Tag Archive for: Sarah Mulkey

borrelia bacteria

First-of-its-kind study on impacts of Lyme disease in pregnancy and infant development

borrelia bacteria

Lyme disease is caused by the bacterium Borrelia burgdorferi.

Understanding the effects of Lyme disease on the developing fetal brain is essential to ensure timely prenatal and postnatal treatments to protect the fetus and newborn. In response to this need, Children’s National Hospital is leading a pilot study to establish the groundwork needed for a larger study to determine the effect of in utero exposure to Lyme disease on pregnancy and early childhood neurodevelopmental outcomes.

Why it’s important

“Insect-borne illnesses have more than doubled during the last twenty years as a result of multiple factors including environmental changes,” says Sarah Mulkey, M.D., Ph.D., principal investigator of the study and prenatal-neonatal neurologist at Children’s National Hospital. Dr. Mulkey is the Co-Director of the Congenital Infection Program at Children’s National Hospital and has led a long-term child outcome study of the mosquito-borne Zika virus infection in pregnancy and impacts on child neurodevelopment. She is now adding Lyme disease to her work on pregnancy and child outcomes. Lyme disease is transmitted to humans via an infected tick and can be acquired throughout much of the United States. “Very little is known about Lyme disease in pregnancy and if and how it may affect the fetus and impact child neurodevelopment,” said Dr. Mulkey.

This pilot study is funded by the Clinical Trials Network for Lyme and other Tickborne Diseases (CTN), supported by the Steven and Alexandra Cohen Foundation. Roberta DeBiasi, M.D., M.S., division chief of infectious diseases at Children’s National, is a CTN Node Principal Investigator. The study team at Children’s National works closely with members of the CTN as well as other Lyme disease-focused organizations and nonprofits to make sure that the pilot study addresses Lyme disease advocates’ research priorities in a scientifically rigorous way. “This is an important opportunity for us to engage with advocacy groups and others who have been stressing the need for this type of research for decades,” says Meagan Williams, M.S.P.H., C.C.R.C., the senior research coordinator for the study. “We know how important it is to maintain a patient-centered and trauma-sensitive lens in our work with families impacted by Lyme disease during pregnancy. We’ve been working hard to build this study in a way that centers our participants’ lived experiences and focuses on the topics they find important. We’re very grateful to have the support of Lyme disease focused organizations and advocates as we embark on this study because they know and have expressed exactly where the gaps are in the literature. It’s our job to do the work to fill those gaps.”

The big picture

This pilot study aims to build upon existing research, case studies and advocacy to assess developmental and other family impacts of Lyme disease exposure during pregnancy.

Especially as tick season begins in Washington, D.C., and surrounding regions, the investigators are determined to make sure that all eligible people diagnosed with Lyme disease during their pregnancy are aware of the study and have the opportunity to participate. Pregnant volunteers can sign up for participation in the study here. Volunteers may be eligible to join if they are currently pregnant, live in the U.S. or Canada and were diagnosed with Lyme disease during pregnancy or have post-treatment Lyme disease syndrome (PTLDS).

Anyone interested in sharing information about the study with their clients or colleagues may email mewilliams@childrensnational.org for access to the team’s recruitment toolkit that includes flyers, FAQs and other resources. “We have resources available for clinicians, public health professionals, friends and family members and anyone else who may be able to help us identify participants and spread the word about this important study,” Williams says.

The study is registered on ClinicalTrials.gov (NCT06026969). If you have questions about the study, please reach out to Meagan at mewilliams@childrensnational.org or email cnhlymestudy@gmail.com.

Members of the Columbia Zika virus research team

School entry neurodevelopmental outcomes of Zika-exposed Colombian children

Members of the Columbia Zika virus research team

The Children’s National Hospital Zika Research Team and collaborators from Biomelab, in Barranquilla, Colombia take a picture after a study visit in Sabanalarga, Colombia following the neurodevelopmental outcomes of children who had in utero exposure to Zika virus. Pictured from Children’s National Hospital: Dr. Sarah Mulkey, Regan Andringa-Seed, Margarita Arroyave-Wessel, and Dr. Madison Berl.

The long-term neurodevelopmental effects of antenatal Zika virus (ZIKV) exposure in children without congenital Zika syndrome (CZS) remain unclear, as few children have been followed to the age of starting primary school.

In a new study published in Pathogens, researchers found children with in utero ZIKV exposure appear to have an overall positive developmental trajectory at 4 to 5 years of age but may experience risks to neurodevelopment in areas of emotional regulation and adaptive mobility.

The hold up in the field

Children who were born during the ZIKV epidemic and who had in utero exposure to ZIKV are only now at the age to start school. Child neurodevelopmental outcome data has not been reported at the age of school entry for children with antenatal ZIKV exposure who do not have the severe birth defects of CZS.

