Limitations of the current study
Limitations of the current study, in addition to the ones highlighted above, are its retrospective nature, the potential biased selection of patients requiring bronchoscopy for the etiological diagnosis of pneumonia, the lack of normalization of CMV DNA loads in BAL fluids to cellular DNA content (although this was reported to be expendable in a previous study) and the use of different DNA extraction platforms and real-time Sweroside assays for CMV DNA quantitation. Nevertheless, this study has several strengths, including the inclusion of consecutive specimens, the use of fresh BAL fluid specimens and highly-sensitive real-time PCR assays for CMV DNA load quantitation, and the performance of a comprehensive and systematic evaluation of specimens for the presence of RVs pathogens using molecular assays.
Conflict of interest
Acknowledgments This research was supported by a grant (12/1992) from FIS (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain). Estela Giménez holds a Río Hortega research contract from the Carlos III Health Institute (Ref. CM16/00200).
Introduction Congenital cytomegalovirus (CMV) infection is the most prevalent and consequential congenital infection among others. Although prevalence varies greatly between developed and developing countries, the overall birth prevalence of CMV-infected newborns is estimated to be 0.6% of all live births worldwide . Most of these CMV-infected infants are asymptomatic, and identification of these infants who would benefit from antiviral treatment (prenatally or postnatally) is one of the greatest challenges faced by obstetricians and pediatricians worldwide . Possible clinical manifestations of congenital CMV infection include jaundice, hepatosplenomegaly, petechiae, microcephaly, sensorineural hearing loss, and developmental delay . The tools with which clinicians attempt to meet this challenge have barely changed over the years. We examined the timing of infection – with ample evidence that the earlier in gestation a woman is infected by CMV, the more likely it has clinical consequences to her fetus. We examined the type of infection – the likelihood of vertical transmission is approximately 30 times higher in primary than in secondary maternal infection. Finally, we tried to gauge the severity of the infection through prenatal sonography and identification of the virus in the amniotic fluid or fetal blood . Recent studies have shown contrasting perceptions that the fetal immune system is surprisingly mature and competent . Fetal immune response may confer protection against congenital CMV infection. New technological advances allow us to assess this immune response and correlate it with disease prognosis. Certainly, these advances are still far from application in the clinic. However, as we attempt to demonstrate in this review, the fetal immune system may ultimately provide clinicians with a more reliable and accurate way to distinguish between congenitally infected fetuses who will and will not become symptomatic, who do and do not require intervention, and who should and should not be terminated. In postnatal life, polymorphonuclear (PMN) cells account for the majority of white blood cells in the peripheral circulation. In the growing fetus, however, lymphocytes predominate throughout the gestation, giving way to PMN cells only toward the very end of gestation . Natural killer (NK) cells constitute a large percentage of leukocytes in the fetal liver, according to Phillips et al., and play a major role in anti-CMV immunity . We therefore focus our review on fetal lymphocytes (B cells, αβT cells, and γδT cells) and NK cells, the leukocytes encumbered with the brunt of the burden of combating CMV , by examining their development throughout gestation and the implications for congenital CMV.
First trimester –budding immunity
Second trimester – accelerated maturation, first signs of functionality