The incidence of genital herpes (GH) has been on the rise in recent years, and infection with herpes simplex virus (HSV) in pregnant women can cause a series of adverse consequences, so vertical transmission of HSV from mother to child is of increasing concern to patients and their families. In clinical practice, the prevention of vertical transmission of HSV from mother to child, the impact of HSV on pregnancy, the monitoring of pregnancy and the choice of delivery methods are often troubling to health care workers.
I. Vertical transmission from mother to child
The most important factor for HSV infection in newborns is the timing of the mother’s first HSV infection. Studies have shown that pregnant women with their first episode of GH during pregnancy, especially before delivery, are more likely to transmit the virus to their fetus or newborn than those infected before pregnancy. The incidence of HSV in infants born to mothers with first HSV infection during pregnancy is nearly 50%, while the incidence of HSV in infants born to patients with recurrent GH is less than 3%.
(1) Trans-placental infection : Less frequent, probably because the syncytial trophectoderm blocks HSV invasion, reduces the expression of HSV invasion mediators, and prevents HSV transmission through the placenta.
(2) Retrograde infection via the cervix: The cervix is an important route for vertical transmission of the virus to the fetus via the mother. In the absence of external genital lesions, cervical infection is usually already present, with a positive rate of cervical infection of 10% to 30%. Therefore, the presence of cervical infection cannot yet be determined when the vulval virus test is negative.
(3) Transnatal transmission: HSV infection in newborns is usually due to exposure to maternal genital tract secretions during delivery, usually through the eye, nasopharyngeal mucosa or secondary injury.
During delivery, the newborn is in close contact with the vaginal mucosa for several hours and only briefly with the vulva, so the newborn is more at risk from exposure to the virus-shed cervix and vagina than to the vulva.
Other risk factors for vertical transmission of HSV include maternal antibody titers, invasive obstetric practices, and timing of rupture of membranes.
II. Characteristics of infection in pregnant women
Pregnancy is generally not considered to affect the disease, incidence and severity of recurrence of GH. However, the results of a small sample of randomized controlled trials have shown that GH patients have a significantly higher rate of clinical recurrence during pregnancy, especially at the time of delivery, than non-pregnant women.
Studies have shown that reduced cytotoxicity of natural killer cells (NK) during pregnancy reduces fetal rejection of the placenta, but makes the mother more susceptible to HSV infection, and the first HSV infection during pregnancy is more severe than in non-pregnant women, leading to herpes encephalopathy, herpetic hepatitis, or disseminated infection.
Fetal infection
1. HSV can infect the fetus via placenta in early pregnancy, causing miscarriage and fetal malformation, such as microcephaly, microphthalmia and retinal dysplasia.
2. The first infection in middle and late pregnancy with or without symptoms may be associated with preterm delivery and fetal growth retardation, while asymptomatic recurrence does not increase the incidence of preterm delivery or low birth weight babies.
IV. Neonatal infection
Neonatal HSV infection has an extremely high morbidity and mortality rate.
The incidence of HSV infection in newborns ranges from 1/3,000 to 1/20,000.
Most infections arise from asymptomatic shedding of cervical virus after the first episode of GH in late pregnancy.
Clinical staging
①Skin, eye and oral infections (SEM).
The most common type of HSV infection in newborns, symptoms usually appear 10-14 d after birth. Sparse herpes is characteristic of the disease, and clusters of herpes are seen at the site of contact with the virus. Ocular damage includes conjunctivitis, keratitis, or chorioretinitis. This type of infection is confined to the skin, eyes, or mouth and has a low mortality rate.
② Central nervous system infection (encephalitis).
Central nervous system HSV infections often occur in the first few weeks of life. Most neonatal herpes diseases are caused by HSV I2, but all herpes encephalopathies are caused by HSV I1.
(iii) Disseminated infections.
Infections of the skin, eyes and mouth are rarely fatal, but disseminated infections of the liver, lungs and/or adrenal glands and infections of the central nervous system have a mortality rate of up to 80% if left untreated . Even if they survive, the majority of neonates will have neurological sequelae.
Characteristics of neonatal infections.
Early symptoms of HSV infection in newborns are nonspecific and often delay treatment. Even with early treatment, some infants develop disseminated infection or central nervous system complications.
(1) Nucleic acid testing.
(1) PCR of cervical secretions, herpes fluid from skin lesions and cerebrospinal fluid of pregnant women is the most routine test to diagnose HSV infection.
Some studies have shown that PCR of amniotic fluid does not predict the risk of HSV infection in newborns, and because invasive amniotic fluid testing increases the risk of vertical transmission from mother to child, PCR of amniotic fluid should not be included in routine testing.
(2) Antibody detection.
The use of glycoprotein IgG ELISA method can effectively distinguish
The use of the glycoprotein IgG ELISA method can effectively differentiate between HSV-2 IgG and HSV-1 IgG antibodies, so that HSV-1 and HSV-2 antibodies can be specifically detected. However, there is no consensus on whether HSV-2 specific serologic tests should be used as routine prenatal screening.
