1. 초음파 통계 2005.05.09 ~2005.05.14

2. GYOB 정밀 초음 파 양수 검사 3-D U/S 도플 러 검 사 총 계총 계 5.09~5.14185734114268 5.02 ~5.07134496300192 5124-2 1476

3. CASE PRESENTATION - OB case - R2 박혜원

4. 유 O 라 / 18 yr C.C: Preg 19 wks c IUFD R/O Fetal hydrops for termination P/Ix : 상기 여환 local OBGY 에서 실시한 triple test 상 NTD 의심되어 본원에서 4 월 29 일 amniocentesis 시행 받은 뒤 f/u U/S 상 IUFD, fetal hydrops 소견 보여 termination 위해 내원

5. OB Hx P 0-0-0-0 LMP :2004.12.24 EDC : 2005.09.30 Mense Hx : regular (interval -30 일 ) duration – 5~6 일 amount – moderate pain – (+) Op Hx : none

6. Past Hx DM / HTN / TBc / Hepatitis (-/-/-/-) Op Hx : none 임신초기 약물치료, Smoking (+)

7. 2005.04.29 OPD Preg 18 wks V/S : 100/70 체중 : 55 kg Urine sugar ( - ) Urine protein ( - ) Triple at local 04.13 MS AFP 228.93 HCG 54.76 u-E3 4.95 04.19 MS AFP 281.75 ( recheck ) Local 에서 NTD (+)  amniocentesis 위해 attending 됨

8. 2005.04.29 U/S vertex IUP at 17+3 weeks no evidence of NTD and cranial sign Cerebellum :1.73 cm C-Mag : 0.44 cm lat ventricle : 0.46, 0.62 cm AFI : adaquate amounts amnio AFP

9. 2005.04.29 U/S

16. 2005.05.06 IUP at 19+0 weeks f/u SONO no fetal heart movement scalp edema(+) pleural effusion(+) ascites(+) skin edema(+)

17. 2005.05.06 U/S Breech EFW 261 gm post placenta Imp) NIHF, IUFD, IUP at 19 weeks post amniocentesis status

26. 2005.05.07 Still birth  M 140gm Grossly nuchal thickness (+)

29. Placental Bx DIAGNOSIS : Placenta, removal ; No chorioamnionitis Two umbilical arteries an one vein No hematoma, blood clot

30. Amniocentesis Amniocentesis chromosomal analysis : No apparent cytogenetic abnormalities Acetylcholin esterase : Negative/ 0.71 Alpa –fetoprotein :8.65

31. Non-immune Hydrops Fetalis

32. Non-immune Hydrops Fetalis definition Presence of excess extra-cellular fluid in two or more sites without any identifiable circulating antibody to red cell antigens Immune Hydrops Fetalis : results when the mother immune system causes breakdown of red blood cells in the fetus. Hydrops is the most dangerous sign of blood group incompatibility between the mother and baby. non-immune Hydrops Fetalis : the most common type; can result when diseases or complications interfere with the baby's ability to manage fluid

33. Non-immune Hydrops Fetalis Generalized skin thickening of more than 5mm and / or two or more of the following ] Pericardial effusion ] Pleural Effusion ] Ascites ] Placental Enlargement edema : not dependent

34. Non-immune Hydrops Fetalis After birth pale coloring severe edema overall, especially in the baby's abdomen enlarged liver and spleen respiratory distress (difficulty breathing)

35. Non-immune Hydrops Fetalis

36. Normal four Chamber Cardiac View

37. Pericardial Effusion Heart

38. Body wall edema in a hydropic fetus

39. Fetal Ascites

43. © http://www.fetalmedicine.ac.uk/fmu.shtml

45. Hydrocele can be an early manifestation in hydrops

46. Placenta of Hydropic Pregnancy Placenta of Normal Pregnancy

47. Soft Tissue shadow and pleural effusion in hydropic neonate

48. Non-immune Hydrops Fetalis incidence 1 in 1500 ~ 4000 delivery

49. Non-immune Hydrops Fetalis pathogenesis  It is an end result of an array of disorders of the fetus, umbilical cord and placenta that leads to deranged fluid homeostasis.  A wide range of fetal organs are involved - No common mechanism is responsible for the signs of hydrops  Fetal regulation of fluid distribution influenced by the placental circulation which receives approximately 40 % fo the fetal combined cardiac output

50. Most frequent causes of hydrops fetalis (60% of cases) Cardiac causes Chromosomal causes Thoracic and pulmonary causes Causes of fetal anemia Fetal infections Monochorionic twinning or Twin transfusion syndrome (TTS)

