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1/1/2009

Nonimmune Hydrops Fetalis

Nonimmune hydrops fetalis (NHF) is the presence of excessive fluid in two or more fetal compartments (skin edema, pleural effusion, pericardial effusion, or ascites), in the absence of red cell alloimmunization.  NHF accounts for 90% of cases and occurs in 1/1,700-1/3,000 pregnancies.   The pathophysiologic fetal mechanisms resulting in hydrops, include Increased hydrostatic capillary pressure (CHF and raised intrathoracic pressure), decreased plasma oncotic pressure (occurs in inborn errors of metabolism, GI disorders), obstruction of lymphatic flow (chromosomal abnormalities) and damage to peripheral capillary integrity (infection).    A thorough antenatal or postnatal evaluation results in a diagnosis in approximately 85% of cases.  Cardiovascular etiologies are the most common, with highest mortality. Although CHF can have cardiovascular, hematologic, renal, and placental etiologies. Twin-twin transfusion syndrome is another etiology.  

The diagnostic evaluation begins with ruling out alloimmunization as a cause, and taking maternal and family history, medication usage, and other exposures. The Kleihauer-Betke smear to assess for fetomaternal hemorrhage, test for parvovirus infection, and parental evaluation for hemoglobinopathy risk, especially alpha thalassemia, should be considered. 

Additional detailed fetal sonography of the fetus(es) and placenta is necessary, including fetal echocardiography and middle cerebral artery Doppler studies to evaluate for anemia.  A fetal karyotype, with chromosomal microarray analysis, is indicated despite the identification of a structural fetal anomaly. Whole-exome sequencing has been shown to yield promising results as well. Depending on the findings, further testing may include amniotic fluid alpha fetoprotein, PCR for CMV and toxoplasmosis, and fetal blood sampling. If all testing is negative, additional testing for skeletal dysplasia lysosomal storage disorders can be helpful.

The prognosis depends on the underlying etiology, response to therapy if treatable, and the gestational age at detection and delivery. Aneuploidy can confer a poor prognosis. Neonatal survival is often less than 50%.  Management may include pregnancy termination, therapeutic interventions when appropriate, and palliative and psychosocial care as needed.  Antepartum surveillance is necessary to identify fetal deterioration. Polyhydramnios, preterm birth, and mirror syndrome are a few of the complications that arise in NIHF. The timing of the delivery is largely individualized and should be considered by 37 weeks in the absence of worsening fetal or maternal health. Mirror syndrome, an uncommon complication where the mother develops edema that “mirrors” that of the hydropic fetus, may be a variant of preeclampsia. A few case reports describe the resolution of mirror syndrome with treatment of the etiology of the nonimmune hydrops fetalis.  In most cases, mirror syndrome necessitates delivery. These pregnancies should be delivered at a facility with the capability to stabilize and treat the underlying etiology of these critically-ill newborns. ¹

In cases of termination of pregnancies with no known etiology, fetal autopsy would be beneficial in understanding the cause further.

Further Reading:

Swearingen C, Colvin ZA, Leuthner SR. Nonimmune Hydrops Fetalis. Clin Perinatol. 2020 Mar;47(1):105-121. doi: 10.1016/j.clp.2019.10.001. Epub 2019 Oct 7. PMID: 32000919.

Society for Maternal-Fetal Medicine (SMFM), Norton ME, Chauhan SP, Dashe JS. Society for maternal-fetal medicine (SMFM) clinical guideline #7: nonimmune hydrops fetalis. Am J Obstet Gynecol. 2015 Feb;212(2):127-39. doi: 10.1016/j.ajog.2014.12.018. Epub 2014 Dec 31.

Initial approval January 2009; Revised January 2018. Reaffirmed July 2019. Revised July 2021. Revised March 2023. Revised November 2024.

 

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