A comprehensive wireless neurological and cardiopulmonary monitoring platform for pediatrics.

Neurodevelopment in the first 10 years of life is a critical time window during which milestones that define an individual's functional potential are achieved. Comprehensive multimodal neurodevelopmental monitoring is particularly crucial for socioeconomically disadvantaged, marginalized, historically underserved and underrepresented communities as well as medically underserved areas. Solutions designed for use outside the traditional clinical environment represent an opportunity for addressing such health inequalities. In this work, we present an experimental platform, ANNE EEG, which adds 16-channel cerebral activity monitoring to the existing, USA FDA-cleared ANNE wireless monitoring platform which provides continuous electrocardiography, respiratory rate, pulse oximetry, motion, and temperature measurements. The system features low-cost consumables, real-time control and streaming with widely available mobile devices, and fully wearable operation to allow a child to remain in their naturalistic environment. This multi-center pilot study successfully collected ANNE EEG recordings from 91 neonatal and pediatric patients at academic quaternary pediatric care centers and in LMIC settings. We demonstrate the practicality and feasibility to conduct electroencephalography studies with high levels of accuracy, validated via both quantitative and qualitative metrics, compared against gold standard systems. An overwhelming majority of parents surveyed during studies indicated not only an overall preference for the wireless system, but also that its use would improve their children's physical and emotional health. Our findings demonstrate the potential for the ANNE system to perform multimodal monitoring to screen for a variety of neurologic diseases that have the potential to negatively impact neurodevelopment.

Mapping the link between socio-economic factors, autistic traits and mental health across different settings.

LAY ABSTRACT: Autistic individuals are more likely than non-autistic individuals to experience a mental health condition in their lifetime, and this includes externalising and internalising symptoms. We know very little about how different environments and family conditions impact these symptoms for autistic individuals. Improving our understanding of these relationships is important so that we can identify individuals who may be in greater need of support. In this article, we seek to improve our understanding of how environmental and family conditions impact externalising and internalising symptoms in autistic and non-autistic people. To do this, we conducted analyses with two cohorts in very different settings - in Europe and South Africa - to ensure our findings are globally representative. We used advanced statistical methods to establish environmental and family conditions that were similar to each other, and which could be combined into specific 'factors'. We found that four similar 'factors' could be identified in the two cohorts. These were distinguished by personal characteristics and environmental conditions of individuals, and were named Person Characteristics, Family System, Parental and Material Resources. Interestingly, just 'Family System' was associated with internalising and externalising symptoms, and this was the same in both cohorts. We also found that having high traits of autism impacted this relationship between Family System and mental health conditions with opposite directions in the two settings. These results show that characteristics in the Family System are associated with internalising and externalising symptoms, and autistic persons are particularly impacted, reinforcing the notion that family stressors are important to consider when implementing policy and practice related to improving the mental health of autistic people.

Association of maternal depression and anxiety with toddler social-emotional and cognitive development in South Africa: a prospective cohort study.

OBJECTIVE: A robust literature has identified associations between prenatal maternal depression and adverse child social-emotional and cognitive outcomes. The majority of prior research is from high-income countries despite increased reporting of perinatal depression in low/middle-income countries (LMICs). Additionally, despite the comorbidity between depression and anxiety, few prior studies have examined their joint impact on child neurodevelopment. The objective of the current analysis was to examine associations between prenatal maternal depression and anxiety with child social-emotional and cognitive development in a cohort from the Western Cape Province of South Africa. DESIGN: Prenatal maternal depression and anxiety were measured using the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory Scale at 20-24 weeks' gestation. Child neurobehaviour was assessed at age 3 using the Brief Infant-Toddler Social Emotional Assessment and the Bayley Scales of Infant Development III Screening Test (BSID-III ST). We used linear regression models to examine the independent and joint association between prenatal maternal depression, anxiety and child developmental outcomes. RESULTS: Participants consisted of 600 maternal-infant dyads (274 females; gestational age at birth: 38.89 weeks±2.03). Children born to mothers with both prenatal depression and trait anxiety had higher social-emotional problems (mean difference: 4.66; 95% CI 3.43 to 5.90) compared with children born to mothers with no prenatal depression or trait anxiety, each condition alone, or compared with mothers with depression and state anxiety. Additionally, children born to mothers with prenatal maternal depression and trait anxiety had the greatest reduction in mean cognitive scores on the BSID-III ST (mean difference: -1.04; 95% CI -1.99 to -0.08). CONCLUSIONS: The observed association between comorbid prenatal maternal depression and chronic anxiety with subsequent child social-emotional and cognitive development underscores the need for targeting mental health support among perinatal women in LMICs to improve long-term child neurobehavioural outcomes.

