Transplacental Infection

Frequency, Testing, and Treatment

Background: Infections transmitted through the placenta are caused by viruses [e.g., cytomegalovirus (CMV) and parvovirus B19 (B19V)], bacteria (e.g., Treponema pallidum spp. pallidum), and protozoa (e.g., Toxoplasma gondii). These infections may have serious consequences for the unborn child. In this article, we discuss current aspects of prevention, testing, and treatment.

Method: This narrative review is based on pertinent publications (1946–1015) retrieved by a selective search in the PubMed/MEDLINE, Cochrane Library, ClinicalTrials.gov, and Google Scholar databases, along with the guidelines of medical societies.

Results: The current incidence of transplacental infection in Germany is ca. 1 : 200 (CMV) to 1 : 500 000 neonates (syphilis). The diagnosis is made by the serological demonstration of antibodies. Before the 20th week of gestation, the rate of vertical transmission is lower, but the potential for permanent harm is markedly higher than in the second half of pregnancy. 5–50% of transplacental infections lead to miscarriage or premature birth. Most infected fetuses are asymptomatic at birth, but there is still a 7–14% risk of sensorineural hearing loss from CMV and a 10–30% risk of retinochoroiditis from toxoplasmosis. Up to 60% of symptomatic neonates have long-term neurocognitive sequelae. Anti-infectious treatment is therefore indicated.

Conclusion: The most important preventive measures are hygiene education for pregnant women and prophylaxis against exposure. Anti-infectious treatment of pregnant women can reduce the risk of transmission, and the treatment of symptomatic neonates can improve the outcome.

Cite this as: Härtel C, Kagan KO, Viemann D, Schneider MO, Enders M: Transplacental infection: Frequency, testing, and treatment. Dtsch Arztebl Int 2026; 123: 312–20. DOI: 10.3238/arztebl.m2025.0227

Infections during gestation pose a significant threat to both mother and child. According to the World Health Organization (WHO), 11 out of every 1,000 pregnant women worldwide have infection-related complications (1). Transplacental infections are caused by viruses including cytomegalovirus (CMV), parvovirus B19 (B19V), rubella virus, human immunodeficiency virus (HIV), and hepatitis B virus, as well as by bacteria (Treponema pallidum, Listeria) and parasites such as Toxoplasma gondii. They usually cause no maternal symptoms but are suspected to contribute to 10–30% of miscarriages and stillbirths (2). The potential role of transplacental infection in congenital malformations, which affect 3 out of 100 live births, is insufficiently characterized (3). Especially in the first trimester, transplacental infection can severely impair organogenesis. 85–95% of infected fetuses are asymptomatic at birth, but 7–30% develop sequelae such as hearing loss or retinochoroiditis during childhood (4, 5). In this CME article, we focus on the types of transplacental infection that were recently addressed in an updated guideline (CMV), those whose epidemiological features are changing (B19V, Treponema), and those for which the proper modes of screening and treatment are currently under debate (Toxoplasma gondii; Table 1).

Table 1

Synopsis of transplacental infections: the treatment of pregnant women and neonates

Learning objectives

This article is intended to enable the reader to:

• give a realistic estimate of the prevalence of common transplacental infections in Germany,
• know the basic principles of diagnostic testing for transplacental infections, and
• evaluate preventive strategies and current treatment approaches for transplacental infections.

The pathogenesis of transplacental infection

The physiology of gestation is characterized by immune adaptations that strike a balance between defense against infection and prevention of fetal “rejection,” as the maternal immune system recognizes the fetus as “semi-foreign” tissue (6). From the 12th week of gestation (WoG) onward, an immunological state of tolerance dominates, with a shift in helper T-cell (Th) immunity toward a Th2 profile (7). This explains the increased susceptibility to infection in pregnant women compared to non-pregnant women. Pathogens can either infect the fetus directly or impair the function of the fetomaternal interface. The placenta is a very effective defensive barrier but can also be a reservoir for tissue cysts in Toxoplasma gondii infection. Treponema pallidum infects the placenta first, then the amniotic cavity (8). The P blood group antigen on trophoblasts is the primary placental target of B19V (9). CMV can be transmitted directly but can also impede cytotrophoblast differentiation and invasion, thereby causing placental fibrosis, which, in turn, impairs the fetal blood supply (10). A better understanding of the pathogenesis of transmission and manifestation of transplacental infections is needed so that targeted treatment can be optimized. Nonetheless, primary prevention through improved public education, hygiene, and exposure prophylaxis is crucial (Table 2).

