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Hydrops fetalis

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Overview

Immune hydrops fetalis is caused by red blood cell alloimmunisation haemolytic disease. All other causes are described as non-immune hydrops fetalis (NIHF). Hydrops is a symptom of a wide range of conditions which have resulted in an imbalance in fetal fluid between the vascular and interstitial space.1

Diagnostic criteria are fluid in at least two body cavities (pleural space, pericardial space, peritoneal space, skin or placental enlargement). The prognosis depends on associated prematurity, the underlying cause, the severity of any associated pulmonary hypoplasia and the severity of the ongoing post-natal fluid accumulation (with problems of infection and malnutrition).2

Studies have found a perinatal mortality rate of up to 57%.3,4,5 Mortality and morbidity appears dependent on cause and gestational age at diagnosis. There is high risk for premature delivery. Neonatal mortality remains high at 35% with an overall mortality of 43% at one year. There is one retrospective review reporting normal developmental outcome in half of 56 cases followed-up at one year and is more likely when NIHF is associated with tachyarrhythmia, congenital chylothorax, meconium peritonitis and parvovirus.4

Resuscitation

Any baby known to have NIHF should be delivered at a tertiary centre. Find out about the size of pleural effusions and severity of the hydrops from obstetric staff before delivery. It is important to prepare equipment before delivery. Resuscitation and stabilisation is often difficult. The level III specialist should be informed and may well need to attend the delivery. A senior neonatal nurse should also attend. It may be necessary to drain pleural effusions or ascites in the delivery room, at the same time as resuscitating the baby.

Associations with Non-Immune Hydrops

There is a long list of possible causes of NIHF - see table below.

Half of the reported causes of NIHF comprise of cardiovascular anomalies/arrhythmias (21.4%), chromosomal abnormalities (12.5%) or are idiopathic - unexplained (18.2%).6

The images to the right demonstrate an infant with hydrops - in this case bilateral pleural effusions, ascites and oedema. The cause of this baby's hydrops was thought to be a congenital chylothorax. Baby was managed with dietary maniuplation using Monogen, without re-accumulation of pleural effusions. Baby was changed to breast feeding uneventfully at three weeks of age.

Congenital Chylothorax

Lymphatic dysplasia, predominantly seen as chylothorax, contributes up to 15% of NIHF cases.6,7 The pleural fluid is serous until milk feeding begins and it turns chylous. Diagnosis is based on a high lymphocyte presence and protein concentration in the pleural fluid, in addition triglyceride and lipoproteins are present with feeding.

There is a risk of loss of anticoagulant factors and immunoglobulins along with malnutrition. Medium chain triglycerides are absorbed directly into the portal vein, bypassing lymphatic drainage. Enteral feeds are usually started with an MCT based formula while waiting for the chylous leakage to improve. The usual clinical course may take longer than 4 weeks to resolve. Note - MCT formulas do not contain essential fatty acids and may need supplementing if used for an extended period.

Evidence for the use of octreotide is based on collective case reports with a range of success.8 There is no standard treatment recommendation for the use of octreotide although it appears to be safe in neonates.9-12

Pathophysiological mechanism of NIHF

(Adapted from reference Bellini 2012)

Pathophysiology

Investigations

Many of these may have been done antenatally. Particular clinical findings may indicate other investigations for aetiology. Target investigations at clinical features. Collect cord blood EDTA and clotted samples.

Anaemia  Evidence of fetal anaemia.
Maternal blood group and antibodies.
Baby blood group and Coombs.
Early haemoglobin/PCV.
Maternal Kleihauer
Biochemistry  Liver function including albumin/protein
Renal function 
Cardiac rhythm in utero  Evidence from ultrasound scans and CTGs.
Post-natal ECG + monitoring 
Fluid examination  Protein and albumin
Cell cytology (commonly finding marked lymphocytosis).
Triglyceride levels after feeding started 
Placenta  Macroscopic examination, histology and Toxoplasma PCR 
Ultrasound  Head, heart, chest, abdomen 
X-rays  Chest, abdomen and long bones (skeletal abnormalities and congenital infection).
Further CT/MRI as indicated by clinical course and other results. 
Genetics   SNP-Array if not performed antenatally +/- targeted gene testing (Discuss with Genetic services).
DNA sample sent for storage
Consider a skeletal survey
Hb electrophoresis   
Metabolic testing If no other cause is found discuss with metabolic services regarding appropriate testing, for example
consider lysosomal disorders.

Infective causes

Parvovirus Fetal anaemia that may have recovered
PCR, IgG and IgM titres
Send baby/cord serum.
CMV  Urine culture/PCR.
Serum for CMV PCR.
Toxoplasma Maternal and baby blood, placenta and amniotic fluid PCR
Baby/cord IgM.
Syphilis  Maternal serology (VDRL)
Baby/cord serology.
Congenital hepatitis Maternal hepatitis B serology
Baby LFTs and liver US.
Rubella Maternal serology before pregnancy
Urine ± CSF PCR.
WBC for rubella PCR
Serum IgM.
Herpes-Simplex WBC PCR.
Varicella   Other features of congenital varicella.

Look for supportive evidence with long bone X-rays, cerebral US/CT and ophthalmic exam.