“As these children approach the early school-age years, we aim to examine whether there are neurodevelopmental differences in executive function, motor ability, language development or scholastic skills as compared to a group of unexposed control participants from the same communities in Colombia,” says Sarah Mulkey, M.D., Ph.D., prenatal-neonatal neurologist in The Zickler Family Prenatal Pediatrics Institute at Children’s National Hospital and lead author of the study.

Moving the field forward

Building on previous findings, this study presents the longitudinal outcomes of a well-characterized Colombian cohort of ZIKV-exposed children without CZS at ages 4 to 5 years. These children have been seen for neurodevelopmental follow-up as infants and toddlers at approximately 6 months, 18 months and 3 years of age as part of an international collaboration between researchers in Barranquilla, Colombia and at Children’s National beginning in 2016. The objective of this study was to assess the multi-domain neurodevelopmental outcomes in 4 to 5-year-old children with antenatal ZIKV exposure without CZS compared to unexposed controls in Colombia.

Why we’re excited

Many of the children who had antenatal ZIKV exposure are making good progress in multiple areas of their neurodevelopment. However, the researchers found that children with antenatal ZIKV exposure have differences in areas of emotional regulation, executive function, mood and behavior which may relate to virus exposure during their early brain development.

“These areas of brain function are important for future academic achievement, employment, mental health and social relationships,” says Dr. Mulkey. “So, it will be important to continue to follow these children at older ages when they start school.”

Children’s National leads the way

Children’s National is a leader in conducting outcome studies of children born following antenatal ZIKV exposure. This study follows children in Colombia who are now 5 years old who were first studied while they were in the womb. These children have contributed unique longitudinal understanding to early child neurodevelopment following in utero exposure to ZIKV.

Dr. Mulkey is committed to studying the long-term neurodevelopmental impacts that viruses like Zika and SARS-CoV-2 have on infants born to mothers who were infected during pregnancy through research with the Congenital Infection Program at Children’s National and in collaboration with colleagues in Colombia.

Additional Children’s National authors include Meagan Williams M.S.P.H., C.C.R.C., senior research coordinator; Regan Andringa-Seed, clinical research coordinator, Margarita Arroyave-Wessel, clinical research coordinator; L. Gilbert Vezina, M.D., director, Neuroradiology Program; Dorothy Bulas, M.D., chief, Diagnostic Imaging and Radiology; Robert Podolsky, biostatistician.

Researchers showing paintings of zika virus

Dr. Sarah Mulkey and Children’s National clinical research coordinators in the Prenatal Pediatrics Institute and the Division of Pediatric Infectious Diseases display their paintings of the Zika virus. Pictured from left to right: Manuela Iglesias, Elizabeth Corn, Dr. Sarah Mulkey, Emily Ansusinha and Meagan Williams.

A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.

Measuring preschoolers’ cognitive development in Latin America

A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.

Neurodevelopment occurs at a rapid pace during the preschool years, research shows.

Measuring and tracking development in early childhood is important for understanding how to best support long-term positive health outcomes for children. However, the art of selecting measurement tools that are appropriate for a given study sample is complex; variations in language, cultural relevance and adaptations, availability of normative data, and more can impact the administration and interpretation of study findings.

In a recent study published in the Journal of Pediatric Psychology, the authors systematically review the standardized neurodevelopmental assessments used to study preschool-aged children’s cognitive development in Spanish-speaking Latin America.

“Thinking critically about the ways we measure these outcomes is an important first step in conducting ethical and accurate global research,” said Meagan Williams, M.S.P.H., C.C.R.C., senior clinical research coordinator for the division of Infectious Diseases and the Zickler Family Prenatal Pediatrics Institute at Children’s National Hospital and corresponding author of the study.

The hold-up in the field

The field of child development research is complicated by the presence and use of many different neurodevelopmental assessment tools, only some of which are standardized and use norms to allow researchers to compare their cohorts’ performance with population-level data.

“Many cognitive assessments, including some of the most commonly used assessments identified in our review of research conducted in Spanish-speaking Latin America, have only been officially normed in the United States,” Williams added. “Others have been translated into Spanish and normed in large countries such as Mexico or Spain, but Latin America is a large and culturally diverse region, and it is unclear whether these normative samples are generalizable and culturally relevant to other regions of Spanish-speaking Latin America.”

This systematic review outlined 41 different neurodevelopmental assessments used in 97 studies, including information about each study’s sample, use of each measurement tool and findings related to child cognitive development. The review goes into detail about the most widely used assessments, including background information of each assessment and trends in how authors of the studies in this review reported their methods and results.

