Reprod 2004;19:2031-35.
  94. Newkirk KM, Chandler HL, Parent AE, et al. Ultraviolet radiation-induced corneal degeneration in 129 mice. Toxicol Pathol 2007;35:819-26.
  95. Pettenati MJ, Sweatt AJ, Lantz P, et al. The human cornea has a high incidence of acquired chromosome abnormalities. Hum Genet 1997;101:26-29.
  96. Snibson GR. Collagen cross-linking: A new treatment paradigm in corneal disease—a review. Clin Experiment Ophthalmol 2010;38:141-53.
  97. Spoerl E, Raiskup-Wolf F, Kuhlisch E, Pillunat LE. Cigarette smoking is negatively associated with keratoconus. J Refract Surg 2008;24:S737-40.
  98. Rabinowitz YS, Nesburn AB, McDonnell PJ. Videokeratography of the fellow eye in unilateral keratoconus. Ophthalmology 1993;100:181-86.
  99. Goodrich DW, Lee WH. The molecular genetics of retinoblastoma. Cancer Surv 1990;9:529-54.
  100. Moodaley LC, Woodward EG, Liu CS, Buckley RJ. Life expectancy in keratoconus. Br J Ophthalmol 1992;76:590-91.
  101. Honein MA, Dawson AL, Petersen EE, Jones AM, Lee EH, Yazdy MM, Ahmad N, Macdonald J, Evert N, Bingham A, et al. Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy. JAMA 2017 Jan 3;317(1):59-68.
  102. Chervenak FA, Jeanty P, Cantraine F, Chitkara U, Venus I, Berkowitz RL, Hobbins JC. The diagnosis of fetal microcephaly. Am J Obstet Gynecol 1984 Jul 1;149(5):512-517.
  103. Papageorghiou AT, Thilaganathan B, Bilardo CM, Ngu A, Malinger G, Herrera M, Salomon LJ, Riley LE, Copel JA. ISUOG Interim Guidance on ultrasound for Zika virus infection in pregnancy: information for healthcare professionals. Ultrasound Obstet Gynecol 2016 Apr;47(4):530-532.
  104. Chibueze EC, Parsons AJ, Lopes KD, Yo T, Swa T, Nagata C, Horita N, Morisaki N, Balogun OO, Dagvadorj A, et al. Diagnostic accuracy of ultrasound scanning for prenatal microcephaly in the context of Zika virus infection: a systematic review and meta-analysis. Sci Rep 2017 May 23;7(1):2310.
  105. Cordeiro MT. Zika virus: laboratory diagnosis. In: Zika in focus. Springer International Publishing; 2017. pp. 59-62.
  106. Mlakar J, Korva M, Tul N, Popović M, Poljšak-Prijatelj M, Mraz J, Kolenc M, Resman Rus K, Vesnaver Vipotnik T, Fabjan Vodušek V, et al. Zika virus associated with microcephaly. N Engl J Med 2016 Mar 10;374(10):951-958.
  107. Zare Mehrjardi M, Keshavarz E, Poretti A, Hazin AN. Neuroimaging findings of Zika virus infection: a review article. Jpn J Radiol 2016 Dec;34(12):765-770.
  108. Oliveira Melo AS, Malinger G, Ximenes R, Szejnfeld PO, Alves Sampaio S, Bispo de Filippis AM. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol 2016 Jan;47(1):6-7.
  109. Araujo AQ, Silva MT, Araujo AP. Zika virus-associated neurological disorders: a review. Brain 2016;139(8):2122-2130.
  110. Brasil P, Pereira JP Jr, Moreira ME, Ribeiro Nogueira RM, Damasceno L, Wakimoto M, Rabello RS, Valderramos SG, Halai UA, Salles TS, et al. Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med 2016 Dec 15;375(24):2321-2334.
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