Invest Clin 65(4): 436 - 444, 2024 https://doi.org/10.54817/IC.v65n4a04
Corresponding author: Li Li, Department of Obstetrics and Gynecology Laboratory, The First Affiliated Hospital
of Soochow University, Suzhou, China. E-mail: lili_edu.suda@hotmail.com
Karyotype analysis of fetus in pregnant
women with different indications
for amniocentesis.
Cen Ma, Lingyan Sun and Li Li
Department of Obstetrics and Gynecology Laboratory, The First Affiliated Hospital
of Soochow University, Suzhou, China.
Keywords: prenatal diagnosis; amniocentesis; karyotype analysis; chromosomal
abnormalities.
Abstract. To analyze the karyotype distribution in 1285 pregnant women
and evaluate the association between karyotype and diagnostic indications of
fetal chromosomal abnormalities, 1285 pregnant women with prenatal diagnos-
tic indications and successful amniocentesis admitted to our hospital from July
2019 to June 2022 were selected as study subjects for fetal karyotype analysis.
The distribution of prenatal diagnostic indications and abnormal karyotypes
were recorded, and the association between abnormal karyotypes and different
diagnostic indications was analyzed. Ninety-six abnormal chromosomal karyo-
types in amniotic fluid cells were detected in the samples, with an abnormal-
ity rate of 7.47%. Chromosome numerical abnormalities accounted for 70.83%
(68/96), and the detection rate was 5.29% (68/1285), the most common cat-
egory of abnormal kariotypes, trisomy 21, was the most common among them,
accounting for 44.79% (43/96). Advanced maternal age and high risk of sero-
logic screening were the main indications for prenatal diagnosis. The highest
detection rates were for abnormal non-invasive prenatal DNA testing and one
parent carrying chromosome abnormality, 27.63% and 42.86%, respectively.
Karyotype analysis of pregnant women with indications for amniocentesis is
effective in screening for fetal chromosomal abnormalities and reducing con-
genital anomalies.
Fetal karyotype analysis and different indications for amniocentesis 437
Vol. 65(4): 436 - 444, 2024
Análisis del cariotipo fetal de embarazadas con diferentes
indicaciones de amniocentesis.
Invest Clin 2024; 65 (4): 436 – 444
Palabras clave: diagnóstico prenatal; amniocentesis; análisis del cariotipo; anomalías
cromosómicas.
Resumen. El objetivo fue analizar la distribución del cariotipo de mujeres
embarazadas y evaluar la asociación entre el cariotipo y las indicaciones diagnós-
ticas de anomalías cromosómicas fetales. Un total de 1285 mujeres embarazadas,
con indicaciones de diagnóstico prenatal y amniocentesis exitosa, admitidas en
nuestro hospital desde julio de 2019 hasta junio de 2022 fueron seleccionadas
como sujetos de estudio para el análisis del cariotipo fetal. Se registró la distribu-
ción de las indicaciones de diagnóstico prenatal y los cariotipos anormales, y se
analizó la asociación entre los cariotipos anormales y las diferentes indicaciones
de diagnóstico. En las muestras se detectó un total de 96 cariotipos cromosómi-
cos anómalos en células de líquido amniótico, con una tasa de anormalidad del
7,47%. Las anomalías numéricas cromosómicas representaron el 70,83% (68/96)
y la tasa de detección fue del 5,29% (68/1285), siendo la categoría más común
de cariotipos anormales. Entre ellas, la trisomía 21 fue la más frecuente, con un
44,79% (43/96). La edad materna avanzada y el alto riesgo de cribado serológi-
co fueron las principales indicaciones para el diagnóstico prenatal. Las tasas de
detección más elevadas correspondieron a las pruebas prenatales no invasivas de
ADN anómalo y a un progenitor portador de anomalía cromosómica, 27,63% y
42,86%, respectivamente. En conclusión, el cariotipo de las mujeres embaraza-
das con indicación de amniocentesis es un cribado eficaz para detectar anomalías
cromosómicas fetales y reducir las anomalías congénitas.
