The association between clinical characteristics and chromosomal abnormalities
The relationship between chromosomal abnormalities and different clinical features is presented in Table 1.Among them, patients with abnormal fetal tissue chromosomal karyotypes had a significantly higher average age than those with normal karyotypes(31.26 ± 4.14 vs. 30.64 ± 3.72,P = 0.029), but there was no significant difference in BMI between the two groups(22.42 ± 2.85 vs. 22.64 ± 2.76,P = 0.267). Moreover, the rate of chromosomal abnormalities was significantly higher in patients with maternal age >35 years than those patients in ≤ 35years(66.38% vs. 53.63%,P = 0.011). Additionally, the rate of fetal chromosomal abnormalities in pregnant women with gestational age < 12 weeks is significantly higher than those with gestational age ≥ 12 weeks (56.58% vs.39.68%, P = 0.022). When comparing the number of previous pregnancy losses, we found that among patients with recurrent pregnancy loss (RPL) who have had ≥ 4 miscarriages (42.59%), as the number of prior miscarriages decreases, the proportion of fetal chromosomal abnormalities increases (once:57.14%; twice:58.28%;3 times:57.01%; P = 0.024).
Table 3 showed the results from multiple logistic analyses. Compared with the corresponding comparison groups, the risk of chromosomal abnormalities was increased in women with advanced age(>35 years,OR,1.841;95%CI,1.205-2.812),an earlier gestational age(<12weeks,OR,2.041;95%CI,1.116-3.732),less number of previous pregnancy loss(once: OR,2.007;95%CI,1.202-3.351;twice:OR,2.039;95%CI,1.296-3.206;3times:OR,1.957;95%CI,1.219-3.143).
The risk of SA patients with normal and abnormal fetal tissue chromosome karyotypes by different clinical characteristics was shown in Table4.The relative risk rate (RR) of ≥ 35 years patients was a significant 1.4-fold higher than < 35 years (RR, 1.4, 95%CI, 1.1–1.8).Meanwhile, the RR of gestational age <12 weeks patients was a significant 1.4-fold higher than those ≥12 weeks(RR,1.4,95%CI,1.1-1.8). Based on the reference group's criteria, individuals who have experienced 1(RR,1.3,95%CI,1.0-1.7), 2(RR,1.4,95%CI,1.1-1.7), and 3(RR,1.3,95%CI,1.1-1.7) pregnancy losses all show significantly higher RR compared to the reference group(≥4 previous pregnancy losses).
Table 3
Multiple logistic regression analyses of clinical risk characteristics for chromosomal variants.
Characteristics
|
Abnormal
|
n
|
Rate(%)
|
95%CI
|
RR
|
95%CI
|
Age(years)
|
|
|
|
|
|
|
≤ 35
|
355
|
662
|
53.6
|
(48.8–57.4)
|
Ref
|
|
>35
|
77
|
116
|
66.4
|
(57.7–75.1)
|
1.4
|
(1.1–1.8)
|
BMI(kg/m2)
|
|
|
|
|
|
|
<18.5
|
24
|
38
|
63.2
|
(47.1–79.2)
|
1.2
|
(0.8–1.8)
|
≥ 18.5, <24.0
|
302
|
540
|
55.9
|
(51.7–60.1)
|
Ref
|
|
≥ 24.0
|
106
|
200
|
53.0
|
(46.0–60.0)
|
1.0
|
(0.8–1.1)
|
Gestational age(weeks)
|
|
|
|
|
|
|
<12
|
413
|
730
|
56.6
|
(53.0-60.2)
|
1.4
|
(1.1–1.8)
|
≥ 12
|
19
|
48
|
39.6
|
(25.2–53.9)
|
Ref
|
|
The number of previous miscarriages(times)
|
|
|
|
|
|
|
1
|
84
|
147
|
57.1
|
(49.0-65.2)
|
1.3
|
(1.0-1.7)
|
2
|
176
|
302
|
58.3
|
(52.7–63.9)
|
1.4
|
(1.1–1.7)
|
3
|
126
|
221
|
57.0
|
(50.4–63.6)
|
1.3
|
(1.1–1.7)
|
≥ 4
|
46
|
108
|
42.6
|
(33.1–52.1)
|
Ref
|
|
Table 4
The risk of SA patients with normal and abnormal fetal tissue chromosome karyotypes by different clinical characteristics.
