Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-669899f699-cf6xr Total loading time: 0 Render date: 2025-05-01T08:56:34.991Z Has data issue: false hasContentIssue false

4 - Stillbirth and intrauterine growth restriction

Published online by Cambridge University Press:  05 September 2014

By
Adrian Charles  and
Yee T. Khong
Edited by
Marta C. Cohen  and
Irene Scheimberg
Adrian Charles
Affiliation:
University of Western Australia
Yee T. Khong
Affiliation:
University of Adelaide
Marta C. Cohen
Affiliation:
Sheffield Children’s Hospital
Irene Scheimberg
Affiliation:
Barts and the London NHS Trust, London
Get access

Summary

Introduction

The causes of stillbirth are varied. Stillbirth may be due to obstetric conditions such as premature labor, fetal abnormalities, infections, intrapartum complications, placental and cord factors, maternal conditions, or drugs. A significant number remain unexplained despite a full investigation [1,2]. The rate of stillbirth in the developed world over the last 20 years has remained much the same or declined very slightly at around three per 1000 births (>28 week gestational age) using international comparisons [3]. This decline in stillbirths has not mirrored the decline in infant deaths, though this may be due to the fact that there are now more older mothers, more maternal obesity [4], and more assisted conceptions, each increasing the risk of stillbirth.

The proportion of stillbirths that are assigned to the various categories depends upon the depth of the investigation and the classification system used. The proportion that is unexplained can vary from around 15–20% with ReCoDe [5] and Perinatal Society of Australia and New Zealand (PSANZ) (e.g., WA data) [6], to 60% with some of the older classification systems. The number of unexplained stillbirths can be reduced considerably by the use of a category of growth restriction, using charts customized to the mother’s parameters and using fetal growth measures derived from ultrasound measures, all of which increase the recognition of a substantial number of growth-restricted fetuses [5]. There are now a number of different classification systems with various benefits and drawbacks [7,8].

Type
Chapter
Information
The Pediatric and Perinatal Autopsy Manual , pp. 62 - 82
Publisher: Cambridge University Press
Print publication year: 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Perinatal Society of Australia and New Zealand Perinatal Mortality Group and ANZSA PSANZ. Clinical practice guideline for perinatal mortality. (accessed 8 October 2013).
Stillbirth Collaborative Research Network Writing Group. Causes of death among stillbirths. JAMA 2011; 306: 2459–68.CrossRefGoogle Scholar
Lawn, J. E., Blencowe, H., Pattinson, R., et al. Stillbirths: Where? When? Why? How to make the data count?Lancet 2011; 377: 1448–63.CrossRefGoogle ScholarPubMed
McIntyre, H. D., Gibbons, K. S., Flenady, V. J., and Callaway, L. K.. Overweight and obesity in Australian mothers: epidemic or endemic?Med J Austral 2012; 196: 184–8.CrossRefGoogle ScholarPubMed
Gardosi, J., Kady, S. M., McGeown, P., Francis, A., and Tonks, A.. Classification of stillbirth by relevant condition at death (ReCoDe): population based cohort study. BMJ 2005; 331: 1113–17.CrossRefGoogle ScholarPubMed
Government of Western Australia, Department of Health. The 13th report of the Perinatal and Infant Mortality Committee of Western Australia for Deaths in the Triennium 2005–07. (accessed 18 June 2013).
