Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.

BACKGROUND: Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS: We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS: Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).

Developmental characteristics and accuracy of autism screening among two-year-old toddlers in the ECHO program.

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

Combining developmental and sleep health measures for autism spectrum disorder screening: an ECHO study.

BACKGROUND: Sleep problems are reported for up to 80% of autistic individuals. We examined whether parsimonious sets of items derived from the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) and the Brief Infant Sleep Questionnaire (BISQ) are superior to the standard M-CHAT-R in predicting subsequent autism spectrum disorder (ASD) diagnoses. METHODS: Participants from 11 Environmental influences on Child Health Outcomes (ECHO) cohorts were included. We performed logistic LASSO regression models with 10-fold cross-validation to identify whether a combination of items derived from the M-CHAT-R and BISQ are superior to the standard M-CHAT-R in predicting ASD diagnoses. RESULTS: The final sample comprised 1552 children. The standard M-CHAT-R had a sensitivity of 44% (95% CI: 34, 55), specificity of 92% (95% CI: 91, 94), and AUROC of 0.726 (95% CI: 0.663, 0.790). A higher proportion of children with ASD had difficulty falling asleep or resisted bedtime during infancy/toddlerhood. However, LASSO models revealed parental reports of sleep problems did not improve the accuracy of the M-CHAT-R in predicting ASD diagnosis. CONCLUSION: While children with ASD had higher rates of sleep problems during infancy/toddlerhood, there was no improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. IMPACT: Parental-reported sleep problems are common in autism spectrum disorder (ASD). We investigated whether the inclusion of parental-reports of infant/toddler sleep patterns enhanced the effectiveness of developmental screening for autism. We reported higher rates of difficulty falling asleep and resisting bedtime during infancy and toddlerhood among children later diagnosed with ASD; however, we did not find an improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. In our sample, the standard M-CHAT-R had a sensitivity of 39% among children of mothers with government insurance compared with a sensitivity of 53% among children of mothers with employer-based insurance.

Pre-pregnancy overweight or obesity moderates the association between prenatal maternal depressive symptoms and infant cord blood omega-3 levels.

BACKGROUND: Empirical evidence has demonstrated associations between pre-pregnancy obesity and perinatal maternal depressive symptoms. Omega-3 is an essential fatty acid derived from dietary sources that is critical for fetal brain development. Pre-pregnancy obesity is associated with higher omega-3 intake, but a weaker association between dietary intake and respective maternal and cord blood omega-3 levels. Further, lower intake of omega-3 during pregnancy has been linked to higher depressive symptoms. Yet, prior studies have not examined the interactive effects of pre-pregnancy overweight or obesity (OWOB) and prenatal maternal mental health symptoms on infant cord blood omega-3 levels. METHODS: Participants included 394 maternal-infant dyads from the NIH Environmental influences on Child Health Outcomes (ECHO) - Safe Passage Study in South Dakota. A pre-pregnancy body mass index (BMI) > 25 was used to dichotomize participants as OWOB (54%) vs. non-OWOB (46%). Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) and prenatal maternal anxiety symptoms were measured using the State-Trait Anxiety Inventory (STAI). We implemented linear regression models to examine the interaction term between pre-pregnancy BMI category and prenatal maternal mental health symptoms on cord blood omega-3 levels. Secondary analyses were stratified by pre-pregnancy BMI category. RESULTS: We observed a significant interaction between pre-pregnancy BMI category and prenatal maternal depressive symptoms with cord blood omega-3 (F(4,379) = 6.21, p < .0001, adj. R2 = 0.05). Stratified models revealed an association between prenatal maternal depressive symptoms with lower cord blood omega-3 levels only among individuals with pre-pregnancy OWOB (ß = -0.06, 95% CI = -0.11, -0.02; F (2,208) = 4.00, p < .05, adj R2 = 0.03). No associations were observed among non-OWOB participants. CONCLUSIONS: Findings suggest maternal-placental transfer of omega-3 may represent one pathway by which maternal metabolic and mental health impacts infant development.

