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Depression in pregnancy negatively affects maternal-child health. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation treatment for depression, has not been evaluated in pregnancy. To conduct a pilot randomized controlled trial (RCT) to evaluate tDCS for antenatal depression. In this pilot RCT in Toronto, Ontario (October 2014 to December 2016), adult pregnant women 14–32 weeks gestation with major depressive disorder who had declined antidepressant medication were considered for inclusion. Participants were randomly assigned 1:1 to tDCS or sham-control. Active tDCS comprised 30-min sessions of 2 mAmp direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 3 weeks. Sham was administered similarly, but with current turned off after 30 s. Main outcomes were feasibility, acceptability, and protocol adherence. Maternal Montgomery Asperg Depression Rating Scale (MADRS) was measured post-treatment and at 4 and 12 weeks postpartum. Of 20 women randomized, 16 completed treatment and provided data (124 tDCS, 122 sham sessions). Views of treatment were positive with no serious adverse events. Post-treatment estimated marginal mean MADRS scores were 11.8 (standard error, SE 2.66) for tDCS and 15.4 (SE 2.51) for sham (p = 0.34). At 4 weeks postpartum, 75.0% of tDCS women were remitted versus 12.5% sham-control (p = 0.04). Results support proceeding to a definitive RCT to evaluate tDCS for antenatal depression. The preliminary efficacy estimates immediately post-treatment and in the postpartum, are encouraging with respect to the potential use of tDCS to improve treatment rates in this population. The trial was registered at: clinical trials.gov (NCT02116127). • Evaluation of transcranial direct current stimulation (tDCS) for depression in pregnancy is feasible. • Views of treatment were positive with no adverse effects. • Results support proceeding to a definitive randomized controlled trial to evaluate tDCS for antenatal depression. • Preliminary efficacy estimates are encouraging with respect to the potential use of tDCS in this under-treated population. [ABSTRACT FROM AUTHOR]

• Prenatal greenspace exposure was associated with reduced odds of ASD. • Results were consistent across 100, 250, and 500 m buffer zones. • No mediating effects were observed through reduced air pollution. • Controlling for air pollutants posthoc attenuated adjusted ORs. Autism spectrum disorder (ASD) incidence has increased in past decades. ASD etiology remains inconclusive, but research suggests genetic, epigenetic, and environmental contributing factors and likely prenatal origins. Few studies have examined modifiable environmental risk factors for ASD, and far fewer have examined protective exposures. Greenspace has been associated with positive child development, but very limited greenspace research has examined ASD risk or prenatal exposures. Only one ecological study in 2017 has evaluated the association between greenspace and ASD, observing protective benefits. Greenspace may have direct effects on ASD risk and indirect effects by reducing air pollution exposure, a growing suspected ASD risk factor. To measure the association between prenatal greenspace exposure and ASD risk and examine if reduced air pollution levels in areas of higher greenspace mediate this association. We linked a population-based birth cohort of all deliveries in Metro Vancouver, Canada, from 2004 to 2009, with follow-up to 2014. Diagnoses were based on Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised instruments. Greenspace was quantified as the average of the annual mean Normalized Difference Vegetation Index (NDVI) within a 250 m buffer of a residential postal code. Air pollutant exposures—particulate matter with a diameter less than 2.5 µm (PM 2.5), nitric oxide (NO), and nitrogen dioxide (NO 2)—were derived from previously developed and temporally adjusted land use regression models. We estimated air pollutant exposures as the mean concentration per month during pregnancy. We calculated odds ratios (ORs) using logistic regression per NDVI interquartile range (IQR) increase, adjusting for child sex, birth month and year, maternal age and birthplace, and neighborhood-level urbanicity and income. To estimate the health impact of greenspace on ASD at the population level, we used the logistic regression model and marginal standardization to derive risk differences (RDs). Lastly, to quantify the mediating effect of greenspace on ASD risk through air pollution reduction, we used marginal structural models and a potential outcomes framework to calculate marginal risk differences (RDs) to decompose the total effect of greenspace on ASD into natural direct and indirect effects. Of 129,222 births, 1,921 (1.5 %) children were diagnosed with ASD. The adjusted OR for ASD per NDVI IQR (0.12) increase was 0.96 (95 % CI: 0.90, 1.02) in 250 m buffer zones and 0.94 (95 % CI: 0.89, 1.00) in 100 m buffer zones. On the additive scale, the adjusted RDs were null. Natural direct, natural indirect, and total effect RDs were null for PM 2.5 , NO, and NO 2 mediation models. Prenatal greenspace exposure was associated with reduced odds of ASD, but in the additive scale, this effect was null at the population level. No mediating effect was observed through reduced air pollution, suggesting that air pollution may act as a confounder rather than as a mediator. [ABSTRACT FROM AUTHOR]

