Approach to newborns exposed to HSV at the time of delivery

Recently the American Academy of Pediatrics issued recommendations that address management of asymptomatic newborns whose mothers have active herpes simplex virus (HSV) lesions noted at the time of delivery. Implementing these recommendations requires proactive coordination between the director of the laboratory and the obstetrical and pediatric providers to ensure success (Pediatrics 2013;131:e635-46).

Approximately 1,500 infants are diagnosed and treated for neonatal HSV infection each year in the United States. Most pediatricians are knowledgeable about the three forms of neonatal HSV infection and the role of prompt diagnosis and utilization of acyclovir. Even so, the outcomes of this disease may be devastating. Skin–eye–mucous membrane disease has the best prognosis (98% neurologically normal), as finding the culprit lesion generally ensures timely diagnosis and treatment. With central nervous system infection or disseminated disease, a skin lesion is not noted in 25%-40% of cases. So the diagnosis is sometimes delayed or missed initially because the initial presentations (seizures in CNS infection; sepsis picture or liver failure in disseminated disease) may sidetrack the provider into considering other working diagnoses, such as bacterial sepsis or metabolic disease. Neurologic sequelae occur in 25% of those with disseminated infection, but in upward of 70% in those with CNS disease.

Ideally, both the obstetrician and the pediatric provider play a role in ensuring appropriate care for the baby whose mother has active HSV lesions at time of delivery. Appropriate care includes preemptive treatment for neonatal HSV infection, which has the potential to improve outcomes and so should be a high priority for all providers.

The new guidance is evidence based and predicated on the availability of HSV typing of the HSV from the maternal lesion and type-specific serology. It allows the provider to define the newborn risk of acquiring HSV infection more explicitly and utilize preemptive evaluation/therapy. Providers should ensure that their hospital laboratory can perform such testing with reasonable turnaround time for results.

Obstetrical role and implications of testing

The obstetric provider should swab the maternal lesion for HSV polymerase chain reaction (PCR) assay/culture and typing (HSV-1 or HSV-2). These data can be utilized with maternal history and serologic results to calculate the neonatal risk for infection.

Calculation of relative neonatal risk

• First episode, primary infection. Defined as the first maternal HSV episode with type-specific serology being negative, this makes the risk of neonatal infection approximately 50%. If maternal history of prior disease is negative AND either the maternal lesion test results or serology results are unavailable, follow the plan of care for first episode primary infection.

• First episode, nonprimary infection. Defined as the first maternal episode but antibody to detected HSV type is not present (e.g., HSV-2 confirmed from lesion, with type 1 but NOT type 2 maternal antibody present; OR HSV-1 confirmed, with type 2 but NOT type 1 maternal antibody present), the risk of neonatal infection is approximately 25%.

• Recurrent. If the mother has a history of genital herpes and the mother’s type-specific antibody is the same as the type detected in the lesions, the risk for neonatal infection is lower and approximately 2%.

Pediatrician’s role and plan of care

The first order of business is to identify neonates who demonstrate signs or symptoms suggestive of HSV infection at birth or in the perinatal period (whether or not any lesions were noted at time of delivery). In this case, all infants should undergo full evaluation for both viral and bacterial causes and should have prompt initiation of preemptive antiviral and antibacterial therapy. The evaluation of an ill-appearing infant at birth should include CBC; liver function studies; blood, urine, and cerebrospinal fluid examination with bacterial cultures of blood, urine, and cerebrospinal fluid, plus blood and cerebrospinal fluid HSV PCR. Also, HSV surface (conjunctivae, nasopharynx, and rectum) and lesion cultures are needed. Infectious disease consultation is recommended if HSV infection is confirmed. Acyclovir should continue for 14 days for skin–eye–mucous membrane disease or 21 days for CNS or disseminated infection. Further evaluation toward the end of therapy can determine if a longer course of therapy should be considered.

The recent guideline addresses care for those infants who are born to mothers with active HSV lesions noted at time of delivery, and should be initiated only if the infant is asymptomatic at birth.

