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BACKGROUND AND PURPOSE: Quantitative susceptibility mapping is an emerging method for characterizing tissue composition and studying myelination and iron deposition. However, accurate assessment of myelin and iron content in the newborn brain using this method is challenging because these two susceptibility sources of opposite signs (myelin, negative; iron, positive) occupy the same voxel, with minimal and comparable content in both sources. In this study, susceptibilities were measured in the normal newborn brain using susceptibility source separation. MATERIALS AND METHODS: Sixty-nine healthy newborns without clinical indications were prospectively recruited for MRI. All newborns underwent gradient echo imaging for quantitative susceptibility mapping. Positive (paramagnetic) and negative (diamagnetic) susceptibility sources were separated using additional information from R2* with linear modeling performed for the newborn brain. Average susceptibility maps were generated by normalizing all susceptibility maps to an atlas space. Mean regional susceptibility measurements were obtained in the cortical GM, WM, deep GM, caudate nucleus, putamen, globus pallidus, thalamus, and the four brain lobes. RESULTS: A total of sixty-five healthy newborns (mean postmenstrual age, 42.8 ± 2.3 weeks; 34 females) were studied. The negative susceptibility maps visually demonstrated high signals in the thalamus, brainstem and potentially myelinated WM regions, whereas the positive susceptibility maps depicted high signals in the GM compared to all WM regions, including both myelinated and unmyelinated WM. The WM exhibited significantly lower mean positive susceptibility and significantly higher mean negative susceptibility than cortical GM and deep GM. Within the deep GM, the thalamus showed a significantly lower mean negative susceptibility than the other nuclei, and the putamen and globus pallidus showed significant associations with newborn age in positive and/or negative susceptibility. Among the four brain lobes, the occipital lobe showed a significantly higher mean positive susceptibility and a significantly lower mean negative susceptibility than the frontal lobe. CONCLUSIONS: This study demonstrates regional variations and temporal changes in positive and negative susceptibilities of the newborn brain, potentially associated with myelination and iron deposition patterns in normal brain development. It suggests that quantitative susceptibility mapping with source separation may be used for early identification of delayed myelination or iron deficiency. ABBREVIATIONS: CGM = cortical gray matter; DGM = deep gray matter; PMA = postmenstrual age; QSM = quantitative susceptibility mapping.
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BACKGROUND, AIMS: Circadian rhythm maturation may be disturbed in premature infants undergoing neonatal intensive care. We used continuous heart rate recordings across the entire neonatal intensive care period to study circadian rhythm development in preterm infants and to evaluate the roles of postmenstrual (PMA) versus postnatal age (PNA). MATERIALS AND METHODS: The circadian rhythm was calculated using a cosine fit of heart rate. The circadian rhythm amplitudes were averaged weekly and studied relative to PMA and PNA using the linear mixed effects models, adjusting for clinical variables that could affect the heart rate. The daily circadian rhythms were used to create grand averages for PMA groups: ≤31, 32-35, and > 35 weeks, and for PNA groups: ≤30, 31-60, and > 60 days. RESULTS: Sixty-six infants were evaluated as part of an ongoing prospective study with gestational ages between 23 and 36 weeks. The PMA (1.47 × 10-2 beats per minute (bpm)/week, P = 2.07 × 10-8) and PNA (1.87 × 10-2 bpm/day; P = 1.86 × 10-6) were significantly associated with the circadian rhythm amplitude independent of covariates. Infants ≤31 weeks' PMA and ≤30 days PNA, the phase of circadian rhythm amplitude grand averages showed a peak at night and a nadir during the day. Hereafter the circadian rhythm phase reversed to that established for mature individuals. The highest circadian rhythm amplitudes present >35 weeks' PMA and > 60 days PNA. CONCLUSIONS: Our results indicate circadian rhythm matures with advancing gestation. The reversed circadian rhythm phase during the early postnatal period could be due to premature exposure to the ex-utero environment and warrant further study.
