Transcript Hydorp fetalis

Hydorp fetalis
นพ.ปวริศร์ วาณิชยเศรษฐกุล
Hydrop fetalis
• Hydrops fetalis is a condition in the fetus
characterized by an abnormal collection of fluid with
at least two of the following:
– Edema
(fluid beneath the skin, more than 5 mm).
– Ascites
(fluid in abdomen)
– Pleural effusion
(fluid in the pleural cavity, the fluid-filled space that
surrounds the lungs)
– Pericardial effusion
(fluid in the pericardial sac, covering that surrounds the
heart)
Hydrop fetalis
• Hydrops fetalis is typically diagnosed during
ultrasound evaluation for other complaints
such as :
– Polyhydramnios
– Size greater than dates
– Fetal tachycardia
– Decreased fetal movement
– Abnormal serum screening
– Antenatal hemorrhage
Etiology
• Hydrops fetalis is found in about 1 per 2,000
births and is categorized as :
– Immune hydrops
– Nonimmune hydrops
Immune hydrops
• Accounts for 10-20%of cases
• Maternal antibodies against red-cells of the fetus
cross the placenta and coat fetal red cells which are
then destroyed (hemolysis) in the fetal spleen.
• The severe anemia leads to
• High-output congestive heart failure.
• Increased red blood cell production by the spleen and liver
leads to hepatic circulatory obstruction (portal
hypertension)
Immune hydrops
• Anti-D, anti-E, and antibodies directed against other
Rh antigens comprise the majority of antibodies
responsible for hemolytic disease of the newborn .
• However, there are numerous, less commonly
encountered, antibodies such as anti-K (Kell), anti-Fya
(Duffy) , and anti-Jka (Kidd) that may also cause hemolytic
disease of the newborn.
Non-immune hydrops
• Accounts for 80 -90% of cases
• Any other cause besides immune.
• In general nonimmune hydrops (NIH) is
caused by a failure of the interstitial fluid (the
liquid between the cells of the body) to return
into the venous system .
Non-immune hydrops
• This may due to:
– Cardiac failure
(High output failure from anemia, sacrococcygeal
teratoma, fetal adrenal neuroblastoma, etc.)
– Impaired venous return
(Metabolic disorders)
– Obstruction to normal lymphatic flow
(Thoracic malformations)
– Increased capillary permeability
– Decreased colloidal osmotic pressure
(Congential nephrosis)
Causes
• Causes can be grouped in 6 broad categories:
– Cardiovascular
– genetic abnormalities
– intrathoracic malformations
– hematological disorders
– infectious conditions
– idiopathic forms
Cardiac causes
• Structural anomalies
– Abnormalities of left ventricular outflow
•
•
•
•
•
•
•
•
•
•
Aortic valvular stenosis
Aortic valvular atresia
Coarctation of the aorta
Aortico-left ventricular tunnel
Atrioventricular canal
Left ventricular aneurysm
Truncus arteriosus
Hypoplastic left heart
Spongiosum heart
Endocardial fibroelastosis
Cardiac causes
• Structural anomalies (cont.)
– Abnormalities of right ventricular outflow
• Pulmonary valvular atresia or insufficiency
• Ebstein anomaly
Cardiac causes
• Structural anomalies (cont.)
– Other vascular malformations
•
•
•
•
•
•
•
•
•
•
•
Arteriovenous malformations
Diffuse hemangiomatosis
Placental hemangioma
Umbilical cord hemangioma
Hepatic hemangioendothelioma
Abdominal hemangioma
Pulmonary arteriovenous fistula
Cervical hemangioendothelioma
Paratracheal hemangioma
Cutaneous cavernous hemangioma
Arteriovenous malformations of the brain
Cardiac causes
• Nonstructural anomalies
– Obstruction of venous return
•
•
•
•
•
Superior or inferior vena cava occlusion
Absent ductus venosus
Umbilical cord torsion or varix
Intrathoracic or abdominal tumors or masses
Disorders of lymphatic drainage
Cardiac causes
• Nonstructural anomalies (cont.)
