Casey Krueger

All Publications

• Respiratory Outcomes of Infants Born Extremely Preterm in the Necrotizing Enterocolitis Surgery Trial. The Journal of pediatrics DeMauro, S. B., Jensen, E. A., McDonald, S. A., Hintz, S., Tyson, J., Stevenson, D. K., Blakely, M. L. 2024: 114391

  Abstract

  The multicenter Necrotizing Enterocolitis Surgery Trial compared initial peritoneal drainage with laparotomy among infants with extremely low birth weight and surgical necrotizing enterocolitis or intestinal perforation. In this post hoc analysis of trial data, initial drainage was associated with adverse respiratory outcomes, both in hospital and through 2 years corrected age.

  View details for DOI 10.1016/j.jpeds.2024.114391

  View details for PubMedID 39521175

• Trends in sex differences in neurodevelopmental outcomes among extremely preterm infants. Archives of disease in childhood. Fetal and neonatal edition Boghossian, N. S., Mack, N., Bell, E. F., Tan, S., Stoll, B., Rysavy, M., Ambalavanan, N., Tyson, J. E., Das, A., Hintz, S. R., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Jobe, A. H., Caplan, M. S., Polin, R. A., Oh, W., Keszler, M., Laptook, A. R., Vohr, B. R., Hensman, A. M., Burke, R. T., Stephens, B. E., Yatchmink, Y., Alksninis, B., Basso, K., Vieira, E., Keszler, L., Knoll, A., Leach, T. M., Leonard, M. R., Noel, L., Pierre, L. S., Vogt, R. A., Watson, V. E., Hibbs, A. M., Fanaroff, A. A., Wilson-Costello, D. E., Newman, N. S., Siner, B. S., Williams, A., Roth, E., Truog, W., Kilbride, H., Parimi, P., Gauldin, C., Scott, A., Johnson, K., Gaetano, L., Merhar, S. L., Poindexter, B. B., Schibler, K., Russell, D., Donovan, E. F., Bridges, K., Steichen, J. J., Yolton, K., Alexander, B., Fischer, E. E., Grisby, C., Mersmann, M. W., Mincey, H. L., Hessling, J., Gratton, T. L., Jackson, L. D., Kirker, K., Muthig, G., Stacey, S., Hayes, D., Thompson, J., Beiersdorfer, T., Goldberg, R. N., Michael Cotten, C., Goldstein, R. F., Auten, K. J., Finkle, J., Fisher, K. A., Foy, K. A., Grimes, S., Gustafson, K. E., Lohmeyer, M. B., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Clark, C. L., Patel, R. M., Carlton, D. P., Adams-Chapman, I., Hale, E. C., Loggins, Y. C., Bottcher, D. I., LaRossa, M. M., Carter, S. L., Sewell, L., Sanders, A., Smikle, G., Mackie, C., Laursen, J., Bremer, A. A., Higgins, R. D., Wright, L. L., McClure, E. M., Archer, S. W., Sokol, G. M., Poindexter, B. B., Lemons, J. A., Dusick, A. M., Papile, L., Harmon, H., Lytle, C., Bohnke, L. G., Eaken, G., Herron, D. E., Hines, A., Miller, L. C., Minnich, H. M., Richard, L., Wilson, L. D., Watkins, D., Gunn, S., Joyce, J., Khan, A. M., Kennedy, K. A., Jones, P. M., Evans, P. W., Akpa, E. G., Alaniz, N. I., Allain, E., Arldt-McAlister, J., Boricha, F., Brandt, P., Burson, K., Guajardo, M. C., Dempsey, A., Dieterich, S. E., Harris, B. F., Franco, C. I., Garcia, C., Green, C., Hall, D., Jiminez, M., John, J., Lis, A. E., Major-Kincade, T., Martin, K., Martin, S. C., Mason, C. M., McDavid, G. E., McKee, S. L., Morris, B. H., Orekoya, P. A., Boral, D. S., Pierce Tate, P. L., Poundstone Lillie, M. L., Reddoch, S., Reddy, T., Rodgers, S., Siddiki, S. K., Simmons, M. C., Sperry, D., Stephens, E., Whitely, L. L., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Kenneth Poole, W., Wallace, D., Newman, J. E., Auman, J. O., Crawford, M. M., Hastings, B. K., McClure, E. M., Petrie Huitema, C. M., Zaterka-Baxter, K. M., Meurs, K. P., Chock, V. Y., Stevenson, D. K., Bethany Ball, M., Adams, M. M., Ahlfors, C. E., Baran, J. M., Bentley, B., Bond, L. E., Brudos, G. K., Davis, A. S., DeAnda, M. E., DeBattista, A. M., Fleisher, B. E., Huffman, L. C., Kohn, J. G., Krueger, C., Lee-Ancajas, J. C., Palmquist, A. W., Proud, M. S., Pyle, R. P., Sivakumar, D., Stebbins, R. D., John, N. H., Weiss, H. E., Frantz, I. D., McGowan, E. C., MacKinnon, B. L., Nylen, E., Furey, A., Brussa, A., Sibley, C., Peralta-Carcelen, M., Nelson, K. G., Bailey, K. J., Biasini, F. J., Chopko, S. A., Collins, M. V., Cosby, S. S., Moses, M. B., Phillips, V. A., Preskitt, J., Rector, R. V., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Finer, N. N., Rasmussen, M. R., Vaucher, Y. E., Wozniak, P. R., Arnell, K., Bridge, R., Demetrio, C., Fuller, M. G., Rich, W., Colaizy, T. T., Widness, J. A., Harmon, H. M., Brumbaugh, J. E., Acarregui, M. J., Johnson, K. J., Eastman, D. L., Walker, J. R., Goecke, C. A., Schmelzel, M. L., Baack, M. L., Hogden, L. A., Henning, M. M., Elenkiwich, C., Broadbent, M., Muyden, S. V., Ellsbury, D. L., Bass, D. B., Tud, T. L., Duara, S., Bauer, C. R., Everett-Thomas, R., Worth, A. M., Allison, M., Diaz, A. N., Mathews, E. E., Hamlin-Smith, K., Jean-Gilles, L., Calejo, M., Eguaras, S. M., Fajardo-Hiriart, S., Gideon, Y. C., Berkovits, M. H., Stoerger, A., Garcia, A., Pierre, H., Roder, G., Riguad, A., Watterberg, K. L., Fuller, J., Ohls, R. K., Papile, L., Lacy, C. B., Hartenberger, C., Brown, S., Lowe, J. R., Montman, R., Beauman, S., Hanson, M., Kuan, E., DeMauro, S. B., Eichenwald, E. C., Schmidt, B., Kirpalani, H., Chaudhary, A. S., Abbasi, S., Cucinotta, D. M., Bernbaum, J. C., Catts, C., Gerdes, M., Ghavam, S., Hurt, H., Mancini, T., Snyder, J., Ziolkowski, K., D'Angio, C. T., Phelps, D. L., Guillet, R., Lakshminrusimha, S., Myers, G. J., Burnell, E., Guilford, S., Horihan, C. A., Hust, D., Jensen, R. L., Johnson, J. B., Kushner, E., Maffett, D., Merzbach, J., Reubens, L. J., Reynolds, A. M., Rowan, M., Wadkins, H. I., Williams, A., Yost, K., Zwetsch, L., Kent, A., Prinzing, D., Scorsone, A. M., Hunn, J., Bowman, M., Orme, C., Binion, K., Sabaratnam, P., Jones, R., Boylin, E., McKee, K., Sacilowski, M., Rochez, D., Li, E., Kachelmeyer, J., Coleman, K., Hartley-McAndrew, M., Farooq, O., Zorn, W., Korones, S. B., Bada, H. S., Hudson, T., Williams, M., Yolton, K., Wyckoff, M. H., Brion, L. P., Sanchez, P. J., Laptook, A. R., Rosenfeld, C. R., Salhab, W. A., Sue Broyles, R., Heyne, R. J., Ipson, M., Adams, S. S., Jeannette Burchfield, P., Chen, L., Leon, M. D., Dooley, C., Eubanks, F., Guzman, A., Hensley, G., Heyne, E. T., Hickman, J. F., Leps, M. H., Madden, L. A., Madison, S., Rebecca McDougald, E., Miller, N. A., Morgan, J. S., Lee, L. E., Pavageau, L., Puentez, A., Sepulveda, P., Tolentino-Plata, K., Boatman, C. T., Vasil, D. M., Waterbury, J., Yoder, B. A., Baseera, M., Faix, R. G., Minton, S. D., Sheffield, M. J., Rau, C. A., Osborne, K. A., Baker, S., Bird, K., Bledsoe, L. C., Burnett, J., Christensen, S., Cunningham, S. D., Davis, B., Elmont, J. O., Hall, B., Jensen, J. J., Jordan, J., Loertscher, M. C., Marchant, T., Maxson, E., McGrath, K. M., Mickelsen, H. G., Zadeh, G. M., Melody Parry, D., Reich, B. A., Schaefer, S. T., Spencer, C., Steffen, M., Stout, K., Stuart, A. L., Tice, K., Weaver-Lewis, K., Winter, S., Woodbury, K. D., Zanetti, K., Michael O'Shea, T., Dillard, R. G., Peters, N. J., Chiu, K., Allred, D. E., Goldstein, D. J., Fond, R. H., Jackson, B. G., Peterson, C., Roberts, D., Waldrep, E. L., Morris, M. W., Hounshell, G. W., Washburn, L. K., Welch, C. D., Shankaran, S., Sood, B. G., Pappas, A., Barks, J., Johnson, Y. R., Bara, R., Goldston, L., Johnson, M. E., Kennedy, D., Muran, G., Billian, E., Sumner, L., Sawaya, K., Woldt, E., Childs, K., Pinnatisect, B., Agarwal, P., DeJesus, L., Natarajan, G., Chawla, S., Christensen, M. K., Wiggins, S. A., White, D., Ehrenkranz, R. A., Butler, C., Jacobs, H., Cervone, P., Close, N., Getter, P., Gilliam, W., Greisman, S., Konstantino, M., Poulsen, J., Romano, E., Taft, J., Williams, J. 2024

  Abstract

  OBJECTIVE: To examine whether changes in survival without moderate or severe neurodevelopmental impairment (NDI) at 18-26 months' corrected age from 1999 to 2018 differed between male and female infants.DESIGN: This retrospective cohort study used data from the NICHD Neonatal Research Network hospitals. Robust Poisson regression models were used to estimate adjusted relative risks (aRRs) and 95% CIs for survival without moderate or severe NDI between males and females. Interactions between sex and time were assessed to evaluate temporal differences in the outcome by sex. Variables adjusted for included centre, maternal age, ethnicity/race, gestational age and small for gestational age.PATIENTS: Inborn infants with gestational age of 22-26 weeks at NICHD Neonatal Research Network hospitals from 1999 to 2018.MAIN OUTCOME MEASURE: Change over time in survival without moderate or severe NDI at 18-26 months' corrected age between male and female infants.RESULTS: Of 26 307 infants, 13 045 (49.6%) were male. Survival without moderate or severe NDI declined for both sexes over time, from 32.9% to 30.6% for males and from 47.4% to 40.0% for females, between 1999-2003 and 2014-2018. Males were less likely than females to survive without moderate or severe NDI (aRR=0.80; 95% CI 0.78 to 0.83). Changes in survival without moderate or severe NDI did not differ between males and females.CONCLUSION: There were no differential changes in survival without moderate or severe NDI between male and female infants.

  View details for DOI 10.1136/archdischild-2024-327239

  View details for PubMedID 39288987

• Surgical Necrotizing Enterocolitis and Spontaneous Intestinal Perforation Lead to Severe Growth Failure in Infants. Annals of surgery Speer, A. L., Lally, K. P., Pedroza, C., Zhang, Y., Poindexter, B. B., Chwals, W. J., Hintz, S. R., Besner, G. E., Stevenson, D. K., Ohls, R. K., Truog, W. E., Stoll, B. J., Rysavy, M. A., Das, A., Tyson, J. E., Blakely, M. L. 2024; 280 (3): 432-443

  Abstract

  We aimed to determine the incidence of growth failure in infants with necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) and whether initial laparotomy versus peritoneal drainage (PD) impacted the likelihood of growth failure.Infants with surgical NEC and SIP have high mortality, and most have neurodevelopmental impairment and poor growth. Existing literature on growth outcomes for these infants is limited.This is a preplanned secondary study of the Necrotizing Enterocolitis Surgery Trial dataset. The primary outcome was growth failure (Z-score for weight <-2.0) at 18 to 22 months. We used logistic regression, including diagnosis and treatment, as covariates. Secondary outcomes were analyzed using the Fisher exact or Pearson χ2 test for categorical variables and the Wilcoxon rank sum test or one-way ANOVA for continuous variables.Among 217 survivors, 207 infants (95%) had primary outcome data. Growth failure at 18 to 22 months occurred in 24/50 (48%) of NEC infants versus 65/157 (42%) SIP (P=0.4). The mean weight-for-age Z-score at 18 to 22 months in NEC infants was -2.05±0.99 versus -1.84±1.09 SIP (P=0.2), and the predicted mean weight-for-age Z-score SIP (Beta -0.27; 95% CI: -0.53, -0.01; P=0.041). Median declines in weight-for-age Z-score between birth and 18 to 22 months were significant in all infants but most severe (>2) in NEC infants (P=0.2).This first ever prospective study of growth outcomes in infants with surgical NEC or SIP demonstrates that growth failure is very common, especially in infants with NEC, and persists at 18-22 months.

  View details for DOI 10.1097/SLA.0000000000006378

  View details for PubMedID 39264354

• Social Determinants of Health and Redirection of Care for Infants Born Extremely Preterm. JAMA pediatrics Brumbaugh, J. E., Bann, C. M., Bell, E. F., Travers, C. P., Vohr, B. R., McGowan, E. C., Harmon, H. M., Carlo, W. A., Hintz, S. R., Duncan, A. F., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Polin, R. A., Laptook, A. R., Keszler, M., Mayne, J., Lamberson, V., Keszler, M. L., Hensman, A. M., Vieira, E., St Pierre, L., Burke, R. T., Alksninis, B., Leach, T. M., Watson, V. E., Knoll, A., Moffat, S., Hibbs, A. M., Newman, N. S., Wilson-Costello, D. E., Siner, B. S., Friedman, H. G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Scott, A., Parimi, P. S., Gaetano, L., Merhar, S. L., Schibler, K., Poindexter, B. B., Kim, J., Yolton, K., Cahill, T. E., Russell, D., Dudley, J., Gratton, T. L., Grisby, C., Henkes, L., Kirker, K., Stacey, S., Wuertz, S., Cotten, C. M., Goldberg, R. N., Laughon, M. M., Goldstein, R. F., Malcolm, W. F., Ashley, P. L., Mago-Shah, D., Finkle, J., Fisher, K. A., Gustafson, K. E., Bose, C. L., Bernhardt, J., Bose, G., Clark, C., Wereszczak, J., Warner, D., Talbert, J., Kicklighter, S. D., Bentley, A., Edwards, L., Rhodes-Ryan, G., White, D., Patel, R. M., Carlton, D. P., Stoll, B. J., Loggins, Y., Adams-Chapman Deceased, I., Sewell, E., Maitre, N., Bottcher, D., Carter, S. L., Hale, E. C., Kendrick-Allwood, S., Laursen, J., Mulligan LaRossa, M., Mackie, C., Sanders, A., Smikle, G., Wineski, L., Walsh, M. C., Bremer, A. A., Higgins, R. D., Wilson Archer, S., Sokol, G. M., Papile, L., Herron, D. E., Hines, A. C., Lytle, C., Smiley, L., Wilson, L. D., Watkins, D., Gunn, S., Joyce Deceased, J., Tyson, J. E., Khan, A. M., Kennedy, K. A., Rysavy, M. A., Mosquera, R. A., Eason, E., Stephens, E., Alaniz, N. I., Allain, E., Arldt-McAlister, J., Boricha, F., Burson, K., Dempsey, A. G., Garcia, C., Hall, D. J., John, J., Jones, P. M., Lillie, M. L., Mason, C. M., Martin, K., Martin, S. C., McDavid, G. E., McKee, S. L., Poe, M., Rennie, K., Reddy, T., Rodgers, S., Khan Siddiki, S., Sperry, D., Pierce Tate, P. L., White, M., Wright, S. L., Zanger, D., Sanchez, P. J., Slaughter, J. L., Nelin, L. D., Jadcherla, S. R., Maitre, N. L., Timan, C., Yeates, K. O., Luzader, P., Batterson, N., Baugher, H., Beckford, D. R., Burkhardt, S., Carey, H., Chao, M., Cira, C., Clark, E., DeSantis, B., Fortney, C. A., Fowler, A., Gutentag, J., Grothause, J. L., Hague, C. D., Keim, S. A., Levengood, K., Marzec, L., McCool, J., Miller, B., Nelin, M. A., Newton, J., Park, C., Pietruszewski, L., Purnell, J., Seabrook, R., Shadd, J. C., Small, K., Stein, M., Sullivan, M., Sullivan, R. A., Warnimont, K., Yossef-Salameh, L., Fearns, E., Das, A., Gantz, M. G., Wiener, L. E., Wallace, D., O'Donnell Auman, J., Crawford, M., Gabrio, J., Newman, J. E., Parlberg, L., Petrie Huitema, C. M., Zaterka-Baxter, K. M., Van Meurs, K. P., Chock, V. Y., Stevenson, D. K., Ball, M. B., Bahmani, D., Adams, M. M., Bentley, B., DeAnda, M. E., DeBattista, A. M., Earhart, B., Huffman, L. C., Krueger, C. E., Lucash, R. E., Proud, M. S., Reichert, E. N., Taylor, H., Weiss, H. E., Williams, R. J., Ambalavanan, N., Peralta-Carcelen, M., Collins, M. V., Cosby, S. S., Bailey, K. J., Biasini, F. J., Chopko, S. A., Domnanovich, K. A., Jno-Finn, C. J., Ladinsky, M., Moses, M. B., Buie, C., McNair, T. E., Phillips, V. A., Preskitt, J., Rector, R. V., Stringer, K., Whitley, S., York Chapman, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Colaizy, T. T., Widness, J. A., Johnson, K. J., Eastman, D. L., Walker, J. R., Goeke, C. A., Schmelzel, M. L., Faruqui, S. E., Coulter, B. J., Schrimper, B. M., Jellison, S. S., Knosp, L. K., Arnold, S. J., Andrews, H. A., Ellsbury, D. L., Bass, D. B., Tud, T. L., Baack, M. L., Richards, L. A., Henning, M. M., Elenkiwich, C., Broadbent, M., Van Muyden, S., Brodkorb, A. T., Watterberg, K. L., Fuller, J., Ohls, R. K., Backstrom Lacy, C., Hartenberger, C., Sundquist Beauman, S., Hanson, M., Lowe, J. R., Kuan, E., DeMauro, S. B., Eichenwald, E. C., Schmidt, B., Kirpalani, H., Abbasi, S., Chaudhary, A. S., Mancini, T., Cucinotta, D. M., Bernbaum, J. C., Gerdes, M., Ghavam, S., Hurt, H., Snyder, J., Ziolkowski, K., Dhawan, M., Booth, L., Catts, C., D'Angio, C. T., Guillet, R., Myers, G. J., Reynolds, A. M., Lakshminrusimha, S., Wadkins, H. I., Sacilowski, M. G., Jensen, R. L., Merzbach, J., Zorn, W., Farooq, O., Maffett, D., Williams, A., Hunn, J., Guilford, S., Yost, K., Rowan, M., Prinzing, D., Bowman, M., Reubens, L. J., Scorsone, A. M., Harley-McAndrew, M., Fallone, C., Binion, K., Orme, C., Sabaratnam, P., Kent, A., Jones, R., Boylin, E., Rochez, D., Li, E., Kachelmeyer, J., McKee, K. G., Coleman, K. R., Moreland, M., Cavanaugh, B., Wyckoff, M. H., Brion, L. P., Heyne, R. J., Vasil, D. M., Adams, S. S., Chen, L., De Leon, M. M., Duran, J., Eubanks, F., McDougald, R., Pavageau, L., Sepulveda, P., Guzman, A., Harrod, M., Heyne, E., Madden, L. A., Lee, L. E., Puentez, A., Tolentino-Plata, K., Twell Boatman, C., Vera, A., Waterbury, J., Yoder, B. A., Baserga, M., Faix, R. G., Minton, S. D., Sheffield, M. J., Rau, C. A., Baker, S., Burnett, J., Christensen, S., Cole Bledsoe, L., Cunningham, S. D., Davis, B., Elmont, J. O., Hall, B., Jensen, E. R., Loertscher, M. C., Marchant, T., Maxson, E., McGrath, K. M., Mickelsen, H. G., Morshedzadeh, G., Parry, D. M., Reich, B. A., Schaefer, S. T., Stout, K., Stuart, A. L., Weaver-Lewis, K., Winter, S., Woodbury, K. D., Osborne, K., Bird, K., Coleman, K., Francom, B. L., Jordan, J., Steffen, M., Tice, K., Shankaran, S., Natarajan, G., Pappas, A., Sood, B. G., Bajaj, M., February, M., Agarwal, P., Chawla, S., Bara, R., Childs, K., Woldt, E., Goldston, L., Wiggins, S. A., Christensen, M. K., Carlson, M., Barks, J., White, D. F. 2024

  Abstract

  Importance: Redirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding.Objective: To examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm.Design, Setting, and Participants: This is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks' gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic).Main Outcomes and Measures: The primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks' gestation, death and neurodevelopmental impairment at 22 to 26 months' corrected age.Results: Of the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type.Conclusions and Relevance: For infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.