Subject(s)
Circadian Rhythm , Heart Rate , Infant, Premature , Humans , Circadian Rhythm/physiology , Infant, Newborn , Infant, Premature/growth & development , Infant, Premature/physiology , Male , Female , Heart Rate/physiology , Gestational Age , Prospective StudiesABSTRACT
Recent studies indicate that differences in cognition among individuals may be partially attributed to unique brain wiring patterns. While functional connectivity (FC)-based fingerprinting has demonstrated high accuracy in identifying adults, early studies on neonates suggest that individualized FC signatures are absent. We posit that individual uniqueness is present in neonatal FC data and that conventional linear models fail to capture the rapid developmental trajectories characteristic of newborn brains. To explore this hypothesis, we employed a deep generative model, known as a variational autoencoder (VAE), leveraging two extensive public datasets: one comprising resting-state functional MRI (rs-fMRI) scans from 100 adults and the other from 464 neonates. VAE models trained on rs-fMRI from both adults and newborns produced superior age prediction performance (with r between predicted- and actual age â¼ 0.7) and individual identification accuracy (â¼45 %) compared to models trained solely on adult or neonatal data. The VAE model also showed significantly higher individual identification accuracy than linear models (=10â¼30 %). Importantly, the VAE differentiated connections reflecting age-related changes from those indicative of individual uniqueness, a distinction not possible with linear models. Moreover, we derived 20 latent variables, each corresponding to distinct patterns of cortical functional network (CFNs). These CFNs varied in their representation of brain maturation and individual signatures; notably, certain CFNs that failed to capture neurodevelopmental traits, in fact, exhibited individual signatures. CFNs associated with neonatal neurodevelopment predominantly encompassed unimodal regions such as visual and sensorimotor areas, whereas those linked to individual uniqueness spanned multimodal and transmodal brain regions. The VAE's capacity to extract features from rs-fMRI data beyond the capabilities of linear models positions it as a valuable tool for delineating cognitive traits inherent in rs-fMRI and exploring individualized imaging phenotypes.
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OBJECTIVE: To determine the association between neighborhood disadvantage (ND) and functional brain development of in utero fetuses. STUDY DESIGN: We conducted an observational study using Social Vulnerability Index (SVI) scores to assess the impact of ND on a prospectively recruited sample of healthy pregnant women from Washington, DC. Using 79 functional magnetic resonance imaging scans from 68 healthy pregnancies at a mean gestational age of 33.12 weeks, we characterized the overall functional brain network structure using a graph metric approach. We used linear mixed effects models to assess the relationship between SVI and gestational age on 5 graph metrics, adjusting for multiple scans. RESULTS: Exposure to greater ND was associated with less well integrated functional brain networks, as observed by longer characteristic path lengths and diminished global efficiency (GE), as well as diminished small world propensity (SWP). Across gestational ages, however, the association between SVI and network integration diminished to a negligible relationship in the third trimester. Conversely, SWP was significant across pregnancy, but the relationship changed such that there was a negative association with SWP earlier in the second trimester that inverted around the transition to the third trimester to a positive association. CONCLUSIONS: These data directly connect ND and altered functional brain maturation in fetuses. Our results suggest that, even before birth, proximity to environmental stressors in the wider neighborhood environment are associated with altered brain development.
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BACKGROUND: Brain magnetic resonance imaging (MRI) is a crucial tool for clinical evaluation of the brain and neuroscience research. Obtaining successful non-sedated MRI in children who live in resource-limited settings may be an additional challenge. OBJECTIVE: To present a feasibility study of a novel, low-cost MRI training protocol used in a clinical research study in a rural/semi-rural region of Colombia and to examine neurodevelopmental factors associated with successful scans. MATERIALS AND METHODS: Fifty-seven typically developing Colombian children underwent a training protocol and non-sedated brain MRI at age 7. Group training utilized a customized booklet, an MRI toy set, and a simple mock scanner. Children attended MRI visits in small groups of two to three. Resting-state functional and structural images were acquired on a 1.5-Tesla scanner with a protocol duration of 30-40 minutes. MRI success was defined as the completion of all sequences and no more than mild motion artifact. Associations between the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Movement Assessment Battery for Children (MABC), Behavioral Rating Inventory of Executive Function (BRIEF), Child Behavior Checklist (CBCL), and Adaptive Behavior Assessment System (ABAS) scores and MRI success were analyzed. RESULTS: Mean (SD) age at first MRI attempt was 7.2 (0.2) years (median 7.2 years, interquartile range 7.1-7.3 years). Twenty-six (45.6%) participants were male. Fifty-one (89.5%) children were successful across two attempts; 44 (77.2%) were successful on their first attempt. Six (10.5%) were unsuccessful due to refusal or excessive motion. Age, sex, and scores across all neurodevelopmental assessments (MABC, TVIP, ABAS, BRIEF, CBCL, NIH Toolbox Flanker, NIH Toolbox Pattern Comparison, WPPSI) were not associated with likelihood of MRI success (P=0.18, 0.19, 0.38, 0.92, 0.84, 0.80, 1.00, 0.16, 0.75, 0.86, respectively). CONCLUSION: This cohort of children from a rural/semi-rural region of Colombia demonstrated comparable MRI success rates to other published cohorts after completing a low-cost MRI familiarization training protocol suitable for low-resource settings. Achieving non-sedated MRI success in children in low-resource and international settings is important for the continuing diversification of pediatric research studies.
