Lee et al.1 recently reported important new evidence from Bangladesh linking exposure of infants born small for gestational age (SGA) to inflammation with the neurodevelopmental delay commonly observed in these infants. They examined levels of various inflammatory markers [cytokines, C-reactive protein (CRP)] in the cord blood from a cohort of 288 Bangladeshi newborn infants, whom they also assessed for neurodevelopmental outcomes at age 2 years using the Bayley Scales of Infant/Toddler Development, Third Edition (Bayley-III). Identification of markers of inflammation in cord blood may reflect exposure of the fetus in utero in the late prenatal period or exposure of the newborn infant at the time of birth. They analyzed associations between markers of inflammation and neurodevelopmental outcomes using several regression models taking various factors into account, including unadjusted analysis; controlling for confounders (maternal parity, gestational age, sex, postnatal age of Bayley-III assessment); controlling for factors preceding the exposure (maternal education, maternal body-mass index, maternal depression); or controlling for postnatal factors in shaping child development, i.e., the home environment. They found no overall differences in mean cytokine levels by preterm (8.9% of infants) or SGA (45.0% of infants, 96% of whom were term SGA) status. In addition, Bayley-III raw z-scores did not significantly differ among infants who were born preterm versus term or SGA versus non-SGA, and regression analyses did not identify differences in mean Bayley-III performance by inflammatory biomarker status for most biomarkers and developmental domains.

When examining the entire cohort for associations of inflammation and developmental delay defined as a z-score <−1, a limited number of models and associations were found to be significant. Notably, an association was found between CRP and IL- 6 elevation with significantly higher odds of fine motor delay in all the regression models. Fine motor activities are needed for children to learn activities of daily living and to become independent in activities such as feeding, toileting, bathing, and self-care, in addition to writing in the preschool and school years; thus, fine motor skill development is fundamental to school readiness and is predictive of educational achievement.2,3 In sub-analysis of SGA but not preterm infants, a number of associations were found, including elevated IL-1α with cognitive delay, IL-8 with language delay, CRP with lower receptive communication z-scores, and IL-1β with lower expressive communication and motor z-scores. What appears to be most salient is that exposure to inflammation (expressed in elevations in a variety of markers of inflammation) during a very sensitive period of brain development was associated with a range of developmental insults in SGA infants.

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