In this interview, we speak to Dr. Dani Dumitriu about her latest research that investigated the development screening test scores for babies born during the COVID-19 pandemic.
I am Dani Dumitriu, MD, Ph.D., pediatrician, and neuroscientist at Columbia University Vagelos College of Physicians and New York-Presbyterian. I spend 80% of my time researching the developmental origins of resilience – my lab is called “the DOOR lab” – and 20% of my time as a pediatric hospitalist providing care in the newborn nursery.
Most recently, I spearheaded Columbia University’s COVID-19 Mother Baby Outcomes (COMBO) Initiative, which broadly seeks to understand the health and wellbeing of infants born during the pandemic and their mothers.
Viral infections during pregnancy often lead to something we call “maternal immune activation” or MIA, and MIA has been associated with adverse outcomes in both animal models and human studies looking at other viral infections. Additionally, data from early in the pandemic did indeed show that pregnant women who contract COVID-19 mount a strong immunological response, meaning – MIA definitely occurs in these women.
Therefore, we and numerous other study groups around the world expected to see certain consequences of this MIA on the future neurodevelopmental trajectories of infants with in utero exposure to the virus.
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In this particular study, which is a small component of the overarching COMBO study, we used the Ages and Stages Questionnaire, 3rd Edition – or ASQ3 – to screen for neurodevelopmental deficits at 6 months of age. The ASQ3 is a standard screening tool widely used in pediatric offices and includes 30 questions that cover skills in 5 domains: communication, gross motor, fine motor, personal-social, and problem-solving.
It asks questions such as “Does your baby pick up a small toy with only one hand?” and “When in front of a large mirror, does your baby smile or coo at herself?” and parents can answer “Yes”, “Sometimes” or “Not yet”. For our study, mothers filled out this questionnaire online when their babies were around 6 months of age.
Our initial question was: “Does maternal infection with SARS-CoV-2 affect neurodevelopmental scores at 6 months?” To answer this, we compared 114 COMBO infants born to mothers with COVID-19 during pregnancy to 141 COMBO infants whose mothers had tested negative for the virus. We found absolutely no difference between these two groups even when we accounted for several things that could influence these scores, such as the sex of the baby, the exact gestational age that the baby was born at, mom’s socioeconomic status, and more.
We were then able to tackle another question: “Does being born during the pandemic affect neurodevelopmental scores at 6 months?” We were fortunate to be able to answer this because the first author Dr. Lauren Shuffrey had been conducting a study on infants born in our same medical center during the three years preceding the onset of the pandemic. Dr. Shuffrey had been investigating completely different questions but had scores from 62 infants at 6 months of age on the same ASQ3 screening tool. Therefore, she and co-first author Dr. Morgan Firestein were able to compare the pooled 255 COMBO infants to this historical cohort. And that’s when we saw a difference. Infants born during the pandemic had slightly lower average scores on gross motor, fine motor, and social skills.
It’s important to note that these differences were small but significant. In this study, we did not investigate the causes for the observed effect on neurodevelopment, but based on prior animal and human research, we believe this effect is likely due to the stress these mothers experienced during pregnancy.
Image Credit: Association of Birth During the COVID-19 Pandemic With Neurodevelopmental Status at 6 Months in Infants With and Without In Utero Exposure to Maternal SARS-CoV-2 Infection
This is a very early developmental timepoint. We gathered this data in 6 month-old babies. Lots is happening during the first few years of life, and because of this, assessments at 6 months of age are poor predictors of long-term outcomes. They are simply a snapshot in time, indicating that we need to pay attention, conduct more research, follow these infants long-term, and begin to formulate a primary prevention response.
Hundreds of millions of babies have been born worldwide since the onset of the pandemic. If – and the “if” is of critical importance – our data replicates across other geographic areas, other pandemic waves (the current study only covers the first wave in New York City), other racial/ethnic groups, other viral strains, etc, this could translate to significant public health consequences.
In our sample of a few hundred babies, we did not see a significant increase in infants who fell below the cutoff for referral. We only saw small differences in average scores. However, if our results generalize to the hundreds of millions of babies born during the pandemic, this would lead to a doubling (or more) in the rate of infants who fall below the referral cutoff, which would translate to millions of infants.