  View details for DOI 10.1001/jamapediatrics.2024.0125

  View details for PubMedID 38466268

• Behavioral Outcomes and Neurodevelopmental Disorders Among Children of Women With Epilepsy. JAMA neurology Cohen, M. J., Meador, K. J., Loring, D. W., Matthews, A. G., Brown, C., Robalino, C. P., Birnbaum, A. K., Voinescu, P. E., Kalayjian, L. A., Gerard, E. E., Gedzelman, E. R., Hanna, J., Cavitt, J., Sam, M. C., French, J. A., Hwang, S. T., Pack, A. M., Pennell, P. B. 2023

  Abstract

  The association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated.To examine the association of fetal ASM exposure with subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age.The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023.Exposures included mother's epilepsy status as well as mother's ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrolled regardless of ASM regimen.The primary outcome was the Adaptive Behavior Assessment System, Third Edition (ABAS-3) General Adaptive Composite (GAC) score among children at 4.5 years of age. Children of women with epilepsy and children of women without epilepsy were compared, and the associations of ASM exposures with outcomes among exposed children were assessed. Secondary outcomes involved similar analyses of other related measures.Primary analysis included 302 children of women with epilepsy (143 boys [47.4%]) and 84 children of women without epilepsy (45 boys [53.6%]). Overall adaptive functioning (ABAS-3 GAC score at 4.5 years) did not significantly differ between children of women with epilepsy and children of women without epilepsy (parameter estimate [PE], 0.4 [95% CI, -2.5 to 3.4]; P = .77). However, in adjusted analyses, a significant decrease in functioning was seen with increasing third-trimester maximum ASM blood concentrations (PE, -7.8 [95% CI, -12.6 to -3.1]; P = .001). This decrease in functioning was evident for levetiracetam (PE, -18.9 [95% CI, -26.8 to -10.9]; P < .001) and lamotrigine (PE, -12.0 [95% CI, -23.7 to -0.3]; P = .04), the ASMs with sample sizes large enough for analysis. Results were similar with third-trimester maximum daily dose.This study suggests that adaptive functioning of children of women with epilepsy taking commonly used ASMs did not significantly differ from that of children of women without epilepsy, but there was an exposure-dependent association of ASMs with functioning. Thus, psychiatric or psychological screening and referral of women with epilepsy and their offspring are recommended when appropriate. Additional research is needed to confirm these findings.

  View details for DOI 10.1001/jamaneurol.2023.4315

  View details for PubMedID 37983058

• Use of term reference infants in assessing the developmental outcome of extremely preterm infants: lessons learned in a multicenter study. Journal of perinatology : official journal of the California Perinatal Association Green, C. E., Tyson, J. E., Heyne, R. J., Hintz, S. R., Vohr, B. R., Bann, C. M., Das, A., Bell, E. F., Debsareea, S. B., Stephens, E., Gantz, M. G., Petrie Huitema, C. M., Johnson, K. J., Watterberg, K. L., Mosquera, R., Peralta-Carcelen, M., Wilson-Costello, D. E., Colaizy, T. T., Maitre, N. L., Merhar, S. L., Adams-Chapman, I., Fuller, J., Hartley-McAndrew, M. E., Malcolm, W. F., Winter, S., Duncan, A. F., Myer, G. J., Kicklighter, S. D., Wyckoff, M. H., DeMauro, S. B., Hibbs, A. M., Stoll, B. J., Carlo, W. A., Van Meurs, K. P., Rysavy, M. A., Patel, R. M., Sánchez, P. J., Laptook, A. R., Cotten, C. M., D'Angio, C. T., Walsh, M. C. 2023

  Abstract

  Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.We assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56-2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001). Difficulty recruiting TR patients at 2 years extended the study by 14 months and affected their demographics.Impairment rates among EP infants appear to be substantially underestimated from Bayley III norms. These rates may be best assessed by comparison with healthy term infants followed with minimal attrition from birth in the same centers.Term Reference (under the Generic Database Study): NCT00063063.

  View details for DOI 10.1038/s41372-023-01729-x

  View details for PubMedID 37542155

  View details for PubMedCentralID 3796892

• Heterogeneity of Treatment Effects of Hydrocortisone by Risk of Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants in the National Institute of Child Health and Human Development Neonatal Research Network Trial: A Secondary Analysis of a Randomized Clinical Trial. JAMA network open Gentle, S. J., Rysavy, M. A., Li, L., Laughon, M. M., Patel, R. M., Jensen, E. A., Hintz, S., Ambalavanan, N., Carlo, W. A., Watterberg, K. 2023; 6 (5): e2315315

  Abstract

  Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death.To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death.This secondary post hoc analysis used data from the NICHD NRN Hydrocortisone Trial, which was a double-masked, placebo-controlled, randomized clinical trial conducted in 19 US academic centers. The NICHD HRN Hydrocortisone Trial enrolled infants born at a gestational age of less than 30 weeks who received mechanical ventilation for at least 7 days, including at the time of enrollment, and who were aged 14 to 28 postnatal days. Infants were enrolled between August 22, 2011, and February 4, 2018, with follow-up between 22 and 26 months of corrected age completed on March 29, 2020. Data were analyzed from September 13, 2021, to March 25, 2023.Infants were randomized to 10 days of hydrocortisone or placebo treatment.Infants' baseline risk of grades 2 to 3 BPD or death was estimated using the NICHD Neonatal BPD Outcome Estimator. Differences in absolute and relative treatment effects by baseline risk were evaluated using interaction terms in models fitted to the efficacy outcome of grades 2 to 3 BPD or death and the safety outcome of moderate or severe NDI or death by follow-up.Among the 799 infants included in the analysis (421 boys [52.7%]), the mean (SD) gestational age was 24.9 (1.5) weeks, and the mean (SD) birth weight was 715 (167) g. The mean estimated baseline risk for grades 2 to 3 BPD or death was 54% (range, 18%-84%) in the study population. The interaction between treatment group and baseline risk was not statistically significant on a relative or absolute scale for grades 2 to 3 BPD or death; the size of the effect ranged from a relative risk of 1.13 (95% CI, 0.82-1.55) in quartile 1 to 0.94 (95% CI, 0.81-1.09) in quartile 4. Similarly, the interaction between treatment group and baseline risk was not significant on a relative or absolute scale for moderate or severe NDI or death; the size of the effect ranged from a relative risk of 1.04 (95% CI, 0.80-1.36) in quartile 1 to 0.99 (95% CI, 0.80-1.22) in quartile 4.In this secondary analysis of a randomized clinical trial, the effect of hydrocortisone vs placebo was not appreciably modified by baseline risk for grades 2 to 3 BPD or death.ClinicalTrials.gov Identifier: NCT01353313.

  View details for DOI 10.1001/jamanetworkopen.2023.15315

  View details for PubMedID 37256621

• Early Life Outcomes in Relation to Social Determinants of Health for Children Born Extremely Preterm. The Journal of pediatrics Brumbaugh, J. E., Vohr, B. R., Bell, E. F., Bann, C. M., Travers, C. P., McGowan, E. C., Harmon, H. M., Carlo, W. A., Duncan, A. F., Hintz, S. R. 2023: 113443

  Abstract

  To characterize the relationships between social determinants of health (SDOH) and outcomes for children born extremely preterm.This is a cohort study of infants born at 22-26 weeks' gestation in NICHD Neonatal Research Network centers (2006-2017) who survived to discharge. Infants were classified by three maternal SDOH: education, insurance, and race. Outcomes included postmenstrual age (PMA) at discharge, readmission, neurodevelopmental impairment (NDI), and death post-discharge. Regression analyses adjusted for center, perinatal characteristics, neonatal morbidity, ethnicity, and two SDOH (eg, group comparisons by education adjusted for insurance and race).Of 7438 children, 5442 (73%) had at least one risk-associated SDOH. PMA at discharge was older (adjusted mean difference 0.37 weeks, 95% confidence interval (CI) 0.06-0.68) and readmission more likely (adjusted odds ratio (aOR) 1.27, 95% CI 1.12-1.43) for infants whose mothers had public/no insurance versus private. Neither PMA at discharge nor readmission varied by education or race. NDI was twice as likely (aOR 2.36, 95% CI 1.86-3.00) and death five times as likely (aOR 5.22, 95% CI 2.54-10.73) for infants with three risk-associated SDOH compared with those with none.Children born to mothers with public/no insurance were older at discharge and more likely to be readmitted than those born to privately insured mothers. NDI and death post-discharge were more common among children exposed to multiple risk-associated SDOH at birth compared with those not exposed. Addressing disparities due to maternal education, insurance coverage, and systemic racism are potential intervention targets to improve outcomes for children born preterm.

  View details for DOI 10.1016/j.jpeds.2023.113443

  View details for PubMedID 37105408

• Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm. JAMA network open Brumbaugh, J. E., Bell, E. F., Do, B. T., Greenberg, R. G., Stoll, B. J., DeMauro, S. B., Harmon, H. M., Hintz, S. R., Das, A., Puopolo, K. M. 2022; 5 (12): e2245826

  Abstract

  Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm.To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months' corrected age.This cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks' gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers.Culture-confirmed LOM.Incidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021).Among 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 (P < .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 (P < .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P < .001) and among those with culture-confirmed LOS (23%-79%, P < .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus, 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection.In this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.

  View details for DOI 10.1001/jamanetworkopen.2022.45826

  View details for PubMedID 36480199

• Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns. The New England journal of medicine Wu, Y. W., Comstock, B. A., Gonzalez, F. F., Mayock, D. E., Goodman, A. M., Maitre, N. L., Chang, T., Van Meurs, K. P., Lampland, A. L., Bendel-Stenzel, E., Mathur, A. M., Wu, T., Riley, D., Mietzsch, U., Chalak, L., Flibotte, J., Weitkamp, J., Ahmad, K. A., Yanowitz, T. D., Baserga, M., Poindexter, B. B., Rogers, E. E., Lowe, J. R., Kuban, K. C., O'Shea, T. M., Wisnowski, J. L., McKinstry, R. C., Bluml, S., Bonifacio, S., Benninger, K. L., Rao, R., Smyser, C. D., Sokol, G. M., Merhar, S., Schreiber, M. D., Glass, H. C., Heagerty, P. J., Juul, S. E., HEAL Consortium, Juul, S. E., Wu, Y. W., Heagerty, P. J., Ahmad, K. A., Baserga, M., Bendel-Stenzel, E., Benninger, K. L., Chalak, L., Chang, T., Flibotte, J., Gonzalez, F. F., Lampland, A. L., Maitre, N. L., Mathur, A. M., Mayock, D. E., Merhar, S., Mietzsch, U., Poindexter, B. B., Rao, R., Riley, D., Smyser, C. D., Sokol, G. M., Van Meurs, K. P., Weitkamp, J., Wu, T., Yanowitz, T. D., Agthe, A. G., Andescavage, N., Bonifacio, S., Chapman, R., Dysart, K., Eichenwald, E., Engelstad, L., Ferriero, D. M., Gano, D., Glass, H. C., Henderson, C., Hintz, S., Ho, E., Isaza, N., Jackson, C., Jackson, L., Johnson, Y., Lawrence, R., Machie, M., Mahmood, B., Massaro, A., Miller, C., Morris, E. A., Morris, H. F., Naik, M., Nedrelow, J., Neumaier, J. R., O'Donnell, B., Rogers, E. E., Sanchez, P. J., Shepherd, J., Thomas, J., Tsuchida, T., Vesoulis, Z., Vijayamadhavan, V., Winter, S., Bataglia, K., Batterson, N., Bernstein, B., Blankenship, S., Burrows, F., Christopher, L., Corrales, A., Cunningham, S., D'Agostino, J. A., DeAnda, M., DeBattista, A., Demauro, S. B., Drury, G., Duncan, A. F., ElTers, N., Neis Farrell, C., Fierro, M., Forero, N., Frey, C., Blanc Friedman, K., Friedman, S., Fuller, J., George, T., Gerdes, M., German, A., German, K., Gogliotti, S., Goldenshteyn, M., Goode, R. H., Haman, M., Hawthorne, C., Hay, A., Hayden, Y., Heyne, R., Hines, A., Hoffman, C., Hutchon, B., Jensen, E., Johnson, B., Keener, K., Kramer, A., Krueger, C., Lawrence, A., Lee, M., Lehman, K., Liebowitz, M., Liggett, M., Lorenzi-Quigley, L., Lundequam, P., Malmud, E., McCall, S., McHugh, K., Morshedzadeh, G., Mouvery, A. L., Myers, E., Natarajan, N., Neel, M. L., Nelin, M. A., Oakes, C., Patel, J., Pietruszewski, L., Plummer, E., Powers, D. A., Rapoport, R., Rauda, H., Rick, L., Scott, L., Siqveland, E., Slaughter, L. A., Stonebraker, L., Stout, K., Stuart, A., Taylor, H., Tolentino-Plata, K., Vanderbilt, D., Vecchiarelli, J., Vierling, A. N., Wager, N., Watkins, D., Wing, S., Wolfe-Christensen, C., Zorn, E., Autelli, V., Baker, S., Ball, B., Barton, A., Bassett, K., Cole Bledsoe, L., Boyle, F., Clopp, B., Corry, K., Drummond, M., Dudley, J., Espinoza, A., Esposito, I., Feltner, J., Fine, D., Fisher, M., Gossett, A., Grisby, C., Hauge, S., Houston, K., Kaletka, B., Kleinman, S., Kohlleppel, K., Lee, L., Li, P., McGowan, M., Nelson, K., Nikirk, S., O'Kane, A., Oskoui, T., Purnell, J., Rakow, H., Rau, C., Reichert, E., Rogers, T., Roth, E., Sepulveda, P., Silvia, A., Stacey, S., Strait, E., Thomas, D., Toda-Eng, B., Weinberg, D. D., Wells, S., Widmayer, A., Worwa, C., Wuertz, S., Yarnell, A., Ziolkowski, K., Comstock, B. A., Heagerty, P. J., Konodi, M. A., Nefcy, C., Ballard, R., Goodman, A. M., Schreiber, M. D., Kuban, K. C., Lowe, J. R., O'Shea, T. M., Bluml, S., McKinstry, R. C., Panigrahy, A., Wisnowski, J. L., Bammler, T., Numis, A. L. 2022; 387 (2): 148-159

  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.).

  View details for DOI 10.1056/NEJMoa2119660

  View details for PubMedID 35830641

• Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia. The New England journal of medicine Watterberg, K. L., Walsh, M. C., Li, L., Chawla, S., D'Angio, C. T., Goldberg, R. N., Hintz, S. R., Laughon, M. M., Yoder, B. A., Kennedy, K. A., McDavid, G. E., Backstrom-Lacy, C., Das, A., Crawford, M. M., Keszler, M., Sokol, G. M., Poindexter, B. B., Ambalavanan, N., Hibbs, A. M., Truog, W. E., Schmidt, B., Wyckoff, M. H., Khan, A. M., Garg, M., Chess, P. R., Reynolds, A. M., Moallem, M., Bell, E. F., Meyer, L. R., Patel, R. M., Van Meurs, K. P., Cotten, C. M., McGowan, E. C., Hines, A. C., Merhar, S., Peralta-Carcelen, M., Wilson-Costello, D. E., Kilbride, H. W., DeMauro, S. B., Heyne, R. J., Mosquera, R. A., Natarajan, G., Purdy, I. B., Lowe, J. R., Maitre, N. L., Harmon, H. M., Hogden, L. A., Adams-Chapman, I., Winter, S., Malcolm, W. F., Higgins, R. D., Eunice Kennedy Shriver NICHD Neonatal Research Network, Polin, R. A., Laptook, A. R., Vohr, B. R., Hensman, A. M., Vieira, E., Pierre, L. S., Burke, R. T., Alksninis, B., Caskey, M., Hoffman, L., Johnson, K., Keszler, M. L., Knoll, A., Leach, T. M., Little, E., Stephens, B. E., Watson, V. E., Payne, A. H., Newman, N. S., Siner, B. S., Bhola, M., Yalcinkaya, G., Pallotto, E. K., Gauldin, C., Holmes, A., Johnson, K., Scott, A., Schibler, K., Yolton, K., Beiersdorfer, T., Cahill, T. E., Dudley, J., Gratton, T. L., Grisby, C., Kirker, K., Thompson, J., Wuertz, S., Goldstein, R. F., Ashley, P. L., Mago-Shah, D., Warren, M., Finkle, J., Fisher, K. A., Gustafson, K. E., Bose, C. L., Bernhardt, J., Bose, G., Wereszczak, J., Warner, D., Talbert, J., Clark, C., Kicklighter, S. D., Bentley, A., Edwards, L., Rhodes-Ryan, G., White, D., Carlton, D. P., Stoll, B. J., Hale, E. C., Loggins, Y., Bottcher, D., Carter, S. L., Kendrick-Allwood, S., Mulligan LaRossa, M., Mackie, C., Smikle, G., Comerford, L. C., Laursen, J., Sanders, A., Bremer, A. A., Wilson Archer, S., Papile, L. A., Harmon, H., Lytle, C., Herron, D. E., Gunn, S., Smiley, L., Wilson, L. D., Tyson, J. E., Duncan, A. F., Alaniz, N., Allain, E., Arldt-McAlister, J., Boral, D. S., Burson, K., Dempsey, A. G., Eason, E., Evans, P. W., Garcia, C., Green, C., Hall, D. J., Jiminez, M., John, J., Jones, P. M., Lillie, M. L., Martin, K., Martin, S. C., Mason, C. M., McDavid, G. E., McKee, S. L., Poe, M., Rennie, K., Rodgers, S. L., Siddiki, S. K., Sperry, D., Stephens, E. K., Pierce Tate, P. L., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Slaughter, J. L., Luzader, P., Burkhardt, S., Carey, H., Chao, M., Clark, E., Fearns, E., Fortney, C. A., Fowler, A., Grothause, J., Gutentag, J., Hague, C., McCool, J., Nelin, M. A., Park, C., Pietruszewski, L., Purnell, J., Shadd, J., Small, K., Stein, M., Sullivan, M., Sullivan, R. A., Timan, C. J., Yeates, K. O., Yoseff-Salameh, L., Keim, S. A., Newton, J., Levengood, K., Batterson, N., Rice, C., Wallace, D., Bann, C. M., Gantz, M. G., O'Donnell Auman, J., Gabrio, J., Leblond, D., Newman, J. E., Petrie Huitema, C. M., vonLehmden, A., Zaterka-Baxter, K. M., Stevenson, D. K., Chock, V. Y., Ball, M. B., Bentley, B., Chitkara, R., Davis, A. S., DeAnda, M. E., DeBattista, A. M., Earhart, B., Huffman, L. C., Krueger, C. E., Lucash, R. E., Proud, M. S., Hitchner Reichert, E. N., Sivakumar, D., Taylor, H., Weiss, H. E., Carlo, W. A., Collins, M. V., Cosby, S. S., Biasini, F. J., Domnanovich, K. A., McNair, T. E., Phillips, V. A., Whitley, S., York Chapman, S., Devaskar, U., Chanlaw, T., Geller, R., Colaizy, T. T., Widness, J. A., Brumbaugh, J. E., Harmon, H. M., Johnson, K. J., Walker, J. R., Goeke, C. A., Schmelzel, M. L., Eastman, D. L., Baack, M. L., Hogden, L. A., Meyer, L., Henning, M. M., Elenkiwich, C., Broadbent, M., Van Muyden, S., Ellsbury, D. L., Campbell, D. B., Tud, T. L., Fuller, J., Hartenberger, C., Kuan, E., Sundquist Beauman, S., Kirpalani, H., Eichenwald, E. C., Abbasi, S., Mancini, T., Chaudhary, A. S., Cucinotta, D. M., Bernbaum, J. C., Freeman Duncan, A., Dysart, K., Gerdes, M., Hurt, H., Jensen, E. A., Snyder, J., Ziolkowski, K., Guillet, R., Myers, G. J., Binion, K., Fallone, C., Farooq, O., Jensen, R. L., Kent, A., Maffett, D., Merzbach, J., Orme, C., Sacilowski, M. G., Sabaratnam, P., Scorsone, A. M., Wadkins, H. I., Wynn, K., Yost, K., Lakshminrusimha, S., Chandrasekharan, P., Guilford, S., Hartley-McAndrews, M. E., Williams, A., Zorn, W., Li, E., Donato, J., McKee, K. G., Coleman, K. R., Bean, S. A., Cole, C. A., Horihan, C. A., Brion, L. P., Vasil, D. M., Adams, S. S., Boss, L., Chen, L., De Leon, M. M., Eubanks, F., Guzman, A., Heyne, E., Lee, L. E., Lira, H., Madden, L. A., McDougald, E. R., Mozaffari, A., Pavageau, L., Sepulveda, P., Twell Boatman, C., Tolentino-Plata, K., Vera, A., Waterbury, J., Wright, R., Ohls, R. K., Baserga, M., Minton, S. D., Sheffield, M. J., Rau, C. A., Burnett, J., Christensen, S., Cole Bledsoe, L., Cunningham, S., Davis, B., Elmont, J. O., Hall, B., Loertscher, M. C., Marchant, T., Maxson, E., McGrath, K. M., Mickelsen, H. G., Morshedzadeh, G., Parry, D. M., Reich, B. A., Schaefer, S. T., Stout, K., Stuart, A. L., Weaver-Lewis, K., Woodbury, K. D., Shankaran, S., Sood, B. G., Bara, R., Agarwal, P., Bajaj, M., Childs, K., February, M., Goldston, L., Johnson, M. E., Panaitescu, B., Hinz Woldt, E., Barks, J., Carlson, M., Christensen, M. K., White, D. F., Wiggins, S. A., Gleason, C. A., Allen, M. C., Boyle, R. J., Clemons, T., D'Alton, M. E., Das, A., O'Shea, T. M., Steinhorn, R., Weiner, S. J., Willinger, M. 2022; 386 (12): 1121-1131

