Zika-Caused Microcephaly Not Evident Until Later in Pregnancy

Diana Phillips

June 13, 2017

Microcephaly in fetuses of mothers infected with the Zika virus is undetectable via prenatal imaging early in pregnancy, a study has shown.

In a case series of pregnancies affected by Zika virus infection, the median time between the onset of Zika virus symptoms and imaging evidence of microcephaly on serial head and brain imaging was 18 weeks. The earliest diagnosis occurred at 24 weeks of gestation, Miguel Parra-Saavedra, MD, PhD, director of maternal-fetal medicine at the Cedifetal Clinic in Barranquilla, Colombia, and colleagues report in an article published online on June 6 in Obstetrics & Gynecology.

The analysis "informs understanding of the natural history of perinatal Zika virus infection and cautions against falsely reassuring patients with normal ultrasound results within a few months from presumed maternal infection," the authors write.

The investigators reviewed the laboratory and imaging outcomes of 17 women with laboratory-confirmed Zika virus who received treatment at one of two private perinatal referral clinics in Colombia between December 2015 and September 2016. The study included women in the analysis if Zika virus RNA was detected by reverse transcription–polymerase chain reaction in maternal or fetal fluid and if findings from fetal ultrasound or MRI were consistent with congenital Zika syndrome.

Of the 17 women, 14 were symptomatic for Zika virus disease, and the median gestational age at which symptoms presented was 10 weeks. In the remaining 3 women, amniotic fluid samples were positive for Zika at gestational weeks 20, 28, and 33, respectively.

Serial ultrasound revealed microcephaly — defined as head circumference less than 3 standard deviations below the mean —  in 15 of the 17 neonates at a median gestational age of 28 weeks.

Three of the neonates showed earlier signs of the congenital Zika syndrome before microcephaly diagnosis, including clubfoot (talipes equinovarus) in 1 case and ventriculomegaly in the other 2 cases.

In the 13 patients with Zika virus symptoms during the first trimester, ultrasound exams between gestational weeks 20 and 24 were not positive for microcephaly, although the next ultrasounds in the series were, the authors write.

In 16 of the 17 patients who opted for fetal MRI at median gestational age of 32.3 weeks, "[t]he MRI confirmed the ultrasound findings and provided additional information including nine cases with involvement of the corpus callosum," the authors write. In addition, evidence of polymicrogyria was observed in 6 cases, they note.

An assessment of birth data showed that the median gestational age at birth was 38 weeks, with 6 of the neonates weighing below the 10th percentile on the basis of International Fetal and Newborn Growth Consortium for the 21st Century standards. Furthermore, 15 of the neonates diagnosed prenatally with microcephaly had an occipital circumference measuring less than the third percentile at birth, the authors report.

In one neonate in whom microcephaly was not diagnosed prenatally and whose only sign of congenital Zika syndrome was dysgenesis of the cerebellar vermis, the head circumference was above the mean for age and sex immediately after birth but was more than 1 standard deviation below the mean 30 days after birth, the authors note.

"This case series provides unique information on the trajectory of fetal head circumference after laboratory-confirmed maternal Zika virus infection for neonates eventually diagnosed with congenital Zika syndrome," the authors write. The findings "can inform maternal–fetal medicine specialists who are managing pregnant women with Zika virus infection, including the more than 1,700 pregnant women with Zika virus infection who have been reported to the U.S. Zika Pregnancy Registry in the 50 U.S. states as of March 2017."

The extended gap between first symptoms of maternal Zika infection and imaging evidence of microcephaly and other signs of congenital Zika syndrome observed in this case series confirms the importance of continued monitoring of pregnant women with serial and detailed neuroimaging examinations, the authors conclude.

This research was supported by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention. The authors have disclosed no relevant financial relationships..

Obstet Gynecol. 2017;130:207-212. Abstract

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