1	Hydrops foetalis Dr Luc Laurier OLIGNY Pediatric pathologist CHU Sainte-Justine Université de Montréal luc_oligny@ssss.gouv.qc.ca
2	Hydrops foetalis is the greatest challenge for foetopathologists
3	Hydrops foetalis is the greatest challenge for foetopathologists > 90 genetic diseases associated with HF
4	Hydrops foetalis is the greatest challenge for foetopathologists Dx crucial for genetic counselling
5	Prenatal Dx of HF by U/S Clinical emergency: Cause must be ascertained for Tx option: - Anemia → Transfusion - Arrhythmia → Anti-arrhythmics - Compressing cysts or effusions → Drainage
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7	HF Pathogenesis Three main mechanisms: - Anemia - Hypoproteinemia - Cardiac failure
8	HF - Genetic causes Mendelian Inheritance in Man (OMIM): http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=omim - Chromosomal abnormalities - 90 genetic disorders listed to cause HF - single gene defects - eg metabolic diseases
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11	HF – Causes & Associations (1644 cases) Cardiovascular 22% Chromosomal 13% Thoracic 10% Anemia 8% Cystic hygroma 7% Monochorionic twinning 7% 6 most common account for 67% of all cases After GA Machin, in Potter’s pathology, 2^nd ed.
12	HF – Dx of 6 most frequent causes Cardiovascular Dissection Chromosomal Karyotype Thoracic U/S, XRay, gross Anemia Histo (↑ nucleated RBC) Cystic hygroma Histo: dilated lymphatics MZ twinning Gross, histo Dx from conventional modalities
13	HF – Causes & Associations (1644 cases) Foetal infection 5% Ascitis / peritonitis 2% Urinary tract malformation 2% Foetal hypomobility 1% Hepatic pathology 0,6% Genetic metabolic disease 0,4% Nephrosis < 0,1% Miscelaneous 2% Idiopathic 20% After GA Machin, in Potter’s pathology, 2^nd ed.
14	HF – Cardiac causes Cardiac malformation in 40% of HF (endocardial fibro- elastosis, AV valve stenosis directly cause heart failure)
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17	HF – Cardiac causes In cardiac malformation, most cases of HF 2^ry to arrhythmias
18	HF – Cardiac causes Malformations A/W arrhythmias: - 75% tachy (Tx: digoxin, verapamil) - 25% brady (R/O maternal SLE) Myocarditis: rare (Parvo B19 & other viruses)
19	HF – Cardiac causes
20	HF – Chromosomal causes 282 fetuses with HF: 52% Turner 25% +21 12% +18 4% +13 6% other chromosomal anomaly 40% Normal karyotype From Potter’s 2nd ed, courtesy Dr Machin
21	HF – Chromosomal causes Turner syndrome (45,X) ± always hydropic HF 2^ry to lymphatic dysplasia/hypoplasia Cardiac hypoplasia frequent ( > 90% lethality in 2^nd trimester)
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24	HF – Chromosomal causes Trisomies 21 & 18 : relatively commonly hydropic Triploid foetuses occasionally hydropic Trisomy 13 rarely hydropic Cause of hydrops in aneuploidies ??
