Table 3.
Non-randomized controlled trials (non-RCTs) on prenatal management in FNAIT.
| Author (publication year) | Type of study | Number of research subjects | ICH in sibling, n (%) | FBS, n (%) | IUPT, n (%) | FBS/IUPT related adverse event, n (%) | IVIg/steroids related side effects, n (%) | ICH, n (%) | Neonatal PLTs (×103/μL) | Conclusions |
|---|---|---|---|---|---|---|---|---|---|---|
| Murphy MF, et al. (1994) (169) | Retrospective | IVIg + IUPT ± steroids: n=8 | 6 (75) | All | All | 1 (12.5) | – | 1 (12.5) (before therapy) | 340 (after IUPT) | Non-invasive treatment is effective for pregnant women with FNAIT, and there are no adverse consequences of invasive treatment. |
| IUPT ± steroids: n=7 | 5 (71.4) | All | All | 0 | – | 2 (28.6) (before therapy) | 305 (after IUPT) | |||
| Kornfeld I, et al. (1996) (170) | Retrospective | IVIg + IUPT: n=4 | 1 (25) | All | All | 1 (25) | 0 | 0 | 182 | IVIg seems to improve the outcomes of infants at risk of FNAIT. |
| IVIg: n=6 | 1 (16.7) | All | 0 | 1 (16.7) | 0 | 0 | 98 | |||
| Kaplan C, et al. (1998) (171) | Retrospective | IVIg: n=27 | 7 (25.9) | All | 1 (3.7) | – | – | 2 (7.4) | 69 | Fetal platelet count must be tested twice during pregnancy to evaluate the effectiveness of the treatment. |
| Steroids: n=10 | – | All | – | – | – | – | – | |||
| Sainio S, et al. (1999) (103) | Retrospective | IVIg ± IUPT: n=11 | 1 (9.1) | All | 9 (81.8) | 2 (18.2) | 1 (9.1) | 0 | 109 | IVIg or platelet transfusion to the fetus is not sufficient to protect severely affected fetuses from FNAIT. |
| IUPT: n=4 | 0 | All | All | 2 (50) | – | 0 | 76 | |||
| Silver RM, et al. (2000) (172) | Prospective | IVIg to the mother: n=8 | 3 (30) | All | – | 2 (20) | – | 0 | – | The inconsistent effect of IVIg on increasing fetal platelet count may be due to maternal or placental factors, rather than the inhibitory effect of IVIg on fetal platelet destruction. |
| IVIg to the fetus: n=2 | All | – | – | 0 | – | |||||
| Tiblad E, et al. (2003) (173) | Retrospective | IVIg (one had prednisolone): n=9 | 5 (55.6) | 0 | 0 | – | – | 0 | 90 | Non-invasive treatment can be applied to FNAIT cases. |
| IUPT: n=3 | 0 | All | All | All | – | 0 | 47 | |||
| No treatment: n=6 | 2 (33.3) | 0 | 0 | – | 1 (16.7) | 9 | ||||
| Birchall JE, et al. (2003) (174) | Retrospective | IVIg ± IUPT: n=18 | 6 (33.3) | All | 6 (33.3) | 3 (16.7) | 1 (5.6) | 1 (5.6) (before therapy) | 81 | FNAIT cases should be stratified based on medical history. |
| IUPT: n=31 | 11 (35.5) | All | All | 10 (32.3) | – | 2 (6.5) (before therapy) | – | |||
| FBS ± IUPT: n=7 | 0 | All | 5 (71.4) | 2 (28.6) | – | 0 | – | |||
| Radder CM, et al. (2004) (108) | Prospective | IVIg ± IUPT: n=37 | 8 (16.0) | 26 (70.3) | 26 (70.3) | 0 | – | 0 | 67 | IVIg treatment during pregnancy did not affect the development of the children’s nervous system. |
| FBS ± IUPT: n=13 | All | 9 (69.2) | 2 (22.2) | – | 2 (15.4) | 32 | ||||
| Kanhai HH, et al. (2006) (175) | Prospective | IVIg 1 g/kg/wk: n=7 | All | 3 (42.9) | 3 (42.9) | – | – | 0 | 39, 14, 15, and 10 for four patients | For severe FNAIT cases and those who have risk factors for cordocentesis, IVIg can be chosen. |
| Bertrand G, et al. (2006) (98) | Prospective | IUPT: n=2 | 0 | All | All | – | – | 0 | 210 | The concentration of anti-HPA-1a antibody can be used to guide invasive management. |
| IVIg: n=4 | 0 | 2 (50) | 2 (50) | – | – | 0 | 204 | |||
| IVIg + corticoids: n=13 | 2 (15.4) | 1 (7.7) | 1 (7.7) | – | – | 0 | 118 | |||
