Infections and Screening During Pregnancy

The clinical challenge of infection management during pregnancy is deciding who to screen for which infection, when and with which test, rather than recognizing individual factors. For some agents (syphilis, hepatitis B, HIV), universal screening and early treatment almost completely prevent congenital disease; in some (CMV, toxoplasma) the screening itself differs between institutions; In hepatitis C, the recommendation has shifted from risk-based screening to universal screening in recent years.

A common principle applies across all topics: the likelihood of vertical transmission and the severity of fetal damage move in opposite directions in most factors. As the pregnancy progresses, placental transition becomes easier; As organogenesis is completed and the fetal immune response matures, the possibility of severe sequelae decreases. Presenting these two curves separately in consultancy creates a more accurate perception of risk than giving a pass rate alone.

Framework for Screening Decisions

Cytomegalovirus (CMV)

CMV is the most common congenital viral infection; In the meta-analysis, the pooled prevalence at birth was 0.67%. Approximately 90% of infected newborns are asymptomatic at birth. Sensorineural hearing loss, the most common late sequela, develops in 33–50% of symptomatic infants and approximately 25% of asymptomatic ones (UpToDate CMV in pregnancy v96.0, 2025).

Primary infection is the acquisition of the virus during pregnancy in a person without pre-pregnancy IgG (diagnosis by seroconversion). Non-primary infection is reactivation or reinfection with a different strain in seroimmune pregnant women. Since the global seroprevalence in women of reproductive age is approximately 86%, most cases develop on a seropositive basis. Preconceptional seroimmunity provides significant but incomplete protection: the risk of fetal infection in this group is approximately 1% (0.15–2%). Because the seroimmune population is much larger, 75% of congenitally infected infants in the United States are attributed to non-primary infection, and the frequency of symptomatic disease and long-term sequelae in these infants is similar to those born after primary infection—the “if the mother is immune, the baby is protected” assumption does not hold (UpToDate CMV in pregnancy v96.0, 2025).

Annual seroconversion in pregnant women was reported as 2.3% (95% CI 2.1–2.4) in a systematic review; In the current study, in which more than 200,000 pregnant women less than 23 weeks of gestation were screened in the USA, serological evidence of primary infection was only 0.35%. The highest risk group is seronegative parents with young children shedding CMV (24% per year, 95% CI 18–30) (UpToDate CMV in pregnancy v96.0, 2025).

Routine serological screening: institutions diverge

As of 2023, no professional organization or government authority was recommending universal CMV serology in the general obstetric population (Xie 2023, Prenat Diagn ). Reasons against: no vaccine to protect seronegatives; seropositives also carry risks; it cannot be reliably predicted whether an infected fetus will develop sequelae; and screening increases unnecessary intervention and termination (in an IgM screening of more than 75,000 pregnant women in Israel, the termination rate was significantly higher in those who did not have amniocentesis than in those who did: 35.6% versus 7.3%).

In contrast, the European Congenital Cytomegalovirus Initiative (ECCI) consensus group convened under the European Society for Clinical Virology in 2024 recommended first-trimester CMV serology as early as possible in all pregnancies, with repeat testing every four weeks until 14–16 weeks in seronegative women (Leruez-Ville 2024, Lancet Reg Health Eur). The rationale is growing evidence that valacyclovir reduces vertical transmission in early primary infection; a 2023 French cost-effectiveness analysis found this combined strategy cost-effective. The two positions reflect different weighings of the same evidence: one emphasizes potential screening-related harms, while the other prioritizes the opportunity for early treatment.

Diagnosis: IgM alone is not sufficient

IgG seroconversion in acute and convalescent sera taken three to four weeks apart is diagnostic. If there is no documented seroconversion, the diagnosis is based on the triad of IgG, IgM, and IgG avidity. IgM is misleading: it is positive only 75–90% of the time in acute infection, can remain positive for more than a year, becomes positive again in reactivation/reinfection, and becomes false positive in other viral infections (e.g. EBV). High avidity suggests the infection is older than three months, low avidity within the last three months; however, the performance and thresholds of commercial tests vary between laboratories (UpToDate CMV in pregnancy v96.0, 2025).

The value of maternal serology in the investigation of fetal anomaly detected in the second–third trimester is limited: the combined negativity of IgG and IgM excludes CMV, but does not exclude the combination of IgG positive / IgM negative after the 16th week, as it may be compatible with first trimester infection.

Transition and sequelae according to gestational age

The risk of severe neurological sequelae is concentrated in periconceptional and first-trimester infections; in the second half of pregnancy, vertical transmission is common and sequelae are rare (Chatzakis 2020, Am J Obstet Gynecol).