Moving the field forward

When researchers use similar methods and valid outcome measures across studies, it becomes possible to combine data between cohorts and draw stronger conclusions about child outcomes. For example, The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) was identified as the most used tool to measure intelligence of young children ages 2-6 in the systematic review. The WPPSI is also one of many assessments that Williams’s research team, led by Sarah Mulkey, M.D., is using to measure neurodevelopment among children exposed to Zika virus in utero.

“If researchers studying longitudinal outcomes after Zika virus exposure also use the WPPSI for their study samples – and if they openly report on their methods, adaptations, and sample characteristics – then it may be possible to harmonize data from multiple cohorts and draw stronger conclusions across studies,” Williams said.

But even the most popular and widespread assessments such as the WPPSI are not without their limitations. While norms exist for regions such as the United States and Mexico, additional work needs to be done to appropriately adapt and validate these tools for use in other populations.

Benefiting patients

Neurodevelopment occurs at a rapid pace during the preschool years. The earlier neurodevelopmental delays can be identified, the earlier experts can administer interventions to respond to these delays and help children get back on track with their peers.

This is particularly salient for research conducted in low- and middle-income countries, where socioeconomic, environmental and other exposures that are known to impact child development differ from those in higher-resource settings. Internationally, there appears to be significant variability in not only the assessment tools which are selected for use, but also in the methods reported across studies to conduct and interpret these assessments.

“By coming together as a field and prioritizing the use and validation of common and culturally appropriate assessments, we can better understand child outcome data on both an individual study level as well as on a broader population level, which will lead to a better understanding of the unique needs and strengths of the children we serve,” Williams said.

The team at Children’s National has been studying the neurodevelopment of children exposed to the Zika virus in Colombia since the beginning of the Zika epidemic.

“As our study on Zika virus has overlapped with the COVID-19 pandemic, we have had the opportunity to collect child outcome data at a very interesting time in history. We are excited that this review revealed that we chose a popular and well-studied assessment for our data collection in this region and we look forward to publishing our 5-year outcome data (which will include WPPSI data) in the coming year,” Williams and Mulkey concluded.

Dr. Mulkey is committed to studying the long-term neurodevelopmental impacts that viruses like Zika and SARS-CoV-2 have on infants born to mothers who were infected during pregnancy through research with the Congenital Infection Program at Children’s National and in collaboration with colleagues in Colombia.

Additional Children’s National authors include Madison Berl, Ph.D.

mother and baby doing a telehealth call

Using telehealth to study babies born to mothers infected with SARS-CoV-2

mother and baby doing a telehealth call

Continued advancements in telehealth methods to follow child neurodevelopment will help ensure robust child follow-up and inclusion of diverse cohorts.

Multiple studies have shown that SARS-CoV-2 infection can impact pregnant mothers and their fetuses but more research is needed to understand the long-term impact on the neurodevelopment of these children as they get older. Child neurodevelopmental evaluations are typically performed in-person. Since the COVID-19 pandemic began, the transition to telehealth methods was needed.

Continued advancements in telehealth methods to follow child neurodevelopment will help ensure robust child follow-up and inclusion of diverse cohorts, says a commentary in JAMA Network Open.

Why it matters

Commentary author Sarah Mulkey, M.D., prenatal-neonatal neurologist at Children’s National Hospital, highlights a new study that used a novel telehealth method to look for neurodevelopmental differences in infants ages 6-12 months born to mothers with SARS-CoV-2 infection compared to nonexposed infants of the same age and found no differences in neurodevelopment among the two cohorts. The study adapted a standardized assessment to a telehealth method.

“The results of this study provide needed reassurance to the many mothers who have experienced SARS-CoV-2 infection during pregnancy,” says Dr. Mulkey.

What’s been the hold up in the field?

“Developmental assessments that rely on observation of infants’ developmental skills can naturally make the transition to a telehealth platform,” says Sarah Mulkey, M.D., prenatal-neonatal neurologist at Children’s National Hospital and commentary author. “General movement assessment is an observation-based assessment of infants that can be captured by a parent or caregiver on video, and it has been used in neurodevelopmental outcomes studies of children after antenatal SARS-CoV-2 exposure.”

Moving the field forward

Child outcomes research can have improved enrollment and continuity of participant follow-up due to the availability of remote assessments. Neurodevelopmental tools are being developed that can be used on a telehealth platform or by parent recorded videos.

Researchers from the Children’s National Congenital Zika Virus Program have also developed telehealth-based methods for child outcome research that has been utilized in international Zika outcome studies funded by the Thrasher Research Fund and the NIH.

Read the full commentary, Use of Telehealth Methods to Track Infant Neurodevelopment After In Utero SARS-CoV-2 Exposure, in JAMA Network Open.

coronavirus and DNA

Will SARS-CoV-2 during pregnancy impact child’s neurodevelopment?

coronavirus and DNA

Sarah Mulkey, M.D., prenatal-neonatal neurologist at Children’s National, will lead the neurodevelopmental evaluations of the infants born to mothers with SARS-CoV-2 infection during pregnancy to understand any long-term neurological effects in offspring.

