Study outcomes
| Reference . | Study arms (risk group in case of stratification) . | N . | ICH in sibling, n (%) . | FBS, n (%) . | IUPT, n (%) . | FBS/IUPT-related AE, n (%) . | Duration IVIG, wk, mean (range) . | SE IVIG/ steroids, n (%) . | ICH, n (%) . | Mean PLTs × 109/L . | PLT < 50 × 109/L, n (%) . | Mortality, n (%) . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Randomized controlled trials | ||||||||||||
| 30 | IVIG 0.5 g | 12 | 0 | 0 | 0 | NA | 10 (7-11) | 0 | 0 | 81 | 3 (25) | 0 |
| IVIG 1 g | 11 | 0 | 0 | 0 | NA | 11 (7-12) | 0 | 0 | 110 | 4 (36) | 0 | |
| 37 | IVIG 2 g | 37 | 0 | All | 0 | 2 (5) | 16 (11-20) | 12 (32) | 1 | 169 | 5 (14) | 0 |
| IVIG 1 g + steroids | 36 | 0 | All | 0 | 2 (6) | 16 (12-19) | 13 (33) | 1 | 134 | 4 (11) | 0 | |
| 35 | IVIG (all) | 40 | 4 (10) | All | 0 | 11 (14) | NR | NR | 3 | 104 | NR | 4 (5) |
| IVIG + steroids (high) | 19 | 3 (16) | All | 0 | NR | NR | 99 | NR | ||||
| Steroids (standard) | 20 | 0 | All | 0 | NA | NR | 108 | NR | ||||
| 20 | IVIG* | 28 | 6 (21) | All | 0 | 5 (9) | 10 | 0 | 0 | 96 | <30 6 (21) | 5 (9)† |
| IVIG + steroids | 26 | 4 (15) | All | 0 | 11 | 2 (8) | 0 | 110 | <30 5 (19) | |||
| Prospective studies | ||||||||||||
| 17 | IVIG ± IUPT | 7 | 7 (100) | 3 (43) | 3 (43) | NR | 17 (8-21) | NR | 0 | 28‡ | 7 (100)‡ | 0 |
| 39 | IUPT predelivery | 2 | 0 | All | 2 (100) | NR | NA | NA | 0 | 210 | 0 | 0 |
| IVIG ± IUPT | 4 | 0 | 2 (50) | 2 (50) | NR | 17 (15-19) | NR | 0 | 204 | 0 | 0 | |
| IVIG + steroids | 13 | 2 (15) | 1 (8) | 1 (8) | NR | 12 (5-20) | NR | 0 | 118 | 4 (31) | 0 | |
| 18 | IVIG ± IUPT | 37 | 8 (19) | 26 (70) | 26 (70) | 0 | 5 (2-15) | NR | 0 | 67 | 17 (46) | 0 |
| FBS ± IUPT | 13 | All | 9 (69) | 2 (22) | NA | NA | 0 | 32 | 7 (54) | 1 (8) | ||
| 23 | IVIG | 8 | 3 (30) | All | NR | 2 (20) | 12 (3-16) | NR | 0 | NR | 1 (13) | 0 |
| Fetal IVIG | 2 | All | NR | 2 (1-2) | NR | 0 | NR | 2 (100) | 0 | |||
| 22 | IVIG | 9 | 5 (56) | All | 1 (11) | NR | NR | NR | 0 | 57 | 4 (44) | NR |
| IVIG + steroids | 9 | 3 (33) | 8 (89) | 0 | NR | NR | 5 (56) | 0 | 64 | 3 (33) | NR | |
| Retrospective studies | ||||||||||||
| 31 | IVIG 1 g (all) | 5 | 2 (40) | 0 | 0 | NA | NR | 0 | 1§ | 63 | 8 (67) | 0 |
