Adipokines measured during pregnancy and at birth are associated with infant negative affect.

BACKGROUND: Increased adiposity during pregnancy may be related to offspring risk for mental health disorders, although the biological mechanisms are poorly understood. One promising hypothesis is that factors secreted from adipocytes such as leptin and adiponectin may explain this association. The current study examined whether pregnancy or umbilical cord blood concentrations of leptin and/or adiponectin a) predict elevated infant negative affect at 6 months (an early life marker of risk for psychopathology); and b) help explain the association between pregnancy adiposity and increased infant negative affect. METHODS: Data came from a prospective cohort (N = 305) of pregnant individuals and their offspring. Second trimester adiposity was assessed using air displacement plethysmography. Concentrations of leptin and adiponectin were measured in second trimester plasma and umbilical cord plasma. Infant negative affect was assessed by standardized observation at 6 months. Second trimester inflammation was assessed using a comprehensive panel of cytokines. RESULTS: Lower second trimester adiponectin was associated with elevated infant negative affect, and mediated the effect of pregnancy adiposity on infant negative affect. This association was independent of the effect of second trimester inflammation. Umbilical cord leptin also predicted higher infant negative affect and mediated the association between pregnancy adiposity and infant negative affect. CONCLUSIONS: This is the first study to link pregnancy adiponectin or cord blood leptin to infant markers of risk for psychopathology, and the first to demonstrate that these adipokines mediate the association between pregnancy adiposity and offspring behavioral outcomes, suggesting novel markers of risk and potential mechanisms of effect.

Delineating early developmental pathways to ADHD: Setting an international research agenda.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent, impairing, and highly heritable condition typically diagnosed in middle childhood. However, it is now recognized that symptoms emerge much earlier in development. Research focused on understanding-using multiple units of analysis-the cascade of early-life (i.e., prenatal-infant-toddler) developmental changes that will later emerge as ADHD has the potential to transform early identification, prevention, and intervention. To this end, we introduce the recently established Early ADHD Consortium, an international network of investigators engaged in prospective, longitudinal studies of risk for ADHD beginning early in life, conducted within a developmental framework, and which incorporate multimethod approaches. This network seeks to harmonize measures and methodological approaches to increase the potential for data sharing and subsequent impact. Methods: This perspective paper highlights the importance of investigating pre-diagnostic markers of ADHD, and potential models and mechanisms of ADHD risk and development, with the long-term objective of facilitating development of preemptive interventions that will minimize the impact of ADHD symptoms on everyday functioning and maximize health and developmental outcomes. Results: We selectively describe key challenges and questions for this field related to theoretical models and developmental mechanisms in ADHD and recommend next steps for the science, including methodological, measurement, and study design considerations. We then describe potential implications for preemptive intervention development. We conclude by considering other issues including ethical concerns and the critical value of incorporating stakeholder input. Conclusions: It is hoped that this perspective puts forth a research agenda that will enhance collaborative efforts and accelerate progress in understanding developmental mechanisms and the early ADHD phenotype, with implications for early intervention enhancement of healthy development for infants, young children, and their families.

COVID-19 pandemic-related trauma symptoms are associated with postpartum alcohol consumption.

OBJECTIVE: The COVID-19 pandemic has led to escalations in substance use, including alcohol consumption. Of particular concern are the potential impacts during the postpartum period, a time of heightened vulnerability to stress and potential transmission of the negative sequelae of substance use to offspring. However, postpartum alcohol consumption during the COVID-19 pandemic has not been well characterized. METHOD: Postpartum drinking habits and COVID-19-related stress were repeatedly assessed (every two weeks for 12 weeks, and at one-, six-, and 12-months postpartum) from N = 378 individuals during the COVID-19 pandemic. Average alcohol use trajectories as well as heterogeneity in trajectories were characterized. COVID-19-related trauma symptoms and coping were examined in relation to alcohol use over time. RESULTS: Average postpartum alcohol use included an initial quadratic increase from one-to-four-months postpartum, followed by a plateau between four-to-12-months. Higher (15.08%), moderate (26.90%), and lower consumption (57.90%) subgroups were identified. Endorsement of COVID-19-related trauma symptoms and using alcohol to cope with stress predicted higher consumption. CONCLUSIONS: Findings suggest a potential sensitive period in establishing postpartum alcohol use patterns from one-to-four-months postpartum. Findings further suggest that postpartum alcohol use is heterogenous and that individual response to major traumatic stressors, like the COVID-19 pandemic, may influence emerging patterns of postpartum alcohol use.