Associations of adverse maternal experiences and diabetes on postnatal maternal depression and child social-emotional outcomes in a South African community cohort.

Previous literature has identified associations between diabetes during pregnancy and postnatal maternal depression. Both maternal conditions are associated with adverse consequences on childhood development. Despite an especially high prevalence of diabetes during pregnancy and maternal postnatal depression in low- and middle-income countries, related research predominates in high-income countries. In a South African cohort with or without diabetes, we investigated associations between adverse maternal experiences with postnatal maternal depression and child social-emotional outcomes. South African mother-child dyads were recruited from the Bishop Lavis community in Cape Town. Participants consisted of 82 mother-child dyads (53 women had GDM or type 2 diabetes). At 14-20 months postpartum, maternal self-report questionnaires were administered to assess household socioeconomic status, food insecurity, maternal depressive symptoms (Edinburgh Postnatal Depression Scale (EPDS)), maternal trauma (Life Events Checklist), and child social-emotional development (Brief Infant Toddler Social Emotional Assessment, Ages and Stages Questionnaires: Social-Emotional, Second Edition). Lower educational attainment, lower household income, food insecurity, living without a partner, and having experienced physical assault were each associated with postnatal maternal depressive symptoms and clinical maternal depression (EPDS ≥ 13). Maternal postnatal depression, lower maternal educational attainment, lower household income, household food insecurity, and living in a single-parent household were each associated with child social-emotional problems. Stratified analyses revealed maternal experiences (education, income, food insecurity, trauma) were associated with postnatal maternal depressive symptoms and child social-emotional problems only among dyads with in utero exposure to diabetes. Women with pre-existing diabetes or gestational diabetes in LMIC settings should be screened for health related social needs to reduce the prevalence of depression and to promote child social-emotional development.

Effects of Prenatal Exposure to Alcohol and Smoking on Fetal Heart Rate and Movement Regulation.

Negative associations of prenatal tobacco and alcohol exposure (PTE and PAE) on birth outcomes and childhood development have been well documented, but less is known about underlying mechanisms. A possible pathway for the adverse fetal outcomes associated with PTE and PAE is the alteration of fetal autonomic nervous system development. This study assessed PTE and PAE effects on measures of fetal autonomic regulation, as quantified by heart rate (HR), heart rate variability (SD-HR), movement, and HR-movement coupling in a population of fetuses at ≥ 34 weeks gestational age. Participants are a subset of the Safe Passage Study, a prospective cohort study that enrolled pregnant women from clinical sites in Cape Town, South Africa, and the Northern Plains region, United States. PAE was defined by six levels: no alcohol, low quit early, high quit early, low continuous, moderate continuous, and high continuous; while PTE by 4 levels: no smoking, quit early, low continuous, and moderate/high continuous. Linear regression analyses of autonomic measures were employed controlling for fetal sex, gestational age at assessment, site, maternal education, household crowding, and depression. Analyses were also stratified by sleep state (1F and 2F) and site (South Africa, N = 4025, Northern Plains, N = 2466). The final sample included 6491 maternal-fetal-dyad assessed in the third trimester [35.21 ± 1.26 (mean ± SD) weeks gestation]. PTE was associated with a decrease in mean HR in state 2F, in a dose dependent fashion, only for fetuses of mothers who continued smoking after the first trimester. In state 1F, there was a significant increase in mean HR in fetuses whose mother quit during the first trimester. This effect was driven by the Norther Plains cohort. PTE was also associated with a significant reduction in fetal movement in the most highly exposed group. In South Africa a significant increase in mean HR both for the high quit early and the high continuous group was observed. In conclusion, this investigation addresses a critical knowledge gap regarding the relationship between PTE and PAE and fetal autonomic regulation. We believe these results can contribute to elucidating mechanisms underlying risk for adverse outcomes.

Association Between Prenatal Exposure to Alcohol and Tobacco and Neonatal Brain Activity: Results From the Safe Passage Study.

