By Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Manifestations of intrauterine Zika infection may not be clinically apparent at birth, warranting the use of early neuroimaging and careful follow-up.

SOURCE: van der Linden V, Pessoa A, Dobyns W, et al. Description of 13 infants born during October 2015–January 2016 with congenital Zika virus infection without microcephaly at birth — Brazil. MMWR Morb Mortal Wkly Rep 2016;65:1343-1348.

Van der Linden and colleagues assessed 13 infants (nine male) with documented intrauterine Zika virus infection but who did not appear to have microcephaly at birth. All had birth weights appropriate for gestational age; two of the 13 were preterm, having been born at 35 and 36 weeks gestation. Six of the mothers reported having had a skin rash that appeared between the second and fifth months of pregnancy. Six infants had craniofacial disproportion, three had redundant scalp skin, and three had hip dysplasia (one of whom with arthrogryposis had bilaterally dislocated hips). Three had chorioretinal abnormalities, while all 11 tested had intact hearing. Subsequent evaluation found that 10 of the infants had dysphagia and seven had epilepsy, while 12 had pyramidal and extrapyramidal findings with dystonic movements.

Despite having normal head circumferences at birth, neuroimaging demonstrated brain abnormalities in all 13 infants. Findings included diminished brain volume, ventriculomegaly, and malformations of the cortex. Follow-up demonstrated deceleration of head growth in all 13 infants, 11 of whom developed frank microcephaly.


A recent study demonstrated that Zika virus preferentially infects neural stem cells (radial glial cells) as a consequence of their high expression of a surface receptor, AXL, which was expressed throughout the cortex and retina during the middle period of intrauterine neurogenesis.1 The findings reported by van der Linden et al demonstrate that the effects of this neural stem cell infection progress post-natally.

This analysis demonstrates that the presence of microcephaly at birth is not an essential hallmark of congenital Zika syndrome. Thus, despite the presence of a normal head circumference at birth, infants may have brain and other abnormalities associated with congenital Zika syndrome — and they subsequently may develop microcephaly. As stated by the authors, “These findings demonstrate the importance of early neuroimaging for infants exposed to Zika virus prenatally and the need for comprehensive medical and developmental follow-up.” The finding by Retallack and colleagues that azithromycin blocks cellular uptake of Zika raises interesting possibilities.1 


  1. Retallack H, Di Lullo E, Arias C, et al. Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc Natl Acad Sci USA 2016;113:14408-14413.