In a recently released article in Pediatrics(10.1542/peds.2017-2169), Dr. Juliane Schneider and colleagues ask how and if enhanced early nutritional support in the first two weeks of life improves neurodevelopment of very premature infants. The first two weeks? At first blush, this seems a very limited window into the care and feeding of tiny babies. But the authors frame their work for us: little is known about the impact of early energy and nutrient intake on regional and total brain growth, and on gray matter and white matter maturation, or about how acute illness modifies these relationships. How much do calories and protein and other elements of nutritional intake really matter in those first two weeks, when so much focus is often appropriately on survival?
The authors prospectively studied a final total of 47 premature infants born at <30 weeks gestational age. Infants had to be free from congenital malformation or severe intraventricular hemorrhage (IVH; infants were excluded for grades 3 or 4), and stable enough to tolerate MRI (magnetic resonance imaging) without sedation. Detailed nutritional and clinical information was collected, and infants underwent 3 serial MRI exams at (1) <2 weeks of age, (2) at 3 weeks chronological age or 34-35 weeks postmenstrual age, and (3) at term equivalent age. At 18 months postmenstrual age a developmental pediatrician, who was unaware of the clinical information, performed a Bayley exam (BSID-II, Bayley Scales of Infant Development, version 2) to assess mental and psychomotor development. While an imperfect predictor of school age cognitive function,1,2 the BSID-II (or the BSID-III) is widely used to assess neurodevelopment in former premature infants.
The statistical analysis was able to account for multiple related data points obtained over time for individual infants: for example, it makes sense that measures of nutritional intake that were calculated daily were interrelated (e.g. total calories and fat calories), and also that the infant’s 24-hour caloric intake depended on how sick he or she was that day. The authors were also able to control for the effect of illness severity, which strengthens their conclusions related to nutritional intake. Breast milk was initiated on day of life one per protocol and comprised 98% of enteral intake in the first two weeks, so all infants got their “best shot” at optimal enteral feeding. Interestingly, results showed that volume of breast milk intake was associated with a measure of white matter maturation but not with other outcomes.
The overall study results take some time to digest, so please read this study for the details which are thought-provoking. It became clear that higher energy intake in the first two weeks did have a positive impact on many measures of brain growth and gray and white matter maturation, and mitigated the impact of illness severity (for example, respiratory disease). But not all results are intuitive – for example, brain volume predicted psychomotor, but not mental, development index on the BSID-2 at 18 months. Since nutrition in the first two weeks of life appears to be significantly associated with measures of later neurodevelopment, not only is this a meaningful arena for focused research related to maximizing early energy intake for premature infants, but I also wonder if we need to explore impact on other childhood outcomes such as body mass index and blood pressure for both term and preterm infants. Lots of food for thought here!
1. Luttikhuizen Dos Santos ES, de Kieviet JF, Konigs M, van Elburg RM, Oosterlaan J. Predictive value of the Bayley Scales of Infant Development on development of very preterm/very low birth weight children: a meta-analysis. Early Human Development 2013; 89(7): 487-496.
2. Hack M, Taylor HG, Drotar D, Schluchter M, Cartar L, Wilson-Costello D, Klein N, Friedman H, Mercuri-Minich N, Morrow M. Poor predictive validity of the Bayley Scales of Infant Development for cognitive function of extremely low birth weight children at school age. Pediatrics. 2005 Aug;116(2):333-41.