Electrophysiological correlates of inhibitory control in children: Relations with prenatal maternal risk factors and child psychopathology.

Inhibitory control plays an important role in children's cognitive and socioemotional development, including their psychopathology. It has been established that contextual factors such as socioeconomic status (SES) and parents' psychopathology are associated with children's inhibitory control. However, the relations between the neural correlates of inhibitory control and contextual factors have been rarely examined in longitudinal studies. In the present study, we used both event-related potential (ERP) components and time-frequency measures of inhibitory control to evaluate the neural pathways between contextual factors, including prenatal SES and maternal psychopathology, and children's behavioral and emotional problems in a large sample of children (N = 560; 51.75% females; Mage = 7.13 years; Rangeage = 4-11 years). Results showed that theta power, which was positively predicted by prenatal SES and was negatively related to children's externalizing problems, mediated the longitudinal and negative relation between them. ERP amplitudes and latencies did not mediate the longitudinal association between prenatal risk factors (i.e., prenatal SES and maternal psychopathology) and children's internalizing and externalizing problems. Our findings increase our understanding of the neural pathways linking early risk factors to children's psychopathology.

Prenatal risk factors for child executive function at 3-5 years of age: the roles of maternal mood, substance use, and socioeconomic adversity in a prospective cohort study.

BACKGROUND: A growing body of literature links prenatal mood and substance use to children's cognitive and behavioral development. The relative contribution of these risk factors on children's executive function (EF) in the context of socioeconomic adversities needs further evaluation. To address this gap, we investigated the role of prenatal maternal anxiety and depression on childhood EF, specifically inhibitory control and working memory, within the context of socioeconomic adversities and prenatal substance use. We hypothesized that higher maternal mood symptoms, higher persistent prenatal drinking and smoking, and lower socioeconomic status would be associated with lower EF skills during early childhood. METHODS: We used data from 334 mother-child dyads followed prospectively through pregnancy and the offspring's childhood. Prenatal maternal depression and anxiety were assessed via standardized questionnaires. Prenatal alcohol and tobacco consumption were assessed via a timeline follow-back interview. The EF touch battery assessed child inhibitory control and working memory at 3-5 years of age (4.76 ± 0.58 years, 171 females). Separate linear regression models were used to estimate the association of prenatal tobacco, alcohol, anxiety, and depression exposure with our two components of child EF, inhibitory control and working memory, while adjusting for gestational age, sex, and age at assessment. The following variables were also included as covariates: maternal educational achievement, employment status, parity, and household crowding index. RESULTS: Children of mothers with high trait anxiety scores had reduced inhibitory control compared to children of mothers without trait anxiety or depression (ß = -0.12, 95% CI:-0.22,-0.01). Children of mothers in the moderate to high continuous smoking group showed lower inhibitory control (ß = - 0.19, 95% CI:-0.38,-0.01) compared to children of mothers in the none smoking group. Additionally, lower maternal education and higher household crowding were each associated with reduced inhibitory control. We found no significant association between prenatal maternal depression, anxiety, or socioeconomic factors with working memory. CONCLUSIONS: These results underscore the need for comprehensive context-specific intervention packages, including mental health support for women to promote healthy inhibitory control development in children.

Measuring Socioeconomic and Stress Disparities in Infant Declarative Memory Using the Visual Paired Comparison Task.

Research suggests that socioeconomic circumstances and stress predict memory skills in adults and older children, yet few studies have addressed this question in infancy. The current study used the visual-paired comparison paradigm to examine whether socioeconomic circumstances, maternal perceived stress, and/or maternal physiological stress, all measured prenatally, predict memory performance among 6-month-old infants. We found no significant associations between infant memory and any measure of socioeconomic circumstance or stress. Potential explanations for these null findings are discussed.

