For the detection of CMV in infants

In otherwise healthy individuals, a Cytomegalovirus (CMV) infection might lead to a mild, non-specific illness. When babies are born with CMV, on the other hand, the virus can cause a range of complications, including organ dysfunction, microcephaly, sensorineural hearing loss, inflammation of the retina and even death. Although babies born with congenital CMV can remain asymptomatic for the rest of their lives, CMV infection can also lead to developmental disabilities or movement disorders. Even children that do not present with any symptoms at birth are at risk of hearing loss. CMV is transmitted through bodily fluids, and so can be passed to pregnant mothers by sharing utensils, sexual contact or by kissing their own infants or other children on the lips. Up to the age of five, children are particularly infectious. The majority of us have previously had a CMV infection, but, after age five, we are less likely to pass it on to each other. Congenital CMV infection occurs when the virus circulates in the mother’s blood and crosses through the placenta to infect the developing foetus.

This typically happens when a pregnant woman is infected with CMV for the first time (leading to a foetal infection rate of 30–35%), or the virus is reactivated during pregnancy (1.1–1.7% foetal infection rate). The virus is present in relatively high levels in urine, making it the sample of choice for testing babies for the virus, but it is not easy to get urine from newborns. The other relevant sample type is saliva, but, although it’s easier and more convenient to swab a baby’s mouth, saliva could lead to a ‘false positive’ result if the child is breastfeeding, as the virus detected may be from the mother if she is shedding CMV in the breast milk.

No US screening

In the US, there is no federal legislation to do any kind of universal screening. This is frustrating because CMV infection in neonates is more prevalent than the 29 other metabolic and endocrine disorders in the recommended US newborn screening panel, and CMV is the most common congenital infection worldwide.

The one FDA-cleared test on the market only uses dry saliva swabs. DiaSorin Molecular’s Simplexa congenital CMV Direct can test both saliva and urine, covering the primary and confirmatory modalities of the test. The benefits of using the Simplexa assay are its ease of use for a minimally trained technician and its hour-long turnaround time. DiaSorin has developed the test so that users can choose either a saliva swab or a urine specimen to assess babies under three weeks of age. For saliva, the company has demonstrated clinical study performance of 94.1% positive predictive agreement, and a negative predictive agreement of 99.7%. For urine, the performance result was positive predictive agreement of 95.3%, and a negative predictive agreement of 99.9%.

The high negative predictive agreement for the test means that if the sample is negative, clinicians can have high confidence that the baby does not have CMV.

Symptomatic of the problem

In the US, the congenital CMV rate is about 0.5% or 0.6% of all births, but only 10% of those babies are symptomatic. For the other 90%, if you don’t test for it, you don’t know they have CMV infection at birth. Molecular testing is appropriate because it can detect active infections in a very sensitive way; DiaSorin Molecular’s test can detect down to around 500 viral copies per millilitre. CMV antibody testing, on the other hand, would identify antibodies passed along from the mother in utero.

It is estimated that identifying one case of CMV with universal molecular screening of all newborns would cost $2,000 to $10,000. With targeted screening, that cost falls to between $500 to $2,800 per birth. In contrast, the cost of supporting a baby with congenital CMV through only the first four years of its life is estimated at $300,000. While policies and mandates for universal or targeted screening are still being justified, the kit available from DiaSorin Molecular has made testing easier and more accessible.