Cardiovascular
SVT
Heart block
Truncus arteriosus
Coxsackie myocarditis
Hypoplastic Left Heart Syndrome
Endocardial fibroelastosis
VSD/AV canal
Premature closure of foramen ovale
Premature closure of PDA
Tumours (rhabdomyomas)
Arterial calcification
Cardiomyopathy (e.g. carnitine deficiency)
AV malformations
Any cause of heart failure
Chromosomal   
Trisomy 21 Triploidy 45XO (Turner's)  Many others reported 
Dysmorphic Syndromes   
Neurological     
Encephalocoele
Agenesis of the corpus callosum
Tuberous sclerosis Vein of Galen aneurysm Arthrogryposis
Gastrointestinal     
Jejunal atresia
Midgut volvolus
Meconium peritonitis
Hepatitic fibrosis 
Hepatic vascular malformations Familial cirrhosis and portal hypertension 
Genitourinary     
Congenital nephrotic syndrome
Urethral obstruction and renal dysplasia 
Polycystic kidneys Renal vein obstruction  Vaginal and uterine abnormalities 
Haematological     
Twin-twin transfusion
Rhesus isoimmunisation 
Feto-maternal haemorrhage
α-thalassaemia (homozygous) 
Fetal anaemia or blood loss
G6PD deficiency 
 Pyruvate kinase deficiency
Lymphatic       
Chylothorax Congenital lymphangectasia  Cystic hygroma of neck  Noonan's Syndrome 
Infective      
Parvovirus
CMV
Toxoplasma 
Syphilis
Leptospirosis
Chagas Disease 
Congenital hepatitis
Rubella
Herpes simplex
Varicella 
Respiratory   
Diaphragmatic hernia
Cystic adenomatoid malformation
Hamartoma
Tracheo-oesophageal fistula 
Atresia of right main bronchus
Sequestration 
Pulmonary lymphangiectasia
Mediastinal teratoma 
Other    
Retroperitoneal fibrosis       
Skeletal    
Osteogenesis imperfecta
Asphyxiating thoracic dystrophy 
Thanatophoric dwarfism
Achondrogenesis 
Hyperphosphatasia  Saldino-Noonan dwarfism 
Tumours    
Teratoma  Neuroblastoma  Haemangioma   
Placental/Umbilical     
True knot  UV thrombosis  Placental chorioangioma  UA aneurysm
Maternal     
Diabetes Preeclampsia Drugs (i.e. indomethacin)  
Metabolic
Gaucher's Disease
GM1 gangliosidosis 
Hurler's Syndrome (MP 1H)
Morquio (MP IVb) 
MP type VII
Mucolipidosis type I and II 
Sialic acid storage disease
Galactosialidosis 

This list is not comprehensive! Also it does not give an idea of how common conditions may be.

References

  1. Bellini C and Hennekam CM. Non-immune hydrops fetalis: A short review of etiology and pathophysiology. Am J Med Genet Part A. 2012;158A:597-605.
  2. Steurer MA, Peyvandi S, Baer RJ et al. Epidemiology of live born infants with nonimmune hydrops fetalis - Insights from a population-based dataset. J Pediatr 2017;187:182-8.
  3. Ota S, Sahara J, Mabuchi A, Yamamoto R, Ishii K, and Mitsuda N. Perinatal and one-year outcomes of non-immune hydrops fetalis by etiology and age at diagnosis. J Obstet Gynaecol Res. 2016;42(4):385-91.
  4. Fukushima K, Morokuma S, Fujita Y, et al. Short-term and long-term outcomes of 214 cases of non-immune hydrops fetalis. Early Human Development 2011;87:571-75.
  5. Sohan K, Carroll SG, De La Fuente S, Soothill P and Kyle P. Analysis of outcome in hydrops fetalis in relation to gestational age at diagnosis, cause and treatment. Acta Obstet Gynecol Scand 2001;80:726-30.
  6. Bellini C, Donarini G, Paladini D et al. Etiology of Non-immune hydrops fetalis: An update. Am J Med Genet Part A. 2015;167A:1082-88.
  7. Abrams ME, Meredith KS, Kinnard P and Clark RH. Hydrops Fetalis: A retrospective review of cases reported to a large national database and identification of risk factors associated with death. Pediatrics 2007;120:84-89.
  8. Shah D., Sinn JK. Octreotide as therapeutic option for congenital idiopathic chylothorax: a case series. Acta Paediatricia. 2012;101(4):e151-5.
  9. Das A, Shah PS. Octreotide for the treatment of chylothorax in neonates. (Review). Cochrane Database of Systematic Reviews 2010, issue 9; No: CD006388.
  10. Bellini C, Ergaz Z, Radicioni M et al. Congenital fetal and neonatal visceral chylous effusions: neonatal chylothorax and chylous ascities revisited. A multicentre retrospective study. Lymphology. 2012;45(3):91-102
  11. Testoni D, Hornik CP, Neely ML et l. Safety of octreotide in hospitalized infants. Early Human Development. 2015;91(7):387-92
  12. Bialkowski A, Poets CF, Franz AR; Erhebungseinheit fur padiatrische Erkrankungen in Deutschland Study Group. Congenital chylothorax: a prospective nationwide epidemiological study in Germany. Archives Dis Child Fetal & Neonatal Ed. 2015;100(2):F169-72.

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Document Control

  • Date last published: 28 February 2018
  • Document type: Clinical Guideline
  • Services responsible: Neonatology
  • Owner: Newborn Services Clinical Practice Committee
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years