Am J Perinatol 2011; 28(10): 793-802
DOI: 10.1055/s-0031-1284229
© Thieme Medical Publishers

The Stillbirth Collaborative Research Network Neuropathologic Examination Protocol

Halit Pinar1 , Matthew A. Koch2 , Hal Hawkins3 , Josefine Heim-Hall4 , Bahig Shehata5 , Vanessa R. Thorsten6 , Steven Chin7 , Marian Willinger8 , Suzanne dela Monte9
  • 1Division of Perinatal Pathology, Women and Infants Hospital, Alpert School of Medicine, Brown University, Providence, Rhode Island
  • 2Department of Statistics and Epidemiology, RTI International, Research Triangle Park, North Carolina
  • 3Department of Pediatric Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas
  • 4University of Texas Health Science Center at San Antonio School of Medicine, San Antonio, Texas
  • 5Pathology Laboratory, Egleston Hospital, Atlanta, Georgia
  • 6Department of Statistics and Data Analysis, RTI International, Kansas City, Missouri
  • 7Huntsman Cancer Institute, Salt Lake City, Utah
  • 8National Institutes of Health, Pregnancy and Perinatology Branch, Bethesda, Maryland
  • 9Rhode Island Hospital, Providence, Rhode Island
Further Information

Publication History

Publication Date:
21 July 2011 (online)

ABSTRACT

We describe the neuropathologic procedure utilized in the Stillbirth Collaborative Research Network (SCRN), focusing on the examination of central nervous system (CNS) in stillbirth (SB). The SCRN was organized to perform a case-control study to determine the scope and causes of SB. Pathologists at all the participating centers agreed on and used the same standardized neuropathologic techniques. Standardized sections were taken and detailed data were collected. Fresh brain tissue was saved for investigative purposes. A total of 663 women with SB were enrolled into the case-control study: 620 delivered a single stillborn, 42 delivered twins, and 1 delivered triplets. Of the 560 (84.5%) who consented to postmortem examination, 465 (70.1%) also gave consent to the examination of the CNS. In the 440 stillborn infants in whom CNS examination was possible, 248 (56.4%) of the brains were intact, 72 were fragmented (16.4%), and 120 (27.3%) were liquefied. In summary, this is the largest prospective study dedicated to investigate the causes of SB and collect essential information and biological samples in the United States. A protocol for neuropathologic examination was instituted, and a brain tissue repository was created to provide samples and related data for future investigations.

