Maternal Prenatal Stress Is Associated With Altered Uncinate Fasciculus Microstructure in Premature Neonates

Abstract

BACKGROUND: Maternal prenatal stress exposure (PNSE) increases risk for adverse psychiatric and behavioral outcomes in offspring. The biological basis for this elevated risk is poorly understood but may involve alterations to the neurodevelopmental trajectory of white matter tracts within the limbic system, particularly the uncinate fasciculus. Additionally, preterm birth is associated with both impaired white matter development and adverse developmental outcomes. In this study we hypothesized that higher maternal PNSE was associated with altered uncinate fasciculus microstructure in offspring. METHODS: In this study, 251 preterm infants (132 male, 119 female) (median gestational age = 30.29 weeks [range, 23.57-32.86 weeks]) underwent brain magnetic resonance imaging including diffusion-weighted imaging around term-equivalent age (median = 42.43 weeks [range, 37.86-45.71 weeks]). Measures of white matter microstructure were calculated for the uncinate fasciculus and the inferior longitudinal fasciculus, a control tract that we hypothesized was not associated with maternal PNSE. Multiple regressions were used to investigate the relationship among maternal trait anxiety scores, stressful life events, and white matter microstructure indices in the neonatal brain. RESULTS: Adjusting for gestational age at birth, postmenstrual age at scan, maternal age, socioeconomic status, sex, and number of days on parenteral nutrition, higher stressful life events scores were associated with higher axial diffusivity (b = .177, q = .007), radial diffusivity (b = .133, q = .026), and mean diffusivity (b = .149, q = .012) in the left uncinate fasciculus, and higher axial diffusivity (b = .142, q = .026) in the right uncinate fasciculus. CONCLUSIONS: These findings suggest that PNSE is associated with altered development of specific frontolimbic pathways in preterm neonates as early as term-equivalent age.

Premature Birth and Developmental Programming: Mechanisms of Resilience and Vulnerability

“…These findings are supported by evidence from fetal stress models demonstrating that full-term and preterm neonates exposed to prenatal stress showed alterations in brain development. More specifically, prenatal stress (e.g., maternal anxiety/depression) was associated with reductions in region-specific gray matter volume [i.e., PFC, temporal lobe (140)], alterations in white matter microstructure (e.g., amygdala, limbic system) (141)(142)(143), and reduced functional and structural connectivity between the amygdala, limbic, and frontal regions in infants (144)(145)(146). The effects of prenatal stress on brain development have been extensively reviewed elsewhere [see (147)(148)(149)].…”

Cognitive function in toddlers with congenital heart disease: The impact of a stimulating home environment

“…Finally, in this study we considered the effect of home environment at 22 months on developmental outcome in CHD. Prenatal as well as postnatal environmental enrichment improves outcome in rats with perinatal hypoxia‐ischemia (Duran‐Carabali et al, 2018; Durán‐Carabali et al, 2019), and we have previously observed altered white matter development in infants born prematurely who experienced prenatal stress exposure (Lautarescu et al, 2019). An improved prenatal environment such as increased maternal exercise or reduced maternal stress may improve brain and cognitive development (Miguel et al, 2019).…”

“…Prenatal as well as postnatal environmental enrichment improves outcome in rats with perinatal hypoxia-ischemia (Duran-Carabali et al, 2018;Durán-Carabali et al, 2019), and we T A B L E 3 Regression coefficients predicting cognitive composite score and language composite score in children with CHD. have previously observed altered white matter development in infants born prematurely who experienced prenatal stress exposure (Lautarescu et al, 2019). An improved prenatal environment such as increased maternal exercise or reduced maternal stress may improve brain and cognitive development (Miguel et al, 2019).…”

Early postnatal maternal trait anxiety is associated with the behavioural outcomes of children born preterm <33 weeks

“…Recent studies have investigated the role of both ante- and postnatal parental stress and anxiety in child development and behaviour ( Bendiksen et al, 2020 ; Kvalevaag et al, 2013 ; Polte et al, 2019 ; Rees et al, 2019 ), although inconsistencies between study methodologies and findings make definite conclusions difficult ( Rees et al, 2019 ; Tarabulsy et al, 2014 ). Postnatal maternal stress and anxiety are believed to have significant long-term implications for child brain maturation ( Lautarescu et al, 2020 ; Qiu et al, 2013 ) and behavioural development ( Field, 2018 ), particularly in very preterm infants ( Hadfield et al, 2017 ). Possible mechanisms mediating these associations include reduced maternal sensitivity ( Kertz et al, 2008 ; Nicol-Harper et al, 2007 ), unpredictability of maternal behaviour ( Davis et al, 2017 ), and altered mother-infant attachment ( Hadfield et al, 2017 ; Stevenson-Hinde et al, 2013 ).…”