Examining the impact of prenatal maternal internalizing symptoms and socioeconomic status on children's frontal alpha asymmetry and psychopathology.

Prenatal maternal internalizing psychopathology (depression and anxiety) and socioeconomic status (SES) have been independently associated with higher risk for internalizing and externalizing problems in children. However, the pathways behind these associations are not well understood. Numerous studies have linked greater right frontal alpha asymmetry to internalizing problems; however, findings have been mixed. Several studies have also linked maternal internalizing psychopathology to children's frontal alpha asymmetry. Additionally, emerging studies have linked SES to children's frontal alpha asymmetry. To date, only a limited number of studies have examined these associations within a longitudinal design, and the majority have utilized relatively small samples. The current preregistered study utilizes data from a large prospective study of young children (N = 415; Meanage  = 7.27 years; Rangeage  = 5-11 years) to examine the association between prenatal maternal internalizing symptoms, children's frontal alpha asymmetry, and behavior problems. Prenatal maternal internalizing symptoms did not predict children's frontal alpha asymmetry, and there was no association between frontal alpha asymmetry and behavior problems. However, mothers' internalizing symptoms during pregnancy predicted children's internalizing and externalizing outcomes. Non-preregistered analyses showed that lower prenatal maternal SES predicted greater child right frontal alpha asymmetry and internalizing problems. Additional non-preregistered analyses did not find evidence for frontal alpha asymmetry as a moderator of the relation between prenatal maternal internalizing psychopathology and SES to children's behavior problems. Future research should examine the impact of SES on children's frontal alpha asymmetry in high-risk samples.

Age-related trends in aperiodic EEG activity and alpha oscillations during early- to middle-childhood.

Age-related structural and functional changes that occur during brain development are critical for cortical development and functioning. Previous electroencephalography (EEG) and magnetoencephalography (MEG) studies have highlighted the utility of power spectra analyses and have uncovered age-related trends that reflect perceptual, cognitive, and behavioural states as well as their underlying neurophysiology. The aim of the current study was to investigate age-related change in aperiodic and periodic alpha activity across a large sample of pre- and school-aged children (N = 502, age range 4 -11-years-of-age). Power spectra were extracted from baseline EEG recordings (eyes closed, eyes open) for each participant and parameterized into aperiodic activity to derive the offset and exponent parameters and periodic alpha oscillatory activity to derive the alpha peak frequency and the associated power estimates. Multilevel models were run to investigate age-related trends and condition-dependent changes for each of these measures. We found quadratic age-related effects for both the aperiodic offset and exponent. In addition, we observed increases in periodic alpha peak frequency as a function of age. Aperiodic measures and periodic alpha power were larger in magnitude during eyes closed compared to the eyes open baseline condition. Taken together, these results advance our understanding of the maturational patterns/trajectories of brain development during early- to middle-childhood.

Prenatal smoking and drinking are associated with altered newborn autonomic functions.

BACKGROUND: Prenatal smoking and drinking are associated with sudden infant death syndrome and neurodevelopmental disorders. Infants with these outcomes also have altered autonomic nervous system (ANS) regulation. We examined the effects of prenatal smoking and drinking on newborn ANS function. METHODS: Pregnant women were enrolled in Northern Plains, USA (NP) and Cape Town (CT), South Africa. Daily drinking and weekly smoking data were collected prenatally. Physiological measures were obtained during sleep 12-96 h post-delivery. RESULTS: In all, 2913 infants from NP and 4072 from CT were included. In active sleep, newborns of mothers who smoked throughout pregnancy, compared to non-smokers, had higher breathing rates (2.2 breaths/min; 95% CI: 0.95, 3.49). Quit-early smoking was associated with reductions in beat-to-beat heart rate variability (HRV) in active (-0.08 s) and quiet sleep (-0.11 s) in CT. In girls, moderate-high continuous smoking was associated with increased systolic (3.0 mmHg, CI: 0.70, 5.24) and diastolic blood pressure (2.9 mmHg, CI: 0.72, 5.02). In quiet sleep, low-continuous drinking was associated with slower heart rate (-4.5 beat/min). In boys, low-continuous drinking was associated with a reduced ratio of low-to-high frequency HRV (-0.11, CI: -0.21, -0.02). CONCLUSIONS: These findings highlight potential ANS pathways through which prenatal drinking and smoking may contribute to neurodevelopment outcomes. IMPACT: In this prospective cohort study of 6985 mother-infant dyads prenatal drinking and smoking were associated with multiple ANS parameters. Smoking was associated with increased neonatal breathing rates among all infants, and heart rate variability (HRV) and blood pressure (BP) among girls. Drinking was associated with reductions in HR and BP among all newborns, and reductions in the ratio of low to-high frequency HRV among boys. These findings suggest that prenatal smoking and drinking alter newborn ANS which may presage future neurodevelopmental disorders.

