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Sarah Mulkey

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

Sarah Mulkey

“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.

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:

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.

Mary Donofrio

Getting to the heart of cardiac malposition with fetal MRI

Mary T. Donofrio, MD, Director of the Fetal Heart Program and Critical Care Delivery Program at Children's National Health System

Mary T. Donofrio, M.D., Director of the Fetal Heart Program and Critical Care Delivery Program at Children’s National Health System

In a small percentage of pregnancies, the fetuses’ hearts develop in the wrong place. In the congenital anomaly known as heterotaxy syndrome that often includes a severe heart defect, the heart is often displaced from its usual position in the left chest. In other instances, the heart starts out in a normal position; however, it is pushed out of its normal position by a mass that grows in the chest cavity, by abnormal development of the lungs, or due to other causes. Although rare, babies born with cardiac malpositions associated with other congenital defects can be the most serious of all possible birth defects.

Sometimes, fetuses with these congenital problems die in the womb. Others do not survive long after birth. In some pregnancies, surgery is performed shortly after childbirth to stabilize the circulation so newborns even have a chance at life.

Correctly diagnosing these cardiac conditions during pregnancy can help doctors and parents alike make the most informed decisions and plan ahead.

However, the tools now used most often to reveal the overall anatomic details of cardiac malpositions — obstetrical ultrasound and fetal echocardiography — often don’t give a full picture. A clear view of the fetus can be obscured by the position of the fetus, insufficient amniotic fluid, or even a mother’s body habitus. Imaging techniques sometimes also have a hard time distinguishing between liver, bowel, and lung because the echogenicity of these tissues — the signature that sound waves make as they bounce back from their targets — is so similar.

“To be able to offer parents the best and most comprehensive counseling, and to begin planning for the type of intensive and multidisciplinary care that many of these babies will require, we need to have access to as much information as we can about each baby, not only relating to the heart but all the other organs as well,” says Mary T. Donofrio, M.D., a pediatric cardiologist who directs the Children’s National Health System Fetal Heart Program and Critical Care Delivery Program. “Unfortunately in some instances, obstetrical ultrasound and fetal echocardiography, the two diagnostic tools used most often in these cases, can be limited in what they tell us.”

What fetal MRI can show

An underutilized technique that gathers more details about the associated abnormalities that often accompany cardiac malposition during pregnancy is fetal magnetic resonance imaging, or fetal MRI, says Dr. Donofrio. Even though this technique is widely used to diagnose other fetal conditions, such as brain anomalies, it’s rarely used to better define the overall anatomy in cardiac malposition.

To determine whether fetal MRI is effective in complementing obstetrical ultrasound and fetal echocardiography, the current standard of care for this condition, Dr. Donofrio and colleagues took a retrospective look at all cases of cardiac malposition in which fetuses were evaluated using MRI between 2008 to 2013 at Children’s National. Their search turned up 42 cases.

Twenty-three cases had been diagnosed with obstetrical ultrasound and fetal echocardiography as having additional abnormalities beyond the heart’s changed position, and 19 had been given the diagnosis of heterotaxy syndrome. Each patient had been assigned to various known subtypes of these conditions, with some classified as having an unknown etiology for the findings.

After fetal MRI, the diagnoses of nearly one-third changed or were better delineated. Seven of the 23 cases of cardiac malposition attributed to an extra cardiac anomaly were reassigned to a cause different from the original diagnosis based on the new, more detailed information provided by fetal MRI, including three in which a complete diagnosis could not be made due to poor visualization by ultrasound. Five of the 19 cases attributed of heterotaxy were reassigned to different subgroups within this disorder or were given a different diagnosis completely after fetal MRI.

In eight of these 12 diagnoses that changed after fetal MRI, doctors were able to confirm these findings postnatally. Other cases were either lost to follow-up, pregnancy termination, or fetal demise.

The research team led by Dr. Donofrio published these results in the August 2016 issue of Prenatal Diagnosis.

Overall, she says the findings demonstrated the benefits of using fetal MRI as an adjunct to obstetrical ultrasound and fetal echocardiography. MRI offers advantages over ultrasound, she explains, including better spatial resolution, a wider field of view, and a way to see through or around maternal body fat, overlying fetal bone, or a fetus whose position is not optimal.

“Determining the etiology of cardiac malposition remains a challenging diagnosis, and the value of accurate prenatal diagnosis has been long recognized,” Donofrio and colleagues write in the study. “Ultimately, fetal MRI can assist with identifying the etiology of cardiac malposition for informative prenatal counseling and multidisciplinary planning.”