The association between food desert severity, socioeconomic status, and metabolic state during pregnancy in a prospective longitudinal cohort.

Poor metabolic health during pregnancy is associated with health concerns for pregnant individuals and their offspring. Lower socioeconomic status (SES) is one risk factor for poor metabolic health, and may be related to limited access to healthful and affordable foods (e.g., living in a food desert). This study evaluates the respective contributions of SES and food desert severity on metabolic health during pregnancy. The food desert severity of 302 pregnant individuals was determined using the United States Department of Agriculture Food Access Research Atlas. SES was measured using total household income adjusted for household size, years of education, and amount of reserve savings. Information about participants' glucose concentrations one hour following an oral glucose tolerance test during the second trimester was extracted from medical records and percent adiposity during the second trimester was assessed using air displacement plethysmography. Information about participants' nutritional intake during the second trimester was obtained by trained nutritionists via three unannounced 24-h dietary recalls. Structural equation models showed that lower SES predicted higher food desert severity (ß = - 0.20, p = 0.008) and higher adiposity (ß = - 0.27, p = 0.016) and consumption of a more pro-inflammatory diet (ß = - 0.25, p = 0.003) during the second trimester of pregnancy. Higher food desert severity also predicted higher percent adiposity during the second trimester (ß = 0.17, p = 0.013). Food desert severity significantly mediated the relationship between lower SES and higher percent adiposity during the second trimester (ßindirect = - 0.03, 95% CI [- 0.079, - 0.004]). These findings indicate that access to healthful and affordable foods is a mechanism by which SES contributes to adiposity during pregnancy and may inform interventions intended to improve metabolic health during pregnancy.

Third Trimester Fetuses Demonstrate Priming, a Form of Implicit Memory, In Utero.

Research examinations of changes in fetal heart rate (HR) to operationalize fetal memory suggests that human memory capacities emerge in utero. However, there is little evidence for a form of implicit memory or priming. The present aim was to determine if priming is evident in utero. Fetal HR, maternal HR and maternal respiratory rate (RR) were examined in 105 women during the third trimester of pregnancy. Women experienced two counterbalanced laboratory tasks, the Stroop task and the paced breathing task, and their cardiorespiratory activity functioned as a stimulus for fetuses. Repeated measures ANOVAs revealed maternal HR increased during the Stroop task but only when the Stroop task was presented first (89.64 bpm to 92.39 bpm) (p = 0.04). Maternal RR increased during the Stroop task, regardless of task order (17.72 bpm to 21.11 bpm; 18.50 bpm to 22.60 bpm) (p < 0.01). Fetal HR increased during the paced breathing task, but only when it followed maternal exposure to the Stroop task (141.13 bpm to 143.97 bpm) (p < 0.01). Fetuses registered maternal HR and RR reactivity to the Stroop task, which influenced their response during maternal engagement with a related task, suggesting priming. Further study of fetal memory may suggest another pathway by which prenatal exposures impact future development.

Geotemporal analysis of perinatal care changes and maternal mental health: an example from the COVID-19 pandemic.

Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and 63% of postpartum participants reported at least one change to their perinatal care between March and August 2020. However, the prevalence and nature of specific perinatal care changes occurred unevenly over time and across geographic locations. The separation of infants and mothers immediately after birth and the cancelation of prenatal visits were associated with worsened depression and anxiety symptoms in mothers after controlling for sociodemographic factors, mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Our analyses reveal widespread changes to perinatal care across the US that fluctuated depending on where and when individuals gave birth. Disruptions to perinatal care may also exacerbate mental health concerns, so focused treatments that can mitigate the negative psychiatric sequelae of interrupted care are warranted.

The association between heightened ADHD symptoms and cytokine and fatty acid concentrations during pregnancy.

Objective: Previous research conducted with samples of children suggest that individuals with attention-deficit/hyperactivity disorder (ADHD) have altered fatty acid concentrations and may have increased systemic inflammation. Whether these differences are also apparent in other populations of individuals with heightened ADHD symptoms (e.g., pregnant adults) is unknown. The goal of the current study was to examine whether there are ADHD-associated differences in polyunsaturated fatty acid concentrations or pro-inflammatory cytokine concentrations during pregnancy, a developmental period when fatty acid concentrations and systemic inflammation have implications for the health of both the pregnant person and the developing child. We hypothesized that plasma levels of the ratio of omega-6s to omega-3s (n-6:n-3) and plasma inflammatory cytokine levels would be higher in individuals with heightened ADHD symptoms, consistent with previous findings in children with ADHD. Methods: Data (N = 68) came from a prospective study of pregnant community volunteers who were oversampled for ADHD symptoms. During the 3rd trimester, plasma concentrations of fatty acids and the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed. Dietary intake was examined in the 3rd trimester using three 24-h recalls conducted by trained dietitians and by examining plasma levels of conjugated linoleic acid (n-6) and α-linolenic acid (n-3), essential fatty acids that must come from dietary intake. Results: The group with heightened ADHD symptoms had higher n-6:n-3s (ß = 0.30, p < 0.01) and higher TNF-α concentrations (ß = 0.35, p < 0.001) relative to controls. There were no group differences in dietary variables, as assessed by self-report and via plasma concentrations of essential fatty acids. IL-6 was not reliably associated with ADHD status in this sample. Conclusion: Pregnant individuals with ADHD, on average, had higher plasma n-6:n-3s and higher TNF-α concentrations relative to controls. A difference was not detected in their dietary intake of fatty acids or other relevant nutrients. Though these null findings are inconclusive, they are consistent with the hypothesis that ADHD-associated differences in plasma fatty acid concentrations are the result of ADHD-associated differences in fatty acid metabolism, rather than simply differences in dietary intake.

Maternal Western-style diet reduces social engagement and increases idiosyncratic behavior in Japanese macaque offspring.

Recent evidence in humans and animals indicates an association between maternal obesity and offspring behavioral outcomes. In humans, increased maternal body mass index has been linked to an increased risk of children receiving a diagnosis of early-emerging neurodevelopmental disorders such as Attention Deficit/Hyperactivity Disorder (ADHD) and/or Autism Spectrum Disorder (ASD). However, a limited number of preclinical studies have examined associations between maternal Western-Style Diet (mWSD) exposure and offspring social behavior. To our knowledge, this is the first study to investigate relationships between mWSD exposure and social behavior in non-human primates. Since aberrant social behavior is a diagnostic criterion for several neurodevelopmental disorders, the current study focuses on examining the influence of maternal nutrition and metabolic state on offspring social behavior in Japanese macaques (Macaca fuscata). We found that mWSD offspring initiated less affiliative social behaviors as well as proximity to a peer. Using path analysis, we found that the association between mWSD consumption and reduced offspring social engagement was statistically mediated by increased maternal interleukin (IL)-12 during the third trimester of pregnancy. Additionally, mWSD offspring displayed increased idiosyncratic behavior, which was related to alterations in maternal adiposity and leptin in the third trimester. Together, these results suggest that NHP offspring exposed to mWSD exhibit behavioral phenotypes similar to what is described in some early-emerging neurodevelopmental disorders. These results provide evidence that mWSD exposure during gestation may be linked to increased risk of neurodevelopmental disorders and provides targets for prevention and intervention efforts.

