Euploid First-Trimester Cystic Hygroma: A More Benign Entity than Previously Thought?

Abstract

<b><i>Objective:</i></b> Studies summarizing the outcome of first-trimester septated cystic hygroma are generally based on small studies or from multiple centers with limited ascertainment. We reviewed the natural history of a large cohort of such cases from a single tertiary referral center, with the aim being to establish contemporary outcome data, particularly in the setting of normal karyotype. <b><i>Methods:</i></b> A retrospective cohort study from 2007 to 2017 was conducted at a single tertiary referral prenatal diagnosis center. Data were analyzed from a prospectively collated fetal anomaly database. Search terms were “increased nuchal translucency (NT),” “cystic hygroma,” and “septated cystic hygroma.” All cases were confirmed to have NT >3 mm with septations. Cases of simple increased NT without septations were excluded. <b><i>Results:</i></b> During the study period, over 110,000 pregnancies were delivered at our center, resulting in 410 cases of septated cystic hygroma diagnosed prior to 14 weeks’ gestation. Pregnancy outcome was obtained in 99% (405/410) of cases, with detailed pathology outcome available in 92% (378/410). A total of 87% (351/405) underwent invasive prenatal testing, and postnatal chromosome status was established in further 27 cases. A total of 61% (230/378) had abnormal chromosomal status. Of the 39% (148/378) with normal chromosomal status, only 13% (19/148) had a significant structural fetal abnormality, which included 7 cardiac and 12 noncardiac abnormalities. Overall, the perinatal loss was 62% (253/405). The total survival rate in the setting of euploid cystic hygroma without structural abnormality was 84% (108/129). <b><i>Conclusions:</i></b> Counseling regarding outcomes in the setting of first-trimester septated cystic hygroma initially focuses on the strong likelihood of an abnormal karyotype, which occurs in 61% of cases. However, once fetal chromosomal abnormality is excluded, our results demonstrate only a 13% incidence of major structural fetal abnormality, which appears significantly less than previously reported. Normal fetuses have a 77% survival rate. These data represent the largest single-center study of first-trimester cystic hygroma with complete outcome data and therefore will be useful for contemporary patient counseling. Such counseling can be more positive than previously expected, once chromosomal abnormality is first excluded.

Current Perspectives of Prenatal Cell-free DNA Screening in Clinical Management of First-Trimester Septated Cystic Hygroma

“…These data have led to increased knowledge regarding the ominous first-trimester sonographic finding of first-trimester septated cystic hygroma. 82 In addition, recently published data regarding 410 cases of first-trimester septated cystic hygroma from among 110,000 pregnancies in Ireland, have confirmed associated abnormal chromosomal findings among such fetuses and an increased likelihood of structural anomalies among euploid fetuses with first-trimester septated cystic hygroma. 83 In a study of 134 cases of first-trimester septated cystic hygroma (generated from the FASTER Trial Research Consortium data (among 38,167 screened patients)) Malone et al in 2005, reported 132 patients with complete follow up.…”

“…These authors concluded that first-trimester cystic hygroma is a frequent finding in a general obstetric screening program. 82 This sonographic finding exhibited the strongest prenatal association with aneuploidy hitherto, with significantly worse outcome in comparison with simple increased nuchal translucency thickness (NT). The majority of pregnancies with normal evaluation at the completion of the second trimester resulted in a healthy infant with a normal neonatal outcome.…”

“…83 In a study of 134 cases of first-trimester septated cystic hygroma (generated from the FASTER Trial Research Consortium data (among 38,167 screened patients)) Malone et al in 2005, reported 132 patients with complete follow up. 82 Chromosomal abnormalities were confirmed in 67 (51%) patients. These included 25 cases of trisomy 21, 19 cases of monosomy X, 13 cases of trisomy 18, and ten others.…”

“…These included 25 cases of trisomy 21, 19 cases of monosomy X, 13 cases of trisomy 18, and ten others. 82 Major structural fetal malformations (predominantly cardiac and skeletal systems) were documented in 22 of the remaining 65 patients (34%). There were 5 cases (8%) of fetal demise and 15 cases of voluntary pregnancy termination, without evidence of abnormality.…”

“…In all, survival with normal neonatal outcome was documented in 17% of cases (22 of 132). 82 In comparison with simple increased nuchal translucency, cystic hygroma is associated with 5, 12, and 6-fold increased risk of aneuploidy, cardiac malformation, and perinatal death, respectively. These authors concluded that first-trimester cystic hygroma is a frequent finding in a general obstetric screening program.…”