Gordijn, S. J., Korteweg, F. J., Erwich, J. J., et al. A multilayered approach for the analysis of perinatal mortality using different classification systems. Eur J Obstet Gynecol Reprod Biol 2009; 144: 99–104.CrossRefGoogle ScholarPubMed
Reddy, U. M., Goldenberg, R., Silver, R., et al. Stillbirth classification: developing an international consensus for research: executive summary of a National Institute of Child Health and Human Development workshop. Obstet Gynecol 2009; 114: 901–14CrossRefGoogle ScholarPubMed
Measey, M. A., Charles, A., d’Espaignet, E. T., et al. Aetiology of stillbirth: unexplored is not unexplained. Aust N Z J Public Health 2007; 31: 444–9.CrossRefGoogle Scholar
Dudley, D. J., Goldenberg, R., Conway, D., et al. A new system for determining the causes of stillbirth. Obstet Gynecol 2010; 116(2 Pt 1): 254–60.CrossRefGoogle ScholarPubMed
Pinar, H., Koch, M. A., Hawkins, H., et al. The stillbirth collaborative research network postmortem examination protocol. Am J Perinatol 2012; 29: 187–202.Google ScholarPubMed
Royal College of Pathologists. Guidelines on Autopsy Practice: best practice scenarios. (accessed 8 October 2013).
Flenady, V., Froen, J. F., Pinar, H., et al. An evaluation of classification systems for stillbirth. BMC Pregnancy Childbirth 2009; 9: 24.CrossRefGoogle ScholarPubMed
London Medical Databases. Welcome to London Medical Databases. (accessed 8 October 2013).
NCBI. Online Mendelian Inheritance in Man (OMIM). (accessed 8 October 2013).
Korteweg, F. J., Bouman, K., Erwich, J. J., et al. Cytogenetic analysis after evaluation of 750 fetal deaths: proposal for diagnostic workup. Obstet Gynecol 2008; 111: 865–74.CrossRefGoogle ScholarPubMed
Pinar, H., Carpenter, M., Martin, B. J., Tantravahi, U.. Utility of fetal karyotype in the evaluation of phenotypically abnormal stillbirths. Pediatr Dev Pathol 2009; 12: 217–21.CrossRefGoogle ScholarPubMed
CESDI. 6th Annual Report. London, Maternal and Child Health Research Consortium, 1999.Google Scholar
Figueras, F. and Gardosi, J.. Intrauterine growth restriction: new concepts in antenatal surveillance, diagnosis, and management. Am J Obstet Gynecol 2011; 204: 288–300.CrossRefGoogle Scholar
Cox, P. and Marton, T.. Pathological assessment of intrauterine growth restriction. Best Pract Res Clin Obstet Gynaecol 2009; 23: 751–64.CrossRefGoogle ScholarPubMed
Chauhan, S. P., Gupta, L. M., Hendrix, N. W., et al. Intrauterine growth restriction: comparison of American College of Obstetricians and Gynecologists practice bulletin with other national guidelines. Am J Obstet Gynecol 2009; 200: e1–6.CrossRefGoogle ScholarPubMed
Sankaran, S. and Kyle, P. M.. Aetiology and pathogenesis of IUGR. Best Pract Res Clin Obstet Gynaecol 2009; 23: 765–77.CrossRefGoogle ScholarPubMed
Haig, D.. Gestational drive and the green-bearded placenta. Proc Nat Acad Sci USA 1996; 93: 6547–51.CrossRefGoogle ScholarPubMed
Burton, G. J. and Fowden, A. L.. The placenta and developmental programming: balancing fetal nutrient demands with maternal resource allocation. Placenta 2012; 33 Suppl: S23–7.CrossRefGoogle ScholarPubMed
Khong, T. Y., Adema, E. D., and Erwich, J. J.. On an anatomical basis for the increase in birth weight in second and subsequent born children. Placenta. 2003; 24: 348–53.CrossRefGoogle ScholarPubMed
Cogswell, M. E. and Yip, R.. The influence of fetal and maternal factors on the distribution of birthweight. Sem Perinatol 1995; 19: 222–40.CrossRefGoogle ScholarPubMed
