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1. Comparing autism phenotypes in children born extremely preterm and born at term.

Author

Yi, Joe, Bauman, Margaret, Frazier, Jean, Santos, Hudson, Douglas, Laurie, Kuban, Karl, Fry, Rebecca, OShea, T, Joseph, Robert, Lai, Emily, and Bishop, Somer

Subjects
autism diagnostic interview-revised, autism diagnostic observation schedule, autism spectrum disorder, phenotypes, preterm birth, sex, Humans, Infant, Newborn, Female, Autism Spectrum Disorder, Autistic Disorder, Infant, Extremely Premature, Retrospective Studies, Phenotype
Abstract

Children born preterm are at increased risk for autism spectrum disorder (ASD). There is limited knowledge about whether ASD phenotypes in children born preterm differ from children born at term. The objective of this study was to compare ASD core symptoms and associated characteristics among extremely preterm (EP) and term-born children with ASD. EP participants (n = 59) from the Extremely Low Gestational Age Newborn Study who met diagnostic criteria for ASD at approximately 10 years of age were matched with term-born participants from the Simons Simplex Collection on age, sex, spoken language level, and nonverbal IQ. Core ASD symptomatology was evaluated with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). Developmental milestones, anthropometrics, seizure disorder, and psychiatric symptoms were also investigated. The EP group had lower parent-reported symptom scores on ADI-R verbal communication, specifically stereotyped language, and restricted, repetitive behaviors. There were no between-group differences on ADI-R nonverbal communication and ADI-R reciprocal social interaction or with direct observation on the ADOS-2. The EP group was more likely to have delayed speech milestones and lower physical growth parameters. Results from female-only analyses were similar to those from whole-group analyses. In sum, behavioral presentation was similar between EP and IQ- and sex-matched term-born children assessed at age 10 years, with the exception of less severe retrospectively reported stereotyped behaviors, lower physical growth parameters, and increased delays in language milestones among EP-born children with ASD.

Published
2023

2. Innovative computational approaches shed light on genetic mechanisms underlying cognitive impairment among children born extremely preterm

Author

Liu, Weifang, Sun, Quan, Huang, Le, Bhattacharya, Arjun, Wang, Geoffery W, Tan, Xianming, Kuban, Karl CK, Joseph, Robert M, O’Shea, T Michael, Fry, Rebecca C, Li, Yun, and Santos, Hudson P

Subjects
Paediatrics, Biomedical and Clinical Sciences, Neurosciences, Pediatric, Prevention, Human Genome, Brain Disorders, Clinical Research, Behavioral and Social Science, Genetics, Aetiology, 2.3 Psychological, social and economic factors, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Mental health, Adolescent, Brain, Child, Child, Preschool, Cognitive Dysfunction, DNA-Binding Proteins, Genome-Wide Association Study, Humans, Infant, Extremely Premature, Infant, Newborn, Muscle Proteins, Prospective Studies, TEA Domain Transcription Factors, Transcription Factors, Young Adult, Cognitive impairment, Neurodevelopment, Preterm children, Genome-wide association study, Latent profile analysis, Genetic mechanisms, Psychology
Abstract

BackgroundAlthough survival rates for infants born extremely preterm (gestation

Published
2022

3. Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.

Author

Wu, Yvonne, Comstock, Bryan, Mayock, Dennis, Goodman, Amy, Maitre, Nathalie, Chang, Taeun, Van Meurs, Krisa, Lampland, Andrea, Bendel-Stenzel, Ellen, Mathur, Amit, Wu, Tai-Wei, Riley, David, Mietzsch, Ulrike, Chalak, Lina, Flibotte, John, Weitkamp, Joern-Hendrik, Ahmad, Kaashif, Yanowitz, Toby, Baserga, Mariana, Poindexter, Brenda, Rogers, Elizabeth, Lowe, Jean, Kuban, Karl, OShea, T, Wisnowski, Jessica, McKinstry, Robert, Bluml, Stefan, Bonifacio, Sonia, Benninger, Kristen, Rao, Rakesh, Smyser, Christopher, Sokol, Gregory, Merhar, Stephanie, Schreiber, Michael, Glass, Hannah, Heagerty, Patrick, Juul, Sandra, and Gonzalez, Fernando

Subjects
Administration, Intravenous, Cerebral Palsy, Double-Blind Method, Erythropoietin, Humans, Hypothermia, Induced, Hypoxia-Ischemia, Brain, Infant, Infant, Newborn, Neuroprotective Agents
Abstract

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57). CONCLUSIONS: The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).

