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BMC Pregnancy and Childbirth
Chromosome analysis offoetal tissue
from1903 spontaneous abortion patients in5
regions ofChina: aretrospective multicentre
study
Jian Zhang1†, Fangxiang Mu1,2†, Zhongjie Guo3, Zhuhua Cai4, Xianghui Zeng1,5, Lirong Du6 and Fang Wang1*
Abstract
Background Abnormal foetal tissue chromosome karyotypes are one of the important pathogenic factors for spon-
taneous abortion (SA). To investigate the age and abnormal foetal karyotypes of 1903 couples who experienced SA.
Methods A retrospective multicentre study collected age and foetal tissue karyotypes CNV-seq data of 1903 SA
couples from 6 hospitals in 5 regions from January 2017 to March 2022. The distribution and correlation of abnormal
foetal tissue karyotypes were evaluated by using regions and age.
Results In our study, 1140 couples (60.5% of the total) had abnormal foetal tissue chromosome karyotypes in all
regions. We found that there were differences in the number of abnormal foetal tissue chromosome karyotypes,
of which the incidence of trisomy was higher. At the same time, the populations situated in the eastern region had
a more triploid (15.5%) distribution, trisomy (58.1%) in the southern region, mosaicism (14.8%) and microduplication
(31.7%) in the southwestern region, microdeletion (16.7%) in the northern region. There are variances across areas,
and it is more common in the north. The incidence risk of prenatal chromosomal abnormalities varied according
to age group.
Conclusion The findings of this study suggest that the karyotypes of patients with abnormal foetal tissue chromo-
some abortion in different regions were different. Meanwhile, patients ≥ 35 years old had a higher risk of abnormal
foetal tissue chromosome abortion.
Keywords Foetal chromosome karyotypes, Spontaneous abortion, Retrospective multicentre study
†Jian Zhang and Fangxiang Mu contributed equally to this work.
*Correspondence:
Fang Wang
ery_fwang@lzu.edu.cn
1 Department of Reproductive Medicine, Lanzhou University Second
Hospital, Lanzhou 730030, China
2 Obstetrics Department, First Affiliated Hospital of Chongqing Medical
University, Chongqing 400042, China
3 Obstetrics Department, Third Hospital Affiliated to Guangdong
Pharmaceutical University, Guangdong 510410, China
4 Gynaecology Department, Rui’an People’s Hospital, Wenzhou 325207,
China
5 Department of Reproductive Medicine, Qinghai Provincial People’s
Hospital, Xining 810007, China
6 Eugenics Clinical Department, Hebei Reproductive Health Hospital,
Shijiazhuang 050090, China
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 2 of 11
Zhangetal. BMC Pregnancy and Childbirth (2023) 23:818
Spontaneous abortion (SA) is one of the most preva-
lent complications during pregnancy. Early spontane-
ous abortion is a condition defined by pregnancy failure
before 12weeks of pregnancy [1]. It was reported that
the risk of SA for women of reproductive age is approxi-
mately 10%. Only 3% to 11% of couples who experienced
an early SA had a partner with chromosomal abnormali-
ties [2–4]. Foetal tissue from couples with SA had a far
higher frequency of chromosomal abnormalities than
couples without SA. e current research indicates that
foetal chromosomal abnormalities are still the most com-
mon cause of SA, accounting for 50% of cases or more [5,
6]. Previous studies have emphasized the need to study
whether the demographic characteristics of patients are
related to the causes of SA [7, 8].
Most studies have reported that the incidence and dis-
tribution of chromosome abnormalities in couples with
SA are different in various countries and regions [9–18].
e incidence of them was less than 15%. e distribu-
tion of chromosome abnormalities among couples with
abortion was mostly concentrated in the structure of the
chromosomes (including translocation, inversion, dupli-
cation, insertion, and so on), the number of abnormal
chromosomes was less, and the distribution of studies in
various countries and regions was different [9, 11, 14, 18].
Compared with the probability of chromosomal abnor-
malities in couples with SA, the percentage of foetal
chromosomal abnormalities is far higher in this part of
the population. Chromosomal abnormalities in couples
directly affect the foetal chromosomes, but even cou-
ples with normal chromosomes can miscarry due to the
foetal chromosomal abnormalities [19]. ere are many
karyotypes including foetal chromosomal abnormalities,
among which aneuploidy and polyploidy are common
[20]. e age is a significant contributor to anomalies in
foetal chromosomes [2, 6].
e purpose of this study was to investigate the age
of 1903 couples with SA and to evaluate abnormal kar-
yotypes among their foetal tissues in 5 regions of China
(6 hospitals). We examined the correlation between the
patient’s age and karyotypes including foetal chromo-
some abnormalities. Additionally, we included the distri-
bution of chromosomes and age in 5 regions.
