In June 2023, we commenced a project to review and update the Maternity and Neonatal eHandbook guidelines with a view to completion in 2024. Please be aware that pending this review, some of the current guidelines may be out of date. In the meantime, we recommend that you also refer to more contemporaneous evidence.
There are a number of organisms that can cause congenital neonatal illness many with devastating long-term consequences.
The timing of infection is important in regards to the severity of neonatal illness and in relation to the organism involved. Primary infection in the mother generally results in greater risk of consequences to the developing fetus compared with ‘reactivation’ of the infection.
Incidence and risk of infection
Issues to note about the incidence of herpes simplex virus (HSV) include:
- HSV 1 and HSV 2 are uncommon, but important, causes of neonatal illness.
- Neonatal infection is usually the result of HSV 2 as this is the main virus associated with genital infection (HSV 1 is usually spread via the respiratory route).
- The overall rate of genital HSV infection varies from country to country and many women (and men) remain asymptomatic, with no history of infection despite shedding virus.
- HSV can remain latent for long periods, with shedding or re-activation occurring at any time.
- There is a 1 per cent chance of women with a history of genital HSV infection shedding virus at the time of delivery.
- In cases of neonatal infection, only 30 per cent of mothers have a history of active genital herpes at the time of delivery.
- Babies born to mothers with a primary genital infection at the time of birth have a 25-50 per cent risk of developing infection, compared with less than <1 per cent in cases of recurrent infection present at the time of delivery.
- Avoid using scalp electrodes where there is a suspicion of active maternal HSV.
Clinical presentation
Clinical presentations of HSV include:
- Neonatal HSV usually presents within two weeks of birth.
- Infection occurs in less than five per 100,000 births (up to 10 times more in the USA).
- 90 per cent are acquired during passage through the birth canal or through ascending infection.
- 5 per cent have 'congenital' HSV infection.
- 5 per cent have postnatal-acquired infection.
Usual clinical presentations
Skin/eye/mouth (SEM) localised disease
Clinical features of skin, eye or mouth disease include:
- isolated vesicles or 'crops’
- occasionally other skin reactions can be present, including zoster-like eruptions
- keratoconjunctivitis with dendritic ulcers
- chorio-retinitis
- single or multiple oral vesicular lesions can be present.
If untreated, more than 70 per cent will progress to disseminated disease; 25 per cent will have virus in CSF at initial presentation.
Disseminated disease
Features of disseminated disease include:
- poor prognosis, with over 70 per cent mortality if untreated
- non-specific presentation with:
Pneumonitis
Features of pneumonitis include:
- tends to occur day 4 to 7
- respiratory distress and can develop into haemorrhagic pneumonitis
- chest x-ray shows diffuse pneumonic change
- rare but dissemination is common if untreated.
Meningo-encephalitis
Features of meningo-encephalitis include:
- isolated or part of disseminated disease
- presents with:
- encephalopathy (mean 11 days of age)
- seizures are common and often intractable
- absent gag-reflex is a particular feature.
EEG
EEG shows characteristic temporal/parieto-temporal focus with periodic slow and fast waves.
Brain imaging (CT/MRI)
Brain imaging (CT/MRI) shows disease particularly affecting the temporal areas.
Later calcification and cerebral atrophy can develop.
Investigations
Neonatal HSV infection is uncommon and a high level of vigilance is needed, since most affected newborns are born to mothers with no history of current genital HSV lesions. Issues to note about investigative procedures:
- The unwell baby should be examined for vesicles including oral.
- Skin vesicles swab for viral culture and HSV PCR.
- Throat and eye swabs should be performed. The use of immunoflourescence can provide rapid evidence of infection. Viral culture can take five days to demonstrate typical cytopathic changes.
- Lumbar puncture is mandatory, with CSF sent for PCR and viral culture. However, negative PCR testing on CSF does not completely rule out HSV infection and the clinical picture of herpes encephalopathy is important in determining treatment.