Developmental trajectories of toddler sleep problems: can a person-centered approach help identify children at risk?

STUDY OBJECTIVES: Previous research examining toddler sleep problems has relied almost exclusively on variable-centered statistical approaches to analyze these data, which provide helpful information about the development of the average child. The current study examined whether person-centered trajectory analysis, a statistical technique that can identify subgroups of children who differ in their initial level and/or trajectory of sleep problems, has the potential to inform our understanding of toddler sleep problems and their development. METHODS: Families (N = 185) were assessed at 12, 24, 30, and 36 months of child age. Latent class growth analysis was used to test for subgroups that differed in their 24-36 month sleep problems. Subgroups were compared on child 36-month externalizing, internalizing, and total problem behaviors, and on 12 month maternal mental health, inter-parental conflict, and maternal parenting behaviors. RESULTS: Results support a four-class solution, with "low, stable," "low, increasing," "high, increasing," and "high decreasing" classes. The classes whose sleep problems persisted or worsened over time had worse behavioral problems than those whose symptoms improved or remained stably low. Additionally, 12 month maternal depression and global symptom severity, intimate partner violence, and maternal harsh-intrusive parenting behaviors discriminated between the classes that had similar levels of 24 month sleep disturbance but who had diverging trajectories over time. CONCLUSIONS: This statistical approach appears to have the potential to increase understanding of sleep problem trajectories in the early years of life. Maternal mental health, intimate partner violence, and parenting behaviors may be clinically useful markers of risk for the persistence or development of toddler sleep problems.

Electroencephalogram aperiodic power spectral slope can be reliably measured and predicts ADHD risk in early development.

The aperiodic exponent of the electroencephalogram (EEG) power spectrum has received growing attention as a physiological marker of neurodevelopmental psychopathology, including attention-deficit/hyperactivity disorder (ADHD). However, its use as a marker of ADHD risk across development, and particularly in very young children, is limited by unknown reliability, difficulty in aligning canonical band-based measures across development periods, and unclear effects of treatment in later development. Here, we investigate the internal consistency of the aperiodic EEG power spectrum slope and its association with ADHD risk in both infants (n = 69, 1-month-old) and adolescents (n = 262, ages 11-17 years). Results confirm good to excellent internal consistency in infancy and adolescence. In infancy, a larger aperiodic exponent was associated with greater family history of ADHD. In contrast, in adolescence, ADHD diagnosis was associated with a smaller aperiodic exponent, but only in children with ADHD who had not received stimulant medication treatment. Results suggest that disruptions in cortical development associated with ADHD risk may be detectable shortly after birth via this approach. Together, findings imply a dynamic developmental shift in which the developmentally normative flattening of the EEG power spectrum is exaggerated in ADHD, potentially reflecting imbalances in cortical excitation and inhibition that could contribute to long-lasting differences in brain connectivity.

Maternal diet and obesity shape offspring central and peripheral inflammatory outcomes in juvenile non-human primates.