  Abstract

  BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown.METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age.RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups.CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).

  View details for DOI 10.1056/NEJMoa2114897

  View details for PubMedID 35320643

• Antiseizure Medication Concentrations During Pregnancy: Results From the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Study. JAMA neurology Pennell, P. B., Karanam, A., Meador, K. J., Gerard, E., Kalayjian, L., Penovich, P., Matthews, A., McElrath, T. M., Birnbaum, A. K., MONEAD Study Group, Cohen, M., Druzin, M., Finnell, R., Holmes, G., Nelson, L., Stowe, Z., Van Marter, L., Wells, P., Yerby, M., Moore, E., May, R., Ippolito, D., Brown, C., Robalino, C., Skinner, J., Davis, L., Shah, N., Leung, B., Friedman, M., Loblein, H., Sheer, T., Strickland, S., Latif, E., Park, Y., Acosta-Cotte, D., Ray, P., Pack, A., Cleary, K., Echo, J., Zygmunt, A., Casadei, C., Gedzelman, E., Dolan, M., Ono, K., Bearden, D., Ghilian, C., Teagarden, D., Newman, M., McCabe, P., Paglia, M., Taylor, C., Delucca, R., Blessing, K., Voinescu, P. E., Boyer, K., Hanson, E., Young, A., Hickey, P., Strauss, J., Madeiros, H., Chen, L., Allien, S., Sheldon, Y., Weinau, T., Barkley, G. L., Spanaki-Varelas, M., Thomas, A., Constantinou, J., Mahmood, N., Wasade, V., Gaddam, S., Zillgitt, A., Anwar, T., Sandles, C., Holmes, T., Johnson, E., Krauss, G., Lawson, S., Pritchard, A., Ryan, M., Coe, P., Hanna, J., Reger, K., Pohlman, J., Olson, A., French, J., Schweizer, W., Morrison, C., MacAllister, W., Clements, T., Hwang, S., Tam, H. B., Cukier, Y., Meltzer, E., Helcer, J., Lau, C., Grobman, W., Coda, J., Miller, E., Bellinski, I., Bachman, E., Krueger, C., Seliger, J., DeWolfe, J., Owen, J., Thompson, M., Hall, C., Labiner, D., Maciulla, J., Moon, J., Darris, K., Cavitt, J., Privitera, M., Flood-Schaffer, K., Jewell, G., Mendoza, L., Serrano, E., Salih, Y., Bermudez, C., Miranda, M., Velez-Ruiz, N., Figueredo, P., Bagic, A., Urban, A., Gedela, S., Patterson, C., Jeyabalan, A., Radonovich, K., Sutcliffe, M., Beers, S., Wiles, C., Alhaj, S., Stek, A., Perez, S., Sierra, R., Tsai, J., Miller, J. W., Mao, J., Phatak, V., Kim, M., Cheng-Hakimian, A., DeNoble, G., Sam, M., Parker, L., Morris, M., Dimos, J., Miller, D. 2022

  Abstract

  Importance: During pregnancy in women with epilepsy, lower blood concentrations of antiseizure medications can have adverse clinical consequences.Objective: To characterize pregnancy-associated concentration changes for several antiseizure medications among women with epilepsy.Design, Setting, and Participants: Enrollment in this prospective, observational cohort study, Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), occurred from December 19, 2012, to February 11, 2016, at 20 US sites. Enrolled cohorts included pregnant women with epilepsy and nonpregnant control participants with epilepsy. Inclusion criteria were women aged 14 to 45 years, an intelligence quotient greater than 70 points, and, for the cohort of pregnant women, a fetal gestational age younger than 20 weeks. A total of 1087 women were assessed for eligibility; 397 were excluded and 230 declined. Data were analyzed from May 1, 2014, to June 30, 2021.Exposure: Medication plasma concentrations in women taking monotherapy or in combination with noninteracting medications. The cohort of pregnant women was monitored through 9 months post partum, with similar time points for control participants.Main Outcomes and Measures: Dose-normalized concentrations were calculated as total or unbound plasma medication concentrations divided by total daily dose. Phlebotomy was performed during 4 pregnancy study visits and 3 postpartum visits for the pregnant women and 7 visits over 18 months for control participants. The primary hypothesis was to test pregnancy changes of dose-normalized concentrations from nonpregnant postpartum samples compared with those of control participants.Results: Of the 351 pregnant women and 109 control participants enrolled in MONEAD, 326 pregnant women (median [range] age, 29 [19-43] years) and 104 control participants (median [range] age, 29 [16-43] years) met eligibility criteria for this analysis. Compared with postpartum values, dose-normalized concentrations during pregnancy were decreased by up to 56.1% for lamotrigine (15.60 mug/L/mg to 6.85 mug/L/mg; P<.001), 36.8% for levetiracetam (11.33 mug/L/mg to 7.16 mug/L/mg; P<.001), 17.3% for carbamazepine (11.56 mug/L/mg to 7.97 mug/L/mg; P=.03), 32.6% for oxcarbazepine (11.55 mug/L/mg to 7.79 mug/L/mg; P<.001), 30.6% for unbound oxcarbazepine (6.15 mug/L/mg to 4.27 mug/L/mg; P<.001), 39.9% for lacosamide (26.14 mug/L/mg to 15.71 mug/L/mg; P<.001), and 29.8% for zonisamide (40.12 mug/L/mg to 28.15 mug/L/mg; P<.001). No significant changes occurred for unbound carbamazepine, carbamazepine-10,11-epoxide, and topiramate, although a decrease was observed for topiramate (29.83 mug/L/mg to 13.77 mug/L/mg; P = .18). Additionally, compared with dose-normalized concentrations from control participants, pregnancy dose-normalized median (SE) concentrations decreased significantly by week of gestational age: carbamazepine, -0.14 (0.06) mug/L/mg (P = .02); carbamazepine unbound, -0.04 (0.01) mug/L/mg (P = .01); lacosamide, -0.23 (0.07) mug/L/mg (P < .001); lamotrigine, -0.20 (0.02) mug/L/mg (P < .001); levetiracetam, -0.06 (0.03) mug/L/mg (P = .01); oxcarbazepine, -0.14 (0.04) mug/L/mg (P < .001); oxcarbazepine unbound, -0.11 (0.03) mug/L/mg (P < .001); and zonisamide, -0.53 (0.14) mug/L/mg (P<.001) except for topiramate (-0.35 [0.20] mug/L/mg per week) and carbamazepine-10,11-epoxide (0.02 [0.01] mug/L/mg).Conclusions and Relevance: Study results suggest that therapeutic drug monitoring should begin early in pregnancy and that increasing doses of these anticonvulsants may be needed throughout the course of pregnancy.

  View details for DOI 10.1001/jamaneurol.2021.5487

  View details for PubMedID 35157004

• Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018. JAMA Bell, E. F., Hintz, S. R., Hansen, N. I., Bann, C. M., Wyckoff, M. H., DeMauro, S. B., Walsh, M. C., Vohr, B. R., Stoll, B. J., Carlo, W. A., Van Meurs, K. P., Rysavy, M. A., Patel, R. M., Merhar, S. L., Sanchez, P. J., Laptook, A. R., Hibbs, A. M., Cotten, C. M., D'Angio, C. T., Winter, S., Fuller, J., Das, A., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Ambalavanan, N. M., Bailey, K. J., Biasini, F. J., Chopko, S. A., Collins, M. V., Cosby, S. S., Domnanovich, K. A., Jno-Finn, C. J., Ladinsky, M. M., McNair, T. E., Moses, M. B., Peralta-Carcelen, M. M., Phillips, V. A., Preskitt, J. P., Rector, R. V., Stringer, K. M., Whitley, S. M., York Chapman, S. P., Alksninis, B. R., Burke, R. T., Hensman, A. M., Keszler, M. M., Keszler, M. L., Knoll, A. M., Leach, T. M., McGowan, E. C., St Pierre, L. B., Vieira, E. R., Watson, V. E., Guilford, S. B., Hartley-McAndrew, M. E., Lakshminrusimha, S. M., Li, E. B., Reynolds, A. M., Sacilowski, M. G., Williams, A. M., Zorn, W. A., Friedman, H. G., Newman, N. S., Siner, B. S., Wilson-Costello, D. E., Cahill, T. E., Gratton, T. L., Grisby, C. B., Kirker, K. C., Poindexter, B. B., Schibler, K. M., Wuertz, S. R., Yolton, K. P., Polin, R. A., Adams, S. S., Brion, L. P., De Leon, M. M., Eubanks, F. R., Guzman, A., Heyne, E. T., Heyne, R. J., Lee, L. E., McDougald, E. R., Pavageau, L. M., Sepulveda, P. R., Twell Boatman, C. M., Vasil, D. M., Vera, A. A., Waterbury, J. D., Ashley, P. L., Finkle, J. R., Fisher, K. A., Goldberg, R. N., Goldstein, R. F., Gustafson, K. E., Mago-Shah, D. M., Malcolm, W. F., Adams-Chapman Deceased, I. M., Bottcher, D. I., Carlton, D. P., Carter, S. L., Hale, E. C., Kendrick-Allwood, S. M., Laursen, J. R., Loggins, Y. C., Mackie, C. B., Mulligan LaRossa, M. R., Sanders, A. P., Smikle, G. V., Wineski, L. N., Allain, E. P., Arldt-McAlister, J. M., Boricha, F. M., Dempsey, A. G., Duncan, A. F., Garcia, C. R., Hall, D. J., John, J. C., Kennedy, K. A., Khan, A. M., Lillie, M. L., Martin, K. R., McDavid, G. E., McKee, S. L., Mosquera, R. A., Poe, M. P., Reddy, T. M., Rennie, K. P., Rodgers, S. R., Sperry, D. K., Stephens, E. K., Tyson, J. E., Wright, S. L., Harmon, H. M., Herron, D. E., Hines, A. C., Lytle, C. M., Papile, L. M., Smiley, L. C., Sokol, G. M., Brumbaugh, J. E., Colaizy, T. T., Eastman, D. L., Goeke, C. A., Johnson, K. J., Schmelzel, M. L., Walker, J. R., Widness, J. A., Bass, D. B., Ellsbury, D. L., Tud, T. L., Gaetano, L. R., Gauldin, C. R., Holmes, A. M., Johnson, K. R., Kilbride, H. W., Pallotto, E. K., Parimi, P. S., Scott, A. R., Truog, W. E., Batterson, N. O., Baugher, H. B., Beckford, D. R., Burkhardt, S. M., Carey, H. P., Chao, M. B., Cira, C. B., Clark, E. B., DeSantis, B. B., Fearns, E., Fortney, C. A., Fowler, A. B., Grothause, J. L., Gutentag, J. R., Hague, C. D., Jadcherla, S. R., Keim, S. A., Levengood, K. P., Luzader, P. R., Maitre, N. L., Marzec, L. M., McCool, J., Miller, B. R., Nelin, L. D., Nelin, M. A., Newton, J. M., Park, C. R., Pietruszewski, L. P., Purnell, J. B., Shadd, J. C., Slaughter, J. L., Small, K. L., Stein, M. R., Sullivan, M. B., Sullivan, R. A., Timan, C. J., Warnimont, K. B., Yeates, K. O., Yossef-Salameh, L. M., Bremer, A. A., Higgins, R. D., Wilson Archer, S. M., Abbasi, S. M., Bernbaum, J. C., Chaudhary, A. S., Cucinotta, D. M., Eichenwald, E. C., Gerdes, M. P., Ghavam, S. M., Hurt, H. M., Kirpalani, H. B., Mancini, T. R., Schmidt, B. M., Snyder, J. M., Ziolkowski, K. C., Binion, K. B., Bowman, M. R., Boylin, E. B., Coleman, K. R., Fallone, C. M., Farooq, O. M., Guillet, R. M., Horihan, C. A., Hunn, J. M., Jensen, R. L., Jones, R., Kachelmeyer, J. B., Kent, A. B., McKee, K. G., Merzbach, J. L., Myers, G. J., Orme, C. B., Prinzing, D. M., Rochez, D. B., Rowan, M. R., Sabaratnam, P. M., Scorsone, A. M., Wadkins, H. I., Yost, K. P., Crawford, M. M., Gabrio, J. M., Gantz, M. G., Newman, J. E., O'Donnell Auman, J. B., Parlberg, L. B., Petrie Huitema, C. M., Wallace, D. P., Zaterka-Baxter, K. M., Baack, M. L., Broadbent, M. R., Elenkiwich, C. R., Henning, M. M., Hogden, L. A., Adams, M. M., Bahmani, D. M., Ball, M. B., Bentley, B. P., Chock, V. Y., DeAnda, M. E., DeBattista, A. M., Earhart, B. A., Huffman, L. C., Krueger, C. E., Lucash, R. E., Proud, M. S., Reichert, E. N., Stevenson, D. K., Taylor, H. L., Weiss, H. E., Williams, R. J., Chanlaw, T. M., Devaskar, U. M., Garg, M. M., Geller, R. R., Purdy, I. B., Bernhardt, J. M., Bose, C. L., Bose, G. R., Laughon, M. M., Talbert, J. M., Warner, D. D., Wereszczak, J. K., Backstrom Lacy, C. R., Hartenberger, C. H., Kuan, E. R., Lowe, J. R., Ohls, R. K., Ruffner Hanson, M. R., Sundquist Beauman, S. M., Watterberg, K. L., Barks, J. M., Carlson, M. D., Christensen, M. K., White, D. F., Wiggins, S. A., Baker, S. R., Baserga, M. M., Burnett, J. R., Christensen, S. R., Cunningham, S. D., Davis, B. R., Elmont, J. O., Faix, R. G., Hall, B. A., Jensen, E. R., Loertscher, M. C., Marchant, T. R., Maxson, E. B., McGrath, K. M., Mickelsen, H. G., Minton, S. D., Morshedzadeh, G. B., Parry, D. M., Rau, C. A., Schaefer, S. T., Sheffield, M. J., Stout, K. P., Stuart, A. L., Weaver-Lewis, K. R., Woodbury, K. D., Yoder, B. A., Bentley, A. M., Edwards, L. M., Kicklighter, S. D., Rhodes-Ryan, G. A., White, D. R., Agarwal, P. M., Bajaj, M. M., Bara, R. R., Chawla, S. M., Childs, K. R., February, M. M., Goldston, L. A., Hinz Woldt, E. R., Natarajan, G. M., Pappas, A. M., Shankaran, S. M., Sood, B. G. 1800; 327 (3): 248-263

  Abstract

  Importance: Despite improvement during recent decades, extremely preterm infants continue to contribute disproportionately to neonatal mortality and childhood morbidity.Objective: To review survival, in-hospital morbidities, care practices, and neurodevelopmental and functional outcomes at 22-26 months' corrected age for extremely preterm infants.Design, Setting, and Participants: Prospective registry for extremely preterm infants born at 19 US academic centers that are part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. The study included 10 877 infants born at 22-28 weeks' gestational age between January 1, 2013, and December 31, 2018, including 2566 infants born before 27 weeks between January 1, 2013, and December 31, 2016, who completed follow-up assessments at 22-26 months' corrected age. The last assessment was completed on August 13, 2019. Outcomes were compared with a similar cohort of infants born in 2008-2012 adjusting for gestational age.Exposures: Extremely preterm birth.Main Outcomes and Measures: Survival and 12 in-hospital morbidities were assessed, including necrotizing enterocolitis, infection, intracranial hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia. Infants were assessed at 22-26 months' corrected age for 12 health and functional outcomes, including neurodevelopment, cerebral palsy, vision, hearing, rehospitalizations, and need for assistive devices.Results: The 10 877 infants were 49.0% female and 51.0% male; 78.3% (8495/10848) survived to discharge, an increase from 76.0% in 2008-2012 (adjusted difference, 2.0%; 95% CI, 1.0%-2.9%). Survival to discharge was 10.9% (60/549) for live-born infants at 22 weeks and 94.0% (2267/2412) at 28 weeks. Survival among actively treated infants was 30.0% (60/200) at 22 weeks and 55.8% (535/958) at 23 weeks. All in-hospital morbidities were more likely among infants born at earlier gestational ages. Overall, 8.9% (890/9956) of infants had necrotizing enterocolitis, 2.4% (238/9957) had early-onset infection, 19.9% (1911/9610) had late-onset infection, 14.3% (1386/9705) had severe intracranial hemorrhage, 12.8% (1099/8585) had severe retinopathy of prematurity, and 8.0% (666/8305) had severe bronchopulmonary dysplasia. Among 2930 surviving infants with gestational ages of 22-26 weeks eligible for follow-up, 2566 (87.6%) were examined. By 2-year follow-up, 8.4% (214/2555) of children had moderate to severe cerebral palsy, 1.5% (38/2555) had bilateral blindness, 2.5% (64/2527) required hearing aids or cochlear implants, 49.9% (1277/2561) had been rehospitalized, and 15.4% (393/2560) required mobility aids or other supportive devices. Among 2458 fully evaluated infants, 48.7% (1198/2458) had no or mild neurodevelopmental impairment at follow-up, 29.3% (709/2419) had moderate neurodevelopmental impairment, and 21.2% (512/2419) had severe neurodevelopmental impairment.Conclusions and Relevance: Among extremely preterm infants born in 2013-2018 and treated at 19 US academic medical centers, 78.3% survived to discharge, a significantly higher rate than for infants born in 2008-2012. Among infants born at less than 27 weeks' gestational age, rehospitalization and neurodevelopmental impairment were common at 2 years of age.

