pregnant Archives

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

October 12, 2022

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.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation

Maternal mental health alters structure and biochemistry of developing fetal brain

January 30, 2020

Even when pregnant women have uncomplicated pregnancies and high socioeconomic status, when they experience elevated anxiety, stress or depression these prenatal stressors can alter the structure of the developing fetal brain and disrupt its biochemistry, according to Children’s National Hospital research published online Jan. 29, 2020, in JAMA Network Open.

The Children’s National research findings “have enormous scientific, clinical and public health implications,” Charles A. Nelson III, Ph.D., Boston Children’s Hospital, writes in a companion editorial.

“Previously we found that 65% of pregnant women who received a diagnosis of fetal congenital heart disease had elevated levels of stress. It’s concerning but not surprising that pregnant women who wonder if their baby will need open heart surgery would feel stress,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s senior author. “In this latest study, we ran the same panel of questionnaires and were surprised to find a high proportion of otherwise healthy pregnant women whose unborn babies are doing well also report high levels of stress.”

Anxiety and depression are the most common mental health problems during pregnancy. To learn more about the implications for the developing fetal brain, the Children’s National research team recruited 119 healthy volunteers with low-risk pregnancies from obstetric clinics in Washington, D.C., from Jan. 1, 2016, to April 17, 2019. The women’s mean age was 34.4 years old. All were high school graduates, 83% were college graduates, and 84% reported professional employment.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation. Segmentation results of total brain (orange), cortical gray matter (green), white matter (blue), deep gray matter (brown), brainstem (yellow), cerebellum (light blue), left hippocampus (purple) and right hippocampus (red) on a 3-Dimensional reconstructed T2-weighted MR image of a fetus at 26.4 gestational weeks. The hippocampus plays a central role in memory and behavioral inhibition and contains high concentrations of corticosteroid receptors and, thus, this brain region is sensitive to stress. Credit: JAMA Network Open.

The team performed 193 fetal brain magnetic resonance imaging (MRI) sessions between 24-40 weeks gestation and measured the volume of the total fetal brain as well as the cortical gray matter, white matter, deep gray matter, cerebellum, brainstem and hippocampus volumes. On the same day as their MRI visit, the pregnant women completed validated questionnaires to measure maternal stress, anxiety and depression, answering questions such as “how do you feel right now,” “how do you generally feel” as well as the degree of stressful feelings they experienced the month prior.

Of the pregnant women in the study:

27% tested positive for stress
26% tested positive for anxiety
11% tested positive for depression
Maternal anxiety and stress were associated with increased fetal cortical gyrification
Elevated maternal depression was associated with decreased creatine and choline levels in the fetal brain
Maternal stress scores decreased with increasing gestational age, while anxiety and depression did not

“We report for the first time that maternal psychological distress may be associated with increased fetal local gyrification index in the frontal and temporal lobes,” says Yao Wu, Ph.D., a research associate working with Limperopoulos at Children’s National and the study’s lead author. “We also found an association with left fetal hippocampal volume, with maternal psychological distress selectively stunting the left hippocampal volumetric growth more than the right. And elevated maternal depression was associated with decreased creatine and choline levels in the fetal brain,” Wu adds.

Late in pregnancy – at the time these women were recruited into the cohort study – the fetal brain grows exponentially and key metabolite levels also rise. Creatine facilitates recycling of adenosine triphosphate, the cell’s energy currency. Typically, levels of this metabolite rise, denoting rapid changes and higher cellular maturation; creatine also is known to support cognitive function. Choline levels also typically rise, marking cell membrane turnover as new cells are generated and support memory, mental focus and concentration.

“These women were healthy, and of high socioeconomic status and educational level, leading us to conclude that the prevalence of prenatal maternal psychological distress may be underestimated,” Limperopoulos adds. “While stress is an everyday reality for most of us, this is different because elevated stress during pregnancy can alter fetal brain programming. Our findings underscore the critical need to universally screen all pregnant women for prenatal psychological distress, even young mothers whose pregnancies wouldn’t otherwise raise red flags.”

In addition to Limperopoulos and Wu, Children’s National study co-authors include Yuan-Chiao Lu, Ph.D., research associate; Marni Jacobs, Ph.D., biostatistician; Subechhya Pradhan, Ph.D., research faculty; Kushal Kapse, MS, staff engineer; Li Zhao, Ph.D., research faculty; Nickie Niforatos-Andescavage, M.D., neonatologist; Gilbert Vezina, M.D., director of the neuroradiology program; and Adré J. du Plessis, M.B.Ch.B., director, Fetal Medicine Institute. Research coordinators Catherine Lopez, MS, Kathryn Lee Bannantine, BSN, and Jessica Lynn Quistorff, MPH, assisted with subject recruitment.

