Key biomarkers for predicting congenital cytomegalovirus

Key biomarkers for predicting congenital cytomegalovirus | Image Credit: © Thanumporn - © Thanumporn - stock.adobe.com.

Combination thrombocytes, β2-microglobulin, and cytomegalovirus (CMV) viral load in fetal blood may be used to determine the prognosis of CMV infection, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

CMV has been estimated in 0.5% to 1% of newborns, making it the most common congenital infection and the primary cause of pediatric nongenetic neurosensory impairment. Only 10% to 15% of children with congenital CMV present with identifiable symptoms immediately after birth.²

In 2021, revisions to the guidelines of the Swiss Society of Obstetrics and Gynecology allowed for first-trimester serologic screening of CMV.¹ Through viral DNA amplification in amniotic fluid, congenital CMV infection may be identified. However, the efficacy of CMV DNA load in amniotic fluid and fetal blood sampling (FMS) for prognosis remains unclear.

Investigators conducted a study to evaluate the efficacy of CMV DNA load in amniotic fluid and FMS toward predicting congenital CMV infection. Participants included fetuses infected with CMV after maternal infection from 4 weeks before the last menstrual period to 6 weeks after the last menstrual period with FBS performed between 2007 and 2022.

Symptom onset or avidity results were used to determine the timing of maternal infection. Congenital infection was determined prenatally through amniocentesis performed after 17 weeks’ gestation (WG), while a prognosis assessment was offered for fetal infection.

Live births underwent follow-up including laboratory tests, transfontanellar ultrasound, magnetic resonance imaging (MRI), serial oto-acoustic emissions screening, serial clinical and neurodevelopmental examinations, and fundoscopy and ophthalmologic follow-up. Autopsies with neuropathologic and histologic examination were performed in stillbirths.

Pregnancies receiving FBS who underwent follow-up for congenital CMV infection and had documented fetal and neonatal outcomes through at least the first 6 months of life were included in the analysis. Those with an absence of data or autopsy, alongside those receiving valacyclovir before amniocentesis or FBS, were excluded.

The presence of severe cerebral abnormalities on autopsy or MRI, 3 or more manifestations at birth or autopsy, or moderate-to-severe disability during follow-up was used to determine severely symptomatic CMV infection. One to 2 isolated and transient manifestations indicated mildly symptomatic infection.

Amniocentesis was performed in 246 patients, 28% of whom had a fetus with confirmed congenital CMV infection. The final analysis included 58 fetuses after exclusion, with 33% of included pregnancies terminated.

Moderate to severe symptomatic infection was reported in 43% of included fetuses, while 33 were controls. Postnatal follow-up occurred for a median 36 months in live births.

Patients were aged a median 21 years when undergoing amniocenteses to confirm congenital CMV infection in the moderately to severely symptomatic group vs 22 WG in the asymptomatic to mildly symptomatic group. Viral loads in amniotic fluid for these groups were 7.0 log10 IU/mL and 5.7 log10 IU/mL, respectively.

The presence of at least 1 ultrasonographic abnormality indicating congenital CMV infection was reported in 76% of the moderately to severely symptomatic group and 24% of the asymptomatic to mildly symptomatic group. Significant differences in viral load distribution in fetal blood was observed between groups.

A CMV DNA load of 6.5 log10 IU/mL or greater in amniotic fluid or 5 log10 IU/mL or higher in fetal blood was identified as a cutoff for moderate to severe congenital CMV infection. Other cutoffs included thrombocytes under 120,000 /mm3, aspartate aminotransferase of 25 IU/L or greater, IgM titer of 3 or greater, and β2m of 12mg/L or greater.

These results highlighted the efficacy of thrombocytes, β2-microglobulin, and CMV viral load toward predicting congenital CMV infection. Investigators concluded pregnant women can be counseled about reducing uncertainty toward their prognosis through FBS.

References

1. Pomar L, Contier A, Stojanov M, et al. Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland. Am J Obstet Gynecol. 2024;231:643.e1-12. doi:10.1016/j.ajog.2024.03.032
2. Townsend CL, Forsgren M, Ahlfors K, Ivarsson SA, Tookey PA, Peckham CS. Long-term outcomes of congenital cytomegalovirus infection in Sweden and the United Kingdom. Clin Infect Dis. 2013;56(9):1232-9. doi:10.1093/cid/cit018