Ultrasound findings and diagnostic amniocentesis

Findings suggestive of congenital CMV: periventricular calcifications (the most characteristic finding is bilateral periventricular hyperechogenicity), ventriculomegaly, microcephaly, periventricular pseudocysts, hyperechoic bowel, growth restriction, ascites, pleural/pericardial effusion, hepatosplenomegaly, hepatic calcifications, polymicrogyria, cerebellar hypoplasia, amniotic fluid abnormalities, hydrops and placental thickening. Signs may appear 12 weeks or more after maternal infection, with some infected fetuses not developing at all. Isolated late-onset fetal growth restriction is not associated with CMV (congenital CMV rate in these cases is 0.2–0.4%, i.e. similar to birth prevalence); SMFM states that routine CMV serology may not be necessary in FGR investigation if there are no risk factors or evidence of fetal infection (UpToDate CMV in pregnancy v96.0, 2025).

Fetal diagnosis is made by CMV DNA PCR in amniotic fluid (sensitivity 70–100%). Since placental infection, transmission to the fetus, replication in the fetal kidney, and excretion into the amniotic fluid take six to eight weeks, the sample should be collected at least eight weeks after maternal infection. For amniocentesis performed at 17–20 weeks and ≥8 weeks after seroconversion, the sensitivity was 95.8% (95% CI 79.8–99.8), and the negative predictive value was 97.7%; No significant difference was shown between before and after the 21st week. The first 1 mL of fluid is discarded to reduce maternal cell contamination.

Maternal valacyclovir

In a double-blind randomized trial, 100 pregnant women with first-trimester or periconceptional primary infection were randomized before 14 weeks to oral valaciclovir (8 g daily, divided into 2–4 doses) or placebo; CMV positivity at amniocentesis after 21 weeks was 30% in the placebo group and 11% in the valaciclovir group (valaciclovir versus placebo: OR 0.29, 95% CI 0.09–0.90). The effect was significant in the first-trimester subgroup (48% in the placebo group and 11% in the valaciclovir group), but was not demonstrated in the periconceptional group; this difference was attributed to a later start of treatment (Shahar-Nissan 2020, Lancet ). In an individual patient data meta-analysis of one randomized and two observational studies (527 participants), valaciclovir reduced vertical transmission from 25.5% to 11.1% (aOR 0.34, 95% CI 0.18–0.61), neonatal infection from 41.1% to 19.2% (aOR 0.30), and CMV-related pregnancy termination from 4.5% to 0.9%; the number needed to treat to prevent a positive amniocentesis was 6.9 (Chatzakis 2024, Am J Obstet Gynecol ).

The ECCI 2024 consensus recommends that in the diagnosis of periconceptional or first trimester primary infection, oral valacyclovir 8 g/day should be started as early as possible, with amniocentesis after the 17th week and at least 8 weeks after diagnosis; If amniocentesis is negative, prophylaxis can be considered successful and discontinued. CMV hyperimmune globulin is not recommended: two randomized studies initiated in the second trimester showed no reduction in congenital infection, death, preterm birth, or symptomatic infection, nor did two-year hearing and developmental outcomes improve (Hughes 2021, N Engl J Med).

Hygiene counseling and newborn

Behavioral measures are reasonable despite low-quality evidence: among pregnant women who were seronegative at 11–12 weeks and received hygiene information, seroconversion was 1.2%, whereas it was 7.6% in the untested and uninformed comparison group. Recommendations include washing hands with soap and water after caring for a young child and avoiding contact with the child's saliva (not sharing food/fork/glass, kissing on the forehead, not the lips).

The time and manner of birth are determined by standard obstetric indications; Detection of CMV in the cervix or urine is not an indication for cesarean section. Newborns considered at risk should be tested within the first 21 days of life, even if the previous amniocentesis was negative (CMV can be detected at birth in at least 8% of these babies). The benefit of breastfeeding in a healthy term newborn outweighs the risk of transmission through milk; In preterm or sick newborns, pediatricians are consulted (UpToDate CMV in pregnancy v96.0, 2025).

Toxoplasmosis

In temperate climate countries, the primary source is bradyzoites in raw, undercooked or cured meat products; Intake of sporozoites through soil-contaminated fruits and vegetables or water is also important and is the main source in some countries. Cat ownership is only weakly associated with acute infection (cats shed oocysts for about three weeks during their lifetime); However, it makes sense to clean the litter box daily by someone else, because fresh feces are not infectious (UpToDate Toxoplasmosis and pregnancy v43.0, 2026).