Financial support for the research described in this post was provided by the National Institutes of Health under grant No. RO1 HL116585-01 and the Thrasher Research Fund under Early Career award No. 14764.

Journal Reference:
Yao Wu, Yuan-Chiao Lu, Marni Jacobs, Subechhya Pradhan, Kushal Kapse, Li Zhao, Nickie Niforatos-Andescavage, Gilbert Vezina, Adré J. du Plessis, Catherine Limperopoulos. “Association of prenatal maternal psychological distress with fetal brain growth, metabolism and cortical maturation,” JAMA Network Open, 3(1): e1919940, 2020

Stressful pregnancies can leave fingerprint on fetal brain

January 13, 2020

“We were alarmed by the high percentage of pregnant women with a diagnosis of a major fetal heart problem who tested positive for stress, anxiety and depression,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s corresponding author.

When a diagnosis of fetal congenital heart disease causes pregnant moms to test positive for stress, anxiety and depression, powerful imaging can detect impaired development in key fetal brain regions, according to Children’s National Hospital research published online Jan. 13, 2020, in JAMA Pediatrics.

While additional research is needed, the Children’s National study authors say their unprecedented findings underscore the need for universal screening for psychological distress as a routine part of prenatal care and taking other steps to support stressed-out pregnant women and safeguard their newborns’ developing brains.

“We were alarmed by the high percentage of pregnant women with a diagnosis of a major fetal heart problem who tested positive for stress, anxiety and depression,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s corresponding author. “Equally concerning is how prevalent psychological distress is among pregnant women generally. We report for the first time that this challenging prenatal environment impairs regions of the fetal brain that play a major role in learning, memory, coordination, and social and behavioral development, making it all the more important for us to identify these women early during pregnancy to intervene,” Limperopoulos adds.

Congenital heart disease (CHD), structural problems with the heart, is the most common birth defect. Still, it remains unclear how exposure to maternal stress impacts brain development in fetuses with CHD.

The multidisciplinary study team enrolled 48 women whose unborn fetuses had been diagnosed with CHD and 92 healthy women with uncomplicated pregnancies. Using validated screening tools, they found:

65% of pregnant women expecting a baby with CHD tested positive for stress
27% of women with uncomplicated pregnancies tested positive for stress
44% of pregnant women expecting a baby with CHD tested positive for anxiety
26% of women with uncomplicated pregnancies tested positive for anxiety
29% of pregnant women expecting a baby with CHD tested positive for depression and
9% women with uncomplicated pregnancies tested positive for depression

All told, they performed 223 fetal magnetic resonance imaging sessions for these 140 fetuses between 21 and 40 weeks of gestation. They measured brain volume in cubic centimeters for the total brain as well as volumetric measurements for key regions such as the cerebrum, cerebellum, brainstem, and left and right hippocampus.

Maternal stress and anxiety in the second trimester were associated with smaller left hippocampi and smaller cerebellums only in pregnancies affected by fetal CHD. What’s more, specific regions — the hippocampus head and body and the left cerebellar lobe – were more susceptible to stunted growth. The hippocampus is key to memory and learning, while the cerebellum controls motor coordination and plays a role in social and behavioral development.

The hippocampus is a brain structure that is known to be very sensitive to stress. The timing of the CHD diagnosis may have occurred at a particularly vulnerable time for the developing fetal cerebellum, which grows faster than any other brain structure in the second half of gestation, particularly in the third trimester.

“None of these women had been screened for prenatal depression or anxiety. None of them were taking medications. And none of them had received mental health interventions. In the group of women contending with fetal CHD, 81% had attended college and 75% had professional educations, so this does not appear to be an issue of insufficient resources,” Limperopoulos adds. “It’s critical that we routinely to do these screenings and provide pregnant women with access to interventions to lower their stress levels. Working with our community partners, Children’s National is doing just that to help reduce toxic prenatal stress for both the health of the mother and for the future newborns. We hope this becomes standard practice elsewhere.”