Table 2

The primary prevention of transplacental infections*

Cytomegalovirus

The incidence of congenital CMV infection (cCMV) in Germany is 2–6 per 1,000 neonates. The most common source of CMV infection in pregnant women is the urine and saliva of CMV-shedding young children (11). Its seroprevalence among pregnant women in Germany is 40–50%. Many women in healthcare professions are CMV-negative when they realize that they are pregnant. Those working in pediatric hospitals as physicians, as well as those employed in daycare centers and schools, are often forbidden to work after a risk assessment pursuant to §10 of the Maternity Protection Act because of potential contact with Risk Group 2 biological agents including CMV. Implementation of mandatory protection for CMV-negative pregnant women within the organizational structure of the hospital or other institution, while enabling continued employment, should be the goal. The S2K Guideline 187–066 on maternal protection, now under consensus review, is intended to help standardize the management of occupationally exposed pregnant women.

The prevalence of primary CMV infection among pregnant women in Germany is 0.5–1%. Less than 1% of seropositive pregnant women have a recurrent CMV infection, i.e., reinfection with a new CMV strain or reactivation of a latent infection; maternal recurrent CMV infection leads to 10–30% of cases of cCMV (11). cCMV infections due to recurrent maternal CMV infection can be severe. Vertical transmission rates are approximately 35% in the first trimester and 65% in the third trimester. Severe developmental abnormalities are mainly due to maternal primary infections in the periconceptional period up to approximately the 20th week of gestation; they affect 10–20% of infected neonates (eTable) (4, 11, 12).

Women whose CMV status is unclear when pregnancy becomes known should be tested promptly for their current infection status (CMV-IgM and CMV-IgG) (11), even though this is not covered by health insurance under the current maternity guidelines (Mu-RL) of the German Joint Federal Committee (13). Serologic testing is always indicated in cases of relevant exposure, clinical suspicion, or abnormalities on ultrasound, with seroconversion confirming a primary infection. CMV IgG avidity testing, which measures the strength of the binding of antibodies against CMV, can help narrow down the timing of the maternal infection. High CMV IgG avidity is inconsistent with a recent primary infection, but low avidity does not prove it (Table 3).

Table 3

Transplacental infections: screening and diagnostic testing

Treatment of pregnant women with valacyclovir (8 mg/day) on detection of a primary CMV infection can markedly lower the transmission rate (14, 15) and tends to improve neonatal outcomes (14) (Table 1). Hyperimmunoglobulin administration is not recommended (4). In cases of primary infection, amniocentesis should be offered from the 18th week of gestation onward for testing of the amniotic fluid for CMV transmission with the polymerase chain reaction (PCR) (4, 11). If the PCR finding is positive, the initiated valaciclovir therapy can be continued (4, 15) or switched to valganciclovir in the presence of marked findings on ultrasound, such as brain calcifications; in a pilot study, this was not found to cause any relevant degree of neonatal neutropenia (Table 4) (16).

Table 4

Transplacental infections: treatment

15–30% of neonates with transplacental CMV infection are symptomatic to vaying degrees (eTable) (12). They carry a 35–50% risk of sensorineural hearing loss (SNHL) of 20 dB or more (detected with auditory brainstem evoked potentials, such as AABR or BERA) or neurocognitive impairment. Asymptomatic neonates with cCMV have a 7–14% risk of developing SNHL later in life. No definitive conclusions can be drawn about their neurological development (4, 11, 12). Follow-up care up to age 6 (e.g., brainstem audiometry, developmental tests) is needed for for asymptomatic CMV-infected children as well.

