Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 323 275 person years.

Reynolds RM, Allan KM, Raja EA, et al.
BMJ. 2013 Aug 13;347:f4539. doi: 10.1136/bmj.f4539

Background

The link between an adverse intrauterine environment and disease later in life is well documented, including an association between low birth weight and subsequent death from cardiovascular disease [1]. Evidence from animal and human studies suggests that maternal obesity also creates an adverse in utero environment, with long-term detrimental effects for the offspring [2,3]. Links have been shown between maternal obesity and obesity in the offspring [4], as well as biomarkers of future atheromatous disease in childhood [5] and young adulthood [6]. It is unknown whether this leads to a long-term increased risk of cardiovascular disease and mortality in the offspring.
This study examined hospital admissions for cardiovascular events and death rates in 37709 individuals (aged 34-61) whose mothers’ BMI was recorded in pregnancy and stored in the Aberdeen Maternity and Neonatal Databank (AMND), accumulating to 1323275 person years of follow-up.

Main results

• All cause mortality was higher in offspring of mothers who were overweight (adjusted HR: 1.11, 95%CI: 1.03-1.19) or obese (adjHR: 1.35, 95%CI: 1.17-1.55), as compared to mothers with normal weight. Similar, but slightly stronger associations were seen for all cause premature mortality in offspring.
  There was no relation between birth weight and all cause mortality, nor an interaction between birth weight and maternal obesity on outcomes.
• More hospital admissions for a cardiovascular event were seen in offspring of overweight (adjHR: 1.07, 95%CI: 0.97-1.17) or obese (adjHR: 1.15, 95%CI: 1.04-1.26) mothers as compared to mothers with normal weight. Associations were also seen between maternal overweight and other cerebrovascular disease, peripheral artery disease and other cardiovascular disease in offspring. 
• Modelling the non-linear relation between offspring mortality rate and maternal BMI indicated that the odds of death in offspring was greater among mothers with low or high BMI as compare with mothers with a BMI of 23. Chances of death among the offspring were lowest among mothers with a BMI of 24-28.

Discussion

The finding that offspring of mothers with increased BMI were more often admitted to hospital for cardiovascular events and showed more premature death in adult life, is a major public health concern, considering the rising rates of excess weight among pregnant women. The observed effects were independent of several possibly confounding factors in the prenatal and postnatal environment. Thus, the intrauterine environment seems to have a long lasting effect on risk of premature mortality in offspring.

Editorial comment [7]

This article is the first to describe associations between maternal obesity and risk of cardiovascular morbidity and mortality in mid-life. While further research will need to shed light on remaining questions on the role of the early postnatal environment, as well as the role of parental obesity and cardiovascular risk in the offspring in midlife, the results of this study suggest that interventions should begin before pregnancy.

References

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4. Lawlor DA, Lichtenstein P, Fraser A, Langstrom N. Does maternal weight gain in pregnancyhave long-term effects on offspring adiposity? A sibling study in a prospective cohort of 146,894 men from 136,050 families. Am J Clin Nutr 2011;94:142-8.
5. Fraser A, Tilling K, Macdonald-Wallis C, Sattar N, Brion MJ, Benfield L, et al. Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood. Circulation 2010;121:2557-64.
6. Hochner H, Friedlander Y, Calderon-Margalit R, et al. Associations of maternal prepregnancy body mass index and gestational weight gain with adult offspring cardiometabolic risk factors. The Jerusalem Perinatal Family Follow-Up Study. Circulation 2012;125:1381-9.
7. Factor-Litvak. Maternal obesity and heart disease in the offspring. BMJ 2013;347

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