
==== Front
Dev Cogn Neurosci
Dev Cogn Neurosci
Developmental Cognitive Neuroscience
1878-9293
1878-9307
Elsevier

S1878-9293(24)00090-2
10.1016/j.dcn.2024.101429
101429
Original Research
Assessing prenatal and early childhood social and environmental determinants of health in the HEALthy Brain and Child Development Study (HBCD)
Cioffredi Leigh-Anne leigh-anne.cioffredi@uvm.edu
a⁎1
Yerby Lea G. yerby002@ua.edu
b⁎⁎1
Burris Heather H. cd
Cole Katherine M. e
Engel Stephanie M. f
Murray Traci M. e
Slopen Natalie g
Volk Heather E. h
Acheson Ashley awacheson@uams.edu
i⁎⁎⁎
the HBCD Social and Environmental Determinants Working Group
a University of Vermont Larner College of Medicine, Vermont Children’s Hospital, USA
b Department of Community Medicine and Population Health, The University of Alabama, USA
c Children’s Hospital of Philadelphia, Division of Neonatology, USA
d University of Pennsylvania Perelman School of Medicine, Department of Pediatrics, USA
e National Institutes of Health/National Institute on Drug Abuse, USA
f Gillings School of Global Public Health, University of North Carolina at Chapel Hill, USA
g Department of Social and Behavioral Sciences, Harvard T. H. Chan School of Public Health, USA
h Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, USA
i Department of Psychiatry and Behavioral Sciences, University of Arkansas for Medical Sciences, USA
⁎ Correspondence to: University of Vermont Larner College of Medicine Department of Pediatrics, Given Courtyard 89 Beaumont Ave Burlington, Burlington, VT 05401, USA leigh-anne.cioffredi@uvm.edu
⁎⁎ Correspondence to: Northeast Medical Bldg 211 Peter Bryce Blvd Box 870326, Tuscaloosa, AL 35487, USA yerby002@ua.edu
⁎⁎⁎ Correspondence to: University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA awacheson@uams.edu
1 Contributed equally.

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https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The charge of the HBCD Social and Environmental Determinants (SED) working group is to develop and implement a battery of assessments to broadly characterize the social and physical environment during the prenatal period and early life to characterize risk and resilience exposures that can impact child growth and development. The SED battery consists largely of measures that will be repeated across the course of the HBCD Study with appropriate modifications for the age of the child and include participant demographics, indicators of socioeconomic status, stress and economic hardship, bias and discrimination (e.g., racism), acculturation, neighborhood safety, child and maternal exposures to adversity, environmental toxicants, social support, and other protective factors. Special considerations were paid to reducing participant burden, promoting diversity, equity, and inclusion, and adopting trauma-informed practices for the collection of sensitive information such as domestic violence exposure and adverse childhood experiences. Overall, the SED battery will provide essential data to advance understanding of child development and approaches to advance health equity across infant and child development.

Keywords

HBCD
Social determinants
Environmental exposures
Toxicants
Child development
Resilience
Neighborhood
Stress
Adverse childhood events
Intimate partner violence
Social services
Social support
Pregnancy
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pmc1 Introduction

This Special Issue describes the broad range of measures collected in the HEALthy Brain and Child Development (HBCD) Study. This ambitious and unprecedented study could not be complete without a thorough assessment to the social and environmental contexts in which children grow. The developmental origins of health and disease model suggests that adaptive reactions to the fetal environment set the stage for differences in brain development, behavior, physical and mental health after birth (Barker, 1990). An abundance of evidence now supports the hypothesis that prenatal stressors influence early childhood brain development thus measuring the presence of risk and resilience factors during pregnancy is foundational to interpreting relationships between postnatal environmental factors and brain development and behavior.

The postnatal developmental, biological and behavioral outcomes measured in the HCBD Study are also shaped by a child’s immediate physical surroundings and lived experiences throughout childhood (Shonkoff et al., 2009). Moreover, those physical surroundings and lived experiences are influenced by neighborhood location, access to basic needs, and social relationships with one’s community. All of these contexts are impacted by societal structural norms, current events and public policies. The complexity of the interplay between prenatal and postnatal experiences, family relationships, social circumstances and environmental exposures requires an in depth yet efficient evaluation of early childhood life (Okuzono et al., 2023).