Abstract: Background: Prenatal exposure to stress and selective serotonin reuptake inhibitors (SSRIs) alter hypothalamic–pituitary–adrenal (HPA) stress reactivity in offspring, however, the effects of combined exposure to HPA activity in human infants is unknown. Objective: To examine HPA basal levels and stress responsiveness in 3-month olds with prenatal exposure to SSRIs. Methods: Salivary cortisol levels in infants of SSRI treated mothers (n =31, mean exposure 230.2±72.2 days) were compared with non-SSRI exposed (n =45) infants in response to a challenge (infant-controlled habituation task) and under basal conditions in the late afternoon/early evening. Mode of feeding, to account for possible postnatal drug exposure via breast milk, as well as measures of pre and postnatal maternal mood, were included as covariates. Results: Lower post-stress cortisol levels were observed in non-SSRI exposed/non-breastfed infants compared with non-SSRI exposed infants who were breastfed at 3 months of age. Stress reactivity patterns among SSRI exposed infants did not differ with mode of feeding. The cortisol reactivity slope (CRS) was significantly lower among non-SSRI exposed non-breastfed infants compared with non-SSRI exposed breastfed infants. Early evening basal cortisol levels were lower in SSRI exposed infants than in non-SSRI exposed infants, controlling for maternal mood and mode of feeding. Postnatal SSRI exposure (infant SSRI drug levels) via breast milk was not associated with stress or basal cortisol levels. Total cortisol, reflected by the AUC measure, did not differ significantly between exposure groups. Conclusions: Prenatal SSRI exposure altered HPA stress response patterns and reduced early evening basal cortisol levels. Stress challenge HPA response differences only became apparent when the moderating effect of method of feeding was accounted for. These findings suggest an early “programming” effect of antenatal maternal mood, prenatal SSRI exposure and postnatal maternal care giving on the HPA system. [Copyright &y& Elsevier]

Fetal programming is a conceptual framework whereby the in utero environment shapes the offspring's neurodevelopment. Maternal depression and treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy are common prenatal exposures that affect critical early life developmental programming processes. Prenatal depression and SSRIs both have been reported to increase the risks for preterm birth, low birth weight, and are associated with behavioral disturbances across the early life span. However, not all exposures lead to adverse developmental outcomes and distinguishing how each exposure contributes to variations in development remains challenging. Advances in neuroimaging, using MR and EEG, offer novel insights into central processes that might reveal the neural correlates of fetal programming. This review focuses on emerging findings from neuroimaging studies reflecting early brain functional and structural development associated with prenatal exposure to maternal depression and SSRI antidepressants. Suggestions for future research directions that use neuroimaging as a tool to advancing our understanding of the early origins of developmental plasticity are offered. [ABSTRACT FROM AUTHOR]

The authors discuss research published within the issue about the effects on child development of selective serotonin reuptake inhibitor (SSRI) antidepressants taken during pregnancy. The study claims that prenatal exposure results in increased risk for early adolescence depression. The authors assert that the study should use a comparison between pregnant women who took SSRI and pregnant women who did not, with both groups having the same severity of depression.

Abstract: Finely tuning levels of the key neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) during early life is essential for brain development and setting pathways for health and disorder across the early life span. Given the central role of 5-HT in brain development, regulation of mood, stress reactivity, and risk for psychiatric disorders, alterations in 5-HT signaling early in life have critical implications for behavior and mental health in childhood and adolescence. This article reviews the developmental consequences of two key influences that alter fetal 5-HT signaling: (1) in utero exposure to 5-HT reuptake inhibitor antidepressants, and (2) genetic variations in the 5-HT transporter gene (SLC6A4). The consequences of altered prenatal 5-HT signaling vary greatly, and developmental outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations), experiential (prenatal drug or maternal mood exposure), and contextual (postnatal social environment) variables. Emerging evidence suggests both exposure to 5-HT reuptake inhibitors and genetic variations that affect 5-HT signaling may increase sensitivity to negative social contexts for some individuals, whereas for others, they may confer sensitivity to positive life circumstances. In this sense, factors that change central 5-HT levels may function less like influences that predict “vulnerability,” but rather act like “plasticity factors.” Understanding the impact of early changes in serotonergic programming offers critical insights that might explain patterns of individual differences in developmental risk and resilience. [Copyright &y& Elsevier]

The hypothalamic-pituitary-adrenal (HPA) axis is impacted by a multitude of pre- and postnatal factors. Developmental programming of HPA axis function by prenatal alcohol exposure (PAE) has been demonstrated in animal models and in human infants, but remains understudied in older children and adolescents. Moreover, early life adversity (ELA), which occurs at higher rates in children with PAE than in non-exposed children, may also play a role in programming the stress response system. In a cohort of children and adolescents with PAE and ELA (PAE + ELA), we evaluated HPA function through assessment of diurnal cortisol activity compared to that in typically developing controls, as well as the associations among specific ELAs, adverse outcomes, protective factors, and diurnal cortisol. Morning and evening saliva samples were taken under basal conditions from 42 children and adolescents (5-18 years) with PAE + ELA and 43 typically developing controls. High rates of ELA were shown among children with PAE, and significantly higher evening cortisol levels and a flatter diurnal slope were observed in children with PAE + ELA, compared to controls. Medication use in the PAE + ELA group was associated with lower morning cortisol levels, which were comparable to controls. Complex associations were found among diurnal cortisol patterns in the PAE + ELA group and a number of ELAs and later adverse outcomes, whereas protective factors were associated with more typical diurnal rhythms. These results complement findings from research on human infants and animal models showing dysregulated HPA function following PAE, lending weight to the suggestion that PAE and ELA may interact to sensitize the developing HPA axis. The presence of protective factors may buffer altered cortisol regulation, underscoring the importance of early assessment and interventions for children with FASD, and in particular, for the many children with FASD who also have ELA. [ABSTRACT FROM AUTHOR]

