Evaluation of Stillbirth

1. Evaluation of Stillbirth Katy Kemnetz, PGY2

2. objectives Evaluation of stillbirth

3. Objectives The participant will be able to: • Identify the conditions that have been best demonstrated to cause stillbirth • Evaluate a stillbirth using the most effective workup • Accurately formulate an etiology for a stillbirth, when possible • Employ the recmomended hospital policies for management of stillbirth

4. Outline • Definitions • Causes of stillbirth • Workup of stillbirth • Other considerations • Conclusions

5. Definitions Evaluation of Stillbirth

6. Spontaneous abortion Intrauterine fetal demise • Miscarriage • <20 weeks gestation or <500g • “Stillbirth” • >20 weeks gestation or >350g—state dependent • 350g is 50%ile for 20 weeks gestation • Illinois: >20 weeks gestation • “Delivery of a fetus showing no signs of life as indicated by the absence of breathing, heart beats, pulsation of the umbilical cord, or definite movements of voluntary muscles” • Does not include terminations of pregnancy or IOL for previable PPROM Definitions

7. Causes Evaluation of stillbirth

8. Causes of stillbirth • >30 classification systems exist • Important to distinguish between • Underlying cause of death • Mechanism of death • Risk factors

9. Classification of stillbirth The National Institute of Child Health and Human Development

10. Classification of Stillbirth • Eunice Kennedy Shriver workshop 2007 • National Institute of Child Health and Human Development • “An optimal classification system would identify the pathophysiological entity initiating the chain of events that irreversibly lead to death”

11. Criteria for “cause” • Epidemiologic data demonstrate an excess of stillbirth associated with that condition • Biologic plausibility that the condition causes stillbirth • Either rarely seen in association with live births or, when seen in live births, results in a significant increase in neonatal death • A dose-response relationship exists • The greater the “dose” of the condition, the greater the risk of fetal death • Associated with evidence of fetal compromise • The stillbirth likely would not have occurred if that condition had not been present

12. Causes of stillbirth Reddy, UM et al. “Stillbirth Classification—Developing an International Consensus for Research.” Obstetrics and Gynecology, Vol 114, No 4, October 2009.

13. Causes of stillbirth—NICHHD workshop consensus Infections

14. Infection • Associated with 10-20% of stillbirths in developed countries • Higher association with preterm birth • Sometimes difficult to prove causality

15. Infection • Ascending infectionamniotic fluid or fetusfetalpneumonitis • Hematogenousspreadvillitis Kumar: Robbins pathologic basis of disease, 8th edition. 2009

16. Mechanism of fetal death • Severe maternal illness • Placental infection that prevents oxygen/ nutrients from crossing to the fetus • Fetal infection that causes a lethal congenital deformity • Fetal infection that damages a vital organ • Precipitation of preterm labor, with intrapartum fetal death

17. Infections must be proven • Signs of infection in the fetus • Evidence on autopsy of extensive organ involvement • Positive fetal cultures • Positive maternal cultures plus chorioamnionitis/ funisitis Kumar: Robbins pathologic basis of disease, 8th edition. 2009

18. Causes of IUFD: Spirochetes Severe placental dysfunction

19. Protozoa Severe placental dysfunction

20. Viruses Causes lethal fetal anomalies

21. Bacteria Damage to vital organs (brain, heart) Severe placental dysfunction Goldenberg RL, Thompson C. The infectious origins of stillbirth. Am J Obstet Gynecol 2003;189:861–73

22. Causes of stillbirth—NICHHD workshop consensus Maternal medical conditions

23. Hypertensive disorders Simpson, LL. Maternal medical disease: Risk of Antepartum Fetal Death. SeminPerinatol, 2002, 26, 47.

24. Mechanism of fetal demise: To consider cause of death: • Placental insufficiency • IUGR • Abruption • If it progresses to eclampsia • If it is associated with placental abruption or fetal growth restriction Hypertensive disorders

25. Diabetes Simpson, LL. Maternal medical disease: Risk of Antepartum Fetal Death. SeminPerinatol, 2002, 26, 47.

26. Mechanism of fetal demise: To consider cause of death: • Congenital abnormality • Placental dysfunction • Obstructed labor and intrapartum death • Macrosomia • Fetal hyperglycemiafetal insulin productionexcessive fetal growthmetabolic acidosis • Signs of intrauterine or intrapartum asphyxia • LGA fetus • SGA fetus • Severe malformation • Placenta demonstrates characteristic histologic findings • Large edematous villi • Increased prominence of cytotrophoblasts Diabetes

27. Thyroid/renal disorders Simpson, LL. Maternal medical disease: Risk of Antepartum Fetal Death. SeminPerinatol, 2002, 26, 47.

