Purpose and Goal: CNEP # 2044

  • Describe the characteristics of nonimmune hydrops fetalis.
  • Identify at least two strategies for the treatment of nonimmune hydrops fetalis.

None of the planners, faculty or content specialists has any conflict of interest or will be presenting any off-label product use. This presentation has no commercial support or sponsorship, nor is it co-sponsored.

Requirements for Successful Completion

  • Successfully complete the post-test.
  • Complete the evaluation form.

Date

  • November 2015 – November 2017

Learning Objectives

  • Describe the etiology of nonimmune hydrops fetalis.
  • Describe the clinical presentation of nonimmune hydrops fetalis.
  • Identify at least two treatment strategies for the care of nonimmune hydrops fetalis.

Introduction

  • Hydrops fetalis was first recognized in 1932.
  • It is a rare, severe, and frequently fatal disorder.
  • Historically it was related to Rh isoimmunization of the fetus.
  • The development of Rh immune globulin (RhoGam) dramatically decreased the incidence of Rh associated hydrops fetalis.
  • Nonimmune hydrops fetalis now accounts for 90% of all hydrops.
  • Nonimmune hydrops fetalis is also known as NIHF.

Definition and Incidence

  • Hydrops fetalis is a condition of excess fluid accumulation.
  • It is characterized by two or more abnormal fetal fluid collections.
  • NIHF occurs in every 1/1500 to 1/4000 births.
  • Chromosomal abnormalities are the most common cause.
  • The mortality rate for fetuses diagnosed with NIHF is 50–80%.
  • The mortality rate for infants born with NIHF is 50%.

Etiologies of NIHF

  • More than 80 conditions are known to cause NIHF.
  • Etiologies include:
    • Cardiovascular abnormalities
    • Placental malformations
    • Hematologic problems
    • Congenital infections
    • Non-cardiac congenital abnormalities
    • Chromosomal abnormalities
    • Genetic syndromes
    • Miscellaneous or idiopathic causes
     

Cardiovascular Abnormalities

  • Congenital heart malformations
    • Atrioventricular septal defects
    • Hypoplastic left and right heart
    • Tetralogy of Fallot
    • Ebstein’s anomaly
    • Truncus arteriosis
     
  • Fetal arrhythmias
    • Atrial flutter
    • Long QT interval
    • Supraventricular tachycardia
    • Bradyarrythmias (heart block)
    • Wolff-Parkinson-White Syndrome
     
  • Premature closure of the foramen ovale
  • Premature closure of the ductus arteriosis
  • Arteriovenous malformations
  • Cardiac or vascular hemangiomas or tumors

Placental Malformations

  • Acardiac twin
  • Twin-to-twin transfusion syndrome

Hematological Problems

  • Hemolytic anemia
  • Alpha-thalassemia
  • Fetomaternal transfusion
  • In utero hemorrhage
  • Red cell enzyme deficiencies
  • Pyruvate kinase deficiency

Congenital Infections

  • Parvovirus
  • Cytomegalovirus
  • Toxoplasmosis
  • Herpes Simplex
  • Syphilis
  • Rubella
  • Coxsackievirus
  • Leptospirosis
  • Listeria

Non-Cardiac Congenital Abnormalities

  • Thoracic abnormalities
    • Diaphragmatic hernia
    • Cystic adenomatoid mass
    • Pulmonary sequestration
     
  • Lymphatic disorders
    • Congenital chylothorax
    • Cystic hygromas
     
  • Neurological disorders
    • Fetal intracranial hemorrhage
    • Fetal hydrocephalus
    • Arnold-Chiari malformations
     
  • Gastrointestinal malformations
    • Volvulus
    • Malrotation
    • Intussusception
    • Meconium ileus
     
  • Genitourinary malformations
    • Polycystic kidney disease
    • Renal vein thrombosis
    • Posterior urethral valves
    • Prune belly syndrome
     

Chromosomal Abnormalities

  • Trisomy 21
  • Trisomy 18
  • Trisomy 13
  • Monosomy 45, X
  • Duplicated 11p

Genetic Syndromes

  • Achondrogenesis
  • Chondrodysplasia
  • Arthrogryposis
  • Inborn errors of metabolism
  • Myotonic dystrophy
  • Noonan’s syndrome
  • Osteogenesis imperfecta
  • Tuberous sclerosis

Idiopathic Causes

  • Miscellaneous causes of NIHF include:
    • Fetal tumors
    • Intrauterine growth restriction
    • Fetal hypomotility
     
  • The etiology of 50–70% of NIHF cannot be determined.
  • NIHF not associated with a specific cause is called idiopathic.

