Challenges and optimization of prenatal diagnosis in cold regions: Combined application of karyotyping and CNV-Seq with seasonal compliance analysis

Luyao Liu; Yuhong Zhang; Yitong Wang; Kai Zheng; Hao Wang; Ying Wang

doi:10.1515/fzm-2026-0011

Challenges and optimization of prenatal diagnosis in cold regions: Combined application of karyotyping and CNV-Seq with seasonal compliance analysis

doi: 10.1515/fzm-2026-0011

The Sixth Affiliated Hospital of Harbin Medical University

Funds: Not applicable

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Corresponding author: Ying Wang, E-mail: lly5319@163.com

摘要

Abstract: Objective Prenatal diagnosis in cold regions faces distinctive challenges related to extreme cold climatic conditions, which can substantially reduce healthcare compliance among pregnant women and limit the accessibility and accuracy of local prenatal diagnostic services. However, targeted research on region-specific diagnostic barriers and optimized combined detection strategies remains insufficient. This study systematically investigated the unique challenges of prenatal diagnosis in cold regions, with particular emphasis on the impact of harsh climatic conditions on healthcare compliance among pregnant women and evaluated the clinical utility of integrating chromosomal karyotyping with copy number variation sequencing (CNV-seq). Methods A retrospective analysis was conducted among high-risk pregnant women over a two-year period. Seasonal differences in prenatal clinic attendance were statistically analyzed to identify key barriers affecting healthcare compliance. Additionally, the clinical efficacy of combined chromosomal karyotyping and CNV-seq was systematically evaluated. Results Retrospective analysis of high-risk pregnancies revealed a statistically significant decline in winter clinic attendance (χ² = 9.51, P < 0.05) over the two-year period, mainly associated with transportation difficulties, concerns regarding nosocomial infection, and local cultural practices. The combined use of chromosomal karyotyping and CNV-seq demonstrated complementary diagnostic value. Karyotyping identified 12 balanced translocations, 23 sex chromosome aneuploidies, and 29 chromosomal polymorphic variants, while CNV-seq detected 19 pathogenic or likely pathogenic microdeletions/microduplications, including 16 pathogenic variants. Together, the two methods increased the overall abnormality detection rate to 18.64% (118/633), representing a 7.42% improvement over single-method detection strategies. Conclusions Based on these findings, several regionally optimized strategies are proposed, including the establishment of a "central laboratory + satellite clinics" network, the promotion of non-invasive prenatal testing (NIPT) combined with first-trimester ultrasound screening to reduce unnecessary invasive procedures, and improved management of high-risk pregnancies through tele-genetic counseling, winter green-channel services, and vitamin D supplementation. This study provides both theoretical and practical frameworks for improving the precision, accessibility, and equity of prenatal diagnostic systems in cold regions.
- prenatal diagnosis /
- karyotyping /
- copy number variation sequencing /
- seasonal compliance /
- microdeletions/microduplications

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Figure 1. Indication distribution of pregnancies undergoing prenatal diagnosis

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Figure 2. Seasonal distribution of pregnancies undergoing prenatal diagnosis

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Table 1. Karyotyping results

Abnormal Karyotype	Number of Abnormalities	Detection Rate (%)	Proportion(%)
47,XN,+21	21	3.32	21.21
47,XN,+18	3	0.47	3.03
47,XNN	13	2.05	13.13
45,X	2	0.32	2.02
Autosomal Mosaicism	3	0.47	3.03
Sex Chromosome Mosaicism	8	1.26	8.08
Balanced Translocation	12	1.90	12.12
Unbalanced Translocation	8	1.26	8.08
Polymorphism	29	4.58	29.29
Total Abnormalities	99	15.64	100.00

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Table 2. 19 microdeletions/microduplications detected by CNV-seq