25	HF – Thoracic causes Intrathoracic tumors: - ↑ Intrathoracic pressure - Obstruct systemic venous return
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27	HF – Thoracic causes Congenital cystic adenomatoid malformation (CCAM = CPAM: congenital pulmonary airway malformation) - Accounts for 30% of thoracic HF
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29	Monochorionic twinning Twin-Twin Transfusion syndrome: - donor & recipient twins both as likely to be hydropic HF results from: - anemia in donor twin - polycythemia (↑ viscosity) in recipient
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33	HF- Anemia Homozygous a-thalassemia accounts for 55% of all cases of HF in some parts of the world Since RhoGAM, non-immune causes are most frequent
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35	HF- Anemia Parvovirus B19 (Fifth disease) most frequent in Europe and Americas: - infects erythrocyte precursors → - ↓ erythrocyte production - haemolysis - infects myocardium (myocarditis)
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37	HF- Anemia Parvovirus B19: ~ 10% foetal mortality in infections < 20 weeks ~ 4% of all cases of HF - intrauterine transfusions in severe hydrops: 85% survival
38	HF- Anemia Placental oedema more severe when HF results from anaemia, compared with other causes
39	HF- Fetal infections Parvovirus TORCHS: Toxoplasmosis Others Rubella Cytomegalovirus Herpes Syphilis (rising)
40	Toxoplasmosis
41	HF – Abdominal causes Intraabdominal tumors: - ↑ intraabdominal pressure - Obstructs systemic venous return - inferior vena cava - umbilical vein
42	HF- Abdominal tumour Megacystis / prune belly syndrome: - posterior urethral valve - urethral atresia Multicystic / polycystic kidneys Congenital mesoblastic nephroma, Wilms & other tumours
43	HF – Hypomobility (all rare) Foetal akinesia (Pena-Shokeir) syndrome Neuromuscular pathology Potter sequence
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45	HF – Prenatal Investigations Detailed foetal and placental ultrasound Echocardiography Foetal karyotyping (amniocentesis, foetal blood sampling, or sampling of hygroma)
46	HF – Prenatal Investigations Foetal blood sampling for: - Haemoglobin (gene and/or protein) - Parvovirus B19 - Metabolic investigations - Serum protein levels - Viscosity studies
47	HF – Prenatal Investigations Maternal blood sampling for: - Kleihauer test (foetomaternal transfusion) - Blood group - Antibody screen (Rh, Lupus) - Serology (TORCHS screen) - Haemoglobinopathies - Red blood cell enzymopathies
48	HF – Autopsic Investigations Close collaboration with obstetrician and geneticist required Ascertain that all prenatal investigations have been performed Perform those that have not yet been done
49	HF – Autopsic Investigations Often clinically straightforward: - Cardiac malformation - Parvovirus, TORCHS - Haemoglobinopathy - Aneuploidy - Isoimmunization - Tumour, etc Corroborate Dx
50	When Dx not apparent: Full autopsy required Special attention to: - Foetal X-Rays - Heart - Metabolic diseases: - Histo: liver, adrenals, brain, muscle - Fibroblast culture for enzyme studies - Freeze (-80^oC, permanent reserve): liver (DNA), serum, effusions, muscle
51	When Dx not apparent: Special attention to lymphatic development: - Lymphocyte counts in free liquid: - ↑ in lymphatic vascular malformations - low in effusions Sample lymphatic vessels in hydropic skin : - hypoplastic, normal, or dilated? - immunohistochemistry for D2-40
52	When Dx not apparent: Lymphatic malformation Vs effusion - distinction is important : Lymphatic vascular malformation has low recurrence risk Effusions more likely to recur: - isoimmunization, metabolic diseases, etc.
53	When Dx not apparent: Special attention to: - Infectious agents: - Cultures (Syphilis, Toxo, viruses) - Histology for inclusions - Molecular identification (eg PCR)
54	HF – Treatment Anemia (including isoimmunization) : in utero blood transfusion Hypoproteinemia : in utero albumin transfusion Arrhythmias: antiarrhythmics
55	Hydrops & in utero surgery - Congenital cystic adenomatoid malformation of lung (CCAM) - Hydrothorax / chylothorax - Laryngeal stenosis / atresia - Heart block (medical Tx more common) - Sacrococcygeal teratoma - Twin-to-twin transfusion (TTT)
56	Hydrops foetalis Overlaps with: - Cystic hygroma - Hydrothorax - Pericardial effusions - Foetal ascites - Lymphatic obstruction / malformation
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58	Hydrops foetalis is the greatest challenge for foetopathologists Dx crucial for genetic counselling
59	"Dr Oligny gratefully acknowledges:" Dr Oligny gratefully acknowledges: - Dr Geoffrey A. Machin, “Hydrops, Cystic Hygroma, Hydrothorax, Pericardial effusions and Fetal ascites” from Potter’s Pathology of the Fetus, Infant and child, 2^nd ed., edited by Enid Gilbert-Barness, Raj P Kapur, Luc Laurier Oligny & Joseph R Seibert & Elsevier publishers