Background

Physical activity has been associated with improvements in cognitive function in both animals and humans. In adult rats and mice, voluntary physical activity has been associated with neurogenesis in the hippocampus (1, 2) and with an increase in long-term potentiation of synaptic efficacy (2). In adult humans, cardiovascular fitness is associated with better performance on cognitive functioning tests (4). In rats and mice, maternal exercise during pregnancy appears beneficial to offspring neurodevelopment. In mice, voluntary wheel running during pregnancy led to differences in offspring's hippocampal cell proliferation (5). In rats, maternal swimming once a day for 10 minutes was associated with offspring having higher levels of neurogenesis in several regions of the hippocampus, higher levels of brain-derived neurotrophic factor, and better short-term memory (6).

The hippocampus may play a key role in the mechanism underlying these beneficial effects of physical activity. Traditionally, the hippocampus has been thought to preserve episodic memories (memories of events) while its role in memorization of facts (semantic memory) is less established. However, recent research has implicated the hippocampus in semantic memory potentially through its role in associative thinking (7, 8). As an example, the hippocampus was recently implicated in acquiring a unique and imaginary lexicon through visual images. Thus, language acquirement through associative learning, as is done in children, may be mediated by the hippocampus (9).

In humans, the effects of physical activity during pregnancy on the neurodevelopment of offspring have been inadequately studied. Three studies of the subject of three slightly different samples of women have been done by JF Clapp. In one study of healthy women with a history of engaging in regular physical activity, women who continued to exercise throughout pregnancy had neonates (N=34) who scored higher in terms of orientation behavior and their ability to regulate state at 5 days after birth as measured by the Brazelton Neonatal Behavioral Assessment Scales when compared to neonates born to women who did not exercise (N=31) (10). In a similar study design, infants of exercising mothers (N=52) at one year of age scored slightly (non-significantly) higher on the mental performance domain of the Bayley Scales of Infant Development when compared to infants of non-exercising mothers (N=52). For psychomotor score, however, infants of exercising mothers scored statistically significantly higher, though the effect was small (11). In the third study, 5 year-old children of women who exercised during pregnancy (N=20) were compared to women who did not exercise (N=20) using the Wechsler Preschool and Primary Scale of Intelligence-Revised, the Peabody Picture Vocabulary Test, the Expressive One Word Picture Vocabulary Test, and the Clinical Evaluation of Language Fundamentals. The children of exercising mothers scored higher in the domains of general intelligence (p=0.01) and oral language skills (p=0.01) (12). The difference in language skills is particularly intriguing given the potential role of the hippocampus in vocabulary acquisition.

Investigation is needed on physical activity during pregnancy in relation to offspring neurodevelopment in humans. Animal evidence supports a biological mechanism for such an effect but the previous human studies suggest a positive association yet are not convincing.

Project Description

We propose an investigation of physical activity during pregnancy in relation to neurodevelopment in offspring using data from ALSPAC. This cohort is ideal for this project for several reasons. We expect that if physical activity influences neurodevelopment the effect may be small and the large sample size in ALSPAC will improve power. Physical activity was assessed by self-administered questionnaire at approximately week 18 of pregnancy for nearly 12,000 women. Of these, we expect over 4,000 will have had IQ measured at age 8 years.

Several questions in section G of the 18 week pregnancy questionnaire have questions on physical activity. Most importantly, question G19 ascertains the number of hours per week, at present, that the woman participated in any of 11 specific exercise-intensive activities.

With respect to outcome, ascertainment was of especially high quality at age 8 compared with other large cohorts that rely on parent-completed questionnaires only. We will follow the analytical plan as presented by Hibbeln et al. (13), in their recent paper on pregnancy seafood consumption in relation to neurodevelopmental outcomes in childhood (except with physical activity scale(s) as the main exposure variable). Their results were adjusted for 26 potentially confounding factors; we might also want to adjust for pregnancy seafood intake.