Abstract: Background: Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants has been associated with delays in early developmental milestones, but there remains uncertainty. Even among a subset of studies examining the Bayley Scales of Infant Development (BSID), some have reported normal mental and psychomotor development while others have suggested a delay in motor development. Given an increasing number of infants exposed to SRIs, furthering our understanding of the possible developmental implications of SRI exposure in utero is critical. Aims: To examine the effects of prenatal serotonin reuptake inhibitor exposure and maternal mood on infant developmental outcomes at 10months of age. Study design: Prospective study of mothers and their 10-month-old infants. Subjects: We examined 31 mother–child pairs exposed prenatally to SRIs and 52 mother–child pairs who were nonexposed. Outcome measure: The Bayley Scales of Infant Development (third edition) scores. Results: Infants exposed prenatally to SRIs scored significantly lower than nonexposed infants on gross motor (P =0.03), social–emotional (P =0.04) and adaptive behavior (P =0.05) subscales of the BSID-III, controlling for pre- and postnatal maternal depressed mood, smoking and alcohol use during pregnancy. No significant differences in any of the BSID-III subscales were observed between infants exposed and infants nonexposed to pre and postnatal maternal depressed mood (P >0.05). Increased levels of maternal positive affect at 10months predicted increased social–emotional scores (P =0.03). Conclusions: Infants prenatally exposed to SRIs score significantly lower on the gross motor, social–emotional and adaptive behavior subscales of the BSID-III, and this was not explained by underlying maternal depression. [Copyright &y& Elsevier]

Abstract: Background:: Preterm and full-term neonates admitted to the neonatal intensive care unit or elsewhere in the hospital are routinely subjected to invasive procedures that can cause acute pain. Despite published data on the complex behavioral, physiologic, and biochemical responses of these neonates and the detrimental short- and long-term clinical outcomes of exposure to repetitive pain, clinical use of pain-control measures in neonates undergoing invasive procedures remains sporadic and suboptimal. As part of the Newborn Drug Development Initiative, the US Food and Drug Administration and the National Institute of Child Health and Human Development invited a group of international experts to form the Neonatal Pain Control Group to review the therapeutic options for pain management associated with the most commonly performed invasive procedures in neonates and to identify research priorities in this area. Objective:: The goal of this article was to review and synthesize the published clinical evidence for the management of pain caused by invasive procedures in preterm and full-term neonates. Methods:: Clinical studies examining various therapies for procedural pain in neonates were identified by searches of MEDLINE (1980–2004), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2004), the reference lists of review articles, and personal files. The search terms included specific drug names, infant-newborn, infant-preterm, and pain, using the explode function for each key word. The English-language literature was reviewed, and case reports and small case series were discarded. Results:: The most commonly performed invasive procedures in neonates included heel lancing, venipuncture, IV or arterial cannulation, chest tube placement, tracheal intubation or suctioning, lumbar puncture, circumcision, and SC or IM injection. Various drug classes were examined critically, including opioid analgesics, sedative/hypnotic drugs, nonsteroidal anti-inflammatory drugs and acetaminophen, injectable and topical local anesthetics, and sucrose. Research considerations related to each drug category were identified, potential obstacles to the systematic study of these drugs were discussed, and current gaps in knowledge were enumerated to define future research needs. Discussions relating to the optimal design for and ethical constraints on the study of neonatal pain will be published separately. Well-designed clinical trials investigating currently available and new therapies for acute pain in neonates will provide the scientific framework for effective pain management in neonates undergoing invasive procedures. [Copyright &y& Elsevier]

Abstract: Background: Acute pain is a significant stressor for preterm infants in neonatal intensive care units (NICU); however, little is known about the effects of acute pain on subsequent motor responses during clusters of tactile handling. Aims: (1) To compare facial, body and heart rate reactivity in preterm infants at 32 weeks gestational age (GA) during routine care-giving tasks following a rest period (RCC: diapering, measuring abdominal girth and axillary temperature, mouth care) with their responses to Clustered Care following blood collection (PCC). (2) To examine how GA at birth affects patterns of stress and self-regulatory behaviors during RCC and PCC. Study Design: Within-group crossover design (random order). Subjects: Preterm infants, N=54 (mean GA at birth 29.3 ± 2.2 weeks; mean birth weight 1257 ± 423 g) were assessed at 32 weeks GA in the NICU. Outcome measures: The Newborn Developmental Care and Assessment Program (NIDCAP®) and Neonatal Facial Coding System (NFCS) were coded from continuous bedside video recordings. Changes in mean heart rate (HR) were computed using custom physiologic software. Results: All infants had heightened facial, body and HR responses when CC followed a painful procedure compared to when they had not been handled prior to CC. Infants born at earlier GA (<30 weeks) had equal numbers of stress cues during RCC and PCC, but dampened self-regulatory behaviors during PCC. Conclusion: Prior pain induces heightened biobehavioral reactivity in preterm infants during subsequent tactile procedures. In addition, clustering care is particularly stressful for infants born at earlier GA. [Copyright &y& Elsevier]