Published
2022

4. Cerebral Palsy and Motor Impairment After Extreme Prematurity: Prediction of Diagnoses at Ages 2 and 10 Years

Author

Rollins, Julie V., Shah, Bhavesh, Van Marter, Linda, Martin, Camilla, Ware, Janice, Rollins, Caitlin, Cole, Cynthia, Perrin, Ellen, Sakai, Christina, Bednarek, Frank, Ehrenkranz, Richard, Benjamin, Jennifer, Montgomery, Angela, O'Shea, T. Michael, Washburn, Lisa, Bose, Carl, Warner, Diane, Engelke, Steve, Higginson, Amanda, Higginson, Jason, Bear, Kelly, Poortenga, Mariel, Pastyrnak, Steve, Karna, Padu, Paneth, Nigel, Lenski, Madeleine, Schreiber, Michael, Hunter, Scott, Klein, Deborah, Pimental, Maureen, Hallisey, Collen, Coster, Taryn, Dolins, Maddie, Mittleman, Maggie, Haile, Hannah, Rohde, Julia, Pujols, Kaysi Herrera, Nylen, Ellen, Neger, Emily, Mattern, Kathryn, Ma, Catherine, Toner, Deanna, Vitaro, Elizabeth, Venuti, Lauren, Powers, Beth, Foley, Ann, EdM, Merk, Taylor, Williams, Joanne, Romano, Elaine, Henry, Christine, Hiatt, Debbie, Peters, Nancy, Brown, Patricia, Ansusinha, Emily, James, Jazmyne, Yang, Nou, Bose, Gennie, Wereszczak, Janice, Bernhardt, Janice, Adams, Joan, Wilson, Donna, Darden-Saad, Nancy, Williams, Bree, Jones, Emily, Morris, Hannah, Sutton, Dinah, Rathbun, Julie, Fagerman, Stephanie, Boshoven, William, Johnson, Jalen, James, Brandon, Gile, Cynthia, Miras, Karen, Solomon, Carolyn, Weiland, Deborah, Ramoskaite, Rugile, Wiggins, Suzanne, Washington, Krissy, Martin, Ryan, Prendergast, Barbara, Lynch, Emma, Hajdarovic, Sabina, Kring, Beth, Smith, Anne, McQuiston, Susan, Butler, Samantha, Wilson, Rachel, McGhee, Kirsten, Lee, Patricia, Asgarian, Aimee, Sadhwani, Anjali, Henson, Brandi, Keller, Cecelia, Walkowiak, Jenifer, Barron, Susan, Miller, Alice, Dessureau, Brian, Wood, Molly, Damon-Minow, Jill, Mayes, Linda, Tsatsanis, Kathy, Chawarska, Katarzyna, Kim, Sophy, Dieterich, Susan, Bearrs, Karen, Waldrep, Ellen, Friedman, Jackie, Hounshell, Gail, Allred, Debbie, Helms, Rebecca, Whitley, Lynn, Stainback, Gary, Bostic, Lisa, Jacobson, Amanda, McKeeman, Joni, Meyer, Echo, Price, Joan, Lloyd, EdS; Megan, Plesha-Troyke, Susan, Scott, Megan, Solomon, Katherine M., Brooklier, Kara, Vogt, Kelly, Marinelli, Timothy, Yi, Joe X., O'Shea, T.Michael, Joseph, Robert M., Hooper, Stephen R., Kuban, Karl C.K., Msall, Michael E., Fry, Rebecca, and Singh, Rachana

Published
2024
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7. Placental genomics mediates genetic associations with complex health traits and disease

Author

Bhattacharya, Arjun, Freedman, Anastasia N, Avula, Vennela, Harris, Rebeca, Liu, Weifang, Pan, Calvin, Lusis, Aldons J, Joseph, Robert M, Smeester, Lisa, Hartwell, Hadley J, Kuban, Karl CK, Marsit, Carmen J, Li, Yun, O’Shea, T Michael, Fry, Rebecca C, and Santos, Hudson P

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Perinatal Period - Conditions Originating in Perinatal Period, Human Genome, Prevention, Pediatric, Biotechnology, Pediatric Research Initiative, Aetiology, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Adaptor Proteins, Signal Transducing, Animals, Disease, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Guanine Nucleotide Exchange Factors, Humans, Infant, Newborn, Mice, Multifactorial Inheritance, Placenta, Pregnancy, Quantitative Trait Loci, RNA-Seq, Transcriptome
Abstract

As the master regulator in utero, the placenta is core to the Developmental Origins of Health and Disease (DOHaD) hypothesis but is historically understudied. To identify placental gene-trait associations (GTAs) across the life course, we perform distal mediator-enriched transcriptome-wide association studies (TWAS) for 40 traits, integrating placental multi-omics from the Extremely Low Gestational Age Newborn Study. At [Formula: see text], we detect 248 GTAs, mostly for neonatal and metabolic traits, across 176 genes, enriched for cell growth and immunological pathways. In aggregate, genetic effects mediated by placental expression significantly explain 4 early-life traits but no later-in-life traits. 89 GTAs show significant mediation through distal genetic variants, identifying hypotheses for distal regulation of GTAs. Investigation of one hypothesis in human placenta-derived choriocarcinoma cells reveal that knockdown of mediator gene EPS15 upregulates predicted targets SPATA13 and FAM214A, both associated with waist-hip ratio in TWAS, and multiple genes involved in metabolic pathways. These results suggest profound health impacts of placental genomic regulation in developmental programming across the life course.

Published
2022

8. CpG methylation patterns in placenta and neonatal blood are differentially associated with neonatal inflammation

Author

Eaves, Lauren A., Enggasser, Adam E., Camerota, Marie, Gogcu, Semsa, Gower, William A., Hartwell, Hadley, Jackson, Wesley M., Jensen, Elizabeth, Joseph, Robert M., Marsit, Carmen J., Roell, Kyle, Santos Jr., Hudson P., Shenberger, Jeffrey S., Smeester, Lisa, Yanni, Diana, Kuban, Karl C. K., O’Shea, T. Michael, and Fry, Rebecca C.

Published
2023
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9. Perinatal Factors and Emotional, Cognitive, and Behavioral Dysregulation in Childhood and Adolescence

Author

Frazier, Jean A., Li, Xiuhong, Kong, Xiangrong, Hooper, Stephen R., Joseph, Robert M., Cochran, David M., Kim, Sohye, Fry, Rebecca C., Brennan, Patricia A., Msall, Michael E., Fichorova, Raina N., Hertz-Picciotto, Irva, Daniels, Julie L., Lai, Jin-Shei, Boles, Richard E., Zvara, Bharathi J., Jalnapurkar, Isha, Schweitzer, Julie B., Singh, Rachana, Posner, Jonathan, Bennett, Deborah H., Kuban, Karl C.K., and O’Shea, T. Michael

Published
2023
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10. Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm

