Table 1.
The impact of perinatal compromise in human studies.
| Pregnancy complication | Participants | Sample size | Hippocampal morphology | Hippocampal function | Reference |
|---|---|---|---|---|---|
| Prematurity | Preterm infants: <36 weeks GA. | 71 participants | ↓ total hippocampal volume. | NA | Ball et al.90 |
| Prematurity | Extremely preterm infants <28 weeks GA vs. term born controls, assessed at 18 years of age. |
Extremely preterm; n = 148 Control; n = 132 |
↓ 8% hippocampal volume in extremely preterm. | Smaller brain volumes associated with lower IQ and poorer educational skills. | Cheong et al.91 |
| Prematurity | Preterm infants (<33 weeks GA) were assessed at 15 years and 19 years of age. |
Preterm; n = 61 Control; n = 35 |
Significant surface deformations reflecting atrophy of the hippocampus. | ↑ right hippocampal volume and bilateral anterior surface deformations were associated with delusional ideation scores. | Cole et al.92 |
| Prematurity | Preterm infants (<32 weeks GA) vs. term-born controls (~40 weeks GA). |
Preterm; n = 53 Control; n = 361 |
↓ 4% volume in the right hippocampi of preterm infants. | NA | Ge et al.93 |
| Prematurity | Preterm infants (25-35 weeks GA), assessed at age 10 to 18 years. | 22 participants | ↓ total hippocampal volume, with left posterior dominance. | Associations between left hippocampal grey matter reductions and verbal memory. | Gimenez et al.94 |
| Prematurity | Extremely preterm infants: <28 weeks GA, admitted to the NICU and exposed to “early-life stress”. |
Low stress preterm; n = 90 High stress preterm; n = 90 |
Infants exposed to high stress showed lower covariance within the default mode network, rendering them at higher risk for stress-related psychopathology. | NA | Lammertink et al.95 |
| Prematurity | Preterm infants (<33 weeks GA), assessed at 20 years of age |
Preterm; n = 21 Control; n = 10 |
↓ fractional anisotropy tracts in the hippocampal region of VPT. | Different pattern of activation during retrieval/recall in hippocampus of VPT. | Salvan et al.96 |
| Prematurity | VPT infants (<32 weeks GA), assessed at 2 years of age. |
VPT; n = 85 Brain injury; n = 73 Control; n = 55 |
↓ 7% hippocampal volumes in very preterm infants. | Smaller hippocampal volumes were related to worse motor performance at age 2. | Strahle et al.97 |
| Prematurity with and without GM-IVH | Preterm birth <37 weeks GA, having a neonatal diagnosis of GM-IVH assessed at age 6 to 16 years old. |
Preterm w/GM-IVH; n = 16 Preterm; n = 20 Control; n = 22 |
↓ left and right global hippocampus volume in high-risk preterm sample with GM-IVH compared to both low-risk preterm and full-term groups. | FIQ was within normal limits in both preterm groups, it was significantly lower compared to full-term children. | Fernandez de Gamarra-Oca et al.98 |
| Prematurity and chorioamnionitis | Preterm birth between 28 and 37 weeks GA, with and without chorioamnionitis, assessed at 8-9 years old. |
Preterm w/chorioamnionitis; n = 11 Preterm; n = 16 |
↓ right hippocampal volume in children exposed to chorioamnionitis. | NA | Hatfield et al.74 |
| Prematurity, VLBW, and perinatal brain injury | VPT (<32 weeks GA) and perinatal brain injury vs. VPT no injury vs. control. |
VPT w/brain injury; n = 16 VPT no injury; n = 13 Control; n = 14 |
↓ 5% total hippocampal volume in very preterm group ↓ 14% total hippocampal volume perinatal brain injury group. |
NA | Froudist-Walsh et al.7 |
| Prematurity/VLBW | Preterm infants: <30 weeks GA or BW < 1250 g. | 227 participants | ↓ total hippocampal volume. | Children with working memory deficits had marginally smaller hippocampi. | Beauchamp et al.3 |
| Prematurity/VLBW | VPT infants born <30 weeks GA or BW < 1250 g, assessed at 13 years |
VPT w/anxiety; n = 16 VPT no anxiety; n = 108 |
VPT children who met anxiety disorder criteria showed slower hippocampal growth trajectories | Impaired hippocampal development associated with anxiety disorder | Gilchrist et al.99 |
| Prematurity/VLBW | Premature born (< 32 weeks GA and/or BW < 1500 g), assessed at 26 years of age. |
Preterm/VLBW; n = 103 Control; n = 109 |
↓ hippocampal subfields volumes. |
Correlations between all left-sided functional hippocampus units and adult FIQ |
Hedderich et al.5 |
| Prematurity/VLBW | VPT infants either <30 weeks GA or a BW of <1250 g, assessment at 2, 5 and 7 years of age. |
VPT; n = 145 Control; n = 34 |
↓ 5% right and ↓ 6% left hippocampal volumes in VPT children. | Neither left nor right hippocampal volumes were associated with performance on memory or learning outcomes. | Omizzolo et al.100 |