Materials andmethods
Patients
From January 2017 to March 2022, patients with SA
were treated in 6 hospitals (Lanzhou University Second
Hospital, Qinghai Provincial People’s Hospital, Hebei
Reproductive Health Hospital, Rui’an People’s Hospital,
Guangdong Pharmaceutical University ird Affiliated
Hospital, and the First Affiliated Hospital of Chongqing
Medical University) was taken as the research objects.
e foetal tissue karyotypes copy number variation
sequencing (CNV-seq) and age data of patients’ foetal tis-
sue were collected in 6 hospitals. e inclusion criteria:
1. Early SA before 12weeks of gestation; 2. e patients
need to perform uterine cavity cleaning operations, and
obtain abortion tissue for CNV-seq and provide exami-
nation report data for scientific research voluntarily;
3. e informed consent was signed by all patients in 6
hospitals. e study used non-identifiable patient data
and was approved by the ethics review committee of the
6 hospitals. Studies were approved by the following ethi-
cal committees: the Ethics Committee of Rui’an People’s
Hospital, the Ethics Committee of Lanzhou University
Second Hospital, the Ethics Committee of Qinghai Pro-
vincial People’s Hospital, the Ethics Committee of First
Affiliated Hospital of Chongqing Medical University, the
Ethics Committee of ird Hospital Affiliated to Guang-
dong Pharmaceutical University, and the Ethics Commit-
tee of Hebei Reproductive Health Hospital. e research
complies with the Declaration of Helsinki. To investi-
gate regional differences, we divided the 6 hospitals into
5 regions for analysis and research. Lanzhou and Qing-
hai belong to Northwest China, Hebei belongs to North
China, Rui’an belongs to East China, Guangdong belongs
to South China, and Chongqing belongs to southwest
China.
In this study, we focused on triploid, trisomy, mosai-
cism, 45,X, microduplication, microdeletion, and mono-
somy in the CNV-seq. Triploid refers to an abnormal
condition in the number of chromosomes in a cell, where
an increase in the number of chromosomes forms trip-
loid, with each chromosome having three times the num-
ber of normal cells [21]. Trisomy refers to a chromosomal
numerical abnormality where there is an extra copy of a
chromosome compared to the normal cell complement.
In trisomic cells, one of the chromosome pairs has an
additional chromosome, resulting in three homologous
chromosomes for that particular chromosome [22–24].
Mosaicism is a gene-related disease that refers to the
presence of cell populations from different genomes in
an organism [25, 26]. When the calculated copy number
of CNV-seq is between 2.1 and 2.8, it indicates trisomic
mosaicism, and between 1.2 and 1.9, there is monosomic/
diploid mosaicism [27–29]. e majority (86.5%) of chi-
merism occurrence in CNV-seq is confined placental
mosaicism (CPM, mosaicism occurs only in the placenta
and not in the fetus), and a small portion (13.5%) is true
fetal mosaicism (TFM, mosaicism occurs both in the pla-
centa and fetus) [30–32]. A few common and well-known
disease-causing rearrangements between the 30 kb
and 5 Mb size-range, are referred to as chromosomal
microdeletion and microduplication [33]. Monosomy
refers to the presence of a single copy of a chromosome,
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Page 3 of 11
Zhangetal. BMC Pregnancy and Childbirth (2023) 23:818
representing a numerical aberration in the chromosome
complement. In normal circumstances, chromosomes
exist in pairs. However, chromosomal aberrations can
lead to the presence of a monosomic chromosome, where
only one copy of the chromosome is present [34–36]. A
common example of chromosomal monosomy is Turner
syndrome, also known as monosomy X (45,X) [37].
Statistical analysis
e SPSS software (IBM, version 26.0) and R software
(version 4.2.1) were used to calculate the data. e
patients’ age and chromosome data were summarized by
mean ± SD and proportions, and the data were compared
across whole groups using chi-squared and Fisher exact
test.