I think the pandemic has the potential to affect the generation born during this worldwide natural disaster. But I am extremely hopeful that it will not. The generation born during the 2-year period during which the 1918 Spanish flu ravaged the world had a 15% lower rate of graduation from high school compared to the generations born in the preceding and succeeding 2-year periods. But we are in a different era now. An era where we can rapidly generate the knowledge of potential effects, such as with our study, and then guide public health policies that will ameliorate or completely prevent long-term consequences.
The brains of 6-month-old infants are very plastic, very malleable, so by talking, singing, playing, interacting with them, and finding safe ways to take them out of the home more often, parents can absolutely help mitigate potential issues down the road. Pediatricians can help support this by placing extra emphasis on neurodevelopment during these times.
Public health policies can help by providing support to parents, especially those from low socioeconomic backgrounds, who are already at increased risk for adverse neurodevelopmental outcomes. And the public can help by enhancing human connection. The pandemic has led to a lot of social isolation, loneliness, and feelings of disconnect. By reconnecting, we can help support each other and get the babies born during this time onto an optimal neurodevelopmental trajectory.
Image Credit: Nutlegal Photographer/Shutterstock.com
Stress during pregnancy, and especially early in pregnancy, can broadly affect neurodevelopment. The precise effects are difficult to predict but depend on timing, type, and duration of stress. There is a vast literature on this topic, with my COMBO co-Chair Dr. Catherine Monk being a thought leader in the Developmental Origins of Health and Disease – or DOHaD.
However, our understanding of how stress specifically during pregnancy during the COVID-19 pandemic will affect DOHaD is in its infancy. We need a lot of additional research, including objective, subjective, and longitudinal measures of stress during pregnancy, which our current study did not address.
Our COMBO team of over 100 researchers, clinicians, and trainees is hard at work gathering data on a large number of outcomes in both mothers and babies and we invite you to visit our website for the most updated information.
We use a combination of longitudinal and cross-sectional study design and to date over 1,200 mother-baby dyads from New York, Utah and Alabama have contributed their time and effort to help us understand the effects of this unprecedented time on mothers and babies. We will share more of their stories soon!
Please find a link to our study page here: www.ps.columbia.edu/COMBO
Please find a link to the full paper here: https://jamanetwork.com/journals/jamapediatrics/fullarticle/2787479
Also please follow us on Twitter: @COMBOstudy
Dr. Dumitriu is trained as a general pediatrician, neuroscientist, and pediatric environmental health scientist. She completed her MD/PhD training, pediatric residency, and pediatric environmental health science fellowship at the Icahn School of Medicine at Mount Sinai, where she was awarded her first major NIH independent funding during her residency, becoming the first female in the US to receive an R01 during clinical training. She joined Columbia University as an Assistant Professor of Pediatrics (in Psychiatry) in November 2018.
She dedicates 80% of her time to research into the neurobiological basis of resilience as the Principal Investigator of the DOOR lab (Developmental Origins of Resilience lab) at the New York State Psychiatric Institute and 20% of time to caring for newborns in the Well Baby Nursery at the NewYork-Presbyterian Morgan Stanley Children’s Hospital.
The mission of the DOOR lab is to broadly uncover and harness the principles of health and resilience across species, lifespan, and investigational scale. Dr. Dumitriu’s work spans animal models of stress with a focus on the resilient subpopulations, human longitudinal observational and interventional studies to prospectively identify the building blocks of lifespan health, and tool development for novel experimental ideas without current technological solutions (e.g., telemetry for wild rats to uncover the principles of their evolutionary fitness).
Most recently, having been a frontline pediatric hospitalist in the newborn nursery as the pandemic swept through New York City – the first and hardest hit epicenter in the US – Dr. Dumitriu spearheaded the COVID-19 Mother Baby Outcomes (COMBO) Initiative. COMBO investigates the independent and combined effects of maternal SARS-CoV-2 infection and the COVID-19 pandemic environment on a range of maternal, infant, and dyadic outcomes. COMBO’s research group now includes over 100 investigators, clinicians, and trainees who span the fields of pediatrics, neonatology, obstetrics, psychiatry, psychology, neurology, otolaryngology, and public health. Experts from each discipline contribute to smaller working groups focusing on specific topics, such as child neurodevelopment, to develop state-of-the-art protocols and assessments.