Clinical characteristics of the entire cohort in the study.
This study included 20,409 singleton pregnancies and 186 cases of fetal SCAs were diagnosed. The clinical significance of fetal SCAs (by year) in the entire cohort is shown in Table 1. Excluding 7 rare fetal SCAs (including 1 case of 48,XXXY, 2 cases of 48,XXXX, 1 case of 48,XXYY and 3 cases of 69,XXX), 179 cases of common fetal SCAs were diagnosed with an incidence rate of 8.77‰ (about 1/114). The most common fetal SCAs was 47,XXY in 70 cases (39.11%), followed by 47,XXX in 44 (24.58%), 47,XYY in 39 (21.79%) and 45,X in 26 (14.53%). The proportion of advanced age women receiving amniocentesis accounted for about half (45.71%, 9329/20409) of the clinical samples. Change in the relative number of amniocentesis and advanced age women (≥ 35) undergoing amniocentesis by year are showed in Fig. 1.(a). A trend in the proportion of women with advanced maternal age undergoing amniocentesis and mean age of the women are compared in Fig. 1.(b). The results showed that the proportion of AMA women and the mean age of the women have been increasing since 2012, and especially in 2016 and 2017, then reduced in 2018. Age of these women ranged from 18 to 52 years, with an average age of 33.09 years (± 5.447). Maternal age distribution of the entire study cohort and the incidence (per 1000) of fetal SCAs by maternal age are shown in Fig. 2 and Table 2. Two birth peaks appeared at 28 and 35 years old. The incidence of 47,XXY, 47,XXX and 47,XYY was found to increase dramatically at the age of 44.
Table 1
Clinical significance of fetal SCAs (by year) in the entire cohort.
Year | No. of patients | AMA | % of AMA | Mean age ± SD | Sex chromosome aneuploidies |
Total | 45,X | 47,XXY | 47,XXX | 47,XYY | 48,XXXY | 48,XXXX | 48,XXYY | 69,XXX |
2011 | 3314 | 1518 | 45.81% | 32.74 ± 5.359 | 9 | 2 | 1 | 2 | 2 | 1 | | | 1 |
2012 | 2364 | 895 | 37.86% | 32.03 ± 5.430 | 10 | 3 | 3 | 1 | 2 | | | | 1 |
2013 | 1840 | 697 | 37.88% | 32.20 ± 5.476 | 16 | 4 | 7 | 2 | 2 | | 1 | | |
2014 | 2520 | 1026 | 40.71% | 32.47 ± 5.282 | 13 | 4 | 2 | 4 | 3 | | | | |
2015 | 2097 | 955 | 45.54% | 32.85 ± 5.347 | 14 | 1 | 6 | 3 | 4 | | | | |
2016 | 2309 | 1294 | 56.04% | 34.26 ± 5.143 | 32 | 3 | 13 | 8 | 7 | | | 1 | |
2017 | 2154 | 1240 | 57.57% | 34.49 ± 5.456 | 22 | 1 | 10 | 5 | 4 | | 1 | | 1 |
2018 | 3811 | 1704 | 44.71% | 33.54 ± 5.530 | 70 | 8 | 28 | 19 | 15 | | | | |
Total | 20409 | 9329 | 45.71% | 33.09 ± 5.447 | 186 | 26 | 70 | 44 | 39 | 1 | 2 | 1 | 3 |
Table 2
The incidence (per 1000) of 45,X, 47,XXY, 47,XXX and 47,XYY by maternal age in the study.
