Indications for prenatal diagnosis and pregnancy outcomes of Turner syndrome with different karyotypes in 205 cases / 中华围产医学杂志

ABSTRACT

Objective:To investigate the indications for prenatal diagnosis and pregnancy outcomes of fetal Turner syndrome (TS) with different karyotypes.Methods:Clinical data of TS cases diagnosed by fetal karyotyping in the Prenatal Diagnostic Center of Guangzhou Women and Children′s Medical Center from January 1, 2010, to June 30, 2021, were analyzed retrospectively. According to the karyotyping results, these cases were divided into two groups monosomy X (45,X) and non-monosomy X groups (including karyotypes of mosaic monosomy X, isochromosome X, X deletion, X rearrangement, pseudodicentric X, and mosaicism with Y or Y deletion). Chi-square test was used to compare the detection rate, indications for prenatal diagnosis, and pregnancy outcomes of the two groups, and the Bonferroni test was conducted for further pairwise comparisons between the subgroups. The Chi-square test (or Fisher's exact test) was used to compare the abnormal ultrasound signs. Mann-Whitney U test was used to compare the nuchal translucency (NT) thickness of the two groups. Results:(1) Invasive prenatal diagnosis was performed on 27 981 pregnancies, and 205 (0.73%) of them were diagnosed with TS, including 135 cases of monosomy X and 70 cases of non-monosomy X (44 with numerical sex chromosome abnormalities, and 26 with structural sex chromosome abnormalities). (2) Out of the 205 pregnancies, 164 (80.0%) had one indication for prenatal diagnosis, and 41 (20.0%) had multiple indications. The detection rate of fetal ultrasonographic abnormalities [85.2% (115/135)] in monosomy X cases was significantly higher than that of three other indications [positive serological screening for Down's syndrome 67.3% (35/52); positive non-invasive prenatal testing (NIPT) for sex chromosome abnormality 60.0% (15/25); and other indications (advanced maternal age, adverse pregnancy history and thalassemia genes carried by both parents) 5.2% (7/135); all P<0.05], and also higher than the figure in non-monosomy X cases [25.7% (18/70), χ 2=71.55, P<0.001]. In non-monosomy X cases, the detection rates of TS among cases with high-risk results from serological screening for Down's syndrome and NIPT for sex chromosome abnormality [54.7% (29/53) and 68.3% (28/41)] were higher than those of the other two indications [fetal ultrasonographic abnormalities 25.7% (18/70), other indications 14.3% (10/70); all P<0.05]. (3) Of the 133 pregnancies with fetal ultrasonographic abnormalities as the indication, 65 (48.9%) had one abnormal ultrasound sign, and 68 (51.1%) had multiple signs. Among the 95 cases with ultrasound abnormalities in the first trimester and 38 cases in the second or third trimester, the incidence of cystic hygroma and hydrops was significantly higher in monosomy X cases than in non-monosomy X cases [in the first trimester 71.8% (61/85) vs 1/10, 34.1% (29/85) vs 0/10; in the second or third trimester 73.3% (22/30) vs 0/8, 50.0% (15/30) vs 0/8; Fisher's exact test, all P<0.05]. NT thickness in monosomy X cases was greater than that of non-monosomy X cases [7.5 mm (1.0-17.4 mm) vs 1.7 mm (0.8-9.5 mm), Z=－5.25, P<0.001]. (4) Among the 72 pregnancies with indications other than ultrasound abnormalities, 68 underwent Down's syndrome screening and 61 underwent NIPT. The detection rates among the cases with positive results in Down's syndrome screening, NIPT for a sex chromosome abnormality, and other indications (advanced maternal age, adverse pregnancy history, and thalassemia genes carried by both parents) were 54.4% (37/68), 59.0% (36/61) and 22.2% (16/72), respectively ( χ 2=22.40, P<0.001). The detection rates of the cases with high-risk results from Down's syndrome screening and NIPT for sex chromosome abnormality were higher than that of the cases with other indications ( χ 2=18.77 and 15.40, both P<0.001). Of the 72 pregnancies, 19 (26.4%) were monosomy X and 53 (73.6%) were non-monosomy X, including 42 (58.3%) with chromosomal mosaicism. (5) Among the 205 cases of TS, 185 were successfully followed up (123 were monosomy X and 62 were non-monosomy X). There was one live birth in monosomy X cases (0.8%, 1/123) and 17 in non-monosomy X cases (27.4%, 17/62), and the difference was statistically significant ( χ2=33.22, P<0.001). Sixty-three TS cases with normal ultrasound findings were followed up (18 were monosomy X and 45 were non-monosomy X). In these cases, all 18 pregnancies with monosomy X and 32 (71.1%, 32/45) with non-monosomy X were terminated and the other 13 (28.9%, 13/45) cases of non-monosomy X were delivered. Of the 18 live births, one (non-monosomy X) was delivered at 36 weeks of gestation and the rest were born at term. Eleven cases of them were followed up. The height of one child with monosomy X was lower than the average height of children of the same age and sex by more than 2 standard deviations (－2 SD). The height of 10 children with non-monosomy X were between－1 SD and +3 SD among the children of the same age and gender. The mental and motor development were good in the 11 cases, and no other structural abnormalities were observed. The remaining seven cases refused to be followed up. Conclusions:Ultrasonographic abnormalities are the main indications of fetal TS with monosomy X, while positive Down's syndrome screening and positive NIPT for sex chromosome abnormality are indicators of non-monosomy X. The termination rate for pregnancies with monosomy X is higher than that for non-monosomy X.