Author

Santos Jr, Hudson P, Bhattacharya, Arjun, Joseph, Robert M, Smeester, Lisa, Kuban, Karl CK, Marsit, Carmen J, O’Shea, T Michael, and Fry, Rebecca C

Subjects
Preterm, Low Birth Weight and Health of the Newborn, Genetics, Perinatal Period - Conditions Originating in Perinatal Period, Intellectual and Developmental Disabilities (IDD), Human Genome, Neurosciences, Mental Health, Biotechnology, Clinical Research, Brain Disorders, Infant Mortality, Pediatric, Autism, Behavioral and Social Science, Prevention, Aetiology, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Mental health, Adult, Algorithms, Biomarkers, Brain, Case-Control Studies, Child, Cognition, CpG Islands, Female, Genome-Wide Association Study, Genomics, Humans, Infant, Extremely Premature, Infant, Newborn, Intellectual Disability, Intelligence Tests, Male, MicroRNAs, Multivariate Analysis, Placenta, Pregnancy, Premature Birth, RNA, Messenger, Social Behavior, Prenatal neurodevelopmental programming, Social and cognitive impairment, Placental gene regulation, Epigenome-wide association, Differential expression analysis, Multi-omic aggregation, Clinical Sciences
Abstract

BackgroundChildren born extremely preterm are at heightened risk for intellectual and social impairment, including Autism Spectrum Disorder (ASD). There is increasing evidence for a key role of the placenta in prenatal developmental programming, suggesting that the placenta may, in part, contribute to origins of neurodevelopmental outcomes.MethodsWe examined associations between placental transcriptomic and epigenomic profiles and assessed their ability to predict intellectual and social impairment at age 10 years in 379 children from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Assessment of intellectual ability (IQ) and social function was completed with the Differential Ability Scales-II and Social Responsiveness Scale (SRS), respectively. Examining IQ and SRS allows for studying ASD risk beyond the diagnostic criteria, as IQ and SRS are continuous measures strongly correlated with ASD. Genome-wide mRNA, CpG methylation and miRNA were assayeds with the Illumina Hiseq 2500, HTG EdgeSeq miRNA Whole Transcriptome Assay, and Illumina EPIC/850 K array, respectively. We conducted genome-wide differential analyses of placental mRNA, miRNA, and CpG methylation data. These molecular features were then integrated for a predictive analysis of IQ and SRS outcomes using kernel aggregation regression. We lastly examined associations between ASD and the multi-omic-predicted component of IQ and SRS.ResultsGenes with important roles in neurodevelopment and placental tissue organization were associated with intellectual and social impairment. Kernel aggregations of placental multi-omics strongly predicted intellectual and social function, explaining approximately 8% and 12% of variance in SRS and IQ scores via cross-validation, respectively. Predicted in-sample SRS and IQ showed significant positive and negative associations with ASD case-control status.LimitationsThe ELGAN cohort comprises children born pre-term, and generalization may be affected by unmeasured confounders associated with low gestational age. We conducted external validation of predictive models, though the sample size (N = 49) and the scope of the available out-sample placental dataset are limited. Further validation of the models is merited.ConclusionsAggregating information from biomarkers within and among molecular data types improves prediction of complex traits like social and intellectual ability in children born extremely preterm, suggesting that traits within the placenta-brain axis may be omnigenic.

Published
2020

11. Psychiatric Outcomes, Functioning, and Participation in Extremely Low Gestational Age Newborns at Age 15 Years

Author

Frazier, Jean A., Cochran, David, Kim, Sohye, Jalnapurkar, Isha, Joseph, Robert M., Hooper, Stephen R., Santos, Hudson P., Jr., Ru, Hongyu, Venuti, Lauren, Singh, Rachana, Washburn, Lisa K., Gogcu, Semsa, Msall, Michael E., Kuban, Karl C.K., Rollins, Julie V., Hanson, Shannon G., Jara, Hernan, Pastyrnak, Steven L., Roell, Kyle R., Fry, Rebecca C., and O’Shea, T. Michael

Published
2022
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13. Retinopathy of prematurity and neurodevelopmental outcome and quality of life at 10 years of age

Author

Sri, Sudhir, primary, Jensen, Elizabeth, additional, Msall, Michael, additional, Yi, Joe, additional, Zhabotynsky, Vasyl, additional, Joseph, Robert, additional, Kuban, Karl, additional, Frazier, Jean, additional, Hooper, Stephen, additional, Santos, Hudson, additional, Gogcu, Semsa, additional, Shenberger, Jeffrey, additional, Fry, Rebecca, additional, and O'Shea, Thomas, additional

Published
2024
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14. The Impact of Erythropoietin on Short- and Long-Term Kidney-Related Outcomes in Neonates of Extremely Low Gestational Age. Results of a Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial

Author

Juul, Sandra E., Comstock, Bryan A., Wadhawan, Rajan, Mayock, Dennis E., Courtney, Sherry E., Robinson, Tonya, Ahmad, Kaashif A., Bendel-Stenzel, Ellen, Baserga, Mariana, LaGamma, Edmund F., Downey, L. Corbin, Rao, Raghavendra, Fahim, Nancy, Lampland, Andrea, Frantz, Ivan D., III, Khan, Janine Y., Weiss, Michael, Gilmore, Maureen M., Ohls, Robin, Srinivasan, Nishant, Perez, Jorge E., McKay, Victor, Vu, Phuong T., Heagerty, Patrick J., Thomas, Billy, Elhassan, Nahed, Mulkey, Sarah, Dydynski, Philip, Vijayamadhavan, Vivek K., Mulrooney, Neil, Yoder, Bradley, Kase, Jordan S., Check, Jennifer, Gogcu, Semsa, Osterholm, Erin, Ramel, Sara, Bendel, Catherine, Gale, Cheryl, George, Thomas, Georgieff, Michael, Gisslen, Tate, Guiang, Sixto, III, Hall, Anne, Johnson, Dana, Pfister, Katie, Podgorski, Heather, Roberts, Kari, Stepka, Erin, Engel, Melissa, Kamrath, Heidi, Scheurer, Johannah, Hanson, Angela, Satrom, Katherine, Pfister, Susan, Simones, Ann, Plummer, Erin, Zorn, Elizabeth, Martin, Camilia R., O'Reilly, Deirdre, Porta, Nicolas, Bazacliu, Catalina, Williams, Jonathan, Rajderkar, Dhanashree, Northington, Frances, Valdez, Raul Chavez, Beauman, Sandra, Saurabhkumar, Patel, Diaz-Barbosa, Magaly, Serize, Arturo, Jordan, Jorge, Ott, Debbie, Mora, Ariana Franco, Hedrick, Pamela, Flynn, Vicki, Silvia, Amy, Clopp, Bailey, Feltner, John B., Esposito, Isabella, Hauge, Stephanie, Nikirk, Samantha, Purnell, Andrea, Loy, Emilie, Sikes, Natalie, Mason, Melanie, McConnell, Jana, Brown, Tiffany, Harrison, Henry, Pearson, Denise, Drake, Tammy, Wright, Jocelyn, Walden, Debra, Guy, Annette, Nason, Jennifer, Talbot, Morgan, Lee, Kristen, Penny, Sarah, Boles, Terri, Drummond, Melanie, Kohlleppel, Katy, Kathen, Charmaine, Kaletka, Brian, Gonzales, Shania, Worwa, Cathy, Fisher, Molly, Richter, Tyler, Ginder, Alexander, Reich, Brixen, Rau, Carrie, Loertscher, Manndi, Bledsoe, Laura, McGrath, Kandace, Lewis, Kimberlee Weaver, Burnett, Jill, Schaefer, Susan, Bird, Karie, Giblin, Clare, Daly, Rita, Lanier, Kristi, Warden, Kelly, Wassenaar, Jenna, Ericksen, Jensina, Davern, Bridget, Osborne, Mary Pat, Gregorich, Brittany, Talele, Neha, Obregon, Evelyn, Ziyeh, Tiglath, Clarke, Molly, Wegner, Rachel E., Patel, Palak, Schau, Molly, Russow, Annamarie, Curry, Kelly, Sinnamon, Susan, Barnhart, Lisa, Parkinson, Charlamaine, Hanson, Mary, Kuan, Elizabeth, Lacy, Conra Backstrom, Galvis, Edshelee M., Bombino, Susana, Martinez, Denise, Bell, Suzi, Long, Corrie, Longa, Cathy, Westerveld, Michael, McConkey, Stacy, Hay, Anne, Natarajan, Niranjana, Gaudette, Shari, Cobb, Sarah, Sharp, Gregory, Schumacher, Elizabeth, Schuschke, Leslie, Frey, Charlotte, Fierro, Mario, Gilmore, Lois, Lundequam, Pamela, Hoekstra, Ronald, Ketko, Anastasia, Perdue, Nina, Cunningham, Sean, Stout, Kelly, Hall, Becky, Morshedzadeh, Galina, Ostrander, Betsy, Winter, Sarah, Cox, Lauren, Rainaldi, Matthew A., Hensley, Sarah, Morris, Melissa, Roberts, Dia, Tuttle, Melissa, Boys, Christopher, Hultgren, Solveig, Pierpont, Elizabeth I., George, Tom, King, Kelly E., Bataglia, Katherine, Neis, Cathy, Bergeron, Mark, Miller, Cristina, Accomando, Cara, Gavin, Jennifer Anne, Maczek, Elizabeth, Marakovitz, Susan, Knorr, Aimee, Smith, Vincent C., Stewart, Jane E., Weissbourd, Marie, deRegnier, Raye-Ann, Matoba, Nana, Heaton, Shelly C., Cascio, Erika M., Brady, Janet, Ghosh, Suman, Ditto, Jessica, Leppert, Mary, Lowe, Jean, Fuller, Janell, DuPont, Tara, Kloska, Pamela, Patel, Saurabh, Carbonell, Lauren, Patino-Fernandez, Anna Maria, de Lerma, Carmen, McDonough, Kelly, De Cortada, Maiana, Chavis, Lacy, Shannon, Jane, Konodi, Mark A., Nefcy, Christopher, Kuban, Karl C.K., Lowe, Jean R., O'Shea, T. Michael, Dighe, Manjiri, Richards, Todd, Shaw, Dennis W.W., Studholme, Colin, Traudt, Christopher M., Ballard, Roberta, Hartman, Adam, Janis, Scott, Ohls, T. Robin, O'Shea, Michael, Guillet, Ronnie, Ball, M. Bethany, Glass, Hannah, Saville, Ben, Schreiber, Michael, Askenazi, David J., Schmicker, Robert H., Brophy, Patrick, Goldstein, Stuart L., and Hingorani, Sangeeta

Published
2021
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15. Academic Achievement Deficits and their Neuropsychological Correlates in Children Born Extremely Preterm

Author

Akshoomoff, Natacha, Joseph, Robert M., Taylor, H. Gerry, Allred, Elizabeth N., Heeren, Timothy, O'Shea, Thomas M., and Kuban, Karl K.