| IVIG 0.5 g (standard) | 17 | 0 | 0 | 0 | NA | NR | 0 | 0 | 104 | 4 (33) | 0 | |
| 32 | IVIG | 27 | 9 (14) | 0 | 0 | NA | 14 | NR | 0 | 89 | 12 (44) | 0 |
| IVIG + steroids | 54 | 0 | 0 | NA | 14 | NR | 0 | 135 | 13 (27) | 0 | ||
| Steroids | 11 | 0 | 0 | NA | NA | NR | 0 | 46 | 8 (73) | 0 | ||
| 24 | IVIG | 17 | 5 (29) | 9 | 0 | 1 (11) | 12 | NR | 0 | 68 | 10 (59) | 0 |
| IVIG + steroids | 6 | 0 | 0 | 0 | NA | 7 | NR | 0 | 78 | 4 (67) | 0 | |
| 19 | IVIG 1 g (high + very high) | 5 | 5 (100) | All | 1 (17) | 3 (8) | 15 (7-25) | NR | 1 | 165 | 0 | 0 |
| IVIG 1 g + steroids (all) | 19 | 19 (100) | All | 0 | 12 (5-25) | NR | 3 | 85 | 6 (40) | 2 (11) | ||
| IVIG 2 g (all) | 4 | 4 (100) | All | 0 | 22 (18-25) | NR | 0 | 112 | 0 | 0 | ||
| IVIG 2 g + steroids (all) | 9 | 9 (100) | All | 0 | 23 (18-27) | NR | 1 | 135 | 0 | 0 | ||
| 21 | Fetal IVIG + IUPT | 10 | NR | All | 10 (100) | 0 | 10 (6-14) | NR | 0 | 189¶ | 0 | 0 |
| 26 | IVIG | 13 | 5 (38) | NR | 2 (15) | NR | NR | NR | 0 | 83 | 6 (46) | 0 |
| 34 | IVIG (all) | 53 | 5 (9) | 0 | 0 | NA | 8 (2-24) | NR | 0 | 125 | 10 (19) | 0 |
| FBS + IVIG (all) | 33 | 11 (33) | All | NR | 3 (7) | 6 (2-21) | NR | 0 | 174 | 0 | 1 (3) | |
| FBS + IUPT (standard) | 13 | 0 | All | 13 (100) | 0 | NA | NA | 0 | 145 | 3 (23) | 0 | |
| 41 | IUPT ± IVIG ± steroids | 40 | NR | All | 40 (100) | 3 (8) | NR | NR | 4 | 107 | NR | 6 (15) |
| IVIG and/or steroids | 7 | NR | NR | 0 | 1 (14) | NR | NR | 0 | 7-219 | NR | 1 (14) | |
| No treatment | 8 | NR | NA | NA | NA | NA | NA | 0 | 6-84 | NR | 0 | |
| 38 | IVIG | 24 | 0 | 4 (17) | 0 | NR | 15 (9-19) | NR | 0 | 118 | <30 2 (8) | 0 |
| No treatment | 6 | 0 | NA | NA | NA | NA | NA | 0 | 24 | <30 4 (67) | 0 | |
| 27 | IVIG* | 9 | 5 (56) | 0 | 0 | NA | NR | NR | 0 | 90 | 4 (44) | 0 |
| IUPT | 3 | 0 | All | 3 (100) | 3 (100) | NA | NA | 0 | 47 | 2 (100) | 1 (33) | |
| No treatment | 6 | 2 (34) | 0 | 0 | NA | NA | NA | 1 | 9 | 4 (80) | 1 (17) | |
| 28 | IVIG ± IUPT* | 18 | 6 (60) | All | 6 (33) | 3 (17) | 9 (1-19) | 1 (6) | 1§ | 81 | 6 (33) | 0 |
| IUPT weekly | 31 | 11 (42) | All | 31 (100) | 10 (30) | NA | NA | 2§ | NR | NR | 3 (10) | |
| FBS ± single IUPT | 7 | 0 | All | 5 (71) | 2 (29) | NA | NA | 0 | NR | NR | 0 | |
| 42 | IVIG ± IUPT* | 11 | 1 (9) | All | 9 (82) | 2 (18) | 6 (1-12) | 1 (9) | 0 | 109 | 5 (45) | 0 |