Subject(s)
Feasibility Studies , Magnetic Resonance Imaging , Rural Population , Humans , Colombia , Male , Female , Magnetic Resonance Imaging/methods , Child , Brain/diagnostic imagingABSTRACT
Importance: Elevated maternal psychological distress during pregnancy is associated with altered fetal brain development. During the COVID-19 pandemic, prenatal maternal psychological distress more than doubled. Objective: To examine the association of the pandemic and rising maternal psychological distress with brain growth in newborns using quantitative 3-dimensional volumetric magnetic resonance imaging (MRI). Design, Setting, and Participants: This prospective cross-sectional study recruited mother-infant dyads at Children's National Hospital, Washington, DC, during the COVID-19 pandemic (June 1, 2020, to June 30, 2022) into a longitudinal infant brain development study and compared them with an existing normative healthy cohort (recruited March 1, 2014, to December 31, 2019). Exclusion criteria included multiple gestation pregnancy, known or suspected congenital infection, documented chromosomal abnormalities, or any maternal contraindication to MRI, as well as prenatal COVID-19 exposure. Infants with structural brain abnormalities or a postnatal confirmation of a genetic syndrome were excluded. Exposure: Psychological distress during COVID-19 pandemic. Main Outcomes and Measures: Prenatal maternal mental health was evaluated using the Spielberger State-Trait Anxiety Inventory and the Perceived Stress Scale. Neonates underwent nonsedated brain MRI. An ordinary least squares linear regression model was used to measure the differences in regional brain volumes of neonates born before vs during the pandemic with and without exposure to elevated prenatal maternal psychological distress after adjustment for neonatal sex and gestational age at MRI and maternal age and educational level. Results: A total of 159 mother-infant dyads were included in the analysis: 103 before and 56 during the pandemic (median gestational age of infants, 39.6 [IQR, 38.4-40.4] weeks; median maternal age, 34.5 [IQR, 31.0-37.0] years). Eighty-three infants (52.2%) were female. Among the mothers, 130 (81.8%) had a college degree and 87 (54.7%) had a graduate degree. Forty-four mothers (27.7%) identified as Asian, Hispanic, or multiracial; 27 (17.0%), as Black; and 88 (55.3%), as White. Scores on anxiety and stress measures were significantly increased in the pandemic cohort. Infants of mothers with elevated maternal distress showed median reductions in white matter (-0.36 [95% CI, -0.61 to -0.11] cm3; Q < .001), right hippocampal (-0.35 [95% CI, -0.65 to -0.06] cm3; Q = .04), and left amygdala (-0.49 [95% CI, -0.84 to -0.13] cm3; Q = .03) volumes compared with infants of mothers with low distress levels. After adjusting for the cohort effect of the pandemic, elevated trait anxiety remained significantly associated with decreased left amygdalar volumes (-0.71 [95% CI, -1.12 to -0.29]; Q < .001). Conclusions and Relevance: In this cross-sectional study of maternal-infant dyads prior to and during the COVID-19 pandemic, regional neonatal brain volumes were associated with elevated maternal psychological distress.