Pandemic beyond the virus: maternal COVID-related postnatal stress is associated with infant temperament.

BACKGROUND: Studies have shown that infant temperament varies with maternal psychosocial factors, in utero illness, and environmental stressors. We predicted that the pandemic would shape infant temperament through maternal SARS-CoV-2 infection during pregnancy and/or maternal postnatal stress. To test this, we examined associations among infant temperament, maternal prenatal SARS-CoV-2 infection, maternal postnatal stress, and postnatal COVID-related life disruptions. METHODS: We tested 63 mother-infant dyads with prenatal maternal SARS-CoV-2 infections and a comparable group of 110 dyads without infections. To assess postnatal maternal stress, mothers completed the Perceived Stress Scale 4 months postpartum and an evaluation of COVID-related stress and life disruptions 6 months postpartum. Mothers reported on infant temperament when infants were 6-months-old using the Infant Behavior Questionnaire-Revised (IBQ-R) Very Short Form. RESULTS: Maternal SARS-CoV-2 infection during pregnancy was not associated with infant temperament or maternal postnatal stress. Mothers with higher self-reported postnatal stress rated their infants lower on the Positive Affectivity/Surgency and Orienting/Regulation IBQ-R subscales. Mothers who reported greater COVID-related life disruptions rated their infants higher on the Negative Emotionality IBQ-R subscale. CONCLUSIONS: Despite no effect of prenatal maternal SARS-CoV-2 infection, stress and life disruptions incurred by the COVID-19 pandemic were associated with infant temperament at 6-months. IMPACT: SARS-CoV-2 infection during pregnancy is not associated with postnatal ratings of COVID-related life disruptions, maternal stress, or infant temperament. Postnatal ratings of maternal stress during the COVID-19 pandemic are associated with normative variation in maternal report of infant temperament at 6 months of age. Higher postnatal ratings of maternal stress are associated with lower scores on infant Positive Affectivity/Surgency and Orienting/Regulation at 6 months of age. Higher postnatal ratings of COVID-related life disruptions are associated with higher scores on infant Negative Emotionality at 6 months of age.

Longitudinal characterization of EEG power spectra during eyes open and eyes closed conditions in children.

This study is the first to examine spectrum-wide (1 to 250 Hz) differences in electroencephalogram (EEG) power between eyes open (EO) and eyes closed (EC) resting state conditions in 486 children. The results extend the findings of previous studies by characterizing EEG power differences from 30 to 250 Hz between EO and EC across childhood. Developmental changes in EEG power showed spatial and frequency band differences as a function of age and EO/EC condition. A 64-electrode system was used to record EEG at 4, 5, 7, 9, and 11 years of age. Specific findings were: (1) the alpha peak shifts from 8 Hz at 4 years to 9 Hz at 11 years, (2) EC results in increased EEG power (compared to EO) at lower frequencies but decreased EEG power at higher frequencies for all ages, (3) the EEG power difference between EO and EC changes from positive to negative within a narrow frequency band which shifts toward higher frequencies with age, from 9 to 12 Hz at 4 years to 32 Hz at 11 years, (4) at all ages EC is characterized by an increase in lower frequency EEG power most prominently over posterior regions, (5) at all ages, during EC, decreases in EEG power above 30 Hz are mostly over anterior regions of the scalp. This report demonstrates that the simple challenge of opening and closing the eyes offers the potential to provide quantitative biomarkers of phenotypic variation in brain maturation by employing a brief, minimally invasive protocol throughout childhood.