Motor development underlies many aspects of education and learning. There has been uncertainty about the impact of exposure of antidepressant medication in pregnancy on child motor outcomes. This paper examines whether exposure to antidepressants in utero increases the risk of poorer motor development in two areas: sensorimotor and visuospatial processing. Data were obtained from 195 women and children across 3 groups: women with untreated depression in pregnancy, women treated with antidepressants and control women. Data were collected across pregnancy, postpartum and until 4 years for mother and child. Maternal depression was established at baseline with the Structured Clinical Interview for DSM-IV. Antidepressant exposure, including type, dose and timing, was measured through repeated self-report across pregnancy and the postpartum, medical records at delivery and in cord blood samples collected at delivery. Child sensorimotor and visuospatial outcomes were assessed at 4 years of age with four subtests from the NEPSY-II. Our study found for sensorimotor development, visuomotor precision completion time was associated with better performance for antidepressant-exposed children compared to those with mothers with untreated depression. Yet another measure of sensorimotor development, motor manual sequences, was poorer in those exposed to antidepressants. One subtest for visuospatial processing, block construction, was associated with poorer performance in antidepressant-exposed children who had poor neonatal adaptation and those exposed to a higher dose of antidepressant. These findings suggest an inconsistent association between sensorimotor development and antidepressant use in pregnancy. However, the findings for visuospatial processing would support further exploration of antidepressant associated poor neonatal adaption and later motor development. [ABSTRACT FROM AUTHOR]

Sex differences are a robust finding in many areas of adult health, including cardiovascular disease, psychiatric disorders, and chronic pain. However, many sex differences are not consistently observed until after the onset of puberty. This has led to the hypothesis that hormones are primary contributors to sex differences in health outcomes, largely ignoring the relative contributions of early developmental influences, emerging psychosocial factors, gender, and the interaction between these variables. In this paper, we argue that a comprehensive understanding of sex and gender contributions to health outcomes should start as early as conception and take an iterative biopsychosocial-developmental perspective that considers intersecting social positions. We present a conceptual framework, informed by a review of the literature in basic, clinical, and social science that captures how critical developmental stages for both sex and gender can affect children's health and longer-term outcomes. The literature on pediatric chronic pain is used as a worked example of how the framework can be applied to understanding different chronic conditions. • Sex and gender influence health across the lifespan. • Differences in girls, boys, and gender-diverse youth are complex and biopsychosocial. • Development is critical for understanding for the interaction of sex, gender, and health. • Intersectionality impacts health outcomes beyond sex and gender alone. • Exploring sex and gender roles in health will inform inclusive, equitable clinical practice. [ABSTRACT FROM AUTHOR]

• Perinatal SSRIs differentially impact offspring affective behaviors. • Maternal mood symptoms are important to consider in addition to SSRIs. • Sex/gender and age of offspring are important factors affecting outcomes. • Environmental and genetic factors need to be considered. • Further research is needed to determine perinatal SSRI effects on offspring. The developmental impact of selective serotonin reuptake inhibitor (SSRI) and other antidepressant treatments during gestation and postpartum on anxiety and depression behaviors in offspring is unclear. This review focuses on how perinatal exposure to SSRI and other antidepressant may have long term consequences for these affective behaviors during early childhood and beyond. Outcomes vary and consideration is given to methodological factors related to how early SSRI exposure affects developments studied in rodent models such as: a) between pre- and early post-natal SSRI exposure, b) sex, c) experimental models of gestational maternal stress and d) impact of non-SSRI antidepressant medications. We will also review how multiple contextual factors (maternal caregiving and gene x environment interactions) may contribute to the effects of perinatal SSRI exposure and maternal mental illness on affective behaviors in children. [ABSTRACT FROM AUTHOR]

Background: Building on research reports that early and chronic exposure to maternal depressive symptoms (MDS) adversely affects children's developing executive function (EF), this longitudinal study examined whether exposure to MDS and Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant treatment during pregnancy predicted individual differences in EF at school age.Methods: In a longitudinal prospective cohort, maternal report of EF using the Behavior Rating Inventory of EF (BRIEF) was obtained from 139 children (77 females; non-exposed n = 88, SSRI exposed n = 51) at age 6 years. Clinician rated and self reports of MDS were also obtained spanning from the 2nd trimester to 6 years postpartum.Results: Higher levels of MDS, especially at 3 years, were associated with poorer maternal reports of EF skills at 6 years. Associations between prenatal SSRI exposure and EF outcomes were not significant, even when controlling for maternal education and MDS at 3 years.Conclusions: Postnatal exposure to MDS adversely effects developing child EF, even when maternal symptoms were treated with an SSRI antidepressant. [ABSTRACT FROM AUTHOR]

