Labour and birth with primary or recurrent Herpes Simplex Virus 1 (HSV-1) Infection

What is Herpes Simplex Virus (HSV)?

Herpes Simplex Viruses (HSV) are viral infections that typically cause open, painful, red-rimmed sores or blisters on the individual. HSV typically spreads via skin to skin contact and there are two different types; HSV type 1 (HSV-1) or HSV type 2 (HSV-2). HSV-1 typically appears as open sores or blisters (‘cold-sores’) in the mouth area resulting in oral herpes, but can also cause genital herpes. HSV-2 is, in the vast majority of instances, transmitted through sexual contact and provides blisters on the moist lining of the genital or anal organs (genital herpes) and on the skin. The blisters or sores will form a scab after a few days and can appear anywhere on the body. Current estimates are that around 67% of people younger than 50 globally have HSV-1 infection, and 13% have HSV-2 infection (World Health Organisation, 2023).  Accordingly, transmission to neonates can occur when the infant is exposed to HSV during pregnancy (rare), birth or postnatally. Though neonatal herpes is very rare, occurring in 0.01% of births (10/100,000) globally (World Health Organisation, 2023), it is a serious condition that can lead to cerebral palsy and significant developmental delays (Jaiyeoba et al., 2012 and James et al., 2014). Here we explore what labour and birth for mothers with herpes can look like. 

Herpes Simplex Virus 1 (HSV-1) during labour and birth

Herpes Simplex Virus type 1 (HSV-1) is a lifelong infection which can impact individuals both orally and genitally and consequently can impact mode of birth and feeding options (see the Breastfeeding with Herpes blog post here). HSV-1 is typically contracted orally through contact with active lesions in or around the mouth (oral herpes or cold sores) and most adults have HSV-1 infection (WHO), with current infection estimates being around 70-80% in Australia. Most individuals infected with HSV-1 have no symptoms or very mild symptoms, with many people completely unaware that they have the infection despite being able to potentially transmit this infection to others. More than 75% of babies with HSV infections are born to women who are unaware that they had HSV.

Symptoms typically include painful, recurring blisters or ulcers in the mouth, nipple and genital area with new infections sometimes also causing fever, body aches, sore throat, headache and swollen lymph nodes (systemic illness signs). Symptoms are typically different during the first outbreak compared to subsequent episodes, and often the early symptoms include tingling, itching or burning near where the sores will appear. People can have repeated outbreaks over time, termed ‘recurrences’, though these are typically less severe and shorter than the initial episode/outbreak during infection. Most new infections in pregnant women are asymptomatic – i.e. can go undetected based on symptoms alone. It is recommended that if a woman is negative for HSV but is with a HSV positive partner, that they use protection throughout the pregnancy to avoid transmission in the last trimester which significantly increases likelihood of neonatal HSV transmission.

What does this mean for labour/birth, why is it an issue?

Given HSV-1 is readily transmissible, the likelihood of contact between the newborn and a woman’s genitals during the birthing process, and the significant risks to the baby if they do contract neonatal herpes (both morbidity and mortality), management of mode of birth and feeding is often quite conservative. Regardless of HSV history, 0.4% of women shed HSV from the genital tract at the time of birth, and in those with confirmed HSV history and recurrent prior infections, 1.4% shed HSV at the time of birth. In this study of almost 16,000 asymptomatic women, of the babies born to women who were shedding HSV at the time of birth, an estimated 12.5% of infants ended up with neonatal HSV. However, women with asymptomatic viral shedding are at lower risk of viral transmission compared to those with a primary infection (i.e. first infection). This article follows experiences of five newborns born to asymptomatic mothers who developed neonatal HSV and how their HSV-1 infection was diagnosed and treated.

Without active lesions at the time of birth or breastfeeding then the potential for transmission was previously thought of as extremely low/non-existent, however to my knowledge there are no studies that have actually quantified the rates of HSV-1 transmission to the neonate in asymptomatic women with a history of HSV-1 infection, however the majority of neonatal HSV infections occur to asymptomatic mothers. That said, for women who are within the first year of primary infection (first exposure and symptoms), asymptomatic shedding (i.e. shedding of the HSV-1 virus into the genital tract despite absence of symptoms) is higher, reported as happening in 64.6% of women at 2 months post exposure and dropping significantly within the first year post primary exposure. Further, the shedding of HSV-1 into the genital tract happens on 12.1% of days at 2 months post primary exposure and decreases rapidly, dropping to 7.1% of days at 11 months post primary exposure, indicating that shedding declines over time as the individual builds antibodies to the disease. Not all neonates born to HSV-1 infected mothers, even with symptoms and active lesions at the time of birth, will be infected with the HSV-1 virus and the likelihood of asymptomatic shedding of the virus is lower in women who are greater than 1 year post primary infection.

