By David Horner
Chairperson: Professor Lotte Lauritzen, University of Copenhagen, Denmark
Opponent: Professor Rikard Landberg, Chalmers University of Technology, Sweden
Opponent: Associate Professor Tuula Hurtig, University of Oulu, Finland
Summary
Nutrition during pregnancy is important for the health and development of children. Adequate maternal nutrition is essential for supporting optimal foetal growth, organ development, and optimal immune functioning. Nutrients obtained through the maternal diet provide both
the building blocks and energy substrate for the developing foetus. Specifically, the intake of essential nutrients such as omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs), found abundantly in fish oil, have been associated with various health benefits for children. Conversely, higher intake of saturated fats, sugars, and processed meats may have detrimental effects on foetal and child health, underscoring the relevance of balanced maternal nutrition. Many studies concentrate on individual nutrients, leading to an incomplete understanding of how maternal dietary patterns during pregnancy may affect child health outcomes, including the risk of infections, neurodevelopmental disorders, and cognitive development in offspring. The aim of this PhD thesis is to investigate the potential impact of maternal dietary patterns during pregnancy on child health and development, and elucidate specific mechanistic insights linking maternal nutrition to child health.
This thesis utilises data from the prospective mother-child cohort study, Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010), of 700 children. COPSAC2010 is well-suited for studying the associations of maternal dietary patterns during pregnancy because it provides comprehensive data on pregnancy diet, two randomised prenatal supplementation interventions, longitudinal blood metabolome profiles, high-resolution infection data in early life, as well as clinically assessed neurodevelopmental and cognitive outcomes.
In Paper 1, we examined the effects of randomised n-3 LCPUFA supplementation during pregnancy on gastroenteritis (vomiting and diarrhoea) in children. I found that maternal prenatal supplementation with n-3 LCPUFAs led to a reduction in the number of days and episodes of gastroenteritis in children, in the first 3 years of life. Further, the effect of supplementation was dependent on pre-intervention levels of n-3 LCPUFA, highlighting the potential for personalised nutrition approaches to tailor interventions based on individual nutritional status. In conclusion, these findings suggested that targeted n-3 LCPUFA supplementation could serve as a preventive measure against gastroenteritis in early childhood.
In Paper 2, we investigated the association between an Unhealthy dietary pattern during pregnancy and neurodevelopmental disorders in children. I found that an Unhealthy dietary pattern during pregnancy was significantly associated with an increased risk of ADHD and autism diagnosis, as well as related symptoms, in 10-year-old children. The associations of the Unhealthy dietary pattern were more pronounced in children with genetic predisposition for neurodevelopmental disorders, male offspring, and higher maternal BMI, highlighting a contextual interplay. This suggests that both the environment and genetic context are important when investigating neurodevelopmental disorders. Furthermore, when juxtaposing pregnancy and child metabolome scores in two independent mother child cohorts, I found that early-to-mid pregnancy time points had the strongest association with neurodevelopmental disorders, suggesting that early pregnancy may be a particularly sensitive period in which dietary effects may impact child neurodevelopment. Our findings for ADHD were further validated in two large, independent mother-child cohorts using blood metabolome modelling. In conclusion, these findings provide robust evidence for targeted prenatal dietary interventions aimed at reducing the risk of neurodevelopmental disorders in children.
In Paper 3, we explored the relationship between an Unhealthy dietary pattern during pregnancy, head circumference growth (a proxy of brain volume growth), and cognition in children. I found that an Unhealthy dietary pattern, modelled objectively via the blood metabolome, was associated with lower cognitive scores at 2½, as well as reduced head circumference growth in early life. Moreover a `Varied dietary pattern` was associated with increased head circumference growth and higher cognitive score at 10 years. These findings were independent of genetics for intelligence and robust to adjustment for child metabolome scores, suggesting that pregnancy may be a sensitive window for dietary pattern effects. Moreover, the association of the Varied dietary pattern on cognitive scores at 10 years was partially mediated by increased head circumference growth, suggesting a complex interplay between brain size and function. These findings further highlight the importance of promoting healthy and balanced maternal dietary patterns during pregnancy for optimal neurodevelopment in children.
These studies provide robust objective evidence for maternal dietary patterns being an important determinant for child health and development. The first study provides evidence for applying a personalised approach with regard to supplementation of n-3 LCPUFAs during pregnancy to reduce gastroenteritis in children. Whereas the latter two studies provide evidence for initiating dietary interventions in pregnancy to mitigate the risk of neurodevelopmental disorders and reduced cognition. Overall, these studies contribute to our understanding of maternal dietary patterns during pregnancy, and their impact on child health and development in early life.