Subject(s)
Brain , COVID-19 , Magnetic Resonance Imaging , Psychological Distress , SARS-CoV-2 , Humans , Female , COVID-19/psychology , COVID-19/epidemiology , Pregnancy , Infant, Newborn , Brain/diagnostic imaging , Brain/pathology , Adult , Cross-Sectional Studies , Prospective Studies , Male , Mothers/psychology , Pandemics , Stress, Psychological , Pregnancy Complications/psychology , Pregnancy Complications/epidemiology , Prenatal Exposure Delayed Effects/psychology , Anxiety/epidemiologyABSTRACT
Over the past decade, a growing body of research in adults has emphasized the role of the cerebellum in social and emotional cognition. This has been further supported by findings of delayed social and emotional development in toddlers with cerebellar injury during the fetal and newborn periods. However, the contributions of the cerebellum to social-emotional development in typically developing newborns are unclear. To bridge this gap in knowledge, we used multimodal MRI to investigate associations between cerebellar structure and function in 88 healthy neonates (mean ± sd of postmenstrual age, = 42.00 ± 1.91 weeks) and social-emotional development at 18-months assessed using the Infant-Toddler Social-Emotional Assessment (ITSEA) (mean age on ITSEA: 18.32 ± 1.19 months old). We found that cerebellar volume was not associated with ITSEA domain scores at 18 months. We further demonstrated cerebellar functional gradient (FGR) defined using principal component analysis (PCA) was associated with Externalizing domain (linear regression model, false-discovery-rate-adjusted p = 0.013). This cluster (FGR7) included the left dentate, right VI, left Vermis VIIIb, and right V lobules. Finally, we demonstrated that either structural or functional features of the cerebellum reliably predicted scores on the Externalizing and Internalizing domains (correlation between actual and predicted scores: for structural, Fisher's z = 0.48 ± 0.01 for Internalizing, p = 0.01; for functional, Fisher's z = 0.45 ± 0.01 for Externalizing, p = 0.02; with permutation test). Collectively, our findings suggest that the cerebellum plays an important role in social-emotional development during the critical early stages of life.
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Atypical perinatal sensory experience in preterm infants is thought to increase their risk of neurodevelopmental disabilities by altering the development of the sensory cortices. Here, we used resting-state fMRI data from preterm and term-born infants scanned between 32 and 48 weeks post-menstrual age to assess the effect of early ex-utero exposure on sensory cortex development. Specifically, we utilized a measure of local correlated-ness called regional homogeneity (ReHo). First, we demonstrated that the brain-wide distribution of ReHo mirrors the known gradient of cortical maturation. Next, we showed that preterm birth differentially reduces ReHo across the primary sensory cortices. Finally, exploratory analyses showed that the reduction of ReHo in the primary auditory cortex of preterm infants is related to increased risk of autism at 18 months. In sum, we show that local connectivity within sensory cortices has different developmental trajectories, is differentially affected by preterm birth, and may be associated with later neurodevelopment.
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Background: Food insecurity during pregnancy is associated with poorer outcomes for both mothers and their newborns. Given the ongoing opioid crisis in the United States, mothers who take opioids during pregnancy may be at particular risk of experiencing food insecurity. Methods: This research utilized data from 254 biological mothers of infants in the Advancing Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW) Outcomes of Babies with Opioid Exposure (OBOE) Study. We examined factors associated with food insecurity among mothers of infants with antenatal opioid exposure and their unexposed (control) counterparts. Chi-square tests and logistic regression were used to compare food insecurity by sociodemographic characteristics, opioid use, prior traumatic experiences, and housing instability. Similar analyses were conducted to examine the relationship between food insecurity during pregnancy and receipt of adequate prenatal care. Results: Overall, 58 (23%) of the mothers screened positive for food insecurity. Food insecurity was more common among mothers who took opioids during pregnancy (28% vs. 14%; p =0.007), had public insurance (25% vs. 8%; p = 0.027), had housing instability (28% vs. 11%, p = 0.002), experienced three or more adverse experiences in their childhood (37% vs. 17%; p < 0.001), and reported physical or emotional abuse during their pregnancy (44% vs. 17%; p < 0.001). Mothers with food insecurity during pregnancy were less likely to have received adequate prenatal care (78% vs. 90%; p = 0.020). This difference remained after controlling for demographic characteristics (AOR (95% CI) = 0.39 (0.16, 1.00), p = 0.049). Conclusions: This study adds to the body of evidence supporting the need for screening and development of interventions to address food insecurity during pregnancy, particularly among mothers of infants with antenatal opioid exposure, for which limited data are available. The findings revealed that food insecurity frequently co-occurs with housing instability and prior trauma, indicating that a multifaceted intervention incorporating principles of trauma-informed health care is needed. Although those with food insecurity are at increased risk for poor pregnancy outcomes, they were less likely to have received adequate prenatal care despite high levels of public insurance coverage among study participants, suggesting additional strategies are needed to address barriers to health care among this population. Trial registration: The Outcomes of Babies with Opioid Exposure (OBOE) Study is registered at Clinical Trials.gov (NCT04149509) (04/11/2019).