51. Non-immune Hydrops Fetalis pathogenesis Cardiac Failure: JCommonest Mechanism JIncrease in Cardiac Size JIncreased Fetal Venous Pressure

52. Non-immune Hydrops Fetalis pathogenesis Cardiac Failure: JDisorders of cardiac function / Structure include 1.Cardiovascular anomaly 2.Structural defect -Ebstien’s anomaly, AV malformation 3.Cardiomyopathies 4.Tachyarythmias 5.Bradycardias (Congenital heart block) 6.Cardiac tumor - Obstructive left heart disease 7.Atrial isomerism

53. Non-immune Hydrops Fetalis pathogenesis Fetal Anemia:  High output cardiac failure  Portal hypertension in severely effected fetuses due to increase in hepatic erythropoetic tissue.  Hypoxia and acidosis predispose to epithelial damage in capillaries that allows loss of fluid to extravascular compartment

54. Non-immune Hydrops Fetalis pathogenesis Fetal Anemia :  Excessive erythrocyte loss - hemolysis, chronic hemorrhage - Secondary to Feto-maternal Hemorrhage - Twin-twin transfusion  insufficient production of erythrocytes - Alpha (  ) Thalasaemia - Other Hemoglobinopathies

55. Non-immune Hydrops Fetalis pathogenesis Thoracic and pulmonary causes  Congenital cystic adenomatoid malformation of lung  Pulmonary sequestration  Right-sided diaphragmatic hernia  Intrathoracic teratoma/neoplasm  Enterogenous, bronchogenic cysts  Dyschondroplasias (achondrogenesis types I and II)  Laryngeal atresia with congenital pulmonary hyperinflation  Chylothorax / Hydrothorax (due to lymphatic obstruction) causes pulmonary hypoplasia and involve only isolated pleural effusions

56. Non-immune Hydrops Fetalis pathogenesis TUMOR teratomas are localized at the sacrococcygeal region Fetal Infections: - TORCH - Parvo Virus B19 Genetic disorders 1. Turner syndrome - 45X (42 % of cases) 2. Trisomies 21 (34 %) and 18 (9 %) 3. Triploidy (5 %) - Trisomy 13, 15, 16 4. Tetraploidy

57. Non-immune Hydrops Fetalis pathogenesis  Obstruction to venous return GI disorder – volvulus, obstruction, omphalocele hepatitis, cirrhosis, necrosis increased extramedullary hematopoiesis, hemochromatosis

58. Non-immune Hydrops Fetalis pathogenesis Reduced Osmotic pressure : Hypoproteiaemia with Subsequent Reduction in Osmotic Pressure  Anemia Along With Destruction of Hepatic Architecture  Congenital Nephrosis  Hypoproteiaemia may be the result of loss of proteins from circulation, rather than the cause.

59. Non-immune Hydrops Fetalis pathogenesis  Associated Maternal Complications : Polyhydramnios Pre-mature labour Oligohydramnios Problems with third stage

60. Investigations  Detailed Ultrasound Scan  Fetal Echocardiography  Doppler Blood Flow Studies  Liquor Volume Assessment (AFI)  Placental Thickness & Echogenicity

61. Investigations  Full Blood Counts  Karyotype  Blood Gas Analysis  Virology screening  Bio-chemical Evaluation  Umbilical Venous Pressure

62. Fetal Blood Sampling Blood Can be Obtained From Various Sites  Placental Insertion of Umbilical Cord  Fetal Insertion of Umbilical Cord  Intra-hepatic Vein  Heart  Procedure related fetal loss is 25% in hydropic fetus

63. Investigations in case of hydrops (Maternal studies ) Blood type and group Full blood count Bacteriological studies CMV, VDRL TORCH & Parvovirus titers Indirect Coombs to rule out immune etiologies SMA20 Antiphospholipid, anticardiolipid and lupus anticoagulant antibodies Antibody screen (AChR, anti RO & LA, etc.) Kleihauer-Bethke test to eliminate the possibility of a fetomaternal hemorrhage Red blood cell enzymopathies G-6-PD G.T.T / Glycosylated Hb Hemoglobin electrophoresis Alfa feto protein serum levels HLA typing of the parents because lack of maternal blocking antibodies may predispose to this condition

64. Investigations in case of hydrops(Amniocentesis ) Karyotype analysis Amniotic fluid analysis with cultures / PCR Alfa feto protein of the amniotic fluid Metabolic tests (Gaucher's, Tay-Sachs, GM1 Gangliosidosis) Restriction endonuclease for Alpha thalassemia Amniotic fluid supernatant analysis (glycosaminoglycans, oligosaccharides, free sialic acid and acid hydrolase activities)

