Prenatal Pediatrics

New program provides science-driven answers about zika virus’s impact on pregnancies

Drs. DeBiasi and du Plessis

Each week, as temperatures rise, the likelihood increases that the United States will experience domestic Zika virus transmission. Indeed, such domestic Zika transmission already is occurring in Puerto Rico and the U.S. Virgin Islands. The Children’s National Health System Fetal Medicine Institute and Division of Pediatric Infectious Disease announced the formation of a Congenital Zika Virus Program to serve as a dedicated resource for referring clinicians and for pregnant women to receive counseling and science-driven answers about the impact of the Zika virus on their pregnancies.

Over years, Children’s National has invested in equipment and highly trained personnel, building expertise in infectious diseases, pediatric neurology, pediatric cardiology, genetics, neurodevelopment, and other specialties. Children’s clinicians are recognized as national leaders in next-generation imaging techniques, such as fetal MRI, and a variety of divisions work together to offer multidisciplinary support and coordinated care to infants born with special needs. As the nation prepares for the Zika virus, Children’s National is facilitating the multi-step process of blood testing, helping to ensure timely and precise information. Children’s National specialists are able to guide Zika-affected pregnancies through the fetal period and can oversee the care of Zika-affected infants after delivery. Care and clinical support is provided by a multidisciplinary team of pediatric neurologists, physical therapists, infectious disease experts, and neurodevelopmental physicians.

Some functional brain connectivity altered in fetuses with CHD

chd_fetus

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What’s Known
Congenital heart disease (CHD), a structural problem with the heart at birth, is the most common birth defect and impacts 8 of every 1,000 newborns.

While many infants with mild disease require no intervention, others have complex CHD that necessitates specialized treatment shortly after birth. Complex defects change how blood flows through the heart and to other organs—including the brain.

What’s New
Newborns with this diagnosis are at an elevated risk for neurodevelopmental disabilities, underscoring the importance of monitoring fetal brain development and function to identify which newborns need additional surveillance and medical intervention. Neuroimaging research in recent years has shown that resting-state functional magnetic resonance imaging (rs-fMRI) can provide critical insights into how the brain functions, at rest. The research team in the Developing Brain Research Laboratory at Children’s National Health System successfully measured brain function in 90 different brain regions in healthy resting fetuses and pregnancies complicated by CHD. The team reports for the first time that there was robust functional connectivity between hemispheres in both fetuses diagnosed with CHD and controls matched by gestational age. The Children’s researchers and clinicians, however, found that some functional connections were weakened in the association and paralimbic regions of the brain that are involved in attention, emotions, and behaviors.

Questions for Future Research
Q: Does decreased regional connectivity in these association and paralimbic brain regions in CHD-complicated pregnancies influence infants’ neurodevelopment after birth?
Q: Can rs-fMRI be used to identify early disturbances in brain development in CHD-complicated pregnancies, and can the imaging technique lead to improved surveillance and more timely therapeutic intervention?

Source: “Functional Brain Connectivity Is Altered in Fetuses With Congenital Heart Disease.” J. De Asis-Cruz, A. Yarish, M. Donofrio, G. Vezina, A. du Plessis, and C. Limperopoulos. Presented during the 2016 American Society of Neuroradiology Annual Meeting, Washington, DC. May 25 2016.
Catherine Limperopoulos

Connection between abnormal placenta and impaired growth of fetuses discovered

CLimperopoulous

A team of researchers used 3-D volumetric magnetic resonance imaging (MRI) in an innovative study that reported that when the placenta fails to grow adequately in a fetus with congenital heart disease (CHD), it contributes to impaired fetal growth and premature birth. Fetal CHD involves an abnormality of the heart and is associated with increased risk for neurodevelopmental morbidity.Until now, CHD in the fetus and its relationship to placental function has been unknown. But the advanced fetal imaging study has shown for the first time that abnormal growth in the fetus with CHD relates to impaired placental growth over the third trimester of pregnancy. Catherine Limperopoulos, PhD, Director of Children’s National Developing Brain Research Laboratory in the Division of Diagnostic Imaging and Radiology, is the senior author of the study published in the September 2015 issue of the journal Placenta, “3-D Volumetric MRI Evaluation of the Placenta in Fetuses With Complex Heart Disease.”

Specifically, the decreased 3-D volumetric MRI measurements of pregnant women reported in this study suggest placental insufficiency related to CHD. The placenta nourishes and maintains the fetus, through the delivery of food and oxygen. Its volume and weight can determine fetal growth and birth weight.

Abnormality in placental development may contribute to significant morbidity in this high risk-population. This study shows impaired placental growth in CHD fetuses is associated with the length of the pregnancy and weight at birth. Nearly 1 in every 100 babies is born in the United States with a congenital heart defect.

Developing the capacity to examine the placenta non-invasively using advanced MRI is needed to identify early markers of impaired placental structure and function in the high-risk pregnancy. This is a critical first step towards developing strategies for improved fetal monitoring and management, Dr. Limperopoulos says.

“We are trying to develop the earliest and most reliable indicators of placental health and disease in high-risk pregnancies. Our goal is to bring these early biomarkers into clinical practice and improve our ability to identify placental dysfunction,” Dr. Limperopoulos says. “If we can develop the capacity to reliably identify when things begin to veer off course, we then have a window of opportunity to develop therapies to restore function.”

The study used in-vivo 3-D MRI studies and explored placental development and its relationship to neonatal outcomes by comparing placental volumetric growth in healthy pregnancies and pregnancies complicated by CHD.

While mortality rates continue to decrease steadily in newborns diagnosed with complex CHD, long-term neurodevelopmental impairments are recognized with increasing frequency in surviving infants, Dr. Limperopoulos says.

“Our goal is to better support the developing fetus with CHD. We can best accomplish this if we develop technology that can allow us to safely and effectively monitor the fetal-placental unit as a whole throughout pregnancy,” Dr. Limperopoulos says.

“This is the new frontier, not only to ensure survival but to safeguard the fetus and to ensure the best possible quality of life,” she says.