| IUPT | 4 | 0 | All | 4 (100) | 2 (50) | NA | NA | 0 | 76 | 2 (50) | 0 | |
| 29 | IVIG | 27 | 7 (26) | All | 1 (4) | NR | 7 (2-15) | NR | 2 | 69 | 13 (48) | 2 (7) |
| Steroids | 10 | NR | All | NR | NR | NA | NR | NR | NR | 6 (60) | NR | |
| 33 | IVIG + IUPT | 4 | 1 (25) | All | 4 (100) | 1 (25) | NR | 0 | 0 | 182 | 0 | 1 (25) |
| IVIG | 6 | 1 (17) | All | 0 | 1 (17) | NR | 0 | 0 | 98 | 2 (33) | 1 (17) | |
| 40 | IVIG + IUPT ± steroids | 8 | 6 (75) | All | 6 (100) | 1 (13) | 9 (4-17) | NR | 1§ | 340¶ | 0¶ | 2 (25) |
| IUPT ± steroids | 7 | 5 (71) | All | 7 (100) | 0 | NA | NR | 2§ | 305¶ | 0¶ | 1 (14) | |
| 36 | IVIG | 2 | NR | All | 0 | NR | 14 (13-14) | 0 | 0 | 60 | 1 (50) | 0 |
| IVIG + steroids | 4 | NR | All | 0 | NR | 11 (5-20) | 0 | 0 | 146 | 0 | 0 | |
| 25 | IUPT | 4 | 1 (20) | All | 5 (100) | 0 | NA | NA | 0 | 200 | 0 | 0 |
| IVIG (5 d) + IUPT | 1 | 0 | All | 1 (100) | 0 | 5 | 0 | 0 | 107 | 0 | 0 | |
| Reference . | Study arms (risk group in case of stratification) . | N . | ICH in sibling, n (%) . | FBS, n (%) . | IUPT, n (%) . | FBS/IUPT-related AE, n (%) . | Duration IVIG, wk, mean (range) . | SE IVIG/ steroids, n (%) . | ICH, n (%) . | Mean PLTs × 109/L . | PLT < 50 × 109/L, n (%) . | Mortality, n (%) . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Randomized controlled trials | ||||||||||||
| 30 | IVIG 0.5 g | 12 | 0 | 0 | 0 | NA | 10 (7-11) | 0 | 0 | 81 | 3 (25) | 0 |
| IVIG 1 g | 11 | 0 | 0 | 0 | NA | 11 (7-12) | 0 | 0 | 110 | 4 (36) | 0 | |
| 37 | IVIG 2 g | 37 | 0 | All | 0 | 2 (5) | 16 (11-20) | 12 (32) | 1 | 169 | 5 (14) | 0 |
| IVIG 1 g + steroids | 36 | 0 | All | 0 | 2 (6) | 16 (12-19) | 13 (33) | 1 | 134 | 4 (11) | 0 | |
| 35 | IVIG (all) | 40 | 4 (10) | All | 0 | 11 (14) | NR | NR | 3 | 104 | NR | 4 (5) |
| IVIG + steroids (high) | 19 | 3 (16) | All | 0 | NR | NR | 99 | NR | ||||
| Steroids (standard) | 20 | 0 | All | 0 | NA | NR | 108 | NR | ||||
| 20 | IVIG* | 28 | 6 (21) | All | 0 | 5 (9) | 10 | 0 | 0 | 96 | <30 6 (21) | 5 (9)† |
| IVIG + steroids | 26 | 4 (15) | All | 0 | 11 | 2 (8) | 0 | 110 | <30 5 (19) | |||
| Prospective studies | ||||||||||||
| 17 | IVIG ± IUPT | 7 | 7 (100) | 3 (43) | 3 (43) | NR | 17 (8-21) | NR | 0 | 28‡ | 7 (100)‡ | 0 |
