Prenatal exposure to air pollution is associated with structural changes in the neonatal brain.

BACKGROUND: Prenatal exposure to air pollution is associated with adverse neurologic consequences in childhood. However, the relationship between in utero exposure to air pollution and neonatal brain development is unclear. METHODS: We modelled maternal exposure to nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) at postcode level between date of conception to date of birth and studied the effect of prenatal air pollution exposure on neonatal brain morphology in 469 (207 male) healthy neonates, with gestational age of ≥36 weeks. Infants underwent MR neuroimaging at 3 Tesla at 41.29 (36.71-45.14) weeks post-menstrual age (PMA) as part of the developing human connectome project (dHCP). Single pollutant linear regression and canonical correlation analysis (CCA) were performed to assess the relationship between air pollution and brain morphology, adjusting for confounders and correcting for false discovery rate. RESULTS: Higher exposure to PM10 and lower exposure to NO2 was strongly canonically correlated to a larger relative ventricular volume, and moderately associated with larger relative size of the cerebellum. Modest associations were detected with higher exposure to PM10 and lower exposure to NO2 and smaller relative cortical grey matter and amygdala and hippocampus, and larger relaive brainstem and extracerebral CSF volume. No associations were found with white matter or deep grey nuclei volume. CONCLUSIONS: Our findings show that prenatal exposure to air pollution is associated with altered brain morphometry in the neonatal period, albeit with opposing results for NO2 and PM10. This finding provides further evidence that reducing levels of maternal exposure to particulate matter during pregnancy should be a public health priority and highlights the importance of understanding the impacts of air pollution on this critical development window.

Neonatal frontal-limbic connectivity is associated with externalizing behaviours in toddlers with Congenital Heart Disease.

Children with Congenital Heart Disease (CHD) are at increased risk of neurodevelopmental impairments. The neonatal antecedents of impaired behavioural development are unknown. 43 infants with CHD underwent presurgical brain diffusion-weighted MRI [postmenstrual age at scan median (IQR) = 39.29 (38.71-39.71) weeks] and a follow-up assessment at median age of 22.1 (IQR 22.0-22.7) months in which parents reported internalizing and externalizing problem scores on the Child Behaviour Checklist. We constructed structural brain networks from diffusion-weighted MRI and calculated edge-wise structural connectivity as well as global and local brain network features. We also calculated presurgical cerebral oxygen delivery, and extracted perioperative variables, socioeconomic status at birth and a measure of cognitively stimulating parenting. Lower degree in the right inferior frontal gyrus (partial ρ = -0.687, p < 0.001) and reduced connectivity in a frontal-limbic sub-network including the right inferior frontal gyrus were associated with higher externalizing problem scores. Externalizing problem scores were unrelated to neonatal clinical course or home environment. However, higher internalizing problem scores were associated with earlier surgery in the neonatal period (partial ρ = -0.538, p = 0.014). Our results highlight the importance of frontal-limbic networks to the development of externalizing behaviours and provide new insights into early antecedents of behavioural impairments in CHD.

Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI.

BACKGROUND: Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI). METHODS: We studied 491 infants (52% male) without focal destructive brain lesions born at < 34 weeks, who underwent structural and dMRI at a specialist Neonatal Imaging Centre. The median (range) gestational age (GA) at birth was 30+ 1 (23+ 2-33+ 5) weeks and median postmenstrual age at scan was 42+ 1 (38-45) weeks. dMRI data were analyzed using tract based spatial statistics and the relationship between dMRI measures in white matter and individual perinatal risk factors was assessed. We tested the hypothesis that increased exposure to perinatal risk factors was associated with lower fractional anisotropy (FA), and higher radial, axial and mean diffusivity (RD, AD, MD) in white matter. Neurodevelopmental performance was investigated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) in a subset of 381 infants at 20 months corrected age. We tested the hypothesis that lower FA and higher RD, AD and MD in white matter were associated with poorer neurodevelopmental performance. RESULTS: Identified risk factors for diffuse white matter injury were lower GA at birth, fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Clinical chorioamnionitis and patent ductus arteriosus were not associated with white matter injury. Multivariate analysis demonstrated that fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition were independently associated with lower FA values. Exposure to cumulative risk factors was associated with reduced white matter FA and FA values at term equivalent age were associated with subsequent neurodevelopmental performance. CONCLUSION: This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white matter injury.