The obesity epidemic affects 40% of adults in the US, with approximately one-third of pregnant women classified as obese. Previous research suggests that children born to obese mothers are at increased risk for a number of health conditions. The mechanisms behind this increased risk are poorly understood. Increased exposure to in-utero inflammation induced by maternal obesity is proposed as an underlying mechanism for neurodevelopmental alterations in offspring. Utilizing a non-human primate model of maternal obesity, we hypothesized that maternal consumption of an obesogenic diet will predict offspring peripheral (e.g., cytokines and chemokines) and central (microglia number) inflammatory outcomes via the diet's effects on maternal adiposity and maternal inflammatory state during the third trimester. We used structural equation modeling to simultaneously examine the complex associations among maternal diet, metabolic state, adiposity, inflammation, and offspring central and peripheral inflammation. Four latent variables were created to capture maternal chemokines and pro-inflammatory cytokines, and offspring cytokine and chemokines. Model results showed that offspring microglia counts in the basolateral amygdala were associated with maternal diet (ß = -0.622, p < 0.01), adiposity (ß = 0.593, p < 0.01), and length of gestation (ß = 0.164, p < 0.05) but not with maternal chemokines (ß = 0.135, p = 0.528) or maternal pro-inflammatory cytokines (ß = 0.083, p = 0.683). Additionally, we found that juvenile offspring peripheral cytokines (ß = -0.389, p < 0.01) and chemokines (ß = -0.298, p < 0.05) were associated with a maternal adiposity-induced decrease in maternal circulating chemokines during the third trimester (ß = -0.426, p < 0.01). In summary, these data suggest that maternal diet and adiposity appear to directly predict offspring amygdala microglial counts while maternal adiposity influences offspring peripheral inflammatory outcomes via maternal inflammatory state.

Longitudinal Temperament Pathways to ADHD Between Childhood and Adolescence.

The current investigation extended prior cross-sectional mapping of etiological factors, transdiagnostic effortful and affective traits, and ADHD symptoms to longitudinal pathways extending from two etiological domains: polygenic and prenatal risk. Hypotheses were (1) genetic risk for ADHD would be related to inattentive ADHD symptoms in adolescence and mediated by childhood effortful control; (2) prenatal smoking would be related to hyperactive-impulsive ADHD symptoms during childhood and mediated by childhood surgency; and (3) there would be age-related variation, such that mediation of genetic risk would be larger for older than younger ages, whereas mediation of prenatal risk would be larger in earlier childhood than at later ages. Participants were 849 children drawn from the Oregon ADHD-1000 Cohort, which used a case control sample and an accelerated longitudinal design to track development from childhood (at year 1 ages 7-13) through adolescence (at year 6 ages 13-19). Results showed the mediational pathway from prenatal smoking through surgency to hyperactivity-impulsivity at Year 1 was significant (indirect effect estimate = .053, p < .01). The mediational pathway from polygenic risk through effortful control to inattention at Year 6 was also significant (indirect effect estimate = .084, p < .01). Both results were independent of the association between inattention and hyperactivity-impulsivity and control for the alternative etiological input and held across parent- and teacher-report of ADHD symptoms. In line with dual pathway models of ADHD, early prenatal risk for hyperactivity-impulsivity appears to operate through surgency, while polygenic genetic risk for inattention appears mediated by effortful control.

Behavioral coping phenotypes and associated psychosocial outcomes of pregnant and postpartum women during the COVID-19 pandemic.

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic.

Effects of Maternal Psychological Stress During Pregnancy on Offspring Brain Development: Considering the Role of Inflammation and Potential for Preventive Intervention.

Heightened psychological stress during pregnancy has repeatedly been associated with increased risk for development of behavior problems and psychiatric disorders in offspring. This review covers a rapidly growing body of research with the potential to advance a mechanistic understanding of these associations grounded in knowledge about maternal-placental-fetal stress biology and fetal brain development. Specifically, we highlight research employing magnetic resonance imaging to examine the infant brain soon after birth in relation to maternal psychological stress during pregnancy. This approach increases capacity to identify specific alterations in brain structure and function and to differentiate between effects of pre- versus postnatal exposures. We then focus on the extensive preclinical literature and emerging research in humans that have found that heightened maternal inflammation during pregnancy as a mechanism through which maternal stress influences the developing fetal brain. We place these findings in the context of recent work identifying psychotherapeutic interventions that have been found to be effective for reducing psychological stress among pregnant individuals and that also show promise for reducing inflammation. We argue that a focus on inflammation, among other mechanistic pathways, may lead to a productive and necessary integration of research focused on the effects of maternal psychological stress on offspring brain development and on prevention and intervention studies aimed at reducing maternal psychological stress during pregnancy. In addition to increasing capacity for common measurements and understanding potential mechanisms of action relevant to maternal mental health and fetal neurodevelopment, this focus may inform and broaden thinking about prevention and intervention strategies.

