Infants scoring high for inflammation are more likely to display poor language development, even when fed thiamine-supplemented breastmilk, according to Dr Jeffrey Measelle, professor of psychology and global health at the University of Oregon.
Measelle, who is also co-director of the university’s Center for Global Health, told an audience at the Micronutrient Forum 6th Global Conference in The Hague last week: “A number of important maternal biological factors are dictating how much thiamine is available in her breastmilk for infants…
“What might be going on in infants that determines how much, or how well, they can take advantage of available milk thiamine?”
Thiamine: An essential neurodevelopmental micronutrient
Thiamine, more commonly known as vitamin B1, is an essential micronutrient that plays a key role in energy metabolism. Thiamine diphosphate, its metabolically active form, constitutes about 80% of total body thiamine.
It was long thought that the fatal disease beriberi was the biggest risk associated with thiamine deficiency among infants and young children – but more recent work has identified a link with delays in cognitive development, specifically in the language domains, Measelle said.
Both human and animal studies have shown thiamine to be important to neurodevelopment: it is critical for myelination in early brain development, hippocampal development and functioning, and neurotransmitter synthesis.
Thiamine supplementation in rice-based diets
In South-East Asia, where diets are high in polished white rice, lactating women are likely to be producing thiamine-poor milk, meaning that infants are at particular risk of cognitive impairment.
Measelle’s team conducted a randomised trial in Cambodia exploring the effect on infant cognition of maternal thiamine supplementation during the first six months of life, splitting subjects into four groups, assigned daily dosages of between zero and 10 mg.
They found that, to achieve 90% of the maximum milk thiamine level, “you needed a dosage level of 3.5 mg daily, which is almost twice what the [World Health Organization] WHO is recommending currently for lactating women”, he said.
Of particular note was the amount of variability found across each of the different groups.
This finding was replicated in a later trial led by Measelle, in which all groups supplemented with thiamine showed important developmental gains between two weeks and six months – but only the 10 mg/day group showed a significant difference.
What’s more, this was only realised in the language domain, not in motor development or visual perception – and of note again was the high rate of variability.
Thiamine uptake and the role of inflammation
These findings led his team to explore the extent to which chronic inflammation – which plays an important role in modulating brain development – was impacting infants’ ability to utilise milk thiamine.
Studies have shown the effects of nutritional supplementation on neurocognitive development to be dependent on a number of factors, including immune functioning as measured by chronic inflammation, Measelle said.
His team ran another study, this time looking “specifically at maternal milk thiamine, infant inflammation at 24 weeks and, importantly, the interaction between inflammation and maternal milk thiamine”.
To unpack the high variability seen in their previous research, they used a method called growth mixture modelling, a person-centred approach that “tries to capture the heterogeneity within the distribution of developmental trajectories and assign individuals to particular developmental groups or trajectory classes, and then use varying independent variables to predict group membership”, he explained.
This allowed them to detect differences in intervention effects for children belonging to different developmental trajectories, “moving away from just looking at our data in terms of the randomised groups and thinking about what might be going on at the level of individual infants”, he said.
Inflammation inhibits infants’ ability to benefit from milk thiamine
The researchers found that while higher milk levels of thiamine held significant benefits for infants’ language development, children measuring high for systemic inflammation were likely to show very little language growth, both in the receptive and expressive domains.
“We're seeing an interaction between maternal milk thiamine and circulating chronic inflammation … such that infants were showing higher levels of inflammation were not able to take advantage of available milk thiamine, and consequently were showing poor language development,” Measelle said.
“Higher maternal milk thiamine levels [are] associated with infants showing more rapid development, especially in the language domains, likely suggesting that language is prioritised or takes advantage of timing in particular,” he added. “However, the effects of systemic inflammation were clear.”
In addition, infants showed a significant drop in both language domains following trial completion, indicating that nutritional interventions beyond six months may be necessary.
Unpacking individual trajectories to inform future interventions
Measelle highlighted his group’s research methodology as being instrumental to their findings.
“I think this has important implications for how we design future intervention studies … in terms of thinking about not only what the placebo group comprises, but what are some of these starting points when we randomly assign individuals?” he said.
He added: “There are a number of critical factors that we need to begin to explore, and growth mixture modelling as a secondary person-centred approach allows you to decompose those trajectories … to be able to begin to understand what factors, both biological and environmental, from infant to parent – mother, in this instance – might be predicting different membership in these class trajectories.”