– Supraventricular tachycardia
– Congenital heart block
– Prenatal closure of the foramen ovale or ductus
arteriosus
– Myocarditis
– Idiopathic arterial calcification or hypercalcemia
– Intrapericardial teratoma
Hematologic causes
• Isoimmunization (hemolytic disease of the
newborn, erythroblastosis)
– Rh (most commonly D; also C, c, E, e)
– Kell (K, k, Kp, Js[B])
– ABO
– MNSs (M, to date)
– Duffy (Fyb )
Hematologic causes
• Other hemolytic disorders
– Glucose phosphate isomerase deficiency
(autosomal recessive)
– Pyruvate kinase deficiency (autosomal recessive)
– G-6-PD deficiency (X-linked dominant)
Hematologic causes
• Disorders of red cell production
– Congenital dyserythropoietic anemia types I and II
(autosomal dominant)
– Diamond-Blackfan syndrome (autosomal dominant)
– Lethal hereditary spherocytosis (spectrin synthesis defects)
(autosomal recessive)
– Congenital erythropoietic porphyria (Günther disease)
(autosomal recessive)
– Leukemia (usually associated with Down or Noonan
syndrome)
– Alpha-thalassemia (Bart hemoglobinopathy)
– Parvovirus B19 (B19V)
Hematologic causes
• Fetal hemorrhage
– Intracranial or intraventricular
– Hepatic laceration or subcapsular
– Placental subchorial
– Tumors (especially sacrococcygeal teratoma)
– Fetomaternal hemorrhage
– Twin-to-twin transfusion
– Isoimmune fetal thrombocytopenia
Infectious causes
•
•
•
•
•
•
•
•
•
•
•
•
B19V
Cytomegalovirus (CMV)
Syphilis
Herpes simplex
Toxoplasmosis
Hepatitis B
Adenovirus
Ureaplasma urealyticum
Coxsackievirus type B
Listeria monocytogenes
Enterovirus10
Lymphocytic choriomeningitis virus (LCMV)11
Inborn errors of metabolism
– Glycogen-storage disease, type IV
– Lysosomal storage diseases
• Gaucher disease, type II (glucocerebroside deficiency)
• Morquio disease (mucopolysaccharidosis, type IV-A)
• Hurler syndrome (mucopolysaccharidosis, type 1H; alpha1–
iduronidase deficiency)
• Sly syndrome (mucopolysaccharidosis, type VII; betaglucuronidase deficiency
• Farber disease (disseminated lipogranulomatosis)
• GM1 gangliosidosis, type I (beta-galactosidase deficiency)
• Mucolipidosis I
• I-cell disease (mucolipidosis II)
• Niemann-Pick disease, type C
Inborn errors of metabolism
– Salla disease (infantile sialic acid storage disorder
[ISSD] or sialic acid storage disease,
neuroaminidase deficiency)
– Hypothyroidism and hyperthyroidism
– Carnitine deficiency
Genetic syndromes
–
–
–
–
–
–
–
–
–
–
Achondrogenesis, type IB (Parenti-Fraccaro syndrome)
Achondrogenesis, type II (Langer-Saldino syndrome)
Arthrogryposis multiplex congenita, Toriello-Bauserman type
Arthrogryposis multiplex congenita, with congenital muscular
dystrophy
Beemer-Langer (familial short-rib syndrome)
Blomstrand chondrodysplasia
Caffey disease (infantile cortical hyperostosis; uncertain inheritance)
Coffin-Lowry syndrome (X-linked dominant)
Cumming syndrome
Eagle-Barrett syndrome (prune-belly syndrome; since 97% males,
probably X-linked)
Genetic syndromes
–
–
–
–
–
–
–
–
–
–
–
Familial perinatal hemochromatosis
Fraser syndrome
Fryns syndrome
Greenberg dysplasia
Lethal congenital contracture syndrome
Lethal multiple pterygium syndrome (excess of males, so probably Xlinked)
Lethal short-limbed dwarfism
McKusick-Kaufman syndrome
Myotonic dystrophy (autosomal dominant)
Nemaline myopathy with fetal akinesia sequence
Noonan syndrome (autosomal dominant with variable penetrance)
Genetic syndromes
– Perlman/familial nephroblastomatosis syndrome (inheritance
uncertain)
– Simpson-Golabi-Behmel syndrome (X-linked [Xp22 or Xp26])
– Sjögren syndrome A (uncertain inheritance)
– Smith-Lemli-Opitz syndrome
– Tuberous sclerosis (autosomal dominant)
– Yellow nail dystrophy with lymphedema syndrome (autosomal
dominant
Chromosomal syndromes
–
–
–
–
–
–
–
–
–
–
–
Beckwith-Wiedemann syndrome (trisomy 11p15)
Cri-du-chat syndrome (chromosomes 4 and 5)
Dehydrated hereditary stomatocytosis (16q23-qter)
Opitz G syndrome (5p duplication)
Pallister-Killian syndrome (isochrome 12p mosaicism)
Trisomy 10, mosaic
Trisomy 13
Trisomy 15
Trisomy 18
Trisomy 21 (Down syndrome)
Turner syndrome (45, X)
Tumor or mass causes
• Intrathoracic tumors or masses
– Pericardial teratoma
– Rhabdomyoma
– Mediastinal teratoma
– Cervical vascular hamartoma
– Pulmonary fibrosarcoma
– Leiomyosarcoma
– Pulmonary mesenchymal malformation
– Lymphangiectasia
Tumor or mass causes
• Intrathoracic tumors or masses (cont.)