	CNV-seq	Type	Indications
1	sseq[GRCh37]22q11.21q11.21(18920346_21630621) × 3 chr22:g.18920346_21630621dup	Pathogenicity	High risk in NIPT
2	sseq[GRCh37]22q11.21q11.21(18882825_21796237) × 3 chr22:g.18882825_21796237dup	Pathogenicity	Parental chromosomal abnormalities
3	sseq[GRCh37]22q11.21q11.22(21746118_22964181) × 1 chr22:g.21746118_22964181del	Likely pathogenicity	Ultrasonic abnormalities, history of adverse pregnancy outcomes
4	sseq[GRCh37]17q12q12(34513616_36299170) × 1 chr17:g.34513616_36299170del	Pathogenicity	Ultrasonic abnormalities
5	sseq[GRCh37]22q11.21q11.22(18815839_21657982) × 1 chr22:g.18815839_21657982del	Pathogenicity	Advanced maternal age, high risk in NIPT
6	sseq[GRCh37]22q11.21q11.22(18882825_21713868) × 3 chr22:g.18882825_21713868dup	Pathogenicity	High-risk maternal serum screening
7	sseq[GRCh37]Xp21.1p21.1(31517704_31746485) × 3 chrX: g.31517704_31746485dup	Likely pathogenicity	High risk in NIPT
8	sseq[GRCh37]16p13.11p13.11(15096074_16425849) × 1 chr16:g.15096074_16425849del	Pathogenicity	High risk in NIPT
9	sseq[GRCh37]17q12q12(34823326_36252160) × 1 chr17:g.34823326_36252160del	Pathogenicity	Ultrasonic abnormalities
10	sseq[GRCh37]22q11.21q11.21(18753368_21746118) × 3 chr22:g.18753368_21746118dup	Pathogenicity	Ultrasonic abnormalities
11	sseq[GRCh37]Xp21.1p21.1(32342723_32537601) × 2 chrX: g.32342723_32537601dup	Likely pathogenicity	Parental chromosomal abnormalities
12	sseq[GRCh37]7q11.23q11.23(7251946_74206383) × 1 chr7:g.7251946_74206383del	Pathogenicity	Ultrasonic abnormalities
13	sseq[GRCh37]5p15.33p13.2(10429_34499283) × 1 chr5:g.10429_34499283del	Pathogenicity	History of adverse pregnancy outcomes
14	sseq[GRCh37]15q11.2q11.2(22724377_23273260) × 1 chr15:g.22724377_23273260del	Pathogenicity	Parental chromosomal abnormalities
15	sseq[GRCh37]15q13.2q13.3(30920060_32491354) × 1 chr15:g.30920060_32491354del	Pathogenicity	Advanced maternal age, history of adverse pregnancy outcomes
16	sseq[GRCh37]15q11.2q13.1(22554928_28861789) × 3 chr15:g.22554928_28861789dup	Pathogenicity	Advanced maternal age
17	sseq[GRCh37]Xp21.1p21.1(31756813_31930826) × 0 chrX: g.31756813_31930826del	Pathogenicity	Parental chromosomal abnormalities
18	sseq[GRCh37]Yq11.223q11.23(24873130_28432569) × 0 chrY: g.24873130_28432569del	Pathogenicity	High-risk maternal serum screening
19	sseq[GRCh37]Xp21.1p21.1(32702698_32878270) × 0 chrX: g.32702698_32878270del	Pathogenicity	Ultrasonic abnormalities

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Table 3. Comparison of detection results between CNV-seq and karyotype analysis

Abnormal Karyotype	Number of Karyotyping	Number of CNV-seq	Number of Combined Detection	Incremental Detection Gain (%)
Chromosome Aneuploidy	39	39	39	0.00
Microduplications/Microdeletions	0	19	19	3.00
Chromosomal Mosaicism	11	5	11	0.95
Balanced Translocation	12	0	12	1.74
Unbalanced Translocation	8	8	8	0.00
Polymorphism	29	0	29	4.58
Total	99	71	118	7.42

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