Adds Yao Wu, Ph.D., a research associate working with Limperopoulos at Children’s National and the study’s lead author: “Our next goal is exploring effective prenatal cognitive behavioral interventions to reduce psychological distress felt by pregnant women and improve neurodevelopment in babies with CHD.”

In addition to Limperopoulos and Wu , Children’s National study co-authors include Kushal Kapse, MS, staff engineer; Marni Jacobs, Ph.D., biostatistician; Nickie Niforatos-Andescavage, M.D., neonatologist; Mary T. Donofrio, M.D., director, Fetal Heart Program; Anita Krishnan, M.D., associate director, echocardiography; Gilbert Vezina, M.D., director, Neuroradiology Program; David Wessel, M.D., Executive Vice President and Chief Medical Officer; and Adré J. du Plessis, M.B.Ch.B., director, Fetal Medicine Institute. Jessica Lynn Quistorff, MPH, Catherine Lopez, MS, and Kathryn Lee Bannantine, BSN, assisted with subject recruitment and study coordination.

Financial support for the research described in this post was provided by the National Institutes of Health under grant No. R01 HL116585-01 and the Thrasher Research Fund under Early Career award No. 14764.

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

January 6, 2020

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.

Novel approach to detect fetal growth restriction

October 28, 2019

Morphometric and textural analyses of magnetic resonance imaging can point out subtle architectural deviations associated with fetal growth restriction during the second half of pregnancy, a first-time finding that has the promise to lead to earlier intervention.

Morphometric and textural analyses of magnetic resonance imaging (MRI) can point out subtle architectural deviations that are associated with fetal growth restriction (FGR) during the second half of pregnancy. The first-time finding hints at the potential to spot otherwise hidden placental woes earlier and intervene in a more timely fashion, a research team led by Children’s National Hospital faculty reports in Pediatric Research.

“We found reduced placental size, as expected, but also determined that the textural metrics are accelerated in FGR when factoring in gestational age, suggesting premature placental aging in FGR,” says Nickie Andescavage, M.D., a neonatologist at Children’s National and the study’s lead author. “While morphometric and textural features can discriminate placental differences between FGR cases with and without Doppler abnormalities, the pattern of affected features differs between these sub-groups. Of note, placental insufficiency with abnormal Doppler findings have significant differences in the signal-intensity metrics, perhaps related to differences of water content within the placenta.”

The placenta, an organ shared by the pregnant woman and the developing fetus, delivers oxygen and nutrients to the developing fetus and ferries away waste products. Placental insufficiency is characterized by a placenta that develops poorly or is damaged, impairing blood flow, and can result in still birth or death shortly after birth. Surviving infants may be born preterm or suffer early brain injury; later in life, they may experience cardiovascular, metabolic or neuropsychiatric problems.

Because there are no available tools to help clinicians identify small but critical changes in placental architecture during pregnancy, placental insufficiency often is found after some damage is already done. Typically, it is discovered when FGR is diagnosed, when a fetus weighs less than 9 of 10 fetuses of the same gestational age.

“There is a growing appreciation for the prenatal origin of some neuropsychiatric disorders that manifest years to decades later. Those nine months of gestation very much define the breath of who we later become as adults,” says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National and the study’s senior author. “By identifying better biomarkers of fetal distress at an earlier stage in pregnancy and refining our imaging toolkit to detect them, we set the stage to be able to intervene earlier and improve children’s overall outcomes.”

The research team studied 32 healthy pregnancies and compared them with 34 pregnancies complicated by FGR. These women underwent up to two MRIs between 20 weeks to 40 weeks gestation. They also had abdominal circumference, fetal head circumference and fetal femur length measured as well as fetal weight estimated.

In pregnancies complicated by FGR, placentas were smaller, thinner and shorter than uncomplicated pregnancies and had decreased placental volume. Ten of 13 textural and morphometric features that differed between the two groups were associated with absolute birth weight.

“Interestingly, when FGR is diagnosed in the second trimester, placental volume, elongation and thickness are significantly reduced compared with healthy pregnancies, whereas the late-onset of FGR only affects placental volume,” Limperopoulos adds. “We believe with early-onset FGR there is a more significant reduction in the developing placental units that is detected by gross measures of size and shape. By the third trimester, the overall shape of the placenta seems to have been well defined so that primarily volume is affected in late-onset FGR.”