  View details for DOI 10.1001/jama.2021.23580

  View details for PubMedID 35040888

• Association of Increased Seizures During Rewarming With Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up: A Nested Multisite Cohort Study. JAMA neurology Chalak, L. F., Pappas, A., Tan, S., Das, A., Sanchez, P. J., Laptook, A. R., Van Meurs, K. P., Shankaran, S., Bell, E. F., Davis, A. S., Heyne, R. J., Pedroza, C., Poindexter, B. B., Schibler, K., Tyson, J. E., Ball, M. B., Bara, R., Grisby, C., Sokol, G. M., D'Angio, C. T., Hamrick, S. E., Dysart, K. C., Cotten, C. M., Truog, W. E., Watterberg, K. L., Timan, C. J., Garg, M., Carlo, W. A., Higgins, R. D., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Ambalavanan, N., Collins, M. V., Cosby, S. S., Peralta-Carcelen, M., Phillips, V. A., Randolph, D. A., Alksninis, B., Burke, R. T., Caskey, M., Guerina, N., Hensman, A. M., Keszler, M., Keszler, M. L., Knoll, A. M., Little, E., McGowan, E. C., Oh, W., Shah, B. A., Sommers, R., Vieira, E., Vohr, B. R., Guilford, S., Lakshminrusimha, S., Reynolds, A. M., Sacilowski, M. G., Williams, A., Wynn, K., Hibbs, A. M., Newman, N. S., Siner, B. S., Stork, E. K., Walsh, M. C., Zadell, A., Caplan, M. S., Polin, R. A., Adams, S. S., Brion, L. P., Chen, L., Guzman, A., Heyne, E. T., Lee, L. E., Madden, L. A., Ramon, E., Sanchez, P. J., Twell Boatman, C., Vasil, D. M., Wyckoff, M. H., Ashley, P. L., Finkle, J., Fisher, K. A., Goldberg, R. N., Goldstein, R. F., Grimes, S., Gustafson, K. E., Malcolm, W. F., Adams-Chapman Deceased, I., Bottcher, D. I., Carlton, D. P., Carter, S. L., Hale, E. C., Loggins, Y. C., Mackie, C., Patel, R. M., Stoll, B. J., Wineski, L., Gunn, S., Harmon, H. M., Herron, D. E., Hines, A. C., Joyce, J., Lytle, C., Miller, L. C., Minnich, H. M., Papile, L., Poindexter, B. B., Richard, L., Smiley, L. C., Wilson, L. D., Acarregui, M. J., Bhavsar, V., Brumbaugh, J. E., Colaizy, T. T., Dagle, J. M., Eastman, D. L., Johnson, K. J., Klein, J. M., Lindower, J. B., McElroy, S. J., Murphy, C. R., Rabe, G. K., Roghair, R. D., Segar, J. L., Walker, J. R., Widness, J. A., Ellsbury, D. L., Gauldin, C., Holmes, A. M., Johnson, K., Kilbride, H. W., Pallotto, E. K., Scott, A., Bapat, R., Bartman, T., Bonachea, E., Carey, H., Chao, M., Chicoine, L. G., Clifford, B., Dion Nist, M., Fearns, E., Fortney, C. A., Fowler, A., Fuller, J., Grothause, J. L., Gulati, I., Gutentag, J., Hague, C. D., Haines, K., Hart, B., Hokenson, M., Jadcherla, S. R., Jones, M. E., Keim, S. A., Luzader, P., Maitre, N. L., McGregor, S., Moorehead, P., Nelin, L. D., Nelin, M. A., Parikh, N. A., Rodgers, E., Seabrook, R., Sharp, T., Shepherd, E. G., Slaughter, J. L., Stein, M., Sullivan, R. A., Ulloa, J. A., Wispe, J., Wolfe, T., Yeates, K. O., Yossef-Salameh, L., Zaghoul, N., Wilson Archer, S., Abbasi, S., Bernbaum, J. C., Chaudhary, A. S., Cucinotta, D. M., DeMauro, S. B., Gerdes, M., Hurt, H., Kirpalani, H., Mancini, T., Schmidt, B., Binion, K., Conway, P., Farooq, O., Guillet, R., Horihan, C. A., Jensen, R. L., Laroira, N., Merzbach, J., Myers, G. J., Sabaratnam, P., Scorsone, A. M., Wadkins, H. I., Yost, K., Bann, C. M., Crawford, M. M., Gabrio, J., Gantz, M. G., McDonald, S. A., Newman, J. E., O'Donnell Auman, J., Petrie Huitema, C. M., Pickett, J. W., VonLehmden, A. M., Wallace, D., Zaterka-Baxter, K. M., Chock, V. Y., DeAnda, M. E., DeBattista, A. M., Huffman, L. C., Krueger, C. E., Lucash, R. E., Proud, M. S., Stevenson, D. K., Taylor, H. L., Weiss, H. E., Chanlaw, T., Devaskar, U., Geller, R., Purdy, I. B., Aliaga, S., Bernhardt, J., Bose, C. L., Clark, C. L., Laughon, M. M., Warner, D. D., Wereszczak, J. K., Backstrom Lacy, C., Duncan, A. F., Fuller, J., Hartenberger, C. H., Lowe, J. R., Ohls, R. K., Sundquist Beauman, S., Barks, J., Christensen, M. K., Wiggins, S. A., Bajaj, M., Chawla, S., Childs, K., De Jesus, L. C., Hinz Woldt, E., Johnson, M. E., Natarajan, G., Panaitescu, B., Prentice, J. E., Sood, B. G. 2021

  Abstract

  Importance: Compared with normothermia, hypothermia has been shown to reduce death or disability in neonatal hypoxic ischemic encephalopathy but data on seizures during rewarming and associated outcomes are scarce.Objective: To determine whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and whether they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy.Design, Setting, and Participants: This prespecified nested cohort study of infants enrolled in the Optimizing Cooling (OC) multicenter Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network trial from December 2011 to December 2013 with 2 years' follow-up randomized infants to either 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, 10 declined consent, and 120 met all predefined inclusion criteria. A total of 112 (90%) had complete data for death or disability. Data were analyzed from January 2018 to January 2020.Interventions: Serial amplitude electroencephalography recordings were compared in the 12 hours prior and 12 hours during rewarming for evidence of electrographic seizure activity by 2 central amplitude-integrated electroencephalography readers blinded to treatment arm and rewarming epoch. Odds ratios and 95% CIs were evaluated following adjustment for center, prior seizures, depth of cooling, and encephalopathy severity.Main Outcomes and Measures: The primary outcome was the occurrence of electrographic seizures during rewarming initiated at 72 or 120 hours compared with the preceding 12-hour epoch. Secondary outcomes included death or moderate or severe disability at age 18 to 22 months. The hypothesis was that seizures during rewarming were associated with higher odds of abnormal neurodevelopmental outcomes.Results: A total of 120 newborns (70 male [58%]) were enrolled (66 in group A and 54 in group B). The mean (SD) gestational age was 39 (1) weeks. There was excellent interrater agreement (kappa, 0.99) in detection of seizures. More infants had electrographic seizures during the rewarming epoch compared with the preceding epoch (group A, 27% vs 14%; P=.001; group B, 21% vs 10%; P=.03). Adjusted odd ratios (95% CIs) for seizure frequency during rewarming were 2.7 (1.0-7.5) for group A and 3.2 (0.9-11.6) for group B. The composite death or moderate to severe disability outcome at 2 years was significantly higher in infants with electrographic seizures during rewarming (relative risk [95% CI], 1.7 [1.25-2.37]) after adjusting for baseline clinical encephalopathy and seizures as well as center.Conclusions and Relevance: Findings that higher odds of electrographic seizures during rewarming are associated with death or disability at 2 years highlight the necessity of electroencephalography monitoring during rewarming in infants at risk.Trial Registration: ClinicalTrials.gov Identifier: NCT01192776.

  View details for DOI 10.1001/jamaneurol.2021.3723

  View details for PubMedID 34661629

• Two-Year-Old Cognitive Outcomes in Children of Pregnant Women With Epilepsy in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study. JAMA neurology Meador, K. J., Cohen, M. J., Loring, D. W., May, R. C., Brown, C., Robalino, C. P., Matthews, A. G., Kalayjian, L. A., Gerard, E. E., Gedzelman, E. R., Penovich, P. E., Cavitt, J., Hwang, S., Sam, M., Pack, A. M., French, J., Tsai, J. J., Pennell, P. B., Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Investigator Group, Birnbaum, A., Druzin, M., Finnell, R., Holmes, G., McElrath, F. T., Nelson, L., Stowe, Z., Van Marter, L., Wells, P., Yerby, M., Moore, E., Ippolito, D., Skinner, J., Davis, L., Shah, N., Leung, B., Friedman, M., Loblein, H., Sheer, T., Strickland, S., Latif, E., Park, Y., Acosta-Cotte, D., Ray, P., Cleary, K., Echo, J., Zygmunt, A., Casadei, C., Dolan, M., Ono, K., Bearden, D., Ghilian, C., Teagarden, D., Newman, M., McCabe, P., Paglia, M., Taylor, C., Delucca, R., Blessing, K., Marter, L., Boyer, K., Hanson, E., Young, A., Hickey, P., Strauss, J., Madeiros, H., Chen, L., Allien, S., Sheldon, Y., Weinau, T., Barkley, G. L., Spanaki-Varelas, M., Thomas, A., Constantinou, J., Mahmood, N., Wasade, V., Gaddam, S., Zillgitt, A., Anwar, T., Sandles, C., Holmes, T., Johnson, E., Krauss, G., Lawson, S., Pritchard, A., Ryan, M., Coe, P., Reger, K., Pohlman, J., Olson, A., Schweizer, W., Morrison, C., MacAllister, W., Clements, T., Tam, H. B., Cukier, Y., Meltzer, E., Helcer, J., Lau, C., Grobman, W., Coda, J., Miller, E., Bellinski, I., Bachman, E., Krueger, C., Seliger, J., DeWolfe, J., Owen, J., Thompson, M., Hall, C., Labiner, D., Maciulla, J., Moon, J., Darris, K., Privitera, M., Flood-Schaffer, K., Jewell, G., Mendoza, L., Serrano, E., Salih, Y., Bermudez, C., Miranda, M., Velez-Ruiz, N., Figueredo, P., Bagic, A., Urban, A., Gedela, S., Patterson, C., Jeyabalan, A., Radonovich, K., Sutcliffe, M., Beers, S., Wiles, C., Alhaj, S., Stek, A., Perez, S., Sierra, R., Miller, J. W., Mao, J., Phatak, V., Kim, M., Cheng-Hakimian, A., DeNoble, G., Parker, L., Morris, M., Dimos, J., Miller, D. 2021

  Abstract

  Importance: The neurodevelopmental risks of fetal exposure are uncertain for many antiseizure medications (ASMs).Objective: To compare children at 2 years of age who were born to women with epilepsy (WWE) vs healthy women and assess the association of maximum ASM exposure in the third trimester and subsequent cognitive abilities among children of WWE.Design, Setting, and Participants: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicenter investigation of pregnancy outcomes that enrolled women from December 19, 2012, to January 13, 2016, at 20 US epilepsy centers. Children are followed up from birth to 6 years of age, with assessment at 2 years of age for this study. Of 1123 pregnant women assessed, 456 were enrolled; 426 did not meet criteria, and 241 chose not to participate. Data were analyzed from February 20 to December 4, 2020.Main Outcomes and Measures: Language domain score according to the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), which incorporates 5 domain scores (language, motor, cognitive, social-emotional, and general adaptive), and association between BSID-III language domain and ASM blood levels in the third trimester in children of WWE. Analyses were adjusted for multiple potential confounding factors, and measures of ASM exposure were assessed.Results: The BSID-III assessments were analyzed in 292 children of WWE (median age,2.1 [range, 1.9-2.5] years; 155 female [53.1%] and 137 male [46.9%]) and 90 children of healthy women (median age,2.1 [range, 2.0-2.4] years; 43 female [47.8%] and 47 male [52.2%]). No differences were found between groups on the primary outcome of language domain (-0.5; 95% CI,-4.1 to 3.2). None of the other 4 BSID-III domains differed between children of WWE vs healthy women. Most WWE were taking lamotrigine and/or levetiracetam. Exposure to ASMs in children of WWE showed no association with the language domain. However, secondary analyses revealed that higher maximum observed ASM levels in the third trimester were associated with lower BSID-III scores for the motor domain (-5.6; 95% CI,-10.7 to -0.5), and higher maximum ASM doses in the third trimester were associated with lower scores in the general adaptive domain (-1.4; 95% CI,-2.8 to -0.05).Conclusions and Relevance: Outcomes of children at 2 years of age did not differ between children of WWE taking ASMs and children of healthy women.Trial Registration: ClinicalTrials.gov Identifier: NCT01730170.

  View details for DOI 10.1001/jamaneurol.2021.1583

  View details for PubMedID 34096986

• Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial. Journal of perinatology : official journal of the California Perinatal Association Adams-Chapman, I., Watterberg, K. L., Nolen, T. L., Hirsch, S., Cole, C. A., Cotten, C. M., Oh, W., Poindexter, B. B., Zaterka-Baxter, K. M., Das, A., Lacy, C. B., Scorsone, A. M., Duncan, A. F., DeMauro, S. B., Goldstein, R. F., Colaizy, T. T., Wilson-Costello, D. E., Purdy, I. B., Hintz, S. R., Heyne, R. J., Myers, G. J., Fuller, J., Merhar, S., Harmon, H. M., Peralta-Carcelen, M., Kilbride, H. W., Maitre, N. L., Vohr, B. R., Natarajan, G., Mintz-Hittner, H., Quinn, G. E., Wallace, D. K., Olson, R. J., Orge, F. H., Tsui, I., Gaynon, M., Hutchinson, A. K., He, Y., Winter, T. W., Yang, M. B., Haider, K. M., Cogen, M. S., Hug, D., Bremer, D. L., Donahue, J. P., Lucas, W. R., Phelps, D. L., Higgins, R. D., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Archer, S. W., Sokol, G. M., Gunn, S., Herron, D. E., Hines, A. C., Hynes, E., Papile, L., Smiley, L., Tyson, J. E., Kennedy, K. A., Khan, A. M., Duncan, A., Mosquera, R., Allain, E., Arldt-McAlister, J., Brown, S., Dempsey, A. G., Eason, E., El-Ali, F., Garcia, C., Kumar, K., John, J., Jones, P. M., Lillie, M. L., Martin, K., Martin, S. C., McDavid, G. E., EdS, S. M., Ozsoy, H., Rodgers, S., Sperry, D., Stephens, E. K., Ta, V., Wong, C., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Graf, A. E., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Rogers, D. L., Golden, R. P., Jordan, C. O., Wallace, D., Gantz, M. G., Bann, C. M., Auman, J. O., Crawford, M. M., Gabrio, J., Huitema, C. M., Pickett, J. W., VonLehmden, A. M., Van Meurs, K. P., Stevenson, D. K., Ball, M. B., Chinn, S., Proud, M. S., Bentley, B., DeAnda, M. E., DeBattista, A. M., Earhart, B., Huffman, L. C., Krueger, C. E., Lucash, R., Weiss, H. E., Carlo, W. A., Ambalavanan, N., Collins, M. V., Cosby, S. S., Quinn, R. J., Denson, B. R., Arciniegas-Bernal, A. M., Biasini, F. J., Johnston, K. C., Patterson, C. S., Phillips, V. A., Whitley, S., Devaskar, U., Garg, M., Chanlaw, T., Geller, R., Bell, E. F., Brumbaugh, J. E., Johnson, K. J., Walker, J. R., Goeke, C. A., Johnson, K. M., Merriss, A., Nohr, J. L., Longmuir, S. Q., Drack, A. V., Eastman, D. L., Larson, S. A., Gertsch, K. R., Bell, V. P., Ohls, R. K., Beauman, S. S., Dupont, T., Hanson, M. R., Hartenberger, C. H., Kuan, E., Kunkel, S. J., Lowe, J., Morgan, N. A., Hallman, M. K., Schmidt, B., Kirpalani, H., Abbasi, S., Chaudhary, A. S., Mancini, T., Anninger, W. V., Bernbaum, J. C., Binenbaum, G., Cook, N., Davidson, S. L., Gerdes, M., Hurt, H., Mills, M. D., Ricciardelli, M., Rockwell, K. J., Snyder, J., Yau, S. M., D'Angio, C., Lakshminrusimha, S., Reynolds, A. M., Bean, S. A., Carmen, M. F., Chess, P. R., Jensen, R., Ramchandran, R. S., Turner, A. M., Williams, A., Sacilowski, M. G., Wadkins, H., Hunn, J., Horan, A., Bowman, M., Hartley-McAndrew, M., Zorn, W., Farooq, O., Yost, K., Merzbach, J., Fallone, C., Binion, K., Orme, C., Sabaratnam, P., Wyckoff, M. H., Brion, L. P., Vasil, D. M., Adams, S. S., Cha, C., Cisneros, J., De Leon, M. M., Eubanks, F., Godowic, L., Grau, L., Guzman, A., Heyne, E., Lee, L. E., Lira, H. C., Mozaffari, A., Pavageau, L., Boatman, C. T., Wright, R., Shankaran, S., Sood, B. G., Bara, R., Agarwal, P., Bajaj, M., Chawla, S., Childs, K., February, M., Goldston, L. A., Johnson, M. E., Lulic-Botica, M., Panaitescu, B., Woldt, E., Gleason, C. A., Allen, M. C., Boyle, R. J., Clemons, T., D'Alton, M. E., Das, A., Everett, D., Kauffman, R. E., Miodovnik, M., O'Shea, T. M., Smith, L., Weiner, S. J., Willinger, M. 2021

  Abstract

  OBJECTIVE: This study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial.STUDY DESIGN: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed.RESULTS: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8±1.3 weeks and mean birthweight was 805±192g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p=0.40).CONCLUSIONS: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data.

