Whole exome sequencing in fetuses with isolated increased nuchal translucency: a systematic review and meta-analysis

Figures & data

Figure 1. Prisma flow diagram.

Table 1. General characteristics of the included studies in the present systematic review.

Authors	Country	Study design	Period considered	Definition of increased NT	Previous Genetic testing	Isolated increased NT (n)	Sequencing Approach
Mellis et al. 2021 [8]	United Stated	Retrospective	2014–2018	>3.5 mm	CMA	159	Trio WES
Xue et al. 2020 [9]	China	Prospective	2014–2017	>3.5 mm	CMA	274	Trio WES
Yang et al. 2020 [13]	China	Prospective	2017–2018	>3.5 mm	CMA	73	Trio CES
Chen et al. 2020 [14]	China	Prospective	NS	>3.5 mm	CMA	18	Trio CES
Daum et al. 2019 [3]	Israel	Retrospective	2012–2017	>3.5 mm	CMA	12	Solo and trio WES
Choy et al. 2019 [12]	China	Retrospective	2014–2018	>3.5 mm	CMA	34	GS
Leung et al. 2018 [15]	China	Retrospective	NS	>3.5 mm or cystic hygroma	CMA	4	Trio WES
Drury et al. 2015 [1]	United Kingdom	Prospective	NS	>3.5 mm	CMA	5	WES, trio and solo

NT: nuchal translucency; WES: whole exome sequencing; CMA: chromosomal microarray; GS: genome sequencing; CES: Capillary electrophoresis sequencing; NS: not specified.

Table 2. Quality assessment of the included studies according to Newcastle-Ottawa Scale (NOS)*.

Authors	Year	Selection	Comparability	Outcome
Mellis et al. 2021 [8]	United States	★★★	★★	★★
Xue et al. 2020 [9]	China	★★	★★	★★
Yang et al. 2020 [13]	China	★★	★★	★★
Chen et al. 2020 [14]	China	★★	★★	★★
Daum et al. 2019 [3]	Israel	★★	★	★
Choy et al. 2019 [12]	China	★★	★★	★
Leung et al. 2018 [15]	China	★★	★	★
Drury et al. 2015 [1]	United Kingdom	★	★	★

*a study can be awarded a maximum of one star for each numbered item within the Selection and Outcome categories. A maximum of two stars can be given for Comparability.

Figure 2. Pooled proportion for the occurrence of pathogenic or likely pathogenic variants in fetuses with isolated increased NT detected exclusively at WES analysis.

Table 3. Pooled proportions (95% CI) for the rate of pathogenetic or likely pathogenic genetic variants and for variants of unknown significance anomalies detected by WES in fetuses with increased NT and normal CMA and karyotype.

Outcome	Studies	Number of fetuses	Pooled proportions 95 CI (%)	I^2 (%) (95% CI)
Cases with isolated increased NT
Pathogenic or likely pathogenic diagnostic variants	8	25/324	8.07 (5.4–11.3)	0 (0–56.3)
NT between 3.0 and 5.5	4	11/25	44.70 (26.8–63.4)	0 (0–67.9)
NT >5.5	4	14/25	55.30 (36.6–73.2)	0 (0–67.9)
Variants of unknown significance	8	19/324	7.84 (1.6–18.2)	82.6 (64–89.5)
Cases with isolated increased NT and no structural anomalies at the anomaly scan
Pathogenic or likely pathogenic diagnostic variants	8	9/276	3.87 (1.6–7.1)	18.5 (0–63.9)
Variants of unknown significance	8	10/276	4.27 (2.2–7.0)	0 (0–56.3)

NT: nuchal translucency; CMA: chromosomal microarray.

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