Received: 06-05-2024 Accepted: 26-07-2024
INTRODUCTION
Chromosomal abnormalities are a com-
mon clinical genetic disorder that affects
one in every 150 infants 1. Infants with these
disorders are often mentally disabled, with
a variety of malformations and stunting 2.
At present, there is no effective treatment
for this type of disease. The primary reliance
is on prenatal screening and termination of
pregnancy to avoid the birth of such fetuses.
The standard prenatal diagnostic methods
are divided into two categories: non-inva-
sive prenatal testing and invasive prenatal
testing3. Non-invasive prenatal DNA testing
(NIPT), ultrasonography and maternal se-
rum screening are commonly used non-inva-
sive screening methods 2, 4, 5. However, these
methods cannot accurately detect genes in
fetal cells, and there are cases of missed di-
agnosis and misdiagnosis 6. Karyotyping af-
ter amniocentesis is still the gold standard
for detecting fetal chromosomal abnormali-
ties 7.
Amniocentesis is usually performed
at 18-24 weeks of pregnancy to detect fetal
chromosomal conditions by extracting and
culturing amniotic fluid cells 8. Karyotype
analysis is highly specific and sensitive, and
the diagnostic rate of fetal chromosomal ab-
438 Ma et al.
Investigación Clínica 65(4): 2024
normalities is almost 100% 9. Prenatal diag-
nostic indications for amniocentesis usually
include abnormal NIPT, high-risk maternal
serum screening, advanced maternal age, ab-
normal ultrasonographic indications, pater-
nal or maternal carrying chromosome abnor-
malities, and adverse pregnancy history 10, 11.
Despite the wealth of data available on
the outcomes of amniocentesis, gaps remain
in the literature, particularly concerning the
comprehensive analysis of karyotype results
by different indications for the procedure.
Previous studies have often focused on single
indications or a small subset of chromosom-
al abnormalities. The novelty of the present
study lies in its comprehensive approach,
analyzing a large, diverse cohort with a
wide range of indications for amniocentesis.
Therefore, this study aimed to assess the re-
lationship between various prenatal diagnos-
tic indications and fetal chromosomal abnor-
malities by performing a karyotype analysis
of amniotic fluid cells in 1285 instances by
amniocentesis in high-risk pregnant women.
PATIENTS AND METHODS
Sample collection
Our study design type is a present ret-
rospective study. One thousand two hundred
eighty-five pregnant women admitted to our
hospital for amniotic fluid karyotyping from
July 2019 to June 2022 were selected as the
study population. The pregnant women aged
19 to 46 and 18 to 24 weeks of gestation.
Detailed demographic and clinical data were
gathered by completing questionnaires,
conducting direct interviews with pregnant
women, and assessing medical records. The
study was approved by the First Affiliated
Hospital ethics committee of Soochow Uni-
versity, and all participants were informed
and signed the consent form.
Inclusion criteria: presence of prena-
tal diagnostic indications, including high
risk of NIPT, advanced maternal age, high
risk of serologic screening, abnormal ultra-
sonographic indications, history of adverse
pregnancy and one parent carrying chromo-
somal abnormalities; amniocentesis for the
first time.
Exclusion criteria: unsuccessful cul-
tures of amniotic fluid cells twice; the pres-
ence of threatened abortion.
Amniocentesis
The pregnant women and their families
were informed of the risks, and an amnio-
centesis was performed after signing the
informed consent. Twenty mL of amniotic
fluid was drawn from the pregnant women
and centrifuged at 2000 r/min for 10 min-
utes. After centrifugation, the supernatant
was discarded, and the cell suspension was
inoculated in the amniocyte culture medium
at 37°C and 5% CO2 for 9 to 10 days. The am-
niotic fluid cells were collected when multi-
ple clones with various metaphase cells were
observed with an inverted microscope. After
harvesting the cells, g-band staining was
performed and canned by a Leica GLS120
Automated Nuclear Scanning System. Thirty
karyotypes were routinely counted, and five
karyotypes were analyzed following the In-
ternational System for Human Cytogenetic
Nomenclature (ISCN) standard 12.