Associations between childhood maltreatment, poor sleep, and prenatal distress in pregnant adolescents.

Childhood maltreatment (CM) is a known risk factor for adolescent pregnancy. Sleep disturbances and psychological distress, both common negative sequelae of CM, often co-occur during pregnancy, although directionality remains unclear. Furthermore, little is known about how CM affects sleep-distress associations during pregnancy. In pregnant adolescents, we examined: (a) whether there are significant predictive associations from CM to sleep quality and distress and (b) bidirectional influences of distress and sleep quality. Healthy pregnant adolescents (n = 204) were recruited before or during the 2nd trimester. CM was assessed at enrollment; sleep quality and distress were assessed in the 2nd and 3rd trimesters. Hypotheses were tested using path analysis. Findings revealed that CM was associated with worse 2nd trimester sleep quality and distress (ß = .19, p < .05 for sleep; ß = .30, p < .001 for distress). Higher levels of 2nd trimester distress were associated with lower 3rd trimester sleep quality (ß = .19, p < .05). Findings provide novel information about (a) associations from CM to prenatal mood and sleep in pregnant adolescents, and (b) sleep-distress directionality over the course of pregnancy. These results have implications for better understanding the ways in which CM potentially exerts influences later in life, and for targeting interventions to address physical and mental health during pregnancy.

Perinatal Western-style diet alters serotonergic neurons in the macaque raphe nuclei.

Introduction: The neurotransmitter serotonin is a key regulator of neurotransmission, mood, and behavior and is essential in neurodevelopment. Dysfunction in this important neurotransmitter system is connected to behavioral disorders such as depression and anxiety. We have previously shown that the developing serotonin system is sensitive to perinatal exposure to Western-style diet (WSD). Methods: To advance our hypothesis that perinatal WSD has a long-term impact on the serotonergic system, we designed a fluorescent immunohistochemistry experiment using antibodies against tryptophan hydroxylase 2 (TPH2) and vesicular glutamate transporter 3 (VGLUT3) to probe protein expression in the raphe subnuclei in 13-month-old Japanese macaques (Macaca fuscata; n = 22). VGLUT3 has been shown to be coexpressed in TPH2+ cells in the dorsal raphe (DR) and median raphe nucleus (MnR) of rodent raphe nuclei and may provide information about the projection site of serotonergic fibers into the forebrain. We also sought to improve scientific understanding of the heterogeneity of the serotonin production center for the central nervous system, the midbrain raphe nuclei. Results: In this immunohistochemical study, we provide the most detailed characterization of the developing primate raphe to date. We utilize multi-level modeling (MLM) to simultaneously probe the contribution of WSD, offspring sex, and raphe anatomical location, to raphe neuronal measurements. Our molecular and morphological characterization revealed that the 13-month-old macaque DR is remarkably similar to that of adult macaques and humans. We demonstrate that vesicular glutamate transporter 3 (VGLUT3), which rodent studies have recently shown can distinguish raphe populations with distinct projection targets and behavioral functions, likewise contributes to the heterogeneity of the primate raphe. Discussion: This study provides evidence that perinatal WSD has a long-term impact on the density of serotonin-producing neurons, potentially limiting serotonin availability throughout the brain. Due to the critical involvement of serotonin in development and behavior, these findings provide important insight into the mechanisms by which maternal nutrition and metabolic state influence offspring behavioral outcomes. Finally, these findings could inform future research focused on designing therapeutic interventions to optimize neural development and decrease a child's risk of developing a mental health disorder.