Maternal age | No. of patients | 45,X | 47,XXY | 47,XXX | 47,XYY | All SCAs |
18 | 7 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
19 | 15 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
20 | 34 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
21 | 100 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
22 | 188 | 0 (0) | 1 (5.32) | 1 (5.32) | 0 (0) | 2 (10.64) |
23 | 314 | 1 (3.18) | 0 (0) | 1 (3.18) | 0 (0) | 2 (6.37) |
24 | 526 | 0 (0) | 1 (1.90) | 1 (1.90) | 0 (0) | 2 (3.80) |
25 | 666 | 0 (0) | 1 (1.50) | 2 (3.00) | 1 (1.50) | 4 (6.01) |
26 | 877 | 2 (2.28) | 0 (0) | 2 (2.28) | 2 (2.28) | 6 (6.84) |
27 | 990 | 5 (5.05) | 1 (1.01) | 0 (0) | 1 (1.01) | 7 (7.07) |
28 | 1245 | 1 (0.80) | 1 (0.80) | 3 (2.41) | 1 (0.80) | 6 (4.82) |
29 | 1153 | 5 (4.34) | 2 (1.73) | 2 (1.73) | 1 (0.87) | 10 (8.67) |
30 | 1089 | 2 (1.84) | 1 (0.92) | 3 (2.75) | 0 (0) | 6 (5.51) |
31 | 1012 | 0 (0) | 2 (1.98) | 2 (1.98) | 3 (2.96) | 7 (6.92) |
32 | 1002 | 4 (3.99) | 1 (1.00) | 1 (1.00) | 6 (5.99) | 12 (11.98) |
33 | 841 | 1 (1.19) | 2 (2.38) | 0 (0) | 1 (1.19) | 4 (4.76) |
34 | 925 | 1 (1.08) | 4 (4.32) | 2 (2.16) | 5 (5.41) | 12 (12.97) |
35 | 1616 | 1 (0.62) | 7 (4.33) | 7 (4.33) | 4 (2.48) | 19 (11.76) |
36 | 1562 | 0 (0) | 11 (7.04) | 3 (1.92) | 2 (1.28) | 16 (10.24) |
37 | 1421 | 0 (0) | 6 (4.22) | 2 (2.11) | 4 (4.22) | 12 (8.44) |
38 | 1256 | 1 (0.80) | 5 (3.98) | 4 (3.18) | 3 (2.39) | 13 (10.35) |
39 | 1088 | 1 (0.92) | 7 (6.43) | 0 (0) | 1 (0.92) | 9 (8.27) |
40 | 866 | 0 (0) | 5 (5.77) | 2 (2.31) | 2 (2.31) | 9 (10.39) |
41 | 644 | 0 (0) | 5 (7.76) | 1 (1.55) | 0 (0) | 6 (9.32) |
42 | 461 | 0 (0) | 3 (6.51) | 1 (2.17) | 1 (2.17) | 5 (10.85) |
43 | 241 | 1 (4.15) | 1 (4.15) | 1 (4.15) | 0 (0) | 3 (12.45) |
44 | 136 | 0 (0) | 2 (14.71) | 3 (22.06) | 1 (7.35) | 6 (44.12) |
45 | 75 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
46 | 28 | 0 (0) | 1(35.71) | 0 (0) | 0 (0) | 1 (35.71) |
47 | 18 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
48 | 8 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
49 | 3 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
51 | 1 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
52 | 1 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Total | 20409 | 26 (1.27) | 70 (3.42) | 44 (2.16) | 39 (1.91) | 179 (8.77) |
The incidence of fetal SCAs depended on clinical indications.
In the study, AMA and positive results of MSS were the most frequent reasons for referral, accounting for 47.69% and 34.65%, respectively. The most of SCAs were detected with the indication of AMA (111/179, 62.01%), followed by abnormal NIPT results (34/179, 19.00%), abnormal ultrasound findings (16/179, 8.94%), positive result of MSS (15/179, 8.38%) and others (3/179, 1.68%). However, the incidence of SCAs varied by indications: 83.74‰ for abnormal NIPT results, 17.98‰ for abnormal ultrasound findings, 11.40‰ for AMA, 2.12‰ for positive results of MSS and 1.30‰ for others. AMA was the most frequent referral indication for 47,XXY, 47,XXX and 47,XYY, while abnormal ultrasound findings were the most frequent referral indication for 45,X. Three pregnant women with the indication of others were found to have fetal SCAs, including 1 case of monogenetic disease, 1 case of a previous child with 5p-, and 1 case of a previous child with 21 trisomy. None of the pregnant women with fetal SCAs were found to have the referral indication of paternal/maternal carrying sex chromosome abnormalities or a family history of a previous child with sex chromosome abnormalities. The incidence and proportion of fetal SCAs by referral indications are showed in Table 3.
Table 3
The frequency and proportion of fetal SCAs by referral indications.