Postnatal treatment id intended to prevent the onset or progression of SNHV. Symptomatic neonates with moderate or severe manifestations (eTable) should be treated with valganciclovir for 6 months (Table 1). In a placebo-controlled, randomized trial, a 6-month course of valganciclovir yielded slightly better outcomes than a 6-week course with regard to hearing development and neurological condition at 12 and 24 months, although no differences were observed in the primary endpoint (hearing impairment at 6 months) (Tables 1, 4) (17). Treatment should be initiated within the first month after birth (18). CMV-infected infants who are asymptomatic except for an abnormal hearing test may have better hearing at 22 months if they are given a 6-week course of valganciclovir (n = 37; odds ratio [OR] 0.1, 95% confidence interval: [0.02; 0.45], p = 0.003) (Table 4) (19). It is unclear whether treating asymptomatic neonates with cCMV infection can prevent the development of hearing impairment over time, and such treatment is not recommended in clinical practice (4).

Parvovirus B19

Symptomatic B19V infection is estimated to affect fewer than 1 in 10,000 neonates per year (20, 21, 22). In Germany, approximately 35% of preschool children and 60–70% of young adults are seropositive (9, 22). The seroconversion rate during pregnancy is under 2% in endemic periods but can rise markedly during an epidemic. Information on epidemic clusters is available from the Robert Koch Institute (RKI) and reference laboratories (9, 20). In 2024, there was a marked rise in detected primary infections in pregnant women (Figure) all over Germany (eFigure). This observation may be related to altered epidemiologic features of B19V after measures related to the COVID pandemic.

Figure

The demonstration of parvovirus B19 (B19V) DNA in the blood of pregnant women by PCR (1 specimen per case) from January 2016 to December 2024 (data from the routine diagnostic laboratory of Prof. Dr. G. Enders MVZ GbR, Stuttgart).

eFigure

B19V is primarily transmitted via respiratory droplets (21). The infection is self-limiting in immunocompetent people; approximately half of the infected individuals develop symptoms such as a rash or transient arthropathy. The typical rash in affected children, called erythema infectiosum, bright red cheeks and a garland-like maculopapular rash.

Serological screening for B19V is not recommended in the maternal health guidelines (13), but seems reasonable for pregnant women with close contact to children of primary-school age, as these women are known to have a higher incidence of B19V (Table 3) (20). As far as is known, only a primary infection during pregnancy causes fetal complications. If the mother is B19V-IgG-positive and IgM-negative, she is considered protected. If abnormal ultrasound findings warrant further investigation, a B19V-PCR test should always be performed in addition to a positive B19V-IgG test. If both IgG and IgM are positive, B19V PCR and, if necessary, additional serological tests—such as IgG avidity or immunoblot—should be performed to confirm a recent infection (Table 3) (9).

In 30–50% of cases of primary infection, B19V is transmitted to the fetus. Infection from the 13th to the 20th week of gestation causes fetal anemia or hydrops fetalisin 7–8% of cases. Infection in the first trimester increases the risk of a non-hydropic spontaneous abortion (eTable) (9).

As 85–95% of complications arise within 10 weeks of maternal infection (22), regular ultrasound or Doppler ultrasound examinations are recommended after confirmation of an infection (9). The flow velocity in the middle cerebral artery should be followed over time for the early detection of anemia before hydrops develops. Aside from anemia, other contributing factors to the development of hydrops may include endothelial damage to the capillary barrier and cardiomyopathy due to myocarditis (9). Hydrops elevates fetal and perinatal mortality to approximately 30%, compared to 4% in cases of anemia without hydrops (23). Among surviving neonates with hydrops, 10% suffer from long-term neurological impairment, presumably because of transient intrauterine oxygen deprivation (24). The standard treatment for severe fetal anemia is intrauterine transfusion, which gains time until normal erythropoiesis is restored (Tables 1 and 4) (9, 25).