In this situation, for babies whose mothers have primary infection (risk 50% for neonatal infection) or first episode, nonprimary infection (risk 25% for neonatal infection):

• Approximately 24 hours after the infant’s birth, obtain blood HSV DNA PCR and HSV surface cultures of conjunctivae, nasopharynx, and rectum as well as from the scalp electrode site if there was one.

• Cerebrospinal fluid examination with HSV DNA PCR testing should be obtained.

• Acyclovir (20 mg/kg per dose every 8 hours IV) should be initiated. Preemptive therapy (acyclovir 20 mg/kg per dose every 8 hours IV) should be continued for 10 days and until all studies are negative.

For babies whose mothers have recurrent infection:

• Cerebrospinal fluid examination may be deferred.

• But the rest of the workup should be completed and IV acyclovir initiated.

• IV acyclovir can be stopped at the time that studies are negative (usually at 48 hours, assuming negative results of blood PCR and preliminary negative surface cultures), with close follow-up of the infant.

Use of this guideline can improve care of infants only when the laboratory and the obstetrical and pediatric providers have established a good working relationship. This ensures the availability of necessary HSV studies, complete implementation, and proper interpretation of testing to guide the newborn’s care.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled "Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions," but said she had no other conflicts of interest to disclose. E-mail her at [email protected].

Recently the American Academy of Pediatrics issued recommendations that address management of asymptomatic newborns whose mothers have active herpes simplex virus (HSV) lesions noted at the time of delivery. Implementing these recommendations requires proactive coordination between the director of the laboratory and the obstetrical and pediatric providers to ensure success (Pediatrics 2013;131:e635-46).

Approximately 1,500 infants are diagnosed and treated for neonatal HSV infection each year in the United States. Most pediatricians are knowledgeable about the three forms of neonatal HSV infection and the role of prompt diagnosis and utilization of acyclovir. Even so, the outcomes of this disease may be devastating. Skin–eye–mucous membrane disease has the best prognosis (98% neurologically normal), as finding the culprit lesion generally ensures timely diagnosis and treatment. With central nervous system infection or disseminated disease, a skin lesion is not noted in 25%-40% of cases. So the diagnosis is sometimes delayed or missed initially because the initial presentations (seizures in CNS infection; sepsis picture or liver failure in disseminated disease) may sidetrack the provider into considering other working diagnoses, such as bacterial sepsis or metabolic disease. Neurologic sequelae occur in 25% of those with disseminated infection, but in upward of 70% in those with CNS disease.

Ideally, both the obstetrician and the pediatric provider play a role in ensuring appropriate care for the baby whose mother has active HSV lesions at time of delivery. Appropriate care includes preemptive treatment for neonatal HSV infection, which has the potential to improve outcomes and so should be a high priority for all providers.

The new guidance is evidence based and predicated on the availability of HSV typing of the HSV from the maternal lesion and type-specific serology. It allows the provider to define the newborn risk of acquiring HSV infection more explicitly and utilize preemptive evaluation/therapy. Providers should ensure that their hospital laboratory can perform such testing with reasonable turnaround time for results.

Obstetrical role and implications of testing

The obstetric provider should swab the maternal lesion for HSV polymerase chain reaction (PCR) assay/culture and typing (HSV-1 or HSV-2). These data can be utilized with maternal history and serologic results to calculate the neonatal risk for infection.

Calculation of relative neonatal risk

• First episode, primary infection. Defined as the first maternal HSV episode with type-specific serology being negative, this makes the risk of neonatal infection approximately 50%. If maternal history of prior disease is negative AND either the maternal lesion test results or serology results are unavailable, follow the plan of care for first episode primary infection.

• First episode, nonprimary infection. Defined as the first maternal episode but antibody to detected HSV type is not present (e.g., HSV-2 confirmed from lesion, with type 1 but NOT type 2 maternal antibody present; OR HSV-1 confirmed, with type 2 but NOT type 1 maternal antibody present), the risk of neonatal infection is approximately 25%.

