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Maternal adiposity—a determinant of perinatal and offspring outcomes?

Abstract

Experimental and animal data suggest that maternal obesity during pregnancy adversely affects offspring health in the short-term and the long-term. Whether these effects occur in humans and influence population health is less clear. This Review explores evidence from intervention studies and observational studies that have used designs (such as family-based comparisons and Mendelian randomization) that might help improve understanding of the causal effects of maternal obesity in humans. Collectively, human studies provide evidence that maternal overweight and obesity is causally related to pregnancy complications, increased offspring weight and adiposity at birth, and the difficulties associated with delivery of large-for-gestational-age infants. The underlying mechanisms for these effects probably involve maternal and fetal dysregulation of glucose, insulin, lipid and amino acid metabolism. Some evidence exists that extreme maternal obesity (BMI ≥40 kg/m2) is causally related to a long-term increase in offspring adiposity, but further exploration of this relationship is needed. High gestational weight gain may result in a long-term increase in offspring adiposity if women are already overweight or have obesity at the start of pregnancy. To date, little high-quality human evidence exists that any of these effects are mediated by epigenetic mechanisms, but approaches to appropriately test this possibility are being developed.

Key Points

  • Maternal obesity is associated with considerable maternal and fetal metabolic perturbation

  • Prospective studies, including those with outcomes reported for first and second pregnancies and before and after bariatric surgery, suggest a causal association of maternal obesity with adverse pregnancy and perinatal outcomes

  • Evidence also exists that extreme maternal obesity (BMI ≥40 kg/m2) is causally related to increased adiposity of offspring during childhood and adulthood

  • A dose–response effect of maternal BMI (across the whole distribution of maternal BMI) on the adiposity of offspring during childhood and adulthood is not supported by current evidence

  • High gestational weight gain is weakly associated with adverse perinatal and long-term offspring outcomes; causal effects may be restricted to subgroups of the population

  • Nutritional experiences related to maternal adiposity in utero can have effects that persist into childhood, and these effects may be mediated by epigenetic modifications, but robust causal evidence is needed

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Figure 1: Summary of the associations of maternal increased adiposity with perinatal and long-term offspring outcomes.

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All authors researched data for the article and reviewed and/or edited the manuscript before submission. D. A. Lawlor and S. M. Nelson provided a substantial contribution to discussion of the content and D. A. Lawlor wrote the manuscript.

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Correspondence to Debbie A. Lawlor.

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Lawlor, D., Relton, C., Sattar, N. et al. Maternal adiposity—a determinant of perinatal and offspring outcomes?. Nat Rev Endocrinol 8, 679–688 (2012). https://doi.org/10.1038/nrendo.2012.176

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