Scientists led by the Lieber Institute for Brain Development are studying how a mother’s SARS-CoV-2 infection during pregnancy affects the biology of the placenta and the corresponding trajectory of the child’s brain development, including the risk for neurodevelopmental disorders such as schizophrenia and autism. The work is made possible by a $3 million, five-year grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, part of the National Institutes of Health.

The project stems from a collaboration between the Lieber Institute for Brain Development on the Johns Hopkins medical campus in Baltimore, Children’s National Hospital in Washington, D.C., and the Women’s Health Integrated Research Center at Inova Health System in Virginia.

The big picture

The group aims for a clearer picture of how a mother’s SARS-CoV-2 infection during pregnancy affects neurodevelopment in utero, the effects of which may manifest early in a child’s life. The researchers hope to understand how the infection interacts with other factors relevant to brain development, including genomic risk for neurodevelopmental disorders, maternal stress and social determinants of health.

The team will study whether the relationship between maternal SARS-CoV-2 infection and offspring brain development is mediated by changes in the biology of the placenta and the activation of the mother’s immune system. They will also gauge any differences in the effects of SARS-CoV-2 between female and male children and in the offspring of vaccinated and unvaccinated mothers.

Why it matters

Preliminary data show that pregnant people with symptomatic SARS-CoV-2 infections are more likely to have a preterm delivery, abnormalities in the placenta and prenatal and perinatal complications such as preeclampsia and fetal growth restriction. All these complications have been found to increase a child’s risk of neurodevelopmental disorders later in life.

What we hope to discover

Sarah Mulkey, M.D., prenatal-neonatal neurologist at Children’s National, will lead the neurodevelopmental evaluations of the infants born to mothers with SARS-CoV-2 infection during pregnancy to understand any long-term neurological effects in offspring. The researchers will evaluate the children’s neurodevelopment at both 24 and 36 months of age. This work builds upon Dr. Mulkey’s longitudinal neurodevelopmental evaluations in children exposed to Zika virus in utero.

“What we’ve learned is that even when babies don’t have Zika-virus-related birth defects, we still find differences in early child development compared to children who weren’t exposed to Zika virus,” said Dr. Mulkey. “With SARS-CoV-2, there is still so much we don’t know. But by better understanding the long-term impact of COVID exposure during pregnancy, we can ultimately find ways to prevent adverse outcomes.”

pregnant woman

Early SARS-CoV-2 exposure may impact infant development

pregnant woman

The study found that some infants with in utero or early-life exposure to SARS-CoV-2 had borderline to low developmental screening scores.

Early SARS-CoV-2 exposure may impact neurodevelopment, especially among infants exposed in utero to symptomatic parents. This is according to a new study led by Sarah Mulkey, M.D., Ph.D., prenatal-neonatal neurologist in the Prenatal Pediatrics Institute at Children’s National Hospital. Dr. Mulkey and team conclude that vaccination and other precautions to reduce early-in-life infection may protect against neurodevelopmental delays. Children with early SARS-CoV-2 exposure should have additional long-term screening for neurodevelopmental delays.

Children’s National Hospital leads the way

The developing brain is vulnerable to both direct and indirect effects of infection during pregnancy and in the early neonatal period. To chart the impact of this exposure, the team created a clinical follow-up protocol in the Congenital Infection Program at Children’s National to chart the development of 34 infants exposed to SARS-CoV-2 in utero or in the neonatal period.

What we hoped to discover

“We conducted this study because we know that infants, when exposed to maternal COVID-19 infection in utero can be exposed to inflammation, fever and an abnormal intrauterine environment. SARS-CoV-2 can also affect the placenta, and in turn, the developing brain,” Dr. Mulkey shared with Healio.

This study aimed to determine if infants with early SARS-CoV-2 exposure developed abnormal neurodevelopment in infancy and the factors that may impact neurodevelopment differences. The study found that some infants with in utero or early-life exposure to SARS-CoV-2 had borderline to low developmental screening scores, most common among babies born to mothers with symptomatic COVID-19. Researchers followed the infants in their first months of life, gauging how the exposure affected their neurologic development. Results were demonstrated using a screening test called the Ages & Stages Questionnaires (ASQ), and those whose scores were borderline or low were most often born to mothers with symptomatic COVID-19.

Why it matters

In conducting this study, the team found that babies born during the pandemic, specifically under these conditions, do, in fact, require additional follow-up in the early stages of life. We may also see more differences in developmental outcomes as children get older.

“Any measure we can take to help prevent infections for mothers in their pregnancy can improve long-term developmental outcomes for children,” says Dr. Mulkey.