Seroprevalence in women of reproductive age is decreasing: 15% in 1988–1994, 7.5% in 2011–2014 in women 15–44 years of age in the USA. In Europe there is wide variation between countries (Norway 7% to Spain 32%). In France, the incidence of seroconversion in seronegative pregnant women is 2.0–2.5 per 1000. Acute maternal infection is ≥80% asymptomatic; The most specific finding is bilateral, non-tender posterior cervical lymphadenopathy that may last for weeks.

Scan: two different national models

National organizations in the United States, Canada, the United Kingdom, and parts of Europe do not recommend routine universal screening because the prevalence and incidence are too low and screening is costly. In the rest of Europe, screening is part of routine prenatal care (monthly, bimonthly or quarterly); In 2020, the expert group of the French College of Obstetricians recommended continuing the monthly screening program; Decision-analytic modeling has calculated that even in a low-incidence setting such as France, screening saves €212 per birth. The benefit of screening-treatment is more evident in South America due to the prevalence of more virulent genotypes (UpToDate Toxoplasmosis and pregnancy v43.0, 2026).

The effectiveness of screening depends on frequency: the window for treatment to prevent fetal infection is the first three weeks after seroconversion. In France, seronegative pregnant women have been shown to miss 19% of expected monthly tests — this is the program's vulnerability.

Serological interpretation

If IgM is positive or equivocal (regardless of IgG) confirmation should be performed in an experienced reference laboratory. IgM negative + IgG positive in the first trimester indicates previous immunity and does not require confirmation; After about the 20th week, the timing interpretation of the same combination becomes unclear. In those whose IgM and IgG are both positive at the end of the first trimester, the probability of the infection occurring after conception is 1–3%. High IgG avidity is indicative of infection older than four months; Low avidity alone does not diagnose acute infection because it persists for years in some people. A twofold or greater increase in IgG titer in two samples three weeks apart suggests recent infection (UpToDate Diagnostic testing for toxoplasmosis v26.0, 2026).

Risk by week of pregnancy

Women infected before conception almost never infect the fetus. In French data, approximately 90% of congenitally infected liveborns are asymptomatic at birth; the most common findings are retinochoroiditis (15.5–26.0%), intracranial calcification (9–13%) and hydrocephalus (1.0–2.4%) (Dunn 1999, Lancet).

Prenatal diagnosis

Amniocentesis in confirmed or strongly suspected recent infection ≥18. week and at least two weeks after seroconversion has been documented (four weeks from the estimated date of infection). In France, sensitivity under these conditions is approximately 90%; negative PCR reduces the residual risk to 1% in the first two trimesters but leaves it at 16% in the third trimester—postnatal follow-up is mandatory. Sonographic findings (intracranial hyperechoic foci, ventricular dilatation, echogenic bowel, hepatosplenomegaly, ascites, hydrops, placental thickening) are nonspecific and indistinguishable from CMV or Zika; In the presence of multiple findings outside the screening program, at least toxoplasma and CMV serology should be requested together. Productivity is very low in isolated fetal growth restriction or isolated polyhydramnios. Findings associated with poor prognosis include ventricular dilatation, large brain abscesses, necrosis, gyrus disorders, and microcephaly; Isolated intracranial hyperechoic nodular foci were not associated with developmental delay.

Treatment

There is no international guideline; general consensus bases medication choice on the gestational age at diagnosis.

• <14 weeks → spiramycin 1 g (3 million IU) orally three times daily on an empty stomach. Long QT syndrome is a contraindication; No laboratory monitoring is required. Spiramycin concentrates in the placenta but passes into the fetal blood at approximately half the maternal level and does not cross the blood-brain barrier; While it may be effective in preventing placental infection, it is insufficient to treat established fetal infection.
• ≥14 weeks → pyrimethamine-sulfadiazine. American Academy of Pediatrics regimen: pyrimethamine 100 mg/day divided into two doses for two days, followed by 50 mg/day + sulfadiazine 75 mg/kg in a single dose, followed by 100 mg/kg/day divided into two doses (up to 4 g/day) + folinic acid 10–20 mg/day. The most commonly used regimen in France: pyrimethamine 50 mg/day + sulfadiazine 3 g/day (divided into 2–3 doses) + folinic acid 50 mg per week. Folic acid is not a replacement for folinic acid. (UpToDate Toxoplasmosis and pregnancy v43.0, 2026).