• Recurrent. If the mother has a history of genital herpes and the mother’s type-specific antibody is the same as the type detected in the lesions, the risk for neonatal infection is lower and approximately 2%.

Pediatrician’s role and plan of care

The first order of business is to identify neonates who demonstrate signs or symptoms suggestive of HSV infection at birth or in the perinatal period (whether or not any lesions were noted at time of delivery). In this case, all infants should undergo full evaluation for both viral and bacterial causes and should have prompt initiation of preemptive antiviral and antibacterial therapy. The evaluation of an ill-appearing infant at birth should include CBC; liver function studies; blood, urine, and cerebrospinal fluid examination with bacterial cultures of blood, urine, and cerebrospinal fluid, plus blood and cerebrospinal fluid HSV PCR. Also, HSV surface (conjunctivae, nasopharynx, and rectum) and lesion cultures are needed. Infectious disease consultation is recommended if HSV infection is confirmed. Acyclovir should continue for 14 days for skin–eye–mucous membrane disease or 21 days for CNS or disseminated infection. Further evaluation toward the end of therapy can determine if a longer course of therapy should be considered.

The recent guideline addresses care for those infants who are born to mothers with active HSV lesions noted at time of delivery, and should be initiated only if the infant is asymptomatic at birth.

In this situation, for babies whose mothers have primary infection (risk 50% for neonatal infection) or first episode, nonprimary infection (risk 25% for neonatal infection):

• Approximately 24 hours after the infant’s birth, obtain blood HSV DNA PCR and HSV surface cultures of conjunctivae, nasopharynx, and rectum as well as from the scalp electrode site if there was one.

• Cerebrospinal fluid examination with HSV DNA PCR testing should be obtained.

• Acyclovir (20 mg/kg per dose every 8 hours IV) should be initiated. Preemptive therapy (acyclovir 20 mg/kg per dose every 8 hours IV) should be continued for 10 days and until all studies are negative.

For babies whose mothers have recurrent infection:

• Cerebrospinal fluid examination may be deferred.

• But the rest of the workup should be completed and IV acyclovir initiated.

• IV acyclovir can be stopped at the time that studies are negative (usually at 48 hours, assuming negative results of blood PCR and preliminary negative surface cultures), with close follow-up of the infant.

Use of this guideline can improve care of infants only when the laboratory and the obstetrical and pediatric providers have established a good working relationship. This ensures the availability of necessary HSV studies, complete implementation, and proper interpretation of testing to guide the newborn’s care.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled "Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions," but said she had no other conflicts of interest to disclose. E-mail her at [email protected].

Recently the American Academy of Pediatrics issued recommendations that address management of asymptomatic newborns whose mothers have active herpes simplex virus (HSV) lesions noted at the time of delivery. Implementing these recommendations requires proactive coordination between the director of the laboratory and the obstetrical and pediatric providers to ensure success (Pediatrics 2013;131:e635-46).

Approximately 1,500 infants are diagnosed and treated for neonatal HSV infection each year in the United States. Most pediatricians are knowledgeable about the three forms of neonatal HSV infection and the role of prompt diagnosis and utilization of acyclovir. Even so, the outcomes of this disease may be devastating. Skin–eye–mucous membrane disease has the best prognosis (98% neurologically normal), as finding the culprit lesion generally ensures timely diagnosis and treatment. With central nervous system infection or disseminated disease, a skin lesion is not noted in 25%-40% of cases. So the diagnosis is sometimes delayed or missed initially because the initial presentations (seizures in CNS infection; sepsis picture or liver failure in disseminated disease) may sidetrack the provider into considering other working diagnoses, such as bacterial sepsis or metabolic disease. Neurologic sequelae occur in 25% of those with disseminated infection, but in upward of 70% in those with CNS disease.