– Bronchopulmonary sequestration
– Cystic adenomatoid malformation of the lung
– Upper airway atresia or obstruction (laryngeal or
tracheal)
– Diaphragmatic hernia
– Eventration of the diaphragm
Tumor or mass causes
• Abdominal tumors or masses
– Metabolic nephroma
– Polycystic kidneys
– Neuroblastoma
– Hepatic mesenchymal hamartoma
– Hepatoblastoma
– Ovarian cyst
Tumor or mass causes
• Other conditions
– Placental choriocarcinoma
– Placental chorangioma
– Cystic hygroma
– Intussusception
– Meconium peritonitis
– Intracranial teratoma
– Sacrococcygeal teratoma
Pathophysiology
• In immune hydrops, excessive and prolonged
hemolysis causes anemia, which in turn
stimulates marked marrow erythroid
hyperplasia
• It also stimulates extramedullary
hematopoiesis in the spleen and liver with
eventual hepatic dysfunction
Pathophysiology
• The precise pathophysiology of hydrops
remains unknown
• Theories includes
– Heart failure form profound anemia and hypoxia
– Portal hypertension due to hepatic parenchymal
disruption caused by extramedullary hemopoiesis
– Decreased colloid oncotic pressure resulting from
liver dysfunction and hypopreteinemia
Pathophysiology
• The degree and duration of anemia is the
major factor causing and influencing the
severity of ascites
• Secondary factors include hypoproteinemia
caused by liver dysfunction and capillary
endothelial leakage resulting from tissue
hypoxia, both of these lead to protein loss and
decreased colloid oncotic pressure
Pathophysiology
Severe anemia
Hepatic extramedullary hematopoeisis
Decreased production of plasma proteins
Decreased plasma COP
Pathophysiology
Congestive heart failure
Increased central venous pressure
Increased capillary hydrostatic pressure
Pathophysiology
Severe tissue hypoxia
Endothelial cell damage
Capillary leak of fluid & protein
Decreased
COP
Increased
CVP
Increased
fluid efflux
from intravascular
space
Capillary
leak
Pathophysiology
• There may be cardiac enlargement and
pulmonary hemmorrhage
• Fluid collects in the fetal thorax, abdominal
cavity, or skin
• The placenta is markedly edematous, enlarge,
and boggy. It contains large, prominent
cotyledons and edematous villi
Pathophysiology
• Pleural effusions may be so severe as to
restrict lung development, which causes
pulmonary compromise after birth
• Ascites, hepatomegaly, and splenomegaly may
lead to severe labor dystocia
• Severe hydropic changes are easily seen with
sonography
Pathophysiology
• Fetuses with hydrops may die in utero from
profound anemia and circulatory failure
• One sign of severe anemia and impending
death is the sinusoidal fetal heart rate pattern
• Hydrops placental changes leading to
placentomegaly can cause preeclampsia
Pathophysiology
• The liveborn hydropic infant appears pale,
edematous, and limp at birth and usually
requires resuscitation
• The spleen and liver are enlarged, and there
may be widespread ecchymosis or scattered
petechiae
• Dyspnea and circulatory collapse are common
Non-immune Hydrops Fetalis
Placenta of Hydropic Pregnancy
Placenta of Normal Pregnancy
Associated complication
•
•
•
•
•
•
•
Polyhydramnios
Placenta abruption
Uterine atony
Pre-mature labour
Hydropic, theickened placenta (> 6 cm)
Retained placenta
Preeclapsia
Associated complication
• In an attempt to compensate for the fetal hypoxia,
placenta increases in size and sometimes also
penetrate deeper into the myometrium. Thus causes
the morbid adherence of placenta and can cause the
problems for third stage of labor necessitating the
manual removal of Placenta.