Toxoplasmosis

The Robert Koch Institute receives 6–23 reports of congenital toxoplasmosis per year; the actual number of infected children is likely higher and is estimated at 350 symptomatic and 1,300 asymptomatic newborns per year (26). The intracellular protozoon Toxoplasma gondii is ubiquitous and can infect almost all domestic and wild animals; domestic cats, which excrete oocysts, are the definitive hosts. In Germany, the main risk factors for Toxoplasma infection are raw meat consumption and the presence of cats in the household. As a rule, only primary infection during pregnancy leads to transplacental infection (exception: severe immunosuppression). In this process, multiplying tachyzoites released from placental foci cross into the fetal compartment (26).

Infections increase the risk of miscarriage in early pregnancy and can lead to the classic triad of retinochoroiditis, cerebral calcifications, and hydrocephalus. With antenatal antiparasitic treatment, the pre- and postnatal risk of hydrocephalus is 0–4% (27, 28, 29, 30). Retinochoroiditis affects approximately 15–30% of children and may not manifest until preschool age or later, sometimes with marked impairment of vision (5, 30, 31, 32, 33).

Women should be told about the risk of toxoplasmosis as early in pregnancy as possible (26). Because the infection is almost always asymptomatic in pregnant women, transplacental transmission can only be diagnosed by the detection of specific IgM and IgG antibodies and treated with the appropriate antiparasitic drugs (eTable) (26).

In cases of latent infection, IgM detectability can persist for years; therefore, if IgM is positive, the antigen-binding strength of IgG antibodies (IgG avidity), which increases the longer the infection has been present, is determined as well. High IgG avidity suggests that the infection occurred weeks to months ago (the test manufacturer’s instructions should be followed in this regard). Low IgG avidity is of limited diagnostic value and necessitates further follow-up testing and the measurement of other parameters (e.g., IgA, IgM) to assess the timing of infection (Table 3).

In cases of primary infection transmission is prevented by continuous antiparasitic therapy, which is begun with spiramycin only (3.0 g = 9 million IU/day) up to gestational week 15+0, because of the teratogenicity of pyrimethamine. From gestational week 15+0 onward, pyrimethamine (50 mg on the first day, 25 mg starting on day 2) is given for at least four weeks in combination with sulfadiazine (50 mg/kg body weight/day, maximum 4 g/day) and folinic acid (10–15 mg/day; discontinue folic acid supplementation from then onward) to lessen the risk of the risk of bone marrow toxicity (25). Through treatment of toxoplasmosis can lower the risk of long-term damage (Table 1) (5, 32, 33, 34, 35). A French study of 2455 mother-child pairs that was conducted after the introduction of screening in 1992 showed a downward secular trend in clinical symptoms in the affected children after treatment of the primary infection (26/177, 14.7%, 2009–2021 versus 55/193, 28.5%, 1992–2008; OR 0.49, [0.28; 0.85]), although retinochoroiditis cannot be completely prevented (13 versus 34 affected children) (35). The need for amniocentesis for the detection of fetal infection after successful treatment is debated. It should be performed no earlier than four weeks after maternal infection and not before 18 weeks of gestation (26). If the pathogen is detected by PCR, treatment is recommended until the child is born. Amniotic fluid PCR is 70–90% sensitive and 98–100% specific; thus, a negative PCR finding does not rule out infection.

The detection of specific IgM and/or IgA antibodies in the blood of the neonate indicates a congenital infection. Its sensitivity, however, is only 40–50% and is especially low in asymptomatic children whose mothers were treated prenatally. Therefore, a comparative immunoblot (parallel testing of infant and maternal serum) or pathogen detection via PCR in EDTA-treated blood or cerebrospinal fluid is recommended as well. As there is no diagnostic test that can definitively rule out a congenital infection, regular serological follow-up is advised until maternal antibodies have are no longer present (Table 3).