Association of Gestational Diabetes Mellitus and Perinatal Maternal Depression with Early Childhood Behavioral Problems: An Environmental Influences on Child Health Outcomes (ECHO) Study.

This study examined the association of gestational diabetes mellitus (GDM), prenatal, and postnatal maternal depressive symptoms with externalizing, internalizing, and autism spectrum problems on the Preschool Child Behavior Checklist in 2379 children aged 4.12 ± 0.60 (48% female; 47% White, 32% Black, 15% Mixed Race, 4% Asian, <2% American Indian/Alaskan Native, <2% Native Hawaiian; 23% Hispanic). Data were collected from the NIH Environmental influences on Child Health Outcomes (ECHO) Program from 2009-2021. GDM, prenatal, and postnatal maternal depressive symptoms were each associated with increased child externalizing and internalizing problems. GDM was associated with increased autism behaviors only among children exposed to perinatal maternal depressive symptoms above the median level. Stratified analyses revealed a relation between GDM and child outcomes in males only.

The immune phenotype of perinatal anxiety.

BACKGROUND: Immune dysregulation has been linked to both psychiatric illness and pregnancy morbidity, including perinatal depression, but little is known about the immune phenotype of perinatal anxiety. Here, we sought to identify the unique immune profile of antenatal anxiety. MATERIALS AND METHODS: Pregnant women (n = 107) were followed prospectively at 2nd and 3rd trimesters (T2, T3) and 6 weeks postpartum (PP6). Each visit included a blood draw and psychological evaluation, with clinical anxiety assessed using the Spielberg State-Trait Anxiety Scale. We enrolled both healthy controls and participants with anxiety alone; those with comorbid depression were excluded. Multiplex cytokine assays and flow cytometry were used to examine the association of anxiety symptoms with secreted immune markers and PBMC-derived immune cells. RESULTS: K cluster means revealed three clusters of anxiety symptomatology; due to low numbers in the highest severity anxiety group, these were collapsed into two groups: Non-Anxiety and Anxiety. Principal components analysis revealed two distinct clusters of cytokine secretion including one cluster that consisted of many innate immune cytokines and differed between groups. Compared to women in the Non-Anxiety group, women in the Anxiety group had lower levels of cytokine expression during pregnancy and an increase in levels into the postpartum, whereas Non-Anxiety women experienced a time-dependent decline. Immune cell populations also differed between our two groups, with the Anxiety group showing a decrease in the ratio of B cells to T cells from pregnancy to postpartum, whereas the Non-Anxiety women showed an increase in this ratio over time. Women in the Anxiety group also demonstrated an increased ratio of cytotoxic to helper T cells throughout pregnancy, a modest increase in the Th1:Th2 ratio across pregnancy, and a lower ratio of Th17:TREG cells in the postpartum as compared with Non-Anxiety women. CONCLUSION: These data suggest that the immune response throughout the antenatal period differs for women with anxiety symptoms compared to those without, suggestive of a unique immune phenotype of perinatal anxiety.

Gestational diabetes mellitus, prenatal maternal depression, and risk for postpartum depression: an Environmental influences on Child Health Outcomes (ECHO) Study.

