Skip to main content
Top
Published in: BMC Medicine 1/2019

Open Access 01-12-2019 | Malnutrition | Research article

Growth faltering is associated with altered brain functional connectivity and cognitive outcomes in urban Bangladeshi children exposed to early adversity

Authors: Wanze Xie, Sarah K. G. Jensen, Mark Wade, Swapna Kumar, Alissa Westerlund, Shahria H. Kakon, Rashidul Haque, William A. Petri, Charles A. Nelson

Published in: BMC Medicine | Issue 1/2019

Login to get access

Abstract

Background

Stunting affects more than 161 million children worldwide and can compromise cognitive development beginning early in childhood. There is a paucity of research using neuroimaging tools in conjunction with sensitive behavioral assays in low-income settings, which has hindered researchers’ ability to explain how stunting impacts brain and behavioral development. We employed high-density EEG to examine associations among children’s physical growth, brain functional connectivity (FC), and cognitive development.

Methods

We recruited participants from an urban impoverished neighborhood in Dhaka, Bangladesh. One infant cohort consisted of 92 infants whose height (length) was measured at 3, 4.5, and 6 months; EEG data were collected at 6 months; and cognitive outcomes were assessed using the Mullen Scales of Early Learning at 27 months. A second, older cohort consisted of 118 children whose height was measured at 24, 30, and 36 months; EEG data were collected at 36 months; and Intelligence Quotient (IQ) scores were assessed at 48 months. Height-for-age (HAZ) z-scores were calculated based on the World Health Organization standard. EEG FC in different frequency bands was calculated in the cortical source space. Linear regression and longitudinal path analysis were conducted to test the associations between variables, as well as the indirect effect of child growth on cognitive outcomes via brain FC.

Results

In the older cohort, we found that HAZ was negatively related to brain FC in the theta and beta frequency bands, which in turn was negatively related to children’s IQ score at 48 months. Longitudinal path analysis showed an indirect effect of HAZ on children’s IQ via brain FC in both the theta and beta bands. There were no associations between HAZ and brain FC or cognitive outcomes in the infant cohort.