Abstract

ObjectiveThe purpose of this study was to examine the risks associated with learning disabilities (LD) in a large sample of children born extremely preterm. We predicted higher than expected rates of LD, particularly in math, and children with LD in math, reading, or both would have lower IQs and specific patterns of neuropsychological deficits.MethodWe evaluated academic achievement, rates of LD, and their neuropsychological correlates in the Extremely Low Gestational Age Newborn (ELGAN) Study cohort of 10-year-old children born at 23 to 27 weeks gestational age. Primary analyses focused on children without intellectual disability (verbal IQ > 70 and nonverbal IQ > 70; N=668). Low achievement was defined as a standard score ≤ 85 on the reading or math measures.ResultsThe risk of low math achievement scores (27%) was 1.5 times higher than the risk of low reading achievement scores (17%). Children were classified as having LD based on low achievement criteria in reading only (RD, 6.4% of sample), math only (MD, 16.2%), both reading and math (RD/MD, 8.3%), or no reading or math disabilities (No LD, 69.1%). Although all three LD groups had multiple neuropsychological weaknesses compared to the No LD group, the RD and MD groups had different patterns of neuropsychological impairment.ConclusionThese children from the ELGAN cohort had higher than expected rates of LD, particularly in mathematics, even after taking socioeconomic status into consideration. These results point to specific cognitive weaknesses that differ between extremely preterm children with RD and MD and the utility of neuropsychological assessments in addressing low academic achievement.

Published
2017

17. Association of Circulating Proinflammatory and Anti-inflammatory Protein Biomarkers in Extremely Preterm Born Children with Subsequent Brain Magnetic Resonance Imaging Volumes and Cognitive Function at Age 10 Years

Author

Ware, Janice, Coster, Taryn, Hanson, Brandi, Wilson, Rachel, McGhee, Kirsten, Lee, Patricia, Asgarian, Aimee, Sadhwani, Anjali, Perrin, Ellen, Neger, Emily, Mattern, Kathryn, Walkowiak, Jenifer, Barron, Susan, Shah, Bhavesh, Singh, Rachana, Smith, Anne, Klein, Deborah, McQuiston, Susan, Venuti, Lauren, Powers, Beth, Foley, Ann, Dessureau, Brian, Wood, Molly, Damon-Minow, Jill, Ehrenkranz, Richard, Benjamin, Jennifer, Romano, Elaine, Tsatsanis, Kathy, Chawarska, Katarzyna, Kim, Sophy, Dieterich, Susan, Bearrs, Karen, Peters, Nancy, Brown, Patricia, Ansusinha, Emily, Waldrep, Ellen, Friedman, Jackie, Hounshell, Gail, Allred, Debbie, Engelke, Stephen C., Darden-Saad, Nancy, Stainback, Gary, Warner, Diane, Wereszczak, Janice, Bernhardt, Janice, McKeeman, Joni, Meyer, Echo, Pastyrnak, Steve, Rathbun, Julie, Nota, Sarah, Crumb, Teri, Lenski, Madeleine, Weiland, Deborah, Lloyd, Megan, Hunter, Scott, Msall, Michael, Ramoskaite, Rugile, Wiggins, Suzanne, Washington, Krissy, Martin, Ryan, Prendergast, Barbara, Scott, Megan, Klarr, Judith, Kring, Beth, DeRidder, Jennifer, Vogt, Kelly, Yamamoto, Hidemi, Ryan, Stanthia, Junaid, Damilola, Dawood, Hassan, Beatty, Noah, Luu, Ngan, Tang, Vanessa, Sassi, Rosaria Rita, Pasicznyk, Jenna-Malia, Kuban, Karl C.K., Jara, Hernan, O'Shea, T. Michael, Heeren, Timothy, Joseph, Robert M., Fichorova, Raina N., Alshamrani, Khalid, Aakil, Adam, Beaulieu, Forrest, Horn, Mitchell, Douglass, Laurie M., Frazier, Jean A., Hirtz, Deborah, Rollins, Julie Vanier, Cochran, David, and Paneth, Nigel

Published
2019
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18. Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age

Author

Freedman, Anastasia N., primary, Roell, Kyle, additional, Engwall, Eiona, additional, Bulka, Catherine, additional, Kuban, Karl C. K., additional, Herring, Laura, additional, Mills, Christina A., additional, Parsons, Patrick J., additional, Galusha, Aubrey, additional, O’Shea, Thomas Michael, additional, and Fry, Rebecca C., additional

Published
2023
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20. Among Children Born Extremely Preterm a Higher Level of Circulating Neurotrophins Is Associated with Lower Risk of Cognitive Impairment at School Age

Author

Ware, Janice, Coster, Taryn, Hanson, Brandi, Wilson, Rachel, McGhee, Kirsten, Lee, Patricia, Asgarian, Aimee, Sadhwani, Anjali, Perrin, Ellen, Neger, Emily, Mattern, Kathryn, Walkowiak, Jenifer, Barron, Susan, Shah, Bhavesh, Singh, Rachana, Smith, Anne, Klein, Deborah, McQuiston, Susan, Venuti, Lauren, Powers, Beth, Foley, Ann, Dessureau, Brian, Wood, Molly, Damon-Minow, Jill, Ehrenkranz, Richard, Benjamin, Jennifer, Romano, Elaine, Tsatsanis, Kathy, Chawarska, Katarzyna, Kim, Sophy, Dieterich, Susan, Bearrs, Karen, Peters, Nancy, Brown, Patricia, Ansusinha, Emily, Waldrep, Ellen, Friedman, Jackie, Hounshell, Gail, Allred, Debbie, Engelke, Stephen C., Darden-Saad, Nancy, Stainback, Gary, Warner, Diane, Wereszczak, Janice, Bernhardt, Janice, McKeeman, Joni, Meyer, Echo, Pastyrnak, Steve, Rathbun, Julie, Nota, Sarah, Crumb, Teri, Lenski, Madeleine, Weiland, Deborah, Lloyd, Megan, Hunter, Scott, Msall, Michael, Ramoskaite, Rugile, Wiggins, Suzanne, Washington, Krissy, Martin, Ryan, Prendergast, Barbara, Scott, Megan, Klarr, Judith, Kring, Beth, DeRidder, Jennifer, Vogt, Kelly, Yamamoto, Hidemi, Ryan, Stanthia, Junaid, Damilola, Dawood, Hassan, Beatty, Noah, Luu, Ngan, Tang, Vanessa, Sassi, Rosaria Rita, Pasicznyk, Jenna-Malia, Kuban, Karl C.K., Heeren, Timothy, O'Shea, T. Michael, Joseph, Robert M., Fichorova, Raina N., Douglass, Laurie, Jara, Hernan, Frazier, Jean A., Hirtz, Deborah, Taylor, H. Gerry, Rollins, Julie Vanier, and Paneth, Nigel