Co-occurrence of preconception maternal childhood adversity and opioid use during pregnancy: Implications for offspring brain development.

Understanding of the effects of in utero opioid exposure on neurodevelopment is a priority given the recent dramatic increase in opioid use among pregnant individuals. However, opioid abuse does not occur in isolation-pregnant individuals abusing opioids often have a significant history of adverse experiences in childhood, among other co-occurring factors. Understanding the specific pathways in which these frequently co-occurring factors may interact and cumulatively influence offspring brain development in utero represents a priority for future research in this area. We highlight maternal history of childhood adversity (CA) as one such co-occurring factor that is more prevalent among individuals using opioids during pregnancy and which is increasingly shown to affect offspring neurodevelopment through mechanisms beginning in utero. Despite the high incidence of CA history in pregnant individuals using opioids, we understand very little about the effects of comorbid prenatal opioid exposure and maternal CA history on fetal brain development. Here, we first provide an overview of current knowledge regarding effects of opioid exposure and maternal CA on offspring neurodevelopment that may occur during gestation. We then outline potential mechanistic pathways through which these factors might have interactive and cumulative influences on offspring neurodevelopment as a foundation for future research in this area.

Innovative methods for remote assessment of neurobehavioral development.

In response to the COVID-19 pandemic, research institutions across the globe have modified their operations in ways that have limited or eliminated the amount of permissible in-person research interaction. In order to prevent the loss of important developmentally-timed data during the pandemic, researchers have quickly pivoted and developed innovative methods for remote assessment of research participants. In this manuscript, we describe methods developed for remote assessment of a parent child cohort with a focus on examining the perinatal environment, behavioral and biological indicators of child neurobehavioral development, parent-child interaction, as well as parent and child mental and physical health. We include recommendations relevant to adapting in-laboratory assessments for remote data collection and conclude with a description of the successful dissemination of the methods to eight research sites across the United States, each of whom are involved in Phase 1 of the HEALthy Brain and Child Development (HBCD) Study. These remote methods were born out of pandemic-related necessity; however, they have much wider applicability and may offer advantages over in-laboratory neurodevelopmental assessments.

Trajectories of perinatal depressive symptoms in the context of the COVID-19 pandemic.

This study sought to advance understanding of the potential long-term consequences of the COVID-19 pandemic for child development by characterizing trajectories of maternal perinatal depression, a common and significant risk factor for adverse child outcomes. Data came from 393 women (86% White, 8% Latina; mean age = 33.51 years) recruited during pregnancy (n = 247; mean gestational age = 22.94 weeks) or during the first year postpartum (n = 146; mean child age = 4.50 months; 55% female). Rates of depression appear elevated, relative to published reports and to a pre-pandemic comparison group (N = 155). This study also provides evidence for subgroups of individuals who differ in their depressive symptom trajectories over the perinatal period. Subgroup membership was related to differences in maternal social support, but not to child birth outcomes.

Parasympathetic response to challenge in infancy moderates the effects of sociodemographic risk on academic achievement at school entry.

Exposure to higher levels of sociodemographic risk is associated with lower levels of academic achievement among young children. However, there is variability in the strength of this association, which may be traced to individual differences in physiological processes underlying self-regulation. In the current study, we examined whether the response of the parasympathetic nervous system to challenge, indexed by change in respiratory sinus arrhythmia (RSA), moderated the association between risk and school readiness at 5 years of age in a diverse sample of young children. We found that parasympathetic response to the Still-Face Paradigm moderated the effects of risk on a measure of school readiness, such that there was no association between risk and school readiness among children who exhibited RSA decreases during challenge at 6 months of age, a purported index of self-regulation at this age. For those infants who did not exhibit RSA withdrawal during this challenge, exposure to early cumulative risk was associated with lower scores on achievement assessment. These results speak to the possibility that certain patterns of parasympathetic response can serve as a protective factor for young children growing up in disadvantaged environments.