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The term fetal alcohol spectrum disorder includes a group of diseases caused by fetal alcohol exposure (FAE). Patients with fetal alcohol spectrum disorder display heterogeneous socioemotional and cognitive deficits, particularly in the domain of executive function, that share symptoms with other neuropsychiatric disorders. Despite the availability of several preclinical models, the developmental brain defects causally linked to behavioral deficits induced by FAE remain poorly understood. Here, we first review the effects of FAE on corticostriatal development and its impact on both corticostriatal pathway function and cognitive abilities. We propose three non-mutually exclusive circuit models of corticostriatal dysfunctions to account for some of the FAE-induced cognitive deficits. One model posits that associative-sensorimotor imbalance causes hyper goal-directed behavior, and a second model implies that alteration of prefrontal-striatal behavioral suppression circuits results in loss of behavioral inhibition. A third model suggests that local striatal circuit deficits affect striatal neuronal ensemble function to impair action selection and performance. Finally, we discuss how preclinical approaches applied to these circuit models could offer potential rescue strategies for executive function deficits in patients with fetal alcohol spectrum disorder., (Published by Elsevier Inc.)

Introduction: Aim of the study was to investigate the association between placental pathology and oligohydramnios in pregnancies complicated by fetal growth restriction (FGR)., Methods: Placentas from 221 consecutive FGR pregnancies and 63 healthy controls were studied. Pathological lesions were described according to consensus nomenclature and standardized criteria; both elementary lesions and constellations of lesions (patterns) were considered. Statistics included analysis of linear trends and multinomial logistic regression., Results: Amniotic fluid index (AFI) was normal in 56 (25.3%) FGR pregnancies, whereas mild, moderate and severe oligohydramnios were diagnosed in 32 (14.5%), 44 (19.9%) and 89 (40.3%) subjects, respectively. In FGR pregnancies, after adjustment for potential confounders, membrane meconium staining (chi-square = 28.6, p < 0.001), chronic villous hypoxia pattern (chi-square = 18.8, p < 0.001) and fetal thrombotic vasculopathy pattern (chi-square = 9.2, p = 0.002) were positively and linearly correlated to AFI decrease. Odds ratios of meconium and chronic villous hypoxia were 9.2 (95% CI = 2.6-32.9) and 4.2 (95% CI = 1.3-13.6) in FGR pregnancies with normal AFI and 25.2 (95% CI = 6.9-91.8) and 9.7 (95% CI = 3-31.5) in those with severe oligohydramnios (p = 0.005 and p = 0.023 compared to normal AFI, respectively)., Discussion: In FGR pregnancies, reduction of amniotic fluid volume is directly correlated to histological features of placental under-perfusion, meconium staining of membranes and fetal vascular damage. These findings support the clinical notion that in FGR pregnancies oligohydramnios is a risk factor of fetal hypoxia and possibly of increased adverse neonatal outcomes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)