MedicalResearch.com Interview with:
Prof. Deborah A Lawlor
MSc(Lond), MBChB, PhD(Bristol), MPH(Leeds), MRCGP, MFPHM
Professor of Epidemiology
MRC Integrative Epidemiology Unit at the University of Bristol
NIHR Bristol Biomedical Research Centre
Population Health Sciences, Bristol Medical School
Oakfield House, Oakfield Grove, Bristol
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: As the obesity epidemic has occurred there has been increasing concern about pregnant women being more adipose (having higher levels of fat) during their pregnancy. One particular concern is that women who are on average fatter will have more extreme changes in pregnancy on their lipid, fatty acid, amino acid and glucose levels. In normal ‘healthy’ pregnancy these metabolites increase during pregnancy as part of the physiological response to pregnancy which ensures that the developing fetus has sufficient fuel (nutrients – fats, proteins, sugars) for healthy growth and development. Women who are more adipose tend to have a more extreme change in these fuels and as a consequence the developing fetus is ‘overfed’. There is a linear relationship between a pregnant woman’s body mass index and her infants birth weight, such that each increment greater adiposity (body mass index) of the mother there is on average and increment greater infant birth weight.
Recently, using a method that uses genetic variants (Mendelian randomization) we have shown that this association is likely to be causal (JAMA 2016). But whether there is a lasting effect on offspring health of being overfed in the uterus is unknown. There are concerns that there will be a lasting effect and that for daughters of more adipose women, this would mean that they go into their pregnancies on average fatter and with higher levels of the metabolites that could then overfeed their developing fetus. If this were the case it would mean the obesity epidemic could be accelerated across generations.
There are associations of mothers body mass index with later offspring body mass index, BUT this might not be anything to do with developmental overfeeding of the feeding in the uterus – it could simply reflect shared lifestyles that offspring adopt from their mother (and father) or shared genetic effects. In this study we tried to separate out whether there was evidence for a long-term offspring effect on their lipids, fatty acids, amino acids, glucose, and an inflammatory marker, of having a mother who was on average fatter during her pregnancy that was due to overfeeding in the uterus, as opposed to shared family lifestyle and genetics. We did this by comparing associations of mothers pre-pregnancy BMI with offspring outcomes to the same associations of fathers pre-pregnancy BMI with the same outcomes.
Our assumption here was that fathers BMI could not directly result in overfeeding of the fetus and so if the associations were similar this would suggest that they were largely driven by family factors.
MedicalResearch.com: What are the main findings?
Response: Our results suggests that the association between mothers body mass in pregnancy and offspring later metabolites is largely due to shared family factors and not an effect of fetal overnutrition.
MedicalResearch.com: What should readers take away from your report?
Response: It is unlikely that interventions for reducing weight (body mass) that target women during their pregnancy, or when they are in adolescence, will improve later offspring health. If we want to reduce overweight and its associated adverse cardio-metabolic health interventions need to target whole families – mother, father and children – and not just focus on mothers.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: I would be useful to confirm these findings in other large studies using different methods to be more confident of the findings. It would also be useful to look at different measurements of fatness. Here we looked at body mass index, which is a good measure of general fatness and its effect on cardio-metabolic health (including high lipids, diabetes, heart disease), but it is possible that measures of fatness around a woman’s abdomen and her liver might have a specific effect (measuring these in pregnancy in large numbers is not easy).
MedicalResearch.com: Is there anything else you would like to add?
Response: I would like to acknowledge our funders and thank the study participants. This study was funded by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement (Grant number 669545; DevelopObese) and the US National Institute of Health (R01 DK10324). The UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. Myself and three other authors (Diana Santos Ferreira, George Davey Smith & Mika Ala-Korpela, work in a Unit that receives support from the UK Medical Research Council.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Diana L. Santos Ferreira, Dylan M. Williams, Antti J. Kangas, Pasi Soininen, Mika Ala-Korpela, George Davey Smith, Marjo-Riitta Jarvelin, Debbie A. Lawlor. Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts. PLOS Medicine, 2017; 14 (8): e1002376 DOI: 10.1371/journal.pmed.1002376
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