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
SeriesInfluence of maternal obesity on the long-term health of 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
References (110)
- et al.
Decreased maternal hypothalamic–pituitary–adrenal axis activity in very severely obese pregnancy: Associations with birthweight and gestation at delivery
Psychoneuroendocrinology
(2016) - et al.
Perinatal risk factors for childhood obesity and metabolic dysregulation
Am J Clin Nutr
(2009) - et al.
Modifiable early-life risk factors for childhood adiposity and overweight: an analysis of their combined impact and potential for prevention
Am J Clin Nutr
(2015) - et al.
Weight gain in pregnancy and childhood body composition: findings from the Southampton Women's Survey
Am J Clin Nutr
(2010) - et al.
Maternal anthropometry is associated with the body mass index and waist:height ratio of offspring at 23 years of age
J Nutr
(2009) - et al.
Maternal physiologic adaptations to early human pregnancy
Am J Obstet Gynecol
(1988) - et al.
Maternal obesity, gestational weight gain, and risk of asthma and atopic disease in offspring: a study within the Danish National Birth Cohort
J Allergy Clin Immunol
(2013) - et al.
The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies
J Allergy Clin Immunol
(2015) - et al.
Epigenetics and prenatal influences on asthma and allergic airways disease
Chest
(2011) - et al.
Diet, metabolites, and “western-lifestyle” inflammatory diseases
Immunity
(2014)
Does maternal diet during pregnancy and lactation affect outcomes in offspring? A systematic review of food-based approaches
Nutrition
Early-life environmental determinants of allergic diseases and the wider pandemic of inflammatory noncommunicable diseases
J Allergy Clin Immunol
Maternal diagnosis of obesity and risk of cerebral palsy in the child
J Pediatr
Association between maternal obesity and autism spectrum disorder in offspring: a meta-analysis
J Autism Dev Disord
The association between maternal obesity and neurodevelopmental outcomes of offspring
J Pediatr
Maternal high fat diet consumption during the perinatal period programs offspring behavior
Physiol Behav
Peri-conception parental obesity, reproductive health, and transgenerational impacts
Trends Endocrinol Metab
Abdominal adipose tissue compartments vary with ethnicity in Asian neonates: Growing Up in Singapore Toward Healthy Outcomes birth cohort study
Am J Clin Nutr
The consequences of obesity and excess weight gain in pregnancy
Proc Nutr Soc
Impact of maternal obesity on offspring obesity and cardiometabolic disease risk
Reproduction
A nationally representative study of maternal obesity in England, UK: trends in incidence and demographic inequalities in 619 323 births, 1989–2007
Int J Obes (Lond)
Determining the consequences of maternal obesity on offspring health
Exp Physiol
Maternal metabolism and obesity: modifiable determinants of pregnancy outcome
Hum Reprod Update
The placental exposome: placental determinants of fetal adiposity and postnatal body composition
Ann Nutr Metab
Childhood consequences of maternal obesity and excessive weight gain during pregnancy
Acta Obstet Gynecol Scand
Maternal obesity during pregnancy and cardiovascular development and disease in the offspring
Eur J Epidemiol
Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis
PLoS One
Risk of childhood overweight or obesity associated with excessive weight gain during pregnancy: a meta-analysis
Arch Gynecol Obstet
Childhood cardiometabolic outcomes of maternal obesity during pregnancy: the Generation R Study
Hypertension
Exploring the developmental overnutrition hypothesis using parental–offspring associations and FTO as an instrumental variable
PLoS Med
Maternal weight gain in different periods of pregnancy and childhood cardio-metabolic outcomes. The Generation R Study
Int J Obes
Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood
Circulation
Maternal gestational weight gain and offspring weight in adolescence
Obstet Gynecol
A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood
Ann Epidemiol
Maternal prepregnancy BMI, offspring's early postnatal growth, and metabolic profile at age 5–6 years: the ABCD Study
J Clin Endocrinol Metab
Maternal weight gain during the first half of pregnancy and offspring obesity at 16 years: a prospective cohort study
BJOG
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
Maternal BMI, parity and pregnancy weight gain: influences on offspring adiposity in young adulthood
J Clin Endocrinol Metab
Gestational weight gain in relation to offspring body mass index and obesity from infancy through adulthood
Int J Obes
Gestational weight gain in normal weight women and offspring cardio-metabolic risk factors at 20 years of age
Int J Obes
Predictors of obesity in childhood, adolescence, and adulthood in a birth cohort
Matern Child Health J
Associations of gestational weight gain with offspring body mass index and blood pressure at 21 years of age: evidence from a birth cohort study
Circulation
Mother's weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study
BMJ
Maternal weight in pregnancy and offspring body composition in late adulthood: findings from the Helsinki Birth Cohort Study (HBCS)
Ann Med
Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 323 275 person years
BMJ
Long-term consequences of maternal overweight in pregnancy on offspring later health: findings from the Helsinki Birth Cohort Study
Ann Med
Longitudinal study of maternal body mass index, gestational weight gain, and offspring asthma
Allergy
The relationship between maTernal adiposity and infant weight gain, and childhood wheeze and atopy
Thorax
Maternal prepregnancy obesity is an independent risk factor for frequent wheezing in infants by age 14 months
Paediatr Perinat Epidemiol
Subcutaneous body fat in pregnant New Zealand women: association with wheeze in their infants at 18 months
Matern Child Health J
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These authors contributed equally