Pyrimethamine is a folic acid antagonist and may cause dose-dependent bone marrow suppression; A weekly complete blood count is required. Sulfadiazine can cause severe hemolysis in G6PD deficiency; Due to the risk of crystalluria, at least 2 liters of fluid per day is recommended. Side effects requiring discontinuation of treatment occurred in 3.4% of those receiving pyrimethamine-sulfonamide and in 1.7% of those receiving spiramycin alone; The main side effect is rash, and treatment is discontinued in case of rash due to the risk of severe cutaneous reactions. If pyrimethamine or sulfadiazine is not available, trimethoprim-sulfamethoxazole (160/800 mg twice daily) is an alternative.

If amniotic fluid PCR is positive, pyrimethamine-sulfadiazine is continued until birth and the baby is treated with the same regimen. There is no consensus on continuing treatment if PCR is negative and ultrasound is normal; The study group in France recommends continuing with spiramycin in periconceptional/first trimester seroconversions, and switching to spiramycin after at least four weeks of pyrimethamine-sulfadiazine in second–third trimester seroconversions.

Evidence of treatment

No randomized trials have been conducted versus placebo.

• TOXOGEST (36 French centres): 143 pregnant women >14 weeks gestational age were randomized to pyrimethamine-sulfadiazine versus spiramycin. Transmission 18.5% (12/65) and 30% (18/60)—OR 0.53 (95% CI 0.23–1.22, did not reach significance); the effect was stronger when started within three weeks after seroconversion. Cerebral ultrasound abnormality was 0/73 in the pyrimethamine-sulfadiazine arm and 6/70 in the spiramycin arm (p=0.01). The study was stopped early due to slow enrollment (Mandelbrot 2018, Am J Obstet Gynecol).
• SYROCOT (20 European cohorts, 1438 participants, individual patient data): treatment started within three weeks after seroconversion reduced transmission compared with starting at eight weeks or later (OR 0.48, 95% CI 0.28–0.80). No reduction in retinochoroiditis was demonstrated in the same analysis.
• In a European cohort of 293 infected fetuses, prenatal treatment reduced the risk of severe neurological sequelae or death by approximately three quarters (OR 0.24, 95% CI 0.07–0.71): when seroconversion occurred at week 10, the absolute risk of severe neurological sequelae or death was 25.7% in those treated and 60.0% in those untreated. To prevent one case, three fetuses need to be treated at 10 weeks and 18 fetuses at 30 weeks (Cortina-Borja 2010, PLoS Med).

These data refer to less virulent strains predominant in Europe and North America; It cannot be directly generalized to Central and South American strains.

Prevention: not drinking unfiltered water; Strict hand hygiene and washing fruits and vegetables after contact with soil; avoiding mucosal contact when preparing raw meat and not tasting it while cooking; cooking meat until the internal temperature reaches 66°C or above or freezing it in a home freezer (below −12°C) for 24 hours; not eating raw shellfish. If people with normal immunity wait at least one to three months after acute infection, the probability of transmission is extremely low (UpToDate Toxoplasmosis and pregnancy v43.0, 2026).

Syphilis

Although the rate of primary and secondary syphilis in women in the USA decreased from 8.7 per 100,000 in 2022 to 6.9 in 2024, congenital syphilis cases increased for the 12th year in a row: 3941 cases in 2024, 109.6 per 100,000 live births. (UpToDate Syphilis in pregnancy v98.0, 2026). On a global scale, the prevalence of maternal syphilis for 2016 was estimated at 0.69% (95% CI 0.57–0.81), while the prevalence of congenital syphilis was estimated at 473 (385–561) per 100,000 live births (Korenromp 2019, PLoS One). Screening based on behavioral risk factors alone is inadequate: approximately 50% of pregnant women with syphilis had none of the 16 traditional risk factors.

Screening timing. It is widely recommended that all pregnant women be screened at the first prenatal visit (UpToDate Grade 1B; the CDC and many national organizations agree). Institutions differ regarding rescreening: ACOG recommends repeat screening for all pregnant women at 28–32 weeks of gestation and at birth, whereas some guidelines recommend late-pregnancy screening only for those at risk. Any woman who has a stillbirth after the 20th week or who has never been screened during pregnancy should be screened at birth (Workowski 2021, MMWR Recomm Rep). Contacts outside of traditional prenatal care (substance abuse center, prison, emergency room, housing services) are screening opportunities: In the USA, 88% of mothers of congenitally infected babies in 2022 data had not been tested at all or in time, had not been treated, or had been inadequately treated. HIV testing is recommended for every pregnant woman diagnosed with syphilis.