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INTRODUCTION: The Central Autonomic Network (CAN) is a hierarchy of brain structures that collectively influence cardiac autonomic input, mediating the majority of brain-heart interactions, but has never been studied in premature neonates. In this study, we use heart rate variability (HRV), which has been described as the "primary output" of the CAN, and resting state functional MRI to characterize brain-heart relationships in premature neonates. METHODS: We studied premature neonates who underwent resting state functional MRI (rsfMRI) at term, (37-weeks postmenstrual age [PMA] or above) and had HRV data recorded during the same week of their MRI. HRV was derived from continuous electrocardiogram data during the week of the rsfMRI scan. For rsfMRI, a seed-based approach was used to define regions of interest (ROI) pertinent to the CAN, and blood oxygen level-dependent signal was correlated between each ROI as a measure of functional connectivity. HRV was correlated with CAN connectivity (CANconn) for each region, and sub-group analysis was performed based on sex and clinical comorbidities. RESULTS: Forty-seven premature neonates were included in this study, with a mean gestational age at birth of 28.1 +/- 2.6 weeks. Term CANconn was found to be significantly correlated with HRV in approximately one-fifth of CAN connections. Two distinct patterns emerged among these HRV-CANconn relationships. In the first, increased HRV was associated with stronger CANconn of limbic regions. In the second pattern, stronger CANconn at the precuneus was associated with impaired HRV maturation. These patterns were especially pronounced in male premature neonates. CONCLUSION: We report for the first time evidence of brain-heart relationships in premature neonates and an emerging CAN, most striking in male neonates, suggesting that the brain-heart axis may be more vulnerable in male premature neonates. Signatures in the heart rate may eventually become an important non-invasive tool to identify premature males at highest risk for neurodevelopmental impairment.
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Epidemiologic studies suggest that prenatal exposures to certain viruses may influence early neurodevelopment, predisposing offspring to neuropsychiatric conditions later in life. The long-term effects of maternal COVID-19 infection in pregnancy on early brain development, however, remain largely unknown. We prospectively enrolled infants in an observational cohort study for a single-site study in the Washington, DC Metropolitan Area from June 2020 to November 2021 and compared these infants to pre-pandemic controls (studied March 2014-February 2020). The primary outcomes are measures of cortical morphometry (tissue-specific volumes), along with global and regional measures of local gyrification index, and sulcal depth. We studied 210 infants (55 infants of COVID-19 unexposed mothers, 47 infants of COVID-19-positive mothers, and 108 pre-pandemic healthy controls). We found increased cortical gray matter volume (182.45 ± 4.81 vs. 167.29 ± 2.92) and accelerated sulcal depth of the frontal lobe (5.01 ± 0.19 vs. 4.40 ± 0.13) in infants of COVID-19-positive mothers compared to controls. We found additional differences in infants of COVID-19 unexposed mothers, suggesting both maternal viral exposures, as well as non-viral stressors associated with the pandemic, may influence early development and warrant ongoing follow-up.
Subject(s)
COVID-19 , Infant , Infant, Newborn , Female , Pregnancy , Humans , SARS-CoV-2 , Brain/diagnostic imaging , Gray Matter , MothersABSTRACT
In-utero exposure to maternal psychological distress is increasingly linked with disrupted fetal and neonatal brain development and long-term neurobehavioral dysfunction in children and adults. Elevated maternal psychological distress is associated with changes in fetal brain structure and function, including reduced hippocampal and cerebellar volumes, increased cerebral cortical gyrification and sulcal depth, decreased brain metabolites (e.g., choline and creatine levels), and disrupted functional connectivity. After birth, reduced cerebral and cerebellar gray matter volumes, increased cerebral cortical gyrification, altered amygdala and hippocampal volumes, and disturbed brain microstructure and functional connectivity have been reported in the offspring months or even years after exposure to maternal distress during pregnancy. Additionally, adverse child neurodevelopment outcomes such as cognitive, language, learning, memory, social-emotional problems, and neuropsychiatric dysfunction are being increasingly reported after prenatal exposure to maternal distress. The mechanisms by which prenatal maternal psychological distress influences early brain development include but are not limited to impaired placental function, disrupted fetal epigenetic regulation, altered microbiome and inflammation, dysregulated hypothalamic pituitary adrenal axis, altered distribution of the fetal cardiac output to the brain, and disrupted maternal sleep and appetite. This review will appraise the available literature on the brain structural and functional outcomes and neurodevelopmental outcomes in the offspring of pregnant women experiencing elevated psychological distress. In addition, it will also provide an overview of the mechanistic underpinnings of brain development changes in stress response and discuss current treatments for elevated maternal psychological distress, including pharmacotherapy (e.g., selective serotonin reuptake inhibitors) and non-pharmacotherapy (e.g., cognitive-behavior therapy). Finally, it will end with a consideration of future directions in the field.
