Fetal Hydrops

Fetal hydrops (hydrops fetalis) is abnormal fluid accumulation in at least two fetal compartments: ascites, pleural effusion, pericardial effusion or skin oedema (more than 5 mm), often with placental oedema (thickness above 4 cm) and polyhydramnios. Incidence is about 1 in 1,700 to 3,000 pregnancies. About 90% is non-immune, and under 10% is immune (red cell alloimmunisation, now rare with anti-D prophylaxis).

The mechanism is an imbalance between interstitial fluid formation and lymphatic return: heart failure with raised central venous pressure, reduced oncotic pressure, increased capillary permeability and lymphatic obstruction or dysfunction. Overall survival is about 20 to 40% for non-immune hydrops, and up to 80% after treatment for immune hydrops.

Causes of non-immune hydrops by frequency:

• Cardiovascular (20 to 25%): structural heart disease (hypoplastic left heart, atrioventricular septal defect, Ebstein anomaly), arrhythmias (supraventricular tachycardia, atrial flutter, complete heart block, long QT syndrome), cardiomyopathy
• Chromosomal and genetic (10 to 30%): Turner syndrome, trisomies 21, 18 and 13, Noonan syndrome and other RASopathies, skeletal dysplasias, lysosomal storage diseases, inborn errors of metabolism
• Haematological (about 10%): alpha thalassaemia major, fetomaternal haemorrhage, G6PD deficiency, red cell membrane defects, Diamond-Blackfan anaemia
• Infections (5 to 10%): parvovirus B19, CMV, toxoplasmosis, syphilis, Chagas disease, Zika
• Thoracic malformations (5 to 10%): congenital pulmonary airway malformation, diaphragmatic hernia, bronchopulmonary sequestration, chylothorax
• Twin related (5 to 10%): twin-to-twin transfusion, twin reversed arterial perfusion, twin anaemia polycythaemia sequence
• Lymphatic dysplasia, fetal tumours (sacrococcygeal teratoma, neuroblastoma), chorioangioma, urinary tract anomalies; and idiopathic (15 to 25%)

• Maternal: polyhydramnios (about 50%), rapid uterine growth, reduced fetal movements, and mirror syndrome (maternal oedema, hypertension, proteinuria and haemodilution in about 20%)
• Fetal: ascites, pleural and pericardial effusions, skin and scalp oedema, cardiomegaly, hepatosplenomegaly, thick placenta
• Neonatal: hydrops at birth with respiratory failure from pulmonary hypoplasia, needing immediate resuscitation with thoracentesis and paracentesis

• A systematic workup is required in every case:
  1. Maternal history: infection, diabetes, medications, family history, consanguinity, travel and ethnicity (thalassaemia)
  2. Maternal blood: group and antibody screen, full blood count, Kleihauer-Betke test, haemoglobin electrophoresis, parvovirus B19, CMV, toxoplasma, syphilis, rubella and herpes serology, G6PD, glucose or HbA1c, anti-Ro and anti-La
  3. Detailed ultrasound and fetal echocardiography (structural heart disease, supraventricular tachycardia, complete heart block), MCA-PSV Doppler for anaemia, assessment for lung masses, diaphragmatic hernia, sacrococcygeal teratoma, thoracic and abdominal anomalies, and twin disease; fetal MRI where needed
  4. Invasive testing: amniocentesis for karyotype, chromosomal microarray and exome sequencing, infection PCR, lysosomal enzymes and metabolic tests; cordocentesis for haemoglobin and blood film
  5. Postnatal or postmortem: placental pathology, autopsy and genetic testing

• Treat the cause when possible:
  • Anaemia (alloimmunisation, parvovirus, fetomaternal haemorrhage): intrauterine transfusion
  • Fetal tachyarrhythmia: maternal digoxin 0.25 to 0.5 mg orally three times daily, flecainide 100 mg twice daily or sotalol 80 to 160 mg twice daily, with amiodarone third line
  • Immune mediated heart block: dexamethasone 4 mg daily (limited evidence)
  • Large pleural effusion or macrocystic lung lesion: thoracoamniotic shunt
  • Microcystic lung lesion: maternal betamethasone 12 mg IM, two doses 24 hours apart
  • Twin-to-twin transfusion or twin reversed arterial perfusion: fetoscopic laser or cord occlusion
  • Fetal tumours: ablation or resection
  • Syphilis: benzathine penicillin G 2.4 million units IM, with Jarisch-Herxheimer precautions

• Drainage of large compressive effusions, though they often recur
• Maternal monitoring for mirror syndrome and pre-eclampsia (blood pressure, proteinuria, oedema, liver and renal function); delivery treats severe mirror syndrome
• Counsel about prognosis, which depends on cause and gestation at onset, about termination options, and about possible fetal demise
• Delivery in a tertiary centre with neonatal intensive care, usually at 34 to 37 weeks if stable (earlier for deterioration after 32 to 34 weeks), with steroids for lung maturity; caesarean for fetal distress
• Neonatal care: airway control, thoracentesis or paracentesis, ventilation, vascular access, and diagnostics (karyotype, metabolic and genetic tests)
• Counsel on recurrence once the cause is known (25 to 50% for genetic causes)