Other members of the Children’s National team that contributed to this work include Roberta L. DeBiasi, M.D., M.S.; Meagan E. Williams, M.S.P.H.; Nadia Jadeed, R.N.C.; Anqing Zhang, Ph.D.; and Smitha Israel, B.S.N.

Dr. Mulkey also published a recent article in the American Journal of Obstetrics & Gynecology that found the COVID-19 vaccine may protect pregnant women from SARS-CoV-2 placentitis and stillbirth. This work builds upon Dr. Mulkey’s longitudinal studies on Zika virus infection in pregnancy and long-term impacts on the child, funded by the Thrasher Research Fund and the National Institutes of Health.

Sarah Mulkey

Exposure to Zika in utero may produce neurodevelopmental differences

Sarah Mulkey

“There are still many unanswered questions about the long-term impacts of Zika on children exposed in utero,” says Sarah Mulkey, M.D., Ph.D., a prenatal-neonatal neurologist in the Prenatal Pediatrics Institute at Children’s National Hospital.

Children who are exposed to the Zika virus while in the womb, but who are not subsequently diagnosed with Zika-related birth defects and congenital Zika syndrome (CZS), may still display differences in some aspects of cognitive development, mood and mobility compared to unexposed children, reports a study published in Pediatric Research. These findings suggest that Zika-exposed children may need some additional support and monitoring as they get older.

“There are still many unanswered questions about the long-term impacts of Zika on children exposed in utero,” says Sarah Mulkey, M.D., Ph.D., a prenatal-neonatal neurologist in the Prenatal Pediatrics Institute at Children’s National Hospital and the study’s first author. “These findings are another piece of the puzzle that provides insight into the long-term neurodevelopment of children with prenatal Zika virus exposure. Further evaluation is needed as these children get older.”

It has not been clear how children who were exposed to the Zika virus in the womb during the 2015–2017 epidemic, but who did not develop CZS and serious neurological complications, will develop as they get older.

Dr. Mulkey and colleagues examined the neurodevelopment of 55 children aged 3-5 years who were exposed to Zika in the womb in Sabanalarga, Colombia, and compared them to 70 control children aged 4-5 years who had not been exposed to Zika. Assessments occurred between December 2020 and February 2021. Health professionals tested the children’s motor skills (such as manual dexterity, aiming and catching, and balance) and their readiness for school (including knowledge of colors, letters, numbers and shapes). Parents completed three questionnaires providing information about their child’s cognitive function (such as memory and emotional control), behavioral and physical conditions (such as responsibility and mobility), and their parenting experience (including whether they felt distress).

Parents of Zika-exposed children reported significantly lower levels of mobility and responsibility compared to control children, although differences in cognitive function scores were not significant. Additionally, parents of 6 (11%) Zika-exposed children reported mood problems compared to 1 (1%) of control children, and Zika-exposed parents were significantly more likely to report parental distress.

Professional testing revealed no significant differences in the Zika-exposed children’s manual dexterity, such as their ability to catch an object or post a coin through a slot, compared to the control children. Both Zika-exposed and control children also scored lowly on readiness for school.

The authors highlight that parental responses may have been influenced by the Zika-exposed children’s parents’ perceptions or increased worry about the development of their child. Some differences in results may also have been caused by the age – and therefore developmental – differences between the groups of children.

The authors conclude that while these Zika-exposed children are making progress as they develop, they may need additional support as they prepare to start school.

Dr. Mulkey is committed to studying the long-term neurodevelopmental impacts that viruses like Zika and SARS-CoV-2 have on infants born to mothers who were infected during pregnancy through research with the Congenital Infection Program at Children’s National and in collaboration with colleagues in Colombia.

pregnant woman getting vaccinated

COVID-19 vaccine may protect pregnant women from SARS-CoV-2 placentitis and stillbirth

pregnant woman getting vaccinated

In a new article published in the American Journal of Obstetrics & Gynecology, researchers conclude that the vaccine not only protects pregnant women but may also be lifesaving for their unborn children.

Stillbirth is a recognized complication of COVID-19 in pregnant women caused by harmful changes to the placenta induced by the virus. Termed SARS-CoV-2 placentitis, it can render the placenta incapable of providing oxygen to the fetus, leading to stillbirth and neonatal death. Researchers now suggest that pregnant women who get the COVID-19 vaccine may be protected from SARS-CoV-2 placentitis and stillbirth. In a new article published in the American Journal of Obstetrics & Gynecology, researchers conclude that the vaccine not only protects pregnant women but may also be lifesaving for their unborn children.