- FBE, LFT's
- EEG and brain imaging are useful adjuncts in cases where diagnosis of CNS infection is in doubt.
- Serological studies are of little value early on as IgM may take two weeks to appear and IgG titres may not rise in babies and may reflect maternal antibody status.
Management
Supportive care as always is vitally important, with attention to general care.
Specific early treatment is with:
- Acyclovir 20 mg/kg/dose IV as 1-2 hour infusion
- If <30 weeks - 24 hourly, if 30-32 weeks - 18 hourly, if >32 weeks - 12 hourly
- Pre-emptive therapy (high risk asymptomatic infant) - 10 days
- Laboratory confirmed or clinical disease confined to skin, eye, mouth 10-14 days
- Encephalitis or disseminated disease 21 days
- Vidarabine 10-15 mg/kg/day 12-hourly, IV for 10 days is also effective but acyclovir has a higher selectivity, lower inhibitory concentration and higher potency
- eye lesions require topical treatment (such as idoxuridine) and ophthalmological referral is essential.
Prognosis
Mortality and morbidity rates for disseminated and CNS disease are very high, even with early and aggressive treatment. Other points to note:
- Even in the setting of localised SEM disease, 10 per cent of infants have long-term neurological sequelae.
- Recurrent skin and eye eruptions can occur.
- Oral acyclovir has a role in this setting.
Survivors of laboratory confirmed infection should be closely monitored for recurrence, eye disease, hearing impairment & neurological sequelae.
Figure 1: An 11 day old premature newborn has had skin lesions as in above figures. The lesion developed on day 7 of life and started at the scalp. Source: Virat Sirisanthana, MD, Department of Pediatrics, Chiang Mai University
Prevention
Babies born to mothers with primary active genital herpes infection at the time of birth are at highest risk.
Preventative issues include:
- The choices are to proceed with vaginal birth (avoiding routine use of instruments) or to have LUSCS. There is currently insufficient information to clearly support one option over the other; however, risk of transmission with vaginal birth is low and must be weighed up against risk of LUSCS to mother.
- Some research also suggests mother’s be treated with Acyclovir from 36 weeks gestation.
- Babies born vaginally in the face of active genital lesions require careful observation.
- Swabs from the baby's eyes, mouth, nasopharyx and skin should be sent at 24-48 hours.
- If swabs are positive, treat the baby with acyclovir systematically. However, consideration to treatment even in the setting of LUSCS should be given, especially if delay in getting results occurs.
- Nosocomial infection can occur and vigorous infection control measures should be used.
- Relatives or staff with 'cold-sores' should be discouraged from handling newborn infants as there is a risk of infection.
- Mothers with cold-sores present a low-risk to the infant as passive antibody protection of the baby should be present.
More information
Further reading
- Palasanthiran, P. (et al). 'Management of Perinatal Infections'. Australian Society for Infectious Diseases. 2014
- Isaacs D, Moxon ER. ‘Handbook of Neonatal Infections - a practical guide’. WB Saunders, London. 1999.
- Remington JS, Klein JO. ‘Infectious Diseases of the Fetus and Newborn Infant" 5Th Ed. WB Saunders, Philadelphia. 2000.
- Davies EG, Elliman DAC, et al. ‘Manual of Childhood Infections’. WB Saunders, London, 1996.
- Jeffries DG, Hudson CN. ‘Viral infections in Obstetrics and Gynaecology’. Arnold, London, 1999.
- Jacobs RF. ‘Neonatal herpes simplex virus infections’. Seminars in Perinatology. 22(1):64-71, 1998 Feb.
- Riley LE. ‘Herpes simplex virus’, Seminars in Perinatology. 22(4):284-92, 1998 Aug.
- Neonatal Pharmacopoeia RWH
- Shann, F. 'Drug Doses'. Royal Children's Hospital Parkville, 2014.
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Version history
First published: August 2016
Review by: August 2019