The focus of this working group is on characterizing the social and environmental determinants of development starting in the prenatal period (Visit 1) though early childhood (Fig. 1). As such, we strove to develop assessments of the environment influencing development, health and behavior spanning the socioecological framework (McLeroy et al., 1988, Bronfenbrenner, 1977) (Fig. 2). First described by Bronfenbrenner, the socioecological framework gives organization to the ecological system in which child development occurs ranging from the immediate environment, such as family or school to the macroenvironment referring to cultural norms (Bronfenbrenner, 1994). This working group chose validated measures at each of the ecological levels depicted to enhance the ability for researchers to evaluate risk and protective factors within multiple systems of moderating factors. Other longitudinal cohorts that share this model of comprehensive assessment across multiple ecological levels include the Environmental influences on Child Health Outcomes (ECHO) observational study. The ECHO cohort boasts a large sample size, aiming to enroll more that 50,000 children and assesses many similar outcomes as HBCD including neurodevelopment and physical health (Park et al., 2024). However, HBCD will enhance the ECHO data by gathering several objective measures of brain growth and development such as EEG, MRI and observed behavioral and cognitive data (Dean et al., 2024, Fox et al., 2024, Kable et al., 2024). The Adolescent Brain Child Development Study (ABCD) (Garavan et al., 2018, Volkow et al., 2018) is another large prospective longitudinal study of child brain development. ABCD follows a similarly broad protocol assessing brain imaging as well as social, environmental and structural exposures spanning the socioecological model. ABCD enrollment began at ages 9–10 years, thus HBCD serves to complement the ABCD study by filling in the critical developmental window that is early childhood.Fig. 1 The HBCD Study’s comprehensive protocol includes assessments of children’s physical, cognitive, behavioral, social, and emotional development, plus surveys of parent/caregiver health and well-being. Assessments are distributed across in-person and remote visits during an initial 5-year period. Visits are scheduled at variable intervals designed to capture developmental trajectories.

Fig. 1

Fig. 2 The HBCD Study constructs within the socioecological model.

Fig. 2

In addition to social and structural exposures, environmental toxicants are increasingly becoming an important part of evaluating developmental differences. Other large cohort studies have elucidated many environmental exposures important to early brain development (Skogheim et al., 2021, Ames et al., 2023, Grippo et al., 2023). Toxicant exposure may also be an important moderator of other social exposures such as early life stress (DeSerisy et al., 2023). The HBCD Study will capture biospecimens for potential evaluation of specific toxicants, and this working group has developed a battery of surveys to supplement the biospecimen data, for additive evaluation of the most critical of environmental toxicant exposures.Table 1 Timing and Measure Selection of Social and Environmental Exposures in the HBCD Study.

Table 1Construct	Measure	Visits administered	
V1	V2	V3	V4	V5	V6	V7	
Demographics	Modified PhenX Toolkit
Household Roster	X
X			X
X		X
X		
Caregiver Disability	American Community Survey				X		X		
Transportation Access					X		X		
Benefits and Services	Baby’s First Years	X				X		X	
Economic Stress	Baby’s First Years	X				X		X	
Perceived Stress	Perceived Stress Scale - 4	X	X	X	X		X		
Social Support	PROMIS Emotional Support	X	X	X	X		X		
Intimate Partner Violence	Extended – Hurt, Insult, Threaten, Scream
Composite Abuse Scale (Revised)	X			X		X		
Neighborhood Characteristics	Residential addresses for geocoding
Neighborhood Safety Questionnaire	X				X		X	
Bias and Discrimination	Everyday Discrimination Scale
Major Experiences of Discrimination	X
X				X
X		X
X	
Acculturation	Vancouver Index of Acculturation					X			
Child Adverse Childhood Experiences (ACEs)	Pediatric ACEs and Related Life Events Screener				X		X		
Caregiver Adverse Childhood Experiences (ACEs)	ACEs Test for Adults				X				
Child Childhood Protective Factors	Protective and Compensatory Experiences (PACEs)					X			
Caregiver Childhood Protective Factors	Protective and Compensatory Experiences (PACEs)	X							
V1: Visit 1 (prenatal); V2: Visit 2 (0–30 days); V3: Visit 3 (3–9 months); V4: Visit 3 (9–15 months); V5: Visit 5, remote (10–17 months); V6: Visit 6 (15–48 months); V7: Visit 7 remote (16–50 months)

Please note that the protocol or procedures for V4 and onward are only current as of the time of manuscript submission and may change during piloting.

After gathering measures across a wide array of constructs, we collectively considered each construct’s importance and contribution to the study as well as the participant burden to complete each measure. When possible, we opted for previously validated measures over developing new ones, and when scientifically appropriate, we opted for shorter measures over longer measures assessing the same constructs. Additionally, we gave particular attention to include experiences of those previously underrepresented in research. In line with the values of the HBCD consortium, we hope the battery of measures chosen will allow for the larger research community to develop thoughtful scientific questions to inform future interventions and public policy and avoid contributing to misperceptions, and the perpetuation of inequities related to child development. Constructs assessed, measures used, and timing of measurement are represented in 1 and Table 2.Table 2 Timing and Measure Selection of Environmental Toxicant Exposures in the HBCD Study.