For infected but clinically asymptomatic neonates or children in congenital toxoplasmosis is only diagnosed later on follow-up laboratory testing (specifically, when specific IgG levels do not continue to decline or begin to rise), no clear treatment recommendation can be made, because of insufficient evidence. Parents should receive individualized counseling, including the recommendation that the child should be examined regularly by an ophthalmologist (Tables 1 and 4).

In symptomatic neonates, after a cerebrospinal fluid examination, combination therapy with pyrimethamine, sulfadiazine, and folinic acid should be initiated within five days (pyrimethamine: 1 mg/kg body weight/day, sulfadiazine 100 mg/kg body weight/day in two divided doses, and folinic acid 10 mg 3 times/week or 50 mg once/week, depending on the regimen). Treatment for symptomatic congenital toxoplasmosis is typically given for 12 months, with regular clinical follow-up (5, 33, 34, 35).

Syphilis

The reported incidence of syphilis in Germany is steadily rising, but the incidence of congenital syphilis steadily remains low (for example, 8 cases in 2024) (36). In the United States, there has been a marked increase in congenital cases because of lack of access to healthcare (8). Syphilis is almost exclusively transmitted by sexual contact (36). Aside from transplacental transmission, syphilis can rarely be transmitted to an infant peri- or postnatally either during vaginal delivery or through breastfeeding if the mother has syphilitic lesions on her breasts.

Syphilis is a systemic infection with a primary stage (painless chancre at the inoculation site), a secondary stage approximately six weeks later with generalized symptoms (e.g., maculopapular rash, lymphadenopathy, alopecia, hepatitis, meningitis), an early latent stage (up to one year after infection), and a late latent stage (more than one year after infection) (8). 70% of untreated infections remain latent, while 30% of untreated patients develop tertiary syphilis 10 to 30 years after the initial infection (37).

In a pregnant woman with untreated or inadequately treated syphilis, there is a risk of transplacental infection. Transmission to the fetus can occur at any stage of pregnancy but is most likely to occur after the 16th week of gestation; if the mother has sustained a primary infection during early pregnancy, the probability of transmission is 50–70% (eTable) (8). In women with late-stage latent syphilis, the risk of transmission is lower, but still substantial. Intrauterine infection can lead to miscarriage, stillbirth, or preterm birth (8). According to the German maternity protection guideline, a syphilis screening test (SST) should be performed as early as possible in pregnancy and documented in the prenatal care record. The SST detects Treponema pallidum-specific IgM and IgG antibodies, typically yielding a positive result 2–3 weeks after infection. As coinfection is common, an HIV test should also be performed if syphilis is detected. This must be confirmed by a second pathogen-specific antibody test. The activity of the infection is tested with Treponema-pallidum-IgM tests (e.g., 19S-IgM-FTA-ABS, IgM-Immunoblot, IgM-EIA) und non-pathogen-specific cardiolipin antibody tests (e.g., VDRL, RPR) (Table 2). Screening and treatment of infected pregnant women (if the infection has been present for less than one year, benzathine penicillin G 2.4 million IU as a single intramuscular injection; if it has ben present for more than one year or for an unknown period of time, benzathine penicillin G 2.4 million IU intramuscularly on days 1, 8, and 15) lower the risk of an adverse outcome of pregnancy and can prevent more than 95% of cases of congenital syphilis (Table 1) (8).

Congenital syphilis is classified into an early stage (lues connata praecox) in the first two years of life and a late stage (lues connata tarda) thereafter, with differing manifestations. Half of the infected neonates are asymptomatic at birth. The first symptom is often rhinitis with thick secretions. The early stage is characterized by respiratory problems, a maculopapular, sometimes vesicular rash (palms, soles, face, and buttocks), bone changes (periostitis, osteitis), nephritis, and hepatobiliary dysfunction. 30–60% of cases have manifestations in the nervous system including meningitis, seizures, stroke, and cranial nerve deficits. Comprehensive organ function tests and imaging should be performed when there is a corresponding clinical suspicion. Typical findings of a late manifestation include the Hutchinson triad, which consists of keratitis (from age 4 onward), barrel-shaped permanent teeth, and sensorineural hearing loss (from age 10 onward). Further indicative changes are seen in the bones, cartilage, and joints (“sword-shaped tibia,” “saddle nose”); perforation of the palate is pathognomonic (eTable) (8).