False positive. In the study examining 75,056 pregnancies, the first screening was positive in 221 patients (0.29%), 83% of whom were found to be false positive; The ratio is similar in traditional and inverse algorithms. Each positive screen should be handled with a confirmatory algorithm, and false positives attributed to pregnancy should be retested at least four to six weeks after birth.

Treatment: penicillin and penicillin alone

Penicillin G benzathine is standard; To date, no clinically significant penicillin-resistant T. pallidum strain has been identified. It treats maternal disease, prevents transmission to the fetus, and treats established fetal disease (Workowski 2021, MMWR Recomm Rep).

Desensitization is mandatory in penicillin allergy. The only acceptable approach in pregnant women with a history of immediate type allergic reaction is desensitization followed by penicillin treatment (Grade 1B); During pregnancy, non-penicillin regimens are either contraindicated (tetracycline), have insufficient efficacy data (ceftriaxone), or do not treat the fetus because they do not fully cross the placenta (erythromycin, azithromycin). 5–10% of pregnant women report penicillin allergy; The story must be verified. Approximately 80% of those who have had an IgE-mediated reaction in the distant past have a negative skin test. Desensitization should be done by an allergist; The oral protocol is simpler and safer, taking about four hours. In settings where desensitization is not possible, WHO alternatives (early syphilis: erythromycin 500 mg 4×/day for 14 days, ceftriaxone 1 g IM/day for 10–14 days, or azithromycin 2 g single dose; late syphilis: erythromycin 500 mg 4×/day for 30 days) have been described; Infants of mothers treated with these regimens should be treated with penicillin after birth.

Jarisch-Herxheimer reaction is not a reason to postpone treatment, but all patients should be informed. The picture, which includes fever, headache, myalgia, rash and hypotension, begins 1-2 hours after treatment, peaks in the 8th hour, and resolves in 24-48 hours. In one series, it was seen in 15 of 33 pregnant women treated for syphilis (primary 3/3, secondary 12/20, latent 0/10). In the second half of pregnancy, the reaction may cause uterine contractions, preterm labor, and an abnormal fetal heart rate pattern; Some clinicians apply continuous fetal monitoring for 12–24 hours in all pregnancies that develop symptoms. Management is supportive; Routine premedication is not recommended.

Fetal and congenital disease

Transplacental transmission can occur from approximately 9–10 weeks onward and at any stage of maternal disease; because fetal abnormalities result from the inflammatory response, they become apparent after week 20. In untreated maternal infection, the risk of congenital infection is 50% in primary and secondary syphilis, 40% in early latent syphilis, and 10% in late syphilis; the risk is 26% in those with a nontreponemal titer ≥8 and 4% in those with a titer <8. Congenital infection occurs in 1–2% of infants born to appropriately treated mothers versus 70–100% of those born to untreated mothers. According to WHO estimates, maternal treatment reduces early fetal death/stillbirth by 82%, preterm birth or low birth weight by 65%, neonatal death by 80%, and clinical disease in the infant by 97%.

Findings suggestive of fetal infection on ultrasound after the 20th week are, in order of frequency: hepatomegaly (83%), anemia with middle cerebral artery Doppler (38%), placentomegaly (34%), ascites (19%), growth restriction (14%), hydrops (12%), polyhydramnios (11%), oligohydramnios (9%). Hepatomegaly and placentomegaly are early findings, anemia-ascites-hydrops are late findings. Abnormal ultrasound is not diagnostic, normal ultrasound does not exclude: congenital syphilis was detected in 39% of babies of seropositive mothers if the ultrasound was abnormal and 12% if the ultrasound was normal.

During follow-up, nontreponemal titer is checked at the time of treatment, eight weeks after treatment, and at birth. A fourfold increase indicates treatment failure or reinfection; A fourfold decrease is the acceptable response. A decrease in maternal titer does not guarantee that fetal treatment is adequate—one study found congenital syphilis in 16% of those with a fourfold decrease and 20% of those without. Interval between treatment and birth ≤30 days, high titer, birth ≤36 weeks, and early-stage infection are associated with treatment failure (UpToDate Syphilis in pregnancy v98.0, 2026).

Hepatitis B

Vertical transmission accounts for approximately half of chronic HBV infections worldwide. The risk of chronicization is inversely proportional to the age of exposure: if prophylaxis is not applied, it reaches 90% in those infected at birth and 20–30% in those acquired in childhood (UpToDate Hepatitis B and pregnancy v33.0, 2025).

