1921
Volume 97, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Exposure to profound adversity can negatively affect the neurodevelopment of children, but biologic mechanisms that underlie this association remain unknown. We sought to determine whether elevated levels of the inflammatory markers C-reactive protein (CRP) and soluble CD14 (sCD14) are associated with neurodevelopmental outcomes in Bangladeshi children. A total of 422 infant–mother pairs from an urban slum in Dhaka, Bangladesh were enrolled at birth and followed prospectively. Inflammation was measured with sCD14, interleukin (IL)-1β, and IL-6 at 18 weeks, and CRP at 6, 18, 40, and 53 weeks. Psychologists assessed cognitive, language, motor, and social emotional development using the Bayley Scales of Infant and Toddler Development at 78 and 104 weeks of age. We tested for the association of inflammatory markers with developmental outcomes, independent of previously identified associations such as malnutrition, family income, and maternal education. Every 10 pg/mL increase in sCD14 was associated with a 1.1–2.0 decrement in cognitive and motor scores at 78 weeks and in all domains at 104 weeks. The cumulative number of CRP elevations that a child experienced in the first year of life, as well as IL-1β and IL-6 at 18 weeks of age, were also negatively associated with Bayley Scales results. CRP, sCD14, IL-1β, and IL-6 were associated with lower neurodevelopmental outcomes. Our findings implicate a role of inflammation in the neurodevelopment of children growing up in adversity.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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2017-09-22
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References

  1. Grantham-McGregor S, Cheung YB, Cueto S, Glewwe P, Richter L, Strupp B, ; International Child Development Steering Group, 2007. Developmental potential in the first 5 years for children in developing countries. Lancet 369: 6070.[Crossref]
  2. Walker SP, Wachs TD, Gardner JM, Lozoff B, Wasserman GA, Pollitt E, Carter JA, ; International Child Development Steering Group, 2007. Child development: risk factors for adverse outcomes in developing countries. Lancet 369: 145157.[Crossref]
  3. Walker SP, Wachs TD, Grantham-McGregor S, Black MM, Nelson CA, Huffman SL, Baker-Henningham H, Chang SM, Hamadani JD, Lozoff B, Gardner JM, Powell CA, Rahman A, Richter L, , 2011. Inequality in early childhood: risk and protective factors for early child development. Lancet 378: 13251338.[Crossref]
  4. Leviton A, Allred EN, Fichorova RN, Kuban KC, Michael O’Shea T, Dammann O, ; ELGAN study investigators, 2016. Systemic inflammation on postnatal days 21 and 28 and indicators of brain dysfunction 2 years later among children born before the 28th week of gestation. Early Hum Dev 93: 2532.[Crossref]
  5. O’Shea TM, Joseph RM, Kuban KC, Allred EN, Ware J, Coster T, Fichorova RN, Dammann O, Leviton A, ; ELGAN Study Investigators, 2014. Elevated blood levels of inflammation-related proteins are associated with an attention problem at age 24 mo in extremely preterm infants. Pediatr Res 75: 781787.[Crossref]
  6. Jiang NM, Tofail F, Moonah SN, Scharf RJ, Taniuchi M, Ma JZ, Hamadani JD, Houpt ER, Azziz-Baumgartner E, Haque R, Petri WA, Jr, 2014. Febrile illness and pro-inflammatory cytokines are associated with lower neurodevelopmental scores in Bangladeshi infants living in poverty. BMC Pediatr 14: 50.[Crossref]
  7. Carlo WA, McDonald SA, Tyson JE, Stoll BJ, Ehrenkranz RA, Shankaran S, Goldberg RN, Das A, Schendel D, Thorsen P, Skogstrand K, Hougaard DM, Oh W, Laptook AR, Duara S, Fanaroff AA, Donovan EF, Korones SB, Stevenson DK, Papile LA, Finer NN, O’Shea TM, Poindexter BB, Wright LL, Ambalavanan N, Higgins RD, ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, 2011. Cytokines and neurodevelopmental outcomes in extremely low birth weight infants. J Pediatr 159: 919925.e3.[Crossref]
  8. Dammann O, O’Shea TM, , 2008. Cytokines and perinatal brain damage. Clin Perinatol 35: 643.[Crossref]
  9. Hao LY, Hao XQ, Li SH, Li XH, , 2010. Prenatal exposure to lipopolysaccharide results in cognitive deficits in age-increasing offspring rats. Neuroscience 166: 763770.[Crossref]
