Genetic Disorders and Pregnancy Outcomes of non-immune Hydrops Fetalis in a Tertiary Referral Center

Abstract Background: Non-immune hydrops fetalis (NIHF) is a nonspecific symptom with a wide variety of disorders, and the prognosis depends on the underlying etiology. The aim of the study was to investigate the incidence of chromosomal abnormalities and α0/α0 thalassemia in non-immune hydrops fetalis NIHF pregnancies in South China.Methods: We retrospectively reviewed NIHF pregnancies referred to the Fujian Provincial Maternity and Children's Hospital during 2014 and 2018. Pregnancies with maternal alloimmunization were excluded. Thalassemia genotyping and routine karyotyping were performed in all enrolled 129 cases, and chromosomal microarray analysis was performed in 35 cases with normal karyotype. Results: α0/α0 thalassemia was detected in 34.9% (45/129) of the cohort, while chromosomal abnormalities were detected in 29.5% (38/129), including 37 cases of aneuploidy and a single case of imbalanced structural abnormality. In 35 cases with normal karyotype, chromosomal microarray analysis (CMA) revealed no additional pathogenic variations. The rates of chromosomal abnormalities subsided with the onset of trimester, with 65%, 30.1%, and 8.3% in the first, second, and third trimester, respectively (p＜0.05 ). Among 46 (35.6%) cases of unknown etiology, 23 cases accompanied with ultrasonic abnormalities resulted in poor outcome, while 7 cases presented only with multiple ascites that resolved or remitted prior to birth, normal development was observed during 3-4 years follow-up.Conclusion: α0/α0 thalassemia and chromosomal abnormalities are the most common genetic etiologies of NIHF in South China. Generalized skin edema and accompanying ultrasonic abnormalities are predictive of adverse outcomes, and intensive monitoring should be provided to NIHF for better pregnancy management.