Nonimmune hydrops fetalis: identifying the underlying genetic etiology

• Published in: Genetics in medicine Vol. 21; no. 6; pp. 1339 - 1344
• Main Authors: Sparks, Teresa N., Thao, Kao, Lianoglou, Billie R., Boe, Nina M., Bruce, Kari G., Datkhaeva, Ilina, Field, Nancy T., Fratto, Victoria M., Jolley, Jennifer, Laurent, Louise C., Mardy, Anne H., Murphy, Aisling M., Ngan, Emily, Rangwala, Naseem, Rottkamp, Catherine A. M., Wilson, Lisa, Wu, Erica, Uy, Cherry C., Valdez Lopez, Priscila, Norton, Mary E.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2019; Elsevier Limited
• Subjects: Adolescent; Adult; Aneuploidy; Biomedical and Life Sciences; Biomedicine; California; Cohort Studies; Etiology; Female; Fetus; Human Genetics; Humans; Hydrops Fetalis - etiology; Hydrops Fetalis - genetics; Infant, Newborn; Laboratory Medicine; Male; Pregnancy; Pregnancy Trimester, First; Prenatal Care; Retrospective Studies; Ultrasonography, Prenatal; California; genetic; hydrops fetalis; diagnostic evaluation; nonimmune; etiology
• ISSN: 1098-3600; 1530-0366
• DOI: 10.1038/s41436-018-0352-6

ABSTRACT Purpose Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF), and the underlying cause often remains unclear. We aimed to determine the proportion of NIHF cases in which the etiology was clearly determined in a large, contemporary, and diverse cohort, as well as to describe the etiologies with a focus on genetic causes. Methods Retrospective review of NIHF cases between 2015 and 2017 from the five University of California Fetal–Maternal Consortium sites. Singleton pregnancies with prenatally diagnosed NIHF were included, and cases with maternal alloimmunization were excluded. Cases were categorized as being of confirmed, suspected, or unknown etiology. Results Sixty-five NIHF cases were identified. Forty-six percent (30/65) remained of unknown etiology, while 9.2% (6/65) had a suspected etiology and 44.6% (29/65) were of confirmed etiology. Among confirmed cases, 11 resulted from aneuploidy; 7 from fetal structural anomalies; 2 each from fetal arrhythmia, Noonan syndrome, and generalized lymphatic dysplasia; and 1 each from arthrogryposis, parvovirus, neonatal alloimmune thrombocytopenia, fetal goiter, and Kasabach–Merritt syndrome. Conclusion In this contemporary, multicenter study, the cause of prenatally diagnosed NIHF was confirmed in only 44% of cases, and a genetic etiology was found in only 25% of those that received standard of care genetic testing.