In order to better understand the relationship between
age and abnormal foetal chromosomes, the ages of
patients were divided by an optimal cutoff value deter-
mined using Youden’s index of the receiver operating
characteristic curves (ROC). To test whether the effect of
age on abnormal foetal chromosomes varied by region,
statistical interaction terms were introduced into sepa-
rate fully adjusted models (Adjustment for multiple
comparisons: Bonferroni). Effect modification was tested
using α = 0.10 threshold.
We presented risk ratios (RRs) and rate differences
(RDs) with 95% confidence interval (95%CI) to compare
foetal tissue chromosomal abnormalities-associated SA
incidence rates in our study population with rates expe-
rienced by ages of SA patients in 5 regions. e RR of dif-
ferent categories of abnormal chromosome karyotypes
was presented in different age groups by using forest
plots. When the p-value was less than 0.05, the results
were deemed statistically significant.
Results
Patient characteristics of5 regions
From January 2017 to March 2022, of 1903 included
patients with SA, the proportions of patients contrib-
uted by region were: East, 21.3% (405); North, 5.4% (103);
Northwest, 15.3% (292); South, 22.7% (432); Southwest,
35.3% (671). Demographic and foetal tissue chromosome
karyotype conditions were presented in Table1. Of these,
A greater proportion (60.5%, 1140/1903) was patients
with abnormal foetal tissue chromosome karyotypes
in all regions. e age was 30.9 ± 7.8 in all patients, the
normal foetal tissue chromosome karyotypes’ mean age
Table 1 Demographic and foetal tissue chromosome karyotypes of SA patients in 5 regions (6 hospitals)
1 Summarized as number (percentage) or mean ± SD. 2Age’s analysis was using the ANOVA test, other indexes were using the Chi-square test or Fisher exact test. 3 The
bold p value was statistically signicant. 4 Multiple-chr: number of abnormal chromosomes ≥ 3
East vs. North a Northwest b, South c Southwest d North vs. Northwest e, South f, Southwest g, Northwest vs. South h, Southwest I, South vs. Southwest j
The p value of comparison was statistically signicant
Characteristic All patients
(n = 1903) 1East
(n = 405) North
(n = 103) Northwest
(n = 292) South
(n = 432) Southwest
(n = 671) Test value2p value3
Age 30.8 ± 4.7 29.2 ± 4.5 abcd 31.3 ± 4.6 31.3 ± 4.4 32.2 ± 4.9 j30.6 ± 4.5 23.8 < 0.001
Age of foetal tissue chromosome karyotypes
Normal 30.6 ± 4.4 28.9 ± 4.3 abcd 31.1 ± 3.8 31.3 ± 4.2 h 31.6 ± 4.3 j30.0 ± 4.5 10.4 < 0.001
Abnormal 30.9 ± 4.9 29.4 ± 4.6 abcd 31.4 ± 5.0 31.2 ± 4.5 hi 32.9 ± 5.3 j30.8 ± 4.6 16.1 < 0.001
Number of foetal tissue chromosome karyotypes
Normal 763(39.5) 145(35.8) 36(35.0) 146(50.0) 228(52.8) 208(31.0) 68.216 < 0.001
Abnormal 1140(60.5) 260(64.2) bc 67(65.0)ef 146(50.0) i204(47.2) j463(69.0)
Number of abnormal foetal tissue chromosome karyotypes 4
One-chr 952(83.5) 198(76.2) bd 54(80.6) eg 97(66.4) hi 168(82.4)j435(94.0) 78.385 < 0.001
Two-chr 76(6.7) 17(6.5) bd 6(9.0) eg 32(21.9) hi 9(4.4) 12(2.5) 53.809 < 0.001
Multiple-chr 112(9.8) 45(17.3) d7(10.4) g17(11.6) i27(13.2) j16(3.5) 44.297 < 0.001
Categories of abnormal foetal tissue chromosome karyotypes
Number n = 1279 n = 284 n = 90 n = 191 n = 234 n = 480
Triploid 102(8.0) 44(15.5) abd 4(4.4) 9(4.7) h27(11.5) j18(3.8) 39.688 < 0.001
Trisomy 584(45.7) 164(57.7) bd 43(47.8) g72(37.7) h136(58.1) j169(35.2) 57.539 < 0.001
Mosaicism 127(9.9) 13(4.6) abd 11(12.2) f24(12.6) h8(3.4) j71(14.8) 37.791 < 0.001
45,X 87(6.8) 28(9.9) b8(8.9) 8(4.2) 13(5.6) 30(6.3) 7.409 0.112
Microduplication 260(20.3) 9(3.2) abcd 9(10.0) eg 58(30.4) h32(13.7) j152(31.7) 113.938 < 0.001
Microdeletion 92(7.2) 20(7.0) a15(16.7) fg 17(8.9) 16(6.8) 24(5.0) 14.301 0.006
Monosomy 27(2.1) 6(2.1) 0(0.0) 3(1.6) 2(0.9) j16(3.3) 6.369 0.148
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Zhangetal. BMC Pregnancy and Childbirth (2023) 23:818
was 30.6 ± 4.5 and the abnormal was 30.9 ± 4.9. e most
common number of abnormal chromosomes was one
chromosome (One-chr, 83.5%, 952/1140) in foetal tissue
chromosome karyotypes. 188 patients had ≥ 2 numbers
and categories of abnormal foetal tissue chromosome
karyotypes in the 1140 patients with abnormal foetal tis-
sue chromosome karyotypes.