BACKGROUND: Prior research has demonstrated bidirectional associations between gestational diabetes mellitus (GDM) and perinatal maternal depression. However, the association between GDM, prenatal depression, and postpartum depression (PPD) has not been examined in a prospective cohort longitudinally. METHODS: Participants in the current analysis included 5,822 women from the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Research Program: N = 4,606 with Neither GDM nor Prenatal Maternal Depression (Reference Category); N = 416 with GDM only; N = 689 with Prenatal Maternal Depression only; and N = 111 with Comorbid GDM and Prenatal Maternal Depression. The PROMIS-D scale was used to measure prenatal and postnatal maternal depressive symptoms. Primary analyses consisted of linear regression models to estimate the independent and joint effects of GDM and prenatal maternal depression on maternal postpartum depressive symptoms. RESULTS: A higher proportion of women with GDM were classified as having prenatal depression (N = 111; 21%) compared to the proportion of women without GDM who were classified as having prenatal depression (N = 689; 13%), however this finding was not significant after adjustment for covariates. Women with Comorbid GDM and Prenatal Maternal Depression had significantly increased postpartum depressive symptoms measured by PROMIS-D T-scores compared to women with Neither GDM nor Prenatal Maternal Depression (mean difference 7.02, 95% CI 5.00, 9.05). Comorbid GDM and Prenatal Maternal Depression was associated with an increased likelihood of PPD (OR 7.38, 95% CI 4.05, 12.94). However, women with GDM only did not have increased postpartum PROMIS-D T-scores or increased rates of PPD. CONCLUSIONS: Our findings underscore the importance of universal depression screening during pregnancy and in the first postpartum year. Due to the joint association of GDM and prenatal maternal depression on risk of PPD, future studies should examine potential mechanisms underlying this relation.

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.

Aperiodic electrophysiological activity in preterm infants is linked to subsequent autism risk.

Approximately 7% of preterm infants receive an autism spectrum disorder (ASD) diagnosis. Yet, there is a significant gap in the literature in identifying prospective markers of neurodevelopmental risk in preterm infants. The present study examined two electroencephalography (EEG) parameters during infancy, absolute EEG power and aperiodic activity of the power spectral density (PSD) slope, in association with subsequent autism risk and cognitive ability in a diverse cohort of children born preterm in South Africa. Participants were 71 preterm infants born between 25 and 36 weeks gestation (34.60 ± 2.34 weeks). EEG was collected during sleep between 39 and 41 weeks postmenstrual age adjusted (40.00 ± 0.42 weeks). The Bayley Scales of Infant Development and Brief Infant Toddler Social Emotional Assessment (BITSEA) were administered at approximately 3 years of age adjusted (34 ± 2.7 months). Aperiodic activity, but not the rhythmic oscillatory activity, at multiple electrode sites was associated with subsequent increased autism risk on the BITSEA at three years of age. No associations were found between the PSD slope or absolute EEG power and cognitive development. Our findings highlight the need to examine potential markers of subsequent autism risk in high-risk populations other than infants at familial risk.

Prenatal Exposure to Tobacco and Alcohol Alters Development of the Neonatal Auditory System.

Prenatal exposures to alcohol (PAE) and tobacco (PTE) are known to produce adverse neonatal and childhood outcomes including damage to the developing auditory system. Knowledge of the timing, extent, and combinations of these exposures on effects on the developing system is limited. As part of the physiological measurements from the Safe Passage Study, Auditory Brainstem Responses (ABRs) and Transient Otoacoustic Emissions (TEOAEs) were acquired on infants at birth and one-month of age. Research sites were in South Africa and the Northern Plains of the U.S. Prenatal information on alcohol and tobacco exposure was gathered prospectively on mother/infant dyads. Cluster analysis was used to characterize three levels of PAE and three levels of PTE. Repeated-measures ANOVAs were conducted for newborn and one-month-old infants for ABR peak latencies and amplitudes and TEOAE levels and signal-to-noise ratios. Analyses controlled for hours of life at test, gestational age at birth, sex, site, and other exposure. Significant main effects of PTE included reduced newborn ABR latencies from both ears. PTE also resulted in a significant reduction of ABR peak amplitudes elicited in infants at 1-month of age. PAE led to a reduction of TEOAE amplitude for 1-month-old infants but only in the left ear. Results indicate that PAE and PTE lead to early disruption of peripheral, brainstem, and cortical development and neuronal pathways of the auditory system, including the olivocochlear pathway.

