Trial of Thiamine Supplementation in Cambodia

To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases human milk total thiamine concentration at 24 weeks postpartum.

To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases infant thiamine diphosphate concentrations (ThDP) 24 weeks postnatally, and assess whether this depends on the presence/absence of a genetic hemoglobin disorder.

To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases human milk total thiamine concentration at 4 and 12 weeks postpartum.

To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases infant transketolase activity at 24 weeks postnatally, and assess whether this depends on the presence/absence of a genetic hemoglobin disorder.

To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases maternal ThDP at 24 weeks postpartum, and assess whether this depends on the presence/absence of a genetic hemoglobin disorder.

To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases maternal ETKac at 24 weeks postpartum, and assess whether this depends on the presence/absence of a genetic hemoglobin disorder.

To test for differences between the 4 randomized groups on human milk total thiamine at 4, 12, and 24 weeks postpartum.

To test for differences between the 4 randomized groups on maternal ThDP at 24 weeks postpartum, and assess whether this depends on the presence/absence of genetic hemoglobin disorder.

To test for differences between the 4 randomized groups on maternal ETKac at 24 weeks postpartum and assess whether this depends on the presence/absence of a genetic hemoglobin disorder.

To estimate usual household salt intake from mean fortnightly salt disappearance (weight lost, in g).

To estimate salt intake among a subset of 100 lactating women, their male partners (if applicable), and their children 24-59 months (if applicable) using observed weighed salt intake records.

To estimate sodium intake using 24 hr urinary sodium concentrations among a subset of 100 lactating women.

To test for differences between the 0 & 10 mg randomized groups on Composite Mullen and the 5 subscales of the Mullen at 24 and 52 weeks postnatally.

Score notes for Mullen Scales of Early Learning

Gross Motor Scale: Raw score range: 0-36 (higher scores reflect better performance) Visual Reception Scale: Raw score range: 0-50 (higher scores reflect better performance) Fine Motor Scale: Raw score range: 0-49 (higher scores reflect better performance) Receptive Language Scale: Raw score range: 0-48 (higher scores reflect better performance) Expressive Language Scale: Raw score range: 0-50 (higher scores reflect better performance)

All raw scores are converted to age-adjusted T-scores (provided by manual).

An optional Early Learning Composite Score can be calculated by summing the T-scores of all but the Gross Motor Scale.

To test for differences between the 0 & 10 mg randomized groups on Visual Paired Comparison Novelty Score and the attention and processing speed subscales at 24 and 52 weeks postnatally.

Score notes for Visual Paired Comparison task

Scale ranges: An overall novelty score is calculated that averages across all face and pattern trials, and is a percentage reflecting the percent of time infants' looked at the novel item during the test phase, calculated as the duration looking to the novel item divided by the sum of the duration of looking to the novel item plus the duration looking to the familiar item.

Sub-scales: Two sub-scales are calculated: the novelty score averaged across face trials, and the novelty score averaged across pattern trials. The total scale composite averages the novelty score across the two sub-scales.

For all scales, he range is 0-100%, and higher novelty scores indicate better outcomes.

To test for differences between the 0 & 10 mg randomized groups on the Language Preference Task Score at 24 weeks postnatally.

To test for differences between 0 & 10 mg randomized groups on oculomotor scores at 24 weeks postnatally.

Score notes for the Oculomotor Test:

The proposed oculomotor test is not a single, published instrument, but instead, combines several standard screening items.

Strabismus: absent or present; score: 0-1 Nystagmus: absent or present; score: 0-1 Amblyopia: absent or present; score 0-1

Saccade:

• guided saccade: absent or present; score 0-1
• scanning: absent or present; score 0-1
• predicted saccade: absent or present; score 0-1

Smooth pursuit:

• overall pursuit: absent or present; score 0-1
• horizontal pursuit: score 0-1
• vertical pursuit: score 0-1

Total oculomotor score (optional): sum of all scored exam items: range 0-9

To determine the effect of inflammation, as measured by C-reactive protein (CRP) and α-1-acid-glycoprotein (AGP) on maternal ThDP at 2 and 24 weeks postpartum, and infant ThDP at 24 weeks postnatal.