ere were 1279 categories of abnormal foetal tissue
chromosome karyotypes in 1140 patients. e number of
patients in all abnormal foetal tissue chromosome karyo-
types was presented in Table1 and Fig.1 (including the
number and percentage stacked histogram). Categories
of abnormal foetal tissue chromosome karyotypes were
trisomy (45.7%, 584/1279), microduplication (20.3%,
260/1279), mosaicism (9.9%, 127/1279), triploid (8%,
102/1279), microdeletion (7.2%, 92/1279), 45,X (6.8%,
87/1279), and monosomy (2.1%, 27/1279). e most
likely occurrence of abnormal foetal tissue chromosome
karyotypes in different regions was different. e popula-
tions situated in the eastern region had a more triploid
(15.5%, 44/284) distribution, trisomy (58.1%, 136/234)
in the southern region, mosaicism (14.8%, 71/480), and
microduplication (31.7%, 152/480) in the southwestern
region, microdeletion (16.7%, 15/90) in the northern
region. ere was no significant difference in the fre-
quency of 45,X and monosomy in each region.
Distribution ofabnormal chromosome karyotypes in23
pairs ofchromosomes
e distribution of the 23 pairs of chromosomes by
region was in Fig. 2 and Supplementary Table 1. e
distribution of all abnormal foetal tissue chromosome
karyotypes was enrichment on chromosomes 16 (18.1%,
193/1066) and 22 (10.2%, 109/1066), and fewest on
chromosome 17 (1.1%, 12/1066). ere was a statistical
difference in the distribution of chromosomes 3, 4, 19, 22,
and X/Y of all abnormal foetal tissue chromosome karyo-
types in each region (p = 0.026, 0.007, 0.029, 0.018, and
p < 0.001, respectively, Fig. 2A). e most common chro-
mosome distribution of trisomy was not random with
more enrichment on chromosomes 16 (22.9%, 134/584)
and 22 (12.8%, 75/584), and fewest on chromosome X/Y
(0.5%, 3/584). ere was a statistical difference in the dis-
tribution of chromosome 22 of trisomy in each region
(p = 0.011, Fig. 2B). e distribution of mosaicism was
enrichment on chromosome X/Y (32.3%, 41/127) and 16
(11.0%, 14/127), and showed no signs on chromosome
10 (0%, 0/127) and 17 (0%, 0/127). ere was a statistical
difference in the distribution of chromosomes 3, 11, and
X/Y of mosaicism in each region (p = 0.032, 0.007, 0.033,
respectively, Fig.2C). e distribution of microduplica-
tion was enrichment on chromosome 16 (16.9%, 44/260),
and fewest on chromosome 5 (0.4%, 1/260). ere was
a statistical difference in the distribution of chromo-
somes 1, 3, 8, 21, and X/Y of microduplication in each
region (p = 0.032, 0.003, 0.027, 0.036, 0.001, respectively,
Fig.2D). e distribution of microdeletion was enrich-
ment on chromosome X/Y (21.7%, 20/92), and fewest on
chromosome 11 (0%, 0/92). ere was a statistical differ-
ence in the distribution of chromosomes 3, 4, 5, 7, and
X/Y of microdeletion in each region (p = 0.043, 0.001,
0.049, 0.022, 0.002, respectively, Fig.2E).
