Women with obesity are advised to lose weight before pregnancy, but evidence is lacking about the effectiveness of weight loss strategies to aid improved perinatal outcomes. Strategies are urgently needed to mitigate the increased risk of long-term effects of maternal obesity on the offspring, including diabetes, obesity, cardiorenal disease and metabolic associated fatty liver disease. This prestigious ESA Ken Wynne Postdoctoral Research Award has facilitated my work investigating the impact of preconception weight loss, with either the GLP-1 receptor agonist liragluitde, or dietary intervention, versus dietary intervention in pregnancy, in a mouse model of maternal obesity.
Methods: Maternal obesity was modelled in C57BL/6 mice; with dams fed a high fat diet (HFD) versus chow diet for 8 weeks and compared to lean chow-fed controls. In obese dams, liraglutide or diet modification (switch to chow) was utilised to induce pre-conception weight loss. Fertility rates were observed after mating. A further group of pregnant dams were switched from HFD to chow diet in early pregnancy. Maternal anthropometric measures, glucose tolerance and metabolic markers were measured at late gestation. Pregnant dams were either allowed to deliver their offspring or sacrificed at gestational Day 18-20 and maternal blood, kidney and placenta were collected. The offspring were weaned onto a HFD and their anthropometric measures, glucose tolerance, metabolic markers, liver and kidney examined at postnatal week 12.
Results: Pre-pregnancy liraglutide was the most effect pre-pregnancy strategy for improving maternal metabolic health, alongside fertility and fecundity. Pre- or post-conception diet intervention was effective at reducing adverse maternal metabolic outcomes in late pregnancy. The offspring of obese mothers were protected from the adverse foetal programming effects of maternal obesity, with improved metabolic and liver health in male offspring observed.
Conclusion: This research strongly supports pre-pregnancy intervention as an effective strategy to improve maternal fertility, and reduce adverse metabolic health in the mothers and the offspring. The challenge of weight management is to sustain long-term weight loss, and pre-pregnancy pharmacotherapy together with dietary intervention maintained in pregnancy, may be a useful strategy for some women with obesity desiring pregnancy.