IMPACT OF POSTNATAL LACTOFERRIN SUPPLEMENTATION ON NEURODEVELOPMENTAL DISORDERS ASSOCIATED WITH LOW BIRTHWEIGHT IN RATS

Low birthweight increases the risk of neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder, autism spectrum disorder and cerebral palsy. Chronic inflammation in the fetus and newborn plays a major role in the emergence of these NDDs, with currently no suitable prophylactic treatment available. Lactoferrin, a major component of colostrum and breast milk is a pleiotropic glycoprotein acting mainly on immunomodulation and antis-inflammatory activities. We developed a rat model of low birthweight based on mild intrauterine hypoperfusion (MIUH), which involves reducing blood perfusion to the fetuses during the last third of gestation. Hypotrophic offspring displayed diffuse brain lesions, spinal and cortical hyperexcitability, sensorimotor and information-processing deficits, exploratory hyperactivity, and memory impairments. This hypoperfusion also increased the expression levels of pro-inflammatory cytokines. We hypothesized that the anti-inflammatory properties of lactoferrin could reduce inflammation during development and thus prevent the early emergence of NDDs. Postnatal maternal supplementation with lactoferrin or an isocaloric soy-based diet (10 g/day/kg of diet) was administered from birth to weaning. In the offspring, we studied the early emergence of sensorimotor reflexes and circulating inflammatory levels, as well as anxiety disorders and short-term memory in adulthood. Compared to rats on the isocaloric diet, postnatal lactoferrin supplementation slightly improves growth retardation in hypotrophic animals and expression levels of pro-inflammatory cytokines, but does not fully restore hyperactivity, anxiety-like behaviors or short-term memory capacities. We therefore observe a moderate impact of postnatal lactoferrin supplementation on NDDs associated with low birthweight.
This work was supported by The Warterloo Fundation and AMU.