There are a number of organisms that can cause congenital neonatal illness - often with devestating long term consequences. Rubella embryopathy was the first documented neonatal congenital infection, being recognised in 1941 by an Australian Ophthalmologist - Sir Norman Grigg.
Congenital infection can occur during pregnancy or the peri-partum period. Primary infection in the mother, generally, results in greater risk of consequences to the developing fetus compared with 're-activation'. The timing of infection is important in regards to the severity of neonatal illness and in relation to the organism involved.
Toxoplasma gondii is a parasitic organism. The domestic cat is the primary host. Infection can be contracted by
Most women have no symptoms. Although 15% of women report acute flu-like illness with lymphadenopathy.
Risk of fetal infection is lowest in early pregnancy but most fetuses infected early have severe consequences.
Risk of fetal infection Severe consequences of infection 1st trimester 10% 70% 3rd trimester 60% <1%
Infants congenitally infected with Toxoplasmosis can be
Infection usually affects the neurological and haemopoietic systems. The classical tetrad described by Sabin in 1942 includes
Haemopoietic manifestations include
Neurological manifestations include
Generalised features include
Antenatal diagnosis can be performed using fetal blood sent for
Postnatal investigations include
Treatment consists of prolonged therapy for the first year of life with
Bone marrow suppression and hepatotoxicity can develop, and fortnightly blood tests are needed.
An alternative regime aimed at minimising toxicity may be used
The addition of steroids in severe infection has been suggested, but no evidence exists for this practice.
Ongoing opthalmological and developmental follow up is mandatory.
Infants symptomatic at birth have high incidence of long term difficulties
Outcome data for infants who are asymptomatic at birth is scant.
In 'asymptomatic' neonates, it appears that a significant number develop long-term sequelae if left untreated. Up to 92% develop long-term problems, usually due to ophthalmological disease. Chorioretinitis may not become evident for many years. Although prolonged therapy reduces the incidence of sequelae compared to untreated infants sequelae may still occur (over 80%).
Prevention of Toxoplasmosis is aimed at preventing ingestion of infected material. Pregnant women should be warned to avoid foods/products that may be contaminated with the oocytes - including care with the family cat (there may be a role for advocating against acquiring a new cat in households with pregnant women).
Most people develop immunity (if not immunised) during childhood. In non-immunised populations, 10-20% of women of child bearing age are susceptible.
Re-infection occurs in around 2% of people but is generally subclinical. Cases of congenital infection have been described with maternal re-infection.
Rubella vaccination is effective in almost totally eliminating congenital rubella infection - provided coverage remains high.
Most congenital infection is the result of primary maternal infection. The mother may have had little, if any, symptoms of infection.
Onset of maternal infection Fetal Complications <12 weeks Congenital rubella syndrome (>90%) 12-18 weeks Sensorineural deafness (20%) >18 weeks Rare
Congenital rubella syndrome is a severe, disabling condition featuring
Diagnosis is usually demonstrated by evidence of maternal seroconversion or rising IgG titres. This occurs some 10 days after contact. IgM assay is useful where exact 'contact time' is not known. IgM persists for around 2 months after primary infection. Re-infection can be identified by seeing a four-fold or more rise in IgG titres.
Fetal diagnosis is possible from
Postnatal diagnosis is by
Other test include
Deafness may be progressive, and therefore serial hearing assessments over the 1st few years of life are essential.
Ophthalmological assessment is also essential and progressive retinal damage can be seen.
Endocrine problems can occur in the long term including diabetes mellitus and hypothyroidism .
There is no specific treatment. Management is supportive and aimed at addressing specific problems present (developmental/sensory/endocrine/cardiac/etc ).
Rubella immunisation is offered to all children in combination with measles and mumps vaccination at 1 year of age. This also reduces the 'viral pool' in the population and helps protect susceptible pregnant women. New arrivals into Australia also are a potential group of susceptible individuals.
All women should be screened at first antenatal clinic appointment, and if found to be rubella susceptible, offered immunisation in the post-partum period.
If rubella infection is confirmed in the pregnant woman, then appropriate counselling is essential to provide the woman with information regarding the likely effects on the unborn child and options for management.
Children with congenital rubella syndrome are likely to have severe developmental issues.
Ongoing hearing and vision assessments are essential in babies whose mothers contracted rubella after 12 weeks gestation.
Rarely, a form of subacute sclerosing panencephalitis, with demonstration of raised rubella antibodies in CSF, has been documented.
CMV is a ubiquitous herpes virus that usually it causes only mild disease. It is commonly acquired in infancy and childhood through 'saliva sharing', particularly in less developed countries where over 90% are infected in childhood compared to around 60% in Western countries.
Overall, around 5 to 10 per 1000 babies are born with congenital CMV infection - with only 5-10% being symptomatic.
Congenital CMV can develop from maternal primary infection or re-activation, with primary infection more likely to result in sequelae. Risk for sequelae is highest after fetal infection during the first trimester.
Around 1% of non-immune women develop primary CMV in pregnancy, approximately 50% of their fetuses become infected.
In women with prior CMV infection, re-activation can occur in pregnancy with 5% of babies developing infection in-utero.