Distribution condition ofpatients indierent age groups
andregions
As the single index, the optimal cut-off value of age was
analyzed by ROC for grouping only. e AUC (95% CI)
of age in all regions was 0.5 (0.5–0.6), p = 0.025. Base d
on the Youden index, the optimal cut-off for age was
34.5years with sensitivity (24.4%) and specificity (82.7%).
Fig. 1 The stacked histogram of distribution for abnormal foetal tissue chromosome karyotypesin all regions. A The number of patients with all
abnormal foetal tissue chromosome karyotypes. B The percentages of patients with all abnormal foetal tissue chromosome karyotypes
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Zhangetal. BMC Pregnancy and Childbirth (2023) 23:818
Fig. 2 The stacked histogram of distribution forthe 23 pairs chromosomes by region in abnormal foetal tissue chromosome karyotypes. A The
number and percentage of distribution for the 23 pairs chromosomes inabnormal foetal tissue chromosome karyotypes. B The distribution
for the 23 pairs chromosomes intrisomy. C The distribution for the 23 pairs chromosomes inmosaicism. D The distribution for the 23 pairs
chromosomes inmicroduplication. E The distribution for the 23 pairs chromosomes inmicrodeletion
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Zhangetal. BMC Pregnancy and Childbirth (2023) 23:818
e patients were divided into the < 35years group and
the ≥ 35years group. We evaluated whether the interac-
tion between age and region was related to the occur-
rence of abnormal foetal tissue chromosome karyotypes
(Fig.3). Regardless of region, patients over 35years old
had more abnormal foetal tissue chromosome karyotypes
than patients under 35years old (Figs.3A and B). ere
was a main effect of age (F = 18.4, p < 0.001, η2 = 0.009)
and region (F = 15.8, p < 0.001, η2 = 0.032), but no inter-
action effect of age * region (F = 0.3, p value for interac-
tion = 0.883, η2 = 0.001). e pairwise comparisons of the
main effect in age and regions were shown in Fig.3. e
results revealed no interaction between age and regions,
and the parallelism test was passed (p value for interac-
tion = 0.883). e covariance analysis findings showed
that age variations may cause considerable changes in
the rate of foetal tissue chromosome abnormalities,
and that when age was controlled for, the abnormality
rate varies dramatically between regions. e covari-
ance results indicate that age differences could lead to
significant changes in the rate of foetal tissue chromo-
some abnormalities, and controlling for age, the abnor-
mality rate varies significantly among different regions
(Table2). Compared with < 35years patients, ≥ 35 years
patients observed increases (mean difference = 0.139,
p < 0.001). e patients in the eastern, north, and south-
western region were more SA with abnormal foetal tis-
sue chromosome karyotypes than northwestern (mean
difference = 0.157, 0.140, 0.186, p = 0.016, 0.038, < 0.001,
respectively) and southern (mean difference = 0.210,
0.157, 0.239, p < 0.001, 0.013, < 0.001, respectively,
Fig.3C).
e proportion of ≥ 35 years patients was slightly
higher than < 35 years (59.7 vs. 68.3%, Chi-square
value = 10.6, p < 0.001). Overall, the relative risk rate (RR)
of ≥ 35 years patients was a significant 1.3-fold higher
than < 35 years in all regions (RR, 1.3, 95%CI, 1.1–1.5),
equating to an absolute RD of 8.6% (95%CI, 6.4–10.3)
(Table3). A very similar situation was observed for each
region but the northern region.
We observed the risk of all categories of abnormal
foetal tissue chromosome karyotypes in different age
groups. Overall, the risk of triploid in ≥ 35 years patients
was lower than that of < 35years (RR, 0.4, 95%CI, 0.2–0.7,
p = 0.031), while the risk of trisomy was a significant
1.2-fold higher in ≥ 35 years patients than that < 35 years
(RR, 1.3, 95%CI, 1.2–1.5, p < 0.001). e risks of other
abnormal foetal tissue chromosome karyotype categories
were not statistically significant in the < 35 and ≥ 35years
groups of patients (p > 0.05, Table4 and Fig.4).