The long-term impact of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment during pregnancy and postpartum on offspring outcomes is still not clear. Specifically, perinatal SSRI exposure may have long-term consequences for body weight and related health outcomes in the newborn period and beyond. This review focuses on the impact of perinatal SSRI exposure on weight using human and animal findings. The impact of maternal mood is also explored. We propose potential mechanisms for weight changes, including how early alterations in serotonin signaling may have implications for weight via changes in metabolism and motor development. As the majority of serotonin is in the gastrointestinal (GI) system we also speculate that perinatal SSRI exposure might alter the brain-gut relationship, via the microbiome, leading to changes in feeding behavior and weight. [ABSTRACT FROM AUTHOR]

Recent research has linked early life exposure to selective serotonin reuptake inhibitor medications (SSRIs) to modifications of social behaviors in children. Serotonin is a key regulator of neurodevelopment, social behaviors and mental health, and with the growing use of SSRIs to treat maternal affective disorders during the perinatal period, questions have been raised about the benefits and risks of perinatal SSRI exposure on the developing child. This review will highlight how perinatal SSRIs affect maternal care and neurodevelopmental outcomes related to social affiliative behaviors in offspring; such as play behaviors, social interactions, reproductive behaviors, and maternal care of the next generation. We will also review how early life exposure to SSRIs can alter related neurobiology, and the epigenome. Both clinical research and findings from animal models will be discussed. Understanding the impact of perinatal SSRIs on neurobehavioral outcomes will improve the health and well-being of subsequent generations. [ABSTRACT FROM AUTHOR]

Background Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) is associated with an enhanced risk of preterm birth. Very preterm-born neonates (<32 weeks’ gestation) antenatally-exposed to SSRIs may show altered brain development. Objective To examine whether antenatal-SSRI exposure was associated with adverse neonatal brain microstructural and metabolic development using diffusion tensor and magnetic resonance spectroscopic imaging. Design/Methods Of 177 neonates enrolled, 14 (8%) were antenatally exposed to SSRIs. Neonates were scanned twice (median week 32; interquartile range [IQR]: 30.4–33.6) and again at term-equivalent age (40.1, IQR: 38.6–42.1). Using a region-of-interest approach, N-acetylaspartate to choline ratios (NAA/Cho), lactate to choline ratios, white and gray matter fractional anisotropy (FA), mean, axial, radial diffusivity (MD, AD, RD) values were extracted from white and gray matter subcortical regions. Neurodevelopment was assessed at 18 months, corrected age. Results SSRI-exposed neonates exhibited increased FA and decreased MD, AD and RD values in the superior white matter ( p < 0.05). FA values in the basal ganglia and thalamus were significantly lower in neonates antenatally exposed to SSRIs, compared to non-exposed ( p = 0.004). Lower NAA/Cho values ( p = 0.04) and higher Lactate/Cho values ( p = 0.004) in posterior gray matter were evident in neonates exposed to SSRIs. No association with antenatal-SSRI exposure and neurodevelopment was evident. Conclusions Given the importance of treating depression in mothers at risk for preterm delivery, the impact of antenatal-SSRIs on early brain development requires further attention. Future research is directed at determining the mechanism of this relationship and the contribution of maternal mood. [ABSTRACT FROM AUTHOR]

Background: Fetal alcohol spectrum disorder (FASD) is broadly associated with impairments to adaptive behavior and dysfunctional sleep. Associations between sleep, adaptive behavior, and physical activity are frequently drawn in discussions of typical development and other clinical conditions.Aims: In this study, we sought to characterize patterns of sleep, adaptive behavior, and physical activity in adolescents with FASD. We also investigated the associations between sleep, adaptive behavior, and physical activity within this population.Methods and Procedures: Twenty-seven adolescents aged 11- to 17-years with a diagnosis of FASD and their caregivers participated in this study. All participants completed parent and youth questionnaires on adaptive behavior, sleep, and physical activity.Outcomes and Results: Adolescents with FASD displayed significant impairments to all domains of adaptive behavior and considerable sleep disturbance. Worse sleep was associated with older age and sleep-related breathing disturbances were associated with poorer social adaptive behavior. Participation in physical activity, particularly organized sport, was strongly associated with better adaptive behavior.Conclusions and Implications: Adolescents with FASD experience considerable challenges with regards to sleep and adaptive behavior. Physical activity, particularly organized sport, may provide opportunities for the improvement of adaptive behavior in this population. [ABSTRACT FROM AUTHOR]