65. Investigations in case of hydrops (Fetal and placental studies) Fetal blood for investigation of : Type and Group Karyotype (also on chorionic villi) Full blood count Direct and indirect Coombs Viral Screen / TORCH IgM, parvovirus CBC SMA20 Serum protein levels Abnormal Hb studies Red blood cell enzyme mutations Viscosity studies Arterial blood gases Doppler Blood Flow Studies (umbilical artery, middle cerebral artery, aorta, umbilical artery pressure)

66. Investigations in case of hydrops (Fetal and placental studies) Complete and detailed fetal and placental ultrasound done by an experienced sonographist Fetal echocardiography (see Blue Cross BlueShield of Tennessee Medical Policy Manual) Blue Cross BlueShield of Tennessee Medical Policy Manual X-Rays (complete babaygram) with examination of the chest, abdomen, cranium, long- bones lengths, deformation and calcification Clinical photographs of the fetus Complete autopsy of the fetus Analysis of fetal pericardial effusions (ascitic/pleural fluid) & cystic hygroma (if any) for protein levels, cell content and lymphocyte count Biochemical, molecular, cytogenetic, virological, bacteriological studies of cultured amniotic fluid, fetal and placental tissue cells Electron microscopy and enzyme assays (for instance, sialidase, B-Glucosidase, B-Galactosidase and Glucuronidase) in culturedfibroblasts Electron microscopy to be used for myocardial mitochondria

67. Investigations in case of hydrops (Fetal and placental studies) Ultrastructural examination to be performed on myocardial fibers Histologic examination of the placenta : Examination of the placenta Examination of the placenta by American Academy of Family Physicians Protocol for Placental and Cord EvaluationProtocol for Placental and Cord Evaluation Wisconsin Stillbirth Service Program Placental ExaminationPlacental Examination by Cedars-Sinai Medical Center of Los Angeles Liver or skeletal muscle biopsy due to the variable involvement of mitochondria in various tissues Macroscopic and histologic examination of viscera Special attention should be focused on the heart, parenchymal organs (liver, spleen, kidney), bone marrow and neuromuscular system (fetal hypomobility). Fetal DNA should be stored for further investigation of syndromes (known and unknown) and confirmation of likely or actual genetic diseases that are diagnosed after the completion of the autopsy

68. Management XMulti-disciplinary XOption of Termination of pregnancy XPostmortem examination, Photographs & X-rays XTherapy should only be commenced in the light of a firm diagnosis XIdeal to wait until fetal karyotype is available

69. Management Prenatal Therapy NTransplacental drug therapy NDirect fetal drug therapy NInvasive procedures

70. Transplacental drug therapy NDrugs are given to the mother and are passed to the fetus through the placenta NThe main conditions which respond to this approach are fetal dysrrhythmias (SVT) NOnce the type of dysrrhythmia is identified, anti-arrhythmic agent is given to the mother, with careful monitoring of her ECG & blood levels. NDrugs: Digoxin, Verapamil, Amiadarone, Flecanide.

71. Direct fetal drug therapy Maternal administration of drugs may be ineffective due to: XMaternal Metabolism XMaternal Side Effects XVariable Passage Across Placenta Routes for direct fetal drug therapy: aIntraperitoneal aIntramuscular aIntravascular

72. Invasive Procedures Blood / Albumen Transfusion to Fetus Intraperitoneal Intravenous XUmbilical Vein XHepatic Vein

73. Invasive Procedures Drainage Procedures: Large Pleural Effusions Ascities  All invasive procedures carry an inherent increased risk of fetal demise or pre- mature labor

74. Obstetric management vRarely straightforward vTemptation to deliver the sick fetus before term should be avoided vCommon maternal complications should also be considered like associated polyhydramnios. vAmniocentesis before delivery makes the delivery easy and less traumatic for both mother & Fetus, and facilitates resuscitation

75. Obstetric management Most of the times such fetuses are delivered with elective cesarean section. No evidence that mode of delivery has a marked effect on outcome. Pediatric team should be aware about the nature of fetal problem before delivery as resuscitation is often difficult and adequate senior assistance must be available. High incidence of third stage complications should not be overlooked.

76. Prognosis Generally very poor with very high peri-natal mortality

77. Treatment fSuccessful therapy can be administered in some cases, yet majority are associated with a poor prognosis. fAppropriate prenatal investigations must be performed to make a correct diagnosis to identify an effected fetus in whom a good outcome may be anticipated