Cortical specialisation to social stimuli from the first days to the second year of life: A rural Gambian cohort.

Brain and nervous system development in human infants during the first 1000days (conception to two years of age) is critical, and compromised development during this time (such as from under nutrition or poverty) can have life-long effects on physical growth and cognitive function. Cortical mapping of cognitive function during infancy is poorly understood in resource-poor settings due to the lack of transportable and low-cost neuroimaging methods. Having established a signature cortical response to social versus non-social visual and auditory stimuli in infants from 4 to 6 months of age in the UK, here we apply this functional Near Infrared Spectroscopy (fNIRS) paradigm to investigate social responses in infants from the first postnatal days to the second year of life in two contrasting environments: rural Gambian and urban UK. Results reveal robust, localized, socially selective brain responses from 9 to 24 months of life to both the visual and auditory stimuli. In contrast at 0-2 months of age infants exhibit non-social auditory selectivity, an effect that persists until 4-8 months when we observe a transition to greater social stimulus selectivity. These findings reveal a robust developmental curve of cortical specialisation over the first two years of life.

Using fNIRS to Study Working Memory of Infants in Rural Africa.

A pilot study was conducted to assess the feasibility of using fNIRS as an alternative to behavioral assessments of cognitive development with infants in rural Africa. We report preliminary results of a study looking at working memory in 12-16-month-olds and discuss the benefits and shortcomings for the potential future use of fNIRS to investigate the effects of nutritional insults and interventions in global health studies.

The effects of maternal iron deficiency on infant fibroblast growth factor-23 and mineral metabolism.

Fibroblast growth factor-23 (FGF23), a phosphate(Phos)-regulating hormone, is abnormally elevated in hypophosphataemic syndromes and an elevated FGF23 is a predictor of mortality in kidney disease. Recent findings suggest iron deficiency as a potential mediator of FGF23 expression and murine studies have shown in utero effects of maternal iron deficiency on offspring FGF23 and phosphate metabolism. Our aim was to investigate the impact of maternal iron status on infant FGF23 and mineral metabolites over the first 2years of life. Infants born to mothers with normal (NIn=25,) and low (LIn=25) iron status during pregnancy, from a mother-infant trial (ISRCTN49285450) in rural Gambia, West Africa, had blood and plasma samples analysed at 12, 24, 52, 78 and 104weeks (wk) of age. Circulating intact-FGF23 (I-FGF23), Phos, total alkaline phosphatase (TALP) and haemoglobin (Hb) decreased and estimated glomerular filtration rate increased over time [all P≤0.0001)]. C-terminal-FGF23 (C-FGF23) and TALP were significantly higher in LI compared with NI, from 52wk for C-FGF23 [Beta coefficient (SE) 18.1 (0.04) %, P=0.04] and from 24wk for TALP [44.7 (29.6) U/L, P=0.04]. Infant Hb was the strongest negative predictor of C-FGF23 concentration [-21% (4%) RU/mL, P≤0.0001], Phos was the strongest positive predictor of I-FGF23 [32.0(3.9) pg/mL, P≤0.0001] and I-FGF23 did not predict C-FGF23 over time [-0.5% (0.5%), P=0.3]. In conclusion, this study suggests that poor maternal iron status is associated with a higher infant C-FGF23 and TALP but similar I-FGF23 concentrations in infants and young children. These findings further highlight the likely public health importance of preventing iron deficiency during pregnancy. Whether or not children who are born to iron deficient mothers have persistently high concentrations of these metabolites and are more likely to be at risk of impaired bone development and pre-disposed to rickets requires further research.

Functional near infrared spectroscopy (fNIRS) to assess cognitive function in infants in rural Africa.

Cortical mapping of cognitive function during infancy is poorly understood in low-income countries due to the lack of transportable neuroimaging methods. We have successfully piloted functional near infrared spectroscopy (fNIRS) as a neuroimaging tool in rural Gambia. Four-to-eight month old infants watched videos of Gambian adults perform social movements, while haemodynamic responses were recorded using fNIRS. We found distinct regions of the posterior superior temporal and inferior frontal cortex that evidenced either visual-social activation or vocally selective activation (vocal > non-vocal). The patterns of selective cortical activation in Gambian infants replicated those observed within similar aged infants in the UK. These are the first reported data on the measurement of localized functional brain activity in young infants in Africa and demonstrate the potential that fNIRS offers for field-based neuroimaging research of cognitive function in resource-poor rural communities.

Optical imaging of brain activation in Gambian infants.

We used optical topography (OT) to investigate cognitive function in infants in rural Gambia. Images of changes in oxyhaemoglobin and deoxyhaemoglobin concentrations were reconstructed using a multispectral algorithm which uses the finite element method (FEM) to model the propagation of light through scattering tissue using the diffusion equation. High quality OT data enabled us to reconstruct images with robust representation of haemodynamic changes. OT is a feasible neuroimage technology for this resource-poor setting.

Helicobacter pylori infection, gastric acid secretion, and infant growth.

BACKGROUND: Helicobacter pylori infection is very common in Gambian infants and children, who are also at risk of chronic diarrhoea and undernutrition. Acute H. pylori infection is associated with depressed gastric acid secretion, and loss of the gastric acid barrier may predispose to enteric infections. METHODS: In a prospective study a noninvasive test of gastric acid output (measurement of change in urine acid output before and after a feed) was performed on a population of Gambian infants at high risk of H. pylori infection. The 13C urea breath tests was used to measure the prevalence of H. pylori infection and growth was measured by serial anthropometry. RESULTS: In 101 infants aged 3 to 12 months, there was a significant relation between H. pylori infection and depressed urine acid output in those aged 6 months, during weaning when growth failure and malnutrition begin. Those infants with sustained H. pylori infection grew less well than those without. CONCLUSIONS: We speculate that H. pylori, acquired in infancy, could be a "key that opens the door" to enteric infection in childhood, leading to recurrent diarrhoea, malnutrition, and growth failure.

Isolation of Helicobacter pylori from human faeces.

Helicobacter pylori is arguably the commonest chronic infection in man. However, its route of transmission is unknown. We have isolated viable H pylori from the faeces of an infected individual from The Gambia. The organism was cultured on selective media after concentration of faecal bacteria by centrifugation in a buffer equilibrated with a microaerophilic gas mixture. Growth characteristics, microscopic appearances, and enzyme activities were the same as those of a typical gastric isolate of H pylori. Protein preparations derived from the new isolate and the typical strain were antigenically similar, and had very similar electrophoretic profiles (including two major protein bands of 62 and 26 kDa, corresponding to the urease enzyme subunits). With the same technique, organisms with the colony morphology, growth requirements, enzyme activities, and microscopic appearances of H pylori were isolated from the faeces of 9 of 23 randomly selected children aged 3-27 months from a Gambian village with a high prevalence of H pylori infection in early life. Faecal-oral transmission is probably important in the spread of infection in such communities.