School Entry Age Outcomes for Infants with Birth Weight ≤800 Grams

Synnes, Anne; Anson, Shelagh; Arkesteijn, Astrid; Butt, Arsalan; Grunau, Ruth E.; Rogers, Marilyn; Whitfield, Michael F.

doi:10.1016/j.jpeds.2010.06.016

“…A Siemens 1.5 Tesla Avanto magnet, standard 12-channel head coil, and VB 16 software were used to obtain the following sequences: 3-dimensional T 1 and axial fluid attenuation inversion recovery (8900/87/220/5/1/ 256 3 154). Neuroradiologist K.J.P., blinded to the child' s medical history, assessed these images for brain injury (ie, evidence of cerebellar hemorrhage, ventriculomegaly, or moderate to severe WM injury, as described previously).…”

Section: Mrimentioning

confidence: 99%

“…Advances in neonatal care have greatly improved survival of infants born very preterm (#32 weeks' gestational age [GA]); however, cognitive impairment may have increased among children with birth weight #800 g. [1][2][3] Even in the absence of severe disability (eg, blindness, nonambulatory cerebral palsy, IQ ,70), cognitive problems and school difficulties are common among children born very preterm. [4][5][6] Infants born very preterm undergo frequentinvasive procedures duringneonatal care.…”

mentioning

confidence: 99%

Invasive Procedures in Preterm Children: Brain and Cognitive Development at School Age

Vinall

¹

,

Miller

²

,

Björnson

³

et al. 2014

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WHAT'S KNOWN ON THIS SUBJECT: Greater numbers of invasive procedures from birth to term-equivalent age, adjusted for clinical confounders, are associated with altered brain microstructure during neonatal care and poorer cognitive outcome at 18 months' corrected age in children born very preterm.WHAT THIS STUDY ADDS: Altered myelination at school age is associated with greater numbers of invasive procedures during hospitalization in very preterm children without severe brain injury or neurosensory impairment. Greater numbers of invasive procedures and altered brain microstructure interact to predict lower IQ. abstract BACKGROUND: Very preterm infants (born 24-32 weeks' gestation) undergo numerous invasive procedures during neonatal care. Repeated skin-breaking procedures in rodents cause neuronal cell death, and in human preterm neonates higher numbers of invasive procedures from birth to term-equivalent age are associated with abnormal brain development, even after controlling for other clinical risk factors. It is unknown whether higher numbers of invasive procedures are associated with long-term alterations in brain microstructure and cognitive outcome at school age in children born very preterm. METHODS:Fifty children born very preterm underwent MRI and cognitive testing at median age 7.6 years (interquartile range, 7.5-7.7). T 1 -and T 2 -weighted images were assessed for the severity of brain injury. Magnetic resonance diffusion tensor sequences were used to measure fractional anisotropy (FA), an index of white matter (WM) maturation, from 7 anatomically defined WM regions. Child cognition was assessed using the Wechsler Intelligence Scale for Children-IV. Multivariate modeling was used to examine relationships between invasive procedures, brain microstructure, and cognition, adjusting for clinical confounders (eg, infection, ventilation, brain injury). RESULTS:Greater numbers of invasive procedures were associated with lower FA values of the WM at age 7 years (P = .01). The interaction between the number of procedures and FA was associated with IQ (P = .02), such that greater numbers of invasive procedures and lower FA of the superior WM were related to lower IQ. CONCLUSIONS:Invasive procedures during neonatal care contribute to long-term abnormalities in WM microstructure and lower IQ. Pediatrics 2014;133:412-421

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“…School-age children who were FGR are more likely to have a range of cognitive deficits, including impaired memory and learning, inattention, abnormal psychosocial function and lower mathematics abilities and IQ scores [2,3,4,5,6,7]. Later in life, adults who were FGR are susceptible to mood and biochemical brain disorders such as depression, schizophrenia and epilepsy and are also at heightened risk for psychiatric hospitalization [5,6,8]. Furthermore, the severity and longevity of these brain disorders are directly proportional to the degree of FGR [1,6,8].…”

Section: Introductionmentioning

confidence: 99%

“…Later in life, adults who were FGR are susceptible to mood and biochemical brain disorders such as depression, schizophrenia and epilepsy and are also at heightened risk for psychiatric hospitalization [5,6,8]. Furthermore, the severity and longevity of these brain disorders are directly proportional to the degree of FGR [1,6,8]. Taken together, these human studies suggest that critical alterations in brain development arise from the suboptimal intrauterine conditions that lead to FGR and underlie the risk for these later neurological disorders.…”

