Very preterm birth (VPT; < 32 weeks of gestation) has been associated with an increased risk to develop cognitive and socio-emotional problems, as well as with increased vulnerability to psychiatric disorder, both with childhood and adult onset. Socio-emotional impairments that have been described in VPT individuals include diminished social competence and self-esteem, emotional dysregulation, shyness and timidity. However, the etiology of socio-emotional problems in VPT samples and their underlying mechanisms are far from understood. To date, research has focused on the investigation of both biological and environmental risk factors associated with socio-emotional problems, including structural and functional alterations in brain areas involved in processing emotions and social stimuli, perinatal stress and pain and parenting strategies. Considering the complex interplay of the aforementioned variables, the review attempts to elucidate the mechanisms underlying the association between very preterm birth, socio-emotional vulnerability and psychopathology. After a comprehensive overview of the socio-emotional impairments associated with VPT birth, three main models of socio-emotional development are presented and discussed. These focus on biological vulnerability, early life adversities and parenting, respectively. To conclude, a developmental framework is used to consider different pathways linking VPT birth to psychopathology, taking into account the interaction between medical, biological, and psychosocial factors.

BackgroundVery preterm birth (VPT; <32 weeks of gestation) has been associated with impairments in emotion regulation, social competence and communicative skills. However, the neuroanatomical mechanisms underlying such impairments have not been systematically studied. Here we investigated the functional integrity of the amygdala connectivity network in relation to the ability to recognize emotions from facial expressions in VPT adults.MethodThirty-six VPT-born adults and 38 age-matched controls were scanned at rest in a 3-T MRI scanner. Resting-state functional connectivity (rs-fc) was assessed with SPM8. A seed-based analysis focusing on three amygdalar subregions (centro-medial/latero-basal/superficial) was performed. Participants’ ability to recognize emotions was assessed using dynamic stimuli of human faces expressing six emotions at different intensities with the Emotion Recognition Task (ERT).ResultsVPT individuals compared to controls showed reduced rs-fc between the superficial subregion of the left amygdala, and the right posterior cingulate cortex (p = 0.017) and the left precuneus (p = 0.002). The VPT group further showed elevated rs-fc between the left superficial amygdala and the superior temporal sulcus (p = 0.008). Performance on the ERT showed that the VPT group was less able than controls to recognize anger at low levels of intensity. Anger scores were significantly associated with rs-fc between the superficial amygdala and the posterior cingulate cortex in controls but not in VPT individuals.ConclusionsThese findings suggest that alterations in rs-fc between the amygdala, parietal and temporal cortices could represent the mechanism linking VPT birth and deficits in emotion processing.

This study investigated the association between attention-deficit/hyperactivity disorder (ADHD) symptomatology in preschool-aged children who were born very preterm (<33 weeks) and cognitive outcomes, clinical risk and socio-demographic characteristics. 119 very preterm children who participated in the Evaluation of Preterm Imaging Study at term-equivalent age were assessed at a mean age of 4.5 years. Parents completed the ADHD Rating Scale IV, a norm-referenced checklist that evaluates ADHD symptomatology according to diagnostic criteria, and the Behavior Rating Inventory of Executive Function-Preschool version. Children completed the Wechsler Preschool and Primary Scales of Intelligence and the Forward Digit Span task. Longitudinal data including perinatal clinical, qualitative MRI classification, socio-demographic variables and neurodevelopmental disabilities were investigated in relation to ADHD symptomatology. All results were corrected for multiple comparisons using false discovery rate. Results showed that although the proportion of very preterm children with clinically significant ADHD did not differ from normative data after excluding those with neurodevelopmental disabilities, 32.7% met criteria for subthreshold ADHD inattentive type and 33.6% for combined type, which was higher than the expected 20% in normative samples. Higher ADHD symptom scores (all) were associated with greater executive dysfunction (inhibitory self-control, flexibility, and emergent metacognition, corrected p<0.001 for all tests). Higher inattentive ADHD symptom scores were associated with lower IQ (ρ = -0.245, p = 0.011) and higher perinatal clinical risk (more days on mechanical ventilation (ρ = 0.196, p = 0.032) and more days on parenteral nutrition (ρ = 0.222, p = 0.015). Higher hyperactive ADHD symptom scores instead were associated with lower socioeconomic status (ρ = 0.259, p = 0.004). These results highlight the importance of monitoring and supporting the development of very preterm children throughout the school PLOS ONE PLOS ONE | https://doi.years, as subthreshold ADHD symptoms represent risk factors for psychosocial problems and for receiving a future clinical diagnosis of ADHD. Methods SampleStudy participants were 119 very preterm born children who were recruited at birth in 2010-2013 as part of the Evaluation of Preterm Imaging Study (e-Prime Eudra: CT 2009-011602-42) PLOS ONE ADHD symptoms in very preterm children PLOS ONE | https://doi.org/10.Qualitative MR rating � No perinatal brain lesions N (%) 35 (29.4) Minor perinatal brain lesions N (%) 64 (53.8) Major perinatal brain lesions N (%) 17 (14.3) Full scale intelligence quotient, mean (range) 106 (50-147) �� Three MRI datasets were corrupted and could not be evaluated https://doi.org/10.1371/journal.pone.0224343.t001 PLOS ONEADHD symptoms in very preterm children PLOS ONE | https://doi.org/10.