Neurocognitive and Health Correlates of Overweight and Obesity among Ten-Year-Old Children Born Extremely Preterm
Olivia Linthavong, T Michael O'Shea, Elizabeth Allred, Eliana Perrin, Melissa Bauserman, Robert M Joseph, Alan Leviton, Timothy C Heeren, Karl C K Kuban, Extremely Low Gestational Age Newborn (ELGAN) Research Study
J Pediatr. 2018 Sep;200:84-90.e4.
BMI category at 10 years was not associated with differences in intelligence, language, or academic achievement. Parents of children with obesity were more likely to report their child had asthma (OR 2.2; 95% CI 1.4-3.5), fair/poor general health (OR 3.2; 95% CI 1.4-7.5), and decreased physical function (OR 1.7; 95% CI 1.1-2.9) but less likely to have physician diagnosed attention-deficit/hyperactivity disorder (OR 0.5; 95% CI 0.3-0.97) or an individualized education plan (OR 0.6; 95% CI 0.4-0.99).
CONCLUSION: Among children born EP, elevated BMI is not associated with a difference in neurocognitive function. However, asthma, fair/poor general health, and decreased physical function more prevalent among participants with obesity, and ADHD and individualized education plan were less prevalent.
Risk factors for chronic lung disease and asthma differ among children born extremely preterm
Wesley M Jackson, Thomas Michael O'Shea, Elizabeth N Allred, Matthew M Laughon, William Adam Gower, Alan Leviton
Pediatr Pulmonol. 2018 Aug 29. doi: 10.1002/ppul.24148.
CLD diagnosed during neonatal admission was associated with bronchodilator use at 12 months and 24 months (P < 0.001), but not with an asthma diagnosis at 10 years (Odds Ratio 1.3; 95% confidence interval 0.98-1.8). While risk factors for CLD include lower gestational age (OR 2.7; 1.5-4.7) and fetal growth restriction (OR 2.3; 1.4-3.7), risk factors for asthma include mother’s eligibility for public insurance (Medicaid) (OR 1.8; 1.1-2.8), and higher weight gain velocity during the first year (OR 1.5; 1.02-2.2) and between the 2nd and 10th year (OR 1.7; 1.2-2.4).
CONCLUSIONS: Among children born EP, the dx of CLD and its antecedents associated with transient preschool wheezing, but not with asthma. Post-NICU factors, such as growth velocity and socioeconomic disadvantage, appear to have stronger associations with asthma than exposures during NICU admission.
Assessing Positive Child Health among Individuals Born Extremely Preterm
Jacqueline T Bangma, Evan Kwiatkowski, Matthew Psioda, Hudson P Santos Jr, Stephen R Hooper, Laurie Douglass, Robert M Joseph, Jean A Frazier, Karl C K Kuban, Thomas M O'Shea, Rebecca C Fry
J Pediatr. 2018 Aug 2. pii: S0022-3476(18)30836-9.
OBJECTIVE: To assess development of a Positive Child Health Index (PCHI) based on 11 adverse outcomes & evaluate association of PCHI with QoL
RESULTS: Among ELGAN children, higher PCHI scores associated with higher QoL scores for all QoL categories. Children with no disorders and a PCHI of 100% had Pediatric QoL Inventory total scores 11 points higher than children with 1 or more adverse outcomes (PCHI of <100%). Boys had lower QoL scores for the total, psychosocial, social, and school categories.
CONCLUSIONS: PCHI was associated with QoL across the ELGAN cohort at school age. In the current study, the PCHI encompassed 11 outcomes assessed.
Among Children Born Extremely Preterm a Higher Level of Circulating Neurotrophins Is Associated with Lower Risk of Cognitive Impairment at School Age
Karl C K Kuban, Timothy Heeren, T Michael O'Shea, Robert M Joseph, Raina N Fichorova, Laurie Douglass, Hernan Jara, Jean A Frazier, Deborah Hirtz, H Gerry Taylor, Julie Vanier Rollins, Nigel Paneth, ELGAN Study Investigators
J Pediatr. 2018 Jul 18. pii: S0022-3476(18)30677-2.
Controlling for the effects of inflammatory proteins, persistently elevated blood levels of ≥4 neurotrophic proteins were associated with reduced risk of moderate (OR, 0.35; 95% CI, 0.18-0.67) and severe cognitive impairment (OR, 0.22; 95% CI, 0.09-0.53). Children with a cluster of elevated proteins including angiopoietin 1, brain-derived neurotrophic factor, and regulated upon activation, normal T-cell expressed, and secreted had a reduced risk of adverse cognitive outcomes (OR range, 0.31-0.6). The risk for moderate to severe cognitive impairment was least with 0-1 inflammatory and >4 neurotrophic proteins.
CONCLUSIONS: Persisting elevations of circulating neurotrophic proteins during the first 2 weeks of life are associated with lowered risk of impaired cognition at 10 years of age, controlling for increases in inflammatory proteins.
Accuracy of the Bayley-II mental development index at 2 years as a predictor of cognitive impairment at school age among children born extremely preterm
Thomas M O'Shea, Robert M Joseph, Elizabeth N Allred, H Gerry Taylor, Alan Leviton, Tim Heeren, Laurie M Douglass, Jean A Frazier, Hernan Jara, Karl C K Kuban, ELGAN Study Investigators
J Perinatol. 2018 Jul;38:908-916.
