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Congenital cytomegalovirus infection is associated with congenital rickets: a retrospective autopsy cohort study

Congenital rickets is characterised by deficient bone mineralisation at the growth plate in utero. A review of published cases of congenital rickets found that maternal vitamin D deficiency likely contributes to its pathogenesis. Two recent studies showed that human cytomegalovirus (CMV) led to a rapid, pronounced and persistent reduction of vitamin D receptor (VDR) mRNA expression in vitro and in vivo. 3 This effect was specific to CMV and was not observed for other common viruses. VDR is essential for mediating the biological function of vitamin D and for bone development. Therefore, we hypothesised that congenital rickets could be observed in fetuses and neonates with congenital CMV (cCMV) infection. We searched our electronic autopsy database and retrospectively identified fetal and neonatal autopsies with a diagnosis of cCMV, performed at Alberta Children’s Hospital from 1 January 2006 to 31 October 2021. All autopsies were performed by perinatal pathologists with informed parental consent. We followed the Centers for Disease Control and Prevention diagnostic guidelines and rendered a diagnosis of cCMV if CMV was detected in the body tissues or fluids of a fetus, or in the body tissues or fluids of a neonate before 21 days of life. For controls, we matched each cCMV autopsy with three fetal or neonatal autopsies, with the same gestational age ±7 days, in which demise was due to acute chorioamnionitis or placental abruption. Additionally, we identified autopsies of fetuses and neonates with common, noncCMV congenital infections, including congenital herpes simplex virus, parvovirus B19, syphilis and Toxoplasma gondii infections. The postmortem wholebody Xrays, which were routinely performed, were independently reviewed by two perinatal radiologists who were blinded to clinical information. A diagnosis of rickets was made if metaphyseal fraying, splaying or cupping was noted in any of the long bones. Results are summarised in table 1. From our autopsy database, we identified 7 fetuses and neonates with cCMV (exposed group), of which, 6 (86%) had Table 1 Characteristics of study cohort