Table 2Construct	Measure	Visits administered	
V1	V2	V3	V4	V5	V6	V7	
Occupational exposures experienced by gestational parent	Occupational Hazard Assessment
Occupational History					X
X		X
X	
Non occupational exposures experienced by gestational parent	Prenatal Biospecimens
Geocoding of Residence and Childcare	X
X	X	X	X		X		
Exposures experienced by child	Housing Quality
Lead Exposure
Environmental tobacco smoke
Child biospecimens		X	X	X	X
X
X	X	X
X
X	
V1: Visit 1 (prenatal); V2: Visit 2 (0–30 days); V3: Visit 3 (3–9 months); V4: Visit 3 (9–15 months); V5: Visit 5, remote (10–17 months); V6: Visit 6 (15–48 months); V7: Visit 7 remote (16–50 months)

Please note that the protocol or procedures for V4 and onward are only current as of the time of manuscript submission and may change during piloting.

2 Demographics

The HBCD Study demographics survey was designed to capture indicators of socioeconomic status including race, ethnicity, nativity, income, maternal education, and occupation, as well as to characterize gender identity, sexual orientation, relationship status, primary residence, and household composition. Careful consideration was given to ensure that questions were inclusive of diverse populations and could capture a wide range of family structures and living situations that may impact child health outcomes. As a result, survey elements available within the PhenX Toolkit and other large-scale NIH studies were reviewed and modified by the SED working group and the HBCD Diversity, Equity, and Inclusion (DEI) Committee to reduce bias and correct for embedded assumptions of heteronormative nuclear-family structures. Although these modifications may limit the harmonization of the HBCD Study data with currently available datasets, they reflect an ongoing dialogue regarding DEI in developmental neuroscience research and an opportunity to expand the catalogue of survey elements for future studies (Garcini et al., 2022). Another key consideration was the relative timing of survey questions to reduce participant burden within each visit while capturing critical information about the birth parent/ primary caregiver and the index child across the duration of the study. The prenatal (Visit 1) demographics survey focuses on both biological parents and includes additional questions about work-related environmental exposures around the time of conception and during pregnancy that may be relevant to child health and development (See 8.2.1). The demographics survey is repeated when the child is between 9 and 15 months of age (Visit 4) and again at all subsequent in-person visits. The Visit 4 demographics survey was designed to capture information from the current primary caregiver, although several questions on prenatal work-related environmental exposures are included for the biological mother. Additional questions were added at this visit to capture the primary caregiver's disability status and access to transportation. The survey also expands to include questions on child race and ethnicity and shifts to focus on capturing a child-centric perspective of current living situations, household composition, household income, and the legal child-caregiver relationship. The household composition matrix captures the details of all household members including age, gender, relationship to the child, relationship to the primary caregiver, and time spent caring for the child. Participants and families who endorse no primary residence, or that they are living in a shelter or treatment facility, are not asked to complete the household matrix, as clear definitions of who constitutes a household member and ascertainment of their demographic information presents additional burden. Although there are no direct questions about the primary caregiver’s spouse/partner in the demographics, details of this relationship can be found within the household composition roster and additional questions regarding education and occupation are found in the Current Employment survey (See 8.2). Future demographics surveys will repeat survey elements from Visit 4 for both the primary caregiver and child.

3 Economic stress and benefits and services received

The HBCD Study includes sets of self-report questions to assess economic stress and benefits and services received by the family in the past 12 months at baseline and on a regular basis across the study. The rationale for assessing these constructs in the HBCD Study is that (a) high levels of financial strain have been shown to negatively impact parent/caregiver mental health and relationships and infant and child outcomes (Duncan and Brooks-Gunn, 1994, Duncan et al., 2017), and (b) receipt of public benefits and services may help alleviate some of the financial pressures experienced by families (Havnes and Mogstad, 2011, Hoynes et al., 2015, Hoynes et al., 2016). This information is a valuable complement to traditional measures of socioeconomic position, such as income-to-needs ratio, education, and occupational status, collected within the demographic questionnaire. The items for these assessments were selected from the Year 1 protocol of Baby’s First Years (Noble et al., 2021), a large NIH-funded study of infant and child development, with some minor modifications, and originated from the Moving to Opportunity (MTO) (Sanbonmatsu et al., 2012) study. We opted for these sets of items given that they had been included in another large study of infant development, they are quick to administer, and they provide information on financial instability, inability to meet basic needs, and services received that could alleviate economic stress. Economic stress was assessed via 9 items, including questions assessing global economic stability (e.g., worry about meeting basic living expenses, availability of savings to cover 1 month of expenses), missed utility and rent or mortgage payments in the past 12 months, experiences of utility shutoffs and eviction, and unmet medical or dental needs for the child or parent/caregiver. Within the same questionnaire, parents/caregivers were asked to report benefits or social services received in the past 12 months, including food stamps (SNAP/EBT), free or reduced child care, Early Head Start, Head Start, Women, Infants and Children (WIC), state unemployment benefits, cash assistance, free or reduced school lunch, housing assistance, or utility assistance, such as the Low Income Home Energy Assistance Program (LIHEAP). Two modifications to the list of benefits and services included in Baby’s First Years were made: (1) we did not include an item asking about Medicaid coverage, as health insurance information is recorded elsewhere in the HBCD Study, and (2) we added the item to assess if anyone in the family received free or reduced school lunch. This assessment is administered in the prenatal period (Visit 1). By administering these items on a regular basis, researchers can study the interplay between financial circumstances, benefits and services received, and other child and parent/caregiver characteristics within a developmental framework that could provide insights into how socioeconomic conditions influence health and development across infancy and childhood. We acknowledge there is a possibility for our study questions (annual income, work status etc.) to identify families who may benefit from services but are not yet receiving them. To balance the ethical obligations to participants with the observational design of the study, all study participants are given information about local and national resources for which they may be eligible. As the questionnaires above are filled out by the participant study team members are unlikely to be aware of opportunities to intervene unless participants have questions about particular items.