Referral indications | No.of patients (%) | SCAs (%) | SCAs (‰) by indications | SCAs |
45,X | 47,XXY | 47,XXX | 47,XYY |
AMA | 9734(47.69%) | 111(62.01%) | 11.40‰ | 5(19.23%) | 57(81.43%) | 26(59.09%) | 23(58.97%) |
Positive results of MSS | 7072(34.65%) | 15(8.38%) | 2.12‰ | 5(19.23%) | 1(1.43%) | 3(6.82%) | 6(15.38%) |
Abnormal ultrasound findings | 890(4.36%) | 16(8.94%) | 17.98‰ | 10(38.46%) | 2(2.86%) | 3(6.82%) | 1(2.56%) |
Abnormal NIPT results | 406(1.99%) | 34(19.00%) | 83.74‰ | 6(23.08%) | 9(12.86%) | 12(27.27%) | 7(17.95%) |
Others | 2307(11.30%) | 3(1.68%) | 1.30‰ | 0(0.00%) | 1(1.43%) | 0(0.00%) | 2(5.13%) |
Total | 20409(100.00%) | 179(100.00%) | 8.77‰ | 26(14.53%) | 70 (39.11%) | 44(24.58%) | 39(21.79%) |
The correlations between maternal age and the incidence of fetal SCAs.
Logistic regression analysis was performed to analyze the correlation between maternal age and the incidence of fetal SCAs, showed in Table 4. According to the results of logistic regression analysis, the incidence of all SCAs was significantly associated with maternal age (P = 0.002), and the odds ratio tended to increase by 1.044 times as maternal age increased by one year. The incidence of 45,X and 47,XXY also showed significant correlation with maternal age (P = 0.017; P = 0.000, respectively), and the odds ratio of 45,X tended to increase by 0.916 times and the odds ratio of 47,XXY tended to increase by 1.127 times as maternal age increased by one year. However, the incidence of 47,XXX and 47,XYY was not found to be significantly correlated with maternal age (P = 0.473; P = 0.272, respectively). Trends in the incidence of fetal SCAs based on maternal age groups are shown in Fig. 3. The incidence of 47,XXY and all SCAs was basically positively correlated with maternal age, respectively, however, a significant inverse relationship with maternal age was found for 45,X at the upper end of the 29–33 age range. Unlike the incidence of 47,XXX being completely independent of maternal age, the incidence of 47,XYY before the 34–38 years was completely dependent on the maternal age, and then decreased sharply.
Table 4
Regression coefficient and standard errors of logistic regression equations for fetal SCAs diagnosed in the study.
| Constant term | Maternal term |
| A | Standard error | B | Standard error | Odds ratio | 95% CI | P value |
45,X | -3.861 | 1.143 | -0.088 | 0.037 | 0.916 | 0.852–0.984 | 0.017 < 0.05 |
47,XXY | -9.817 | 0.894 | 0.119 | 0.024 | 1.127 | 1.074–1.182 | 0.000 < 0.05 |
47,XXX | -6.807 | 0.953 | 0.020 | 0.028 | 1.020 | 0.966–1.078 | 0.473 > 0.05 |
47,XYY | -7.360 | 1.030 | 0.033 | 0.030 | 1.033 | 0.975–1.096 | 0.272 > 0.05 |
All SCAS | -6.186 | 0.490 | 0.043 | 0.014 | 1.044 | 1.016–1.073 | 0.002 < 0.05 |
Comparison of the incidence of SCAs among different age groups.
A chi-square test was performed to compare the incidence of fetal SCAs among different age groups; the statistical results are shown in Table 5. The incidence of all SCAs was significantly different among groups (χ2 = 10.197, P = 0.037), but there were no significant differences between adjacent groups (P > 0.05). The incidence of 45,X and 47,XXY was also significantly different among groups (χ2 = 10.977, P = 0.027; χ2 = 29.159, P = 0.000, respectively), while the incidence of 47,XXX and 47,XYY was not found to be significantly different among groups (χ2 = 2.027, P = 0.731; χ2 = 5.145, P = 0.273, respectively). We further compared the incidence of 45,X and 47,XXY between adjacent groups, and found that the incidence of 45,X and 47,XXY was significantly different only between the 29–33 years and the 34–38 years (P = 0.004; P = 0.002, respectively) (Table 6). However, the incidence of 45,X in the 34–38 years (0.44‰, 1:2272) was lower than the 29–33 years (2.35‰, 1:426), while the incidence of 47,XXY was the opposite (4.87‰, 1:205 vers 1.57‰, 1:637). We further conducted statistical analysis between the advanced maternal aged group (≥ 34 years, including the 34–38 years and the ≥ 39 years) and the non-advanced maternal aged group (< 34 years old, including the ≤ 23 years, the 24–28 years and the 29–33 years) (Table 7). The incidence of 45,X, 47,XXY and all SCAs in the advanced maternal aged groups was significantly different from that of the non-advanced maternal aged groups (χ2 = 9.223, P < 0.05; χ2 = 10.323, P < 0.05; χ2 = 26.513, P < 0.05, respectively). However, the incidence of 47,XXX and 47,XYY between the advanced maternal aged group (≥ 34 years) and the non-advanced maternal-aged group (< 34 years) was not found to be statistically significant difference (χ2 = 1.238, P > 0.05; χ2 = 1.067, P > 0.05, respectively).