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Objectives: Brain injury is commonly seen on magnetic resonance imaging in infants with complex congenital heart disease. The impact of perioperative brain injury on neurodevelopmental outcomes is not well understood. We evaluate the association of brain injury and other markers on neurodevelopmental outcomes in patients undergoing surgery for congenital heart surgery during infancy. Methods: Term newborns with infant cardiac surgery performed between 2008 and 2019 at a single tertiary center, and both preoperative and postoperative brain magnetic resonance imaging were included. Those with underlying genetic conditions were excluded. Brain injury was characterized using an magnetic resonance imaging scoring system. Neurodevelopmental outcomes were assigned using the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Independent risk factors for poor neurodevelopmental outcomes were determined by multivariable Cox regression. Results: A total of 122 patients were included. New or progressive postoperative brain injury was noted in 69 patients (57%). A total of 101 patients (83%) had at least 1 neurodevelopmental assessment (median age 36 months) with an early assessment (5-24 months) performed in 95 children. Multivariable Cox regression analysis of early neurodevelopmental outcomes identified new stroke on postoperative magnetic resonance imaging to be an independent predictor of poor neurodevelopmental outcome. Postoperative peak lactate was an independent predictor of poor outcome assessed by the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Conclusions: Our study reveals that evidence of new stroke on magnetic resonance imaging after infant congenital heart surgery is a predictor of poor neurodevelopmental outcomes in early childhood. Postoperative lactic acidosis is associated with poor neurodevelopmental outcome and may be a surrogate biomarker for ischemic brain injury.
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OBJECTIVE: To study the association between neurodevelopmental outcomes and functional brain connectivity (FBC) in healthy term infants. METHODS: This is a retrospective study of prospectively collected High-density electroencephalography (HD-EEG) from newborns within 72 hours from birth. Developmental assessments were performed at two years of age using the Bayley Scales of Infant Development-III (BSID-III) measuring cognitive, language, motor, and socio-emotional scores. The FBC was calculated using phase synchronization analysis of source signals in delta, theta, alpha, beta, and gamma frequency bands and its association with neurodevelopmental score was assessed with stepwise regression. RESULTS: 47/163 had both HD-EEG and BSID-III scores. The FBC of frontal region was associated with cognitive score in the theta band (corrected p, regression coefficients range: p < 0.01, 1.66-1.735). Language scores were significantly associated with connectivity in all frequency bands, predominantly in the left hemisphere (p < 0.01, -2.74-2.40). The FBC of frontal and occipital brain regions of both hemispheres was related to motor score and socio-emotional development in theta, alpha, and gamma frequency bands (p < 0.01, -2.16-2.97). CONCLUSIONS: Functional connectivity of higher-order processing is already present at term age. SIGNIFICANCE: The FBC might be used to guide interventions for optimizing subsequent neurodevelopment even in low-risk newborns.
Subject(s)
Brain , Electroencephalography , Infant , Child , Humans , Infant, Newborn , Retrospective Studies , Brain/diagnostic imaging , EmotionsABSTRACT
This study examined the relationship between perceived stigma in healthcare settings during pregnancy and psychological distress and well-being in the postpartum period among individuals who took opioids while pregnant. Analyses included 134 birth mothers of opioid-exposed infants. At 0-1 months postpartum, perceived stigma and psychological distress were measured using the Prenatal Opioid use Perceived Stigma scale and measures from the Patient-Reported Outcome Measurement Information System (PROMIS). Food insecurity, housing instability, and Adverse Childhood Experiences (ACEs) were also assessed. Linear and generalized linear mixed-effect models were conducted to compare PROMIS scale scores and unmet needs by stigma, adjusting for site/location, age, race/ethnicity, marital status, education, public insurance, and parity. More than half of participants (54%) perceived stigma in healthcare settings. Individuals reporting stigma had higher depression, anxiety, and anger scores (p < 0.001) indicating greater psychological distress in the postpartum period compared to those reporting no stigma, after controlling for demographic characteristics. In addition, they scored significantly lower on the PROMIS meaning and purpose scale, an indicator of well-being (p = 0.002). Those reporting stigma were more likely to have food insecurity (p = 0.003), three or more ACEs (p = 0.040), verbal or physical abuse during pregnancy (p < 0.001), and less emotional support (p = 0.006) than those who did not. An association was observed between perceived stigma in the prenatal period and psychological distress in the postpartum period, providing support for stigma reduction interventions and education for healthcare providers on trauma-informed care.