28. Thyroid disorders Renal disorders • Graves disease, where thyroid-stimulating hormone receptor antibody causes fetal toxicosis • Untreated thyroid disorders • Linear relationship between maternal creatinine and risk of fetal demise Systemic Lupus Erythematosus • Stillbirth rates are higher in the presence of HTN, nephritis, or APL • Circulating auto-antibodies, anti-Ro, anti-La • Congenital heart block, hydrops Thyroid/renal disorders

29. Maternal medical conditions • Risk is a continuum Reddy, UM et al, 2009

30. Causes of stillbirth—NICHHD workshop consensus thrombophilias

31. Antiphospholipid syndrome Inherited thrombophilias • Inflammation, thrombosis, and infarction in the placenta • Clear histopathological or clinical evidence of placental insufficiency • Factor V Leiden mutation, antithrombin III deficincy, prothrombin gene mutation, protein C deficiency, protein S deficiency • Placental infarction and thrombosis • Thrombophilias should only be considered as the cause of stillbirth with: • Evidence of placental insufficiency such as fetal growth restriction or infarction and • Recurrent fetal loss Two large prospective cohort studies found no association between factor V Leiden mutation and pregnancy loss or placental insufficiency Thrombophilias are common in healthy women with normal outcomes Thrombophilias

32. Causes of stillbirth—NICHHD workshop consensus alloimmunization

33. Red cell alloimmunization Platelet alloimmunization • Anti-Rhesus D, anti-Rhesus C, anti-Kell • Must have a positive indirect Coombs test • Antibody titers more than 1:16 (or 1:8 for anti-Kell) • Evidence of fetal anemia with hydrops • Evidence of fetal extramedullaryhematopoeisis • HPA-1a, HPA-5a, HPA-4 • Maternal antibodies against paternal and fetal platelet antigens • Parental platelet incompatibility for the pertinent antigen • Fetal thrombocytopenia • Massive intracranial hemorrhage Alloimmunization

34. Causes of stillbirth—NICHHD workshop consensus Congenital malformationschromosomal abnormalities

35. Criteria • Epidemiologic data demonstrating an excess of intrauterine mortality • Seen rarely in liveborn neonates • When seen in liveborn neonates, it frequently results in neonatal death • Biologic plausibility that it can result in death

36. Congenital malformations Reddy, UM et al. “Stillbirth Classification—Developing an International Consensus for Research.” Obstetrics and Gynecology, Vol 114, No 4, October 2009.

37. Incidence • Cytogenetic abnormalities account for 6-13% of all stillbirths • This may be higher because 40-50% attempted karyotypes fail to grow • 23% monosomy X, 23% trisomy 21, 21% trisomy 18, 8% trisomy 13 Chromosomal abnormalities Kumar: Robbins pathologic basis of disease, 8th edition. 2009

38. Autosomal recessive disorders Autosomal dominant disorders • Alpha thalessemia, Smith LemliOpitz • Phenotype in lethal cases may differ from live cases • Skeletal dysplasias • More often spontaneous mutations Chromosomal abnormalities Firestein: Kelley’s Textbook of Rheumatology, 9th ed. Saunders 2012

39. Causes of stillbirth—NICHHD workshop consensus Fetomaternal hemorrhage

40. Fetomaternal hemorrhage • The cause 4% of all stillbirths • Risk factors: • Placental abruption • Abdominal trauma • Multiple gestation • Abnormal fetal testing

41. Fetomaternal hemorrhage • Risk of stillbirth depends on • Amount of hemorrhage • Acute/chronic • Gestational age • A threshold of 20 mL/kg of fetal bleeding is associated with increased risk of stillbirth • Autopsy confirmation of fetal anemia and hypoxia

42. Causes of stillbirth—NICHHD workshop consensus Placental causes

43. Placental causes • Placenta previa, vasaprevia, neoplasms • Placental abruption has 8.9 relative risk of stillbirth • May be considered the cause of death if >30% of the placenta shows signs of abruption Reddy, UM et al, 2009

44. Placental causes • Any disease that causes an SGA placenta may result in stillbirth • <5% expected weight for gestational age • Preeclampsia, DM, HTN, renal, chronic infections • Any disease that causes an LGA placenta may result in stillbirth • >95% expected weight for gestational age • Hydropsfetalis, DM, syphilis

45. Stillbirth classification—NICHHD workshop consensus Umbilical cord pathology

46. Umbilical cord pathology • Account for 3.4-15% of stillbirths • Velamentous insertion • If it leads to a vasaprevia or bleeding during labor • Umbilical cord prolapse • Associated with prematurity, malpresentation, mutiparity, obstetric manipulation • Umbilical cord occlusion • Cord prolapse, entanglement (mono-mono twins) • Torsion • Rupture, strictures, hematomas

47. Velamentous insertion

48. Umbilical cord pathology Isolated finding of a nuchal cord or a true knot at the time of delivery is insufficient evidence that cord accident is the cause of stillbirth • Nuchal cord • Occurs in up to 30% of normal pregnancies • Not associated with an increased risk of stillbirth in study of 14,000 deliveries • True knot • Also common in live births • Grooving of the cord, constriction of the umbilical vessels, edema, congestion, thrombosisrequired to claim it is the etiology • Exclude other relevant causes of stillbirth • Find evidence of hypoxia and cord occlusion on postmortem examination

49. Stillbirth classification—NICHHD workshop consensus Multifetal gestation

50. Complications of multifetal gestation • Monochorionicplacentation • Twin-twin transfusion syndrome occurs in 9% of mono-di twins • Mortality can be 90% in untreated cases