Etiology and Outcome of non-immune Hydrops Fetalis in Southern China: report of 1004 cases

Abstract

Non-immune hydrops fetalis (NIHF) is a complex condition with a high mortality and morbidity rate. Here we report the etiology and outcome of 1004 fetuses with NIHF, in a large single Maternal and Children’s hospital of Southern China, since the year of 2009 to 2016. Among these 1004 fetuses with NIHF, the etiology was identified prenatally in 722 of them (72%). The most common ones were hematologic diseases and chromosomal abnormalities. There were eight spontaneous abortions, 18 intrauterine fetal demise, 672 pregnancy terminations and 87 were lost to follow-up. 219 of the 1004 fetuses were live-born and the overall survival rate was 21.8% at this point. After birth 16 perinatal or early neonatal deaths were encountered and five lost to follow-up. Of the remaining 198 newborns, 153 thrived without apparent morbidity. The most significant factors associated with mortality were prematurity and low birthweight. In conclusion, we described the largest report of underlying causes and outcome of NIHF in Southern China. Etiologies were identified for 72% of 1004 fetuses with NIHF. And two poor prognostic factors for survival are preterm birth at less than 36.5 weeks and birthweight lower than 2575 g respectively.

Non‐immune hydrops fetalis was rare in Sweden during 1997‐2015, but cases were associated with complications and poor prognosis

“…In a study including ultrasound examination during pregnancy over an 8‐year period, 8 for example, 103 cases of NIHF were identified in 25 200 women, corresponding to an incidence of 40.9 per 10 000 pregnancies compared with the 1.6 per 10 000 at birth reported in the present study. Other large patient series suggest that the incidence during pregnancy may be even higher 10,25 . Thus, many pregnancies affected by NIHF are ending prematurely.…”

Clinical characteristics and risk factors of mirror syndrome: a retrospective case-control study

“…Since maternal edema is related to fetal hydrops and placental edema, any of the conditions associated with fetal hydrops or placental edema may cause MS. In southern China, alpha thalassemia major, which accounts for 28.4–55.1% of non-immune hydrops fetalis [ 10 , 11 ], is also the common cause of MS. In our study, nearly half (17/37, 45.9%) of hydropic fetuses in the second and third trimesters were caused by alpha thalassemia major, and seven cases (7/17, 41.2%) developed MS.…”

A homozygous variant in growth and differentiation factor 2 (GDF2) may cause lymphatic dysplasia with hydrothorax and nonimmune hydrops fetalis

“…Fourth, with SNP-array analysis and massive parallel sequencing other major genetic causes of NIHF were excluded. This included hematological disease, chromosomal aneuploidies, and variants in genes known to cause lymphatic dysplasia including RASopathies, (generalized) lymphedema, or inborn errors of metabolism (Bellini et al, 2015;Hakami, Dillon, Lebo, & Mason-Suares, 2016;Houweling et al, 2010;Johnston et al, 2018;Joyce et al, 2016;Mardy et al, 2019;Martin-Almedina et al, 2016;Mason-Suares et al, 2017;Meng et al, 2019;Moreno et al, 2013;Pagnamenta et al, 2019;Quinlan-Jones et al, 2019;Stuurman et al, 2019;Sudrie-Arnaud et al, 2018;Weissbach et al, 2019;Yates et al, 2017). Finally, no other causes for the NIHF, such as intra-uterine infections and cardiac abnormalities, were present.…”

“…Finally, no other causes for the NIHF, such as intra-uterine infections and cardiac abnormalities, were present. The mosaic trisomy 20 observed in cultured amnion cells from the deceased fetal sibling is unlikely to have played a role as no single case of (mosaic) trisomy 20 was identified among 1,004 cases (including 199 with chromosomal abnormalities) with NIHF in the series published by Meng et al (Meng et al, 2019) and for reasons outlined below (see "the pathophysiological mechanism").…”