  View details for DOI 10.1038/s41372-021-01018-5

  View details for PubMedID 33758387

• Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy. The New England journal of medicine Pennell, P. B., French, J. A., May, R. C., Gerard, E., Kalayjian, L., Penovich, P., Gedzelman, E., Cavitt, J., Hwang, S., Pack, A. M., Sam, M., Miller, J. W., Wilson, S. H., Brown, C., Birnbaum, A. K., Meador, K. J., MONEAD Study Group, Meador, K. J., Pennell, P. B., May, R., Birnbaum, A., Cohen, M. J., Druzin, M., Finnell, R., French, J., Loring, D. W., McElrath, T. F., Nelson, L., Stowe, Z., Van Marter, L., Wells, P., Yerby, M., Moore, E., Wilson, S. H., Brown, C., Ippolito, D., Nair, A., Ayre, B., Skinner, J., Davis, L., Hendrickson, L., Shah, N., Leung, B., Arias, M., Robalino, C., Birnbaum, A. K., Karanam, A., Strickland, S., Latif, E., Park, Y., Acosta-Cotte, D., Ray, P., Boyer, K., Hanson, E., Young, A., Hickey, P., Strauss, J., Madeiros, H., Pennell, P., McElrath, F. T., Walsh, A., Chen, L., Allien, S., Lee, T., Sheldon, Y., Weinau, T., Pack, A., Cleary, K., Echo, J., Zygmunt, A., Casadei, C., Irobunda, I., Gedzelman, E., Dolan, M., Ono, K., Bearden, D., Ghilian, C., Teagarden, D., Newman, M., McCabe, P., Paglia, M., Taylor, C., Delucca, R., Barkley, G. L., Spanaki-Varelas, M., Thomas, A., Constantinou, J., Anwar, T., Holmes, T., Johnson, E., Krauss, G., Lawson, S., Pritchard, A., Ryan, M., Coe, P., Penovich, P., Hanna, J., Reger, K., Meehan, S., Olson, A., Schweizer, W., Rosenberg, J., Smith, A., Hwang, S., Tam Tam, H. B., Cukier, Y., Meltzer, E., DiCarlo, G., Lau, C., Smith, B., Gerard, E., Grobman, W., Coda, J., Miller, E., Bellinski, I., Bachman, E., Meador, K., Krueger, C., Seliger, J., DeWolfe, J., Owen, J., Thompson, M., Hall, C., Willia, V., Labiner, D., Maciulla, J., Moon, J., Kunnaz, L., Cavitt, J., Privitera, M., Flood-Schaffer, K., Jewell, G., McElroy, B., Mendoza, L., Serrano, E., Salih, Y., Bermudez, C., Miranda, M., Velez-Ruiz, N., Figueredo, P., Bagic, A., Popescu Urban, A., Gedela, S., Patterson, C., Jeyabalan, A., Radonovich, K., Sutcliffe, M., Beers, S., Wiles, C., Mosovsky, S., Kalayjian, L., Stek, A., Perez, S., Sierra, R., Miller, J. W., Mao, J., Phatak, V., Kim, M., Cheng-Hakimian, A., Oliva, A., Sam, M., Parker, L., Morris, M., Dimos, J., Miller, D. 2020; 383 (26): 2547–56

  Abstract

  BACKGROUND: Among women with epilepsy, studies regarding changes in seizure frequency during pregnancy have been limited by the lack of an appropriate nonpregnant comparator group to provide data on the natural course of seizure frequency in both groups.METHODS: In this prospective, observational, multicenter cohort study, we compared the frequency of seizures during pregnancy through the peripartum period (the first 6 weeks after birth) (epoch 1) with the frequency during the postpartum period (the following 7.5 months after pregnancy) (epoch 2). Nonpregnant women with epilepsy were enrolled as controls and had similar follow-up during an 18-month period. The primary outcome was the percentage of women who had a higher frequency of seizures that impaired awareness during epoch 1 than during epoch 2. We also compared changes in the doses of antiepileptic drugs that were administered in the two groups during the first 9 months of epoch 1.RESULTS: We enrolled 351 pregnant women and 109 controls with epilepsy. Among the 299 pregnant women and 93 controls who had a history of seizures that impaired awareness and who had available data for the two epochs, seizure frequency was higher during epoch 1 than during epoch 2 in 70 pregnant women (23%) and in 23 controls (25%) (odds ratio, 0.93; 95% confidence interval [CI], 0.54 to 1.60). During pregnancy, the dose of an antiepileptic drug was changed at least once in 74% of pregnant women and in 31% of controls (odds ratio, 6.36; 95% CI, 3.82 to 10.59).CONCLUSIONS: Among women with epilepsy, the percentage who had a higher incidence of seizures during pregnancy than during the postpartum period was similar to that in women who were not pregnant during the corresponding epochs. Changes in doses of antiepileptic drugs occurred more frequently in pregnant women than in nonpregnant women during similar time periods. (Funded by the National Institutes of Health; MONEAD ClinicalTrials.gov number, NCT01730170.).

  View details for DOI 10.1056/NEJMoa2008663

  View details for PubMedID 33369356

• Limitations of Conventional Magnetic Resonance Imaging as a Predictor of Death or Disability Following Neonatal Hypoxic-Ischemic Encephalopathy in the Late Hypothermia Trial. The Journal of pediatrics Laptook, A. R., Shankaran, S., Barnes, P., Rollins, N., Do, B. T., Parikh, N. A., Hamrick, S., Hintz, S. R., Tyson, J. E., Bell, E. F., Ambalavanan, N., Goldberg, R. N., Pappas, A., Huitema, C., Pedroza, C., Chaudhary, A. S., Hensman, A. M., Das, A., Wyckoff, M., Khan, A., Walsh, M. C., Watterberg, K. L., Faix, R., Truog, W., Guillet, R., Sokol, G. M., Poindexter, B. B., Higgins, R. D., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network 2020

  Abstract

  OBJECTIVE: To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours.STUDY DESIGN: Sub-group analysis of infants ≥ 36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by two central readers using the NICHD injury score (six levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age.RESULTS: Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n=119) or died (n=9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted Kappa 0.56, 95% confidence interval 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% confidence interval 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively.CONCLUSION: MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia-ischemia.

  View details for DOI 10.1016/j.jpeds.2020.11.015

  View details for PubMedID 33189747

• Timing of postnatal steroids for bronchopulmonary dysplasia: association with pulmonary and neurodevelopmental outcomes JOURNAL OF PERINATOLOGY Harmon, H. M., Jensen, E. A., Tan, S., Chaudhary, A. S., Slaughter, J. L., Bell, E. F., Wyckoff, M. H., Hensman, A. M., Sokol, G. M., DeMauro, S. B., Caplan, M. S., Laptook, A. R., Keszler, M., Vohr, B. R., Alksninis, B., Basso, K. M., Burke, R., Caskey, M., Johnson, K., Keszler, M., Knoll, A. M., Leach, T. M., Little, E., McGowan, E. C., Vieira, E., Watson, V. E., Ventura, S., Walsh, M. C., Hibbs, A., Wilson-Costello, D. E., Newman, N. S., Payne, A. H., Siner, B. S., Bhola, M., Yalcinkaya, G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Scott, A., Schibler, K., Donovan, E. F., Grisby, C., Bridges, K., Alexander, B., Fischer, E. E., Mincey, H. L., Hessling, J., Gratton, T. L., Jackson, L., Kirker, K., Muthig, G., Steichen, J. J., Tepe, S., Yolton, K., Goldberg, R. N., Cotten, C., Goldstein, R. F., Ashley, P. L., Malcolm, W. F., Auten, K. J., Fisher, K. A., Grimes, S., Gustafson, K. E., Lohmeyer, M. B., Finkle, J., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Warner, D., Wereszczak, J., Carlton, D. P., Stoll, B. J., Adams-Chapman, I., Hale, E. C., Loggins, Y., Blackwelder, A., Wineski, L. C., LaRossa, M., Carter, S. L., Higgins, R. D., Archer, S., Poindexter, B. B., Dusick, A. M., Papile, L., Gunn, S., Hamer, F., Herron, D. E., Hines, A. C., Lytle, C., Minnich, H. M., Smiley, L., Wilson, L., Kennedy, K. A., Tyson, J. E., McDavid, G. E., Alaniz, N., Arldt-McAlister, J., Burson, K., Dempsey, A. G., Duncan, A. F., Evans, P. W., Green, C. E., Harris, B., Jiminez, M., John, J., Jones, P. M., Lillie, L. M., Lis, A. E., Martin, S. C., Morris, B. H., Poundstone, M., Rodgers, S., Siddiki, S., Simmons, M. C., Sperry, D., Tate, P., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Das, A., Wallace, D., Gantz, M. G., Poole, W., Newman, J. E., Auman, J., Crawford, M. M., Gabrio, J., Huitema, C., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Hintz, S. R., Ball, M., Davis, A. S., Palmquist, A. W., Proud, M. S., Bentley, B., Bruno, E., DeAnda, M., DeBattista, A. M., Earhart, B., Huffman, L. C., Kohn, J. G., Krueger, C., Weiss, H. E., Frantz, I. D., Fiascone, J. M., MacKinnon, B. L., Furey, A., Nylen, E., Sibley, C. E., Brussa, A. K., Carlo, W. A., Ambalavanan, N., Peralta-Carcelen, M., Collins, M., Cosby, S. S., Biasini, F. J., Johnston, K. C., Nelson, K. G., Patterson, C. S., Phillips, V. A., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Finer, N. N., Vaucher, Y. E., Kaegi, D., Rasmussen, M. R., Arnell, K., Demetrio, C., Fuller, M. G., Rich, W., Colaizy, T. T., Acarregui, M. J., Brumbaugh, J. E., Ellsbury, D. L., Widness, J. A., Johnson, K. J., Campbell, D. B., Eastman, D. L., Walker, J. R., Duara, S., Bauer, C. R., Everett-Thomas, R., Fajardo-Hiriart, S., Rigaud, A., Calejo, M., Eguaras, S., Berkowits, M., Garcia, A., Pierre, H., Stoerger, A., Watterberg, K. L., Lowe, J. R., Fuller, J. F., Ohls, R. K., Lacy, C., Montman, R., Beauman, S., Schmidt, B., Kirpalani, H., Abbasi, S., Mancini, T., Cucinotta, D. M., Bernbaum, J. C., Gerdes, M., Hurt, H., D'Angio, C. T., Phelps, D. L., Guillet, R., Lakshminrusimha, S., Johnson, J., Reubens, L. J., Horihan, C. A., Hust, D., Jensen, R. L., Kushner, E., Merzbach, J., Myers, G. J., Wadkins, H. M., Guilford, S., Maffett, D., Farooq, O., Prinzing, D., Reynolds, A., Rowan, M., Sacilowski, M. G., Williams, A., Wynn, K., Yost, K., Zorn, W., Zwetsch, L., Brion, L. P., Heyne, R. J., Salhab, W. A., Rosenfeld, C. R., Vasil, D. M., Chen, L., Guzman, A., Hensley, G., Leps, M. H., Miller, N. A., Morgan, J. S., Adams, S. S., Boatman, C., Heyne, E. T., Madden, L. A., Lee, L. E., Faix, R. G., Yoder, B. A., Osborne, K. A., Spencer, C., Weaver-Lewis, K., Baker, S., Bird, K., Burnett, J., Steffen, M., Jensen, J. J., Winter, S., Zanetti, K., O'Shea, T., Dillard, R. G., Washburn, L. K., Jackson, B. G., Peters, N., Chiu, K., Allred, D., Goldstein, D. J., Halfond, R., Peterson, C., Waldrep, E. L., Welch, C. D., Morris, M., Hounshell, G., Shankaran, S., Pappas, A., Barks, J., Bara, R., Goldston, L. A., Natarajan, G., Bajaj, M., Chawla, S., De Jesus, L. C., Sood, B. G., Christensen, M., Wiggins, S. A., White, D., Ehrenkranz, R. A., Jacobs, H., Butler, C. G., Cervone, P., Greisman, S., Konstantino, M., Poulsen, J., Taft, J., Williams, J., Romano, E., Eunice Kennedy Shriver Natl Inst 2020

  Abstract

  To determine the associations between age at first postnatal corticosteroids (PNS) exposure and risk for severe bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI).Cohort study of 951 infants born <27 weeks gestational age at NICHD Neonatal Research Network sites who received PNS between 8 days of life (DOL) and 36 weeks' postmenstrual age was used to produce adjusted odds ratios (aOR).Compared with infants in the reference group (22-28 DOL-lowest rate), aOR for severe BPD was similar for children given PNS between DOL 8 and 49 but higher among infants treated at DOL 50-63 (aOR 1.77, 95% CI 1.03-3.06), and at DOL ≥64 (aOR 3.06, 95% CI 1.44-6.48). The aOR for NDI did not vary significantly by age of PNS exposure.For infants at high risk of BPD, initial PNS should be considered prior to 50 DOL for the lowest associated odds of severe BPD.

  View details for DOI 10.1038/s41372-020-0594-4

  View details for Web of Science ID 000511094300001

  View details for PubMedID 32020038

• Behavior Profiles at 2Years for Children Born Extremely PretermwithBronchopulmonary Dysplasia. The Journal of pediatrics Brumbaugh, J. E., Bell, E. F., Grey, S. F., DeMauro, S. B., Vohr, B. R., Harmon, H. M., Bann, C. M., Rysavy, M. A., Logan, J. W., Colaizy, T. T., Peralta-Carcelen, M. A., McGowan, E. C., Duncan, A. F., Stoll, B. J., Das, A., Hintz, S. R., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Caplan, M. S., Polin, R. A., Laptook, A. R., Keszler, M., Hensman, A. M., Vieira, E., Little, E., Burke, R. T., Stephens, B. E., Alksninis, B., Bishop, C., Keszler, M. L., Leach, T. M., Watson, V. E., Knoll, A. M., Walsh, M. C., Fanaroff, A. A., Newman, N. S., Wilson-Costello, D. E., Payne, A., Bhola, M., Yalcinkaya, G., Siner, B. S., Friedman, H. G., Roth, E., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Knutson, A., Schibler, K., Poindexter, B. B., Merhar, S., Yolton, K., Gratton, T. L., Grisby, C., Kirker, K., Wuertz, S., Carlton, D. P., Adams-Chapman, I., Hale, E. C., Loggins, Y. C., Bottcher, D. I., Mackie, C., Carter, S. L., LaRossa, M. M., Wineski, L. C., Smikle, G. V., Leon-Hernandez, A., Kendrick-Allwood, S., Cotten, C. M., Goldberg, R. N., Goldstein, R. F., Malcolm, W. F., Ashley, P. L., Finkle, J., Fisher, K. A., Grimes, S., Gustafson, K. E., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Warner, D., Wereszczak, J., Kicklighter, S. D., Rhodes-Ryan, G., Higgins, R. D., Wilson Archer, S., Poindexter, B. B., Sokol, G. M., Papile, L. A., Hines, A. C., Herron, D. E., Gunn, S., Smiley, L., Kennedy, K. A., Tyson, J. E., Arldt-McAlister, J., Burson, K., Dempsey, A. G., Evans, P. W., Garcia, C., Jiminez, M., John, J., Jones, P. M., Lillie, M. L., Martin, K., Martin, S. C., McDavid, G. E., Rodgers, S., Siddiki, S. K., Sperry, D., Pierce Tate, P. L., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Wallace, D., Gantz, M. G., Newman, J. E., Auman, J. O., Crawford, M., Gabrio, J., Leblond, D., Petrie Huitema, C. M., Zaterka-Baxter, K. M., Van Meurs, K. P., Chock, V. Y., Stevenson, D. K., Adams, M. M., Ball, M. B., Bentley, B., DeAnda, M. E., Debattista, A. M., Earhart, B., Huffman, L. C., Ismael, M., Krueger, C. E., Palmquist, A. W., Proud, M. S., Reichert, E. N., Sankar, M. N., St John, N. H., Taylor, H. L., Weiss, H. E., Frantz, I. D., Fiascone, J. M., MacKinnon, B. L., Nylen, E., Furey, A., Sibley, C. E., Brussa, A. K., Carlo, W. A., Ambalavanan, N., Bailey, K. J., Biasini, F. J., Collins, M. V., Cosby, S. S., Phillips, V. A., Rector, R. V., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Finer, N. N., Vaucher, Y. E., Kaegi, D., Rasmussen, M. R., Arnell, K., Demetrio, C., Fuller, M. G., Rich, W., West, R., Baack, M. L., Ellsbury, D. L., Hogden, L. A., Klein, J. M., Dagle, J. M., Johnson, K. J., Tud, T. L., Elenkiwich, C., Henning, M. M., Broadbent, M., Schmelzel, M. L., Walker, J. R., Goeke, C. A., Baack, M. L., Ellsbury, D. L., Hogden, L. A., Klein, J. M., Dagle, J. M., Johnson, K. J., Tud, T. L., Elenkiwich, C., Henning, M. M., Broadbent, M., Schmelzel, M. L., Walker, J. R., Goeke, C. A., Watterberg, K. L., Ohls, R. K., Backstrom Lacy, C., Brown, S., Fuller, J., Hartenberger, C., Lowe, J. R., Sundquist Beauman, S., Hanson, M. R., Dupont, T., Kuan, E., Schmidt, B., Kirpalani, H., Chaudhary, A. S., Abbasi, S., Mancini, T., Cucinotta, D. M., Bernbaum, J. C., Gerdes, M., Hurt, H., D'Angio, C. T., Guillet, R., Myers, G. J., Lakshminrusimha, S., Reynolds, A. M., Hartley-McAndrew, M. E., Wadkins, H. I., Sacilowski, M. G., Reubens, L. J., Jensen, R. L., Merzbach, J., Zorn, W., Farooq, O., Maffett, D., Williams, A., Hunn, J., Guilford, S., Yost, K., Rowan, M., Prinzing, D. M., Wynn, K., Fallone, C., Scorsone, A. M., Wyckoff, M. H., Sanchez, P. J., Brion, L. P., Heyne, R. J., Vasil, D. M., Adams, S. S., Chen, L., De Leon, M. M., Eubanks, F., Guzman, A., Heyne, E. T., Madden, L. A., Miller, N. A., Lee, L. E., Pavageau, L., Sepulveda, P., Boatman, C. T., Faix, R. G., Yoder, B. A., Baserga, M., Osborne, K. A., Baker, S., Bird, K., Burnett, J., Christensen, S., Davis, B., Elmont, J. O., Jensen, J. J., Loertscher, M. C., Marchant, T., Maxson, E., Minton, S. D., Parry, D. M., Rau, C. A., Schaefer, S. T., Sheffield, M. J., Spencer, C., Steffen, M., Weaver-Lewis, K., Winter, S., Woodbury, K. D., Zanetti, K., Shankaran, S., Chawla, S., Sood, B. G., Pappas, A., Natarajan, G., Bajaj, M., Bara, R., Johnson, M. E., Goldston, L., Wiggins, S. A., Christensen, M. K., Carlson, M., Barks, J., White, D. F., Ehrenkranz, R. A., Jacobs, H., Butler, C. G., Cervone, P., Greisman, S., Konstantino, M., Poulsen, J., Taft, J., Romano, E. 2020

  Abstract

  OBJECTIVE: To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD).STUDY DESIGN: We studied children born at 22-26weeks of gestation and assessed at 22-26months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior.RESULTS: Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P<.001) and pervasive developmental problems (P<.001) increased with worsening BPD grade. Sleep problems (P=.008) and aggressive behavior (P=.023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values<.05).CONCLUSIONS: BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.

  View details for DOI 10.1016/j.jpeds.2019.12.028

  View details for PubMedID 32008764

• Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants. The New England journal of medicine Kirpalani, H. n., Bell, E. F., Hintz, S. R., Tan, S. n., Schmidt, B. n., Chaudhary, A. S., Johnson, K. J., Crawford, M. M., Newman, J. E., Vohr, B. R., Carlo, W. A., D'Angio, C. T., Kennedy, K. A., Ohls, R. K., Poindexter, B. B., Schibler, K. n., Whyte, R. K., Widness, J. A., Zupancic, J. A., Wyckoff, M. H., Truog, W. E., Walsh, M. C., Chock, V. Y., Laptook, A. R., Sokol, G. M., Yoder, B. A., Patel, R. M., Cotten, C. M., Carmen, M. F., Devaskar, U. n., Chawla, S. n., Seabrook, R. n., Higgins, R. D., Das, A. n. 2020; 383 (27): 2639–51

  Abstract

  Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia.We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity.A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively.In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).

