Antecedents and early correlates of high and low concentrations of angiogenic proteins in extremely preterm newborns
Alan Leviton, Stanthia Ryan, Elizabeth N Allred, Raina N Fichorova, T Michael O'Shea, Karl Kuban, Olaf Dammann, ELGAN Study Investigators
Clin Chim Acta. 2017 Aug;471:1-5
BACKGROUND: To identify antecedents & very early correlates of low concentrations of angiogenic proteins in blood of extremely preterm newborns in first postnatal month. RESULTS: Delivery for medical indications or severely IUGR were more likely to have low day-1 blood concentrations of VEGF, VEGF-R2, Ang-1, and PIGF. Systemic inflammation accompanied top quartile concentrations of all 6 angiogenic proteins. CONCLUSIONS: Low day-1 values of angiogenic proteins associated w/placenta insufficiency/dysfunction. High concentrations associated w/inflammation in first month.
Newborn blood gas derangements of children born extremely preterm and neurocognitive dysfunctions at age 10 years
Alan Leviton, Elizabeth N Allred, Robert M Joseph, T Michael O'Shea, Karl C K Kuban, ELGAN Study Investigators
Respir Physiol Neurobiol. 2017 Aug;242:66-72
Abstract Among 740 children born extremely preterm, children who had hypoxemia, hyperoxemia, hypocapnia, hypercapnia, and acidemia, sometimes on only one day, and sometimes on two or more days, were more likely than others to have a high illness severity score (within the first 12 postnatal hours), and 10 years later to have multiple dysfunctions compatible with possibility that blood gas derangements are indicators of physiologic instability/vulnerability/immaturity.
Observer variability identifying attention deficit/hyperactivity disorder in 10-year-old children born extremely preterm
Alan Leviton, Scott J Hunter, Megan N Scott, Stephen R Hooper, Robert M Joseph, Thomas Michael O'Shea, Elizabeth N Allred, Karl Kuban
Acta Paediatr. 2017 Aug;106:1317-1322.
AIM: A DSM-5 diagnosis of (ADHD) requires that symptoms be present in two settings. We wanted to see how teachers and parents compare on their assessments.
METHODS: We evaluated how well (CSI-4) reports from 871 parents and 634 teachers of provided information about indicators of school dysfunction.
RESULTS: Kappa values for parent and teacher agreement of any ADHD were at best fair to poor (<0.41). Nevertheless, ADHD identified by each alone provided a moderate amount of information about such indicators of school dysfunction as grade repetition.
CONCLUSION: ADHD identified by a single observer can provide appreciable information about a range of the child’s functions needed for success in school.
The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm
Elizabeth T Jensen, Jelske W van der Burg, Thomas M O'Shea, Robert M Joseph, Elizabeth N Allred, Tim Heeren, Alan Leviton, Karl C K Kuban, Extremely Low Gestational Age Newborns Study Investigators
J Pediatr. 2017 Aug;187:50-57.
OBJECTIVE: To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm.
RESULTS: Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments.
CONCLUSION: In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function.
Antecedents and correlates of blood concentrations of neurotrophic growth factors in very preterm newborns
Alan Levito, Elizabeth N Allred, Hidemi Yamamoto, Raina N Fichorova, Karl Kuban, T Michael O'Shea, Olaf Dammann, ELGAN Study Investigators
Cytokine. 2017 Jun;94:21-28
AIM:To identify antecedents and early correlates of low concentrations of neurotrophic growth factors in blood of extremely preterm newborns during the first postnatal month. RESULTS / CONCLUSIONS: The concentrations of 2 neurotrophic proteins, NT4 and BDNF, were low among children delivered for medical (maternal, fetal) indications, and among those who were growth restricted. Children who had top quartile concentrations of NT4, BDNF, and bFGF tended to have elevated concentrations of inflammation-related proteins that day. This pattern persisted for much of the first postnatal month.
Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes
Sloane K Tilley, Robert M Joseph, Karl C K Kuban, Olaf U Dammann, T Michael O'Shea, Rebecca C Fry
PLoS One. 2017 May 11;12(5):e0176953.