In addition to Dr. Andescavage and Limperopoulos, study co-authors include Sonia Dahdouh, Sayali Yewale, Dorothy Bulas, M.D., chief of the Division of Diagnostic Imaging and Radiology, and Biostatistician, Marni Jacobs, Ph.D., MPH, all of Children’s National; Sara Iqbal, of MedStar Washington Hospital Center; and Ahmet Baschat, of Johns Hopkins Center for Fetal Therapy.

Financial support for research described in this post was provided by the National Institutes of Health under award number 1U54HD090257, R01-HL116585, UL1TR000075 and KL2TR000076, and the Clinical-Translational Science Institute-Children’s National.

Fewer than 60% of young women diagnosed with STIs in emergency departments fill scripts

May 29, 2019

Fewer than 60% of young women diagnosed with sexually transmitted infections (STIs) in the emergency department fill prescriptions for antimicrobial therapy to treat these conditions, according to a research letter published online May 28, 2019, by JAMA Pediatrics.

Adolescents make up nearly half of the people diagnosed with sexually transmitted infections each year. According to the Centers for Disease Control and Prevention, untreated sexually transmitted diseases in women can cause pelvic inflammatory disease (PID), an infection of the reproductive organs that can complicate getting pregnant in the future.

“We were astonished to find that teenagers’ rates of filling STI prescriptions were so low,” says Monika K. Goyal, M.D., MSCE, assistant chief of Children’s Division of Emergency Medicine and Trauma Services and the study’s senior author. “Our findings demonstrate the imperative need to identify innovative methods to improve treatment adherence for this high-risk population.”

The retrospective cohort study, conducted at two emergency departments affiliated with a large, urban, tertiary care children’s hospital, enrolled adolescents aged 13 to 19 who were prescribed antimicrobial treatment from Jan. 1, 2016, to Dec. 31, 2017, after being diagnosed with PID or testing positive for chlamydia.

Of 696 emergency department visits for diagnosed STIs, 208 teenagers received outpatient prescriptions for antimicrobial treatments. Only 54.1% of those prescriptions were filled.

“Teenagers may face a number of hurdles when it comes to STI treatment, including out-of-pocket cost, access to transportation and confidentiality concerns,” Dr. Goyal adds.

Future studies will attempt to identify barriers to filling prescriptions in order to inform development of targeted interventions based in the emergency department that promote adherence to STI treatment.

In addition to Dr. Goyal, study co-authors include Lead Author, Alexandra Lieberman, BA, The George Washington University School of Medicine & Health Sciences; and co-authors Gia M. Badolato, MPH, and Jennifer Tran, PA-C, MPH, both of Children’s National.

Placental function linked to brain injuries associated with autism

April 29, 2019

“We saw long-term cerebellar white matter alterations in male experimental models, and behavioral testing revealed social impairments and increased repetitive behaviors, two hallmark features of ASD,” says Claire-Marie Vacher, Ph.D., lead study author.

Allopregnanolone (ALLO), a hormone made by the placenta late in pregnancy, is such a potent neurosteroid that disrupting its steady supply to the developing fetus can leave it vulnerable to brain injuries associated with autism spectrum disorder (ASD), according to Children’s research presented during the Pediatric Academic Societies 2019 Annual Meeting.

In order to more effectively treat vulnerable babies, the Children’s research team first had to tease out what goes wrong in the careful choreography that is pregnancy. According to the Centers for Disease Control and Prevention, about 1 in 10 babies is born preterm, before 37 weeks of gestation. Premature birth is a major risk factor for ASD.

The placenta is an essential and understudied organ that is shared by the developing fetus and the pregnant mother, delivering oxygen, glucose and nutrients and ferrying out waste products. The placenta also delivers ALLO, a progesterone derivative, needed to ready the developing fetal brain for life outside the womb.

ALLO ramps up late in gestation. When babies are born prematurely, their supply of ALLO stops abruptly. That occurs at the same time the cerebellum – a brain region essential for motor coordination, posture, balance and social cognition– typically undergoes a dramatic growth spurt.

“Our experimental model demonstrates that losing placental ALLO alters cerebellar development, including white matter development,” says Anna Penn, M.D., Ph.D., a neonatologist in the divisions of Neonatology and Fetal Medicine, and a developmental neuroscientist at Children’s National. “Cerebellar white matter development occurs primarily after babies are born, so connecting a change in placental function during pregnancy with lingering impacts on later brain development is a particularly striking result.”

The research team created a novel experimental model in which the gene encoding the enzyme responsible for producing ALLO is deleted in the placenta. They compared these preclinical models with a control group and performed whole brain imaging and RNAseq gene expression analyses for both groups.