Statistical analysis
Statistical analysis was performed using
the IBM® SPSS 24.0® software. Count data
were expressed using frequency and rate (%)
and analyzed by chi-square test. p<0.05 was
considered a statistically significant difference.
RESULTS
Distribution of different diagnostic
indications
Among the 1285 pregnant women
with diagnostic indications, most cases
were prompted by high-risk maternal se-
rum screening, accounting for 573 cases
(44.59%), followed by advanced maternal
age with 522 cases (40.62%). Less frequent
indications included abnormal results from
non-invasive prenatal testing (NIPT), which
Fetal karyotype analysis and different indications for amniocentesis 439
Vol. 65(4): 436 - 444, 2024
led to 76 cases (5.91%), and abnormal ultra-
sonographic findings, which accounted for
67 cases (5.21%). The least common reasons
for amniocentesis were a history of adverse
pregnancy outcomes and parental chromo-
somal abnormalities, with 26 cases (2.02%)
and 21 cases (1.63%) respectively (Table 1).
Classification and detection rate
of abnormal karyotypes
The study examined 1,285 cases of
amniotic fluid samples from high-risk
pregnant women. Of these, 96 (7.47%)
cases showed chromosomal abnormalities.
Numerical abnormalities were the most
common, accounting for 68 (70.83%)
abnormal karyotypes. The most frequent
numerical abnormality was Trisomy 21,
which was observed in 43 (44.79%) cases,
followed by Trisomy 18 in 10 (10.42%)
cases, Trisomy 13 in 2 (2.08%) cases,
47 XXX (trisomy X) in 2 (2.08%) cases,
47 XYY (Jacob’s syndrome) in 1 (1.04%)
case, and 47 XXY (Klinefelter syndrome)
in 2 (2.08%) cases. Additionally, 1 (1.04%)
case of 45 X (Turner Syndrome or TS) was
detected. Structural abnormalities were
observed in 28 (29.17%) cases, including
6 (6.25%) translocations, 13 (13.54%) in-
versions, and 9 (9.38%) chromosome poly-
morphisms (Table 2).
Table 1
Distribution of different diagnostic indications.
Clinical indicator Cases Proportion (%)
High-risk maternal
serum screening
573
44.59
Advanced maternal age 522 40.62
Abnormal
ultrasonographic
indications
67
5.21
Abnormal NIPT 76 5.91
Paternal/maternal
carrying chromosome
abnormality
21
1.63
Adverse pregnancy
history
26
2.02
Total 1285 100
Table 2
Classification and detection rate of abnormal karyotypes.
Chromosomal karyotype Number
(n)
Occupancy%
(n/96)
Detection rate%
(n/1285)
Numerical abnormalities 68 70.83 5.29
Trisomy 21 43 44.79 3.35
Trisomy 18 10 10.42 0.78
Trisomy 13 2 2.08 0.16
47, XXX 2 2.08 0.16
47, XYY 1 1.04 0.08
47, XXY 2 2.08 0.16
45, X 1 1.04 0.08
Mosaicism 7 7.29 0.54
Structural abnormalities 28 29.17 2.18
Translocation 6 6.25 0.47
Inversion 13 13.54 1.01
Chromosome polymorphism 9 9.38 0.70
Total 96 100.00 7.47
440 Ma et al.
Investigación Clínica 65(4): 2024
Distribution of diagnostic indications
in pregnant women with amniotic fluid
karyotype abnormalities
The abnormal karyotype detection rate
of one parent carrying a chromosome abnor-
mality was 42.86% (9/21; calculation formu-
la of detection rate (%): n/number of preg-
nant women per diagnostic indication in
1285 cases (Table 3)), which was the highest
detection rate of all indications, followed by
high-risk NIPT (27.63%) and abnormal ultra-
sonographic indications (14.93%). The more
significant number of karyotype abnormali-
ties was found in advanced maternal age,
accounting for 30.21% (29/96), followed by
high-risk maternal serum (26.04%) and ab-
normal NIPT (21.88%).
