Outcomes Studied

Prenatal insults have been associated with a number of adverse childhood health consequences, including congenital defects, increased risk of asthma, changes in breastfeeding and sleep health practices and more. Our dedicated team of health care workers are therefore monitoring overall child health using both chart review and parental surveys.

Prenatal infections and other events leading to maternal immune activation can affect the developing fetus, heralding long-term consequences for neurodevelopment. Often, these effects are subtle. Given the prevalence of COVID-19, however, millions of children worldwide will have been exposed to SARS-CoV-2 in utero by the time the pandemic ends. Therefore, even small effect sizes can have large public health relevance. It took decades for researchers to recognize these types of subtle effects in uninfected children who were exposed to maternal HIV infection in utero. COMBO seeks to rapidly generate knowledge on potential adverse effects of in utero SARS-CoV-2 exposure on neurodevelopment. The goal, if such effects are recognized, is more immediate development of both treatments and prevention efforts. To assess neurodevelopment, we administer parental-report and standardized observational assessments of child cognitive ability, social communication and emotional function, temperament, language ability, attention and memory, and motor skills that are assessed longitudinally across several developmental time points.

Prenatal viral infections can result in insults to the development of the nervous system, which can lead to increased risk of disabilities, seizures, delays in motor development, behavioral problems, and other neurological disorders. A dedicated team of pediatric neurologists contribute to the development of our neurodevelopmental assessments and review our data to ensure rapid identification of these types of problems in children with in utero exposure to SARS-CoV-2.

Many changes to the mother's health during pregnancy, including infections, are known to impact the health of the developing fetus. Differences in growth and body size are often the first sign of an effect in the infant which can indicate risk for longer term differences in brain and heart health. COMBO’s pediatric endocrinology team are carefully monitoring the birth size and growth of infants who were exposed to SARS-CoV-2 during pregnancy. To identify potential subtle effects, participants can also opt to have a state-of-the-art body composition test of their infants called quantitative magnetic resonance (QMR). Infants are placed in a machine with a weak magnetic field that can measure the exact amount of muscle/lean mass, fat and water, providing more in-depth information than simple measurements of weight and length.

Postnatal brain development has been shown to be affected by prenatal events in the mother’s life. Changes in developmental trajectories of various brain regions and circuits have been observed following maternal immune activation, maternal stress, and other experiences during pregnancy. Additionally, maternal brain changes have also been seen in relation to pregnancy itself, as well as following various illnesses. A subset of COMBO participants are therefore invited to participate in multimodal brain imaging of both mother and infant.

Pregnant women are considered a high risk group. At the beginning of the pandemic, little was known about their potential increased susceptibility to severe COVID-19 disease. Additionally, COVID-19 is now known to disproportionally affect already high-risk populations, such as ethnic and racial minorities and women with medical comorbidities like gestational diabetes and hypertension. Our dedicated team from the Department of Obstetrics and Gynecology have been gathering important data describing COVID-19 in pregnant women, and have been rapidly disseminating their findings to inform the evolving guidance from national and international organizations on best practices for the care of pregnant and peripartum women.

Maternal psychiatric illness is the most common complication of childbirth. Postpartum depression and anxiety, as well as depression and anxiety during pregnancy, are broadly described as perinatal mood and anxiety disorders (PMADs). One out of 7 women experiences PMADs; up to 70% experience life stress. Women living in poverty, disproportionately women of color, more often experience these mood disturbances. COVID-19 is exacerbating these already high numbers through common experiences of loss, isolation, and uncertainty as well as possible virus-related immune activation affecting brain functioning. We study women’s mental health outcomes, as well as other factors in their lives such as social support and sleep health, to learn new information to help prevent PMADs for all women.

COVID-19 is now recognized to have serious neurological manifestations, such as loss of smell and taste, headaches, seizures, and even stroke. Additionally, there is evolving data on long-term neurological sequelae in a subset of patients, including mental fog, memory problems, headache, weakness, and sleep disturbance. Because child wellness is intricately connected to maternal wellbeing, our Adult Neurology team is investigating the prevalence of neurological symptoms and sequelae in mothers enrolled in COMBO, to identify targets for treatment, intervention, and support.

The health and well-being of mother and child are inexorably linked to each other. Mother-infant relational health is one of the most potent predictors of future physical and mental health of both members of the dyad. To study the potential effects of the COVID-19 pandemic on the socio-emotional functioning of the mother-infant dyad, we conduct telehealth video visits and assess quality of mother-baby interactions using two theoretical approaches: attachment theory based on classical work by John Bowlby and Mary Ainsworth, and autonomic emotional connection based on foundational work by our partners at the Nurture Science Program.

A subset of COMBO mothers are invited into a randomized controlled trial of Family Nurture Intervention, an intervention pioneered by the Nurture Science Program, to test the short and long-term effects of a brief intervention on mitigating pandemic-induced adverse effects on mother-child emotional connection.

As part of the COMBO Study, participating mother-infant dyads have the option to provide biological samples during and after pregnancy. We are currently collecting maternal blood during pregnancy, umbilical cord blood and placental tissue at birth, and infant stool and breastmilk during the first several months after delivery. Using these samples, we will explore how maternal immune activation, stress, and changes to daily life as a result of the COVID-19 pandemic may impact biological processes, including immune function, placental development and gene regulation, colonization and composition of the infant microbiome, and others.

Among the many challenges imposed by the COVID-19 pandemic is the large number of research participation invitations afflicted individuals receive. While the science COMBO conducts is key, our most important goal is the safety, well-being, and protection of our participants, all of whom are first and foremost our patients. This is why our motto is: “Partnering with our community, for our community." To ensure highest standards of protection for our participants, several measures have been put in place. First, MaCRO, from which COMBO originated, was specifically formed with this goal in mind and several COMBO members are core members of MaCRO, including Co-Chairs Dani Dumitriu and Catherine Monk. Second, we regularly communicate with our Institutional Review Board and frequently seek their advice on various topics related to our protocols. Third, a COMBO-specific Ethics team meets routinely to brainstorm about participant protection, engagement, compensation, and satisfaction. These conversations inform the ongoing design of our research.

COMBO’s collaborative nature enables exciting and important scientific discoveries to emerge rapidly. However, with nearly 100 members, COMBO also poses serious administrative challenges. A dedicated team consisting of faculty, trainees, and staff meet regularly to keep the scientific progress on track!