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In pregnancies complicated by fetal growth restriction (FGR) caused by placental dysfunction, brain development is adversely impacted, with evidence of reduced total and hippocampal brain volume in childhood and cognitive deficits. The cellular basis for hippocampal maldevelopment and dysfunction in FGR is unknown.<\/jats:p>\n                  <jats:p>In this study we employed complementary preclinical and clinical investigations of hippocampal developmental trajectory in growth-restricted neonates to address this knowledge gap. In the preclinical study (FGR n = 18, control n = 19), FGR was induced in fetal sheep via surgical induction of placental insufficiency at 89 days\u2019 gestational age (dGA, term is 148 dGA), and after near-term birth (136 dGA), postnatal memory function was measured over 4 weeks. Neuronal dendritogenesis (dendrite length, branching, complexity) was assessed using Golgi\u2013Cox staining of individual hippocampal cornu ammonis 1 (CA1) neurons at two neonatal time points, newborn age at 24\u2005h after birth and 4 weeks of age, to compare the trajectory of hippocampal neuron development in FGR and control lambs.<\/jats:p>\n                  <jats:p>Results show that, in control lambs, total dendrite length and branching of CA1 hippocampal neurons significantly increased between newborn age and 4 weeks. In FGR lamb brains, neither dendrite length nor branching increased over this period, and dendrite deficits were worse in FGR lambs at 4 weeks, corresponding to reduced hippocampal area. In 4-week-old lambs, we observed a significant correlation between total dendrite length of CA1 neurons and memory function.<\/jats:p>\n                  <jats:p>Hippocampal growth trajectory and function deficits were corroborated in small-for-gestational-age (SGA) infants born very preterm. MRI was performed in very preterm infants in early life and repeated at term-equivalent age, showing that the trajectory of anterior hippocampal growth was significantly reduced in SGA infants (n = 20) compared to appropriate-for-gestational age (n = 139) infants. Within the SGA infant cohort, reduced anterior hippocampal volume was significantly associated with lower Bayley Cognitive Composite scores at 18 months corrected age, controlling for gestational age at birth and infant sex. Together, these findings demonstrate that the trajectory of hippocampal growth is significantly impaired in SGA\/FGR infants, caused by disturbed neuronal dendritogenesis that is programmed by an adverse fetal environment and persists, or worsens, after birth. Results in the clinical cohort provide the critical link between programming of reduced dendritogenesis, hippocampal volume deficit and cognitive dysfunction in SGA infants.<\/jats:p>","DOI":"10.1093\/brain\/awag061","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:55:12Z","timestamp":1771505712000},"page":"3538-3551","source":"Crossref","is-referenced-by-count":1,"title":["Hippocampal growth and function are reduced in the newborn following fetal growth restriction"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8809-3448","authenticated-orcid":false,"given":"Tegan A","family":"White","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J","family":"Camm","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charmaine R","family":"Rock","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margie","family":"Castillo-Melendez","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Dudink","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Ahmadzadeh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1377-0878","authenticated-orcid":false,"given":"Justin","family":"Dean","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences, The University of Auckland , Auckland 1010 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7421-6291","authenticated-orcid":false,"given":"Kirsten R","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]},{"name":"Women\u2019s Health Research Program, Monash Health , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9664-4182","authenticated-orcid":false,"given":"Atul","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Department of Paediatrics, Monash University , Clayton 3168 ,","place":["Australia"]},{"name":"Monash Newborn, Monash Children\u2019s Hospital , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5866-4262","authenticated-orcid":false,"given":"Ting","family":"Guo","sequence":"additional","affiliation":[{"name":"Neurosciences and Mental Health, The Hospital for Sick Children Research Institute , Toronto , M5G 1X8","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth J","family":"Allison","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Hospital for Sick Children and the University of Toronto , Toronto , M5G 1X8","place":["Canada"]},{"name":"Department of Pediatrics, BC Children's Hospital Research Institute and University of British Columbia , Vancouver , V5Z 4H4","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne L","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Ritchie Centre , Monash University, Clayton 3168 ,","place":["Australia"]},{"name":"Hudson Institute of Medical Research , Clayton 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"2026100419574171100_awag061-B1","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1038\/s41586-022-05300-0","article-title":"Publisher correction: Brain charts for the human lifespan","volume":"610","author":"Bethlehem","year":"2022","journal-title":"Nature"},{"key":"2026100419574171100_awag061-B2","volume-title":"Volpe\u2019s neurology of the 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