Zhang, J., Merialdi, M., Platt, L. D., and Kramer, M. S.. Defining normal and abnormal fetal growth: promises and challenges. Am J Obstet Gynecol 2010; 202: 522–8.CrossRefGoogle ScholarPubMed
Hutcheon, J. A., Zhang, X., and Platt, R. W.. The benefits of customizing for maternal factors or the benefits of using an intrauterine standard at preterm ages?Am J Obstet Gynecol 2008; 199: e18–19; author reply e9–20.CrossRefGoogle ScholarPubMed
Gardosi, J., Figueras, F., Clausson, B., and Francis, A.. The customised growth potential: an international research tool to study the epidemiology of fetal growth. Paediatr Perinat Epidemiol 2011; 25: 2–10.CrossRefGoogle Scholar
Wigglesworth, J. S.. Monitoring perinatal mortality: a pathophysiological approach. Lancet 1980; 2: 684–6.CrossRefGoogle ScholarPubMed
Wingate, M. S. and Alexander, G. R.. The healthy migrant theory: variations in pregnancy outcomes among US-born migrants. Soc Sci Med 2006; 62: 491–8.CrossRefGoogle ScholarPubMed
Liu, Y., Zhang, J. and Li, Z.. Perinatal outcomes in native Chinese and Chinese-American women. Paediatr Perinat Epidemiol 2011; 25: 202–9.CrossRefGoogle ScholarPubMed
Lim, J. W., Lee, J. J., Park, C. G., Sriram, S., and Lee, K. S.. Birth outcomes of Koreans by birthplace of infants and their mothers, the United States versus Korea, 1995–2004. J Korean Med Sci 2010; 25: 1343–51.CrossRefGoogle ScholarPubMed
Gardosi, J., Clausson, B., and Francis, A.. The value of customised centiles in assessing perinatal mortality risk associated with parity and maternal size. BJOG 2009; 116: 1356–63.CrossRefGoogle ScholarPubMed
Pinar, H., Koch, M. A., Hawkins, H., et al. The Stillbirth Collaborative Research Network (SCRN) placental and umbilical cord examination protocol. Am J Perinatol 2011; 28: 781–92.CrossRefGoogle ScholarPubMed
Beeksma, F. A., Erwich, J. J., and Khong, T. Y.. Placental fetal vascular thrombosis lesions and maternal thrombophilia. Pathology 2012; 44: 24–8.CrossRefGoogle ScholarPubMed
Gruenwald, P. and Minh, H. N.. Evaluation of body and organ weights in perinatal pathology: II. Weight of body and placenta of surviving and of autopsied infants. Am J Obstet Gynecol 1961; 82: 312–19.CrossRefGoogle ScholarPubMed
Parker, C. B., Hogue, C. J., Koch, M. A., et al. Stillbirth Collaborative Research Network: design, methods and recruitment experience. Paediatr Perinat Epidemiol 2011; 25: 425–35.CrossRefGoogle ScholarPubMed
Stillbirth Collaborative Research Network Writing Group. Association between stillbirth and risk factors known at pregnancy confirmation. JAMA 2011; 306: 2469–79.CrossRefGoogle Scholar
Breeze, A. C. and Lees, C. C.. Prediction and perinatal outcomes of fetal growth restriction. Semin Fetal Neonatal Med 2007; 12: 383–97.CrossRefGoogle ScholarPubMed
Korteweg, F. J., Bouman, K., Erwich, J. J., et al. Cytogenetic analysis after evaluation of 750 fetal deaths: proposal for diagnostic workup. Obstet Gynecol 2008; 111: 865–74.CrossRefGoogle ScholarPubMed
Maroun, L. L. and Graem, N.. Autopsy standards of body parameters and fresh organ weights in nonmacerated and macerated human fetuses. Pediatr Dev Pathol 2005; 8: 204–17.CrossRefGoogle ScholarPubMed
Becker, M. J.. Pathology of Late Fetal Stillbirth. Edinburgh, Churchill Livingstone, 1989.Google Scholar
Pinar, H., Koch, M. A., Hawkins, H., et al. The Stillbirth Collaborative Research Network neuropathologic examination protocol. Am J Perinatol 2011; 28: 793–802.CrossRefGoogle ScholarPubMed