BACKGROUND: Aim to identify genomic biomarkers of IU inflammation in umbilical cord tissue in preterm infants that predict cognitive impairment at 10 years of age. RESULTS / CONCLUSION: Placental indicators of inflammation associated with changes in mRNA expression of 445 genes in umbilical cord. Prenatal intrauterine inflammation is associated with altered gene expression that encode for proteins involved in neuronal development.in umbilical cord tissue. A set of six of the differentially expressed genes predict cognitive impairment later in life, suggesting that the fetal environment is associated with significant adverse effects on neurodevelopment that persist into later childhood.
Neurocognitive Correlates of Attention-Deficit Hyperactivity Disorder Symptoms in Children Born at Extremely Low Gestational Age
Megan N Scott, Scott J Hunter, Robert M Joseph, Thomas Michael OʼShea, Stephen R Hooper, Elizabeth N Allred, Alan Leviton, Karl Kuban
J Dev Behav Pediatr. 2017 May;38:249-259.
OBJECTIVE: Our analyses aimed to evaluate the neuropsychological correlates of ADHD symptoms in ELGANs. METHODS: CSI-4 reports from parents (n = 871) & teachers (n=634) & participants completed standardized neurocognitive & academic function assessments. RESULTS: Children w/ADHD symptoms were at ▲risk for neurocognitive limitations. Associations were weaker if limited to IQ ≥70 or ≥85. Even with IQ ≥85 ADHD sxs more likely have deficits on Working Memory Cluster & NEPSY-II Auditory Response subtest. The risks for impaired academic performance (Z ≤ -1) on components of the WIAT-III were 2-to-3 times higher than ELGANs not having ADHD symptoms. CONCLUSION: In children born EP with ADHD sxs more likely to have neurocognitive impairment. When IQ nl, ADHD associated w/deficits in EF.
Early postnatal illness severity scores predict neurodevelopmental impairments at 10 years of age in children born extremely preterm
J W Logan, O Dammann, E N Allred, C Dammann, K Beam, R M Joseph, T M O'Shea, A Leviton, K C K Kuban
J Perinatol. 2017 May;37:606-614
OBJECTIVE: We sought to evaluate to what extent SNAP-II is predictive of cognitive and other neurodevelopmental impairments at 10 years of age.
RESULTS: An undesirably high SNAP-II (⩾30), present in 23% of participants, was associated with an increased risk of cognitive impairment (IQ, executive function, language ability), adverse neurological outcomes (epilepsy, impaired gross motor function), behavioral abnormalities (attention deficit disorder and hyperactivity), social dysfunction (autistic spectrum disorder) and education-related adversities (school achievement and need for educational supports.
CONCLUSION: Among very preterm newborns, physiologic derangements present in the first 12 postnatal hours are associated with dysfunctions in several neurodevelopmental domains at 10 years of age.
Postnatal systemic inflammation and neuro-ophthalmologic dysfunctions in extremely low gestational age children
Mari Holm, Dordi Austeng, Raina N Fichorova, Elizabeth N Allred, Karl C Kuban, T Michael O'Shea, Olaf Dammann, Alan Leviton, ELGAN Study Investigators
Acta Paediatr. 2017 Mar;106(3):454-45
AIM: We explore whether children born very preterm who have visual dysfunctions are at higher risk for having neonatal systemic inflammation.
RESULTS/CONCLUSION: Only one of 80 assessments (16 proteins on five different days) was significant for visual field deficit, and one for impaired fixation at 2 years. No association was found between strabismus and any inflammatory mediator.
Sexual epigenetic dimorphism in the human placenta: implications for susceptibility during the prenatal period
Elizabeth Martin, Lisa Smeester, Paige A Bommarito, Matthew R Grace, Kim Boggess, Karl Kuban, Margaret R Karagas, Carmen J Marsit, T Michael O'Shea, Rebecca C Fry
Epigenomics. 2017 Mar;9:267-278
AIM: Evaluate placental epigenome sex-based differences in the ELGAN cohort
METHODS: Placental DNA methylation was assessed at more than 480,000 CpG sites from male and female infants enrolled in the extremely low gestational age newborns cohort (ELGAN) and validated in a separate US-based cohort.
RESULTS: A total of n = 2745 CpG sites, representing n = 587 genes, were identified as differentially methylated (p < 1 × 10-7). The majority (n = 582 or 99%) of these were conserved among the New Hampshire Birth Cohort. The identified genes encode proteins related to immune function, growth/transcription factor signaling and transport across cell membranes.
CONCLUSION: Sex-dependent epigenetic patterning in placenta provide insight into infant outcome differences and responses to perinatal environment.