  View details for DOI 10.1056/NEJMoa2020248

  View details for PubMedID 33382931

• Developmental Outcomes of Extremely Preterm Infants with a Need for Child Protective Services Supervision JOURNAL OF PEDIATRICS McGowan, E. C., Laptook, A. R., Lowe, J., Peralta-Carcelen, M., Chowdhury, D., Higgins, R. D., Hintz, S. R., Vohr, B. R., Polin, R. A., Laptook, A. R., Keszler, M., Hensman, A. M., Alksninis, B., Basso, K. M., Burke, R., Caskey, M., Johnson, K., Keszler, M., Knoll, A. M., Leach, T. M., Little, E., Vieira, E., Watson, V. E., Ventura, S., Walsh, M. C., Fanaroff, A. A., Hibbs, A., Wilson-Costello, D. E., Newman, N. S., Payne, A. H., Siner, B. S., Bhola, M., Yalcinkaya, G., Friedman, H. G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Knutson, A., Schibler, K., Donovan, E. F., Grisby, C., Bridges, K., Alexander, B., Fischer, E. E., Mincey, H. L., Hessling, J., Gratton, T. L., Jackson, L., Kirker, K., Muthig, G., Steichen, J. J., Tepe, S., Yolton, K., Goldberg, R. N., Cotten, C., Goldstein, R. F., Ashley, P. L., Malcolm, W. F., Auten, K. J., Fisher, K. A., Grimes, S., Gustafson, K. E., Lohmeyer, M. B., Finkle, J., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Clark, C., Manor, L., Warner, D., Wereszczak, J., Carlton, D. P., Stoll, B. J., Adams-Chapman, I., Hale, E. C., Loggins, Y., Archer, S., Sokol, G. M., Poindexter, B. B., Dusick, A. M., Papile, L., Gunn, S., Hamer, F., Herron, D. E., Hines, A. C., Lytle, C., Minnich, H. M., Smiley, L., Wilson, L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Das, A., Wallace, D., Gantz, M. G., Poole, W., Newman, J. E., Auman, J., Crawford, M. M., Huitema, C., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Ball, M., Davis, A. S., Palmquist, A. W., Proud, M. S., Bentley, B., Bruno, E., DeAnda, M., DeBattista, A. M., Earhart, B., Huffman, L. C., Kohn, J. G., Krueger, C., Weiss, H. E., Frantz, I. D., Fiascone, J. M., MacKinnon, B. L., Furey, A., Nylen, E., Carlo, W. A., Ambalavanan, N., Collins, M., Cosby, S. S., Biasini, F. J., Johnston, K. C., Nelson, K. G., Patterson, C. S., Phillips, V. A., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Finer, N. N., Vaucher, Y. E., Kaegi, D., Rasmussen, M. R., Arnell, K., Demetrio, C., Fuller, M. G., Rich, W., Bell, E. F., Colaizy, T. T., Acarregui, M. J., Ellsbury, D. L., Widness, J. A., Johnson, K. J., Campbell, D. B., Eastman, D. L., Walker, J. R., Brumbaugh, J. E., Duara, S., Bauer, C. R., Everett-Thomas, R., Fajardo-Hiriart, S., Rigaud, A., Calejo, M., Eguaras, S., Berkowits, M., Garcia, A., Pierre, H., Stoerger, A., Watterberg, K. L., Lowe, J. R., Fuller, J. F., Ohls, R. K., Lacy, C., Duncan, A. F., Montman, R., Schmidt, B., Kirpalani, H., DeMauro, S. B., Chaudhary, A. S., Abbasi, S., Mancini, T., Cucinotta, D. M., Bernbaum, J. C., Gerdes, M., Hurt, H., D'Angio, C. T., Phelps, D. L., Guillet, R., Lakshminrusimha, S., Johnson, J., Reubens, L. J., Horihan, C. A., Hust, D., Jensen, R. L., Kushner, E., Merzbach, J., Myers, G. J., Rowan, M., Wadkins, H. M., Bowman, M., Hunn, J., Guilford, S., Maffett, D., Osman, F., Prinzing, D., Reynolds, A., Sacilowski, M. G., Williams, A., Wynn, K., Yost, K., Zorn, W., Zwetsch, L., Kennedy, K. A., Tyson, J. E., McDavid, G. E., Alaniz, N., Arldt-McAlister, J., Burson, K., Evans, P. W., Garcia, C., Green, C., Harris, B., Jiminez, M., John, J., Jones, P. M., Lillie, L. M., Lis, A. E., Martin, K., Martin, S. C., Morris, B. H., Poundstone, M., Robichaux, P., Rodgers, S., Siddiki, S., Simmons, M. C., Sperry, D., Tate, P., Wright, S. L., Wyckoff, M. H., Brion, L. P., Heyne, R. J., Salhab, W. A., Rosenfeld, C. R., Vasil, D. M., Chen, L., Guzman, A., Hensley, G., Leps, M. H., Miller, N. A., Morgan, J. S., Adams, S. S., Boatman, C., Heyne, E. T., Madden, L. A., Torres, L. E., Faix, R. G., Yoder, B. A., Osborne, K. A., Spencer, C., Weaver-Lewis, K., Baker, S., Bird, K., Burnett, J., Steffen, M., Jensen, J. J., Winter, S., Zanetti, K., O'Shea, T., Dillard, R. G., Washburn, L. K., Jackson, B. G., Peters, N., Chiu, K., Allred, D., Goldstein, D. J., Halfond, R., Peterson, C., Waldrep, E. L., Welch, C. D., Morris, M., Hounshell, G., Shankaran, S., Pappas, A., Barks, J., Bara, R., Goldston, L. A., Natarajan, G., Christensen, M., Wiggins, S. A., White, D., Ehrenkranz, R. A., Jacobs, H., Butler, C. G., Cervone, P., Greisman, S., Konstantino, M., Poulsen, J., Taft, J., Williams, J., Romano, E., Eunice Kennedy Shriver Natl Inst C 2019; 215: 41-+

  View details for DOI 10.1016/j.jpeds.2019.01.063

  View details for Web of Science ID 000498003100010

• Gastrostomy Tube Feeding in Extremely Low Birthweight Infants: Frequency, Associated Comorbidities, and Long-term Outcomes JOURNAL OF PEDIATRICS Warren, M. G., Do, B., Das, A., Smith, P., Adams-Chapman, I., Jadcherla, S., Jensen, E. A., Goldstein, R. F., Goldberg, R. N., Cotten, C., Bell, E. F., Malcolm, W. F., Caplan, M. S., Laptook, A. R., Keszler, M., Vohr, B. R., Hensman, A. M., Alksninis, B., Basso, K. M., Burke, R., Caskey, M., Johnson, K., Keszler, M., Knoll, A. M., Leach, T. M., Little, E., McGowan, E. C., Vieira, E., Watson, V. E., Ventura, S., Walsh, M. C., Hibbs, A., Wilson-Costello, D. E., Newman, N. S., Payne, A. H., Siner, B. S., Bhola, M., Yalcinkaya, G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Scott, A., Schibler, K., Donovan, E. F., Grisby, C., Bridges, K., Alexander, B., Fischer, E. E., Mincey, H. L., Hessling, J., Gratton, T. L., Jackson, L., Kirker, K., Muthig, G., Steichen, J. J., Tepe, S., Yolton, K., Ashley, P. L., Auten, K. J., Fisher, K. A., Grimes, S., Gustafson, K. E., Lohmeyer, M. B., Finkle, J., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Warner, D., Wereszczak, J., Carlton, D. P., Stoll, B. J., Hale, E. C., Loggins, Y., Blackwelder, A., Wineski, L. C., LaRossa, M., Carter, S. L., Higgins, R. D., Archer, S., Sokol, G. M., Poindexter, B. B., Dusick, A. M., Papile, L., Gunn, S., Hamer, F., Harmon, H. M., Herron, D. E., Hines, A. C., Lytle, C., Minnich, H. M., Smiley, L., Wilson, L., Kennedy, K. A., Tyson, J. E., McDavid, G. E., Alaniz, N., Arldt-McAlister, J., Burson, K., Dempsey, A. G., Duncan, A. F., Evans, P. W., Green, C. E., Harris, B., Jiminez, M., John, J., Jones, P. M., Lillie, L. M., Lis, A. E., Martin, S. C., Morris, B. H., Poundstone, M., Rodgers, S., Siddiki, S., Simmons, M. C., Sperry, D., Tate, P., Wright, S. L., Sanchez, P. J., Nelin, L. D., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Wallace, D., Gantz, M. G., Poole, W., Newman, J. E., Auman, J., Crawford, M. M., Gabrio, J., Huitema, C., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Hintz, S. R., Ball, M., Davis, A. S., Palmquist, A. W., Proud, M. S., Bentley, B., Bruno, E., DeAnda, M., DeBattista, A. M., Earhart, B., Huffman, L. C., Kohn, J. G., Krueger, C., Weiss, H. E., Frantz, I. D., Fiascone, J. M., MacKinnon, B. L., Furey, A., Nylen, E., Sibley, C. E., Brussa, A. K., Carlo, W. A., Ambalavanan, N., Peralta-Carcelen, M., Collins, M., Cosby, S. S., Biasini, F. J., Johnston, K. C., Nelson, K. G., Patterson, C. S., Phillips, V. A., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Finer, N. N., Vaucher, Y. E., Kaegi, D., Rasmussen, M. R., Arnell, K., Demetrio, C., Fuller, M. G., Rich, W., Colaizy, T. T., Acarregui, M. J., Brumbaugh, J. E., Ellsbury, D. L., Widness, J. A., Johnson, K. J., Campbell, D. B., Eastman, D. L., Walker, J. R., Duara, S., Bauer, C. R., Everett-Thomas, R., Fajardo-Hiriart, S., Rigaud, A., Calejo, M., Eguaras, S., Berkowits, M., Garcia, A., Pierre, H., Stoerger, A., Watterberg, K. L., Lowe, J. R., Fuller, J. F., Ohls, R. K., Lacy, C., Montman, R., Beauman, S., Schmidt, B., Kirpalani, H., DeMauro, S. B., Chaudhary, A. S., Abbasi, S., Mancini, T., Cucinotta, D. M., Bernbaum, J. C., Gerdes, M., Hurt, H., D'Angio, C. T., Phelps, D. L., Guillet, R., Lakshminrusimha, S., Johnson, J., Reubens, L. J., Horihan, C. A., Hust, D., Jensen, R. L., Kushner, E., Merzbach, J., Myers, G. J., Wadkins, H. M., Guilford, S., Maffett, D., Farooq, O., Prinzing, D., Reynolds, A., Rowan, M., Sacilowski, M. G., Williams, A., Wynn, K., Yost, K., Zorn, W., Zwetsch, L., Wyckoff, M. H., Brion, L. P., Heyne, R. J., Salhab, W. A., Rosenfeld, C. R., Vasil, D. M., Chen, L., Guzman, A., Hensley, G., Leps, M. H., Miller, N. A., Morgan, J. S., Adams, S. S., Boatman, C., Heyne, E. T., Madden, L. A., Lee, L. E., Faix, R. G., Yoder, B. A., Osborne, K. A., Spencer, C., Weaver-Lewis, K., Baker, S., Bird, K., Burnett, J., Steffen, M., Jensen, J. J., Winter, S., Zanetti, K., O'Shea, T., Dillard, R. G., Washburn, L. K., Jackson, B. G., Peters, N., Chiu, K., Allred, D., Goldstein, D. J., Halfond, R., Peterson, C., Waldrep, E. L., Welch, C. D., Morris, M., Hounshell, G., Shankaran, S., Pappas, A., Barks, J., Bara, R., Goldston, L. A., Natarajan, G., Bajaj, M., Chawla, S., De Jesus, L. C., Sood, B. G., Christensen, M., Wiggins, S. A., White, D., Ehrenkranz, R. A., Jacobs, H., Butler, C. G., Cervone, P., Greisman, S., Konstantino, M., Poulsen, J., Taft, J., Williams, J., Romano, E., Eunice Kennedy Shriver Natl Inst 2019; 214: 41-+

  Abstract

  To assess the frequency of gastrostomy tube (GT) placement in extremely low birth weight (ELBW) infants, associated comorbidities, and long-term outcomes.Analysis of ELBW infants from 25 centers enrolled in the National Institute of Child Health and Human Development Neonatal Research Network's Generic Database and Follow-up Registry from 2006 to 2012. Frequency of GT placement before 18-22 months, demographic and medical factors associated with GT placement, and associated long-term outcomes at 18-22 months of corrected age were described. Associations between GT placement and neonatal morbidities and long-term outcomes were assessed with logistic regression after adjustment for center and common co-variables.Of the 4549 ELBW infants included in these analyses, 333 (7.3%) underwent GT placement; 76% had the GT placed postdischarge. Of infants with GTs, 11% had birth weights small for gestational age, 77% had bronchopulmonary dysplasia, and 29% severe intraventricular hemorrhage or periventricular leukomalacia. At follow-up, 56% of infants with a GT had weight <10th percentile, 61% had neurodevelopmental impairment (NDI), and 55% had chronic breathing problems. After adjustment, small for gestational age, bronchopulmonary dysplasia, intraventricular hemorrhage/periventricular leukomalacia, poor growth, and NDI were associated with GT placement. Thirty-two percent of infants with GTs placed were taking full oral feeds at follow-up.GT placement is common in ELBW infants, particularly among those with severe neonatal morbidities. GT placement in this population was associated with poor growth, NDI, and chronic respiratory and feeding problems at follow-up. The frequency of GT placement postneonatal discharge indicates the need for close nutritional follow-up of ELBW infants.ClinicalTrials.gov: NCT00063063.

  View details for DOI 10.1016/j.jpeds.2019.06.066

  View details for Web of Science ID 000492192700010

  View details for PubMedID 31427096

  View details for PubMedCentralID PMC6815700

• Developmental Outcomes of Extremely Preterm Infants with a Need for Child Protective Services Supervision. The Journal of pediatrics McGowan, E. C., Laptook, A. R., Lowe, J., Peralta-Carcelen, M., Chowdhury, D., Higgins, R. D., Hintz, S. R., Vohr, B. R., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Polin, R. A., Abbott R Laptook, Martin Keszler, Angelita M Hensman, Alksninis, B., Basso, K. M., Burke, R., Caskey, M., Johnson, K., Keszler, M. L., Knoll, A. M., Leach, T. M., Little, E., McGowan, E. C., Vieira, E., Watson, V. E., Ventura, S., Walsh, M. C., Fanaroff, A. A., Hibbs, A. M., Wilson-Costello, D. E., Newman, N. S., Payne, A. H., Siner, B. S., Bhola, M., Yalcinkaya, G., Friedman, H. G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Knutson, A., Schibler, K., Donovan, E. F., Grisby, C., Bridges, K., Alexander, B., Fischer, E. E., Mincey, H. L., Hessling, J., Gratton, T. L., Jackson, L., Kirker, K., Muthig, G., Steichen, J. J., Tepe, S., Yolton, K., Goldberg, R. N., Cotten, C. M., Goldstein, R. F., Ashley, P. L., Malcolm, W. F., Auten, K. J., Fisher, K. A., Grimes, S., Gustafson, K. E., Lohmeyer, M. B., Finkle, J., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Clark, C., Manor, L., Warner, D., Wereszczak, J., Carlton, D. P., Stoll, B. J., Adams-Chapman, I., Hale, E. C., Loggins, Y., Archer, S. W., Sokol, G. M., Poindexter, B. B., Dusick, A. M., Papile, L., Gunn, S., Hamer, F., Herron, D. E., Hines, A. C., Lytle, C., Minnich, H. M., Smiley, L., Wilson, L. D., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Das, A., Wallace, D., Gantz, M. G., Poole, W. K., Newman, J. E., O'Donnell Auman, J., Crawford, M. M., Petrie Huitema, C. M., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Hintz, S. R., Ball, M. B., Davis, A. S., Palmquist, A. W., Proud, M. S., Bentley, B., Bruno, E., DeAnda, M. E., DeBattista, A. M., Earhart, B., Huffman, L. C., Kohn, J. G., Krueger, C., Weiss, H. E., Frantz, I. D., Fiascone, J. M., MacKinnon, B. L., Furey, A., Nylen, E., McGowan, E. C., Carlo, W. A., Ambalavanan, N., Peralta-Carcelen, M., Collins, M. V., Cosby, S. S., Biasini, F. J., Johnston, K. C., Nelson, K. G., Patterson, C. S., Phillips, V. A., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Finer, N. N., Vaucher, Y. E., Kaegi, D., Rasmussen, M. R., Arnell, K., Demetrio, C., Fuller, M. G., Rich, W., Bell, E. F., Colaizy, T. T., Acarregui, M. J., Ellsbury, D. L., Widness, J. A., Johnson, K. J., Campbell, D. B., Eastman, D. L., Walker, J. R., Brumbaugh, J. E., Duara, S., Bauer, C. R., Everett-Thomas, R., Fajardo-Hiriart, S., Rigaud, A., Calejo, M., Frade Eguaras, S. M., Berkowits, M. H., Garcia, A., Pierre, H., Stoerger, A., Watterberg, K. L., Lowe, J. R., Fuller, J. F., Ohls, R. K., Lacy, C. B., Duncan, A. F., Montman, R., Schmidt, B., Kirpalani, H., DeMauro, S. B., Chaudhary, A. S., Abbasi, S., Mancini, T., Cucinotta, D. M., Bernbaum, J. C., Gerdes, M., Hurt, H., D'Angio, C. T., Phelps, D. L., Guillet, R., Lakshminrusimha, S., Johnson, J. B., Reubens, L. J., Horihan, C. A., Hust, D., Jensen, R. L., Kushner, E., Merzbach, J., Myers, G. J., Rowan, M., Wadkins, H. I., Bowman, M., Hunn, J., Guilford, S., Maffett, D., Osman, F., Prinzing, D., Reynolds, A. M., Rowan, M., Sacilowski, M. G., Williams, A., Wynn, K., Yost, K., Zorn, W., Zwetsch, L., Kennedy, K. A., Tyson, J. E., McDavid, G. E., Alaniz, N. I., Arldt-McAlister, J., Burson, K., Evans, P. W., Duncan, A. F., Garcia, C., Green, C., Harris, B. F., Jiminez, M., John, J., Jones, P. M., Lillie, L. M., Lis, A. E., Martin, K., Martin, S. C., Morris, B. H., Poundstone, M. L., Robichaux, P., Rodgers, S., Siddiki, S., Simmons, M. C., Sperry, D., Pierce Tate, P. L., Wright, S. L., Wyckoff, M. H., Brion, L. P., Heyne, R. J., Salhab, W. A., Rosenfeld, C. R., Vasil, D. M., Chen, L., Guzman, A., Hensley, G., Leps, M. H., Miller, N. A., Morgan, J. S., Adams, S. S., Boatman, C. T., Heyne, E. T., Madden, L. A., Torres, L. E., Faix, R. G., Yoder, B. A., Osborne, K. A., Spencer, C., Weaver-Lewis, K., Baker, S., Bird, K., Burnett, J., Steffen, M., Jensen, J. J., Winter, S., Zanetti, K., O'Shea, T. M., Dillard, R. G., Washburn, L. K., Jackson, B. G., Peters, N., Chiu, K., Allred, D. E., Goldstein, D. J., Halfond, R., Peterson, C., Waldrep, E. L., Welch, C. D., Morris, M. W., Hounshell, G. W., Shankaran, S., Pappas, A., Barks, J., Bara, R., Goldston, L. A., Natarajan, G., Christensen, M., Wiggins, S. A., White, D., Ehrenkranz, R. A., Jacobs, H., Butler, C. G., Cervone, P., Greisman, S., Konstantino, M., Poulsen, J., Taft, J., Williams, J., Romano, E. 2019

  Abstract

  OBJECTIVE: To evaluate neurodevelopmental outcomes of preterm infants with need for Child Protective Services (CPS) supervision at hospital discharge compared with those discharged without CPS supervision.STUDY DESIGN: For infants born at <27weeks of gestation between 2006 and 2013, prospectively collected maternal and neonatal characteristics and 18- to 26-month corrected age follow-up data were analyzed. Bayley-III cognitive and language scores of infants with discharge CPS supervision were compared with infants without CPS supervision using regression analysis while adjusting for potentially confounding variables, including entering CPS after discharge from the hospital.RESULTS: Of the 4517 preterm infants discharged between 2006 and 2013, 255 (5.6%) were discharged with a need for CPS supervision. Mothers of infants with CPS supervision were significantly more likely to be younger, single, and gravida ≥3; to have less than a high school education; and to have a singleton pregnancy and less likely to have received prenatal care or antenatal steroids. Despite similar birth weight and medical morbidities, the CPS group had longer hospital stays compared with the non-CPS group. In adjusted analysis, cognitive scores were points lower (B = -1.94; 95% CI, -3.88 to -0.08; P = .04) in the CPS at discharge group compared with the non-CPS group. In children who entered CPS supervision after hospital discharge (an additional 106 infants), cognitive scores were 4 points lower (beta=-4.76; 95% CI, -7.47 to -2.05; P<.001) and language scores were 5 points lower (beta=-4.93; 95% CI, -8.00 to -1.86; P=.002).CONCLUSION: Extremely preterm infants discharged from the hospital with CPS supervision or entering CPS postdischarge are at increased risk for cognitive delay at 2years of age. Opportunities exist to intervene and potentially improve outcomes in this vulnerable group of children.