Ideally, both the obstetrician and the pediatric provider play a role in ensuring appropriate care for the baby whose mother has active HSV lesions at time of delivery. Appropriate care includes preemptive treatment for neonatal HSV infection, which has the potential to improve outcomes and so should be a high priority for all providers.

The new guidance is evidence based and predicated on the availability of HSV typing of the HSV from the maternal lesion and type-specific serology. It allows the provider to define the newborn risk of acquiring HSV infection more explicitly and utilize preemptive evaluation/therapy. Providers should ensure that their hospital laboratory can perform such testing with reasonable turnaround time for results.

Obstetrical role and implications of testing

The obstetric provider should swab the maternal lesion for HSV polymerase chain reaction (PCR) assay/culture and typing (HSV-1 or HSV-2). These data can be utilized with maternal history and serologic results to calculate the neonatal risk for infection.

Calculation of relative neonatal risk

• First episode, primary infection. Defined as the first maternal HSV episode with type-specific serology being negative, this makes the risk of neonatal infection approximately 50%. If maternal history of prior disease is negative AND either the maternal lesion test results or serology results are unavailable, follow the plan of care for first episode primary infection.

• First episode, nonprimary infection. Defined as the first maternal episode but antibody to detected HSV type is not present (e.g., HSV-2 confirmed from lesion, with type 1 but NOT type 2 maternal antibody present; OR HSV-1 confirmed, with type 2 but NOT type 1 maternal antibody present), the risk of neonatal infection is approximately 25%.

• Recurrent. If the mother has a history of genital herpes and the mother’s type-specific antibody is the same as the type detected in the lesions, the risk for neonatal infection is lower and approximately 2%.

Pediatrician’s role and plan of care

The first order of business is to identify neonates who demonstrate signs or symptoms suggestive of HSV infection at birth or in the perinatal period (whether or not any lesions were noted at time of delivery). In this case, all infants should undergo full evaluation for both viral and bacterial causes and should have prompt initiation of preemptive antiviral and antibacterial therapy. The evaluation of an ill-appearing infant at birth should include CBC; liver function studies; blood, urine, and cerebrospinal fluid examination with bacterial cultures of blood, urine, and cerebrospinal fluid, plus blood and cerebrospinal fluid HSV PCR. Also, HSV surface (conjunctivae, nasopharynx, and rectum) and lesion cultures are needed. Infectious disease consultation is recommended if HSV infection is confirmed. Acyclovir should continue for 14 days for skin–eye–mucous membrane disease or 21 days for CNS or disseminated infection. Further evaluation toward the end of therapy can determine if a longer course of therapy should be considered.

The recent guideline addresses care for those infants who are born to mothers with active HSV lesions noted at time of delivery, and should be initiated only if the infant is asymptomatic at birth.

In this situation, for babies whose mothers have primary infection (risk 50% for neonatal infection) or first episode, nonprimary infection (risk 25% for neonatal infection):

• Approximately 24 hours after the infant’s birth, obtain blood HSV DNA PCR and HSV surface cultures of conjunctivae, nasopharynx, and rectum as well as from the scalp electrode site if there was one.

• Cerebrospinal fluid examination with HSV DNA PCR testing should be obtained.

• Acyclovir (20 mg/kg per dose every 8 hours IV) should be initiated. Preemptive therapy (acyclovir 20 mg/kg per dose every 8 hours IV) should be continued for 10 days and until all studies are negative.

For babies whose mothers have recurrent infection:

• Cerebrospinal fluid examination may be deferred.

• But the rest of the workup should be completed and IV acyclovir initiated.

• IV acyclovir can be stopped at the time that studies are negative (usually at 48 hours, assuming negative results of blood PCR and preliminary negative surface cultures), with close follow-up of the infant.

Use of this guideline can improve care of infants only when the laboratory and the obstetrical and pediatric providers have established a good working relationship. This ensures the availability of necessary HSV studies, complete implementation, and proper interpretation of testing to guide the newborn’s care.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled "Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions," but said she had no other conflicts of interest to disclose. E-mail her at [email protected].