Conclusions

The association observed between child growth and brain FC may reflect a broad deleterious effect of malnutrition on children’s brain development. The mediation effect of FC on the relation between child growth and later IQ provides the first evidence suggesting that brain FC may serve as a neural pathway by which biological adversity impacts cognitive development.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Briend A, Khara T, Dolan C. Wasting and stunting--similarities and differences: policy and programmatic implications. Food Nutr Bull. 2015;36(1 Suppl):S15–23.PubMedCrossRef Briend A, Khara T, Dolan C. Wasting and stunting--similarities and differences: policy and programmatic implications. Food Nutr Bull. 2015;36(1 Suppl):S15–23.PubMedCrossRef
3.
go back to reference Fink G, et al. Schooling and wage income losses due to early-childhood growth faltering in developing countries: national, regional, and global estimates. Am J Clin Nutr. 2016;104(1):104–12.PubMedCrossRef Fink G, et al. Schooling and wage income losses due to early-childhood growth faltering in developing countries: national, regional, and global estimates. Am J Clin Nutr. 2016;104(1):104–12.PubMedCrossRef
4.
go back to reference Monk C, Georgieff MK, Osterholm EA. Research review: maternal prenatal distress and poor nutrition - mutually influencing risk factors affecting infant neurocognitive development. J Child Psychol Psychiatry. 2013;54(2):115–30.PubMedCrossRef Monk C, Georgieff MK, Osterholm EA. Research review: maternal prenatal distress and poor nutrition - mutually influencing risk factors affecting infant neurocognitive development. J Child Psychol Psychiatry. 2013;54(2):115–30.PubMedCrossRef
5.
go back to reference Boersma M, et al. Network analysis of resting state EEG in the developing young brain: structure comes with maturation. Hum Brain Mapp. 2011;32(3):413–25.PubMedCrossRef Boersma M, et al. Network analysis of resting state EEG in the developing young brain: structure comes with maturation. Hum Brain Mapp. 2011;32(3):413–25.PubMedCrossRef
6.
go back to reference Bathelt J, et al. Functional brain network organisation of children between 2 and 5 years derived from reconstructed activity of cortical sources of high-density EEG recordings. Neuroimage. 2013;82:595–604.PubMedCrossRef Bathelt J, et al. Functional brain network organisation of children between 2 and 5 years derived from reconstructed activity of cortical sources of high-density EEG recordings. Neuroimage. 2013;82:595–604.PubMedCrossRef
7.
go back to reference Debnath R, et al. Mu rhythm desynchronization is specific to action execution and observation: evidence from time-frequency and connectivity analysis. Neuroimage. 2019;184:496–507.PubMedCrossRef Debnath R, et al. Mu rhythm desynchronization is specific to action execution and observation: evidence from time-frequency and connectivity analysis. Neuroimage. 2019;184:496–507.PubMedCrossRef
8.
go back to reference Haartsen R, et al. Functional EEG connectivity in infants associates with later restricted and repetitive behaviours in autism; a replication study. Transl Psychiatry. 2019;9(1):66.PubMedPubMedCentralCrossRef Haartsen R, et al. Functional EEG connectivity in infants associates with later restricted and repetitive behaviours in autism; a replication study. Transl Psychiatry. 2019;9(1):66.PubMedPubMedCentralCrossRef
9.
go back to reference Shephard E, et al. Oscillatory neural networks underlying resting-state, attentional control and social cognition task conditions in children with ASD, ADHD and ASD+ADHD. Cortex. 2019;117:96–110.PubMedCrossRef Shephard E, et al. Oscillatory neural networks underlying resting-state, attentional control and social cognition task conditions in children with ASD, ADHD and ASD+ADHD. Cortex. 2019;117:96–110.PubMedCrossRef
10.
go back to reference Rudolph MD, et al. Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and predicts future working memory in offspring. Nat Neurosci. 2018;21(5):765–72.PubMedPubMedCentralCrossRef Rudolph MD, et al. Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and predicts future working memory in offspring. Nat Neurosci. 2018;21(5):765–72.PubMedPubMedCentralCrossRef
12.
go back to reference Cordero ME, et al. Dendritic development in neocortex of infants with early postnatal life undernutrition. Pediatr Neurol. 1993;9(6):457–64.PubMedCrossRef Cordero ME, et al. Dendritic development in neocortex of infants with early postnatal life undernutrition. Pediatr Neurol. 1993;9(6):457–64.PubMedCrossRef
13.
go back to reference Hulshoff Pol HE, et al. Prenatal exposure to famine and brain morphology in schizophrenia. Am J Psychiatry. 2000;157(7):1170–2.PubMedCrossRef Hulshoff Pol HE, et al. Prenatal exposure to famine and brain morphology in schizophrenia. Am J Psychiatry. 2000;157(7):1170–2.PubMedCrossRef
14.
go back to reference Coti Bertrand P, O'Kusky JR, Innis SM. Maternal dietary (n-3) fatty acid deficiency alters neurogenesis in the embryonic rat brain. J Nutr. 2006;136(6):1570–5.PubMedCrossRef Coti Bertrand P, O'Kusky JR, Innis SM. Maternal dietary (n-3) fatty acid deficiency alters neurogenesis in the embryonic rat brain. J Nutr. 2006;136(6):1570–5.PubMedCrossRef
15.
go back to reference Morgane PJ, et al. Prenatal malnutrition and development of the brain. Neurosci Biobehav Rev. 1993;17(1):91–128.PubMedCrossRef Morgane PJ, et al. Prenatal malnutrition and development of the brain. Neurosci Biobehav Rev. 1993;17(1):91–128.PubMedCrossRef