  View details for DOI 10.1016/j.jpeds.2019.07.063

  View details for PubMedID 31500860

• Outcomes of Extremely Preterm Infants With Birth Weight Less Than 400 g JAMA PEDIATRICS Brumbaugh, J. E., Hansen, N. I., Bell, E. F., Sridhar, A., Carlo, W. A., Hintz, S. R., Vohr, B. R., Colaizy, T. T., Duncan, A. F., Wyckoff, M. H., Baack, M. L., Rysavy, M. A., DeMauro, S. B., Stoll, B. J., Das, A., Higgins, R. D., Polin, R. A., Caplan, M. S., Laptook, A. R., Keszler, M., Hensman, A. M., Alksninis, B., Burke, R. T., Caskey, M., Hoffman, L., Johnson, K., Keszler, M., Leach, T. M., McGowan, E. C., Stephens, B. E., Basso, K., Vieira, E., Little, E., St Pierre, L., Watson, V. E., Walsh, M. C., Hibbs, A., Newman, N. S., Wilson-Costello, D. E., Skier, B. S., Bhola, M., Yalcinkaya, G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Scott, A., Parimi, P. S., Gaetano, L., Poindexter, B. B., Schibler, K., Kallapur, S. G., Yolton, K., Alexander, B., Gratton, T. L., Grisby, C., Kirker, K., Jackson, L. D., Steichen, J. J., Wuertz, S., Cotten, C., Goldberg, R. N., Goldstein, R. F., Malcolm, W. F., Ashley, P. L., Finkle, J., Fisher, K. A., Grimes, S., Gustafson, K. E., Lohmeyer, M. B., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Wereszczak, J., Kicklighter, S. D., Rhodes-Ryan, G., Archer, S., Carlton, D. P., Adams-Chapman, I., Hale, E. C., Loggins, Y., Bottcher, D., Carter, S. L., Kendrick-Allwood, S., LaRossa, M., Mackie, C., Seabrook, I., Smikie, G., Wineski, L., Sokol, G. M., Poindexter, B. B., Dusick, A. M., Hamer, F., Herron, D. E., Hines, A. C., Lytle, C., Miller, L. C., Minnich, H. M., Papile, L., Richard, L., Smiley, L., Wilson, L., Kennedy, K. A., Tyson, J. E., Arldt-McAlister, J., Burson, K., Dempsey, A. G., Eason, E., Evans, P. W., Garcia, C., Green, C., Hall, D., Harris, B., Jiminez, M., John, J., Jones, P. M., Lillie, M., Martin, K., Martin, S. C., McDavid, G. E., Rodgers, S., Siddiki, S., Sperry, D., Stephens, E. K., Tate, P., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Wallace, D., Gantz, M. G., Auman, J., Crawford, M., Gabrio, J., Newman, J. E., Huitema, C., Poole, W., Zaterka-Baxter, K. M., Frantz, I. D., Fiascone, J. M., McGowan, E. C., MacKinnon, B. L., Furey, A., Nylen, E., Church, P. T., Van Meurs, K. P., Stevenson, D. K., Adams, M. M., Ball, M., Bentley, B., Bruno, E., DeAnda, M., DeBattista, A. M., Huffman, L. C., Ismael, M., Kohn, J. G., Krueger, C., Palmquist, A., Proud, M. S., St John, N. H., Weiss, H., Ambalavanan, N., Peralta-Carcelen, M., Nelson, K. G., Bailey, K. J., Biasini, F. J., Chopko, S. A., Collins, M. V., Cosby, S. S., Johnston, K. C., Moses, M., Patterson, C. S., Phillips, V. A., Preskitt, J., Rector, R. V., Whitley, S., Devaskar, U., Gary, M., Purdy, I. B., Chanlaw, T., Geller, R., Widness, J. A., Acarregui, M. J., Ellsbury, D. L., Johnson, K. J., Walker, J. R., Goeke, C. A., Eastman, D. L., Campbell, D. B., Tud, T. L., Watterberg, K. L., Ohls, R. K., Lacy, C., Brown, S., Fuller, J., Hartenberger, C., Lowe, J. R., Thomson, R. A., Beauman, S., Hanson, M., Kuan, E., Schmidt, B., Kirpalani, H., Chaudhary, A. S., Abbasi, S., Mancini, T., Cucinotta, D. M., Bernbaum, J. C., Gerdes, M., Hurt, H., Snyder, J., D'Angio, C. T., Phelps, D. L., Guillet, R., Myers, G. J., Lakshminrusimha, S., Reynolds, A., Reubens, L. J., Burnell, E., Scorsone, A., Binion, K., Orme, C., Wadkins, H. M., Sacilowski, M. G., Jensen, R. L., Merzbach, J., Zorn, W., Farooq, O., Maffett, D., Williams, A., Hunn, J., Guilford, S., Yost, K., Rowan, M., Prinzing, D., Wynn, K., Bowman, M., Brion, L. P., Sanchez, P. J., Heyne, R. J., Vasil, D. M., Adams, S. S., Chen, L., De Leon, M. M., Eubanks, F., Guzman, A., Heyne, E. T., Lee, L. E., Leps, M. H., Madden, L. A., Miller, N. A., Morgan, J. S., Pavageau, L., Sepulveda, P., Boatman, C., Yoder, B. A., Baserga, M., Faix, R. G., Minton, S. D., Sheffield, M. J., Rau, C. A., Winter, S., Osborne, K. A., Spencer, C., Weaver-Lewis, K., Baker, S., Burnett, J., Steffen, M., Loertscher, M. C., Woodbury, K. D., Reich, B. A., Schaefer, S. T., Cole-Bledsoe, L., Elmont, J. O., Parry, D., Marchant, T., Christensen, S., Maxson, E., Davis, B., Shankaran, S., Sood, B. G., Pappas, A., Natarajan, G., Chawla, S., Bajaj, M., Bara, R., Childs, K., Panaitescu, B., Johnson, M. E., Goldston, L. A., Wiggins, S. A., Christensen, M. K., Carlson, M., Barks, J., Ehrenkranz, R. A., Jacobs, H., Butler, C. G., Cervone, P., Greisman, S., Konstantino, M., Poulsen, J., Taft, J., Williams, J., Romano, E., Natl Inst Child Hlth Human Dev 2019; 173 (5): 434–45

  View details for DOI 10.1001/jamapediatrics.2019.0180

  View details for Web of Science ID 000467505200011

• Discordance in Antenatal Corticosteroid Use and Resuscitation Following Extremely Preterm Birth JOURNAL OF PEDIATRICS Rysavy, M. A., Bell, E. F., Iams, J. D., Carlo, W. A., Li, L., Mercer, B. M., Hintz, S. R., Stoll, B. J., Vohr, B. R., Shankaran, S., Walsh, M. C., Brumbaugh, J. E., Colaizy, T. T., Das, A., Higgins, R. D., Caplan, M. S., Polin, R. A., Laptook, A. R., Hensman, A. M., Oh, W., Keszler, M., Burke, R., Caskey, M., Johnson, K., Alksninis, B., Leach, T. M., Stephens, B. E., Watson, V. E., Ventura, S., Basso, K. M., Vieira, E., Halbrook, A., Fanaroff, A. A., Hibbs, A., Wilson-Costello, D. E., Newman, N. S., Siner, B. S., Bhola, M., Yalcinkaya, G., Friedman, H. G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Schibler, K., Donovan, E. F., Bridges, K., Alexander, B., Grisby, C., Hessling, J., Fischer, E. E., Jackson, L. D., Kirker, K., Mincey, H. L., Muthig, G., Gratton, T. L., Steichen, J. J., Yolton, K., Goldberg, R. N., Goldstein, R. F., Fisher, K. A., Auten, K. J., Foy, K. A., Grimes, S., Finkle, J., Gustafson, K. E., Lohmeyer, M. B., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Clark, C., Carlton, D. P., Hale, E. C., Adams-Chapman, I., LaRossa, M., Carter, S. L., Archer, S., Poindexter, B. B., Dusick, A. M., Cook, A. B., Herron, D. E., Hamer, F., Lytle, C., Miller, L. C., Minnich, H. M., Wilson, L., Nelin, L. D., Jadcherla, S. R., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Poole, W., Wallace, D., Newman, J. E., Auman, J., Crawford, M. M., Huitema, C., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Adams, M. M., Ball, M., Palmquist, A. W., Proud, M. S., Bruno, E., DeAnda, M., DeBattista, A. M., Kohn, J. G., Krueger, C. E., Weiss, H. E., Frantz, I. D., Fiascone, J. M., MacKinnon, B. L., Nylen, E., Furey, A., McGowan, E. C., Sibley, C. E., Brussa, A. K., Ambalavanan, N., Peralta-Carcelen, M., Collins, M., Cosby, S. S., Biasini, F. J., Johnston, K. C., Nelson, K. G., Patterson, C. S., Phillips, V. A., Whitley, S., Soong, A. D., Kiser, C., Smith, L., Kryzwanski, S., Rector, R., Ryan, S., Domnanovich, K., Rodrigues, L., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Finer, N. N., Vaucher, Y. E., Kaegi, D., Rasmussen, M. R., Arnell, K., Demetrio, C., Fuller, M. G., Henderson, C., Rich, W., West, R., Ellsbury, D. L., Widness, J. A., Johnson, K. J., Campbell, D. B., Walker, J. R., Eastman, D. L., Duara, S., Bauer, C. R., Everett-Thomas, R., Hiriart-Fajardo, S., Rigaud, A., Calejo, M., Eguaras, S., Berkowits, M., Garcia, A., Pierre, H., Stoerger, A., Watterberg, K. L., Ohls, R. K., Fuller, J. F., Lacy, C., Montman, R. A., Lowe, J. R., Duncan, A., Brown, S., Wussow, T., Hartenberger, C., Rohr, J., Schmidt, B., Kirpalani, H., DeMauro, S. B., Chaudhary, A. S., Abbasi, S., Mancini, T., Cucinotta, D., Phelps, D. L., Myers, G. J., Reubens, L. J., Burnell, E., Hust, D., Johnson, J., Jensen, R. L., Kushner, E., Merzbach, J., Yost, K., Zwetsch, L., Lakshminrusimha, S., Reynolds, A., Farooq, O., Williams, A., Kennedy, K. A., Alaniz, N., Burson, K., Evans, P. W., Green, C., Harris, B., Jiminez, M., Lis, A. E., Martin, S., McDavid, G. E., Morris, B. H., Poundstone, M., Robichaux, P., Siddiki, S., Simmons, M. C., Tate, P., Wright, S. L., Sanchez, P. J., Heyne, R. J., Salhab, W. A., Rosenfeld, C. R., Brion, L. P., Chen, L., Guzman, A., Leps, M. H., Miller, N. A., Vasil, D. M., Torres, L. E., Hensley, G., Adams, S. S., Madden, L. A., Heyne, E., Morgan, J. S., Boatman, C., Faix, R. G., Yoder, B. A., Bodnar, A., Osborne, K. A., Baker, S., Bird, K., Burnett, J., Jensen, J. J., Spencer, C., Steffen, M., Weaver-Lewis, K., Winter, S., Zanetti, K., O'Shea, T., Dillard, R. G., Washburn, L. K., Jackson, B. G., Peters, N., Chiu, K., Allred, D., Goldstein, D. J., Halfond, R., Peterson, C., Waldrep, E. L., Welch, C. D., Morris, M., Hounshell, G., Pappas, A., Barks, J., Bara, R., Goldston, L. A., Johnson, M., Muran, G., Sumner, L., Sawaya, K., Weingarden, K., Christensen, M., Wiggins, S., Ehrenkranz, R. A., Jacobs, H., Butler, C. G., Cervone, P., Greisman, S., Konstantino, M., Poulsen, J., Taft, J., Williams, J., Romano, E., Eunice Kennedy Shriver Natl Inst C 2019; 208: 156-+

  View details for DOI 10.1016/j.jpeds.2018.12.063

  View details for Web of Science ID 000465236700029

• Neurodevelopmental outcomes among extremely premature infants with linear growth restriction JOURNAL OF PERINATOLOGY Meyers, J. M., Tan, S., Bell, E. F., Duncan, A. F., Guillet, R., Stoll, B. J., D'Angio, C. T., Caplan, M. S., Laptook, A. R., Keszler, M., Vohr, B. R., Hensman, A. M., Vieira, E., Little, E., Alksninis, B., Keszler, M., Knoll, A. M., Leach, T. M., McGowan, E. C., Watson, V. E., Walsh, M. C., Fanaroff, A. A., Hibbs, A., Newman, N. S., Payne, A. H., Wilson-Costello, D. E., Siner, B. S., Bhola, M., Yalcinkaya, G., Friedman, H. G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Knutson, A., Poindexter, B. B., Schibler, K., Alexander, B., Grisby, C., Gratton, T. L., Jackson, L., Kirker, K., Muthig, G., Tepe, S., Yolton, K., Goldberg, R. N., Cotten, C., Goldstein, R. F., Malcolm, W. F., Ashley, P. L., Fisher, K. A., Finkle, J., Gustafson, K. E., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Wereszczak, J., Carlton, D. P., Hale, E. C., Adams-Chapman, H., Loggins, Y., Carter, S. L., LaRossa, M., Wineski, L. C., Bottcher, D., Mackie, C., Higgins, R. D., Archer, S., Sokol, G. M., Papile, L., Harmon, H. M., Hines, A. C., Wilson, L., Herron, D. E., Gunn, S., Smiley, L., Kennedy, K. A., Tyson, J. E., Allain, E., Arldt-McAlister, J., Dempsey, A. G., Garcia, C., John, J., Jones, P. M., Lillie, L. M., Martin, K., Martin, S. C., McDavid, G. E., Rodgers, S., Siddiki, S., Sperry, D., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Fortney, C. A., Luzader, P., Besner, G. E., Parikh, N. A., Das, A., Wallace, D., Newman, J. E., Auman, J., Crawford, M., Gabrio, J., Gantz, M. G., Huitema, C., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Hintz, S. R., Ball, M., Proud, M. S., Bentley, B., DeAnda, M., DeBattista, A. M., Earhart, B., Huffman, L. C., Krueger, C. E., Lucash, R., Weiss, H. E., Carlo, W. A., Ambalavanan, N., Peralta-Carcelen, M., Collins, M., Cosby, S. S., Biasini, F. J., Johnston, K. C., Patterson, C. S., Phillips, V. A., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Colaizy, T. T., Brumbaugh, J. E., Ellsbury, D. L., Johnson, K. J., Walker, J. R., Campbell, D. B., Eastman, D. L., Watterberg, K. L., Lowe, J. R., Fuller, J. F., Ohls, R. K., Lacy, C., Duncan, A. F., Dupont, T., Kuan, E., Beauman, S., Schmidt, B., Kirpalani, H., DeMauro, S. B., Chaudhary, A. S., Abbasi, S., Mancini, T., Bernbaum, J. C., Gerdes, M., Hurt, H., Cook, N., Cucinotta, D. M., Lakshminrusimha, S., Reynolds, A., Jensen, R. L., Merzbach, J., Myers, G. J., Williams, A., Yost, K., Zorn, W., Wynn, K., Maffett, D., Prinzing, D., Hunn, J., Guilford, S., Osman, F., Rowan, M., Sacilowski, M. G., Wadkins, H. M., Bowman, M., Fallone, C., Binion, K., Orme, C., Scorsone, A., Andrews-Hartley, M., Wyckoff, M. H., Brion, L. P., Vasil, D. M., Chen, L., Heyne, R. J., Adams, S. S., Heyne, E., Guzman, A., Lee, L. E., Boatman, C., Shankaran, S., Pappas, A., Natarajan, G., Chawla, S., Bajaj, M., February, M., Agarwal, P., Childs, K., Woldt, E., Bara, R., Goldston, L. A., Barks, J., Christensen, M., Wiggins, S., White, D., Eunice Kennedy Shriver Natl Inst 2019; 39 (2): 193–202

  Abstract

  To compare neurodevelopmental outcomes in linear growth-restricted (LGR) infants born <29 weeks with and without weight gain out of proportion to linear growth.We compared 2-year neurodevelopmental outcomes between infants with and without LGR and between LGR infants with and without weight gain out of proportion to linear growth. The outcomes were Bayley-III cognitive, motor, and language scores, cerebral palsy, Gross Motor Function Classification System (GMFCS) level ≥ 2, and neurodevelopmental impairment.In total, 1227 infants were analyzed. LGR infants were smaller and less mature at birth, had higher BMI, and had lower Bayley-III language scores (82.3 vs. 85.0, p < 0.05). Among infants with LGR, infants with high BMI had lower language scores compared with those with low-to-normal BMI (80.8 vs. 83.3, p < 0.05), and were more likely to have GMFCS level ≥2 and neurodevelopmental impairment.Among infants with LGR, weight gain out of proportion to linear growth was associated with poorer neurodevelopmental outcomes.

  View details for PubMedID 30353080

• Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy. Neurology Meador, K. J., Pennell, P. B., May, R. C., Van Marter, L. n., McElrath, T. F., Brown, C. n., Gerard, E. n., Kalayjian, L. n., Gedzelman, E. n., Penovich, P. n., Cavitt, J. n., French, J. n., Hwang, S. n., Pack, A. M., Sam, M. n., Birnbaum, A. K., Finnell, R. n. 2019

  Abstract

  To examine occurrence of severe adverse fetal outcomes (SAO), including fetal loss and major congenital malformations (MCMs), in pregnant women with epilepsy (PWWE) vs healthy pregnant women (HPW).The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes for both mother and child, which enrolled women December 2012 through January 2016.The 351 PWWE had 365 conceptions, and 105 HPW had 109 conceptions. SAOs occurred more often in PWWE (7.9%) vs HPW (1.9%) (p = 0.025) with odds ratio (OR) 4.45 (95% confidence intervals [CI] 1.04-19.01). There were no significant differences for fetal loss (2.8% vs 0%, p = 0.126) or MCMs (5.2% vs 1.9%, p = 0.185; OR 2.86, 95% CI 0.65-12.53) individually. No fetal losses in PWWE appeared to be related to acute seizures. Outcomes were not affected by periconceptional folate, unplanned/unwanted pregnancies, prior maternal pregnancy history, or antiepileptic drug (AED) blood levels, except for an AED level effect for fetal loss that appeared to be due to polytherapy. Combined maternal or paternal family history of MCM was marginally associated with increased SAOs (p = 0.046).The findings provide additional information on risks of SAOs in PWWE, assessing effects of both AED levels and periconceptional folate. Group differences in average enrollment gestational age could have affected fetal loss results. Analyses are limited by small sample sizes as the MONEAD study was not powered for these secondary outcomes. The large majority of pregnancies in women with epilepsy do not have SOAs.