4 Perceived stress and emotional support

Psychosocial stressors during pregnancy have been associated with differences in developmental outcomes and early brain development (Lautarescu et al., 2020, Entringer et al., 2015, Pulli et al., 2019). Additionally, the experience of stress is not uniform across pregnant people. For example, pregnant people who identify with minoritized racial and ethnic groups and those with low incomes have been reported to have greater immune dysregulations associated with chronic stress (Corwin et al., 2013). Moreover, the burden of stress during pregnancy is not uniform. Pregnant individuals in rural areas are more likely to experience stress due to lack of access to obstetric care (Woodward et al., 2023), and mental health care (Ferris-Day et al., 2021, Chen et al., 2022) in addition to the economic disparities that impact rural communities. To capture overall daily stress burden, we chose the Perceived Stress Scale - 4 (Cohen et al., 1983) as a longitudinal measure of stress throughout pregnancy and parenthood. This 4-question measure is a shortened version of the longer PSS-10 or PSS-14. The questions are intentionally general which allows for a snap shot of overall stress burden (Cohen et al., 1994), and the PSS measure has been validated across several cultures (Eskildsen et al., 2015, Remor, 2006).

In addition, social and behavioral factors can also buffer the biologic impact of chronic stress during pregnancy and early childhood (Orr, 2004, Bedaso et al., 2021, Giesbrecht et al., 2013). Thus, to evaluate stress exposures within the context of presence or absence of protective factors is necessary. For example, higher parenting quality has been demonstrated to be protective in the relationship between prenatal stressors and lower early childhood cognitive function (Ahmad et al., 2022). Parenting is measured throughout the protocol via measures chosen by the Behavior and Child-Caregiver interaction working group (Edwards et al., 2024). Within the scope of our working group, three caregiver-stress protective factors were considered: Caregiver sleep quality (Fu et al., 2023, Maghami et al., 2021), caregiver physical activity (Ahmad et al., 2022), and caregiver social support. Of these, social support has the most established body of literature and has been directly associated with differences in early childhood brain development (Maghami et al., 2021, Manning et al., 2022). The Patient-Reported Outcomes Measurement Information System (PROMIS) measures include a 4 question short form measurement of social support (Hahn et al., 2010) allowing for standardized repeated measurement thorough the protocol without adding substantial time burden. After review of both the measures (PSS-4 and PROMIS emotional support) by the DEI working group, the instruments were piloted with original wording and remained unchanged after early visit pilots.

5 Intimate partner violence

The HBCD Study utilizes two measures of Interpersonal Violence, the Extended – Hurt, Insult, Threaten, Scream (E-HITS) (Portnoy et al., 2018) and the Composite Abuse Scale (Revised) – Short Form (CASR-SF) (Ford-Gilboe et al., 2016).

An estimated 3–9 % of birthing parents experience IPV during pregnancy (Alhusen et al., 2015, Martin et al., 2001, Saltzman et al., 2003) and these parents’ infants are more likely to witness violence or experience neglect (Borrego et al., 2008, Carpenter and Stacks, 2009). The literature suggests an intergenerational transmission of risk (Miller-Graff et al., 2019), with parents that experienced violence in the home as children having a decreased prenatal attachment to their fetus and increased stress response to infant-crying stimulus (Sancho-Rossignol et al., 2018). Further research reveals that the fetuses of parents with a history of abuse may have reduced heart rate variability (Cordero et al., 2017), lower cortical gray matter as a newborn (Moog et al., 2018), altered hypothalamus-pituitary-adrenal axis (Cordero et al., 2017), and changes in the prefrontal cortex regulation (Jedd et al., 2015, Weissman et al., 2020). Additionally, these infants are at an increased risk of forming a disorganized attachment style and decreased emotional regulation which puts them at increased likelihood for later behavioral problems, reduced focus, and difficulty forming social relationships (Carpenter and Stacks, 2009, Schore, 2002).