Neonatal EEG linked to individual differences in socioemotional outcomes and autism risk in toddlers.

Research using electroencephalography (EEG) as a measure of brain function and maturation has demonstrated links between cortical activity and cognitive processes during infancy and early childhood. The current study examines whether neonatal EEG is correlated with later atypical socioemotional behaviors or neurocognitive delays. Parental report developmental assessments were administered to families with children ages 24 to 36 months who had previously participated in a neonatal EEG study (N = 129). Significant associations were found between neonatal EEG (higher frequencies in the frontal polar, temporal, and parietal brain regions) and BITSEA ASD risk scores. Infants with lower EEG power in these brain areas were more likely to have higher risk of socioemotional problems. When examining sex differences, significant links were found for males but not for females. These results demonstrate some promising associations between early neural biomarkers and later risk for atypical behaviors, which may shape early neurobehavioral development and could lead to earlier identification and intervention.

In Utero Exposure to Alcohol and Tobacco and Electroencephalogram Power During Childhood.

Importance: Prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) are risk factors associated with adverse neurobehavioral and cognitive outcomes. Objective: To quantify long-term associations of PAE and PTE with brain activity in early and middle childhood via electroencephalography (EEG). Design, Setting, and Participants: This cohort study included participants enrolled in the Safe Passage Study (August 2007 to January 2015), from which a subset of 649 participants were followed up in the Environmental Influences on Child Health Outcomes Program. From September 2018 through November 2022, EEG recordings were obtained at ages 4, 5, 7, 9, or 11 years. Data were analyzed from November 2022 to November 2023. Exposures: Maternal self-reported consumptions of alcohol and tobacco during pregnancy were captured at the recruitment interview and at up to 3 visits during pregnancy (20-24, 28-32, and ≥34 weeks' gestation). Classifications of PAE (continuous drinking, quit-early drinking, and nondrinking) and PTE (continuous smoking, quit-early smoking, and nonsmoking) were previously obtained. Main Outcomes and Measures: EEG band powers (theta, alpha, beta, gamma) were extracted from the EEG recordings. Linear regression models were used to estimate the associations of PAE and PTE with EEG estimates. Results: The final sample included 649 participants (333 [51.3%] female) aged 4, 5, 7, 9, or 11 years. Children whose mothers were in the quit-early drinking cluster had increased alpha power (0.116 [95% CI, 0.023 to 0.209] µV2; P = .02) compared with individuals without PAE. The magnitude of this increase was approximately double for children exposed to continuous drinking (0.211 [95% CI, 0.005 to 0.417] µV2; P = .04). Children whose mothers were in the continuous smoking cluster had decreased beta power (-0.031 [95% CI, -0.059 to -0.003] µV2; P = .03) and gamma power (-0.020 [95% CI, -0.039 to -0.000] µV2; P = .04) compared with the nonsmoking cluster. In exploratory sex-stratified models, male participants in the quit-early PAE cluster had greater EEG power in the alpha band (0.159 [95% CI, 0.003 to 0.315] µV2; P = .04) compared with those with no PAE, and the difference was approximately double for male participants with continuous PAE (0.354 [95% CI, 0.041 to 0.667] µV2; P = .03). Male participants in the continuous PTE cluster had decreased beta (-0.048 [95% CI, -0.090 to - 0.007] µV2; P = .02) and gamma (-0.032 [95% CI, -0.061 - 0.002] µV2; P = .04) power compared with those with no PTE. Conclusions and Relevance: These findings suggest that even low levels of PAE and PTE were associated with long-term alterations of brain activity.