Summary of findings 2. Performance of gNIPT for detection of T21.

Performance of gNIPT for detection of T21
Test strategy	Number of studies	Number of affected pregnancies (Number of unaffected pregnancies)a	Sensitivity % (95% CI)	Specificity % (95% CI)	Median prevalenceb % (range)	Missed cases (FN)c	False positives (FP)d
Unselected pregnant women
MPSS	1	8 (1733)	100 (67.6 to 100)	100 (99.8 to 100)	0.46 (0.24 to 5.21)	0	0
TMPS	4	88 (20,679)	99.2 (78.2 to 100)	100 (> 99.9 to 100)		4	0
Traditional screening teste	1	38 (15,803)	78.9 (63.7 to 88.9)	94.6 (94.2 to 94.9)		97	5375
Implications	460 of 100,000 pregnancies expected to be affected by T21; MPSS will detect all cases and no pregnant woman will undergo an unnecessary invasive test; with TMPS, 4 cases will be missed and no pregnant woman will undergo unnecessary invasive test; and with traditional screening tests, 363 cases will be detected and 5375 unaffected pregnant women will undergo unnecessary invasive test.
Selected high‐risk pregnant women
MPSS	30	1048 (15,937)	99.7 (98.0 to 100)	99.9 (99.8 to 100)	4.95 (0.44 to 27.66)	15	95
TMPS	6	246 (4380)	99.2 (96.8 to 99.8)	100 (99.8 to 100)		40	0
Difference between MPSS and TMPS			0.53 (‐0.73 to 1.78)	‐0.03 (‐0.11 to 0.04)	NA
Implications	4950 of 100,000 pregnancies expected to be affected by T21; 4936 and 4911 cases will be detected while 15 and 40 cases will be missed by MPSS and TMPS, respectively; and of 95,050 expected pregnancies unaffected by T21, 95 and 0 pregnant women will undergo unnecessary invasive tests with MPSS and TMPS, respectively.

MPSS: massively parallel shotgun sequencing, NA; not applicable, TMPS: targeted massively parallel sequencing, T21: trisomy 21.

^aUnaffected pregnancies: we included patients with any other aneuploidy than the one under analysis with all euploid cases as "unaffected" pregnancies.

^bThe median prevalence and range were calculated by using all prospective or retrospective studies for each category considered.

^cMissed cases per 100,000 tested. FN: false negatives.

^dFalse positives per 100,000 tested. A false positive result may lead to unnecessary invasive tests depending on choices by the pregnant woman.

^eTraditional screening tests are first‐trimester combined test, second‐trimester quadruple test, second‐trimester fully integrated test, second‐trimester sequential test or second‐trimester triple test.