| Prematurity/VLBW | VPT infants either <30 weeks GA or a BW of <1250 g, MRI at term equivalent age, assessed at 5 years old | 165 participants | ↓ right and left hippocampal volumes | In females, smaller hippocampal volumes were associated with hyperactivity, inattention and peer problems. | Rogers et al.101 |
| Prematurity/VLBW | Preterm infants: <30 weeks GA or BW < 1250 g vs. full-term infants: >37 weeks GA. |
Preterm; n = 184 Control; n = 32 |
↓ 3% hippocampal volumes in preterm group. | Infants with reduced corrected hippocampal volume at 2 years showed reduced MDI scores. | Thompson et al.6 |
| Prematurity/VLBW | VPT infants: <30 weeks GA or BW < 1250 g vs. full-term infants: >37 weeks GA, assessed at 7 years of age |
VPT; n = 184 Control; n = 32 |
VPT children showed less hippocampal infolding ↓ growth between infancy and 7 years in VPT | Hippocampal developmental trajectory did not predict learning and memory deficits. | Thompson et al.102 |
| VLBW | Infants born with BW < 1500 g, vs. control, assessed at 19 years of age. |
VLBW; n = 44 Control; n = 61 |
↓ 5% total intracranial volume. ↓ 7% absolute hippocampal volume. |
Inferior memory function correlated to the volume of hippocampi, BW, and perinatal morbidity. | Aanes et al.103 |
| VLBW | School aged children (6−11 years) born preterm <34 weeks GA and <1500 g, vs. control |
VLBW; n = 34 Control; n = 104 |
↓ 3% left hippocampal volume. ↓ hippocampal subfield volume. |
↓ scores on spatial span and digit span assessments, for verbal and visual working memory. |
Aanes et al.104 |
| VLBW | VLBW: <30 weeks GA and <1500 g vs. control: median GA 39.5 weeks, median BW 3622 g. |
VLBW; n = 11 Control; n = 8 |
↓ 15% hippocampal volumes in VLBW children compared with age-matched, full-term controls. | VLBW children had deficits in everyday memory. | Isaacs et al.8 |
| SGA | SGA: BW and/or birth length -2 SD of normal vs. control, assessed at 4−7 years old. |
SGA; n = 34 Control; n = 18 |
SGA children showed less activation in the left parahippocampal region compared to control. | SGA children had lower IQ scores than control children and had slower performance in encoding and recognition tasks | De Bie et al.105 |
| FGR | Premature infants (32 weeks GA) born with FGR (<3rd centile) vs. premature control infants. |
FGR; n = 13 Control; n = 13 |
↓ GM volume of both hippocampi and ↓ 9% total hippocampal volume. |
↓ APIB scores in FGR infants. ↓ mean MDI in FGR infants. |
Lodygensky et al.106 |
| FGR | Premature infants (<34 weeks GA) with FGR (<3rd centile) vs. premature infants with appropriate BW vs. control, assessed at 12 months old. |
Preterm FGR; n = 18 Preterm; n = 15 Control; n = 15 |
↓ WM in hippocampus of FGR infants vs. control. | ↓ scores on motor, fine motor and adaptive behaviour on the BSITD. | Padilla et al.107 |
| FGR | Preterm infants (<33 weeks GA), born FGR (<3rd centile) vs. AGA. MRI at term equivalent age, assessment at 22 months age. |
VPT FGR; n = 49 VPT Control; n = 265 |
↓ volume of GM in limbic brain regions (including the hippocampus). |
↓cognitive and motor outcomes. ↑ autism screening risk at 22 months. |
Sacchi et al.108 |
| Perinatal hypoxia-ischaemia | Infant brain cases taken from autopsies, six diagnosed as hypoxic. |
Hypoxia; n = 6 Control; n = 4 |
↓ somatostatin and neuropeptide expression in pyramidal cell layer and stratum oriens of CA1. | NA | González Fuentes et al.109 |
| Perinatal hypoxia- ischaemia | Children born >36 weeks GA, acute perinatal asphyxia, with and without therapeutic hypothermia. |
HIE w/hypothermia; n = 15 HIE; n = 17 |
Atrophy of the hippocampal and parahippocampal white matter with HIE. |
Neurocognitive and memory problems at 10 years of age. |
Annink et al.110 |
| Perinatal hypoxia-ischaemia | Term-born children with mild and moderate HIE. |
Mild HIE; n = 26 Moderate HIE; n = 26 Control; n = 37 |
↓ hippocampal volumes with moderate HIE. | ↓ hippocampal volumes were associated with poorer long-term visuospatial memory. | Annink et al.111 |
| Hypoxic ischaemic encephalopathy | Term-born children with neonatal HIE, treated with hypothermia |
HIE; n = 10 Controls; n = 8 |
↓ hippocampal volumes with HIE. |
Within-group correlation between the hippocampal volume and memory scores in children with HIE. |
Pfister et al.112 |
APIB assessment of preterm infants’ behaviour, BSITD Bayley scale for infant and toddler development, BW birth weight, FIQ full intelligence quotient, GA gestational age, GM grey matter, GM-IVH germinal matrix-intraventricular haemorrhage, HIE hypoxic-ischaemic encephalopathy, IQ intelligence quotient, MDI mental development index, MRI magnetic resonance imaging, NA not assessed, VLBW very low birth weight, VPT very preterm, SGA small for gestational age, w/ with, WM white matter.