All pregnant women should be screened for HBsAg in each pregnancy, preferably at the first visit (irrespective of immunization status and previous testing). In HBsAg positive patients, HBeAg, anti-HBe, HBV DNA, transaminases and fibrosis are evaluated. Pregnant women who are anti-HBs and anti-HBc negative and still at risk may be offered hepatitis B vaccine during pregnancy (it is not a live vaccine) and HBsAg is repeated at approximately the 28th week.

The most important determinant of transmission is maternal viral load: in those with HBV DNA >200,000 IU/mL at birth, transmission may reach up to 10%, even if timely passive-active immunoprophylaxis is administered to the baby. In pregnant women not receiving treatment, HBV DNA is measured at 24–28 weeks; an antiviral is recommended if the threshold is exceeded (Grade 1A).

• Agent: Tenofovir (TDF or TAF); The most extensive safety data in pregnancy belongs to TDF and resistance is rare. Lamivudine is not preferred due to its resistance rate; entecavir should not be used during pregnancy—patients who are planning pregnancy or become pregnant are converted to tenofovir. Interferon is avoided.
• Timing: It starts at the 28th week in environments where HBIG is available, and at the 16th week in environments where HBIG is not available. HBV DNA is checked after four weeks; At least a 2–3 log decrease is expected.
• Evidence: In a meta-analysis of 31 studies, TDF reduced transmission by 90% (RR 0.10, 95% CI 0.07–0.16); TDF and TAF efficacy are similar (Pan 2024, Clin Infect Dis). In 200 HBeAg-positive pregnant women with HBV DNA >200,000 IU/mL, transmission with TDF initiated at 30–32 weeks was 5% versus 18% (Pan 2016, N Engl J Med). A randomized trial in Thailand showed no difference (0% vs. 2%); In this study, HBIG and the first vaccine dose were administered an average of 1.3 hours after birth, and a total of five doses of vaccine were given (Jourdain 2018, N Engl J Med).
• Duration: However, treatment started to prevent transmission can be stopped after birth; ALT is monitored every three months for six months for postpartum exacerbation.

Within 12 hours after birth, at separate injection sites, the newborn is given one dose of HBIG and the first dose of hepatitis B vaccine; the vaccine series is completed, and the baby’s HBV status is assessed at 9–15 months. Newborn immunization is given even if the mother is taking antiviral medication. Cesarean birth is not recommended solely to reduce HBV transmission. Babies who have received immunoprophylaxis can be breastfed ; bleeding from cracked nipples should be prevented (UpToDate Hepatitis B and pregnancy v33.0, 2025).

Hepatitis C

In 2020, the CDC recommended screening for hepatitis C in every pregnancy except in settings where the prevalence is less than 0.1% (Schillie 2020, MMWR Recomm Rep ). Vertical transmission occurs only in HCV RNA positive individuals; Those who are anti-HCV positive but RNA negative do not transmit. The pooled transmission rate is approximately 5% in monoinfection and approximately 10% in HIV coinfection; modeling of three European cohorts found 7.2% (95% CI 5.6–8.9) and 12.1% (95% CI 8.6–16.8), respectively (Ades 2023, Clin Infect Dis ). Other risk factors are high viral load, history of injecting drug use, and peripheral blood mononuclear cell infection (Benova 2014, Clin Infect Dis).

Labor management is based on reducing fetal exposure to maternal blood: prolonged rupture of membranes and invasive intrapartum procedures are avoided (aOR 9.3, 95% CI 1.5–180.0 in one study of rupture of six hours or more; fetal scalp electrode OR 6.7, 95% CI 1.1–36.0). In contrast, the mode of birth is not associated with the transition; If there is no other indication, cesarean section is not recommended. Breastfeeding is supported, interrupted when nipples are cracked or bleeding (UpToDate Vertical transmission of HCV v39.0, 2026).

Antiviral treatment during pregnancy is not the standard of care. In 54 individuals treated with sofosbuvir-velpatasvir, SVR was reported as 96% (presented as an abstract only) and no vertical transmission was detected; In contrast, congenital anomalies were reported in 9 (12%) of 74 live births exposed to sofosbuvir and whose outcome was documented in the manufacturer's database. It seems reasonable to avoid sofosbuvir-containing regimens if treatment is to be attempted outside a clinical trial; All pregnant women should be referred to postnatal treatment.

HIV

HIV testing with an opt-out approach is recommended for all pregnant women; When the syphilis screening is repeated, the HIV test is also repeated. With the widespread use of ART in countries with sufficient resources, vertical transmission has decreased to less than 1%. All pregnant women should receive ART, regardless of CD4 count and viral load; Treatment is started without waiting for the resistance test result and is adjusted according to the result.

