Maternal prenatal uncertainty stress and child neurocognitive development: data from the COVID-19 pandemic

• In Event: The biological signatures of exposure to COVID-19 lockdown during the first 1000 days of life.

Abstract

Introduction: Maternal prenatal stress is a risk factor for atypical offspring biobehavioral development. The vast majority of studies addressing this important topic conceptualize stress as a general factor. However, there is recognition that stress is a complex construct and that the way stress is defined in research is highly variable. The goal of the current study is to address a specific form of stress, uncertainty, and to ask whether prenatal maternal uncertainty plays an important role in fetal programming. A further goal is to determine whether we can dissociate uncertainty effects from the influence of a general stress/mental health factor.
Hypothesis: Uncertainty is a bioenergetically expensive affective state. We evaluate whether uncertainty as a unique feature of maternal prenatal psychological health, and whether uncertainty has an influence on infant biobehavioral development. We address this in the context of the COVID-19 pandemic, which introduced financial and health uncertainty at a broad scale.
Study Population: More than 1,200 mother-infant dyads comprise the study cohort. At the time of this analysis, a subset of 652 participants completed the baseline survey during pregnancy, and a subset of ~140 have also completed developmental follow up at newborn, 6- and/or 12-months. Participants were pregnant between November 2019 and March 2022 and represent the racial/ethnic diversity of New York City.
Methods: An exploratory factor analysis (EFA) was employed to test whether stress is best represented as multiple factors. Network analysis was conducted on resulting factors. MRI data was collected in infants at one and twelve months, cortisol and behavioral data were collected at 6- and 12-months. The influence of resulting factors was tested in these multi-level outcome data. Specific analyses include testing whether uncertainty stress (US) is predictive of delayed infant brain maturation, indexed by strength of cross-hemispheric resting-state functional connectivity (RSFC).
Results: EFA isolated five dissociable stress factors: illness anxiety, uncertainty about the future, disruption to employment, general stress/mental health, and social isolation, and network analysis revealed that the general stress/mental health factor was a hub connecting factors, reflected in high betweenness and eigenvector centrality values. RSFC analysis revealed that the general stress/mental health factor was predictive of decreased homotopic connectivity in the infant cingulate, insula and lateral frontal regions, in mothers reporting higher US (p < 0.025, kmin = 45). Notably, this significant effect was present both in the newborn and in 12-month MRI cases, suggesting this may be a reproducible and stable effect. In addition, we confirmed that uncertainty was predictive of the opposite direction of effects; almost all findings related to uncertainty reflected increased connectivity in infants born to mothers reporting higher uncertainty stress during the pandemic. Regions associated with uncertainty included infant striatum, thalamus, dorsal medial anterior cingulate (dmACC), and sensorimotor regions. Results of this preliminary analysis support our hypothesis that maternal prenatal uncertainty is dissociable from general stress and has relevance for infant neurological development.

Authors

• Moriah E. Thomason, New York University School of Medicine
  Presenting Author

• Cassandra Lei Hendrix, New York University School of Medicine

• Lanxin Ji, New York University Grossman School of Medicine

• Amyn Majbri, New York University Grossman School of Medicine