Distribution of abnormal karyotypes for
different prenatal diagnostic indications
As shown in Table 4, trisomy 21 was
most common in pregnant women with ad-
vanced maternal age. Trisomy 21 also has
the highest proportion in other abnormal
karyotypes of older pregnant women. Fetal
chromosomal structural abnormalities are
mainly distributed in abnormal serological
screening, and one parent carries the ab-
normal chromosome. Fetal chromosomal
numerical abnormalities are mainly distrib-
uted in advanced maternal age, abnormal
NIPT, and high-risk maternal serum screen-
ing. However, in terms of the total number,
fetal chromosomal abnormalities are mainly
distributed between advanced maternal age
and high-risk maternal serum screening.
DISCUSSION
This study aimed to assess the relation-
ship between various prenatal diagnostic in-
dications and fetal chromosomal abnormali-
ties by performing a karyotype analysis of
amniotic fluid cells in 1,285 high-risk preg-
nant women. The most common indications
for amniocentesis were high-risk maternal
serum screening (44.59%) and advanced ma-
ternal age (40.62%), followed by abnormal
NIPT results (5.91%) and abnormal ultraso-
nographic findings (5.21%). Karyotype anal-
ysis detected chromosomal abnormalities in
96 cases, resulting in an abnormality rate
of 7.47%. Numerical chromosomal abnor-
malities were more common, accounting for
70.83% of the abnormalities, with trisomy
21 being the most frequent (44.79%). Struc-
tural chromosomal abnormalities comprised
29.17% of the abnormalities, with inversions
being the most common (13.54%).
The findings of this study are consistent
with previous research on the distribution
of prenatal diagnostic indications and the
detection rates of chromosomal abnormali-
ties. A study by Grgić et al. reported that the
most common indication for amniocentesis
was advanced maternal age 13. Additionally,
a study by Golshahi et al. reported that the
most common indication for amniocentesis
Table 3
Distribution of diagnostic indications in pregnant women with amniotic fluid karyotype abnormalities.
Clinical indication Abnormal karyotype(n) Detection rate (%) Proportion (%)
High-risk maternal serum screening 25 4.36 26.04
Advanced maternal age 29 5.56 30.21
Abnormal ultrasonographic indications 10 14.93 10.42
Abnormal NIPT 21 27.63 21.88
Paternal/maternal carrying
chromosome abnormality
9
42.86
9.38
Adverse pregnancy history 2 7.69 2.08
Total 96 7.47 100.00
Fetal karyotype analysis and different indications for amniocentesis 441
Vol. 65(4): 436 - 444, 2024
was abnormal serum screening, similar to
the results of the current study 14. Also, this
study’s overall chromosomal abnormality
detection rate of 7.47% is similar to other
studies 15, 16. However, the study of Sun et
al. reported the detection rate of abnormal
karyotypes to be 2.02%, which may be due to
the sample size and methods used 17.
The high detection rate of numerical
chromosomal abnormalities, particularly
trisomy 21, is well-documented in the lit-
erature. A review by Liu et al. found that
trisomy 21 was the most common chromo-
somal abnormality detected prenatally, ac-
counting for 46.77% of all abnormalities,
which aligns with the 44.79% reported in
the current study 18. Additionally, the study
of Ocak et al. confirms this finding with 46%
of all abnormalities 19. Regarding structural
chromosomal abnormalities, the findings of
this study are also consistent with previous
research. A study by Liu et al. reported that
deletion, duplication, inversion, and trans-
location were the most common structural
abnormalities detected prenatally 18.
The distribution of chromosomal abnor-
malities among the different prenatal diag-
nostic indications also aligns with previous
studies. Advanced maternal age and abnormal
serum screening have been consistently associ-
ated with higher rates of chromosomal abnor-
malities, particularly numerical abnormalities
like trisomy 21 20. The higher detection rate of
structural abnormalities in cases with parental
chromosomal abnormalities or abnormal NIPT
results has also been reported in the literature
21, 22. The abnormal NIPT group, a new kind of
prenatal screening in which fetal DNA was ex-
tracted from maternal serum for testing, had
the second-highest detection rate. It is com-
monly used in pregnancy screening because
of its excellent safety and specificity 23. NIPT
mainly targets the detection of autosomal an-
euploidy, and 12 cases of autosomal aneuploidy
were detected in the NIPT high-risk group, in-
cluding 8 cases of trisomy 21, 3 cases of trisomy
18 and 1 case of trisomy 13. However, accord-
ing to the statistical results, the high risk of
NIPT also implied the possibility of mosaicism,
inversion, and translocation.