| 39 | IUPT predelivery | 2 | 0 | All | 2 (100) | NR | NA | NA | 0 | 210 | 0 | 0 |
| IVIG ± IUPT | 4 | 0 | 2 (50) | 2 (50) | NR | 17 (15-19) | NR | 0 | 204 | 0 | 0 | |
| IVIG + steroids | 13 | 2 (15) | 1 (8) | 1 (8) | NR | 12 (5-20) | NR | 0 | 118 | 4 (31) | 0 | |
| 18 | IVIG ± IUPT | 37 | 8 (19) | 26 (70) | 26 (70) | 0 | 5 (2-15) | NR | 0 | 67 | 17 (46) | 0 |
| FBS ± IUPT | 13 | All | 9 (69) | 2 (22) | NA | NA | 0 | 32 | 7 (54) | 1 (8) | ||
| 23 | IVIG | 8 | 3 (30) | All | NR | 2 (20) | 12 (3-16) | NR | 0 | NR | 1 (13) | 0 |
| Fetal IVIG | 2 | All | NR | 2 (1-2) | NR | 0 | NR | 2 (100) | 0 | |||
| 22 | IVIG | 9 | 5 (56) | All | 1 (11) | NR | NR | NR | 0 | 57 | 4 (44) | NR |
| IVIG + steroids | 9 | 3 (33) | 8 (89) | 0 | NR | NR | 5 (56) | 0 | 64 | 3 (33) | NR | |
| Retrospective studies | ||||||||||||
| 31 | IVIG 1 g (all) | 5 | 2 (40) | 0 | 0 | NA | NR | 0 | 1§ | 63 | 8 (67) | 0 |
| IVIG 0.5 g (standard) | 17 | 0 | 0 | 0 | NA | NR | 0 | 0 | 104 | 4 (33) | 0 | |
| 32 | IVIG | 27 | 9 (14) | 0 | 0 | NA | 14 | NR | 0 | 89 | 12 (44) | 0 |
| IVIG + steroids | 54 | 0 | 0 | NA | 14 | NR | 0 | 135 | 13 (27) | 0 | ||
| Steroids | 11 | 0 | 0 | NA | NA | NR | 0 | 46 | 8 (73) | 0 | ||
| 24 | IVIG | 17 | 5 (29) | 9 | 0 | 1 (11) | 12 | NR | 0 | 68 | 10 (59) | 0 |
| IVIG + steroids | 6 | 0 | 0 | 0 | NA | 7 | NR | 0 | 78 | 4 (67) | 0 | |
| 19 | IVIG 1 g (high + very high) | 5 | 5 (100) | All | 1 (17) | 3 (8) | 15 (7-25) | NR | 1 | 165 | 0 | 0 |
| IVIG 1 g + steroids (all) | 19 | 19 (100) | All | 0 | 12 (5-25) | NR | 3 | 85 | 6 (40) | 2 (11) | ||
| IVIG 2 g (all) | 4 | 4 (100) | All | 0 | 22 (18-25) | NR | 0 | 112 | 0 | 0 | ||
| IVIG 2 g + steroids (all) | 9 | 9 (100) | All | 0 | 23 (18-27) | NR | 1 | 135 | 0 | 0 | ||
| 21 | Fetal IVIG + IUPT | 10 | NR | All | 10 (100) | 0 | 10 (6-14) | NR | 0 | 189¶ | 0 | 0 |
| 26 | IVIG | 13 | 5 (38) | NR | 2 (15) | NR | NR | NR | 0 | 83 | 6 (46) | 0 |
| 34 | IVIG (all) | 53 | 5 (9) | 0 | 0 | NA | 8 (2-24) | NR | 0 | 125 | 10 (19) | 0 |
| FBS + IVIG (all) | 33 | 11 (33) | All | NR | 3 (7) | 6 (2-21) | NR | 0 | 174 | 0 | 1 (3) | |
| FBS + IUPT (standard) | 13 | 0 | All | 13 (100) | 0 | NA | NA | 0 | 145 | 3 (23) | 0 | |