(3) Viral culture.
HSV virus culture of herpes fluid and cervical secretions is also commonly used as a test.
(2) Surveillance
There is no evidence that weekly HSV culture before delivery predicts the risk of neonatal infection. Viral titers in asymptomatic viral shedders are 10 to l00 times higher than in symptomatic individuals, and the sensitivity of using viral cultures to predict HSV infection in asymptomatic individuals is even lower. Therefore, weekly viral culture of HSV-infected pregnant women before delivery is not advocated for the time being.
(ii) Antiviral therapy: In pregnant women, the use of drugs such as acyclovir is controversial.
The use of drugs such as acyclovir in pregnant women is controversial and should be weighed against the pros and cons if needed
and with informed consent of the patient. The following are currently advocated
(1) oral acyclovir for primary genital herpes.
(2) for complications, intravenous acyclovir should be administered.
(3) In pregnant women with frequent recurrent or recent genital herpes infections, acyclovir treatment may be used to reduce the incidence of active damage near term, thereby reducing the rate of cesarean delivery.
(4) Treatment with acyclovir may not be necessary for pregnant women with a previous history of recurrent genital herpes but no signs of recurrence at near term.
The use of acyclovir and valacyclovir in pregnant women: their safety has not been confirmed, but studies have found that the incidence of malformations in pregnant women with acyclovir is not increased compared to the normal population, but no reliable conclusions have been reached regarding the risk of acyclovir to pregnancy and the fetus.
Mode of delivery
Management of recurrent attacks
1. Treatment of primary
If the membranes are not broken or if primary GH is found within 4h after rupture of membranes, cesarean delivery should be performed.
2. Management of recurrent episodes
(1) If there is no active genital damage at the time of delivery, delivery can be performed from
(1) If there is no active genital damage during delivery, vaginal delivery can be performed without cesarean section. Cesarean section cannot completely prevent HSV infection in newborns, and should only be considered for women who excrete HSV virus during delivery.
(2) In the last trimester, the recurrence of HSV is transient and can be delivered vaginally as long as there is no active damage at the time of delivery.
(3) Those with clinical evidence of active GH at the time of delivery may be managed as follows.
(1) In the absence of contraindications, caesarean section may be performed before rupture of membranes.
(6) Management of the newborn
1. If the pregnant woman has HSV-2 infection in the birth canal, the newborn can be given gammaglobulin prophylaxis immediately after delivery and eye drops with iodoside and cytarabine to treat herpetic keratitis effectively, but not to prevent recurrence.
2. Newborns suspected of having HSV infection should be carefully evaluated for.
(1) Pregnant women with a previous history of recurrent genital herpes and those who acquired the infection in the first half of pregnancy have a low risk of transmitting HSV to the newborn (<1%) and therefore do not support prophylactic treatment of such asymptomatic newborns with acyclovir.
(2) Pregnant women infected with genital herpes near the time of delivery have a higher risk of transmitting HSV to the newborn (30%-50%), and HSV culture at the time of pregnancy is not predictive of detoxification at the time of delivery; therefore, cesarean delivery and acyclovir 20 mg/kg daily in an intravenous drip for 10 ～The duration of treatment is between 10 and 21 days.
Prevention
(1) Avoid multiple sexual partners with regular partners.
(2) Pregnant women with a history of recurrent genital herpes in men.
(1) Sexual activity must be avoided when damage occurs or when there are prodromal symptoms.
(2) During seizure-free periods, sexual contact should occur using condoms as much as possible.
(3) Some scholars believe that such pregnant women should abstain from sex from 34 weeks of gestation to reduce the chance of HSV infection.
(3) Pregnant women with recurrent GH are less infectious to the fetus or newborn because their immune system has already produced anti-HSV antibodies, which can be passed to the fetus through the umbilical cord blood. To date, there are no measures to prevent HSV infection in pregnant women with recurrent GH.
(2) During pregnancy, especially in late pregnancy, the titer of the virus is high and the mother does not have time to produce protective antibodies to pass to the fetus. Therefore, the main measure to prevent fetal or neonatal infection is the prevention and control of HSV infection during pregnancy.
VII. Vaccination
Vaccination against genital herpes and neonatal herpes simplex has been shown to be effective in animal studies and has not been confirmed in clinical trials.
Further studies of the immune response mediated by natural HSV infection in adults and neonates will offer great promise for the prevention of acute episodes and recurrences of GH, but faster progress is needed to establish better animal models.
VIII. Conclusion
The first GH infection in late pregnancy is the greatest risk factor for vertical transmission of HSV; therefore, prevention and management of late pregnancy HSV infection is crucial to reduce fetal or neonatal infection. Whether viral culture, HSV-2 specific serologic testing should be used as routine prenatal screening and whether cesarean section can reduce the rate of HSV infection in newborns need to be further investigated.
Acyclovir has been shown to reduce genital herpes recurrence and viral shedding during delivery, and vaccine studies will offer new hope for the prevention and treatment of GH in pregnancy.