Almost two-thirds of children with a low MDI had a normal IQ (≥ 70) at 10 years. Concordance between MDI and IQ was highest among children with major motor and/or sensory impairment, and when MDI was adjusted for gestational age.
CONCLUSION: Most children born extremely preterm with low BSID-II MDI at 2 years have normal intelligence at school age.
Elevated protein concentrations in newborn blood and the risks of autism spectrum disorder, and of social impairment, at age 10 years among infants born before the 28th week of gestation
Steven J Korzeniewski, Elizabeth N Allred, T Michael O'Shea, Alan Leviton, Karl C K Kuban, ELGAN study investigators
Transl Psychiatry. 2018 Jun 8;8(1):115.
ASD (N = 36) assessed at age 10 years is associated with recurrent top quartile concentrations of inflammation-related proteins during the first post-natal month (e.g., SAA odds ratio (OR); 95% confidence interval (CI): 2.5; 1.2-5.3) and IL-6 (OR; 95% CI: 2.6; 1.03-6.4)). Top quartile concentrations of neurotrophic proteins appear to moderate the increased risk of ASD associated with repeated top quartile concentrations of inflammation-related proteins. High (top quartile) concentrations of SAA are associated with elevated risk of ASD (2.8; 1.2-6.7) when Ang-1 concentrations are below the top quartile, but not when Ang-1 concentrations are high (1.3; 0.3-5.8). Similarly, high concentrations of TNF-α are associated with heightened risk of SRS-defined social impairment (N = 130) (2.0; 1.1-3.8) when ANG-1 concentrations are not high, but not when ANG-1 concentrations are elevated (0.5; 0.1-4.2).
Socioemotional dysfunctions at age 10 years in extremely preterm newborns with late-onset bacteremia
Kikelomo Babata, H. Reeve Bright, Elizabeth N. Allred, Carmina Erdei, Karl C. K. Kuban, Robert M. Joseph, T. Michael O’Shea, Olaf Dammann, Alan Leviton, The ELGAN Study Investigators
Early Hum Dev. 2018 Jun;121:1-7.
We sought to identify communication and socioemotional characteristics associated with suspected and definite late-bacteremia among 10-y-o children born EP. Definite late-bacteremia was associated with a small but non-statistically significant increased risk of autism on the Autism Diagnostic Observation Schedule-2. Definite late-bacteremia was not associated with behavioral problems identified with the Child Symptom Inventory-4. Compared to peers without bacteremia, those born EP who had suspected or definite late-bacteremia were at increased risk of social and communication impairments identified by SRS and Children’s Communication Checklist-2.
Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life
Sloane K Tilley, Elizabeth M Martin, Lisa Smeester, Robert M Joseph, Karl C K Kuban, Tim C Heeren, Olaf U Dammann, T Michael O'Shea, Rebecca C Fry
PLoS One. 2018 Mar 7;13(3):e0193271.
Genome-wide placental CpG methylation levels were compared between spontaneous versus indicated deliveries from EP births (EPTBs) (n = 84). Spontaneous EPTB associated with differential CpG methylation levels in 250 CpG sites (217 unique genes) with the majority displaying hypermethylation. The identified genes known to play a role in neurodevelopment. The placental CpG methylation levels for 17 of these sites predicted cognitive function at ten years of age. CONCLUSION: A hypermethylation signature is present in DNA from placentas in infants with spontaneous EPTB. CpG methylation levels of critical neurodevelopment genes in the placenta predicted later life cognitive function.
Placental CpG methylation of HPA-axis genes is associated with cognitive impairment at age 10 among children born extremely preterm
C J Meakin, E M Martin, H P Santos Jr, I Mokrova, K Kuban, T M O'Shea, R M Joseph, L Smeester, R C Fry
Horm Behav. 2018 Mar 5. pii: S0018-506X(17)30336-7.
We set out to determine if CpG methylation of HPA axis-associated genes in the placenta was predictive of children’s health outcomes. 14 genes known to play a role in HPA axis function were examined across 84 placental samples from the ELGAN cohort and included in a multi-variable logistic regression model. The methylation levels for a set of nine HPA axis-associated genes were significantly (p<0.05) associated with LPA score at 10 years of age. Overall, 9 HPA axis associated genes were significantly associated with LPA score later in life and play key roles in regulating HPA axis function and also play integral roles in memory, learning, and the development of psychological disorders. Given the plasticity of the epigenome during the prenatal period, these alterations could be influenced by exposure to environmental contaminants, including EDCs.
Are Extremely Low Gestational Age Newborns Born to Obese Women at Increased Risk of Cerebral Palsy at 2 Years?
Jelske W van der Burg, T Michael O'Shea, Karl Kuban, Elizabeth N Allred, Nigel Paneth, Olaf Dammann, Alan Leviton
J Child Neurol. 2018 Mar;33(3):216-224.
Overweight and obese women were not at increased risk of giving birth to a child who had CP. The risk ratios associated with overweight varied between 1.1 for quadriparesis (95% CI = 0.5, 2.1) to 2.0 for hemiparesis (95% CI = 0.4, 9.8). The risk ratios associated with obesity varied between 0.7 for diparesis (95% CI = 0.2, 2.5) to 2.5 for hemiparesis (95% CI = 0.4, 13).