Characteristics
|
Abnormal
|
n
|
Rate(%)
|
95%CI
|
RR
|
95%CI
|
Age(years)
|
|
|
|
|
|
|
≤ 35
|
355
|
662
|
53.6
|
(48.8–57.4)
|
Ref
|
|
>35
|
77
|
116
|
66.4
|
(57.7–75.1)
|
1.4
|
(1.1–1.8)
|
BMI(kg/m2)
|
|
|
|
|
|
|
<18.5
|
24
|
38
|
63.2
|
(47.1–79.2)
|
1.2
|
(0.8–1.8)
|
≥ 18.5, <24.0
|
302
|
540
|
55.9
|
(51.7–60.1)
|
Ref
|
|
≥ 24.0
|
106
|
200
|
53.0
|
(46.0–60.0)
|
1.0
|
(0.8–1.1)
|
Gestational age(weeks)
|
|
|
|
|
|
|
<12
|
413
|
730
|
56.6
|
(53.0-60.2)
|
1.4
|
(1.1–1.8)
|
≥ 12
|
19
|
48
|
39.6
|
(25.2–53.9)
|
Ref
|
|
The number of previous miscarriages(times)
|
|
|
|
|
|
|
1
|
84
|
147
|
57.1
|
(49.0-65.2)
|
1.3
|
(1.0-1.7)
|
2
|
176
|
302
|
58.3
|
(52.7–63.9)
|
1.4
|
(1.1–1.7)
|
3
|
126
|
221
|
57.0
|
(50.4–63.6)
|
1.3
|
(1.1–1.7)
|
≥ 4
|
46
|
108
|
42.6
|
(33.1–52.1)
|
Ref
|
|
Fetal tissue chromosomal characteristics and the distribution of abnormal chromosome karyotypes in 23 pairs of chromosomes
Figure 1 and Table 1 provide a detailed description of the types and distribution percentages of all embryo chromosomes. Among all fetal tissue chromosomes, the proportion of abnormal chromosomes is slightly higher than that of normal chromosomes (55.53%,432/778 vs. 44.47%,346/778). Categories of abnormal fetal tissue chromosome karyotypes were trisomy (26.09%,203/778),45,X(6.56%,51/778),microduplication(4.88%,38/778),triploid(4.37%,34/778),microdeletion(3.34%,26/778),mosaicism(1.93%,15/778),monosomy(0.26%,2/778)and others[8.10%,63/778,among them, multiple-chr(number of abnormal chromosomes ≥ 2, 7.46%,58/778), uniparental disomy(UPD,0.26%,2/778)and tetraploid(0.26%,2/778)].
Figure 1The number of patients with all fetal tissue chromosome karyotypes.
The distribution of the 23 pairs of chromosomes was in Fig.2. The distribution of abnormal fetal tissue chromosome karyotypes was concentrated on the sex chromosomes (20.30%,68/335), chromosome 16(19.40%,65/335), and chromosome 22(10.15%,34/335), and fewest on chromosome 12(0.60%,2/335). Trisomy is the most common type of abnormality among chromosomes, and it is predominantly found in chromosome 16(25.25%,51/202), followed by chromosomes 22(14.36%,29/202), 21(8.91%,18/202), 13(8.42%,17/202), and 2(6.93%,14/202), and showed no signs on chromosome 12(0%,0/202). The distribution of mosaicism was also enrichment on chromosome 16(26.67%,4/15), and showed no signs on chromosomes 1,6,7,8,10,13,14,15,17,18,20,21and X/Y (all 0%,0/15). The distribution of microduplication was enrichment on chromosome 16(17.95%,7/39), followed by chromosome 10(12.82%,5/39), but chromosomes 3,4,7,9,14 and 18 did not show this kind of abnormality (all 0%,0/39). The distribution of microdeletion was enrichment on chromosome X/Y(16.67%,4/24),and fewest on chromosomes 2,3,6,7,8,10,12,13,20 and 21(all 0%,0/24).