| 41 | IUPT ± IVIG ± steroids | 40 | NR | All | 40 (100) | 3 (8) | NR | NR | 4 | 107 | NR | 6 (15) |
| IVIG and/or steroids | 7 | NR | NR | 0 | 1 (14) | NR | NR | 0 | 7-219 | NR | 1 (14) | |
| No treatment | 8 | NR | NA | NA | NA | NA | NA | 0 | 6-84 | NR | 0 | |
| 38 | IVIG | 24 | 0 | 4 (17) | 0 | NR | 15 (9-19) | NR | 0 | 118 | <30 2 (8) | 0 |
| No treatment | 6 | 0 | NA | NA | NA | NA | NA | 0 | 24 | <30 4 (67) | 0 | |
| 27 | IVIG* | 9 | 5 (56) | 0 | 0 | NA | NR | NR | 0 | 90 | 4 (44) | 0 |
| IUPT | 3 | 0 | All | 3 (100) | 3 (100) | NA | NA | 0 | 47 | 2 (100) | 1 (33) | |
| No treatment | 6 | 2 (34) | 0 | 0 | NA | NA | NA | 1 | 9 | 4 (80) | 1 (17) | |
| 28 | IVIG ± IUPT* | 18 | 6 (60) | All | 6 (33) | 3 (17) | 9 (1-19) | 1 (6) | 1§ | 81 | 6 (33) | 0 |
| IUPT weekly | 31 | 11 (42) | All | 31 (100) | 10 (30) | NA | NA | 2§ | NR | NR | 3 (10) | |
| FBS ± single IUPT | 7 | 0 | All | 5 (71) | 2 (29) | NA | NA | 0 | NR | NR | 0 | |
| 42 | IVIG ± IUPT* | 11 | 1 (9) | All | 9 (82) | 2 (18) | 6 (1-12) | 1 (9) | 0 | 109 | 5 (45) | 0 |
| IUPT | 4 | 0 | All | 4 (100) | 2 (50) | NA | NA | 0 | 76 | 2 (50) | 0 | |
| 29 | IVIG | 27 | 7 (26) | All | 1 (4) | NR | 7 (2-15) | NR | 2 | 69 | 13 (48) | 2 (7) |
| Steroids | 10 | NR | All | NR | NR | NA | NR | NR | NR | 6 (60) | NR | |
| 33 | IVIG + IUPT | 4 | 1 (25) | All | 4 (100) | 1 (25) | NR | 0 | 0 | 182 | 0 | 1 (25) |
| IVIG | 6 | 1 (17) | All | 0 | 1 (17) | NR | 0 | 0 | 98 | 2 (33) | 1 (17) | |
| 40 | IVIG + IUPT ± steroids | 8 | 6 (75) | All | 6 (100) | 1 (13) | 9 (4-17) | NR | 1§ | 340¶ | 0¶ | 2 (25) |
| IUPT ± steroids | 7 | 5 (71) | All | 7 (100) | 0 | NA | NR | 2§ | 305¶ | 0¶ | 1 (14) | |
| 36 | IVIG | 2 | NR | All | 0 | NR | 14 (13-14) | 0 | 0 | 60 | 1 (50) | 0 |
| IVIG + steroids | 4 | NR | All | 0 | NR | 11 (5-20) | 0 | 0 | 146 | 0 | 0 | |
| 25 | IUPT | 4 | 1 (20) | All | 5 (100) | 0 | NA | NA | 0 | 200 | 0 | 0 |
| IVIG (5 d) + IUPT | 1 | 0 | All | 1 (100) | 0 | 5 | 0 | 0 | 107 | 0 | 0 | |
AE, adverse event; NA, not applicable; NR, not reported; SE, side effect.
One or 2 patients also received steroids (supplemental Table 1).
Five fetuses exsanguinated and were excluded from other analyses.
Platelet count before predelivery IUPT.
ICH occurred before start of therapy.
Platelet count after IUPT.