Associated complication
• Mirror syndrome
• The mother develops preeclampsia along with
severe edema that is similar to that of the fetus
• Caused by vascular changes in the swollen,
hydropic placenta, this likely related to
antiangiopenic factors produced by
hyperplacentosis
History
• A history suggesting the presence of any of
the following factors should trigger an
extensive diagnostic study for hydrops fetalis:
• Maternal history
– Rh negative (d;d) blood type
– Known presence of isoimmune blood group
antibodies
– Prior administration of blood products
– Risks of illicit drug use
History
• Maternal history (cont.)
– Collagen-vascular disease
– Thyroid disease or diabetes
– Organ transplant (liver, kidney)
– Blunt abdominal trauma (abuse, auto accident)
– Coagulopathy
– Use of indomethacin, sodium diclofenac, or
potentially teratogenic drugs during pregnancy
– Younger (<16 y) or older (>35 y) maternal age
History
• Maternal history (cont.)
– Risk factors for sexually transmitted diseases
– Hemoglobinopathy (especially with Asian or
Mediterranean ethnicity)
– Occupational exposure to infants or young
children
– Pet cat
– Current or recent community epidemic of viral
illness
History
• Family history
– Jaundice in other family members or in previous
child
– Family history of twinning (specifically,
monozygotic)
– Family history of genetic disorders, chromosomal
abnormalities, or metabolic diseases
– Congenital malformation in previous child
– Previous fetal death
History
• Family history (cont.)
– Hydramnios in earlier pregnancies
– Prior hydrops fetalis
– Previous fetomaternal transfusion
– Congenital heart disease in previous child
Physical
• The presence of any of the following maternal
or fetal physical findings should prompt
further diagnostic evaluation:
– Twinning
– Hydramnios
– Exanthem or other evidence of intercurrent viral
illness
– Herpetic lesion or chancre
– Decrease in fetal movements
Laboratory Studies
• Diagnostic studies may be considered best by
temporal grouping (ie, fetal, maternal,
placental, neonatal, postmortem).
• Assessments generally proceed from low-risk
noninvasive tests to higher-risk invasive
techniques as required for precise and
complete diagnosis to properly manage the
individual pregnancy.
Maternal laboratory studies
• Assessment of maternal blood type (red cells)
and antibody screen (identification, and
quantitation when indicated, of maternal
plasma antibodies)
• Qualitative and quantitative estimates of the
proportion of red cells containing fetal
hemoglobin in the maternal circulation
Maternal laboratory studies
• The search for maternal-fetal infection
– Syphilis serology
• Antibody screens for common fetal infections
– toxoplasmosis, other infections, rubella, CMV
infection, and herpes simplex [TORCH]
• Hemoglobin electrophoresis for alphathalassemia heterozygosity
Maternal laboratory studies
• Maternal serum screening tests
– AFP levels
– Unconjugated estriol (uE3)
– Human chorionic gonadotropin levels
– inhibin-A levels
– Maternal serum IgG placental alkaline
phosphatase levels
Laboratory Studies
• Ultrasound - a diagnostic imaging technique
which uses high-frequency sound waves and a
computer to create images of blood vessels,
tissues, and organs. Ultrasounds are used to
view internal organs as they function, and to
assess blood flow through various vessels.
Laboratory Studies
• Level II sonogram with Doppler measurement
of the peak systolic velocity (PSV) in the fetal
middle cerebral artery (MCA) to assess for
fetal anemia. If there is evidence for anemia or
equivocal result obtain:
• Maternal blood counts and hemoglobin electrophoresis
(with hemoglobin DNA analysis), Kleihauer-Betke stain,
glucose 6-phosphate dehydrohgenase deficiency
screen.
• Maternal TORCH titers, RPR, listeria, parvovirus B19,
coxsackie, adenovirus, and varicella IgG and IgM, as
indicated.
Laboratory Studies
• Fetal echocardiogram
– Consider fetal heart rate monitoring for 12 to 24
hours if fetal arrhythmia is suspected.
• Amniocentesis for fetal karyotype and PCR
(polymerase chain reaction) for infections
• Fetal percutaneous blood sampling for same and in
addition fetal liver function; and metabolic testing if
indicated.