Published
2018
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24. Neurocognitive Outcomes at 10 Years of Age in Extremely Preterm Newborns with Late-Onset Bacteremia

Author

Ware, Janice, Coster, Taryn, Hanson, Brandi, Wilson, Rachel, McGhee, Kirsten, Lee, Patricia, Asgarian, Aimee, Sadhwani, Anjali, Perrin, Ellen, Neger, Emily, Mattern, Kathryn, Walkowiak, Jenifer, Barron, Susan, Shah, Bhavesh, Singh, Rachana, Smith, Anne, Klein, Deborah, McQuiston, Susan, Venuti, Lauren, Powers, Beth, Foley, Ann, Dessureau, Brian, Wood, Molly, Damon-Minow, Jill, Ehrenkranz, Richard, Benjamin, Jennifer, Romano, Elaine, Tsatsanis, Kathy, Chawarska, Katarzyna, Kim, Sophy, Dieterich, Susan, Bearrs, Karen, Peters, Nancy, Brown, Patricia, Ansusinha, Emily, Waldrep, Ellen, Friedman, Jackie, Hounshell, Gail, Allred, Debbie, Engelke, Stephen C., Darden-Saad, Nancy, Stainback, Gary, Warner, Diane, Wereszczak, Janice, Bernhardt, Janice, McKeeman, Joni, Meyer, Echo, Pastyrnak, Steve, Rathbun, Julie, Nota, Sarah, Crumb, Teri, Lenski, Madeleine, Weiland, Deborah, Lloyd, Megan, Hunter, Scott, Msall, Michael, Ramoskaite, Rugile, Wiggins, Suzanne, Washington, Krissy, Martin, Ryan, Prendergast, Barbara, Scott, Megan, Klarr, Judith, Kring, Beth, DeRidder, Jennifer, Vogt, Kelly, Bright, H. Reeve, Babata, Kikelomo, Allred, Elizabeth N., Erdei, Carmina, Kuban, Karl C.K., Joseph, Robert M., O'Shea, T. Michael, Leviton, Alan, and Dammann, Olaf

Published
2017
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25. The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm

Author

Shah, Bhavesh, Singh, Rachana, Smith, Anne, Klein, Deborah, McQuiston, Susan, Rollins, Julie, Douglass, Laurie, Ware, Janice, Coster, Taryn, Henson, Brandi, Wilson, Rachel, McGhee, Kirsten, Lee, Patricia, Asgarian, Aimee, Sadhwani, Anjali, Perrin, Ellen, Neger, Emily, Mattern, Kathryn, Walkowiak, Jenifer, Barron, Susan, Frazier, Jean, Venuti, Lauren, Powers, Beth, Foley, Ann, Dessureau, Brian, Wood, Molly, Damon-Minow, Jill, Ehrenkranz, Richard, Benjamin, Jennifer, Romano, Elaine, Tsatsanis, Kathy, Chawarska, Katarzyna, Kim, Sophy, Dieterich, Susan, Bearrs, Karen, O'Shea, T. Michael, Peters, Nancy, Brown, Patricia, Ansusinha, Emily, Waldrep, Ellen, Friedman, Jackie, Hounshell, Gail, Allred, Debbie, Engelke, Stephen C., Darden-Saad, Nancy, Stainback, Gary, Warner, Diane, Wereszczak, Janice, Bernhardt, Janice, McKeeman, Joni, Meyer, Echo, Pastyrnak, Steve, Burdo-Hartman, Wendy, Rathbun, Julie, Nota, Sarah, Crumb, Teri, Lenski, Madeleine, Weiland, Deborah, Lloyd, Megan, Hunter, Scott, Msall, Michael, Ramoskaite, Rugile, Wiggins, Suzanne, Washington, Krissy, Martin, Ryan, Prendergast, Barbara, Scott, Megan, Klarr, Judith, Kring, Beth, DeRidder, Jennifer, Vogt, Kelly, Jensen, Elizabeth T., van der Burg, Jelske W., O'Shea, Thomas M., Joseph, Robert M., Allred, Elizabeth N., Heeren, Tim, Leviton, Alan, and Kuban, Karl C.K.

Published
2017
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29. A multi‐omic approach identifies an autism spectrum disorder ( ASD ) regulatory complex of functional epimutations in placentas from children born preterm

Author

Freedman, Anastasia N., primary, Clark, Jeliyah, additional, Eaves, Lauren A., additional, Roell, Kyle, additional, Oran, Ali, additional, Koval, Lauren, additional, Rager, Julia, additional, Santos, Hudson P., additional, Kuban, Karl, additional, Joseph, Robert M., additional, Frazier, Jean, additional, Marsit, Carmen J., additional, Burt, Amber A., additional, O'Shea, T. Michael, additional, and Fry, Rebecca C., additional

Published
2023
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31. Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

