Table 2.

Overview of cases with abnormal non‐invasive prenatal test (NIPT) result other than trisomy 21, 18 or 13, in 251 pregnancies with ultrasound anomaly

Case	Indication for genetic testing	NIPT		Diagnostic genetic testing			Outcome	Classification of aberration
		Timing	Result	Timing	Test	Result
3	IUGR	15 weeks	T16	16 weeks	QF‐PCR, karyotype, FISH	46,XX 46,XX D16Z3 × 2	Preterm LB with no congenital anomaly, extreme dysmaturity, perinatal death	Causative
				Postnatal	Microarray	arr 16p13.3p13.2(89,561‐8,914,906) × 2 hmz = UPD (16)mat*
4	NT 4.7 mm	13 weeks	Gain of 8p†	16 weeks	Karyotype, microarray	46,XX,del(8)(p23.3p23.1), dup(8)(p23.1p11.21) arr 8p23.3p23.1(158,049‐6,976,182) × 1 dn, 6.8 Mb, 8p23.1p11.21(11,936,001‐40,905,009) × 3 dn, 29 Mb	TOP	Causative
5	IUGR	21 weeks	Gain of 21q‡	22 weeks	Maternal microarray	arr 21q22.11(33,522,970‐33,889,304) × 3, ∼370 kb (6 genes)	LB with no congenital anomaly	Incidental
6	IUGR	21 weeks	Gain of 18p§	NP			LB, two small VSDs (resolved spontaneously), mild dysmorphisms

^*Maternal uniparental disomy of chromosome 16, most likely due to ‘trisomy 16 rescue’; placental material not available for testing.

^†Software analysis showed 30‐Mb gain of 8p; visual inspection of plots showed also a (smaller) 8p terminal loss.

^‡Software analysis showed 10‐Mb gain of 21q; visual inspection of plots showed relatively high region‐specific Z‐score, therefore, maternal origin was suspected; consultation with clinical geneticist revealed no maternal dysmorphic features or physical or neurodevelopmental anomaly; copy number variant therefore classified as most probably benign.

^§Software analysis showed 15‐Mb gain of 18p.

FISH, fluorescent in‐situ hybridization; IUGR, intrauterine growth restriction; kb, kilobases; LB, live birth; Mb, megabases; NP, not performed; NT, nuchal translucency thickness; QF‐PCR, quantitative fluorescent polymerase chain reaction; T16, trisomy 16; TOP, termination of pregnancy; VSD, ventricular septal defect.