MRI and ultrasound imaging detect the spectrum of Zika’s impact

Worldwide, thousands of babies have been born to mothers who were infected during pregnancy with Zika, a virus associated with neurological deficits, impaired vision and neurodevelopmental disabilities, among other birth defects. These birth defects are sometimes severe, causing lifelong disability. But they’re also relatively rare compared with the overall rates of infection.

Predicting how many Zika-exposed babies would experience neurological birth defects has been challenging.

However, an international study led by Children’s faculty suggests that ultrasound (US) imaging performed during pregnancy and after childbirth revealed most Zika-related brain abnormalities experienced by infants exposed to the Zika virus during pregnancy, according to a prospective cohort study published online Nov. 26, 2018, in JAMA Pediatrics. Some Zika-exposed infants whose imaging had been normal during pregnancy had mild brain abnormalities detected by US and magnetic resonance imaging (MRI) after they were born.

“A combination of prenatal MRI and US was able to detect Zika-related brain abnormalities during pregnancy, giving families timely information to prepare for the potential complex care needs of these infants,” says Sarah B. Mulkey, M.D., Ph.D., a fetal-neonatal neurologist at Children’s National Health System and the study’s lead author. “In our study, we detected mild brain abnormalities on postnatal neuroimaging for babies whose imaging was normal during pregnancy. Therefore, it is important for clinicians to continue to monitor brain development for Zika-exposed infants after birth.”

As of Nov. 20 2018, nearly 2,500 pregnant women in the U.S. had laboratory confirmed Zika infection, and about 2,400 of them had given birth, according to the Centers for Disease Control and Prevention (CDC). While more than 100 U.S. infants were born with Zika-associated birth defects, the vast majority of Zika-exposed U.S. infants were apparently normal at birth. The sequential neuroimaging study Dr. Mulkey leads seeks to determine the spectrum of brain findings in infants exposed to Zika in the womb using both US and MRI before and after birth.

The international research team enrolled 82 women in the study from June 15, 2016, through June 27, 2017. All of the women had been exposed to Zika during pregnancy; all but one experienced clinical symptoms by a mean gestational age of 8.2 weeks. Eighty of those women lived in or near Barranquilla, Colombia, and were exposed to Zika there. Two U.S. study participants were exposed to the primarily mosquito-borne illness during travel to Zika hot zones.

All women received fetal MRIs and US during the second and/or third trimester of pregnancy. After their infants were born, the children received brain MRI and cranial US. Blood samples from both mothers and babies were tested for Zika using polymerase chain reaction and serology.

Fetal MRI was able to discern Zika-related brain damage as early as 18 weeks gestation and picked up significant fetal brain abnormalities not fully appreciated in US imaging. In one case, the US remained normal while fetal MRI alone detected brain abnormalities. Three fetuses (4 percent) had severe fetal brain abnormalities consistent with Zika infection, including:

• Two cases of heterotopias and malformations in cortical development, and
• One case of parietal encephalocele, Chiari II malformation and microcephaly.

Seventy-five infants were born at term. One pregnancy was terminated at 23 weeks gestation due to the gravity of the fetal brain abnormalities. One fetus with normal imaging died during pregnancy. One newborn who was born with significant fetal brain abnormalities died at age 3 days.

Cranial US and brain MRI was performed on the majority of infants whose prenatal imaging had been normal.  Seven of 53 (13 percent) Zika-exposed infants had mild brain abnormalities detected by MRI after birth. In contrast, postnatal cranial US was better at detecting changes of lenticulostriate vasculopathy, cysts within the brain’s choroid plexus (cells that produce cerebrospinal fluid), germinolytic/subependymal cysts and/or calcifications, which were seen in 21 of 57 (37 percent) infants.

“Sequential neuroimaging revealed that the majority of Zika-exposed fetuses had normal brain development. Tragically, in a small number of pregnancies, Zika-related brain abnormalities were quite severe,” Dr. Mulkey adds. “Our data support the CDC’s recommendation that cranial US be performed after Zika-exposed babies are born. In addition, there is clearly a need to follow these babies over time to gauge whether the brain anomalies we see in imaging affects language, motor and social skills.”

Companion editorial: Revealing the effects of Zika

In addition to Dr. Mulkey, study co-authors include Dorothy I. Bulas, M.D., Gilbert Vezina, M.D., Margarita Arroyave-Wessel, MPH,  Stephanie Russo, B.S, Youssef A. Kousa, D.O, Ph.D., Roberta L. DeBiasi, M.D., MS, Senior Author Adré J. du Plessis, M.B.Ch.B., MPH, all of Children’s National; Christopher Swisher, BS, Georgetown University and Caitlin Cristante, BS, Loyola University, both of  whose contributions included research performed at Children’s National; Yamil Fourzali, M.D., Armando Morales, M.D., both of Sabbag Radiologos; Liliana Encinales, M.D., Allied Research Society; Nelly Pacheco, Bacteriologa, Bio-Nep; Robert S. Lanciotti, Ph.D., Arbovirus Diseases Branch, Centers for Disease Control and Prevention; and Carlos Cure, M.D., BIOMELAB.

Research reported in this news release was supported by the IKARIA fund.