What are the statistics around neonatal Herpes Simplex Virus infection?

An estimated 0.005% – 0.03% of infants will become infected with HSV in the neonatal period. The greatest risk for neonatal HSV-1 infection is if the mother is first infected (i.e. has a primary HSV-1 infection) in the third trimester of pregnancy, particularly if within six weeks of birth when shedding of the virus continues before the mother develops protective antibodies against the virus. The way a primary infection is diagnosed and separated from a recurrent/previous infection is through testing for HSV-1 and HSV-2 using PCR tests and IgG tests – if the PCR test comes back positive for HSV-1 but the IgG is negative for HSV-1 this tells us that no immunoglobulins (antibodies) have been created against HSV-1, and consequently with a positive PCR, this indicates recent infection. Conversely, if the PCR is positive for HSV-1 and the IgG test is positive for HSV-1 then this indicates a recurrent infection rather than a recent/primary episode. Due to the higher likelihood (25-60%) of neonatal HSV infection in babies born to a woman with a primary infection within 6 weeks of birth, caesarean section is strongly recommended alongside antiviral treatment with acyclovir and valaciclovir to reduce severity and risk of neonatal HSV transmission. Certain interventions can also increase the risk of neonatal HSV infection in infected mothers including invasive procedures like the use of a fetal scalp electrode, instrumental birth and fetal blood sampling, so these should be avoided as much as possible.

For situations where a woman has a recurrent HSV infection and is seropositive (i.e. infected and creating antibodies, some of which are passed to the neonate) prior to pregnancy, the risk of transmission to the neonate has previously been considered as somewhat dependent on whether there are active lesions at the time of birth, though women can transmit HSV-1 even when asymptomatic. The risk of a woman with active lesions at the time of birth with a previously transmitted infection of HSV transmitting HSV to her baby is 1-3%, which is higher than the risk of transmission without active lesions. Although >75% of neonatal HSV infections occur with an asymptomatic mother, 1/3 of these infections happen in a mother with an asymptomatic primary (i.e. first) infection within the 6 weeks prior to birth, and their infants are 10 times more likely than women with a recurrent asymptomatic infection to end up with neonatal HSV. What this means is that a mother who has a recurrent HSV infection and has no active lesions at the time of birth is likely to have a <1% chance of transmitting the virus to the neonate, though the actual statistic for this is yet to be quantified. This article has a really great summary of the differences between different infections and the likelihood of the baby becoming infected with neonatal HSV under different circumstances.

Due to these risk factors, alongside the risks of caesarean section, the standard recommendations for women with recurrent HSV infection are:
a) Use suppressive antiviral therapy (acyclovir) from 36 weeks gestation to reduce outbreaks in the leadup to and during labour – this reduces the likelihood of an outbreak of HSV from 15% to 4% in the later weeks of pregnancy regardless of dosage amount, and reduces viral shedding (as per Cochrane collaboration review), consequently reducing the  likelihood of recommendation for caesarean birth. However, there is insufficient research to indicate a reduction in neonatal HSV and limited information exists regarding impacts of antenatal acyclovir administration on the neonate.
b) If no active lesions at the time of birth, offer vaginal birth and monitor for symptoms at the onset of labour
c) If active lesions at the onset of labour, advise a caesarean section, especially if waters have been broken for <6 hours. If waters have been broken for >6 hours then consider that cervical transmission may have already occurred – in this situation, serology testing of the newborn is recommended post birth.  However, some hospitals do still recommend vaginal birth despite active lesions due to the 1-3% rate of transmission to the newborn being compared to a higher risk to future pregnancies of caesarean section.

Summary Table

What happens if a baby gets neonatal herpes?

Neonatal herpes is associated with high morbidity and mortality, with acquisition at the time of birth accounting for around 85% of all cases. There are small rates of transplacental transmission (becoming infected through the placenta) or ascending infection from the cervix (increased likelihood with repeated vaginal exams, waters being broken) which make up 5% of all neonatal HSV transmission cases, and the remainder of cases occur due to postnatal infection (10%) from contact with an individual with HSV-1.