  10. Mondal D, Minak J, Alam M, Liu Y, Dai J, Korpe P, Liu L, Haque R, Petri WA, Jr, 2012. Contribution of enteric infection, altered intestinal barrier function, and maternal malnutrition to infant malnutrition in Bangladesh. Clin Infect Dis 54: 185192.[Crossref]
  11. Taniuchi M, Platts-Mills JA, Begum S, Uddin MJ, Sobuz SU, Liu J, Colgate ER, Carmolli MP, Dickson DM, Nayak U, Kirkpatrick BD, Haque R, Petri WA, Jr Houpt ER, , 2016. Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants. Vaccine 34: 30683075.[Crossref]
  12. Korpe PS, Petri WA, Jr, 2012. Environmental enteropathy: critical implications of a poorly understood condition. Trends Mol Med 18: 328336.[Crossref]
  13. Naylor C, Lu M, Haque R, Mondal D, Buonomo E, Nayak U, Mychaleckyj JC, Kirkpatrick B, Colgate R, Carmolli M, Dickson D, van der Klis F, Weldon W, Steven Oberste M, ; PROVIDE study teams, Ma JZ, Petri WA Jr, 2015. Environmental enteropathy, oral vaccine failure and growth faltering in infants in Bangladesh. EBioMedicine 2: 17591766.[Crossref]
  14. Petri WA, Jr Naylor C, Haque R, , 2014. Environmental enteropathy and malnutrition: do we know enough to intervene? BMC Med 12: 187.[Crossref]
  15. Donowitz JR, Haque R, Kirkpatrick BD, Alam M, Lu M, Kabir M, Kakon SH, Islam BZ, Afreen S, Musa A, Khan SS, Colgate ER, Carmolli MP, Ma JZ, Petri WA, Jr, 2016. Small intestine bacterial overgrowth and environmental enteropathy in Bangladeshi children. MBio 7: e02102e02115.[Crossref]
  16. Dinh DM, Volpe GE, Duffalo C, Bhalchandra S, Tai AK, Kane AV, Wanke CA, Ward HD, , 2015. Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection. J Infect Dis 211: 1927.[Crossref]
  17. Severance EG, Gressitt KL, Stallings CR, Origoni AE, Khushalani S, Leweke FM, Dickerson FB, Yolken RH, , 2013. Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia. Schizophr Res 148: 130137.[Crossref]
  18. Levy O, , 2005. Innate immunity of the human newborn: distinct cytokine responses to LPS and other Toll-like receptor agonists. J Endotoxin Res 11: 113116.[Crossref]
  19. Martinez-Lopez DG, Funderburg NT, Cerissi A, Rifaie R, Aviles-Medina L, Llorens-Bonilla BJ, Sleasman J, Luciano AA, , 2014. Lipopolysaccharide and soluble CD14 in cord blood plasma are associated with prematurity and chorioamnionitis. Pediatr Res 75: 6774.[Crossref]
  20. Tapping RI, Tobias PS, , 2000. Soluble CD14-mediated cellular responses to lipopolysaccharide. Chem Immunol 74: 108121.[Crossref]
  21. Kirkpatrick BD, Colgate ER, Mychaleckyj JC, Haque R, Dickson DM, Carmolli MP, Nayak U, Taniuchi M, Naylor C, Qadri F, Ma JZ, Alam M, Walsh MC, Diehl SA, PROVIDE Study Teams, Petri WA Jr., 2015. The “Performance of Rotavirus and Oral Polio Vaccines in Developing Countries” (PROVIDE) study: description of methods of an interventional study designed to explore complex biologic problems. Am J Trop Med Hyg 92: 744–751.
  22. Murray L, Carothers AD, , 1990. The validation of the Edinburgh Post-natal Depression Scale on a community sample. Br J Psychiatry 157: 288290.[Crossref]
  23. Gausia K, , Hamadani JD, Islam MM, Ali M, Algin S, Yunus M, Fisher C, Oosthuizen J, 2007. Bangla translation, adaptation and piloting of Edinburgh Postnatal Depression Scale. Bangladesh Med Res Counc Bull 33: 8187.[Crossref]
  24. Cox JL, Holden JM, Sagovsky R, , 1987. Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry 150: 782786.[Crossref]
  25. Nelson CA, III, 2015. An international approach to research on brain development. Trends Cogn Sci 19: 424426.[Crossref]
  26. Krastinova E, Lecuroux C, Leroy C, Seng R, Cabie A, Rami A, Venet A, Meyer L, Goujard C, Cohort ANRSPRIMO, , 2015. High soluble CD14 levels at primary HIV-1 infection predict more rapid disease progression. J Infect Dis 212: 909913.[Crossref]
  27. Levy E, Xanthou G, Petrakou E, Zacharioudaki V, Tsatsanis C, Fotopoulos S, Xanthou M, , 2009. Distinct roles of TLR4 and CD14 in LPS-induced inflammatory responses of neonates. Pediatr Res 66: 179184.[Crossref]
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  • Received : 04 Feb 2017
  • Accepted : 28 Apr 2017

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