16.
go back to reference Soto-Moyano R, et al. Prenatal malnutrition-induced functional alterations in callosal connections and in interhemispheric asymmetry in rats are prevented by reduction of noradrenaline synthesis during gestation. J Nutr. 1998;128(7):1224–31.PubMedCrossRef Soto-Moyano R, et al. Prenatal malnutrition-induced functional alterations in callosal connections and in interhemispheric asymmetry in rats are prevented by reduction of noradrenaline synthesis during gestation. J Nutr. 1998;128(7):1224–31.PubMedCrossRef
19.
go back to reference Victora CG, et al. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics. 2010;125(3):e473–80.PubMedCrossRef Victora CG, et al. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics. 2010;125(3):e473–80.PubMedCrossRef
20.
go back to reference Richards JE, Xie W. Brains for all the ages: structural neurodevelopment in infants and children from a life-span perspective. In: Benson J, editor. Advances in Child Development and Behavior. Philadephia: Elsevier; 2015. p. 1–52. Richards JE, Xie W. Brains for all the ages: structural neurodevelopment in infants and children from a life-span perspective. In: Benson J, editor. Advances in Child Development and Behavior. Philadephia: Elsevier; 2015. p. 1–52.
21.
go back to reference Nelson CA 3rd, et al. Cognitive recovery in socially deprived young children: the Bucharest Early Intervention Project. Science. 2007;318(5858):1937–40.PubMedCrossRef Nelson CA 3rd, et al. Cognitive recovery in socially deprived young children: the Bucharest Early Intervention Project. Science. 2007;318(5858):1937–40.PubMedCrossRef
25.
go back to reference Benasich AA, et al. Early cognitive and language skills are linked to resting frontal gamma power across the first 3 years. Behav Brain Res. 2008;195(2):215–22.PubMedPubMedCentralCrossRef Benasich AA, et al. Early cognitive and language skills are linked to resting frontal gamma power across the first 3 years. Behav Brain Res. 2008;195(2):215–22.PubMedPubMedCentralCrossRef
26.
go back to reference Pierce LJ, Thompson BL, Gharib A, Schlueter L, Reilly E, Valdes V, Nelson CA. Association of Perceived Maternal Stress During the Perinatal Period With Electroencephalography Patterns in 2-Month-Old Infants. JAMA Pediatr. 2019;173(6):561–70.PubMedCrossRefPubMedCentral Pierce LJ, Thompson BL, Gharib A, Schlueter L, Reilly E, Valdes V, Nelson CA. Association of Perceived Maternal Stress During the Perinatal Period With Electroencephalography Patterns in 2-Month-Old Infants. JAMA Pediatr. 2019;173(6):561–70.PubMedCrossRefPubMedCentral
27.
go back to reference Jensen SKG, Berens AE, Nelson CA. Effects of poverty on interacting biological systems underlying child development. Lancet Child Adolesc Health. 2017;1(3):225–39.PubMedCrossRef Jensen SKG, Berens AE, Nelson CA. Effects of poverty on interacting biological systems underlying child development. Lancet Child Adolesc Health. 2017;1(3):225–39.PubMedCrossRef
29.
go back to reference Kirkpatrick BD, et al. 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. 2015;92(4):744–51.PubMedPubMedCentralCrossRef Kirkpatrick BD, et al. 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. 2015;92(4):744–51.PubMedPubMedCentralCrossRef
30.
go back to reference Jensen SKG, et al. Child development in the context of biological and psychosocial hazards among poor families in Bangladesh. PLoS One. 2019;14(5):e0215304.PubMedPubMedCentralCrossRef Jensen SKG, et al. Child development in the context of biological and psychosocial hazards among poor families in Bangladesh. PLoS One. 2019;14(5):e0215304.PubMedPubMedCentralCrossRef
31.
go back to reference Hamadani JD, et al. Critical windows of exposure for arsenic-associated impairment of cognitive function in pre-school girls and boys: a population-based cohort study. Int J Epidemiol. 2011;40(6):1593–604.PubMedCrossRef Hamadani JD, et al. Critical windows of exposure for arsenic-associated impairment of cognitive function in pre-school girls and boys: a population-based cohort study. Int J Epidemiol. 2011;40(6):1593–604.PubMedCrossRef
32.
go back to reference Kippler M, et al. Early-life cadmium exposure and child development in 5-year-old girls and boys: a cohort study in rural Bangladesh. Environ Health Perspect. 2012;120(10):1462–8.PubMedPubMedCentralCrossRef Kippler M, et al. Early-life cadmium exposure and child development in 5-year-old girls and boys: a cohort study in rural Bangladesh. Environ Health Perspect. 2012;120(10):1462–8.PubMedPubMedCentralCrossRef
34.
go back to reference Richards JE, et al. A database of age-appropriate average MRI templates. Neuroimage. 2016;124:1254–9.PubMedCrossRef Richards JE, et al. A database of age-appropriate average MRI templates. Neuroimage. 2016;124:1254–9.PubMedCrossRef
35.
go back to reference Shattuck DW, et al. Construction of a 3D probabilistic atlas of human cortical structures. Neuroimage. 2008;39(3):1064–80.PubMedCrossRef Shattuck DW, et al. Construction of a 3D probabilistic atlas of human cortical structures. Neuroimage. 2008;39(3):1064–80.PubMedCrossRef
36.
go back to reference Vinck M, et al. An improved index of phase-synchronization for electrophysiological data in the presence of volume-conduction, noise and sample-size bias. Neuroimage. 2011;55(4):1548–65.PubMedCrossRef Vinck M, et al. An improved index of phase-synchronization for electrophysiological data in the presence of volume-conduction, noise and sample-size bias. Neuroimage. 2011;55(4):1548–65.PubMedCrossRef