Fig. 3 The main effect and interaction effect in age and regions. A The occurrence of abnormal foetal tissue chromosome karyotypes for 5 regions
stratified byage. B The occurrence of abnormal foetal tissue chromosome karyotypes for < 35 and ≥ 35 years stratified by 5 regions. C The heatmap
of main effect in age and regions. Red meant more abnormal foetal tissue chromosome karyotypes on the left than on the top. Blue meant
the less on the left. One cell included mean difference value and pvalue. blank cells indicated that there was no significant interaction effectin age
*region (p = 0.883)
Table 2 The covariance analysis results of SA patients with
normal and abnormal foetal tissue chromosome karyotypes by
age in all regions
The region results of covariance analysis when maternal age was controlled. The
bold p value was statistically signicant
Variables OR 95%CI Z value p value
Region (South) Ref 3.0 (1.5–5.9) 3.1 < 0.001
Region (East) 0.5 (0.3–0.7) -3.3 < 0.001
Region (North) 0.9 (0.6–1.2) -0.9 0.364
Region (Northwest) 0.5 (0.3–0.6) -5.4 < 0.001
Region (Southwest) 0.4 (0.3–0.5) -7.5 < 0.001
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Zhangetal. BMC Pregnancy and Childbirth (2023) 23:818
Discussion
Abnormal foetal tissue chromosome karyotypes have
long been recognized as the major cause of SA, with
abnormal foetal tissue chromosome karyotypes account-
ing for nearly half of all SAs [38]. e incidence of
abnormal foetal tissue chromosome karyotypes differs
geographically. Our study found that the incidence of
abnormal foetal tissue chromosome karyotypes in most
regions was more 50%, among which the incidence in the
eastern, northern, and southwestern regions was more
than 60%.
e region plays an important role in the pathogenesis
of embryo chromosome abnormalities, but the research
on embryo chromosomal abnormalities is different in dif-
ferent regions. It is unknown climate, living environment,
eating habits, ethnic differences, and other regional fac-
tors affect the distribution of embryo chromosome
abnormalities. At present, there are few reports on the
relevant regional environments and abnormal chro-
mosome distributions, and the karyotypes needs to be
further studied. A study in Northeast China found that
trisomy 22 and trisomy 16 were more prevalent, and the
incidence of foetal tissue chromosomal abnormalities
in pregnant women over 40years old was significantly
higher than that in other age groups [39]. According to
Swedish research, trisomy 16 and sex chromosomal
abnormalities accounted for a high proportion of all
chromosomal abnormalities. e autosomal and X chro-
mosomes were positively associated with the age, but the
X single chromosome and polyploidy were negatively
related to the age [40]. Korean research discovered a high
prevalence of trisomy 22 but did not examine the asso-
ciation between age and chromosomal abnormalities
[20]. Most previous studies reported foetal tissue chro-
mosomal abnormalities, focusing on the overall distribu-
tion of the number of abnormal karyotypes in 23 pairs
of chromosomes. Moreover, relatively few studies on the
various regions and age distributions of patients with
abnormal foetal tissue chromosome karyotypes have
been reported in association with SA.
is study reviewed the foetal tissue chromosome kar-
yotypes study of 1903 patients, who belong to our cohort
study on SA. e present study encompassed patients
within 5 defined geographic regions in China, without
Table 3 TheriskofSApatients with normal and abnormal foetal tissue chromosome karyotypes by age in allregions
The bold p value was statistically signicant
Region Age Abnormal N Chi-square p value Rate(%) 95%CI RR 95%CI RD% 95%CI
All < 35 886 1484 10.6 < 0.001 59.7 (57.2–62.2) Ref (1.1–1.5) Ref (6.4–10.3)
≥ 35 286 419 68.3 (63.6–72.5) 1.3 8.6
East < 35 219 353 5.6 0.018 62 (57.0–67.1) Ref (1.1–1.5) Ref (3.0–27.1)
≥ 35 41 52 78.8 (67.7–89.9) 1.3 16.8
North < 35 48 78 1.8 0.187 61.5 (50.7–72.3) Ref (0.9–1.6) Ref (-7.4–31.2)
≥ 35 19 25 76 (59.3–92.7) 1.2 14.5
Northwest < 35 109 233 4.8 0.029 46.8 (40.4–53.2) Ref (1.1–1.7) Ref (1.7–28.8)
≥ 35 37 59 62.7 (50.4–75.1) 1.3 15.9
South < 35 125 291 6.5 0.011 43.0 (37.4–48.7) Ref (1.1–1.6) Ref (10.4–15.3)
≥ 35 79 141 56.0 (47.8–64.0) 1.3 13.0
Southwest < 35 385 547 4.5 0.038 71.2 (67.2–74.8) Ref (0.9–1.7) Ref (0.9–7.9)