Squier, M. and Keeling, J. W.. The incidence of prenatal brain injury. Neuropathol Appl Neurobiol 1991; 17: 29–38.CrossRefGoogle ScholarPubMed
Reddy, U. M., Page, G. P., and Saade, G. R., et al. Karyotype versus microarray testing for genetic abnormalities after stillbirth. N Engl J Med 2012; 367: 2185–93.CrossRefGoogle ScholarPubMed
Kraus, F. T., Redline, R. W., Gersell, D. J., Nelson, D. M., and Dicke, J. M.. Placental Pathology (Atlas of Nontumor Pathology). Washington, DC, American Registry of Pathology, 2004.Google Scholar
Fox, H. S. N. and Sebire, N. J.. Pathology of the Placenta. 3rd edition. Philadelphia, PA, Saunders, 2007.Google Scholar
Benirschke, K.Burton, G. J. and Baergen, R. N.. Pathology of the Human Placenta. 6th edition. New York, Springer, 2011.Google Scholar
Faye-Petersen, O. M., Heller, D. S., and Joshi, V. V.. Handbook of Placental Pathology. 2nd edition. London, CRC Press, 2004.Google Scholar
Whitley, G. S. and Cartwright, J. E.. Cellular and molecular regulation of spiral artery remodelling: lessons from the cardiovascular field. Placenta 2010; 31: 465–74.CrossRefGoogle ScholarPubMed
Smith, G. C., Shah, I., Crossley, J. A., et al. Pregnancy-associated plasma protein A and alpha-fetoprotein and prediction of adverse perinatal outcome. Obstet Gynecol 2006; 107: 161–6.CrossRefGoogle ScholarPubMed
Smith, G. C., Stenhouse, E. J., Crossley, J. A., et al. Early pregnancy levels of pregnancy-associated plasma protein A and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab 2002; 87: 1762–7.CrossRefGoogle ScholarPubMed
Burton, G. J., Woods, A. W., Jauniaux, E., and Kingdom, J. C.. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta 2009; 30: 473–82.CrossRefGoogle ScholarPubMed
Steegers, E. A., von Dadelszen, P., Duvekot, J. J., and Pijnenborg, R.. Pre-eclampsia. Lancet 2010; 376: 631–44.CrossRefGoogle ScholarPubMed
Khong, Y. and Brossens, I.. Defective deep placentation. Best Prac Res Clin Obstetr Gynaecol 2011; 25: 301–11.CrossRefGoogle ScholarPubMed
Fitzgerald, B., Kingdom, J., and Keating, S.. Distal villous hypoplasia. Diagnostic Histopathology 2012; 18: 195–200.CrossRefGoogle Scholar
Redline, R. W., Boyd, T., Campbell, V., et al. Maternal vascular underperfusion: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol 2004; 7: 237–49.Google ScholarPubMed
Salafia, C. M., Pezzullo, J. C., Minior, V. K., and Divon, M. Y.. Placental pathology of absent and reversed end-diastolic flow in growth-restricted fetuses. Obstet Gynecol 1997; 90: 830–6.CrossRefGoogle ScholarPubMed
Redline, R. W.. Villitis of unknown etiology: noninfectious chronic villitis in the placenta. Human Pathol 2007; 38: 1439–46.CrossRefGoogle ScholarPubMed
Khong, T. Y., Staples, A., Moore, L., and Byard, R. W.. Observer reliability in assessing villitis of unknown aetiology. J Clin Pathol 1993; 46: 208–10.CrossRefGoogle ScholarPubMed
Boyd, T. K. and Redline, R. W.. Chronic histiocytic intervillositis: a placental lesion associated with recurrent reproductive loss. Human Pathol 2000; 31: 1389–96.CrossRefGoogle ScholarPubMed
Uxa, R., Baczyk, D., Kingdom, J. C., et al. Genetic polymorphisms in the fibrinolytic system of placentas with massive perivillous fibrin deposition. Placenta. 2010; 31: 499–505.CrossRefGoogle ScholarPubMed