Pathophysiology

  • The primary factor in the development of NIHF is abnormal fluid movement between fetal plasma and tissues.
  • Fluid accumulates in fetal tissues or body cavities.
    • Production of fluid exceeds rate of reabsorption.
    • Production of fluid exceeds rate of removal by capillary and lymphatic systems.
     
  • Four theories have been identified as possible causes:
    • Increase in hydrostatic capillary pressure
    • Reduction in plasma osmotic pressure
    • Obstruction of lymphatic flow
    • Damage to peripheral capillary integrity
     

Increase in Hydrostatic Capillary Pressure

  • Hydrostatic pressure within capillaries rises:
    • In response to increased central venous pressure
    • In response to increased arterial pressure
    • In response to obstructed venous drainage
     
  • Results from primary or secondary heart failure.
  • Results from obstruction of venous return.
  • Increased capillary pressure causes excessive filtration of fluid into the interstitial tissues.

Reduction in Plasma Osmotic Pressure

  • Plasma or intravascular pressure is decreased:
    • In response to an inadequate volume of fluid
    • In response to a loss of filtration pressure
    • In response to decreased fluid reabsorption
     
  • Results from decreased albumin production.
  • Results from increased albumin loss:
    • Capillary leak
    • Chylothorax
    • Nephrotic syndrome
     
  • Decreased plasma or intravascular pressure causes significant loss of fluid volume into interstitial spaces.

Obstruction of Lymphatic Flow

  • Lymphatic flow is obstructed:
    • In response to external compression
    • In response to elevated central venous pressure
    • In response to reduced lymph flow
     
  • Results from congenital malformations or masses.
  • Results from congestive heart failure.
  • Results from fetal hypomotility.
  • Obstruction or reduction of lymph flow causes an ineffective clearance of excess interstitial fluid.

Damage to Peripheral Capillary Integrity

  • Peripheral capillary integrity is damaged:
    • In response to hypoxic damage to cell walls
    • In response to inflammatory mediator release
    • In response to endotoxin release due to sepsis
     
  • Results from fetal anemia.
  • Results from uteroplacental insufficiency.
  • Results from maternal infectious disease.
  • Damage to capillaries increases capillary wall permeability allowing excess fluid to leak into interstitial spaces.

Clinical Presentation and Diagnosis

 

  • A fetus or infant with NIHF presents with abnormal fluid accumulations.
  • Diagnosis of NIHF is based on ultrasound.
  • It is identified by the presence of two or more findings:
    • Ascites
    • Pleural effusions
    • Pericardial effusions
    • Skin edema
    • Polyhydramnios
    • Placentomegaly
     
  • Uterine size may be large for dates.
  • Decreased fetal movement may be present.

 

Laboratory Evaluation

 

  • Maternal evaluation
    • CBC with RBC indices
    • Hemoglobin electrophoresis
    • Blood type and antibody screen
    • Serologies
      • Cytomegalovirus
      • Toxoplasmosis
      • Rubella
      • Parvovirus
      • Syphilis
       
    • Kleihauer-Betke acid elution
     
  • Fetal (or infant) evaluation
    • CBC with RBC indices
    • Hemoglobin electrophoresis
    • Blood type and antibody screen
    • TORCH studies via PCR
    • Parvovirus B19 via PCR
    • Karyotype
    • Genetic microarray
    • Metabolic evaluation
     

 

Prognosis and Outcome

 

  • NIHF is associated with a high mortality rate.
    • Overall 50–80% rate of mortality
     
  • Prognosis depends on the underlying etiology.
  • The earlier NIHF occurs, the poorer the outcome.
  • Pleural effusions and polydramnios <20 weeks
    • Poor outcomes
    • Pulmonary hypoplasia
    • Increased preterm labor
     
  • Risk or recurrence depends on underlying etiology.