The diagnosis of congenital syphilis is complex and is based on information about the treatment of the maternal infection, the infant’s symptoms, and laboratory findings. All infants born to mothers with syphilis should undergo postnatal testing for Treponema-specific antibodies and cardiolipin antibodies. The detection of specific IgM antibodies suggests that the infant has developed an immune response to Treponema pallidum. A Venereal Disease Research Laboratory (VDRL) test or a cardiolipin microagglutination test (CMT) showing a ≥ 4-fold increase in the maternal titer likewise strongly suggests intrauterine exposure. Cerebrospinal fluid analysis is indicated for all symptomatic neonates as well as for asymptomatic neonates with abnormal laboratory findings or after inadequate treatment during pregnancy. Children with a potential prenatal exposure should be monitored until maternal antibodies are no longer detectable (Table 2) (40).

A possible infection cannot be ruled out if the mother was treated inadequately or only in the last 30 days of pregnancy, or if adherence to follow-up care is uncertain. In cases of probable or possible infection, the infant is treated with penicillin G 50,000 IU/kg IV twice daily (first week of life), three times daily (weeks 2–4), and finally four to six times daily for 10 days (starting in week 5)(Tables 1 and 3) (8, 39). Children in the early stages of the disease are contagious via their nasal secretions and skin lesions. The risk of transmission ceases just 24 hours after the initiation of treatment.

Overview

Preventing transplacental infections through education and counseling (hygiene, exposure prophylaxis) has high priority. In addition to the screening tests recommended in the German maternal protection guideline, serological testing should be performed liberally in case of exposure to pathogens known to cause transplacental infection and should be repeated during pregnancy if clinical suspicion arises. Secondary preventive measures include anti-infective treatment of the pregnant woman to lower the risk of transmission. Decisions about postnatal treatment of affected neonates should be made in consideration of the timing of the infection, the treatment that the mother has undergone during gestation, and the child’s clinical manifestations.

Conflict of interest statement
CH is vice president of the German Society for Pediatrics and Adolescent Medicine.

ME received study support from Biotest AG.

KOK was involved in the development of the German guideline “Prevention, Diagnosis, and Treatment of CMV Infection in Pregnant Women and Congenital CMV Infection in Neonates and Children.”

DV and MOS state that they have no conflict of interest.

Manuscript received on 26 April 2025 and accepted after revision on 26 November 2025.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Christoph Härtel

References

1. WHO Global Maternal Sepsis Study (GLOSS) Research Group: Frequency and management of maternal infection in health facilities in 52 countries (GLOSS): A 1-week inception cohort study. Lancet Glob Health 2020; 8: e661–e71.

2. Fouks Y, Many A, Shulman Y, Bak S, Shinar S: The contribution of an infectious workup in understanding stillbirth. Am J Perinatol 2021; 38: 377–82

3. Boyle B, Addor MC, Arriol L, et al.: Estimating global burden of disease due to congenital anomaly: An analysis of European data. Arch Dis Child Fetal Neonatal Ed 2018; 103: F22–F8

4. Leruez-Ville M, Chatzakis C, Lilleri D, et al.: Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI). Lancet Reg Health Eur 2024; 40: 100892

5. Garweg JG, Kieffer F, Mandelbrot L, Peyron F, Wallon M: Long-term outcomes in children with congenital toxoplasmosis—a systematic review. Pathogens 2022; 11: 1187

6. Abu-Raya B, Michalski C, Sadarangani M, Lavoie PM: Maternal immunological adaptation during normal pregnancy. Front Immunol 2020; 11: 575197

