A major challenge in designing large-scale, multi-site studies is developing a core, scalable protocol that retains the innovation of scientific advances while also lending itself to the variability in experience and resources across sites. In the development of a common Healthy Brain and Child Development (HBCD) protocol, one of the chief questions is "is fetal MRI ready for prime-time?" While there is agreement about the value of prenatal data obtained non-invasively through MRI, questions about practicality abound. There has been rapid progress over the past years in fetal and placental MRI methodology but there is uncertainty about whether the gains afforded outweigh the challenges in supporting fetal MRI protocols at scale. Here, we will define challenges inherent in building a common protocol across sites with variable expertise and will propose a tentative framework for evaluation of design decisions. We will compare and contrast various design considerations for both normative and high-risk populations, in the setting of the post-COVID era. We will conclude with articulation of the benefits of overcoming these challenges and would lend to the primary questions articulated in the HBCD initiative.

Background: Disruptions in perinatal care and support due to the COVID-19 pandemic was an unprecedented but significant stressor among pregnant women. Various neurostructural differences have been re-ported among fetuses and infants born during the pandemic compared to pre-pandemic counterparts. The relationship between maternal stress due to pandemic related disruptions and fetal brain is yet unexamined. Methods: Pregnant participants with healthy pregnancies were prospectively recruited in 2020–2022 in the greater Los Angeles Area. Participants completed multiple self-report assessments for experiences of pandemic related disruptions, perceived stress, and coping behaviors and underwent fetal MRI. Maternal perceived stress exposures were correlated with quantitative multimodal MRI measures of fetal brain development using multivariate models. Results: Increased maternal perception of pandemic related stress positively correlated with normalized fetal brainstem volume (suggesting accelerated brainstem maturation). In contrast, increased maternal perception of pandemic related stress correlated with reduced global fetal brain temporal functional variance (suggesting reduced functional connectivity). Conclusions: We report alterations in fetal brainstem structure and global functional fetal brain activity associated with increased maternal stress due to pandemic related disruptions, suggesting altered fetal programming. Long term follow-up studies are required to better understand the sequalae of these early multi-modal brain disruptions among infants born during the COVID-19 pandemic.

Background: While breastfeeding benefits early child neurocognition, its influences into adolescence, a period of intense brain remodeling and heightened mental health risk, remain unclear. Methods: Breastfeeding and neurocognitive longitudinal associations were explored over a two-year period in the Adolescent Brain Cognitive Development (ABCD) Study® ( n _baseline = 5098, ages 9–10, 49% female; n _follow-up = 3810, ages 11–12, 48% female). Breastfeeding duration was reported as never breastfed (15.8%), 1–6 months (34.6%), 7–12 months (26.4%), and >12 months (23.1%). MRI-derived estimates of cortical thickness, surface area, and cortical myelin were calculated across 148 brain regions alongside fluid cognition measures. Linear mixed-effects models tested the influence of breastfeeding duration and its interaction with age on neurocognitive outcomes. Significant cortical thickness and surface area associations were explored for cortical myelin differences. Parallel mediation analyses examined whether cortical features mediated the breastfeeding-fluid cognition relationship. Results: Breastfeeding duration was positively associated with cortical thickness (31 regions), surface area (45 regions), and fluid cognition (all p values < 0.05), and with greater cortical myelin in four regions and increases by follow-up in 12 regions (all p values < 0.05). Surface area mediated the breastfeeding-fluid cognition link ( β = 0.008, CI _boot 95% = 0.005, 0.012). Conclusions: These findings emphasize the importance of extending breastfeeding practices for optimal adolescent neurocognition. Impact: Does breastfeeding influence neurocognition during early adolescence, and does it impact neurocognitive development at this stage? In this longitudinal study, breastfeeding demonstrated dose-dependent, lasting positive influences on neurocognition that remained stable over a 2-year period spanning late childhood to early adolescence. Specifically, individuals who were breastfed longer showed increased cortical thickness, surface area, cortical myelin, and fluid cognition, predictors of positive outcomes in later life, including physical and mental health. Our findings highlight the importance of breastfeeding and support its extended practice for optimal neurodevelopment and potential late-life benefits.

The relationship between maternal risk factors (MRFs) (particularly pre-gravid obesity, diabetes, and hypertension) and congenital heart disease (CHD) to placental and fetal brain outcomes is poorly understood. Here, we tested the hypothesis that MRF and CHD would be associated with reduced intrinsic placental and fetal brain function using a novel non-invasive technique. Pregnant participants with and without MRF and fetal CHD were prospectively recruited and underwent feto-placental MRI. Using intrinsic properties of blood oxygen level dependent imaging (BOLD) we quantified spatiotemporal variance of placenta and fetal brain. MRFs and CHD were correlated with functional characteristics of the placenta and fetal brain. Co-morbid MRF (hypertension, diabetes, and obesity) reduced spatiotemporal functional variance of placenta and fetal brain (p < 0.05). CHD predicted reduced fetal brain temporal variance compared to non-CHD (p < 0.05). The presence of both MRF and CHD was associated with reduced intrinsic pBOLD temporal variance (p = 0.047). There were no significant interactions of MRFs and CHD status on either temporal or spatial variance of intrinsic brain BOLD. MRF and CHD reduced functional characteristic of placenta and brain in fetuses. MRF modification and management during pregnancy may have the potential to not only provide additional risk stratification but may also improve neurodevelopmental outcomes.