Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Feb 18:14:50.
doi: 10.1186/1471-2431-14-50.

Febrile illness and pro-inflammatory cytokines are associated with lower neurodevelopmental scores in Bangladeshi infants living in poverty

Nona M Jiang, Fahmida Tofail, Shannon N Moonah, Rebecca J Scharf, Mami Taniuchi, Jennie Z Ma, Jena D Hamadani, Emily S Gurley, Eric R Houpt, Eduardo Azziz-Baumgartner, Rashidul Haque, William A Petri Jr  1
Affiliations

Febrile illness and pro-inflammatory cytokines are associated with lower neurodevelopmental scores in Bangladeshi infants living in poverty

Nona M Jiang et al. BMC Pediatr. .

Abstract

Background: An estimated one-third of children younger than 5 years in low- and middle-income countries fail to meet their full developmental potential. The first year of life is a period of critical brain development and is also when most of the morbidity from infection is suffered. We aimed to determine if clinical and biological markers of inflammation in the first year of life predict cognitive, language, and motor outcomes in children living in an urban slum in Bangladesh.

Methods: Children living in Dhaka, Bangladesh were observed from birth until 24 months of age. Febrile illness was used as a clinical marker of inflammation and elevated concentrations of inflammation-related cytokines (IL-1β, IL-6, TNF-α, IL-4, IL-10) in sera collected from a subset of the cohort (N = 127) at 6 months of age were used as biomarkers of inflammation. Psychologists assessed cognitive, language, and motor development using a culturally adapted version of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 12 (N = 398) and 24 months of age (N = 210). We tested for the ability of febrile illness and elevated cytokine levels to predict developmental outcomes, independent of known predictors of stunting, family income, and maternal education.

Results: Every additional 10 days of fever was associated with a 1.9 decrease in language composite score and a 2.1 decrease in motor composite score (p = 0.005 and 0.0002, respectively). Elevated levels of the pro-inflammatory cytokines IL-1β (> 7.06 pg/mL) and IL-6 (> 10.52 pg/mL) were significantly associated with a 4.9 and 4.3 decrease in motor score, respectively. Conversely, an elevated level of the Th-2 cytokine IL-4 (> 0.70 pg/mL) was associated with a 3.6 increase in cognitive score (all p < 0.05).

Conclusions: Clinical and biological markers of inflammation in the first year of life were significantly associated with poor neurodevelopmental outcomes. Conversely, a Th2-like response was associated with a better outcome. These findings suggest that markers of inflammation could serve as prognostic indicators and potentially lead to immune-based therapies to prevent developmental delays in at-risk children.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Duration of febrile illness is associated with decreased motor development scores at 12 months.
Figure 2
Figure 2
Cytokine levels in 6-month sera are associated with developmental outcomes at 12 months.
See this image and copyright information in PMC

References

    1. Grantham-McGregor S, Cheung YB, Cueto S, Glewwe P, Richter L, Strupp B. Developmental potential in the first 5 years for children in developing countries. Lancet. 2007;369(9555):60–70. doi: 10.1016/S0140-6736(07)60032-4. - DOI - PMC - PubMed
    1. Walker SP, Wachs TD, Gardner JM, Lozoff B, Wasserman GA, Pollitt E, Carter JA. Child development: risk factors for adverse outcomes in developing countries. Lancet. 2007;369(9556):145–157. doi: 10.1016/S0140-6736(07)60076-2. - DOI - PubMed
    1. Mondal D, Minak J, Alam M, Liu Y, Dai J, Korpe P, Liu L, Haque R, Petri WA Jr. Contribution of enteric infection, altered intestinal barrier function, and maternal malnutrition to infant malnutrition in Bangladesh. Clin Infect Dis. 2012;54(2):185–192. doi: 10.1093/cid/cir807. - DOI - PMC - PubMed
    1. Bartelt LA, Lima AA, Kosek M, Penataro Yori P, Lee G, Guerrant RL. “Barriers” to child development and human potential: the case for including the “neglected enteric protozoa” (NEP) and other enteropathy-associated pathogens in the NTDs. PLoS Negl Trop Dis. 2013;7(4):e2125. doi: 10.1371/journal.pntd.0002125. - DOI - PMC - PubMed
    1. Guerrant DI, Moore SR, Lima AA, Patrick PD, Schorling JB, Guerrant RL. Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil. Am J Trop Med Hyg. 1999;61(5):707–713. - PubMed

Publication types