7. Rowe JH, Ertelt JM, Aguilera MN, Farrar MA, Way SS: Foxp3(+) regulatory T cell expansion required for sustaining pregnancy compromises host defense against prenatal bacterial pathogens. Cell Host Microbe 2011; 10: 54–64

8. Stafford IA, Workowski KA, Bachmann LH: Syphilis complicating pregnancy and congenital syphilis. N Engl J Med 2024; 390: 242–53

9. Kagan KO, Hoopmann M, Geipel A, Sonek J, Enders M: Prenatal parvovirus B19 infection. Arch Gynecol Obstet 2024; 310: 2363–71

10. Pereira L: Congenital viral infection: Traversing the uterine-placental interface. Annu Rev Virol 2018; 5: 273–99

11. Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF). S2k-Leitlinie 093–003: Prävention, Diagnostik und Therapie der CMV-Infektion bei Schwangeren und der konnatalen CMV-Infektion bei Neugeborenen und Kindern. Version 1.0. 2025. https://register.awmf.org/assets/guidelines/093-003l_S2k_Praevention-Diagnostik-Therapie-CMV-Infektion-Schwangere-konnatalen-CMV-Infektion-Neugeborene-Kinder_2025-04.pdf (last accessed on 19 October 2025).

12. Keymeulen A, De Leenheer E, Casaer A, et al.: Neurodevelopmental outcome in children with congenital cytomegalovirus infection: A prospective multicenter cohort study. Early Hum Dev 2023; 182: 105777

13. Gemeinsamer Bundesausschuss (G-BA). Mutterschafts-Richtlinien (Mu-RL). G-BA; 2023. www.g-ba.de/downloads/62-492-3335/Mu-RL_2023-09-28_iK-2023-12-19.pdf (last accessed on 18 October 2025).

14. Shahar-Nissan K, Pardo J, Peled O, et al.: Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: A randomised, double-blind, placebo-controlled trial. Lancet 2020; 396: 779–85

15. Chatzakis C, Shahar-Nissan K, Faure-Bardon V, et al.: The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis. Am J Obstet Gynecol 2024; 230: 109–17

16. Bourgon N, Lopez R, Fourgeaud J, et al.: In utero treatment of congenital cytomegalovirus infection with valganciclovir: An observational study on safety and effectiveness. J Antibiot Chemoth 2024; 79: 2500–08

17. Kimberlin DW, Jester PM, Sánchez PJ, et al.: Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 2015; 372: 933–43

18. Kimberlin DW, Aban I, Peri K, et al.: Oral valganciclovir initiated beyond 1 month of age as treatment of sensorineural hearing loss caused by congenital cytomegalovirus infection: A randomized clinical trial. J Pediatr 2024; 268: 113934

19. Chung PK, Schornagel FAJ, Soede W, et al.: Valganciclovir in infants with hearing loss and clinically inapparent congenital cytomegalovirus infection: A nonrandomized controlled trial. J Pediatr 2024; 268: 113945

20. Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF): S2k-Leitlinie 093–001: Labordiagnostik schwangerschaftsrelevanter Virusinfektionen. Version 1.0. 2022. https://register.awmf.org/assets/guidelines/093-001l_S2k_Labordiagnostik-schwangerschaftsrelevanter-Virusinfektionen_2022-02.pdf (last accessed on 12 February 2026).

21. Röhrer C, Gärtner B, Sauerbrei A, et al.: Seroprevalence of parvovirus B19 in the German population. Epidemiol Infect 2008; 136: 1564–75

22. Enders M, Weidner A, Zoellner I, Searle K, Enders G: Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: Prospective evaluation of 1018 cases. Prenat Diagn 2004; 24: 513–8

23. Bascietto F, Liberati M, Murgano D, et al.: Outcome of fetuses with congenital parvovirus B19 infection: Systematic review and meta-analysis. Ultrasound Obstet Gynecol 2018; 52: 569–76