The extensive examination of published literature involved reviewing nearly 100 papers looking at COVID-19’s impacts on pregnant women and the effects on the placenta and pregnancy outcome. Sarah Mulkey, M.D., Ph.D., a prenatal-neonatal neurologist in the Division of Prenatal Pediatrics at Children’s National Hospital and co-author of the article, says the findings make a strong case for vaccination.

“The COVID-19 virus fortunately does not cause birth defects like other viruses such Zika, but it can cause severe injury to the placenta that can result in stillbirth and other pregnancy complications,” says Dr. Mulkey. “I hope patients who are pregnant or planning to become pregnant can learn how the COVID vaccine may help keep them and their baby healthy throughout pregnancy from some of the worst effects of this virus.”

While stillbirths can have many causes, the data analyzed supports that the COVID-19 vaccine is beneficial for pregnancies and for reducing the risk of stillbirth by reducing the risk of the virus impacting the placenta.

“In the multiple reports of SARS-CoV-2 placentitis that have been associated with stillbirths and neonatal deaths, none of the mothers had received COVID-19 vaccinations,” says David Schwartz, M.D., lead author, epidemiologist and perinatal pathologist. “And although not constituting proof, we’re not aware, either personally, via collegial networks, or in the published literature, of any cases of SARS-CoV-2 placentitis causing stillbirths among pregnant women having received the COVID-19 vaccine.”

Earlier in 2022, Dr. Schwartz led a team from 12 countries that found SARS-CoV-2 placentitis destroyed an average of 77.7% of placental tissue, resulting in placental insufficiency and fetal death, all occurring in unvaccinated mothers.

Fortunately, the large majority of pregnancies affected by a COVID-19 infection do not result in stillbirth. The development of SARS-CoV-2 placentitis is complex and likely involves both viral and immunological factors. The characteristics of a SARS-CoV-2 variant may also affect risk.

“Placental pathology is an important component in understanding the pathophysiology of SARS-CoV-2 infection during pregnancy,” says Dr. Mulkey.

As part of the Congenital Infection Program at Children’s National, Dr. Mulkey has been following infants born to mothers who had SARS-CoV-2 infection during pregnancy since the beginning of the pandemic. She will present the results of the early neurodevelopment of these infants at ID Week in Washington, D.C., on Oct. 22, 2022. Dr. Mulkey will also lead the neurodevelopmental follow-up of a large cohort of infants born to mothers with SARS-CoV-2 infection during pregnancy to better understand any long-term neurological effects to offspring.

The study builds upon Dr. Mulkey’s longitudinal studies on Zika virus infection in pregnancy and long-term impacts on the child that is funded by the Thrasher Research Fund.

zika virus

The importance of following the Zika population long-term

zika virus

Invited commentary by Sarah Mulkey, M.D., Ph.D., prenatal-neonatal neurologist in the Division of Prenatal Pediatrics at Children’s National Hospital, emphasizes importance of studying the Zika population long term.

A simple measuring tape could be the key to identifying which children could develop neurological and developmental abnormalities from Zika virus exposure during gestation. This is according to an invited commentary published July 7, 2020 in JAMA Network Open and written by Sarah Mulkey, M.D., Ph.D., prenatal-neonatal neurologist in the Division of Prenatal Pediatrics at Children’s National Hospital.

Zika virus (ZIKV), first isolated in 1947 in the Zika Forest in Uganda, made headlines in 2015-2016 for causing a widespread epidemic that spread through parts of North and South America, several islands in the Pacific and parts of Southeast Asia. Although previously linked with no or mild symptoms, researchers discovered during this epidemic that Zika can cross from a pregnant woman to her gestating fetus, leading to a syndrome marked by microcephaly (decreased brain growth), abnormal neurologic tone, vision and hearing abnormalities and joint contractures.

“For the 90% to 95% of ZIKV-exposed infants who fortunately were not born with severe abnormalities at birth and were normocephalic, our hope was that these children would have normal neurodevelopmental outcomes,” Dr. Mulkey writes in the commentary. “Unfortunately, this has not been the case.”

Her commentary expands on a study in the same issue entitled “Association between exposure to antenatal Zika virus and anatomic and neurodevelopmental abnormalities in children” by Cranston et al. In this study, the researchers find that head circumference — a simple measure taken regularly at postnatal appointments in the U.S. — can provide insight into which children were most likely to develop neurologic abnormalities. Their findings show that 68% of those whose head circumference was in the “normal” range at birth developed neurologic problems. Those whose head circumference was at the upper end of this range were significantly less likely to have abnormalities than those at the lower end.

Just this single measurement offers considerable insight into the risk of developing neurologic problems after Zika exposure. However, notes Dr. Mulkey, head circumference growth trajectory is also key. Of the 162 infants whose heads were initially in the normocephalic range at birth, about 10.5% went on to develop microcephaly in the months after birth.