≥ 35 99 124 76.2 (68.1–82.7) 1.2 5.0
Table 4 The risk of all abnormal foetal tissue chromosome karyotypes by age in all regions
The bold p value was statistically signicant
Abnormal foetal tissue
chromosome karyotypes All East North Northwest South Southwest Z value p value
Triploid 0.4(0.2–0.7) 0.8(0.4–1.9) 0.0(0.0–0.0) 0.4(0.0–2.8) 0.3(0.1–0.8) 0.2(0.0–1.4) 2.16 0.031
Trisomy 1.3(1.2–1.5) 1.3(1.1–1.6) 1.9(1.4–2.5) 1.1(0.8–1.6) 1.3(1.1–1.6) 1.2(0.9–1.5) 5.33 < 0.001
Mosaicism 0.6(0.4–1.0) 0.0(0.0–0.0) 0.8(0.2–3.6) 1.4(0.6–3.3) 1.6(0.3–7.6) 0.4(0.2–0.7) 1.36 0.174
45,X 0.6(0.4–1.1) 0.4(0.1–1.7) 1.0(0.2–4.4) 1.8(0.4–7.0) 0.3(0.1–1.3) 0.8(0.3–1.9) 1.44 0.149
Microduplication 1.2(0.9–1.5) 0.0(0.0–0.0) 1.5(0.4–5.2) 1.1(0.7–1.8) 1.2(0.6–2.6) 1.2(0.9–1.6) 1.44 0.149
Microdeletion 0.6(0.4–1.1) 0.3(0.0–2.0) 0.0(0.0–0.0) 0.6(0.2–2.1) 0.8(0.3–2.2) 1.3(0.5–3.2) 0.52 0.604
Monosomy 0.4(0.1–1.2) 2.7(0.5–14.1) 0.0(0.0–0.0) 0.0(0.0–0.0) 0.0(0.0–0.0) 0.2(0.0–1.6) 0.29 0.771
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 8 of 11
Zhangetal. BMC Pregnancy and Childbirth (2023) 23:818
Fig. 4 The forest plots forrisk of all categories of abnormal foetal tissue chromosome karyotypes in different age groups. A The forest plots for RR
of triploid in all regions. B The forest plots for RR of trisomy in all regions. C The forest plots for RR of mosaicism in all regions. D The forest plots for RR
of 45,X in all regions. E The forest plots for RR of microduplication in all regions. F The forest plots for RR of microdeletion in all regions. G The forest
plots for RR of monosomyin all regions. The no-effect line was 1. The left side of no-effect line was < 35 years group, and right was ≥ 35 years group
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 9 of 11
Zhangetal. BMC Pregnancy and Childbirth (2023) 23:818
selection for age. e most frequent abnormal foetal tis-
sue chromosome karyotype among SA patients was tri-
somy. e present study statistically validated that there
were significant differences in the regional distribution
depending on the abnormal karyotype, unlike the previ-
ously mentioned earlier study. In our study, nearly half
of the patients had trisomy. e distribution of trisomy
patients in the East and South was greater than that in
the West and North. e distributions of other karyo-
types (triploid, mosaicism, microduplication, microde-
letion) were also different in different regions. We also
confirmed that the incidence of foetal chromosomal
abnormalities in SA patients over 35years old was higher.
At the same time, the karyotypes of abnormal embryos in
different age groups were found to be different.
Triploid has been identified as a significant contribu-
tor to spontaneous abortion. It may have anything to do
with the father’s age [41]. Trisomy is one of major cause
of spontaneous abortion. is chromosomal abnormal-
ity interferes with normal foetal development, leading
to problems such as incomplete foetal growth, organ
malformations, and functional impairments, ultimately
resulting in the inability to sustain pregnancy or sponta-
neous abortion. It is important to note that not all cases
of trisomy result in spontaneous abortion. Some trisomy
abnormalities may lead to the birth of children with a
range of genetic disorders and developmental disabilities
rather than abortion during pregnancy [42, 43]. Research
has shown that chromosomal abnormalities resulting
from mosaicism may be associated with abnormal foetal
development, thereby increasing the risk of spontaneous
abortion [44, 45]. Beyond the risk of spontaneous abor-
tion, CPM have a major clinical impact on foetal placen-
tal development and are detectable through noninvasive
prenatal testing and chorion villous sampling. ese
include the risks of stunted foetal growth, small for ges-
tational age, foetal growth restriction, and hypertensive
disorders [30, 46, 47]. Microduplication and microdele-
tion have been linked to miscarriage, however their role
in this phenomenon has been little studied [48, 49]. e
most common single chromosome is 45, X, also known
as Turner syndrome, and not all monosomy could cause
miscarriage. 45, X mainly affects the reproduction, intel-
ligence, and body development of the fetus [50, 51]. By
clearing out these mysteries, we may advance towards
more effective clinical and patient management.