38.
go back to reference Thorpe SG, Cannon EN, Fox NA. Spectral and source structural development of mu and alpha rhythms from infancy through adulthood. Clin Neurophysiol. 2016;127(1):254–69.PubMedCrossRef Thorpe SG, Cannon EN, Fox NA. Spectral and source structural development of mu and alpha rhythms from infancy through adulthood. Clin Neurophysiol. 2016;127(1):254–69.PubMedCrossRef
39.
go back to reference Tokariev A, et al. Preterm birth changes networks of newborn cortical activity. Cereb Cortex. 2019;29(2):814–26.PubMedCrossRef Tokariev A, et al. Preterm birth changes networks of newborn cortical activity. Cereb Cortex. 2019;29(2):814–26.PubMedCrossRef
40.
go back to reference Hamadani JD, et al. Use of family care indicators and their relationship with child development in Bangladesh. J Health Popul Nutr. 2010;28(1):23–33.PubMedPubMedCentralCrossRef Hamadani JD, et al. Use of family care indicators and their relationship with child development in Bangladesh. J Health Popul Nutr. 2010;28(1):23–33.PubMedPubMedCentralCrossRef
41.
go back to reference Klimesch W. EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Res Brain Res Rev. 1999;29(2–3):169–95.PubMedCrossRef Klimesch W. EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Res Brain Res Rev. 1999;29(2–3):169–95.PubMedCrossRef
42.
go back to reference Kopell N, Whittington MA, Kramer MA. Neuronal assembly dynamics in the beta1 frequency range permits short-term memory. Proc Natl Acad Sci U S A. 2011;108(9):3779–84.PubMedPubMedCentralCrossRef Kopell N, Whittington MA, Kramer MA. Neuronal assembly dynamics in the beta1 frequency range permits short-term memory. Proc Natl Acad Sci U S A. 2011;108(9):3779–84.PubMedPubMedCentralCrossRef
43.
go back to reference Gola M, et al. EEG beta band activity is related to attention and attentional deficits in the visual performance of elderly subjects. Int J Psychophysiol. 2013;89(3):334–41.PubMedCrossRef Gola M, et al. EEG beta band activity is related to attention and attentional deficits in the visual performance of elderly subjects. Int J Psychophysiol. 2013;89(3):334–41.PubMedCrossRef
44.
go back to reference Zhan Y, et al. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci. 2014;17(3):400–6.PubMedCrossRef Zhan Y, et al. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci. 2014;17(3):400–6.PubMedCrossRef
45.
go back to reference Couperus JW, Nelson CA. Early brain development and plasticity. In: McCartney K, Phillips D, editors. The Blackwell handbook of early childhood development. Malden: Blackwell publishing; 2006. p. 85–105.CrossRef Couperus JW, Nelson CA. Early brain development and plasticity. In: McCartney K, Phillips D, editors. The Blackwell handbook of early childhood development. Malden: Blackwell publishing; 2006. p. 85–105.CrossRef
46.
go back to reference Spann MN, et al. Maternal immune activation during the third trimester is associated with neonatal functional connectivity of the salience network and fetal to toddler behavior. J Neurosci. 2018;38(11):2877–86.PubMedPubMedCentralCrossRef Spann MN, et al. Maternal immune activation during the third trimester is associated with neonatal functional connectivity of the salience network and fetal to toddler behavior. J Neurosci. 2018;38(11):2877–86.PubMedPubMedCentralCrossRef
48.
go back to reference Segalowitz SJ, Santesso DL, Jetha MK. Electrophysiological changes during adolescence: a review. Brain Cogn. 2010;72(1):86–100.PubMedCrossRef Segalowitz SJ, Santesso DL, Jetha MK. Electrophysiological changes during adolescence: a review. Brain Cogn. 2010;72(1):86–100.PubMedCrossRef
49.
go back to reference Marshall PJ, Bar-Haim Y, Fox NA. Development of the EEG from 5 months to 4 years of age. Clin Neurophysiol. 2002;113(8):1199–208.PubMedCrossRef Marshall PJ, Bar-Haim Y, Fox NA. Development of the EEG from 5 months to 4 years of age. Clin Neurophysiol. 2002;113(8):1199–208.PubMedCrossRef
50.
go back to reference Walker SP, et al. Inequality in early childhood: risk and protective factors for early child development. Lancet. 2011;378(9799):1325–38.PubMedCrossRef Walker SP, et al. Inequality in early childhood: risk and protective factors for early child development. Lancet. 2011;378(9799):1325–38.PubMedCrossRef
52.
go back to reference Nelson CA 3rd. Hazards to early development: the biological embedding of early life adversity. Neuron. 2017;96(2):262–6.PubMedCrossRef Nelson CA 3rd. Hazards to early development: the biological embedding of early life adversity. Neuron. 2017;96(2):262–6.PubMedCrossRef
53.
go back to reference Drakesmith M, et al. Overcoming the effects of false positives and threshold bias in graph theoretical analyses of neuroimaging data. Neuroimage. 2015;118:313–33.PubMedCrossRef Drakesmith M, et al. Overcoming the effects of false positives and threshold bias in graph theoretical analyses of neuroimaging data. Neuroimage. 2015;118:313–33.PubMedCrossRef
Metadata
Title
Growth faltering is associated with altered brain functional connectivity and cognitive outcomes in urban Bangladeshi children exposed to early adversity
Authors
Wanze Xie
Sarah K. G. Jensen
Mark Wade
Swapna Kumar
Alissa Westerlund
Shahria H. Kakon
Rashidul Haque
William A. Petri
Charles A. Nelson
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Malnutrition
Published in
BMC Medicine / Issue 1/2019
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-019-1431-5

Other articles of this Issue 1/2019

BMC Medicine 1/2019 Go to the issue