Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child

Abstract

Obesity is the most common medical condition in women of reproductive age. Obesity during pregnancy has short term and long term adverse consequences for both mother and child. Obesity causes problems with infertility, and in early gestation it causes spontaneous pregnancy loss and congenital anomalies. Metabolically, obese women have increased insulin resistance in early pregnancy, which becomes manifest clinically in late gestation as glucose intolerance and fetal overgrowth. At term, the risk of cesarean delivery and wound complications is increased. Postpartum, obese women have an increased risk of venous thromboembolism, depression, and difficulty with breast feeding. Because 50-60% of overweight or obese women gain more than recommended by Institute of Medicine gestational weight guidelines, postpartum weight retention increases future cardiometabolic risks and prepregnancy obesity in subsequent pregnancies. Neonates of obese women have increased body fat at birth, which increases the risk of childhood obesity. Although there is no unifying mechanism responsible for the adverse perinatal outcomes associated with maternal obesity, on the basis of the available data, increased prepregnancy maternal insulin resistance and accompanying hyperinsulinemia, inflammation, and oxidative stress seem to contribute to early placental and fetal dysfunction. We will review the pathophysiology underlying these data and try to shed light on the specific underlying mechanisms.

Conflict of interest statement

Competing interests: The authors have read and understood BMJ policy on declaration of interests and have no conflicts to declare.

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Figures

Fig 1

Differential expression of placental metabolic genes in lean women with type 1 diabetes and obese women with gestational diabetes (gene expression increases as the color changes from blue (downregulated) to red (upregulated). Unsupervised hierarchical clustering of metabolic genes that are modified in the placenta of obese women with gestational diabetes (GDM) and lean women with type 1 diabetes (type 1 DM). When the placental transcriptome at term was compared between lean women with type 1 DM and obese women with GDM, genes related to lipid metabolism were preferentially activated in obese women with GDM. Eleven genes related to lipid transport and activation and seven genes related to lipid metabolism were enhanced

Fig 2

Longitudinal changes in body composition in lean and obese women before pregnancy through to late gestation. (A) Changes in lean body mass (kg; mean and standard deviation) in lean (n=5) and obese (n=6) women: prepregnancy, early pregnancy (12-14 weeks), and late pregnancy (34-36 weeks). Change over time, P=0.0001 and between groups, P=0.34. (B) Longitudinal changes over time (kg; mean and standard deviation) of fat mass in lean (n=5) and obese (n=6) women: prepregnancy, early pregnancy (12-14 weeks) and late pregnancy (34-36 weeks). Change over time, P=0.0001 and between groups, P=0.02

Fig 3

Longitudinal changes in insulin sensitivity in lean and obese women before pregnancy through to late gestation. Longitudinal changes over time in insulin sensitivity (mean and standard deviation) as estimated by the hyperinsulinemic-euglycemic clamp (mg/kg.ffm/min) in lean (n=5) and obese (n=6) women: prepregnancy, early pregnancy (12-14 weeks) and late pregnancy (34-36 weeks). Change over time, P=0.0001 and between groups, P=0.07

Fig 4

Longitudinal changes in free fatty acid concentrations in lean and obese women before pregnancy through to late gestation. (A) Longitudinal changes over time in basal free fatty acid concentration (mE/L; mean and standard deviation) in lean (n=5) and obese (n=6) women: prepregnancy, early pregnancy (12-14 weeks), and late pregnancy (34-36 weeks). Change over time, P=0.02 and between groups, P=0.30. (B) Longitudinal changes over time in free fatty acid concentration (mE/L; mean and standard deviation) during the hyperinsulinemic-euglycemic clamp in lean (n=5) and obese (n=6) women: prepregnancy, early pregnancy (12-14 weeks) and late pregnancy (34-36 weeks). Change over time, P=0.0004 and between groups, P=0.82

Fig 5

Maternal-placental crosstalk and fetal growth. Because of the reduced insulin sensitivity in obese compared with lean women, there is an increase in the insulin response in early pregnancy which affects early placental growth and gene expression. This then results in the release of placental factors that decrease insulin sensitivity in maternal tissue (skeletal muscle, liver, and adipose tissue), thereby resulting in increased nutrient availability for feto-placental growth. Increased availability of nutrients such as glucose and lipids thereby contributes to fetal adiposity, which becomes manifest only in late gestation

Fig 6

Overview of potential mechanisms influencing the risk of obesity in the offspring of obese mothers. Pregravid obesity has important effects on reproductive function and the development of the oocyte. Persistent effects of maternal obesity can be mediated through resetting of epigenetic marks in early developmental stages, which may influence the commitment and renewal of stem cells. Maternal obesity and high energy diets also alter the growth of the offspring by altering nutrient transport through the placenta, perhaps as a result of altered placental development caused by placental inflammation and alterations in nutrient sensing pathways. Effects of maternal obesity and poor diets may also be perpetuated in the offspring through programming of neonatal growth, with alterations in milk composition and restructuring of the infant’s microbiome having pleiotropic effects on the offspring’s health