The E-HITS is a 5 question screener for experiences of psychological aggression, physical assault, sexual coercion, and injury created for quick administration in a health care setting and validated in US female veterans (Portnoy et al., 2018). The CASR-SF is a 15 item scale indexing lifetime and current experiences and frequency (in the past 12 months) with physical, sexual, and psychological abuse (Ford-Gilboe et al., 2016). The E-HITS is given prenatally, and the CASR-SF is given in later study visits. While these are short measures with demonstrated reliability and validity, they carry an emotional burden for the participant and have not been validated in ethnically or gender diverse populations or multiple environments (Portnoy et al., 2018, Ford-Gilboe et al., 2016). These assessments are participant self-administered in a private setting away from any additional adults or companions that may accompany the participant to the visit. Study staff are alerted when participant E-HITS and CASR-SF scores indicate they are experiencing violence or forced sexual activity. HBCD protocol requires each site to have an approved emergency management plan documenting the detailed site-specific response to these alerts, including referral to local resources and immediate assistance if needed.

6 Neighborhood characteristics

Prenatal and early-life exposure to stressful environments, including neighborhood-level factors, have been associated with adverse child health outcomes (Holaday et al., 2023) and alterations in early life neurodevelopmental trajectories (Brady et al., 2022) At the first prenatal visit current and previous residential addresses are collected and any residential moves are prospectively recorded at each point of follow up for both parent/caregiver and child. Childcare addresses are also obtained following birth when appropriate. Address histories are reviewed for accuracy at each visit and are geocoded for future area-level linkage with physical and social exposures that vary in space and time. Examples of exposures that will be available will include, but not be limited to, neighborhood deprivation, violence, and air pollution, all of which may affect brain development (Holaday et al., 2023, Brady et al., 2022, Singh and Ghandour, 2012, Jackson et al., 2019, Volk et al., 2021). Collection of residential addresses for use in geocoding will be an important part of the HBCD Study’s assessment of both social and environmental exposures, including neighborhood-level factors. However, geocoding information does not capture an individual's experience within that neighborhood. Use of the Neighborhood Safety Questionnaire (Mujahid et al., 2007), a brief three-item survey available on PhenX (Hamilton et al., 2011), is aimed to assess a participants self-reported experience in neighborhood safety, violence, and crime. This assessment is first administered prenatal, and then approximately yearly.

7 Bias and discrimination (e.g., racism) and acculturation

Stress related to discrimination and acculturation during pregnancy has been shown to impact the pregnant individual as well as the developing infant brain. These experiences can lead to depression and anxiety for the pregnant individual and poor health outcomes such as preterm birth and low birth weight (Spann et al., 2024). Adding these measures to the HBCD Study will provide much-needed research on the cognitive effects in infants.

The Everyday Discrimination Scale, Major Experiences of Discrimination, and Vancouver Index of Acculturation are among the most widely used measures to assess discrimination and acculturation. These assessments have been validated across different populations in several previous studies (Harnois et al., 2019, Kim et al., 2014, Lewis et al., 2012, Testa et al., 2019).

For the HBCD Study, these measures are self-administered, and the abbreviated versions of the Everyday Discrimination Scale and Major Experiences of Discrimination were used to reduce participant burden. Additional revisions to the HBCD Study’s version of these measures included changes to measure instructions, response options, and logic patterns. For example, the original instructions for Major Experiences of Discrimination state, “In the following questions, we are interested in the way other people have treated you or your beliefs about how other people have treated you.” For the HBCD Study, the instructions were simplified to state, “In the following questions, we are interested in your perceptions about the way other people have treated you.”

Two optional response options (your shade of skin color and your tribe) for the Everyday Discrimination Scale’s perceived reasons for discrimination were not included and one option (substance use/addiction) was added to capture the experiences of participants reporting substance use or addiction. Based on participant feedback, we replaced “a physical disability” with “a disability” and added three new options: “mental health or neurodivergence”, “physical health”, and “a reason not listed”. The revised logic pattern for the discrimination measures included moving the follow-up question of perceived reasons for discrimination to the end. It is asked only once to capture the main reasons for any items marked “a few times a year” (Everyday Discrimination Scale) or any items marked “yes” (Major Experiences of Discrimination) instead of asking for each endorsement.

For the Vancouver Index of Acculturation, we use the terms “family culture” for a participant’s heritage/ethnic cultural practices and “American culture” for cultural practices that are part of mainstream American culture. Some immigrants may consider American culture as their family culture. They can select “none” to indicate they do not identify with a culture other than American and will not continue the assessment. We attempted to capture many different countries, ethnicities, and religions for participants to select. However, if a participant’s family culture is not listed, they can select “None of these apply/My family culture is not listed”.