HSV-1 can be localised to the skin, eyes and/or mouth with symptoms developing within 10-12 days, but HSV can also spread and involve the local central nervous system (CNS). Skin-eye-mouth (SEM) disease typically accounts for ~35-45% infections, CNS disease accounts for around 30% or presentations and disseminated infection (disease that has spread from the original site of infection) for around 30% of presentations. The CNS infection can develop up to 6 weeks post birth with signs including irritability, lethargy, refusal to feed, fever, hypothermia, bulging fontanel or seizures, and sometimes (in 35% of cases) these are accompanied by lesions on the skin. If a baby is infected and multiple organs are involved then this results in the worst prognosis for the neonate. Without targeted treatment regimens, neonatal HSV infection within the first 30 days of life leads to around a 75% mortality rate and severe neurologic impairment in survivors, though with early PCR diagnosis and IV acyclovir treatment mortality rates have improved. However, there are questions around the acyclovir treatment in instances where there isn’t disseminated infection, because of the lower mortality rate in these cases and also the high rate of neutropenia and nephrotoxicity with acyclovir treatment in the newborn. There are recommended flowcharts for care provider decision making surrounding neonatal HSV infection included in this article.

Treatment of neonatal herpes

Neonatal herpes is typically treated with IV antiviral therapy using medications like acyclovir, vidarabine or valcyclovir. However, research on the efficacy of these drugs on treating neonatal herpes is limited and consequently requires further evaluation. Some research has looked at adverse events related to acyclovir administration and indicate that while adverse events may be common, these could actually be symptoms caused by the neonatal herpes infection, and adverse reactions to the acyclovir were not normally severe. Early testing and treatment is imperative for improving outcomes, but even with treatment mortality rates remain high.

How is the transmission of herpes to the neonate by an infected mother reduced?

One key way that care providers can help reduce the transmission of herpes from mother to neonate is through offering a caesarean section for mode of birth. While this is a valid option, especially in cases where a mother has active herpetic lesions on her genitals and is in the primary incidence of infection (within 6 weeks of birth), it does not completely mitigate the risk of herpes transmission (5% of neonatal herpes cases occur through transplacental transmission, 10% occur postnatally) and holds other risks for mother and neonate. Supporting women to undergo antiviral therapy in the later weeks of pregnancy to help reduce the likelihood of shedding is still considered a key way of reducing likelihood of transmission, and furthermore, avoiding the use of invasive obstetrical interventions can also help reduce the likelihood of neonatal HSV-1 transmission.

Key takeaways

• HSV-1 is a lifelong infection that is highly transmissible through contact with bodily fluids, and can result in neonatal infection which can be fatal.
• Given HSV-1 can be transmitted through contact with genital or oral lesions, and can also be shed from asymptomatic women, this poses a risk to babies born to HSV-1 positive mothers of contracting neonatal HSV.
• The likelihood of a HSV-1 positive mother passing on HSV to her newborn is:
  a) ~25-60% if her first infection with HSV-1 is within the 6 weeks prior to birth
  b) ~1-3% if she has active genital lesions at the time of birth and this is a recurrent infection (i.e. not the first incidence of infection)
  c) <1% (but not statistically represented in current research) if the mother has no active lesions at the time of birth. However, it is worth noting that ~75% of neonatal herpes infections occur to asymptomatic women.
• 005-0.003% of newborns end up with neonatal HSV. Mortality and morbidity rates are high.
• There are treatments available for babies with neonatal herpes, but they aren’t always successful at improving the prognosis. Early and effective treatment improves outcomes.
• Cases of neonatal herpes infection can be reduced by:
  a) Avoiding vaginal birth in instances where a woman has active lesions and has a primary (first) infection of HSV-1
  b) Offering antiviral medications to women who have a history of recurrent HSV-1 in the weeks leading up to birth to help avoid an outbreak of active lesions
  c) Avoiding vaginal birth in instances where a woman has active lesions at the time of birth, and ensuring birth occurs within 6 hours of waters breaking
  d) Avoiding the use of interventions that increase infection risks including breaking of waters, instrumental birth, use of fetal scalp electrodes and fetal blood sampling
  e) Monitoring babies post birth born to HSV-1 positive women

It is up to each woman to decide what risks they feel most comfortable accepting surrounding HSV-1 infection and the birth of their baby, and the potential risks of HSV-1 infection and transmission to the neonate with vaginal birth need to be weighed against the risks to both mother and baby associated with caesarean birth.