Laboratory Studies
• In the presence of a family history of an
inheritable metabolic disorder or recurrent
nonimmune hydrops test for :
• Storage disorders such as Gaucher’s, gangliosidosis,
sialidosis, beta-glucuronidase deficiency, and
mucopolysaccharidosis
– Enzyme analysis and carrier testing in parents and/or analysis
of fetal or neonatal blood or urine.
– Histological examination of fetal tissues.
• Maternal thyroid antibodies
Normal
four
Chamber
Cardiac
View
Pericardial Effusion
Heart
Body wall
edema in a
hydropic
fetus
www.thefetus.net
Fetal Ascites
Fetal Ascites
Fetal Ascites
© www.thefetus.net
©
©
©
Hydrocele can
be an early
manifestation
in hydrops
Soft Tissue
shadow and
pleural
effusion in
hydropic
neonate
Treatment
Cause
Treatment
Fetal anemia
Fetal blood sampling followed by in utero
transfusion
Fetal Arrhythmia
Medications such as digoxin, sotalol,
propanolol , flecainide, amiodarone
Intrinsic thoracic malformations
Thoracentesis or thoracoamniotic shunt
for pleural effusions in select cases
Twin to twin transfusion
Fetoscopic laser ablation of
communicating vessels
Syphilis
Penicillin
Treatment
• Transplacental drug therapy
– Drugs are given to the mother and are passed to the
fetus through the placenta
– The main conditions which respond to this approach
are fetal dysrrhythmias (SVT)
– Once the type of dysrrhythmia is identified, antiarrhythmic agent is given to the mother, with careful
monitoring of her ECG & blood levels.
– Drugs: Digoxin, Verapamil, Amiadarone, Flecanide.
– Careful Maternal & Fetal Monitoring is Essential
Treatment
• Direct fetal drug therapy
– Maternal administration of drugs may be
ineffective due to:
• Maternal Metabolism
• Maternal Side Effects
• Variable Passage Across Placenta
– Routes for direct fetal drug therapy:
• Intraperitoneal
• Intramuscular
• Intravascular
Treatment
• Invasive Procedures
– Blood / Albumin Transfusion to Fetus
• Intraperitoneal
• Intravenous
– Umbilical Vein
– Hepatic Vein
Treatment
• Invasive Procedures
– Drainage Procedures:
• Large Pleural Effusions
• Ascities
• All invasive procedures carry an inherent
increased risk of fetal demise or pre-mature
labor.
Counseling
• Long term prognosis depends on underlying
cause and severity of the heart failure.
• If the cause of NIH cannot be determined, the
perinatal mortality is approximately 50%
• Prognosis is much poorer if diagnosed at less
than 24 weeks , pleural effusion is present, or
structural abnormalities are present .
– Pulmonary hypoplasia is a common cause of death in
neonates with plerual effusions.
– Fetal hydrops associated with a structural heart defect
is associated with an almost 100% mortality rate.
Counseling
• If early in pregnancy (less than 24 weeks) with
no treatable cause the option of termination
may be a consideration.
• Recurrence is uncommon unless related to
blood group incompatibility (isoimmunization)
or inheritable disorder.
Antepartum
• Follow up of the fetus will depend on the
gestational age of the fetus, and the mother's
wishes regarding intervention.
• If treatment has been successful or hydrops is
resolving spontaneously, the fetus may be
followed with repeat sonograms every 1 to 2
weeks and antenatal testing.
– Patients treated for immune hydrops are
usually delivered at 37 weeks' or when fetal lung
maturity has been confirmed.
Antepartum
• Consultation with the neonatologist may help
to decide when it is appropriate to proceed
with preterm delivery for possible postnatal
treatment .
• The mother should be evaluated frequently
for signs of "mirror" syndrome.
Delivery
• The fetus should be delivered at tertiary care
center with neonatologists and other
appropriate specialists.
• There is no evidence that delivery by cesarean
section has a marked effect on outcome.
• Cord blood should be obtained at delivery for
hemoglobin concentration and direct Coombs
testing
Delivery
• A postmortem evaluation should be
performed in all cases of hydrops that result in
neonatal death. One study showed that a
combined approach of a thorough antenatal
assessment and autopsy may be more likely to
determine the cause of non-immune hydrops .
A hydropic neonate under extensive
Thank you for your attention