Is There a Best Way to Grow?

7/30/2014 4:30:00 PM

The Nature vs Nurture debate investigates the joint roles of genes and environment in determining complex traits in humans. This discussion is an old one and has challenged fields as seemingly diverse as cancer, behavior and cognitive development. Often the evidence is inconclusive and has led us to choose the safe response, 'It is likely both'. This debate is particularly pertinent when it comes to physical growth of different populations. Why do South Asians seem shorter than Northern Europeans? A paper published on July 7th in The Lancet, Diabetes and Endocrinology, which is the first in what will be a series of papers reporting the results of the INTERGROWTH 21st study sheds some light on this question.

The work, led by Stephen Kennedy and Jose Villar at Oxford University measured how the fetus grows when the mother has optimal care and minimal pregnancy complications across eight different geographies (India, China, Thailand, Kenya, Oman, Italy, US, UK and Brazil). Serial ultrasound measurements were obtained from 4607 mothers at multiple time points in the pregnancy and at birth to generate length and head circumference measurements. The work was meticulous in ensuring that measures were done to gold standard and with equal rigor across all sites involved.

The results show remarkable similarities of growth across the geographies. It has often been thought that the difference in the levels of stunting across different countries (e.g. ~50% in India to ~2% in Denmark) can be attributed to inherent genetic properties of the population. However, data from this study shows that the variability attributed to between-site differences is much smaller than among individuals from the same site (2.6% vs 18.6%).

This is consistent with the previous data from the WHO Multicenter Growth Reference Study (MGRS) that examined growth from birth till 5 years of age in 6 countries. Similar growth patterns across these geographies led to pooling of the data to produce global postnatal growth standards that are now accepted worldwide. The INTERGROWTH 21st study complements this work by extending the growth standards into pregnancy and provides the opportunity to create, for the first time, global growth standards from post-conception until 5 years of age. Upcoming papers will also present, for the first time, new fetal growth curves that are specific to babies who are born preterm.

This data needs to be interpreted in the context of trans-generational factors. We need more research to understand the links between factors we know are highly heritable characters—adult height, body mass index (BMI), and other growth parameters—to delineate the effects of environment and environment-induced changes to genes through epigenetics. Thus the degree to which stunting might be reversed in a single generation is still unknown. However, the data from countries which have seen rapid reductions of stunting such as Brazil, or data from studies of immigrant children showing catch up with moving from resource poor settings to developed countries affords hope that some of these effects can be reduced in single generations. Continued work on finding the best packages and timing of interventions and the mechanisms underlying successful interventions can be pursued with renewed vigor after seeing this ground breaking work.

This high quality serial ultrasound data provides an opportunity to develop new tools that can enable assessments of intrauterine growth by even semi-skilled personnel in low and middle income countries.  In a sub-study called INTERBIO 21st there is a complementary effort to compare the trajectory of healthy fetal growth to those in pregnancies complicated by conditions that may affect fetal growth such as preeclampsia and intra-uterine growth restriction. A subset of the children born to both of these cohorts is being assessed with a battery of neurodevelopmental tests when they reach two years of age. The two studies, together, for the first time may allow us to understand the three interlinked outcomes (preterm birth, physical growth and neurocognitive development) in a comprehensive manner so that we can package our interventions in the first 1000 days, to maximize the impact on both early mortality and morbidity throughout the life-cycle.

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