“We saw long-term cerebellar white matter alterations in male experimental models, and behavioral testing revealed social impairments and increased repetitive behaviors, two hallmark features of ASD,” says Claire-Marie Vacher, Ph.D., lead study author. “These male-specific outcomes parallel the increased risk of brain injury and ASD we see in human babies born prematurely.”

ALLO binds to specific GABA receptors, which control most inhibitory signaling in the nervous system.

“Our findings provide a new way to frame poor placental function: Subtle but significant changes in utero may set in motion neurodevelopmental disorders that children experience later in life,” adds Dr. Penn, the study’s senior author. “Future directions for our research could include identifying new targets in the placenta or brain that could be amenable to hormone supplementation, opening the potential for earlier treatment for high-risk fetuses.”

Pediatric Academic Societies 2019 Annual Meeting presentation

“Placental allopregnanolone loss alters postnatal cerebellar development and function.”
- Sunday, April 28, 2019, 5:15 p.m. to 5:30 p.m. (EST)

Claire-Marie Vacher, Ph.D., lead author; Jackie Salzbank, co-author; Helene Lacaille, co-author; Dana Bakalar, co-author; Jiaqi O’Reilly, co-author; and Anna Penn, M.D., Ph.D., a neonatologist in the divisions of Neonatology and Fetal Medicine, developmental neuroscientist and senior study author.

How does diet during pregnancy impact allergies in offspring?

December 17, 2018

A small percentage of women said they consumed fewer allergens during pregnancy to stave off food allergies in their newborns, according to preliminary research Karen Robbins, M.D., presented during the American College of Asthma Allergy and Immunology 2018 Annual Scientific Meeting.

Pregnant women routinely swear off alcohol and tobacco to boost their chances of having a healthy baby. What about common food allergens like nuts and milk?

There are scant data that describe how often pregnant women deliberately stop eating a specific food item in order to prevent future food allergies in their newborns. As a first step toward addressing this data gap, a research team led by Karen Robbins, M.D., an allergist at Children’s National Health System, pored through a longitudinal study conducted by the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention.

About 4,900 pregnant women completed the Infant Feeding Practices Study II prenatal questionnaire from May 2005 to June 2007. The study tracked 2,000 pregnant women from the third trimester of pregnancy and their infants through the first year of life. A small percentage of women said they had consumed fewer allergens during pregnancy to stave off food allergies in their newborns, according to a poster Dr. Robbins presented during the American College of Asthma Allergy and Immunology 2018 Annual Scientific Meeting. While their numbers were small, most of these women reported giving up major allergens like nuts, milk or eggs during pregnancy, including:

144 (2.9 percent) reported restricting their diet in some way to prevent future food allergies in their offspring
84 women (1.7 percent) ate fewer nuts
15 women (.3 percent) ate fewer eggs and
2 women (.04 percent) ate/drank consumed less dairy/milk.

“At the time the survey was conducted, few pregnant women in this large data set said they gave up certain foods with the express aim of avoiding a food allergy in their babies,” Dr. Robbins says. “However, mothers who had an older child with a food allergy or who had food allergies themselves had significantly higher odds of trying this food avoidance strategy.”

Despite the diet changes, infants born to these expectant mothers were twice as likely to experience problems with food at age 4 months – though not at age 9 months or 12 months. And these infants were no more likely to be diagnosed with a food allergy.

According to the FDA, millions of Americans suffer a food allergy each year. Reactions can range from mild to life-threatening and can begin soon after eating a problematic food item or an ingredient from that food. Among the most common allergenic foods are milk, eggs, fish, shellfish, tree nuts, peanuts, wheat and soybeans.

“We really need to know more about how often targeted food avoidance occurs among U.S. pregnant women who have a family history of food allergies,” Dr. Robbins adds. “We hope to learn what factors into these women’s decision-making as well as why many of them settled on food avoidance as a potential strategy to try to prevent food allergy in their infants.”

American College of Asthma Allergy and Immunology 2018 Annual Scientific Meeting presentation

“Prenatal food allergen avoidance practices for food allergy prevention.”

Karen Robbins M.D., lead author; Ashley Ramos Ph.D., co-author; Marni Jacobs, Ph.D., co-author; Kate Balas BS, co-author; and Linda Herbert, Ph.D., director of Children’s Division of Allergy and Immunology’s psychosocial clinical program, and senior author.

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