Importance: Research to date has not determined a safe level of alcohol or tobacco use during pregnancy. Electroencephalography (EEG) is a noninvasive measure of cortical function that has previously been used to examine effects of in utero exposures and associations with neurodevelopment. Objective: To examine the association of prenatal exposure to alcohol (PAE) and tobacco smoking (PTE) with brain activity in newborns. Design, Setting, and Participants: This prospective cohort study enrolled mother-newborn dyads from December 2011 through August 2015, with data analyzed from June 2018 through June 2019. Pregnant women were recruited from clinical sites in Cape Town, South Africa, and the Northern Plains region of the US. Participants were a subset of newborns enrolled in the Safe Passage Study. Exclusions included birth at less than 37 or more than 41 weeks' gestation, multiple birth, or maternal use of psychiatric medication during pregnancy. Exposures: PAE and PTE groups were determined by cluster analysis. Main Outcomes and Measures: Analyses of covariance were run on EEG spectral power at 12 scalp locations across the frequency spectrum from 1 to 45 Hz in 3-Hz bins by sleep state. Results: The final sample consisted of 1739 newborns (median [interquartile range] gestational age at birth, 39.29 [1.57] weeks; 886 [50.9%] were female; median [interquartile range] newborn age at assessment, 48.53 [44.96] hours). Newborns whose mothers were in the low continuous (95% CI, -0.379 to -0.031; P < .05; 95% CI, -0.379 to -0.045; P < .05), quit (95% CI, -0.419 to -0.127; P < .001; 95% CI, -0.398 to -0.106; P < .005), and moderate or high continuous (95% CI, -0.430 to -0.124; P < .001; 95% CI, -0.420 to -0.119; P < .005) PAE clusters had increased 4- to 6-Hz and 7- to 9-Hz left-temporal EEG power. Newborns with moderate or high continuous PTE had decreased 19- to 21-Hz (95% CI, 0.034 to 0.327; P < .05) and 22- to 24-Hz (95% CI, 0.022 to 0.316; P < .05) right-central EEG compared with newborns with no PTE. Newborns with moderate or high continuous PTE had significantly decreased 22- to 36-Hz right-central EEG power compared with the quit smoking group (22-24 Hz, 95% CI, 0.001 to 0.579; P < .05; 25-27 Hz, 95% CI, 0.008 to 0.586; P < .05; 28-30 Hz, 95% CI, 0.028 to 0.607; P < .05; 31-33 Hz, 95% CI, 0.038 to 0.617; P < .05; 34-36 Hz, 95% CI, 0.057 to 0.636; P < .05). Conclusions and Relevance: These findings suggest that even low levels of PAE or PTE are associated with changes in offspring brain development.

Transabdominal recordings of fetal heart rate in extremely small fetuses.

INTRODUCTION: As part of the fetal assessment for the Safe Passage Study, we recorded raw data of the fetal ECG via five maternal abdominal wall electrodes from 20 weeks to 23 weeks 6 days' gestation. MATERIALS: For this study were extracted and analyzed the FHR patterns from the stored raw data in 16 stillbirths where the fetus weighed less than 1000 g and where autopsy was performed. RESULTS: Birth weights ranged from 190 to 970 g. The proportion FHR signal loss ranged from 0.3% to 21.1%. In the smallest fetus the heart weighed 1.3 g, yet the FHR signal loss was only 0.9%.

Fetal heart rate, heart rate variability, and heart rate/movement coupling in the Safe Passage Study.

OBJECTIVE: To determine normative values for heart rate patterns in healthy fetuses. METHODS: This research is from the Safe Passage Study conducted by the Prenatal Alcohol and SIDS and Stillbirth (PASS) Network. A standardized protocol assessed fetal heart rate (FHR), heart rate variability (HRV), and movement from 1655 fetuses at three-time points during gestation (20-24 weeks, 28-32 weeks, 34-38 weeks gestation). RESULTS: FHR decreased while HRV increased over gestation. At the latter two ages, males had significantly lower FHR than females while there were no sex differences in FHR at 20-24 weeks. When accounting for the fetal state during late gestation (34-28 weeks), we found that males had significantly lower FHR than females in the active fetal state only. CONCLUSION: Results demonstrate significant state, gestational age, and sex-related changes in cardiac activity, somatic activity, and autonomic function as the fetus approaches birth.

Effects of low maternal heart rate on fetal growth and birthweight.

OBJECTIVE: To evaluate the association between birthweight and maternal heart rate (MHR) or heart rate variability (HRV) under resting conditions at 20-24 gestational weeks and 34 weeks or later (34+ weeks). METHODS: Data were retrospectively reviewed from the Safe Passage Study, a prospective longitudinal cohort study of alcohol use in pregnancy and birth outcomes in Cape Town, South Africa, between August 2007 and January 2015. Using custom-designed software, MHR and indicators of HRV were obtained from the recorded maternal electrocardiograms and compared with birthweight and z-scores of birthweight adjusted for gestation and gender. RESULTS: Data from 5655 women were included. MHR increased from 84.6 bpm at 20-24 weeks to 88.3 bpm at 34+ weeks. Increasing MHR from 70-80 to 80-90 and 90-100 bpm at 20-24 weeks was associated with increasing birthweight from 2940 to 2998 and 3032 g, respectively (P<0.05). MHR and HRV contributed 29% to the variability associated with birthweight, whereas maternal body mass index at recruitment contributed 44%. Similar associations were observed for MHR at 34+ weeks. CONCLUSION: The observed association of low maternal heart rate with birthweight might help to identify pregnancies at risk of poor fetal growth.