8 Early life stress and protective factors

Decades of research demonstrates associations between early life stress and delayed cognitive development, poor physical growth, and increased risk of behavioral problems in children (Bos et al., 2011, Zeanah et al., 2009, Felitti et al., 1998, Anda et al., 2006). More recent evidence suggests that the impact of early life stressors may be moderated by individual genetic differences, timing and duration of traumatic experiences and the presence of protective experiences (Calkins, 2015). Furthermore, the impact of intergenerational transmission of early stressors continues to be investigated with current literature suggesting parental early life stress is associated with differences in child developmental outcomes and stress regulation (Brand et al., 2010, Keenan-Devlin et al., 2023, Buss et al., 2017). Morris et al. suggest a framework of intergenerational pathways of risk and resilience to describe childhood trajectories toward stress induced biological and behavioral dysregulation or resilience pathways toward regulation (Fig. 3). Evaluation of all these factors, parental early life stress, as well as childhood early stressors and protective factors in HBCD will significantly advance understanding of these relationships as they relate to child development. We have aimed to assess these factors comprehensively and concisely by inclusion of measurement of both adverse and protective childhood experiences in adult and child participants as follows:Fig. 3 The Framework of intergenerational pathways of risk and resilience, adapted from Morris et al (Wolfe et al., 1996).

Fig. 3

8.1 Child and caregiver adverse childhood experiences

Adverse childhood experiences (ACEs) are defined as stressful and traumatic life events experienced before age 18 and are associated with broad spectrum of adverse health outcomes including increased risk for addiction and other psychopathology, cardiovascular diseases, obesity, and cancer (Felitti et al., 1998). ACEs are critically important to assess in the HBCD Study both in the context of studying normal childhood development and in the context of studying impacts such as prenatal substance exposures as parental substance misuse is associated with robust increases in adverse childhood experiences in offspring (Acheson et al., 2018, Charles et al., 2015).

The Pediatric ACEs and Related Life Events Screener (PEARLS) (Koita et al., 2018) was selected for ongoing monitoring of ACEs in the HBCD Study child participants starting at Visit 4. We intend to give a more comprehensive measure of early life adversity (ELA) for children at later visits and/or derive more detailed information about ELA from the trauma screeners of to be administered psychiatric diagnostic assessment measures. While these will rely on retrospective reporting for more detailed assessments of ELA events, the PEARLS was selected for ongoing monitoring of ELA in young children to minimize under-reporting of recent events. The ACEs Test for Adults (Bhushan et al., 2020) was selected for adult caregivers at Visit 4 only, primarily because of the much longer administration times required for more comprehensive measures such as the Life Stressor Checklist – Revised (Wolfe et al., 1996). We intend to administer a more comprehensive measure of ELA to adult caregivers at a later visit, time permitting. For both the PEARLS and the adult ACEs measure, participants are asked to provide a sum total of ACEs experienced rather than endorse individual ACE items. Total ACEs only are collected to limit under reporting, as previous studies indicate aggregate level responses have higher rates of disclosure, particularly in individuals identifying as black or male (Long et al., 2022). Studies of the impact of ACEs on child and adult health have historically focused on the cumulative total number of ACEs experienced as a predictor of outcomes (Felitti et al., 1998, Nelson et al., 2020, Schalinski et al., 2016). However, the growing body of literature continues to evaluate the differential impact of individual exposures and timing of those exposures on outcomes. We considered the limitation of collecting cumulative responses to ACE questionnaires and concluded the risk of underestimating the impact of ACEs due to underreporting outweighed the desire to be able to identify risks associated with individual experiences. We anticipate the data collected in HBCD will lead to more specified research questions regarding specific ACEs and child development in the future.

Both the PEARLS and the Adult ACEs measure are planned to be administered in-person in the HBCD Study rather than remote in a private setting due to concerns about confidentiality of reporting. After, all participants are provided information about resources for trauma exposure. Clinical alerts are triggered for participants who endorse a high number of ACE events on the PEARLS. Study staff members remind participants about limits of confidentiality and reporting requirements before enquiring about ACE events the child may have been exposed to. No DEI concerns were raised that required modifications to either measure.