Subject(s)
Analgesics, Opioid , Psychological Distress , Pregnancy , Infant , Female , Humans , Stress, Psychological/psychology , Postpartum Period/psychology , Delivery of Health CareABSTRACT
BACKGROUND: Infants born very and extremely premature (V/EPT) are at a significantly elevated risk for neurodevelopmental disorders and delays even in the absence of structural brain injuries. These risks may be due to earlier-than-typical exposure to the extrauterine environment, and its bright lights, loud noises, and exposures to painful procedures. Given the relative underdeveloped pain modulatory responses in these infants, frequent pain exposures may confer risk for later deficits. METHODS: Resting-state fMRI scans were collected at term equivalent age from 148 (45% male) infants born V/EPT and 99 infants (56% male) born at term age. Functional connectivity analyses were performed between functional regions correlating connectivity to the number of painful skin break procedures in the NICU, including heel lances, venipunctures, and IV placements. Subsequently, preterm infants returned at 18 months, for neurodevelopmental follow-up and completed assessments for autism risk and general neurodevelopment. RESULTS: We observed that V/EPT infants exhibit pronounced hyperconnectivity within the cerebellum and between the cerebellum and both limbic and paralimbic regions correlating with the number of skin break procedures. Moreover, skin breaks were strongly associated with autism risk, motor, and language scores at 18 months. Subsample analyses revealed that the same cerebellar connections strongly correlating with breaks at term age were associated with language dysfunction at 18 months. CONCLUSIONS: These results have significant implications for the clinical care of preterm infants undergoing painful exposures during routine NICU care, which typically occurs without anesthesia. Repeated pain exposures appear to have an increasingly detrimental effect on brain development during a critical period, and effects continue to be seen even 18 months later.
Subject(s)
Infant, Premature , Neurodevelopmental Disorders , Infant , Infant, Newborn , Humans , Male , Female , Neurodevelopmental Disorders/etiology , Magnetic Resonance Imaging , Cognition , Pain/etiologyABSTRACT
BACKGROUND: During gestation, stressors to the fetus, including viral exposure or maternal psychological distress, can fundamentally alter the neonatal epigenome, and may be associated with long-term impaired developmental outcomes. The impact of in utero exposure to the COVID-19 pandemic on the newborn epigenome has yet to be described. METHODS: This study aimed to determine whether there are unique epigenetic signatures in newborns who experienced otherwise healthy pregnancies that occurred during the COVID-19 pandemic (Project RESCUE). The pre-pandemic control and pandemic cohorts (Project RESCUE) included in this study are part of a prospective observational and longitudinal cohort study that evaluates the impact of elevated prenatal maternal stress during the COVID-19 pandemic on early childhood neurodevelopment. Using buccal swabs collected at birth, differential DNA methylation analysis was performed using the Infinium MethylationEPIC arrays and linear regression analysis. Pathway analysis and gene ontology enrichment were performed on resultant gene lists. RESULTS: Widespread differential methylation was found between neonates exposed in utero to the pandemic and pre-pandemic neonates. In contrast, there were no apparent epigenetic differences associated with maternal COVID-19 infection during pregnancy. Differential methylation was observed among genomic sites that underpin important neurological pathways that have been previously reported in the literature to be differentially methylated because of prenatal stress, such as NR3C1. CONCLUSIONS: The present study reveals potential associations between exposure to the COVID-19 pandemic during pregnancy and subsequent changes in the newborn epigenome. While this finding warrants further investigation, it is a point that should be considered in any study assessing newborn DNA methylation studies obtained during this period, even in otherwise healthy pregnancies.