Perinatal and postnatal infection can occur through birth canal secretions and breast milk or blood. If affected the clinical syndrome is usually mild and self-limiting. Severe infection can result in transfusion-acquired disease. Use of CMV negative donor blood or deglycerolised frozen blood transfused through a leucocyte filter prevents this problem.
Symptomatic babies can be variously affected including
A high index of suspicion is needed.
Investigation is warranted in
Tests performed include
Culture and PCR should be performed as soon as possible in the first 2 weeks of life as CMV detected after this time can indicate peri/post natal infection.
Attention to 'general' measures include management of
Specific treatment with foscarnet of ganciclovir has not been shown to be associated with long-term benefits in congenital infection. There is a role for their use in life-threatening CMV infection (particularly post-natal disease in preterm babies) or in the setting of chorio-retinitis but this will not reverse damage that has already been done.
Long-term follow-up is essential with attention to
Two groups require consideration
After infection viral shedding can either persist for months or occur transiently and then recur intermittently. Testing for viral shedding will not guarantee a baby is not shedding virus at other times.
Seronegative staff members have a low risk (around 1-5%) of developing a primary infection.
Attention to prevention through use of standard precautions is important.
Likewise, it is difficult to advise parents of babies with documented CMV infection as to what to tell friends/family. Re-assurance and explanation about prevention of spread through scrupulous attention to hand washing after performing baby care are the most valuable tools.
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.
The overall rate of genital HSV infection varies from country to country and many women (amd 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% chance of a women with a past history of genital HSV infection shedding virus at the time of delivery.
In cases of neonatal infection, most women do not give a history of active genital herpes at the time of delivery.
Babies born to mothers with a primary genital infection at the time of delivery have a 50% risk of developing infection, compared with <5% in cases of recurrent infection present at the time of delivery.
Neonatal HSV usually presents within 2 weeks of birth
Infection occurs in less than 5 per 100,000 deliveries (up to 10 times more in the USA).
Usual clinical presentations are
Neonatal HSV infection is uncommon and a high level of vigilance is needed, particularly since most affected newborns are born to mothers with no history of current genital HSV lesions.
The unwell baby should be examined for vesicles including oral.
Specimens from lesions, throat and eye swabs should be performed. The use of immunoflourescence can provide rapid evidence of infection. Viral culture can take 5 days to demonstrate typical cytopathic changes.
Lumbar puncture is mandatory, with CSF sent for PCR and 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.
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 2 weeks to appear and IgG titres may not rise in babies and may reflect maternal antibody status.
Specific early treatment is with
Supportive care as always is vitally important with attention to general care.
Eye lesions require topical treatment (eg. Idoxuridine) and ophthalmological referral is essential.
Mortality and morbidity rates for disseminated and CNS disease are very high, even with early and aggressive treatment.
Even in the setting of localised SEM disease, 10% have long-term neurological sequelae.
Recurrent skin and eye eruptions can occur. Oral acyclovir has a role in this setting.
Babies born to mothers with active genital herpes lesions, particulary primary infection, at the time of delivery are at high risk. LUSCS should be performed as soon as possible, particularly within 6 hours of ROM. Swabs from the baby's eyes and throat should be sent and if positive, the baby treated with acyclovir sysemtically. However, consideration to treatment even in the setting of CS should be given - especially if there delay in getting results occurs. Babies born vaginally in the face of active genital lesions should be treated systemically.
Nosocomial infection can occur and vigorous infection control measures should be instituted.
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, but in this setting the wearing of masks/rigorous handwashing and topical cold-sore treatment should be advocated.
Congenital syphilis is rare in Australia, disadvantaged groups are at higher risk.
Screening at the initial antenatal visit is part of routine obstetric care since women may have asymptomatic latent disease.
Untreated maternal syphilis can result in
Transmission rates are around 50% for primary, secondary or early latent syphilis. In established latent syphilis, vertical transmission occurs in around 10%.
Treponema pallidum infection remains treatable with penicillin.
The infected baby can
Pregnant women are screened with non-specific treponemal tests (RPR and VDRL titre). If positive, then a specific TPHA/FTA-Abs titre will be performed.
Serum IgM in newborn babies with congenital syphilis is positive in around 90%.
Diagnosis of congenital infection can be confirmed by demonstration of treponema pallidum on dark ground microscopy on specimens from lesions on skin, placenta or other tissues.
A fourfold rise in the baby's antibody titre over the first 3 months is considered diagnostic.
Babies born to mothers who have not been adequately treated should be considered as infected.
Infants with suspected or confirmed infection should be treated with penicillin for at least 10 days.
Benzyl penicillin, 30mg/kg per dose 12 hourly, IM or IV or
Procaine penicillin, 30mg/kg daily, IM
Infants with low antibody levels whose mother was treated appropriately and has evidence of falling RPR/VDRL titres, is unlikely to be at risk. Ongoing follow up will be needed and if follow up cannot be assured, the baby should be treated.
Babies should be evaluated at 3-monthly intervals over the first year of life, with serological tests performed at each visit.. In cases of neurosyphilis, ongoing serum and CSF analysis should be undertaken 6-monthly for the first 5 years of life. Re-treatment is needed if titres do not fall, or clincial signs of disease persist or develop.
Prevention relies upon adequate antenatal services and screening facilities.