 

Treatment and Clinical Management

 

  • Prenatal diagnosis allows adequate preparation.
    • Maternal–Fetal Medicine consultation
    • Neonatology consultation
    • Fetal echocardiogram if needed
    • Intrauterine therapies
    • Complex resuscitation planning
    • Improved infant outcomes
     
  • Initial infant management is aimed at decreasing effects of excess interstitial fluid on body function.
    • Supporting adequate ventilation
    • Supporting adequate oxygenation
    • Supporting adequate perfusion
     
  • Infants often present in respiratory failure.
  • Infants often present in hypovolemic shock.
  • Pleural effusions require drainage with chest tubes.
  • Ascites requires drainage via abdominal taps or drains.
  • Umbilical catheters should be placed.
  • Fluid resuscitation is critical.
    • Intravascular volume is depleted.
    • Immediate normal saline replacement
    • Inotropic and vasopressor support
     
  • Blood or exchange transfusions may be required.
    • If severe anemia is suspected
    • O-negative unmatched blood
     
  • Hyperbilirubinemia is common with severe anemia.
    • In utero anemia leads to massive RBC formation
    • Bilirubin levels rise as RBCs are destroyed
    • In utero, maternal circulation manages RBCs
    • At birth, hyperbilirubinemia occurs within 60 minutes
     
  • Severe hypoglycemia is common.
    • Occurs as soon as 15 minutes
    • Aggressive dextrose support may be needed
     
  • Fluids and medications should be based on dry weight.
    • Estimated at 50th percentile for gestational age
     
  • An immediate echocardiogram may be required.
  • Comfort measures are essential.
  • Pain management is also essential.
  • Parent and family support should be a priority:
    • To support family coping mechanisms
    • To facilitate parent-infant bonding
     

 

Intrauterine Therapies

 

  • Several fetal therapies have been developed.
    • Anemia – fetal intravascular blood transfusions
    • Arrhythmias – transplacental antiarrhythmics or pacing
    • Cardiac defects – in utero fetal heart surgery
    • Hypoalbuminemia – fetal intravascular albumin transfusions
    • Infection – transplacental antiviral or antibiotic therapy
    • Obstructive uropathy – fetal bladder shunt or ex utero surgery
    • Pleural effusions – fetal intrathoracic decompression
    • Pulmonary cysts – fetal intrathoracic shunt or ex utero surgery
    • Thoracic congenital anomaly – fetal ex utero surgery
      • Ex utero intrapartum treatment
      • Also known as EXIT procedure
       
    • Tumors – fetal in utero resection
    • Twin-to-twin transfusion syndrome
      • Serial amnioreduction
      • Fetal septostomy
      • Fetoscopic laser photocoagulation of vascular anastomoses
       
     

 

Summary

 

  • NIHF is a symptom of underlying disease.
  • Accurate diagnosis of the etiology is critical.
  • Specific treatment options are directed at correcting the underlying pathophysiology involved.
  • Prognosis remains poor despite new treatments.
  • Poor neurodevelopmental outcome is common.
  • Surviving infants should be followed closely.
    • Early developmental support may be beneficial.
    • Early intervention can support developmental delays.
     

 

References

 

  1. Lockwood, C.J & Julien, S. 2014. Nonimmune Hydrops Fetalis. Up-To-Date.
  2. Philips. J.B. 2013. Etiology, Clinical Manifestations, Diagnosis and Evaluation of Pleural Effusions in the Neonate. Up-To-Date.
  3. Speer, M.E. 2012. Postnatal Care of Hydrops Fetalis. Up-To-Date.
  4. Randenberg, A.L. 2010. Nonimune Hydrops Fetalis Part I: Etiology and Pathophysiology. Neonatal Network, 29 (5), p. 281-295.
  5. Randenberg, A.L. 2010. Nonimmune Hydrops Fetalis Part II: Does Etiology Influence Mortality? Neonatal Network, 29 (6), p. 367-380.
  6. Murphy, J.H. 2004. Nonimmune Hydrops Fetalis. NeoReviews, 5 (1), p. e5-e14.
  7. White, L.E. 1999. Nonimmune Hydrops Fetalis. Neonatal Network, 18 (4), p. 25-30.

 

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