8.2 Other protective factors

To complement the assessment of ACES, the HBCD Study will include measurement of protective and compensatory experiences (PACEs) using the 10-question scale recently developed by Morris et al. (2018). Like the ACEs questionnaire PACEs assess exposure to positive experiences during childhood, through age 18 that one may have experienced. Examples include having a best friend, being regularly involved in organized sports groups, engaging in a hobby, having a trusted adult one could rely on, and having clear rules at one’s home. Scores range between 0 and 10. The questions assess childhood relationships, feeling of connectedness as well as access to physical resources. PACE scores have been negatively correlated with ACEs (Morris et al., 2021). Additionally, early evidence indicates higher PACEs may buffer some negative impacts of ACEs. For instance, in a recent evaluation on the impact of ACEs and PACEs on parenting, ACEs were associated with harsh parenting attitudes only when PACEs were low (Morris et al., 2021). This new scale represents a low burden, efficient way to measure positive experiences in childhood. The inclusion of this measure in the HBCD Study is instrumental in providing rich context to childhood exposures. Measurement will occur for both the pregnant individual during the prenatal visit and the child at the remote V5 visit when child participants are 10–17 months.

9 Environmental toxicants – the HBCD Study occupational and physical environmental data

9.1 Overview and theoretical orientation

Toxic environmental exposures, including but not limited to lead, methylmercury, and organophosphate pesticides, can impact child neurodevelopment and behavior (Bellinger, 2012). Many toxic environmental exposures are also unequally distributed across sociodemographic groups and geographic space, with higher exposures to many toxicants disproportionately impacting people of color, urban residential spaces, and low-income populations (Nair et al., 2023, Temkin et al., 2022). Parental occupation is an important contributor to child’s risk of exposure to hazardous substances (Colt and Blair, 1998, Ren et al., 2023, Van Maele-Fabry et al., 2013) in the prenatal period, as well as through take-home exposures during childhood (Bemanalizadeh et al., 2022, Costet et al., 2018). Environmental exposures vary across residential and occupational settings and are associated with other risk factors for neurodevelopmental delay including low socioeconomic position and substance use disorders (Gilman et al., 2017, Smith and Wilson, 2016, Tyrrell et al., 2013). These complex and interrelated factors (environmental, behavioral, social, and biological/biomedical) may act independently and synergistically to influence the developing brain, exerting varying levels of influence across windows of development (Fig. 2).

9.2 The HBCD Study approach

We sought to characterize occupational and non-occupational exposures to hazardous substances using geospatial, survey, and biomonitoring approaches, taking into consideration relevant time-frames of exposure, and seeking to minimize participant burden (Table 2). At each visit, residential and childcare (if applicable) addresses are obtained for geographic information system (GIS) linkage to area-level environmental monitoring data such air toxics, toxic release inventory, proximity to roadways, noise and climate data. In addition, residential/childcare addresses can be geocoded in relation to area-level social determinants of health, such as the area deprivation index, social vulnerability index, environmental justice index, and other constructs that address census-level community characteristics, access to healthcare, greenspace, and food deserts

9.2.1 Prenatal period (Visit 1)

Workplace hazards experienced by the gestational parent during pregnancy are potential contributors to fetal exposure. We utilized a screening questionnaire for occupational and hobby exposures during pregnancy to characterize hazardous exposures to the gestational parent (Zachek et al., 2019) To capture general occupational stressors and conditions, we modified the PhenX Occupation/Occupational History Toolkit, to obtain information on all jobs worked during pregnancy, with more detailed information collected for jobs that individuals worked at for at least one month, and for at least 20 hours per week. We additionally obtained employment information for the job held by the other biological parent at approximately the time of conception. An integrated measure of total exposure to toxicants (occupational and non-occupational sources) may be obtained through analysis of biological media, collected from the gestational parent in the 3rd trimester (Fig. 1). While not all toxicants have validated biomarkers, a wide range of relevant exposures are readily measured (National Report on Human Exposure to Environmental Chemicals, 2023).

9.2.2 Infancy (Visit 2 and 4)

At the in-person postnatal visits, updated addresses are collected for geocoding, and child urine is obtained. Urine may be used for biomonitoring of a range of rapidly metabolized xenobiotics (Calafat et al., 2015), including some pesticides, endocrine disrupting exposures, toxic metals, and other hazardous compounds.

9.2.3 Toddlerhood (visit 5, 10–17 M)

At the next remote visit, we collect information on current parental employment, household chemical exposures, environmental tobacco smoke exposures and lead exposure risk. To assess whether participants might have elevated lead levels, the HBCD Study uses modified, existing governmental lead screening forms for blood lead level testing decisions which ascertain age of housing, home repairs, and use of potentially lead-containing cosmetics, candies, or ceramics (District of Coumbia Department of Energy and Envirionment, 2023). For other household and occupational chemical exposures, the HBCD Study uses modified questionnaires from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program and the occupation list from the US Census (United States Census Bureau, 2023, Blaisdell et al., 2022) The benefit of these measures is that they are non-invasive questionnaires. However, misclassification of exposures can occur without biomonitoring of human samples to obtain more accurate environmental exposure data. Nonetheless, the HBCD Study’s attention to chemical, in addition to non-chemic exposures, is critical to disentangling the impact prenatal substance exposure from other environmental contributors to brain development, and for characterizing any joint or synergistic effects.