| Yinon Y, et al. (2006) (176) | Retrospective | IVIg: n=24 | 0 | 7 (29.2) | 0 | – | – | 0 | 118 | For FNAIT fetuses, IVIg treatment is effective and safe. |
| No treatment: n=6 | 0 | 0 | – | – | – | 0 | 24 | |||
| te Pas AB, et al. (2007) (158) | Retrospective | IVIg: n=13 | 5 (38.5) | – | 2 (15.4) | – | – | 0 | 83 | They do not recommend IVIg treatment for FNAIT cases. |
| van den Akker ES, et al. (2007) (177) | Retrospective | IVIg: n=53 | 5 (9.4) | 0 | 0 | – | – | 0 | 125 | Non-invasive treatment for FNAIT is effective and safe. |
| FBS + IVIg: n=33 | 11 (33.3) | All | – | 3 (9.1) | – | 0 | 174 | |||
| FBS + IUPT: n=13 | 0 | All | All | 0 | – | 0 | 145 | |||
| Ghevaert C, et al. (2007) (143) | Retrospective | IUPT ± IVIg ± corticosteroids: n=40 | – | All | All | 3 (7.5) | – | 4 (10) | 107 | There is a relatively high risk of injecting platelets into the fetus. |
| IVIg and/or corticosteroids: n=7 | – | – | 0 | 1 (14.3) | – | 0 | 7-219 | |||
| No treatment: n=8 | – | – | – | – | – | 0 | 6-84 | |||
| Giers G, et al. (2010) (178) | Retrospective | IVIg to the fetus + IUPT: n=10 | – | All | All | 0 | – | 0 | 189 (for the fetus) | After weekly administration of IVIg, fetal IgG levels increased, but fetal platelet count did not change. |
| Bertrand G, et al. (2011) (86) | Retrospective | IVIg 1 g/kg/wk: n=27 | 9 (9.8) | 0 | 0 | – | – | 0 | 89 | The concentration of maternal anti-HPA-1a antibody before 28 weeks can predict fetal status. |
| IVIg 1 g/kg/wk + prednisone 0.5 mg/kg/d: n=54 | 0 | 0 | – | – | 0 | 135 | ||||
| Prednisone 0.5 mg/kg/d: n=11 | 0 | 0 | – | 0 | 46 | |||||
| Mechoulan A, et al. (2011) (179) | Retrospective | IVIg: n=17 | 5 (29.4) | 9 (52.9) | 0 | 1 (11.1) | – | 0 | 68 | IVIg treatment achieved good results. |
| IVIg + corticosteroids: n=6 | 0 | 0 | 0 | – | – | 0 | 78 | |||
| Bussel JB, et al. (2010) (13) | Retrospective | IVIg 1 g/kg/wk: n=5 | All | All | 1 (20) | 3 (60) | – | 1 (20) | 165 | Patients should be stratified according to the occurrence of ICH in siblings. |
| IVIg 1 g/kg/wk + prednisone 1 mg/kg/d: n=19 | All | All | 0 | 0 | – | 3 (15.8) | 85 | |||
| IVIg 2 g/kg/wk: n=4 | All | All | 0 | 0 | – | 0 | 112 | |||
| IVIg 2 g/kg/wk + prednisone 1 mg/kg/d: n=9 | All | All | 0 | 0 | – | 1 (11.1) | 135 | |||
| Van Der Lugt NM, et al. (2015) (14) | Retrospective | IVIg 1 g/kg/wk: n=5 | 2 (40) | 0 | 0 | – | – | 1 (20) | 63 | Non-invasive treatment is effective for pregnant women with a history of FNAIT. |
| IVIg 0.5 g/kg/wk: n=17 | 0 | 0 | 0 | – | – | 0 | 104 | |||
| Lakkaraja M, et al. (2016) (104) | Prospective | IVIg 2 g/kg/wk: n=51 | 0 | 42 (82.4) | 17 (33.3) | 4 (7.8) | The most common: headache 11 (21.6) | 3 (3) | 169 | The two recommended treatment options can effectively increase fetal platelet count and are very safe. It may be considered to cancel invasive examinations. |
| IVIg 1 g/kg/wk + prednisone 0.5 mg/kg/d: n=49 | 0 | 38 (77.6) | 20 (40.8) | 6 (12.2) | The most common: headache 10 (20.4) | 135.3 | ||||
| Wienzek-Lischka S, et al. (2020) (110) | Retrospective | IVIg: n=12 | – | 0 | 0 | – | The most common: headache 11 (91.7) | 1 (8.3) | 187 | IVIg treatment is effective, and invasive treatments should be abandoned. |
| Ernstsen SL, et al. (2022) (111) | Retrospective | IVIg: n=403 | 90 (22.3) | – | – | – | – | 7 (1.7) | – | For low-risk pregnant women, no treatment did not increase the risk of fetal/neonatal ICH. |
| No treatment: n=71 | 7 (9.9) | 0 | 0 | 0 | – | 2 (2.8) | – |
ICH, intracranial hemorrhage; FBS, fetal blood sampling; IUPT, intrauterine platelet transfusion; IVIg, intravenous immunoglobulin; “-”, not known or not applicable.