• Vegetated land cover exposure was positively associated with childhood development. • Positive associations were stronger for tree cover relative to grass cover. • Exposure to paved land cover was negatively associated with childhood development. Growing evidence suggests that exposure to green space is associated with improved childhood health and development, but the influence of different green space types remains relatively unexplored. In the present study, we investigated the association between early-life residential exposure to vegetation and early childhood development and evaluated whether associations differed according to land cover types, including paved land. Early childhood development was assessed via kindergarten teacher-ratings on the Early Development Instrument (EDI) in a large population-based birth cohort (n = 27,539) in Metro Vancouver, Canada. The residential surrounding environment was characterized using a high spatial resolution land cover map that was linked to children by six-digit residential postal codes. Early-life residential exposure (from birth to time of EDI assessment, mean age = 5.6 years) was calculated as the mean of annual percentage values of different land cover classes (i.e., total vegetation, tree cover, grass cover, paved surfaces) within a 250 m buffer zone of postal code centroids. Multilevel models were used to analyze associations between respective land cover classes and early childhood development. In adjusted models, one interquartile range increase in total vegetation percentage was associated with a 0.33 increase in total EDI score (95% CI: 0.21, 0.45). Similar positive associations were observed for tree cover (β-coefficient: 0.26, 95% CI: 0.15, 0.37) and grass cover (β-coefficient: 0.12, 95% CI: 0.02, 0.22), while negative associations were observed for paved surfaces (β-coefficient: −0.35, 95% CI: −0.47, −0.23). Our findings indicate that increased early-life residential exposure to vegetation is positively associated with early childhood developmental outcomes, and that associations may be stronger for residential exposure to tree cover relative to grass cover. Our results further indicate that childhood development may be negatively associated with residential exposure to paved surfaces. These findings can inform urban planning to support early childhood developmental health. [ABSTRACT FROM AUTHOR]

Highlights: [•] Investigated impact of depression & SRI treatment on early mother–infant interactions. [•] Despite prenatal SRI treatment, depressed mothers interrupt infants more frequently. [•] SRI exposure & higher prenatal depression severity increases infant responsiveness. [•] Without SRI exposure, higher postnatal depression decreases infant responsiveness. [ • ] Infant responsiveness following prenatal SRI exposure may reflect ‘fetal programming’. [Copyright &y& Elsevier]

• Greenness was associated with a lower incidence of childhood ADHD. • PM 2.5 , but not NO 2 or noise, was associated with an increased incidence of ADHD. • There was a disproportionate risk of ADHD in high PM 2.5 and low greenness areas. • Vegetation percentage is a novel and precise greenness estimate. Emerging studies have associated low greenspace and high air pollution exposure with risk of child attention deficit/hyperactivity disorder (ADHD). Population-based studies are limited, however, and joint effects are rarely evaluated. We investigated associations of ADHD incidence with greenspace, air pollution, and noise in a population-based birth cohort. We assembled a cohort from administrative data of births from 2000 to 2001 (N ∼ 37,000) in Metro Vancouver, Canada. ADHD was identified by hospital records, physician visits, and prescriptions. Cox proportional hazards models were applied to assess associations between environmental exposures and ADHD incidence adjusting for available covariates. Greenspace was estimated using vegetation percentage derived from linear spectral unmixing of Landsat imagery. Fine particulate matter (PM 2.5) and nitrogen dioxide (NO 2) were estimated using land use regression models; noise was estimated using a deterministic model. Exposure period was from birth until the age of three. Joint effects of greenspace and PM 2.5 were analysed in two-exposure models and by categorizing values into quintiles. During seven-year follow-up, 1217 ADHD cases were diagnosed. Greenspace was associated with lower incidence of ADHD (hazard ratio, HR: 0.90 [0.81–0.99] per interquartile range increment), while PM 2.5 was associated with increased incidence (HR: 1.11 [1.06–1.17] per interquartile range increment). NO 2 (HR: 1.01 [0.96, 1.07]) and noise (HR: 1.00 [0.95, 1.05]) were not associated with ADHD. There was a 50% decrease in the HR for ADHD in locations with the lowest PM 2.5 and highest greenspace exposure, compared to a 62% increase in HR in locations with the highest PM 2.5 and lowest greenspace exposure. Effects of PM 2.5 were attenuated by greenspace in two-exposure models. We found evidence suggesting environmental inequalities where children living in greener neighborhoods with low air pollution had substantially lower risk of ADHD compared to those with higher air pollution and lower greenspace exposure. [ABSTRACT FROM AUTHOR]

Background: There have been contradictory reports on the risks of persistent pulmonary hypertension (PPHN) in infants exposed to SSRIs in utero. However, there has been no assessment of fetal pulmonary arterial dynamics in such pregnancies. AIMS AND SUBJECTS: To measure fetal right pulmonary artery (RPA) variables using Doppler ultrasound at 36 weeks gestation in fetuses of mothers taking SSRI antidepressants (n=23) and in a control, normal pregnancy group (n=35). Outcome Measures: At 36 weeks gestation, Doppler ultrasound estimates of Pulsatility Index (PI), Resistance Index (RI), vessel diameter, peak systolic velocity, mean velocity and volume flow were obtained from the fetal right pulmonary artery in a morning session (~0830), before the SSRI mothers took their daily drug dose and in an afternoon session (~1300). Venous blood was drawn at 5 time points across the day (~08:30AM, ~10:30AM, ~13:00PM, ~13:45PM, and ~15:00PM) from the SSRI treated mothers for measurement of plasma SSRI concentration using high performance liquid chromatography tandem mass spectrometry. Results: There were no differences in the RPA Doppler measures between the control and SSRI-exposed fetuses. However 8 of the 23 latter fetuses experience transient respiratory difficulties at birth and, in these RPA flow was significantly higher than in the SSR-exposed fetuses without respiratory problems. There were, however, no differences in RPA PI and RI between the 2 groups. Conclusions: In SSRI-exposed infants with transient postnatal respiratory difficulties, fetal RPA flow in increased, likely due to partial constriction of the ductus arteriosus. However, this was not associated with PPHN. [ABSTRACT FROM AUTHOR]