In a meta-analysis of 82,723 mother–child pairs, no perinatal transmission was observed among 4675 women who received ART before conception and had a viral load <50 copies/mL near delivery. In France, among 14,630 women receiving antepartum ART between 2000–2017, transmission was 0.14% in those receiving ART at conception and 0.99% in those who started ART during pregnancy (0.52%, 0.75%, and 1.67%, according to the trimester of initiation). No transmission occurred in any of the 5482 infants whose mothers had started ART before conception, continued it, and had a viral load <50 copies/mL at delivery (Sibiude 2023, Clin Infect Dis).

The preferred regimen in the treatment-naïve pregnant woman is an integrase inhibitor or boosted protease inhibitor on a dual NRTI backbone with a documented history of safety in pregnancy; UpToDate recommends the combination of tenofovir alafenamide-emtricitabine + bictegravir (Grade 2C). Dolutegravir is an equally effective and safe alternative; Concern for neural tube defects is not supported by current data. In patients presenting late in pregnancy (e.g. >28 weeks) and with viremia, an integrase inhibitor-containing regimen is recommended (Grade 1B). In patients whose suppression was achieved before pregnancy, the current regimen is usually maintained; In cobicistat-boosted regimens, viral load is monitored monthly as drug levels decrease in the third trimester.

Mode of birth and intrapartum antiretroviral

Both decisions are based on maternal viral load measured within four weeks before birth. ART is continued as much as possible throughout labor and delivery or planned caesarean section.

Evidence for the protective effect of caesarean section comes from the pre-combined ART era: in a meta-analysis of 15 prospective cohorts, transmission was 8.4% (72/857) at caesarean section and 16.7% (1280/7676) at vaginal birth (International Perinatal HIV Group 1999, N Engl J Med; Kennedy 2017, AIDS). In contrast, in a meta-analysis of studies after combined ART, prelabor cesarean section at 38 weeks did not reduce transmission compared with vaginal birth in mothers on suppressive ART at birth. If labor begins or membranes are ruptured before planned cesarean section, the decision is individualized: in advanced labor or if membrane rupture has lasted ≥4 hours, the benefit of cesarean section may be lost and vaginal birth is considered. Of 493 pregnant women under ART and with a viral load <1000 copies/mL, no transmission was observed, although membrane rupture exceeded four hours in 144 (Cotter 2012, Am J Obstet Gynecol).

Zidovudine administration: 2 mg/kg loading followed by continuous infusion of 1 mg/kg/h until birth; It is administered regardless of the presence of zidovudine resistance. Infusion is started at least three hours before planned cesarean section and immediately in the patient admitted in labor. Oral zidovudine is not a substitute for intravenous administration. In the French Perinatal Cohort, intrapartum zidovudine did not reduce transmission in 7917 women with HIV RNA <400 copies/mL at birth (0.6% vs. 0%), but did in those with HIV RNA ≥1000 copies/mL (2.9% vs. 7.5%) (Briand 2013, Clin Infect Dis).

Other intrapartum precautions: monitoring with a fetal scalp electrode is avoided as much as possible; If the viral load is ≥50 copies/mL, amniotomy and operative vaginal delivery (forceps, vacuum) are generally avoided. Delayed cord clamping does not affect the risk of transmission and is recommended by ACOG. Timing of birth in PPROM is determined by best obstetric practice; The presence of HIV does not change management and antenatal corticosteroids are administered if appropriate (ACOG Committee Opinion 751, 2018).

Breastfeeding

• Mother who is not virally suppressed or not receiving ART during the third trimester and at birth: it is recommended not to breastfeed (Grade 1A). In contrast, the mother who chooses to breastfeed is given harm reduction counseling—ART adherence and antiretroviral prophylaxis to the baby.
• Mother on ART with an undetectable viral load (<50 copies/mL) at least through the third trimester and at birth: the risk of transmission through breast milk appears to be below 1% but is not zero; Breastfeeding is an option to be discussed with the patient. In a meta-analysis of thirteen studies, the pooled risk of transmission per month of breastfeeding was 0.1% at viral load <50 copies/mL and 0.5% at ≥50 copies/mL (RR 6.3, 95% CI 1.2–34.6) (Dugdale 2025, Lancet).

Recommended practices for the virally suppressed mother who chooses to breastfeed: consultation with a pediatric infectious disease specialist during the antepartum period maternal viral load measurement every 1–2 months throughout breastfeeding breast care to prevent milk excess, stasis and engorgement rapid recognition and treatment of cracked, sore or bleeding nipples, fungal infection, mastitis and abscess exclusive breastfeeding for up to six months (mixed feeding increased the risk of viral transmission in pre-ART studies; whether this remains a risk factor under sustained viral suppression has not been studied) · gradual weaning over two–four weeks during weaning (sudden weaning has been associated with increased shedding of virus into breast milk) (Kuhn 2008, N Engl J Med).