“Because early head growth trajectory is associated with cognitive outcomes in early childhood,” Dr. Mulkey writes, “following the head circumference percentile over time can enable recognition of a child with increased risk for poor outcome who could benefit from early intervention therapies.”

This simple assessment could be significantly augmented with neuroimaging, she adds. The study by Cranston et al., as well as others in the field, have shown that brain imaging often reveals problems in ZIKV-exposed children, such as calcifications and cerebral atrophy, even in those with normal head circumferences. This imaging doesn’t necessarily need to take place at birth, Dr. Mulkey says. Postnatal development of microcephaly, failure to thrive or developmental delay can all be triggers for imaging later on.

Together, Dr. Mulkey says, the study by Cranston et al. and others that focus on ZIKV-exposed children support the need for following these patients long term. Children exposed to ZIKV in the epidemic nearly five years ago are now approaching school age, a time fraught with more complicated cognitive and social demands. Through her own research at Children’s National’s Congenital Zika Virus Program and collaboration with colleagues in Colombia, Dr. Mulkey is following multiple cohorts of ZIKV exposed children as they grow. She recently published a study on neurological abnormalities in one of these cohorts in JAMA Pediatrics in January 2020.

“It’s really important to follow these children as long as possible so we’ll really know the outcomes of this virus,” Dr. Mulkey says.

Vittorio Gallo and Mark Batshaw

Children’s National Research Institute releases annual report

Vittorio Gallo and Marc Batshaw

Children’s National Research Institute directors Vittorio Gallo, Ph.D., and Mark Batshaw, M.D.

The Children’s National Research Institute recently released its 2019-2020 academic annual report, titled 150 Years Stronger Through Discovery and Care to mark the hospital’s 150th birthday. Not only does the annual report give an overview of the institute’s research and education efforts, but it also gives a peek in to how the institute has mobilized to address the coronavirus pandemic.

“Our inaugural research program in 1947 began with a budget of less than $10,000 for the study of polio — a pressing health problem for Washington’s children at the time and a pandemic that many of us remember from our own childhoods,” says Vittorio Gallo, Ph.D., chief research officer at Children’s National Hospital and scientific director at Children’s National Research Institute. “Today, our research portfolio has grown to more than $75 million, and our 314 research faculty and their staff are dedicated to finding answers to many of the health challenges in childhood.”

Highlights from the Children’s National Research Institute annual report

  • In 2018, Children’s National began construction of its new Research & Innovation Campus (CNRIC) on 12 acres of land transferred by the U.S. Army as part of the decommissioning of the former Walter Reed Army Medical Center campus. In 2020, construction on the CNRIC will be complete, and in 2012, the Children’s National Research Institute will begin to transition to the campus.
  • In late 2019, a team of scientists led by Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, traveled to the Democratic Republic of Congo to collect samples from 60 individuals that will form the basis of a new reference genome data set. The researchers hope their project will generate better reference genome data for diverse populations, starting with those of Central African descent.
  • A gift of $5.7 million received by the Center for Translational Research’s director, Lisa Guay-Woodford, M.D., will reinforce close collaboration between research and clinical care to improve the care and treatment of children with polycystic kidney disease and other inherited renal disorders.
  • The Center for Neuroscience Research’s integration into the infrastructure of Children’s National Hospital has created a unique set of opportunities for scientists and clinicians to work together on pressing problems in children’s health.
  • Children’s National and the National Institute of Allergy and Infectious Diseases are tackling pediatric research across three main areas of mutual interest: primary immune deficiencies, food allergies and post-Lyme disease syndrome. Their shared goal is to conduct clinical and translational research that improves what we know about those conditions and how we care for children who have them.
  • An immunotherapy trial has allowed a little boy to be a kid again. In the two years since he received cellular immunotherapy, Matthew has shown no signs of a returning tumor — the longest span of time he’s been tumor-free since age 3.
  • In the past 6 years, the 104 device projects that came through the National Capital Consortium for Pediatric Device Innovation accelerator program raised $148,680,256 in follow-on funding.
  • Even though he’s watched more than 500 aspiring physicians pass through the Children’s National pediatric residency program, program director Dewesh Agrawal, M.D., still gets teary at every graduation.

Understanding and treating the novel coronavirus (COVID-19)

In a short period of time, Children’s National Research Institute has mobilized its scientists to address COVID-19, focusing on understanding the virus and advancing solutions to ameliorate the impact today and for future generations. Children’s National Research Institute Director Mark Batshaw, M.D., highlighted some of these efforts in the annual report:

  • Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, is looking at whether or not the microbiome of bacteria in the human nasal tract acts as a defensive shield against COVID-19.
  • Catherine Bollard, M.D., MBChB, director of the Center for Cancer and Immunology Research, and her team are seeing if they can “train” T cells to attack the invading coronavirus.
  • Sarah Mulkey, M.D., Ph.D., an investigator in the Center for Neuroscience Research and the Fetal Medicine Institute, is studying the effects of, and possible interventions for, coronavirus on the developing brain.

