Offspring neurodevelopment after maternal preconception nutrition supplement: Evaluating a new tool
Nancy Krebs, MD, MS
Recent estimates indicate that 250 million children (43%) under age 5 years in low and middle income countries (LMIC) are at risk of not achieving their developmental potential. This represents an enormous loss of human potential. Among several risk factors for neurocognitive impairment (NCI), malnutrition is particularly important due to its high prevalence and its potential for modification. The critical window represented by the “1000 days” represents a period with both opportunity and vulnerability for neurodevelopment. Very few nutrition intervention trials in LMICs specifically address offspring neurodevelopment, in part, because of limitations of tests appropriate for low resource settings and the requirement for specially trained personnel. The recent availability of a new, holistic, population-based neurodevelopment assessment tool – the INTERGROWTH-21ST Neurodevelopment Assessment Package (INTER-NDA) offers great potential to assess neurodevelopment specifically in young children in LMIC. The opportunity to compare results of the INTER-NDA to a widely accepted assessment tool for neurodevelopment, the Bayley Scales of Infant Development-III (BID-III), provides an important “real world” test of the underlying premises of the INTER-NDA. The intervention implemented in the Preconception Maternal Nutrition (“Women First”) trial, conducted in 4 diverse LMIC offers a unique opportunity to compare the effects on early child neurodevelopment of improved maternal nutrition prior to conception and through pregnancy vs maternal nutrition intervention initiated in the 2nd trimester vs a non-intervention group.
BACKGROUND: The absence of a multi-dimensional neurodevelopmental assessment tool suitable for populations in low resource settings that is easy and rapid to administer in the field limits comparability among studies of nutrition and early child development. Also lacking are large cohorts in low resource settings for whom detailed information is available regarding potential risks and protective factors for early child development.
GAP: The gap in availability of a multi-dimensional assessment tool for early childhood development will be addressed by testing the “INTERGROWTH-21st Neurodevelopment Package” (INTER-NDA) in 2 year olds from 4 low-middle income countries (Democratic Republic of the Congo, Guatemala, India, Pakistan) whose mothers participated in the “Women First” (WF) trial, an RCT nutrition intervention initiated prior to conception and through pregnancy (Arm 1) vs the same intervention initiated in 2nd trimester (Arm 2) vs a non-intervention control group (Arm 3).
• H-1: Scores on the cognition domain of the INTER-NDA for the offspring of women in Arm 1 (pre-conception + prenatal) will be significantly higher than those for offspring of women in Arm 2 (prenatal), or than the offspring of women in Arm 3 (control).
• H-2: Independent of group, length for age Z-score (LAZ) and change in LAZ between 6 and 24 months will be correlated with scores for cognition on INTER-NDA.
• H-3: Cognitive scores from INTER-NDA and the Bayley Scales of Infant Development (BSID-III) tests will exhibit similarly strong associations to LAZ and/or ΔLAZ, and the ratio of the slopes of these relationships will be similar to that of existing direct comparisons of INTER-NDA and BSID-III cognitive scores.
METHODS: This project provides a cross-sectional comparison of INTER-NDA results among three arms for the WF offspring. Testing will be conducted in a randomly selected subgroup at each of 4 sites, representing 1/3 of children/arm; BSID-III will be administered in 2/3 of children in each arm. Longitudinal growth and anthropometric measurements will be obtained in all subjects. In addition to primary outcome of cognitive domain for comparison to BSID-III, the INTER-NDA includes assessment of vision; auditory function; and language, behavior, motor skills and attention, all of which will be compared among arms.
Subjects are 24 month old offspring of mothers who completed the WF trial through the 6 mo post-partum) and whose growth was measured at 12, 18 and 24 months of age.
IMPACT: Demonstration of the feasibility and utility of a simple, less expensive tool to holistically assess neurodevelopment in young children in LMIC will fill an important gap in gauging the burden of impaired early childhood development and evaluating the impact of interventions.