Author

Ware, Janice, Coster, Taryn, Hanson, Brandi, Wilson, Rachel, McGhee, Kirsten, Lee, Patricia, Asgarian, Aimee, Sadhwani, Anjali, Perrin, Ellen, Neger, Emily, Mattern, Kathryn, Walkowiak, Jenifer, Barron, Susan, Shah, Bhavesh, Singh, Rachana, Smith, Anne, Klein, Deborah, McQuiston, Susan, Venuti, Lauren, Powers, Beth, Foley, Ann, Dessureau, Brian, Wood, Molly, Damon-Minow, Jill, Ehrenkranz, Richard, Benjamin, Jennifer, Romano, Elaine, Tsatsanis, Kathy, Chawarska, Katarzyna, Kim, Sophy, Dieterich, Susan, Bearrs, Karen, Peters, Nancy, Brown, Patricia, Ansusinha, Emily, Waldrep, Ellen, Friedman, Jackie, Hounshell, Gail, Allred, Debbie, Engelke, Stephen C., Darden-Saad, Nancy, Stainback, Gary, Warner, Diane, Wereszczak, Janice, Bernhardt, Janice, McKeeman, Joni, Meyer, Echo, Pastyrnak, Steve, Rathbun, Julie, Nota, Sarah, Crumb, Teri, Lenski, Madeleine, Weiland, Deborah, Lloyd, Megan, Hunter, Scott, Msall, Michael, Ramoskaite, Rugile, Wiggins, Suzanne, Washington, Krissy, Martin, Ryan, Prendergast, Barbara, Scott, Megan, Klarr, Judith, Kring, Beth, DeRidder, Jennifer, Vogt, Kelly, Kuban, Karl C.K., Joseph, Robert M., O'Shea, Thomas M., Allred, Elizabeth N., Heeren, Timothy, Douglass, Laurie, Stafstrom, Carl E., Jara, Hernan, Frazier, Jean A., Hirtz, Deborah, and Leviton, Alan

Published
2016
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32. Weight Status in the First 2 Years of Life and Neurodevelopmental Impairment in Extremely Low Gestational Age Newborns

Author

Lee, Kathleen, McGovern, Anne, Gambardella, Jill, Ursprung, Susan, Kristen Ecklund, Ruth Blomquist, Bassan, Haim, Butler, Samantha, Duplessis, Adré, Hahn, Cecil, Limperopoulos, Catherine, Khwaja, Omar, Soul, Janet S., Shah, Bhavesh, Christianson, Karen, Hampf, Frederick, Gilmore, Herbert, McQuiston, Susan, Martin, Camilia R., Hallisey, Colleen, Hurley, Caitlin, Creixell, Miren, Share, Jane, Van Marter, Linda J., Durfee, Sara, Insoft, Robert M., Wilson, Jennifer G., Pimental, Maureen, Westra, Sjirk J., Krishnamoorthy, Kalpathy, Cole, Cynthia, Fiascone, John M., Madden, Janet, Nylen, Ellen, Furey, Anne, McCauley, Roy, Church, Paige T., Keller, Cecelia, Miller, Karen J., Bednarek, Francis, Naples, Mary, Powers, Beth, Wellman, Jacqueline, Adair, Robin, Bream, Richard, Miller, Alice, Scheiner, Albert, Stine, Christy, Ehrenkranz, Richard, Williams, Joanne, Romano, Elaine, Miller, Cindy, Close, Nancy, O'Shea, T. Michael, Gordon, Debbie, Harold, Teresa, Specter, Barbara, Allred, Deborah, Dillard, Robert, Goldstein, Don, Hiatt, Deborah, Hounshell, Gail, Waldrep, Ellen, Washburn, Lisa, Welch, Cherrie D., Engelke, Stephen C., Moseley, Sherry, Pare, Linda, Smart, Donna, Wilson, Joan, Adler, Ira, Buckwald, Sharon, Helms, Rebecca, Kerkering, Kathyrn, MacGilvray, Scott S., Resnik, Peter, Bose, Carl, Bose, Gennie, Fordham, Lynn A., Bostic, Lisa, Marshall, Diane, Milowic, Kristi, Wereszczak, Janice, Poortenga, Mariel, Sutton, Dinah, Betz, Bradford W., Bezinque, Steven L., Junewick, Joseph, Burdo-Hartman, Wendy, Fagerman, Lynn, Lohr, Kim, Pastyrnak, Steve, Solomon, Carolyn, Cavenagh, Ellen, Caine, Victoria J., Olomu, Nicholas, Price, Joan, Paneth, Nigel, Karna, Padmani, Lenski, Madeleine, Schreiber, Michael D., Yoon, Grace, Feinstein, Kate, Caldarelli, Leslie, O'Connor, Sunila E., Msall, Michael, Plesha-Troyke, Susan, Batton, Daniel, Kring, Beth, Brooklier, Karen, Oca, Melisa J., Solomon, Katherine M., Belfort, Mandy B., Kuban, Karl C.K., Allred, Elizabeth N., Ehrenkranz, Richard A., and Leviton, Alan

Published
2016
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34. Growth During Infancy After Extremely Preterm Birth: Associations with Later Neurodevelopmental and Health Outcomes

Author

O’Shea, T. Michael, primary, Register, Hannah M., additional, Yi, Joe X., additional, Jensen, Elizabeth T., additional, Joseph, Robert M., additional, Kuban, Karl C.K., additional, Frazier, Jean A., additional, Washburn, Lisa, additional, Belfort, Mandy, additional, South, Andrew M., additional, Santos, Hudson P., additional, Shenberger, Jeffrey, additional, Perrin, Eliana M., additional, Thompson, Amanda L., additional, Singh, Rachana, additional, Rollins, Julie, additional, Gogcu, Semsa, additional, Sanderson, Keia, additional, Wood, Charles, additional, and Fry, Rebecca C., additional

Published
2023
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39. Association of prenatal modifiable risk factors with attention-deficit hyperactivity disorder outcomes at age 10 and 15 in an extremely low gestational age cohort

