Impacts on prenatal development of the human cerebellum: a systematic review

Abstract

Current literature on associations between parental environmental exposures, intrinsic factors and human cerebellar development is scarce. Yet, this systematic review provided an essential overview of human studies demonstrating the vulnerability of the cerebellum to the intra-uterine environment.

Descriptive epidemiology of cerebellar hypoplasia in the National Birth Defects Prevention Study

“…The existing literature has identified some potential risk factors, mainly through animal studies and case reports, that we did not find among NBDPS cerebellar hypoplasia cases. Several studies, reviews, and case reports have found associations between prenatal infections, particularly viral infections, and cerebellar hypoplasia (Ceballos et al, ; de Fatima Vasco Aragao et al, ; Hazin et al, ; Koning et al, ; Melo et al, ; Meneses et al, ; Patel & Barkovich, ; Poretti, Wolf, & Boltshauser, ; Steinlin et al, ). Yet, the possible role of an infectious etiology remains unclear from our NBDPS results.…”

“…In addition, a meta-analysis of prospective studies (including 1,255 carbamazepine exposure pregnancies) found an increased rate of neural tube defects, cardiovascular birth defects, urinary tract anomalies and cleft palate, in addition to a pattern of minor congenital anomalies and developmental delays (Matalon, Schechtman, Goldzweig, & Ornoy, 2002). We also explored maternal behavioral risk factors, including cocaine use, alcohol use, and smoking, all of which have been associated with cerebellar hypoplasia previously (Bellini et al, 2000;Ekblad et al, 2010;Koning et al, 2016;Norman et al, 2009). No mother of a cerebellar hypoplasia case in the NBDPS reported cocaine use.…”

“…Because it is rare, few studies have been able to identify nongenetic, epidemiological risk factors for cerebellar hypoplasia (Koning et al, ). The majority of evidence for potential prenatal risk factors comes from animal studies or case reports (Koning et al, ; Poretti et al, ), although Zika virus infection has drawn attention to the posterior fossa, including cerebellar hypoplasia. Maternal exposures linked to cerebellar hypoplasia include smoking (Ekblad et al, ), alcohol use (Norman, Crocker, Mattson, & Riley, ), cocaine use (Bellini, Massocco, & Serra, ), valproic acid use (Main & Kulesza, ; Squier, Hope, & Lindenbaum, ), mifepristone use for failed termination (Afadapa & Elsapagh, ; Sitruk‐Ware, Davey, & Sakiz, ), family history (Hunter, ; Murray, Johnson, & Bird, ), and congenital infections (Silasi et al, ) such as cytomegalovirus infection (Ceballos, Ch'ien, Whitley, & Brans, ; Patel & Barkovich, ; Poretti et al, ; Steinlin, Nadal, Eich, Martin, & Boltshauser, ), and Zika virus infection (Araujo Junior, Carvalho, Tonni, & Werner, ; de Fatima Vasco Aragao et al, ; Hazin et al, ; Melo et al, ; Meneses et al, ; Schuler‐Faccini et al, ).…”

“…Cerebellar hypoplasia can occur in isolation, but is a component of Dandy-Walker malformation, a feature of several malformation syndromes, and associated with several metabolic disorders and neurodegenerative disorders (Parisi & Dobyns, 2003;Poretti et al, 2014;Wassmer, Davies, Whitehouse, & Green, 2003). Cerebellar development begins early in embryogenesis, before most brain structures, but cerebellar maturation continues throughout pregnancy and through 20 months of postnatal life for complete cellular differentiation (Goldowitz & Hamre, 1998;Hunter, 2006;Koning et al, 2016;Parisi & Dobyns, 2003;Patel & Barkovich, 2002;Rodriguez & Dymecki, 2000).…”

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin

“…Recently, based on the CBG knock‐out mice models, CBG and cortisol have been reported to be associated with neurocognitive functions (Meyer et al, ). Children exposed to an imbalance of cortisol in‐utero have cerebellar developmental problems (Koning et al, ). Of relevance are several adverse effects of exposure to long‐chain phthalates, such as DEHP in children (reviewed in [Braun et al, ]).…”