Series
Influence of maternal obesity on the long-term health of offspring

https://doi.org/10.1016/S2213-8587(16)30107-3Get rights and content

Summary

In addition to immediate implications for pregnancy complications, increasing evidence implicates maternal obesity as a major determinant of offspring health during childhood and later adult life. Observational studies provide evidence for effects of maternal obesity on her offspring's risks of obesity, coronary heart disease, stroke, type 2 diabetes, and asthma. Maternal obesity could also lead to poorer cognitive performance and increased risk of neurodevelopmental disorders, including cerebral palsy. Preliminary evidence suggests potential implications for immune and infectious-disease-related outcomes. Insights from experimental studies support causal effects of maternal obesity on offspring outcomes, which are mediated at least partly through changes in epigenetic processes, such as alterations in DNA methylation, and perhaps through alterations in the gut microbiome. Although the offspring of obese women who lose weight before pregnancy have a reduced risk of obesity, few controlled intervention studies have been done in which maternal obesity is reversed and the consequences for offspring have been examined. Because the long-term effects of maternal obesity could have profound public health implications, there is an urgent need for studies on causality, underlying mechanisms, and effective interventions to reverse the epidemic of obesity in women of childbearing age and to mitigate consequences for offspring.

Introduction

Maternal obesity before and during pregnancy is widely recognised to have immediate implications in terms of pregnancy complications, including gestational diabetes, pre-eclampsia, and delivery of large-for-gestational-age infants.1 Recognition that developmental effects can have long-term consequences on offspring health and wellbeing has led to attention being focused on the potential for maternal obesity to be one of the influences contributing to the “developmental origins of health and disease”.2 The high prevalence of maternal obesity associated with the global obesity epidemic means that determination of any such long-term effects is now an urgent priority.3

Although to control for potentially confounding variables remains a challenge in human observational studies, extensive experimental work in rodents and non-human primates has demonstrated that maternal obesity induced by dietary intervention leads to obesity, diabetes, raised blood pressure, fatty liver, and behaviour changes in offspring.4 These studies have shown that maternal obesity can permanently alter various metabolic control processes in fetuses, including the hypothalamic response to leptin and subsequent regulation of appetite and pancreatic β-cell physiology.4 Mechanisms are probably multifactorial, but could include maternal metabolic changes, such as changes in glucose and fatty acids,5 altered maternal hypothalamic–pituitary–adrenal axis activity,6 and changes in placental function and inflammation.7

In this Series paper, we review the evidence linking maternal obesity with long-term consequences for offspring. We focus on body composition, cardiometabolic, allergic, immune, infectious, and neurobehavioural outcomes, and discuss altered epigenetic processes as a probable major mechanism underlying long-term effects of maternal obesity on offspring.

Section snippets

Body composition and cardiometabolic outcomes

An accumulating body of evidence suggests that maternal pre-pregnancy obesity and excessive gestational weight gain are associated with an increased risk of obesity in offspring during childhood.8, 9, 10, 11 Although the initial focus was on severe maternal obesity, the results of several studies12, 13, 14, 15 over the past decade suggest that higher maternal pre-pregnancy BMI across the full spectrum is associated with greater childhood adiposity and an adverse body-fat distribution. Excessive

Allergic and atopic outcomes

The global rise in maternal obesity has been implicated in the parallel rising burden of asthma, allergic disease, and other early immune diseases, with speculation that this burden could be among the multisystem consequences of obesity-related inflammation for offspring (table 1). A meta-analysis46 of 14 studies and 108 321 mother–child pairs showed that maternal overweight or obesity in pregnancy was associated with increased risks of childhood asthma or wheeze ever (odds ratio [OR] 1·31, 95%

Other immune and infectious-disease-related outcomes

Whether maternal obesity increases susceptibility of offspring to other immune and infectious-disease-related outcomes has been less well studied, but is important to consider in view of the rising prevalence of obesity in low-income and middle-income countries,54 where the burden of infection during pregnancy and childhood is high. With dampened maternal immunity to tolerate the semi-allogeneic offspring, pregnancy represents a period of increased susceptibility to infection, and maternal

Neurocognitive and behavioural outcomes in offspring

Despite the potential public health importance, few cohort studies have been done to examine associations between maternal obesity and detailed neurodevelopmental outcomes in offspring (table 2). Some human data have shown that higher pre-pregnancy weight is associated with poorer cognitive outcomes in offspring, and higher (but not excessive) weight gain during pregnancy has been associated with better cognitive outcomes.73, 74 However, published data do not allow for definitive conclusions to

Epigenetic modifications: a potential underlying mechanism

Epigenetic processes are emerging as an important mechanism through which the memory of developmental exposures is held, with pathophysiological consequences for various organs and systems. Epigenetic modifications have been proposed as a key causal mechanism linking maternal adiposity and outcomes in offspring.82 Furthermore, evidence is now emerging that epigenetic processes can act over three or more generations and through the paternal line.83 Epigenetic modifications result in alterations

Methodological considerations

Fixed genetic variants shared by mother and offspring are important confounders of proposed links between metabolic factors associated with maternal obesity and offspring outcomes, as are shared postnatal influences on diet and lifestyle behaviours97 and microbiome-related mechanisms.98 However, abdominal fat depots already differ at birth between groups with different risks of later metabolic disease,99 and at least some of the effects of maternal obesity are probably mediated through prenatal

Conclusion

Although initial research linking developmental influences with major non-communicable disorders in later life focused on the effects of fetal undernutrition, increasing evidence suggests that exposure to maternal obesity also leads to an increased risk of disease in offspring. Observational studies have provided evidence for associations between maternal obesity and an increase in their offspring's risk of obesity, coronary heart disease, stroke, type 2 diabetes, and asthma. Emerging evidence

Search strategy and selection criteria

We systematically reviewed MEDLINE, Embase, and the Cochrane library with the search terms “maternal obesity”, “pre-conception”, “pregnancy”, “intergenerational”, and “offspring” or “infant” or “child” in combination with the terms “fetal programming”, “epigenetic”, “methylation”, “disease”, “immunity”, “cardiovascular”, “type 2 diabetes”, “infection”, “HIV”, “malaria”, “proinflammatory”, “cognition”, “school performance”, “psychopathology”, “mental health”, “ADHD”, “autism”, “affective

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