9.2.4 Early childhood (Visit 6)

At the next in person visit, updated addresses are collected for geocoding, and child urine is obtained, which may be used for exposure biomonitoring.

10 Diversity, equity, and inclusion considerations

Special considerations for diversity, equity, and inclusion (DEI) were implemented across the HBCD Study including the measurement selection process. Our working group aimed to promote inclusivity and cultural sensitivity in data collection, analysis, and dissemination related to social and environmental determinants of health. To do so, we selected measures with various constructs addressing the intersectionality of diverse identities, lived experiences, and exposures on child growth and development.

Each measure underwent a thorough review from the HBCD DEI Committee which evaluated measures for bias related to race/ethnicity, culture, gender, heteronormative or nuclear family assumptions, ableism, or socioeconomic status. Most DEI Committee feedback for our working group focused on using more gender-neutral and inclusive language for describing the family structure.

11 Conclusion

The HBCD SED working group was charged with taking a socioecological approach to identifying a comprehensive set of factors influencing parents, caregivers, and children in their daily lives and home, work, childcare, and community settings. The working group chose measures to capture the complex interplay and combined impact of social and environmental factors on brain development in both the presence and absence of verified substance exposure in a sample representative of communities across the nation and across multiple developmental stages. The working group considered the importance and limitations of inclusion of each construct and instrument with a desire to enhance the breadth of assessments, which meant sacrificing in-depth assessment of some domains to limit participant burden. The data collected will provide important information on the relative impact of various exposures on neurodevelopmental trajectories as well as which resilience factors may mitigate these impacts from the prenatal stage through early and middle childhood. While impossible to measure all important exposures, the working group has developed a large battery of social and environmental determinants of health that will allow researchers to both study impacts of these variables as well as more accurately isolate exposures of interest such as prenatal substance exposure across child development.

A major contribution of this work is the detailed review of these standardized measures to make them increasingly inclusive and representative of families across the HBCD Study consortium and nation. This study is ongoing, therefore the assessment protocol included here is subject to change and adaptations may be presented in future papers.

Funding

In addition to the aforementioned NIH funding, this work was supported in part by the following grants 10.13039/100000139 EPA RD-84021901 , 10.13039/100000002 NIH R01 ES033518 , P30 ES010126 , R34DA050261 , R34DA050261-S1 , R34DA050261-S2 , National Institutes of Health Sponsor Award No 000531916-SC001 , 10.13039/100000102 Health Resources and Services Administration Sponsor Award No 000524849-SC001 .

CRediT authorship contribution statement

Katherine M. Cole: Writing – review & editing, Writing – original draft. Heather H. Burris: Writing – review & editing, Writing – original draft, Methodology. Lea G. Yerby: Writing – review & editing, Writing – original draft, Methodology, Conceptualization. Leigh-Anne Cioffredi: Writing – review & editing, Writing – original draft, Methodology, Conceptualization. Ashley Acheson: Writing – review & editing, Writing – original draft, Methodology, Conceptualization. Heather E. Volk: Writing – original draft, Methodology. Natalie Slopen: Writing – original draft, Methodology. Traci M. Murray: Writing – original draft, Methodology. Stephanie M. Engel: Writing – original draft, Methodology.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper

Acknowledgements

Data/Processes/Plans/Concepts (select as appropriate) used in the preparation of this article were obtained from the Healthy Brain and Child Development (HBCD) Study (https://hbcdstudy.org/). This is a multisite, longitudinal study designed to recruit over 7000 families and follow them from pregnancy to early childhood. The HBCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA055352, U01DA055353, U01DA055366, U01DA055365, U01DA055362, U01DA055342, U01DA055360, U01DA055350, U01DA055338, U01DA055355, U01DA055363, U01DA055349, U01DA055361, U01DA055316, U01DA055344, U01DA055322, U01DA055369, U01DA055358, U01DA055371, U01DA055359, U01DA055354, U01DA055370, U01DA055347, U01DA055357, U01DA055367, U24DA055325, U24DA055330. A full list of supporters is available at https://hbcdstudy.org/about/federal-partners/. A listing of participating sites and a complete listing of the study investigators can be found at https://hbcdstudy.org/study-sites/. HBCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or HBCD consortium investigators. Drs. Cole and Murray substantially participated in the preparation, review, and approval of the manuscript, consistent with their roles as Scientific Program Manager and Scientific Advisor for JEDI (Justice, Equity, Diversity, and Inclusion) for the HBCD Consortium study, respectively. Dr. Cole was substantially involved in U24DA055330 consistent with her role as Scientific Officer. The views and opinions expressed in this manuscript are those of the authors only and do not necessarily represent the views, official policy or position of the U.S. Department of Health and Human Services or any of its affiliated institutions or agencies.
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