You can view the entire Children’s National Research Institute academic annual report online.

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False negatives: Delayed Zika effects in babies who appeared normal at birth

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Colombian infants exposed to Zika virus in the womb showed neurodevelopmental delays as toddlers, despite having “normal” brain imaging and head circumference at birth, a finding that underscores the importance of long-term neurodevelopmental follow-up for Zika-exposed infants.

Colombian infants exposed to Zika virus in the womb showed neurodevelopmental delays as toddlers, despite having “normal” brain imaging and head circumference at birth, a finding that underscores the importance of long-term neurodevelopmental follow-up for Zika-exposed infants, according to a cohort study published online Jan. 6, 2020, in JAMA Pediatrics.

“These infants had no evidence of Zika deficits or microcephaly at birth. Neurodevelopmental deficits, including declines in mobility and social cognition, emerged in their first year of life even as their head circumference remained normal,” says Sarah B. Mulkey, M.D. Ph.D., a fetal/neonatal neurologist at Children’s National Hospital and the study’s first author. “About one-third of these newborns who underwent postnatal head ultrasound had nonspecific imaging results, which we believe are the first published results finding a link between subtle brain injuries and impaired neuromotor development in Zika-exposed children.”

The multi-institutional research group led by Children’s National enrolled pregnant women in Atlántico Department, which hugs the Caribbean coast of Colombia, who had been exposed to Zika, and performed a series of fetal magnetic resonance images (MRI) and ultrasounds as their pregnancies progressed.

Even though their mothers had laboratory-confirmed Zika infections, 77 out of 82 of their offspring were born with no sign of congenital Zika syndrome, a constellation of birth defects that includes severe brain abnormalities, eye problems and congenital contractures, and 70 underwent additional testing of neurodevelopment during infancy. These apparently normal newborns were born between Aug. 1, 2016, and Nov. 30, 2017, at the height of the Zika epidemic, and had normal head circumference.

When they were 4 to 8 months or 9 to 18 months of age, the infants’ neurodevelopment was evaluated using two validated tools, the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (a 50-item test of such skills as self-care, mobility, communication and social cognition) and the Alberta Infant Motor Scale (a motor examination of infants in prone, supine, sitting and standing positions). Some infants were assessed during each time point.

Women participating in the study were highly motivated, with 91% following up with appointments, even if it meant traveling hours by bus. In addition to Children’s National faculty traveling to Colombia to train staff how to administer the screening instruments, videotaped assessments, MRIs and ultrasounds were read, analyzed and scored at Children’s National. According to the study team, the U.S. scoring of Alberta Infant Motor Scale tests administered in Colombia is also unprecedented for a research study and offers the potential of remote scoring of infants’ motor skill maturity in regions of the world where pediatric specialists, like child neurologists, are lacking.

“Normally, neurodevelopment in infants and toddlers continues for years, building a sturdy neural network that they later use to carry out complex neurologic and cognitive functions as children enter school,” Dr. Mulkey adds. “Our findings underscore the recommendations by the Centers for Disease Control and Prevention (CDC) that all infants exposed to Zika in the womb undergo long-term follow-up, providing an opportunity to intervene earlier.”

An accompanying editorial by CDC staffers concurs, saying the study reported “intriguing data” that add “to the growing evidence of the need for long-term follow-up for all children with Zika virus exposure in utero to ensure they receive the recommended clinical evaluations even when no structural defects are identified at birth.”

In addition to Dr. Mulkey, study co-authors include Margarita Arroyave-Wessel, MPH, Dorothy I. Bulas, M.D., chief of Diagnostic Imaging and Radiology, JiJi Jiang, MS, Stephanie Russo, BS, Robert McCarter, ScD, research section head, design and biostatistics,  Adré J. du Plessis, M.B.Ch.B., MPH, chief of the Division of Fetal and Transitional Medicine, and co-Senior Author, Roberta L. DeBiasi, MD, MS, chief of the Division of Pediatric Infectious Diseases, all of Children’s National; Colleen Peyton, PT, DPT, of Northwestern University; Yamil Fourzali, M.D., of Sabbag Radiologos, Barranquilla, Colombia; Michael E. Msall, M.D., of University of Chicago Comer Children’s Hospital; and co-Senior Author, Carlos Cure, M.D., BIOMELab, Barranquilla, Colombia.

Funding for the research described in this post was provided by the Thrasher Research Fund, the National Institutes of Health under award Nos. UL1TR001876 and KL2TR001877, and the Leadership Education in Neurodevelopmental and Related Disorders Training Program under grant HRSA/MCHB T73 MC11047.