Summary of findings 4. Performance of gNIPT for detection of T13.

Performance of gNIPT for detection of T13
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	1 (1740)	100 (20.7 to 100)	100 (99.8 to 100)	0. 12 (0.01 to 0.52)	0	0
TMPS	3	8 (14,154)	65.1 (9.16 to 97.2)	100 (99.9 to 100)		41	0
Traditional screening teste	1	2 (11,183)	50.0 (9.45 to 90.5)	99.7 (99.6 to 99.8)		59	300
Implications	118 of 100,000 pregnancies expected to be affected by T13; MPSS will detect all cases and no unaffected pregnant woman will undergo an unnecessary invasive test; with TMPS, 41 cases will be missed and no unaffected pregnant woman will undergo unnecessary invasive test; and with traditional screening tests, 59 cases will be missed and 300 unaffected pregnant women will undergo unnecessary invasive test.
Selected high‐risk pregnant women
MPSS	20	128 (13,810)	95.8 (86.1 to 98.9)	99.8 (99.8 to 99.9)	1.09 (0.04 to 3.54)	46	198
TMPS	2	20 (293)	100 (83.9 to 100)f	100 (98.7 to 100)f		0	0
Implications	1087 of 100,000 pregnancies expected to be affected by T13; 1041 and 1087 cases will be detected while 46 and 0 cases will be missed by MPSS and TMPS, respectively; and of 98,913 expected unaffected by T13, 198 and 0 pregnant women will undergo unnecessary invasive test with MPSS and TMPS, respectively.

MPSS: massively parallel shotgun sequencing, NA: not applicable, TMPS: targeted massively parallel sequencing, T13: trisomy 13.

^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.

^fSimple pooling used to obtain summary estimates of sensitivity, specificity or both.