  View details for DOI 10.1212/WNL.0000000000008687

  View details for PubMedID 31806691

• Behavioral problems are associated with cognitive and language scores in toddlers born extremely preterm EARLY HUMAN DEVELOPMENT Lowe, J. R., Fuller, J. F., Do, B. T., Vohr, B. R., Das, A., Hintz, S. R., Watterberg, K. L., Higgins, R. D., Caplan, M. S., Laptook, A. R., Keszler, M., Hensman, A. M., Vieira, E., Little, E., Alksninis, B., Keszler, M., Knoll, A. M., Leach, T. M., McGowan, E. C., Watson, V. E., Walsh, M. C., Hibbs, A., Newman, N. S., Payne, A. H., Wilson-Costello, D. E., Siner, B. S., Bhola, M., Ross, E., Taylor, H., Yalcinkaya, G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Knutson, A., Poindexter, B. B., Schibler, K., Merhar, S., Grisby, C., Gratton, T. L., Tepe, S., Yolton, K., Goldberg, R. N., Cotten, C., Goldstein, R. F., Malcolm, W. F., Ashley, P. L., Fisher, K. A., Finkle, J., Gustafson, K. E., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Wereszczak, J., Carlton, D. P., Hale, E. C., Adams-Chapman, I., Loggins, Y., Carter, S. L., LaRossa, M., Wineski, L. C., Bottcher, D., Mackie, C., Archer, S., Sokol, G. M., Poindexter, B. B., Papile, L., Harmon, H. M., Hines, A. C., Wilson, L., Herron, D. E., Gunn, S., Smiley, L., Kennedy, K. A., Tyson, J. E., Allain, E., Arldt-McAlister, J., Dempsey, A. G., Duncan, A. F., Garcia, C., Eason, E., John, J., Jones, P. M., Lillie, M., Martin, K., Martin, S. C., McDavid, G. E., McKee, S., Rodgers, S., Sperry, D., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Fortney, C. A., Luzader, P., Besner, G. E., Parikh, N. A., Wallace, D., Newman, J. E., Auman, J., Crawford, M., Gabrio, J., Gantz, M. G., Huitema, C., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Ball, M., Proud, M. S., Bentley, B., DeAnda, M., DeBattista, A. M., Earhart, B., Huffman, L. C., Krueger, C. E., Lucash, R., Weiss, H. E., Carlo, W. A., Ambalavanan, N., Peralta-Carcelen, M., Collins, M., Cosby, S. S., Biasini, F. J., Johnston, K. C., Patterson, C. S., Phillips, V. A., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Bell, E. F., Colaizy, T. T., Brumbaugh, J. E., Ellsbury, D. L., Johnson, K. J., Walker, J. R., Campbell, D. B., Eastman, D. L., Tud, T. L., Ohis, R. K., Lacy, C., Duncan, A. F., Dupont, T., Kuan, E., Beauman, S., Hanson, M., Schmidt, B., Kirpalani, H., DeMauro, S. B., Chaudhary, A. S., Abbasi, S., Mancini, T., Bernbaum, J. C., Gerdes, M., Hurt, H., Cook, N., Cucinotta, D. M., D'Angio, C. T., Lakshminrusintha, S., Guillet, R., Reynolds, A., Jensen, R. L., Merzbach, J., Myers, G. J., Williams, A., Yost, K., Zorn, W., Wynn, K., Maffett, D., Prinzing, D., Hunn, J., Guilford, S., Farooq, O., Rowan, M., Sacilowski, M. G., Wadkins, H. M., Bowman, M., Fallone, C., Binion, K., Orme, C., Scorsone, A., Andrews-Hartley, M., Wyckoff, M. H., Sanchez, P. J., Brion, L. P., Vasil, D. M., Chen, L., Heyne, R. J., Adams, S. S., Heyne, E., Guzman, A., Lee, L. E., Boatman, C., Shankaran, S., Pappas, A., Natarajan, G., Chawla, S., Bajaj, M., February, M., Agarwal, P., Childs, K., Woldt, E., Bara, R., Goldston, L. A., Barks, J., Christensen, M., Wiggins, S., White, D., Eunice Kennedy Shriver Natl Inst, Human Dev Neonatal Res Network 2019; 128: 48–54

  View details for DOI 10.1016/j.earlhumdev.2018.11.007

  View details for Web of Science ID 000458094300008

• Behavioral problems are associated with cognitive and language scores in toddlers born extremely preterm. Early human development Lowe, J. R., Fuller, J. F., Do, B. T., Vohr, B. R., Das, A., Hintz, S. R., Watterberg, K. L., Higgins, R. D., Eunice Kennedy Shriver National Institute of Child Health, Human Development Neonatal Research Network 2018; 128: 48–54

  Abstract

  OBJECTIVE: To evaluate the relationship of parent-reported child behaviors on the Child Behavior Checklist (CBCL) to cognition, language, and motor skills on the Bayley Scales of Infant and Toddler Development - III (Bayley-III) in toddlers born extremely preterm.STUDY DESIGN: Toddlers born extremely preterm (gestational ages 22 0/7 to 26 6/7 weeks) were tested at 22-26 months corrected age with Bayley-III while parents completed the CBCL. Socio-demographic variables and medical history were recorded. Linear regression models were used to assess the relationship of Bayley-III cognitive, motor, and language scores with CBCL scores, adjusting for medical and socio-demographic factors.RESULTS: Internalizing, affective, and pervasive development problem behavior scores on the CBCL correlated significantly with lower Bayley-III cognitive, language, and motor scores on unadjusted and adjusted analyses. Although externalizing and anxiety problems were significantly associated with cognitive and language scores on unadjusted analysis, the relationships were not significant after adjusting for socio-economic factors. CBCL scores were similar for boys and girls, with the exception of the pervasive developmental problem scale; boys had significantly more problems than girls (p = 0.02).CONCLUSIONS: This study showed that parent reported behavior problems were related to lower cognitive, language, and motor development in toddlers born extremely preterm. Early findings of behavioral problems in toddlers born extremely premature may help identify children at greater risk for later learning difficulties. Adding a measure of behavior to the evaluation of these children may help better understand factors that can contribute to delays, especially in cognition and language.

  View details for PubMedID 30522091

• Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy EPILEPSY & BEHAVIOR Meador, K. J., Pennell, P. B., May, R. C., Gerard, E., Kalayjian, L., Velez-Ruiz, N., Penovich, P., Cavitt, J., French, J., Hwang, S., Pack, A. M., Sam, M., Moore, E., Ippolito, D. M., MONEAD Investigator Grp 2018; 84: 10–14

  View details for DOI 10.1016/j.yebeh.2018.04.009

  View details for Web of Science ID 000436923800002

• Outcome of Preterm Infants with Transient Cystic Periventricular Leukomalacia on Serial Cranial Imaging Up to Term Equivalent Age JOURNAL OF PEDIATRICS Sarkar, S., Shankaran, S., Barks, J., Do, B. T., Laptook, A. R., Das, A., Ambalavanan, N., Van Meurs, K. P., Bell, E. F., Sanchez, P. J., Hintz, S. R., Wyckoff, M. H., Stoll, B. J., Carlo, W. A., Eunice Kennedy Shriver Natl Inst C 2018; 195: 59-+

  Abstract

  To determine the outcome of preterm infants whose cystic periventricular leukomalacia "disappeared" on serial screening cranial imaging studies.Infants ≤26 weeks of gestation born between 2002 and 2012 who had cranial imaging studies at least twice, the most abnormal study at <28 days of age and another closest to 36 weeks, were reviewed. The outcome of late death (after 36 weeks postmenstrual age) or neurodevelopmental impairment (NDI) in surviving infants at 18-26 months corrected age was compared between the infants with no cystic periventricular leukomalacia on both studies and cystic periventricular leukomalacia that disappeared (cystic periventricular leukomalacia at <28 days but not at 36 weeks), persisted (cystic periventricular leukomalacia on both studies), or appeared late (cystic periventricular leukomalacia only at 36 weeks). Predictors of NDI were evaluated by logistic regression.Of 7063 eligible infants, 433 (6.1%) had cystic periventricular leukomalacia. Among the 433 infants with cystic periventricular leukomalacia, cystic periventricular leukomalacia disappeared in 76 (18%), persisted in 87 (20%), and 270 (62%) had late cystic periventricular leukomalacia. Loss to follow-up ranged between 3% and 13%. Death or NDI was more common in infants with disappeared cystic periventricular leukomalacia compared with those with no cystic periventricular leukomalacia (38 of 72 [53%] vs 1776 of 6376 [28%]; OR [95% CI] 2.8 [1.8-4.6]). Disappeared, persistent, and late cystic periventricular leukomalacia were all also independently associated with NDI (OR 1.17, 1.21, and 1.16, respectively).Infants with "disappeared" cystic periventricular leukomalacia are at increased risk of adverse outcome similar to infants with persistent or late cystic periventricular leukomalacia.

  View details for PubMedID 29398046

• Treatment of methylmalonic acidemia by liver or combined liver-kidney transplantation. journal of pediatrics Niemi, A., Kim, I. K., Krueger, C. E., Cowan, T. M., Baugh, N., Farrell, R., Bonham, C. A., Concepcion, W., Esquivel, C. O., Enns, G. M. 2015; 166 (6): 1455-61 e1

  Abstract

  To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic acidemia/acid (MMA).A retrospective chart review (December 1997 to May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard Children's Hospital at Stanford.Fourteen patients underwent LT (n = 6) or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were diagnosed during the neonatal period, including 6 by newborn screening. All underwent deceased donor transplantation; 12 (86%) received a whole liver graft. Postoperative survival was 100%. At a mean follow-up of 3.25 ± 4.2 years, patient survival was 100%, liver allograft survival 93%, and kidney allograft survival 100%. One patient underwent liver re-transplantation because of hepatic artery thrombosis. After transplantation, there were no episodes of hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the time of transplantation was 1648 ± 1492 μmol/L (normal <0.3, range 99-4420). By 3 days, post-transplantation levels fell on average by 87% (mean 210 ± 154 μmol/L), and at 4 months, they were 83% below pre-transplantation levels (mean 305 ± 108 μmol/L). Developmental delay was present in 12 patients (86%) before transplantation. All patients maintained neurodevelopmental abilities or exhibited improvements in motor skills, learning abilities, and social functioning.LT or LKT for MMA eradicates episodes of hyperammonemia, results in excellent long-term survival, and suggests stabilization of neurocognitive development. Long-term follow-up is underway to evaluate whether patients who undergo early LT need kidney transplantation later in life.

  View details for DOI 10.1016/j.jpeds.2015.01.051

  View details for PubMedID 25771389

• Treatment of Methylmalonic Acidemia by Liver or Combined Liver-Kidney Transplantation JOURNAL OF PEDIATRICS Niemi, A., Kim, I. K., Krueger, C. E., Cowan, T. M., Baugh, N., Farrell, R., Bonham, C. A., Concepcion, W., Esquivel, C. O., Enns, G. M. 2015; 166 (6): 1455-?

  Abstract

  To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic acidemia/acid (MMA).A retrospective chart review (December 1997 to May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard Children's Hospital at Stanford.Fourteen patients underwent LT (n = 6) or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were diagnosed during the neonatal period, including 6 by newborn screening. All underwent deceased donor transplantation; 12 (86%) received a whole liver graft. Postoperative survival was 100%. At a mean follow-up of 3.25 ± 4.2 years, patient survival was 100%, liver allograft survival 93%, and kidney allograft survival 100%. One patient underwent liver re-transplantation because of hepatic artery thrombosis. After transplantation, there were no episodes of hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the time of transplantation was 1648 ± 1492 μmol/L (normal <0.3, range 99-4420). By 3 days, post-transplantation levels fell on average by 87% (mean 210 ± 154 μmol/L), and at 4 months, they were 83% below pre-transplantation levels (mean 305 ± 108 μmol/L). Developmental delay was present in 12 patients (86%) before transplantation. All patients maintained neurodevelopmental abilities or exhibited improvements in motor skills, learning abilities, and social functioning.LT or LKT for MMA eradicates episodes of hyperammonemia, results in excellent long-term survival, and suggests stabilization of neurocognitive development. Long-term follow-up is underway to evaluate whether patients who undergo early LT need kidney transplantation later in life.

  View details for DOI 10.1016/j.jpeds.2015.01.051

  View details for Web of Science ID 000355018200025

  View details for PubMedID 25771389

• Liver transplantation for urea cycle disorders in pediatric patients: A single-center experience PEDIATRIC TRANSPLANTATION Kim, I. K., Niemi, A., Krueger, C., Bonham, C. A., Concepcion, W., Cowan, T. M., Enns, G. M., Esquivel, C. O. 2013; 17 (2): 158-167

  Abstract

  LT has emerged as a surgical treatment for UCDs. We hypothesize that LT can be safely and broadly utilized in the pediatric population to effectively prevent hyperammonemic crises and potentially improve neurocognitive outcomes. To determine the long-term outcomes of LT for UCDs, charts of children with UCD who underwent LT were retrospectively reviewed at an academic institution between July 2001 and May 2012. A total of 23 patients with UCD underwent LT at a mean age of 3.4 yr. Fifteen (65%) patients received a whole-liver graft, seven patients (30%) received a reduced-size graft, and one patient received a living donor graft. Mean five-yr patient survival was 100%, and allograft survival was 96%. Mean peak blood ammonia (NH(3) ) at presentation was 772 μmol/L (median 500, range 178-2969, normal <30-50). After transplantation, there were no episodes of hyperammonemia. Eleven patients were diagnosed with some degree of developmental delay before transplantation, which remained stable or improved after transplantation. Patients without developmental delay before transplantation maintained their cognitive abilities at long-term follow-up. LT was associated with the eradication of hyperammonemia, removal of dietary restrictions, and potentially improved neurocognitive development. Long-term follow-up is underway to evaluate whether LT at an early age (<1 yr) will attain improved neurodevelopmental outcomes.

  View details for DOI 10.1111/petr.12041

  View details for PubMedID 23347504

• Relationships between maternal emotion regulation, parenting, and children's executive functioning in families exposed to intimate partner violence. Journal of interpersonal violence Samuelson, K. W., Krueger, C. E., Wilson, C. 2012; 27 (17): 3532-50

  Abstract

  Recently researchers have begun to explore the extent to which children's cognitive development is influenced by experiences in the family environment. Assessing mother-child dyads exposed to intimate partner violence (IPV), a population at risk for emotional and neurocognitive problems, we examined relationships between maternal emotional regulation, parenting, and children's executive functioning (including working memory, inhibitory control, cognitve flexibility and set shifting, and planning). Positive parenting practices, as reported by the children, were correlated with children's planning and problem solving performance. Controlling for children's own emotion regulation and gender, mothers' self-reported emotion regulation abilities predicted children's performance on a task of cognitive flexibility. Girls exhibited superior emotion regulation and executive functioning performance compared to boys, and mothers of girls reported better emotion regulation abilities compared to mothers of boys. These findings add to a nascent literature suggesting that parenting and parental emotional functioning may play important roles in children's neurocognitive functioning. In addition, they help to explain the mechanisms by which children exposed to IPV experience executive functioning deficits.

  View details for DOI 10.1177/0886260512445385

  View details for PubMedID 22610834

• Know Thyself: Real-World Behavioral Correlates of Self-Appraisal Accuracy CLINICAL NEUROPSYCHOLOGIST Krueger, C. E., Rosen, H. J., Taylor, H., Espy, K. A., Schatz, J., Rey-Casserly, C., Kramer, J. H. 2011; 25 (5): 741–56

  Abstract

  Accurate appraisal of one's own abilities is one metacognitive skill considered to be an important factor affecting learning and behavior in childhood. The present study measured self-appraisal accuracy in children using tasks of executive function, and investigated relations between self-appraisal and informant ratings of real-world behaviors measured by the BRIEF. We examined self-appraisal accuracy on fluency tasks in 91 children ages 10-17. More accurate self-appraisal was correlated with fewer informant ratings of real-world behavior problems in inhibition and shifting, independent of actual performance. Findings suggest that self-appraisal represents cognitive processes that are at least partially independent of other functions putatively dependent on the frontal lobes, and these self-appraisal-specific processes have unique implications for optimal daily function.

  View details for DOI 10.1080/13854046.2011.569759

  View details for Web of Science ID 000299559000004

  View details for PubMedID 21547852

  View details for PubMedCentralID PMC3586194

• Neuropsychological functioning in children with posttraumatic stress disorder. Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence Samuelson, K. W., Krueger, C. E., Burnett, C., Wilson, C. K. 2010; 16 (2): 119-33

  Abstract

  Posttraumatic stress disorder (PTSD) has been associated with deficits in the areas of verbal memory and learning, executive functioning, working memory, and attention in adults. Findings have been less consistent in the few studies examining neuropsychological functioning in childhood PTSD, which are often limited by comparing children with PTSD to children without trauma histories, making it unclear whether observed neuropsychological deficits are related to trauma exposure or to PTSD symptomatology. In an ethnically diverse sample of 62 children who witnessed intimate partner violence (n = 27 PTSD+ and 35 PTSD-), children with PTSD exhibited slower and less effective learning, heightened sensitivity to interference, and impaired effect of rehearsal on memory acquisition on the California Verbal Learning Test - Children's Version, a word list learning task. Both groups performed in the below average range on measures of executive functioning, attention, and intellectual ability.

  View details for DOI 10.1080/09297040903190782

  View details for PubMedID 19787496

• Longitudinal Rates of Lobar Atrophy in Frontotemporal Dementia, Semantic Dementia, and Alzheimer's Disease ALZHEIMER DISEASE & ASSOCIATED DISORDERS Krueger, C. E., Dean, D. L., Rosen, H. J., Halabi, C., Weiner, M., Miller, B. L., Kramer, J. H. 2010; 24 (1): 43–48

  Abstract

  This study compared rates of regional atrophy in Alzheimer disease (AD), frontotemporal dementia (FTD), and semantic dementia (SD). Cross-sectional studies have shown that different dementia syndromes are associated with different patterns of regional brain tissue loss. Rates of atrophy over time may be useful for differential diagnosis, and could be used to monitor disease progression, serving as an outcome measure for clinical trials. We studied patients with AD (n=12), FTD (n=13), SD (n=20), and normal controls (n=23) longitudinally with structural magnetic resonance imaging, using BRAINS2 software to measure frontal, temporal, and parietal lobe volumes. In FTD the rate of frontal lobe atrophy over 1 year was greater than in any other group, whereas SD showed the highest rate in the temporal lobes. Atrophy in these regions progressed twice as quickly in FTD and SD compared with AD. Atrophy was not significantly faster for AD in any brain region compared with the other groups. Regional atrophy over time was significantly faster in FTD and SD compared with AD, and the regions of greatest atrophy were specific for each syndrome. Measuring specific regions of cerebral volume changes by serial neuroimaging may serve as a useful biomarker outcome measure for clinical trials in neurodegenerative diseases.

  View details for DOI 10.1097/WAD.0b013e3181a6f101

  View details for Web of Science ID 000275197700006

  View details for PubMedID 19571735

  View details for PubMedCentralID PMC2837112

• Conflict monitoring in early frontotemporal dementia NEUROLOGY Krueger, C. E., Bird, A. C., Growdon, M. E., Jang, J. Y., Miller, B. L., Kramer, J. H. 2009; 73 (5): 349–55

  Abstract

  Despite the extensive frontal atrophy and behavioral disinhibition that characterizes behavioral variant frontotemporal dementia (bvFTD), many studies of early bvFTD suggest normal executive functioning (EF). The current study examined cognitive control in patients with bvFTD who otherwise seemed cognitively normal.Subjects included 7 patients with bvFTD with normal neuropsychological test scores, 7 patients with bvFTD matched for Mini-Mental State Examination score but with impaired neuropsychological test scores, and 14 normal controls. A flanker paradigm and other measures of EF were administered to participants. A semiautomated parcellation program was used to analyze structural MRI scans.On the flanker task, multivariate analysis of variance revealed a significant condition X diagnosis interaction. Both bvFTD groups showed a larger congruency effect than normal controls, i.e., they displayed disproportionately reduced speed and accuracy on incongruent trials relative to congruent trials. Imaging data illustrated significant orbitofrontal atrophy in patients with early bvFTD as compared with controls.Patients with behavioral variant frontotemporal dementia (bvFTD) who performed within normal limits on clinical tests of executive functioning demonstrated a select impairment on an experimental test of cognitive control, suggesting a subtle impairment in inhibiting attention or response to the irrelevant stimuli. Measures of neuropsychological functioning sensitive to the ventromedial prefrontal cortex may be useful in early diagnosis of patients with bvFTD. Our understanding of this syndrome may be increased by considering the efficiency of selective inhibition, a fundamental component of executive cognitive control.

  View details for DOI 10.1212/WNL.0b013e3181b04b24

  View details for Web of Science ID 000268640300004

  View details for PubMedID 19652138

  View details for PubMedCentralID PMC2725928