Griffin, A. C., Strauss, A. W., Bennett, M. J., and Ernst, L. M.. Mutations in long-chain 3-hydroxyacyl coenzyme a dehydrogenase are associated with placental maternal floor infarction/massive perivillous fibrin deposition. Pediatr Dev Pathol 2012; 15: 368–74.CrossRefGoogle ScholarPubMed
Armes, J. E., McGown, I., Williams, M., et al. The placenta in Beckwith–Wiedemann syndrome: genotype-phenotype associations, excessive extravillous trophoblast and placental mesenchymal dysplasia. Pathology 2012; 44: 519–27.CrossRefGoogle ScholarPubMed
Kalousek, D. K. and Vekemans, M.. Confined placental mosaicism. J Med Genet 1996; 33: 529–33.CrossRefGoogle ScholarPubMed
Machin, G. A., Ackerman, J., and Gilbert-Barness, E.. Abnormal umbilical cord coiling is associated with adverse perinatal outcomes. Pediatr Dev Pathol. 2000; 3: 462–71.CrossRefGoogle ScholarPubMed
Khong, T. Y.. Evidence-based pathology: umbilical cord coiling. Pathology. 2010; 42: 618–22.CrossRefGoogle ScholarPubMed
David, A. L., Tan, A., and Curry, J.. Gastroschisis: sonographic diagnosis, associations, management and outcome. Prenat Diag. 2008; 28: 633–44.CrossRefGoogle ScholarPubMed
Whitington, P. F. and Hibbard, J. U.. High-dose immunoglobulin during pregnancy for recurrent neonatal haemochromatosis. Lancet 2004; 364: 1690–8.CrossRefGoogle ScholarPubMed
Lumey, L. H., Stein, A. D., Kahn, H. S., et al. Cohort profile: the Dutch Hunger Winter families study. Int J Epidemiol 2007; 36: 1196–204.CrossRefGoogle ScholarPubMed
Tobi, E. W., Slagboom, P. E., van Dongen, J., et al. Prenatal famine and genetic variation are independently and additively associated with DNA methylation at regulatory loci within IGF2/H19. PloS one. 2012; 7: e37933.CrossRefGoogle ScholarPubMed
Meyer, K. M., Koch, J. M., Ramadoss, J., Kling, P. J., and Magness, R. R.. Ovine surgical model of uterine space restriction: interactive effects of uterine anomalies and multifetal gestations on fetal and placental growth. Biol Reprod 2010; 83: 799–806.CrossRefGoogle ScholarPubMed
Malabarey, O. T., Balayla, J., Klam, S. L., Shrim, A., and Abenhaim, H. A.. Pregnancies in young adolescent mothers: a population-based study on 37 million births. J Pediatr Adolesc Gynecol. 2012; 25: 98–102.CrossRefGoogle ScholarPubMed
Quintero, R. A., Dickinson, J. E., Morales, W. J., et al. Stage-based treatment of twin–twin transfusion syndrome. Am J Obstet Gynecol 2003; 188: 1333–40.CrossRefGoogle ScholarPubMed
Wee, L. Y., Taylor, M., Watkins, N., et al. Characterisation of deep arterio-venous anastomoses within monochorionic placentae by vascular casting. Placenta 2005; 26: 19–24.CrossRefGoogle ScholarPubMed
De Paepe, M. E., Shapiro, S., Young, L., Luks, F. I.. Placental characteristics of selective birth weight discordance in diamniotic-monochorionic twin gestations. Placenta 2010; 31: 380–6.CrossRefGoogle ScholarPubMed
Marton, T., Hargitai, B., Bowen, C., and Cox, P.. Elevated brain weight/liver weight ratio in normal bodyweight centile term perinatal deaths: an indicator of terminal intrauterine malnourishment?Pediatr Dev Pathol 2013; 16: 267–71.CrossRefGoogle Scholar
Guttmacher, A. E., Spong, C. Y., and Willinger, M.. Long QT syndrome susceptibility mutations and pregnancy loss: another piece of a still unfinished puzzle?JAMA 2013; 309: 1525–6.CrossRefGoogle ScholarPubMed
Frost, J. M. and Moore, G. E.. The importance of imprinting in the human placenta. PLoS genetics. 2010; 6: e1001015.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×