Author

Cochran, David M., primary, Jensen, Elizabeth T., additional, Frazier, Jean A., additional, Jalnapurkar, Isha, additional, Kim, Sohye, additional, Roell, Kyle R., additional, Joseph, Robert M., additional, Hooper, Stephen R., additional, Santos, Hudson P., additional, Kuban, Karl C. K., additional, Fry, Rebecca C., additional, and O’Shea, T. Michael, additional

Published
2022
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41. Extremely low gestational age and very low birthweight for gestational age are risk factors for autism spectrum disorder in a large cohort study of 10-year-old children born at 23–27 weeks’ gestation

Author

Joseph, Robert M., Korzeniewski, Steven J., Allred, Elizabeth N., OʼShea, Michael T., Heeren, Tim, Frazier, Jean A., Ware, Janice, Hirtz, Deborah, Leviton, Alan, Kuban, Karl, Ware, Janice, Coster, Taryn, Henson, Brandi, Wilson, Rachel, McGhee, Kirsten, Lee, Patricia, Asgarian, Aimee, Sadhwani, Anjali, Perrin, Ellen, Neger, Emily, Mattern, Kathryn, Walkowiak, Jenifer, Barron, Susan, Frazier, Jean, Venuti, Lauren, Powers, Beth, Foley, Ann, Dessureau, Brian, Wood, Molly, Damon-Minow, Jill, Ehrenkranz, Richard, Benjamin, Jennifer, Romano, Elaine, Tsatsanis, Kathy, Chawarska, Katarzyna, Kim, Sophy, Dieterich, Susan, Bearrs, Karen, OʼShea, Michael T., Peters, Nancy, Brown, Patricia, Ansusinha, Emily, Waldrep, Ellen, Friedman, Jackie, Hounshell, Gail, Allred, Debbie, Engelke, Stephen C., Darden-Saad, Nancy, Stainback, Gary, Warner, Diane, Wereszczak, Janice, Bernhardt, Janice, McKeeman, Joni, Meyer, Echo, Pastyrnak, Steve, Burdo-Hartman, Wendy, Rathbun, Julie, Nota, Sarah, Crumb, Teri, Lenski, Madeleine, Weiland, Deborah, Lloyd, Megan, Hunter, Scott, Msall, Michael, Ramoskaite, Rugile, Wiggins, Suzanne, Washington, Krissy, Martin, Ryan, Prendergast, Barbara, Scott, Megan, Klarr, Judith, Kring, Beth, DeRidder, Jennifer, and Vogt, Kelly

Published
2017
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43. Placental transcriptional signatures associated with cerebral white matter damage in the neonate

Author

Fry, Rebecca C., Roell, Kyle, O'Shea, T. Michael, Kuban, Karl, and Marable, Carmen Amelia

Subjects
General Neuroscience
Abstract

Cerebral white matter is the most common anatomic location of neonatal brain injury in preterm newborns. Factors that predispose preterm newborns to white matter damage are understudied. In relation to studies of the placenta-brain-axis, dysregulated placental gene expression may play a role in preterm brain damage given its implication in programming early life origins of disease, including neurological disorders. There is a critical need to investigate the relationships between the placental transcriptome and white matter damage in the neonate. In a cohort of extremely low gestational age newborns (ELGANs), we aimed to investigate the relationship between the placental transcriptome and white matter damage as assessed by neonatal cranial ultrasound studies (echolucency and/or ventriculomegaly). We hypothesized that genes involved in inflammatory processes would be more highly expressed in placentas of ELGANs who developed ultrasound-defined indicators of white matter damage. Relative to either form of white matter damage, 659 placental genes displayed altered transcriptional profiles. Of these white matter damage-associated genes, largely distinct patterns of gene expression were observed in the study (n = 415/659 genes). Specifically, 381 genes were unique to echolucency and 34 genes were unique to ventriculomegaly. Pathways involved in hormone disruption and metabolism were identified among the unique echolucency or ventriculomegaly genes. Interestingly, a common set of 244 genes or 37% of all genes was similarly dysregulated in the placenta relative to both echolucency and ventriculomegaly. For this common set of white matter damage-related genes, pathways involved in inflammation, immune response and apoptosis, were enriched. Among the white matter damage-associated genes are genes known to be involved in Autism Spectrum Disorder (ASD) and endocrine system disorders. These data highlight differential mRNA expression patterning in the placenta and provide insight into potential etiologic factors that may predispose preterm newborns to white matter damage. Future studies will build upon this work to include functional measures of neurodevelopment as well as measures of brain volume later in life.

Published
2022

45. The placenta epigenome–brain axis: placental epigenomic and transcriptomic responses that preprogram cognitive impairment

Author

Freedman, Anastasia N, primary, Eaves, Lauren A, additional, Rager, Julia E, additional, Gavino-Lopez, Noemi, additional, Smeester, Lisa, additional, Bangma, Jacqueline, additional, Santos, Hudson P, additional, Joseph, Robert M, additional, Kuban, Karl CK, additional, O'Shea, Thomas Michael, additional, and Fry, Rebecca C, additional

Published
2022
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46. CpG methylation patterns in placenta and neonatal blood are differentially associated with neonatal inflammation

Author

Eaves, Lauren A., primary, Enggasser, Adam E., additional, Camerota, Marie, additional, Gogcu, Semsa, additional, Gower, William A., additional, Hartwell, Hadley, additional, Jackson, Wesley M., additional, Jensen, Elizabeth, additional, Joseph, Robert M., additional, Marsit, Carmen J., additional, Roell, Kyle, additional, Santos, Hudson P., additional, Shenberger, Jeffrey S., additional, Smeester, Lisa, additional, Yanni, Diana, additional, Kuban, Karl C. K., additional, O’Shea, T. Michael, additional, and Fry, Rebecca C., additional

Published
2022
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