Other Factors and Immunization

Parvovirus B19: The main source is respiratory infection in young children. IgG and IgM should be checked in pregnant women who come into contact or show symptoms, and those with acute infection should be monitored for fetal anemia and hydrops.

Varicella: Protection is based on pre-pregnancy immunization. ACIP recommends varicella-zoster immunoglobulin to all non-immune pregnant women who come into contact with varicella; Live varicella vaccine is not administered during pregnancy.

Rubella: Determination of immune status is a standard component of initial prenatal evaluation; In seronegative cases, vaccination is postponed until the postpartum period.

Listeria and food safety: Frequent hand washing; thorough cooking of meat, fish, poultry and eggs; avoiding unpasteurized dairy products; rinsing fresh fruits and vegetables under running water for about 30 seconds; avoiding raw sprouts; Washing surfaces and equipment that come into contact with raw meat with hot soapy water.

Asymptomatic bacteriuria: Found in an estimated 2–10% of pregnant women and is associated with pyelonephritis. USPSTF recommends screening pregnant women with urine culture (recommendation B); recommends against screening in non-pregnant adults (recommendation D) (USPSTF, 2019).

Immunization: The four vaccines routinely administered during pregnancy are COVID-19, influenza (independent of the stage of pregnancy), Tdap (in the third trimester of each pregnancy, regardless of previous vaccination) and RSV (RSVpreF, a single dose between 32+0 and 36+6 weeks during the RSV season; alternatively nirsevimab to the baby after birth) (UpToDate Prenatal care v126.0, 2026).

Clinical Summary

• Universal screening: Syphilis (first visit; ACOG also 28–32 weeks and birth), HBsAg, HIV (opt-out), hepatitis C (CDC 2020), asymptomatic bacteriuria (urine culture, USPSTF B).
• CMV: North America and most authorities do not recommend routine serology; ECCI 2024 recommends universal first-trimester serology, repeated every four weeks in seronegative women until 14–16 weeks. IgM alone is insufficient, IgG avidity is decisive. Amniocentesis ≥8 weeks after maternal infection. In early primary infection, valaciclovir 8 g/day reduces vertical transmission (aOR 0.34), but the GRADE is very low with 2.1% severe maternal adverse events.
• Toxoplasma: Transmission increases with gestational age (13/26/36 weeks: 15%/44%/71%), while symptomatic disease decreases (61%/25%/9%). <14 weeks: spiramycin; ≥14 weeks: pyrimethamine-sulfadiazine + folinic acid. The critical variable is timing — treatment initiated within three weeks of seroconversion reduces transmission (SYROCOT OR 0.48). Amniocentesis at ≥18 weeks and ≥2 weeks after seroconversion.
• Syphilis: Congenital cases have been increasing in the USA for 12 years. The only valid treatment is penicillin G benzathine; Desensitization is mandatory in penicillin allergy. Jarisch-Herxheimer onset occurs in 1–2 hours and may trigger preterm labor. A decrease in maternal titer does not guarantee the adequacy of fetal treatment.
• Hepatitis B: HBV DNA >200,000 IU/mL → tenofovir at week 28 (week 16 if HBIG is not available). HBIG+ vaccine to newborn within 12 hours. Cesarean section is not recommended for HBV alone; The baby who has received immunoprophylaxis can be breastfed.
• Hepatitis C: Transmission occurs only in RNA-positive mothers (~5%; ~10% with HIV co-infection). Prolonged membrane rupture and scalp electrode are avoided; Mode of birth and breastfeeding do not affect the transition. Antiviral treatment during pregnancy is not the standard of care.
• HIV: ART for all pregnant women; Perinatal transmission was 0.2% when viral load was <50 copies/mL and zero transmission was reported in 5482 preconception ART-suppressed pregnancies. Integrase inhibitor-containing regimen for late presentation (Grade 1B). The decision on mode of delivery and intrapartum zidovudine is based on viral load in the four weeks before birth: >1000 copies/mL → prelabor cesarean section (Grade 1A) + IV zidovudine (Grade 1B) at 38 weeks; ≤50 copies/mL → obstetric indication only, IV zidovudine is not recommended. Breastfeeding is not recommended unless there is suppression (Grade 1A); The risk of transmission with undetectable viral load is below 1% but is not zero and is discussed with the patient.

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