Summary: Background: Serotonin influences the development of the hypothalamic–pituitary–adrenal (HPA) system; therefore prenatal exposure to selective serotonin reuptake inhibitor antidepressants (SSRIs) may alter HPA axis development and function. To address this, prenatal exposure to SSRIs and maternal mood were examined in relation to neonatal and infant levels of cortisol and its binding protein, corticosteroid-binding globulin (CBG). Methods: Serum cortisol and CBG levels were assayed from SSRI-exposed and non-exposed mothers and their neonates at delivery. Maternal mood symptoms were documented at 36 weeks gestation. To determine the long-term implications of changes in CBG, levels of salivary cortisol were assessed in infants at 3 months of age. Results: Prenatal SSRI exposure significantly increased serum CBG levels in neonates after vaginal delivery (p ≤0.038), even when controlling for maternal depression. Neonatal serum cortisol levels did not vary with SSRI exposure or antenatal maternal mood, but were significantly higher following vaginal delivery (p ≤0.003). Neonatal serum CBG levels were associated with infant salivary levels of evening cortisol (p ≤0.051). In SSRI-exposed infants, increased levels of neonatal CBG predicted a smaller diurnal change in infant salivary cortisol (p ≤0.028), regardless of maternal depression. Conclusions: Prenatal SSRI exposure affects the developing HPA system by altering serum CBG levels in neonates and infant salivary cortisol levels. Further research is warranted on the long-term functional implications of the effect of prenatal SSRI exposure on fetal hepatic CBG gene expression and the developing HPA system. [ABSTRACT FROM AUTHOR]

Abstract: We examined the role of physiological regulation (heart rate, vagal tone, and salivary cortisol) in short-term memory in preterm and full-term 6-month-old infants. Using a deferred imitation task to evaluate social learning and memory recall, an experimenter modeled three novel behaviors (removing, shaking, and replacing a glove) on a puppet. Infants were tested immediately after being shown the behaviors as well as following a 10-min delay. We found that greater suppression of vagal tone was related to better memory recall in full-term infants tested immediately after the demonstration as well as in preterm infants tested later after a 10-min delay. We also found that preterm infants showed greater coordination of physiology (i.e., tighter coupling of vagal tone, heart rate, and cortisol) at rest and during retrieval than full-term infants. These findings provide new evidence of the important links between changes in autonomic activity and memory recall in infancy. They also raise the intriguing possibility that social learning, imitation behavior, and the formation of new memories are modulated by autonomic activity that is coordinated differently in preterm and full-term infants. [Copyright &y& Elsevier]

Abstract: Objective: To address the maternal and neonatal risks of both depression and antidepressant exposure and develop algorithms for periconceptional and antenatal management. Method: Representatives from the American Psychiatric Association, the American College of Obstetricians and Gynecologists and a consulting developmental pediatrician collaborated to review English language articles on fetal and neonatal outcomes associated with depression and antidepressant treatment during childbearing. Articles were obtained from Medline searches and bibliographies. Search keywords included pregnancy, pregnancy complications, pregnancy outcomes, depressive disorder, depressive disorder/dt, abnormalities/drug-induced/epidemiology, abnormalities/drug-induced/et. Iterative draft manuscripts were reviewed until consensus was achieved. Results: Both depressive symptoms and antidepressant exposure are associated with fetal growth changes and shorter gestations, but the majority of studies that evaluated antidepressant risks were unable to control for the possible effects of a depressive disorder. Short-term neonatal irritability and neurobehavioral changes are also linked with maternal depression and antidepressant treatment. Several studies report fetal malformations in association with first trimester antidepressant exposure but there is no specific pattern of defects for individual medications or class of agents. The association between paroxetine and cardiac defects is more often found in studies that included all malformations rather than clinically significant malformations. Late gestational use of selective serotonin reuptake inhibitor antidepressants is associated with transitory neonatal signs and a low risk for persistent pulmonary hypertension in the newborn. Psychotherapy alone is an appropriate treatment for some pregnant women; however, others prefer pharmacotherapy or may require pharmacological treatment. Conclusions: Antidepressant use in pregnancy is well studied, but available research has not yet adequately controlled for other factors that may influence birth outcomes including maternal illness or problematic health behaviors that can adversely affect pregnancy. [Copyright &y& Elsevier]