Table 5
Comparison of the incidence of fetal SCAs among different age groups.
Age groups | No. of patients | 45,Xa | 47,XXYb | 47,XXXc | 47,XYYd | All SCAse |
≤ 23 | 658 | 1(1.52) | 1(1.52) | 2(3.04) | 0(0) | 4(6.08) |
24–28 | 4304 | 8(1.86) | 4(0.93) | 8(1.86) | 5(1.16) | 25(5.81) |
29–33 | 5097 | 12(2.35) | 8(1.57) | 8(1.57) | 11(2.16) | 39(7.65) |
34–38 | 6780 | 3(0.44) | 33(4.87) | 18(2.65) | 18(2.65) | 72(10.62) |
≥ 39 | 3570 | 2(0.56) | 24(6.72) | 8(2.24) | 5(1.40) | 39(10.92) |
Total | 20409 | 26(1.27) | 70(3.43) | 44(2.16) | 39(1.91) | 179(8.77) |
Data are presented as n (per 1000), unless otherwise indicated. |
a The incidence of 45,X was significantly different among the groups(χ2 = 10.977, P = 0.027 < 0.05). |
b The incidence of 47,XXY was significantly different among the groups(χ2 = 29.159, P = 0.000 < 0.05). |
c The incidence of 47,XXX was significantly different among the groups(χ2 = 2.027, P = 0.731 > 0.05). |
d The incidence of 47,XYY was significantly different among the groups(χ2 = 5.145, P = 0.273 > 0.05). |
e The incidence of all SCAs was significantly different among the groups(χ2 = 10.197, P = 0.037 < 0.05). |
Table 6
Comparison of the incidence of 45,X and 47,XXY between the 29–33 years and the 34–38 years.
Age groups | No.of patients | 45,X | 47,XXY |
Number/Incidence | PPV | χ2 | P | Number/Incidence | PPV | χ2 | P |
29–33 | 5097 | 12 (2.35) | 1:426 | 8.432 | 0.004 | 8 (1.57) | 1:637 | 9.198 | 0.002 |
34–38 | 6780 | 3 (0.44) | 1:2272 | 33 (4.87) | 1:205 |
Data are presented as n (per 1000), unless otherwise indicated. |
PPV: positive predictive value |
Table 7
Comparison of the incidence of common SCAs between the advanced maternal aged women and the non-advanced maternal-aged women.
Age groups | No. of patients | 45,Xa | 47,XXYb | 47,XXXc | 47,XYYd | All SCAse |
< 34 | 10059 | 21(2.08) | 13(1.29) | 18(1.79) | 16(1.59) | 68(6.76) |
≥ 34 | 10350 | 5(0.48) | 57(5.51) | 26(2.51) | 23(2.22) | 111(10.72) |
Data are presented as n (per 1000), unless otherwise indicated. |
a The incidence of 45,X was statistically significant between the ≥ 34 age group and the < 34 age group (χ2 = 10.323, P < 0.05). |
b The incidence of 47,XXY was statistically significant between the ≥ 34 age group and the < 34 age group (χ2 = 26.513, P < 0.05). |
c The incidence of 47,XXX was not statistically significant between the ≥ 34 age group and the < 34 age group (χ2 = 1.238, P > 0.05). |
d The incidence of 47,XYY was not statistically significant between the ≥ 34 age group and the < 34 age group (χ2 = 1.067, P > 0.05). |
e The incidence of all the SCAs was statistically significant between the ≥ 34 age group and the < 34 age group (χ2 = 9.223, P < 0.05). |