Subject(s)
COVID-19 , Prenatal Exposure Delayed Effects , Female , Humans , Infant, Newborn , Pregnancy , COVID-19/genetics , COVID-19/metabolism , DNA Methylation , Epigenesis, Genetic , Fetal Blood/metabolism , Genome-Wide Association Study , Longitudinal Studies , Maternal Exposure , Pandemics , Prenatal Exposure Delayed Effects/genetics , Prenatal Exposure Delayed Effects/metabolismABSTRACT
BACKGROUND: Congenital heart disease (CHD) remains a significant risk factor for neurologic injury because altered fetal hemodynamics may be unable to support typical brain development during critical periods of growth and maturation. OBJECTIVES: The primary objective was to assess differences in the cerebral biochemical profile between healthy fetuses and fetuses with complex CHD and to relate these with infant outcomes. METHODS: Pregnant participants underwent fetal magnetic resonance imaging with cerebral proton magnetic resonance spectroscopy acquisitions as part of a prospective observational study. Cerebral metabolites of N-acetyl aspartate, creatine, choline, myo-inositol, scyllo-inositol, lactate, and relevant ratios were quantified using LCModel. RESULTS: We acquired 503 proton magnetic resonance spectroscopy images (controls = 333; CHD = 170) from 333 participants (controls = 221; CHD = 112). Mean choline levels were higher in CHD compared with controls (CHD 2.47 IU [Institutional Units] ± 0.44 and Controls 2.35 IU ± 0.45; P = 0.02), whereas N-acetyl aspartate:choline ratios were lower among CHD fetuses compared with controls (CHD 1.34 ± 0.40 IU vs controls 1.44 ± 0.48 IU; P = 0.001). Cerebral lactate was detected in all cohorts but increased in fetuses with transposition of the great arteries and single-ventricle CHD (median: 1.63 [IQR: 0.56-3.27] in transposition of the great arteries and median: 1.28 [IQR: 0-2.42] in single-ventricle CHD) compared with 2-ventricle CHD (median: 0.79 [IQR: 0-1.45]). Cerebral lactate also was associated with increased odds of death before discharge (OR: 1.75; P = 0.04). CONCLUSIONS: CHD is associated with altered cerebral metabolites in utero, particularly in the third trimester period of pregnancy, which is characterized by exponential brain growth and maturation, and is associated with survival to hospital discharge. The long-term neurodevelopmental consequences of these findings warrant further study.
Subject(s)
Heart Defects, Congenital , Transposition of Great Vessels , Pregnancy , Infant , Female , Humans , Transposition of Great Vessels/diagnostic imaging , Magnetic Resonance Spectroscopy/methods , Magnetic Resonance Imaging/methods , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/complications , Fetus/metabolism , Brain/diagnostic imaging , Brain/metabolism , Lactic Acid/metabolism , Choline/metabolismABSTRACT
BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with cognitive-behavioral deficits in very preterm (VPT) infants, often in the absence of structural brain injury. Advanced GABA-editing techniques like Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) can quantify in-vivo gamma-aminobutyric acid (GABA+, with macromolecules) and glutamate (Glx, with glutamine) concentrations to investigate for neurophysiologic perturbations in the developing brain of VPT infants. OBJECTIVE: To investigate the relationship between the severity of BPD and basal-ganglia GABA+ and Glx concentrations in VPT infants. METHODS: MRI studies were performed on a 3 T scanner in a cohort of VPT infants [born ≤32 weeks gestational age (GA)] without major structural brain injury and healthy-term infants (>37 weeks GA) at term-equivalent age. MEGA-PRESS (TE68ms, TR2000ms, 256averages) sequence was acquired from the right basal-ganglia voxel (â¼3cm3) and metabolite concentrations were quantified in institutional units (i.u.). We stratified VPT infants into no/mild (grade 0/1) and moderate-severe (grade 2/3) BPD. RESULTS: Reliable MEGA-PRESS data was available from 63 subjects: 29 healthy-term and 34 VPT infants without major structural brain injury. VPT infants with moderate-severe BPD (n = 20) had the lowest right basal-ganglia GABA+ (median 1.88 vs. 2.28 vs. 2.12 i.u., p = 0.025) and GABA+/choline (0.73 vs. 0.99 vs. 0.88, p = 0.004) in comparison to infants with no/mild BPD and healthy-term infants. The GABA+/Glx ratio was lower (0.34 vs. 0.44, p = 0.034) in VPT infants with moderate-severe BPD than in infants with no/mild BPD. CONCLUSIONS: Reduced GABA+ and GABA+/Glx in VPT infants with moderate-severe BPD indicate neurophysiologic perturbations which could serve as early biomarkers of future cognitive deficits.