Strengths andlimitations
is study’s major strength was its capture of SA
patients with data on the foetal chromosomes from 5
regions across China (6 hospitals). A total of 1140 SA
patients with abnormal foetal tissue chromosome kar-
yotypes from 5 years in 6 hospitals were included, and
disregarding patients’ abortion status enabled a more
thorough understanding of distribution for abnormal
foetal tissue chromosome karyotypes. In addition, we
ascertained the age and regions considering the distribu-
tion of abnormal foetal tissue chromosome karyotypes
and distinguished among the occurrence of categories
and 23 pairs of chromosomes. Our study also had limita-
tions, including the fact that more potential factors were
not used for descriptive analysis in this study. For mosai-
cism, we could not distinguish between CPM and TFM.
Conclusion
Overall, the findings of this study suggest that the inci-
dence rate of SA among patients with abnormal foetal
tissue chromosome karyotypes was more than half of
patients with SA. In addition, correlations between the
abnormal foetal tissue chromosome karyotypes and the
patient’s demographic data (age or region distribution)
were observed. With a large cohort, we were able to pro-
vide a wide spectrum of data on the frequency and differ-
ent types of chromosomal abnormalities. us, our study
provides valuable data for a better understanding of chro-
mosome analysis in couples experiencing SA.
Supplementary Information
The online version contains supplementary material available at https:// doi.
org/ 10. 1186/ s12884- 023- 06108-0.
Additional le1: Supplementary Table1. The number of percentage of
distribution for the 23 pairs chromosomes in abnormal fetal karyotypes.
Supplementary Table2. The distribution for the 23 pairs chromosomes
in trisomy. Supplementary Table3. The distribution for the 23 pairs
chromosomes in trisomy mosaicism. Supplementary Table4. The
distribution for the 23 pairs of chromosomes in trisomy microduplication.
Supplementary Table5. The distribution for the 23 pairs chromosomes
in trisomy microdeletion.
Acknowledgements
We acknowledge the support received from the Lanzhou University Second
Hospital. Meanwhile, we acknowledge the department leaders (Fangxiang
Mu, Zhongjie Guo, Zhuhua Cai, Xianghui Zeng, and Lirong Du) of other hos-
pitals and their hospitals (The First Affiliated Hospital of Chongqing Medical
University, Guangdong Pharmaceutical University Third Affiliated Hospital,
Rui’an People’s Hospital, Qinghai Provincial People’s Hospital, and Hebei
Reproductive Health Hospital) that have provided data. In particularly, useful
suggestions and supports given by Professor Fang Wang.
Authors’ contributions
The study conception and design were performed by J.Z and F.W. Material
preparation, data collection, and analysis were performed by J.Z. and FX.M. J.Z
and FX.M contributed equally to this work. FX.M, ZJ.G, ZH.C, XH.Z, LR.D, and
F.W provided raw data. All authors commented on previous versions of the
manuscript. All authors read and approved the final manuscript.
Funding
This work was funded by the Science Foundation of Lanzhou University (Grant
No. 071100132 and 071100186), the Medical Innovation and Development
Project of Lanzhou University (Grant No. lzuyxcx-2022-137), and the Science
Foundation of Lanzhou University Second Hospital (Grant No. YJS-BD-19).
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 10 of 11
Zhangetal. BMC Pregnancy and Childbirth (2023) 23:818
Availability of data and materials
The data that support the findings of this study are available on request
from the corresponding author. Researchers who are interested in working
together on our study are more than welcome to collaborate. Contact the
paper’s corresponding author, Fang Wang, [ery_fwang@lzu.edu.cn].
Declarations
Ethics approval and consent to participate
The informed consent was signed by all patients in 6 hospitals. The study used
non-identifiable patient data and was approved by the ethics review commit-
tee of the 6 hospitals. The research complies with the Declaration of Helsinki.
Competing interests
The authors declare no competing interests.
Received: 9 August 2023 Accepted: 4 November 2023
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