24. Lindenburg IT, van Klink JM, Smits-Wintjens VE, van Kamp IL, Oepkes D, Lopriore E: Long-term neurodevelopmental and cardiovascular outcome after intrauterine transfusions for fetal anaemia: A review. Prenat Diagn 2013; 33: 815–22

25. Kosian P, Hellmund A, Geipel A, et al.: Intrauterine transfusion in 103 fetuses with severe anemia caused by parvovirus infection. A multicenter retrospective study. Arch Gynecol Obstet 2023; 308: 117–25

26. Schneider MO, Faschingbauer F, Kagan KO, Gross U, Enders M, Kehl S: Toxoplasma-gondii-Infektion in der Schwangerschaft – Empfehlungen der Arbeitsgemeinschaft Geburtshilfe und Pränatalmedizin (AGG – Sektion Maternale Erkrankungen). Geburtsh Frauenheilk 2023; 83: 1431–45

27. Zeinali S, Khademvatan S, Jafari R, Vazifekhah S, Yousefi E, Behroozi-Lak T: Prevalence and risk factors of toxoplasma gondii infection among women with miscarriage and their aborted fetuses in the northwest of Iran. PLoS One 2023; 18: e0283493

28. Hutson SL, Wheeler KM, McLone D, et al.: Patterns of hydrocephalus caused by congenital toxoplasma gondii infection associated with parasite genetics. Clin Infect Dis 2015; 61: 1831–4

29. Mandelbrot L, Kieffer F, Sitta R, et al.: Prenatal therapy with pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission of toxoplasmosis: A multicenter, randomized trial. Am J Obstet Gynecol 2018; 219: 386.e1–e9

30. McLeod R, Kieffer F, Sautter M, Hosten T, Pelloux H: Why prevent, diagnose and treat congenital toxoplasmosis? Mem Inst Oswaldo Cruz 2009; 104: 320–44

31. Wallon M, Kodjikian L, Binquet C, et al.: Long-termocular prognosis in 327 children with congenital toxoplasmosis. Pediatrics 2004; 113: 1567–72

32. Strang AGGF, Ferrari RG, do Rosário DK, et al.: The congenital toxoplasmosis burden in Brazil: Systematic review and meta-analysis. Acta Trop 2020; 211: 105608

33. Wallon M, Peyron F, Cornu C, et al.: Congenital toxoplasma infection: Monthly prenatal screening decreases transmission rate and improves clinical outcome at age 3 years Clin. Infect Dis 2013; 56: 1223–31

34. Journé A, Garweg J, Ksiazek E, Peyron F, Binquet C, Wallon M: Long-term ocular outcomes in congenital toxoplasmosis treated perinatally. Pediatrics 2024; 153: e2023064114

35. Wallon M, Ksiazek E, Journe A, et al.: Congenital toxoplasmosis: Fewer clinical signs at 3 years of age over the last 15 years but stable risk of materno-fetal transmission. Clin Infect Dis 2025; 81: 648–50

36. Jansen K, Bremer V: Syphilis in Deutschland in den Jahren 2023 und 2024 – Neuer Höchststand von Infektionen mit Verlangsamung der Dynamik. Epid Bull 2025; 39: 3–24.

37. Gjestland T: The Oslo study of untreated syphilis: An epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material. Acta Derm Venereol Suppl (Stockh)1955; 35 (Suppl 34): 3–368.

38. Tong H, Heuer A, Walker N: The impact of antibiotic treatment for syphilis, chlamydia, and gonorrhoea during pregnancy on birth outcomes: A systematic review and meta-analysis. J Glob Health 2023; 13: 04058

39. Walker GJ, Walker D, Molano Franco D, Grillo-Ardila CF: Antibiotic treatment for newborns with congenital syphilis. Cochrane Database Syst Rev 2019; 2: CD012071

40. https://derma.de/fileadmin/derma/1_derma.de_WebRoot/Aerzte/Leitlinien/059-002l_S2k_Diagnostik_Therapie_Syphilis_2014_07.pdf (last accessed on 12 February 2026).