Rationale
Brain development occurs rapidly during early childhood and continues throughout middle childhood. Early and later windows of opportunity exist to alter developmental trajectories. Few studies in low- and middle-income countries have examined the importance of the timing of exposure to risks for poor pre-adolescent cognitive and social-emotional outcomes.

Methods
We assessed 359 children who participated in two follow-up studies of the Supplementation with Multiple Micronutrients Intervention Trial conducted in Indonesia in 2001–2004: at 3.5 years in 2006 and 9–12 years in 2012–2014. Using structural equation models, we examined indicators of early childhood (3.5 y) and pre-adolescent (9–12 y) exposure to risks (child height-for-age z-score [HAZ], hemoglobin [Hb], maternal depressive symptoms [MDS], home environment [HOME]), with two developmental outcomes: cognitive ability and social-emotional problems. We characterized patterns of change by calculating residuals of indicators measured earlier (3.5 y) predicting the same indicators measured later (9–12 y), for example, the residual of 3.5 y MDS predicting 9–12 y MDS (rMDS).

Results
Three early risk indicators (HOME, Hb, and MDS) were indirectly associated with pre-adolescent cognitive scores through early cognitive scores (HOME: 0.15, [95% CI 0.09, 0.21]; Hb: 0.08 [0.04, 0.12], MDS: −0.07 [-0.12, −0.02]). Pre-adolescent cognitive scores were also associated with change in MDS (rMDS: −0.13 [-0.23, −0.02]) and Hb (rHb: 0.10 [0.00, 0.20]) during middle childhood. For pre-adolescent social-emotional problems, both early childhood MDS (0.31 [0.19, 0.44]) and change in MDS during middle childhood (rMDS: 0.48 [0.37, 0.60]) showed strong direct associations with this outcome.

Conclusions
Our findings confirm those of previous studies that prevention of risk exposures during early childhood is likely to support long-term child development. It also adds evidence to a previously scarce literature for the middle childhood period. Prevention of maternal depressive symptoms and child anemia during middle childhood should be assessed for effectiveness to support child development.