Section: Introductionmentioning

confidence: 99%

Synaptic Development and Neuronal Myelination Are Altered with Growth Restriction in Fetal Guinea Pigs

Piorkowska

¹

,

Thompson²,

Nygard³

et al. 2014

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This study examines aberrant synaptogenesis and myelination of neuronal connections as possible links to neurological sequelae in growth-restricted fetuses. Pregnant guinea pig sows were subjected to uterine blood flow restriction or sham surgeries at midgestation. The animals underwent necropsy at term with fetuses grouped according to body weight and brain-to-liver weight ratios as follows: appropriate for gestational age (n = 12); asymmetrically fetal growth restricted (aFGR; n = 8); symmetrically fetal growth restricted (sFGR; n = 8), and large for gestational age (n = 8). Fetal brains were perfusion fixed and paraffin embedded to determine immunoreactivity for synaptophysin and synaptopodin as markers of synaptic development and maturation, respectively, and for myelin basic protein as a marker for myelination, which was further assessed using Luxol fast blue staining. The most pertinent findings were that growth-restricted guinea pig fetuses exhibited reduced synaptogenesis and synaptic maturation as well as reduced myelination, which were primarily seen in subareas of the hippocampus and associated efferent tracts. These neurodevelopmental changes were more pronounced in the sFGR compared to the aFGR animals. Accordingly, altered hippocampal development involving synaptogenesis and myelination may represent a mechanism by which cognitive deficits manifest in human growth-restricted offspring in later life.

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“…Accepted for publication Dec 16, 2013 Advances in neonatal care have greatly improved survival of infants born very preterm (#32 weeks' gestational age [GA]); however, cognitive impairment may have increased among children with birth weight #800 g. [1][2][3] Even in the absence of severe disability (eg, blindness, nonambulatory cerebral palsy, IQ ,70), cognitive problems and school difficulties are common among children born very preterm. [4][5][6] Infants born very preterm undergo frequentinvasive procedures duringneonatal care.…”

mentioning

confidence: 99%

Invasive Procedures in Preterm Children: Brain and Cognitive Development at School Age

2014

PEDIATRICS

0

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WHAT'S KNOWN ON THIS SUBJECT: Greater numbers of invasive procedures from birth to term-equivalent age, adjusted for clinical confounders, are associated with altered brain microstructure during neonatal care and poorer cognitive outcome at 18 months' corrected age in children born very preterm.WHAT THIS STUDY ADDS: Altered myelination at school age is associated with greater numbers of invasive procedures during hospitalization in very preterm children without severe brain injury or neurosensory impairment. Greater numbers of invasive procedures and altered brain microstructure interact to predict lower IQ. abstract BACKGROUND: Very preterm infants (born 24-32 weeks' gestation) undergo numerous invasive procedures during neonatal care. Repeated skin-breaking procedures in rodents cause neuronal cell death, and in human preterm neonates higher numbers of invasive procedures from birth to term-equivalent age are associated with abnormal brain development, even after controlling for other clinical risk factors. It is unknown whether higher numbers of invasive procedures are associated with long-term alterations in brain microstructure and cognitive outcome at school age in children born very preterm. METHODS:Fifty children born very preterm underwent MRI and cognitive testing at median age 7.6 years (interquartile range, 7.5-7.7). T 1 -and T 2 -weighted images were assessed for the severity of brain injury. Magnetic resonance diffusion tensor sequences were used to measure fractional anisotropy (FA), an index of white matter (WM) maturation, from 7 anatomically defined WM regions. Child cognition was assessed using the Wechsler Intelligence Scale for Children-IV. Multivariate modeling was used to examine relationships between invasive procedures, brain microstructure, and cognition, adjusting for clinical confounders (eg, infection, ventilation, brain injury). RESULTS:Greater numbers of invasive procedures were associated with lower FA values of the WM at age 7 years (P = .01). The interaction between the number of procedures and FA was associated with IQ (P = .02), such that greater numbers of invasive procedures and lower FA of the superior WM were related to lower IQ. CONCLUSIONS:Invasive procedures during neonatal care contribute to long-term abnormalities in WM microstructure and lower IQ. Pediatrics 2014;133:412-421

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School Entry Age Outcomes for Infants with Birth Weight ≤800 Grams

Cited by 59 publications

References 18 publications

Invasive Procedures in Preterm Children: Brain and Cognitive Development at School Age

Invasive Procedures in Preterm Children: Brain and Cognitive Development at School Age

Synaptic Development and Neuronal Myelination Are Altered with Growth Restriction in Fetal Guinea Pigs

Invasive Procedures in Preterm Children: Brain and Cognitive Development at School Age

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