Table 4
Distribution of abnormal karyotypes for different prenatal diagnostic indications.
Diagnosis indicator Chromosomal karyotype
a b c d e f Total
Trisomy 21 7 23 5 8 43
Trisomy 18 2 3 2 3 10
Trisomy 13 1 1 2
47, XXX 1 1 2
47, XYY 1 1
47, XXY 2 2
45, X 1 1
Mosaicism 3 4 7
Translocation 1 2 2 1 6
Inversion 3 2 2 6 13
Chromosome polymorphism 5 2 2 9
Total 25 29 10 21 9 2 96
a, High-risk maternal serum screening; b, Advanced maternal age; c, Abnormal ultrasonographic indications; d,
Abnormal NIPT; e, Paternal/maternal carrying chromosome abnormality; f, Adverse pregnancy history.
442 Ma et al.
Investigación Clínica 65(4): 2024
Prenatal ultrasonography cannot di-
rectly detect fetal chromosomal abnormali-
ties, but it can detect some ultrasound soft
markers associated with genetic abnormali-
ties. These soft indicators include thickened
nuchal fold, echogenic focus in the heart,
choroid plexus cyst and others 24. Positive
ultrasound soft indicators showed an in-
creased risk of aneuploidy in the fetus. In
our study, abnormal karyotypes were de-
tected in 10 pregnant women with abnormal
ultrasound findings, with a detection rate of
14.93% (10/67), 8 of which were aneuploid.
Ultrasonography in the middle of pregnancy
is essential for prenatal screening of chro-
mosomal abnormalities, especially in fetuses
with chromosomal aneuploidy.
While traditional karyotyping via am-
niocentesis remains the gold standard for
prenatal chromosomal analysis, new tech-
nologies are emerging that offer alterna-
tives or supplements to this invasive proce-
dure. Non-invasive prenatal testing (NIPT)
using cell-free fetal DNA from the mother’s
blood has become an increasingly common
screening tool, with an abnormal NIPT re-
sult prompting 5.91% of the amniocenteses
in this study. NIPT has high detection rates
for common aneuploidies like trisomies 21,
18, and 13, though it has limitations in iden-
tifying structural chromosomal abnormali-
ties 25. Additionally, chromosomal micro-
array analysis (CMA) and next-generation
sequencing (NGS) are newer technologies
offering higher resolution and the capabil-
ity to detect submicroscopic chromosomal
alterations that karyotyping might miss 26.
In conclusion, 96 karyotype abnor-
malities were detected in 1285 high-risk
pregnant women, with an abnormality rate
of 7.47%. NIPT, ultrasound, and serological
screening help detect fetal chromosomal ab-
normalities. Nevertheless, karyotype analy-
sis is still irreplaceable. Karyotype analy-
sis of amniotic fluid cells is recommended
for all pregnant women with indications of
prenatal diagnosis. However, this study has
limitations in that only the main indications
were included in the statistics for pregnant
women who met several indications. The
sample size was small, and more research is
required in future work.
Funding
None.
Conflict of competence
The authors declare no conflict of interest.
Authors’ ORCID number
• Cen M (CM):
0009-0004-8751-3120
• Lingyan Sun (LS):
0000-0002-8818-3563
• Li Li (LL):
0009-0003-8984-8373
Contribution of authors
CM: Contributed to the conception
of the work, data collection, conducting
the study, and data analysis, and agreed to
all aspects of the work. LS: Contributed to
the conception of the work, conducted the
study, revised the draft, approved the final
version of the manuscript, and agreed to all
aspects of the work. LL: Collection and entry
of data, manuscript writing, translation and
editing. All authors: Final approval of the
manuscript.
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