Using prospectively collected data from nine cohort studies in five countries, we found that a higher burden of diarrhoea prior to 24 months of life was associated with a greater frequency of stunting at 24 months of age. The effect of diarrhoea on stunting was consistent across studies, and we did not detect confounding by SES. Furthermore, the magnitude of this effect was not affected when we excluded children who were stunted before 6 months of age. Our analysis supports the hypothesis that a higher cumulative burden of diarrhoea adversely affects a child's nutritional status during early childhood and that catch-up growth does not appear to make up for this deficit.
This analysis shows that both cumulative incidence and longitudinal prevalence of diarrhoea prior to 24 months have a statistically significant ‘dose–response’ relationship with stunting at 24 months of age. Although both measures of cumulative burden appear to describe the effects of diarrhoea on stunting equally well, longitudinal prevalence (expressed as a proportion of time spent ill with diarrhoea) may be a more appealing measure of cumulative exposure than incidence because each observed day of diarrhoea can be represented as a lost opportunity to gain height. A critical assumption is that any day of diarrhoea has an equally adverse effect on the odds of stunting. However, we cannot exclude the possibility that unmeasured confounders, such as prevalence of zinc deficiency and infections other than diarrhoea, may affect the observed relationship between the cumulative burden of diarrhoea and stunting.
We approached individual investigators to request original data from longitudinal studies that collected daily records of diarrhoeal surveillance and regular anthropometric measurements per child over time. We identified several advantages of pooling original data from multiple studies over a classical meta-analysis approach. First, we applied a standard definition for a diarrhoeal episode across all studies. Second, we compared all anthropometric measurements against the same international growth reference. And third, we applied the same analytical method for all studies to test our hypothesis.
The effects of the history of diarrhoea prior to 24 months of life on stunting at 24 months of age were similar across studies despite differences in study design, and despite the heterogeneity in the prevalence of stunting and in the history of diarrhoea across studies. While other investigators have performed comprehensive reviews on this topic,36,37
we do not know of any published investigation that has attempted a pooled analysis, as we have done. Moreover, the results of our pooled analysis are easy to understand and easy to translate to other populations, while the methods can be used to examine the effects of other childhood infections on stunting.
Nonetheless, we encountered some methodological challenges in pooling data across multiple studies. For example, not all studies recorded the number of loose stools on each day of surveillance, but relied instead on maternal reporting to define a day of diarrhoea. We also did not have data on breastfeeding or food intake; however, one of the included longitudinal studies measured energy intake quantitatively and found that the effect of energy intake on growth was independent from the effect of diarrhoea on growth.38
Additionally, in the Peru 1995 study, we previously documented that breastfeeding did not confound the effect of diarrhoea on linear growth.21
Each study used a different definition for SES and this could explain why we did not detect an association between SES and stunting. One limitation is that our analysis uses only a subset of children who were followed for at least 250 days and who had an anthropometric measurement at 24 months of age, which may limit generalizability due to the increased likelihood that children of the subset were alive at that age. Another limitation is that we did not have information on other concurrent infections that may also affect growth. Our study has the potential for publication bias as a reason for the overall positive finding, as studies that did not find an association between diarrhoea and nutritional status may be less likely to be published.
There are other analytical approaches that we could have considered for this study, such as a longitudinal growth analysis or a time-to-event analysis. Any of these analyses, however, would have changed the inferential objective. We used the prevalence of stunting at 24 months as an outcome because, in developing countries, stunting is a common condition that is usually regarded as a manifestation of chronic malnutrition.39
Although the mechanisms that lead to stunting are not well understood, it is likely to be the product of cumulative nutritional insults.40
Thus, it is plausible that a higher cumulative burden of diarrhoea increases the chance of childhood stunting. An advantage of using stunting as the outcome is that the prevalence of stunting is generally low in the first months of life. In our study, 14% of children were stunted before 6 months of age. Moreover, there appears to be limited reversibility once a child becomes stunted.41
Our data showed that reversibility of stunting was relatively uncommon within the 2 years of life. That is, only 6% of children who were stunted at 6 months of age recovered from stunting at 24 months of age beyond regression to the mean. Moreover, stunting is a fairly robust measurement of nutritional status in that it appears to be only affected by sustained or multiple, frequent nutritional insults, in contrast to underweight where large fluctuations are common as a result of a nutritional insult.
Stunting is also a useful outcome from a health policy perspective. Stunting is an age-and-sex corrected health statistic that produces valid and reliable measurements when performed. It is an easy and inexpensive measurement to conduct in large-scale cross-sectional surveys. For example, stunting at 24 months of age is collected by Demographic Health Surveys worldwide. Furthermore, stunting is also a comparable health statistic across countries.
Finally, our analysis of the longitudinal prevalence of diarrhoea on stunting suggests a 24-month-old child with more days of diarrhoea had a greater chance of becoming stunted than a 24-month-old child with fewer days of diarrhoea. It follows that an episode of persistent diarrhoea (i.e. lasting 14 days or longer) contributes to a greater chance of stunting than an episode that lasts <14 days. On the other hand, our analysis showed that the proportion of episodes that were persistent did not contribute to stunting above and beyond the effect of cumulative incidence of diarrhoea. This suggests that the greater chance of stunting associated with a persistent episode is due only to its duration.
In summary, we found that a higher cumulative burden of diarrhoea prior to 24 months of life was associated with an increased prevalence of stunting at 24 months of age. The magnitude of this effect was constant across a range of different contexts. Therefore, prevention of early childhood diarrhoea should be fully integrated into programmes that aim to reduce the incidence of childhood stunting.