Table 1. Synopsis of transplacental infections: the treatment of pregnant women and neonates.

Study	Design	Intervention	Results	Remarks
Treatment during pregnancy
Shahar-Nissan, 2020 (14) CMV	•RCT, double-blind, placebo-controlled	•8.0 g of valacyclovir per day for primary CMV infection in the first trimester until amniocentesis	•Transmission rate ↓ 5/45 (11%) in the intervention group vs. 14/47 (30%) in the placebo group (OR 0.29, 95% CI: [0.09; 0.9], p = 0.027), fetal CMV-related morbidities (OR 0.38, [0.09; 1.56]	•3 pregnancy terminations (1 i ntervention, 2 placebo) due to CMV abnormalities, 3 terminations due to CMV-PCR-positive amniotic fluid
Kosian, 2023 (25) B19V	•Retrospective case series	•Intrauterine transfusion for severe anemia due to B19V	•186 transfusions in 103 fetuses, overall survival 87/103 (84.5%); first transfusion at 19+3 weeks of gestation (range: 13-31 weeks)	•Risk factors for IUF: hydrops, lower mean hemoglobin, lower platelet counts
Mandelbrot, 2018 (29) toxoplasmosis	•Open-label RCT, multicenter	•Pyrimethamine + sulfa (PS) vs. spiramycin (S) in cases of confirmed toxoplasmosis in the first trimester	•Transmission rate, definite congenital toxoplasmosis (↓): 12/65 (18.5%) in the PS group vs. 18/60 (30%) in the S group (p = 0.147); Prenatal ultrasound abnormalities: 0% in the PS group vs. 8.6% in the S group (p = 0.012)	•6 children affected despite negative PCR in amniocentesis; effect of PS stronger when treatment begins < 3 weeks after seroconversion
Tong, 2023 (38) syphilis	•Meta-analysis of observational studies	•Penicillin treatment for active syphilis	•Preterm birth rate ↓: OR 0.48 [0.39; 0.58]; n = 11,043, 15 studies; stillbirth rate ↓: OR 0.21 [0.12; 0.35]; n = 14,667, 8 studies; low birth weight ↓: OR 0.5 [0.42; 0.59]; n = 9778, 7 studies); perinatal mortality and pregnancy complications ↓	•No adjustment for potential confounding factors (evidence level classified as low)
Treatment of congenitally infected neonates
Ki mberlin, 2015 (17) cCMV	•RCT, double-blind, placebo-controlled	•6 months: 16 mg/kg body weight (twice daily) of valganciclovir for symptomatic cCMV infection (placebo: 6 weeks)	No improvement in hearing after 6 months (intervention: 36/47 vs. placebo: 37/49, p = 0.41) At 24 months: Improvement in hearing with intervention 77% vs. 64%; OR 2.61; [1.05; 6.43], p = 0.04; and higher scores on the Bayley Scales of Infant and Toddler Development (Language)	•Adverse effects of valganciclovir: neutropenia (19%), elevated liver enzymes; lower risk of hearing impairment with lower viral load; monitoring of viral load is controversial
Journé, 2024 (34) toxoplasmosis	•Case series, France (1987–2021)	664 infected newborns 521 (80.7%) antenatal PS/S 632 (97.8%) postnatal PS/S*	12-year follow-up: 187/664 (29%) children had at least one ocular lesion, with peaks at 7 and 12 years	•Substantial risk of retinochoroiditis despite screening and ante-/postnatal atreatment
Walker 2019 (39) syphilis	•Cochrane	•Benzathine penicillin vs. no intervention for suspected neonatal syphilis	Congenital syphilis (↓) due to antibiotic treatment (RR 0.12, [0.001; 2.09], n = 22), serological “cure”: RR 2.13 [1.06; 4.27]	•Study terminated prematurely (four infants in the untreated group had contracted syphilis)

^*529 children received pyrimethamine-sulfadoxine

B19V, parvovirus B19; BW, body weight; cCMV, congenital CMV infection; CI, confidence interval; CMV, cytomegalovirus; IUF, intrauterine fetal death; OR, odds ratio; PCR, polymerase chain reaction; RCT, randomized controlled trial; RR, relative risk; vs., versus