REFERENCES

  • 1 Goldenberg R L, Kirby R, Culhane J F. Stillbirth: a review.  J Matern Fetal Neonatal Med. 2004;  16 79-94
  • 2 Fretts R C, Boyd M E, Usher R H, Usher H A. The changing pattern of fetal death, 1961–1988.  Obstet Gynecol. 1992;  79 35-39
  • 3 Fretts R C. Etiology and prevention of stillbirth.  Am J Obstet Gynecol. 2005;  193 1923-1935
  • 4 Committee on Genetics . ACOG Committee Opinion No. 383: Evaluation of stillbirths and neonatal deaths.  Obstet Gynecol. 2007;  110 (4) 963-966
  • 5 Silver R M, Varner M W, Reddy U et al.. Work-up of stillbirth: a review of the evidence.  Am J Obstet Gynecol. 2007;  196 433-444
  • 6 Grafe M R, Kinney H C. Neuropathology associated with stillbirth.  Semin Perinatol. 2002;  26 83-88
  • 7 Gilles F H, Dooling E, Fulchiero A. Sequence of myelination in the human fetus.  Trans Am Neurol Assoc. 1976A;  101 244-246
  • 8 Gilles F H. Myelination in the neonatal brain.  Hum Pathol. 1976B;  7 244-248
  • 9 Chi J G, Dooling E C, Gilles F H. Gyral development of the human brain.  Ann Neurol. 1977;  1 86-93
  • 10 Dooling E C, Chi J G, Gilles F H. Ependymal changes in the human fetal brain.  Ann Neurol. 1977;  1 535-541
  • 11 Brody B A, Kinney H C, Kloman A S, Gilles F H. Sequence of central nervous system myelination in human infancy. I. An autopsy study of myelination.  J Neuropathol Exp Neurol. 1987;  46 283-301
  • 12 Kinney H C, Brody B A, Kloman A S, Gilles F H. Sequence of central nervous system myelination in human infancy. II. Patterns of myelination in autopsied infants.  J Neuropathol Exp Neurol. 1988;  47 217-234
  • 13 McLennan J E, Gilles F H. A growth model for the total weight of the prenatal human brain.  Trans Am Neurol Assoc. 1976;  101 271-272
  • 14 Kinney H C. Human myelination and perinatal white matter disorders.  J Neurol Sci. 2005;  228 190-192 (Review)
  • 15 Billiards S S, Haynes R L, Folkerth R D et al.. Development of microglia in the cerebral white matter of the human fetus and infant.  J Comp Neurol. 2006;  497 199-208
  • 16 Dorovini-Zis K, Dolman C L. Gestational development of brain.  Arch Pathol Lab Med. 1977;  101 192-195
  • 17 Marín-Padilla M. Ontogenesis of the pyramidal cell of the mammalian neocortex and developmental cytoarchitectonics: a unifying theory.  J Comp Neurol. 1992;  321 223-240
  • 18 Marín-Padilla M. Prenatal development of fibrous (white matter), protoplasmic (gray matter), and layer I astrocytes in the human cerebral cortex: a Golgi study.  J Comp Neurol. 1995;  357 554-572
  • 19 Marín-Padilla M. Three-dimensional structural organization of layer I of the human cerebral cortex: a Golgi study.  J Comp Neurol. 1990;  299 89-105
  • 20 Armstrong C L, Hawkes R. Pattern formation in the cerebellar cortex.  Biochem Cell Biol. 2000;  78 551-562
  • 21 Haynes R L, Borenstein N S, Desilva T M et al.. Axonal development in the cerebral white matter of the human fetus and infant.  J Comp Neurol. 2005;  484 156-167
  • 22 Kinney H C, Belliveau R A, Trachtenberg F L, Rava L A, Paterson D S. The development of the medullary serotonergic system in early human life.  Auton Neurosci. 2007;  132 81-102
  • 23 Feess-Higgins A, Laroche J-C. Development of the Human Foetal Brain: An Anatomical Atlas. Paris: INSERM; 1987
  • 24 Huang H, Xue R, Zhang J et al.. Anatomical characterization of human fetal brain development with diffusion tensor magnetic resonance imaging.  J Neurosci. 2009;  29 4263-4273
  • 25 Habas P A, Kim K, Rousseau F, Glenn O A, Barkovich A J, Studholme C. A spatio-temporal atlas of the human fetal brain with application to tissue segmentation.  Med Image Comput Comput Assist Interv. 2009;  12 (Pt 1) 289-296
  • 26 Habas P A, Kim K, Yang P et al.. A Spatio-temporal Atlas of the Human Fetal Brain with Application to Tissue Segmentation: Medical Image Computing and Computer-Assisted Intervention. MICCAI 2009 Lecture Notes in Computer Science. Berlin/Heidelberg: Springer; 2009
  • 27 Bove K E. Autopsy Committee of the College of American Pathologists . Practice guidelines for autopsy pathology: the perinatal and pediatric autopsy.  Arch Pathol Lab Med. 1997;  121 368-376
  • 28 Barnes E G ed.. Handbook of Pediatric Autopsy Pathology. New York, NY: Humana Press; 2004
  • 29 McPherson T A, Valdes-Dapena M. The perinatal autopsy. In: Wigglesworth J S, Singer D B, eds. Textbook of Fetal and Perinatal Pathology. 2nd ed. Boston: Blackwell Scientific Publications; 1998: 87-110
  • 30 Keeling J. The perinatal necropsy. In: Keeling J, ed. Fetal and Neonatal Pathology. 3rd ed. London: Springer-Verlag; 2001: 1-45
  • 31 Genest D R, Williams M A, Greene M F. Estimating the time of death in stillborn fetuses: I. Histologic evaluation of fetal organs; an autopsy study of 150 stillborns.  Obstet Gynecol. 1992A;  80 575-584
  • 32 Genest D R, Singer D B. Estimating the time of death in stillborn fetuses: III. External fetal examination; a study of 86 stillborns.  Obstet Gynecol. 1992B;  80 593-600
  • 33 Hori A, Fischer G, Dietrich-Schott B, Ikeda K. Dimyelia, diplomyelia, and diastematomyelia.  Clin Neuropathol. 1982;  1 23-30
  • 34 Hutchins G M, Meuli M, Meuli-Simmen C, Jordan M A, Heffez D S, Blakemore K J. Acquired spinal cord injury in human fetuses with myelomeningocele.  Pediatr Pathol Lab Med. 1996;  16 701-712
  • 35 Griffiths P D, Variend D, Evans M et al.. Postmortem MR imaging of the fetal and stillborn central nervous system.  AJNR Am J Neuroradiol. 2003;  24 22-27
  • 36 Sims M E, Turkel S B, Halterman G, Paul R H. Brain injury and intrauterine death.  Am J Obstet Gynecol. 1985;  151 721-723
  • 37 Grafe M R. The correlation of prenatal brain damage with placental pathology.  J Neuropathol Exp Neurol. 1994;  53 407-415
  • 38 Becher J C, Bell J E, Keeling J W, Liston W A, McIntosh N, Wyatt B. The Scottish Perinatal Neuropathology Study—clinicopathological correlation in stillbirths.  BJOG. 2006;  113 310-317
  • 39 Pinar H, Burke S H, Huang C W, Singer D B, Sung C J. Reference values for transverse cerebellar diameter throughout gestation.  Pediatr Dev Pathol. 2002;  5 489-494

Halit PinarM.D. 

Division of Perinatal Pathology, Women and Infants Hospital, Alpert Medical School, Brown University

101 Dudley Street, Providence, RI 02905

Email: halit.pinar@gmail.com

    >