Abstract: Objective:: The purpose of this article is to summarize the clinical, methodologic, and ethical considerations for researchers interested in designing future trials in neonatal analgesia and anesthesia, hopefully stimulating additional research in this field. Methods:: The MEDLINE, PubMed, EMBASE, and Cochrane register databases were searched using subject headings related to infant, newborn, neonate, analgesia, anesthesia, ethics, and study design. Cross-references and personal files were searched manually. Studies reporting original data or review articles related to these topics were assessed and critically evaluated by experts for each topical area. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were abstracted and synthesized in a systematic manner and refined by group members. Data synthesis and results were reviewed by a panel of independent experts and presented to a wider audience including clinicians, scientists, regulatory personnel, and industry representatives at the Newborn Drug Development Initiative workshop. Recommendations were revised after extensive discussions at the workshop and between committee members. Results:: Designing clinical trials to investigate novel or currently available approaches for analgesia and anesthesia in neonates requires consideration of salient study designs and ethical issues. Conditions requiring treatment include pain/stress resulting from invasive procedures, surgical operations, inflammatory conditions, and routine neonatal intensive care. Study design considerations must define the inclusion and exclusion criteria, a rationale for stratification, the confounding effects of comorbid conditions, and other clinical factors. Significant ethical issues include the constraints of studying neonates, obtaining informed consent, making risk-benefit assessments, defining compensation or rewards for participation, safety considerations, the use of placebo controls, and the variability among institutional review boards in interpreting federal guidelines on human research. For optimal study design, investigators must formulate well-defined study questions, choose appropriate trial designs, estimate drug efficacy, calculate sample size, determine the duration of the studies, identify pharmacokinetic and pharmacodynamic parameters, and avoid drug-drug interactions. Specific outcome measures may include scoring on pain assessment scales, various biomarkers and their patterns of response, process outcomes (eg, length of stay, time to extubation), intermediate or long-term outcomes, and safety parameters. Conclusions:: Much more research is needed in this field to formulate a scientifically sound, evidence-based, and clinically useful framework for management of anesthesia and analgesia in neonates. Newer study designs and additional ethical dilemmas may be defined with accumulating data in this field. [Copyright &y& Elsevier]

The aims of this study were to examine preterm infant reactions to pain in detail over prolonged time periods using multiple measures, and to assess the value of including specific body movements of the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP) system to evaluate pain. Ten preterm infants born at 31 weeks mean gestational age (GA) and mean birth weight 1676 g were studied during a routine blood collection in a Level III neonatal intensive care unit (NICU). At 32-week post-conceptional age, computerized physiologic and video recordings were obtained continuously for 60 min (prior to, during and after lance). Motor and facial behaviors were coded independently, using the NIDCAP and the NFCS (Neonatal Facial Coding System), respectively, and compared with heart rate (HR) and oxygen saturation responses. Of the movements hypothesized to be stress cues in the NIDCAP model, extension of arms and legs (80%) and finger splay (70%) were the most common following lance. Contrary to the model, most infants (70%) had lower incidence of twitches and startles post-lance compared to baseline. Whereas all infants showed some NFCS response to lance, for three infants, the magnitude was low. HR increased and oxygen saturation decreased post-lance. Infants with more prior pain exposure, lower Apgar, and lower GA at birth, displayed more motor stress cues but less facial activity post-lance. Extension of extremities and finger splay, but not twitches and startles, from the NIDCAP, appear to be stress cues and show promise as clinical pain indicators to supplement facial and physiological pain measures in preterm infants. [Copyright &y& Elsevier]

• Maternal depression is associated with lower infant cortisol reactivity. • Early pregnancy depression is associated with reduced placental NR3C2 DNA methylation. • No association of maternal depression and cortisol with placental or infant buccal NR3C1 DNA methylation. • No association of antidepressant use with cortisol and placental or infant buccal NR3C1 and NR3C2 DNA methylation. • Association between infant cortisol reactivity and maternal depression was suppressed by placental NR3C2 DNA methylation. Understanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early development. Two genes involved in stress response regulation, the glucocorticoid and mineralocorticoid receptors (NR3C1 and NR3C2) have been a focus in understanding stressful exposures and mental health outcomes. Data were obtained from 236 pregnant women from the Mercy Pregnancy Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort, recruited in early pregnancy. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeated measures of the Edinburgh Postnatal Depression Scale (EPDS). Antidepressant use, stressful events and anxiety symptoms were measured. NR3C1 and NR3C2 DNA methylation was measured in placental and infant buccal samples. Infant cortisol was measured in repeat saliva samples across a task. This study found maternal early pregnancy depressive disorder and symptoms were associated with lower DNA methylation at NR3C2 CpG_24 in placental tissue. There were no significant differences for depression or antidepressant use for DNA methylation of NR3C1. Antenatal depression was associated with lower infant cortisol reactivity at 12 months. DNA methylation in CpG_24 site in NR3C2 in placental samples suppressed the relationship between early maternal depressive symptoms and infant cortisol reactivity. These findings show a relationship between antenatal depression, NR3C2 DNA methylation and infant cortisol response providing support for a specific fetal programming pathway. Further research is required to examine the stability of this epigenetic mark across childhood and long-term mental health outcomes. [ABSTRACT FROM AUTHOR]