Best Practice & Research Clinical Obstetrics & Gynaecology
7Placental dysfunction in obese women and antenatal surveillance strategies
Introduction
Obesity has become a global epidemic. It is estimated that 205 million men and 297 million women were obese in 2008 [1]. Obesity in pregnancy is defined as a body mass index (BMI) of ≥30 kg/m2 at booking. One in five women in the UK is obese at antenatal booking; this is a threefold increase since 1980 [2]. Body fat distribution differs with race. Asian populations have more fat and more co-morbidity for any given BMI; therefore, it has been suggested to use lower BMI cut-off points for these populations [3]. Maternal obesity is associated with an increased risk of feto-maternal complications. Maternal obesity causes not only risks during the perinatal period but also long-term complications for the offspring. It creates a significant risk for the next generations with metabolic compromise already apparent at birth. The risks of developing adulthood obesity, hypertension, diabetes and metabolic syndromes are engineered in fetal life. The financial implications of obesity results in the rise in the health-care cost by 23% among overweight women and 37% among obese women after adjusting for maternal age, parity, ethnicity and co-morbidity, when compared with women with normal weight [4]. The present review is aimed at providing a comprehensive view on placental dysfunction in obese women and the need for antenatal surveillance strategies.
Section snippets
Molecular basis of placental dysfunction in obesity
In pregnancy, the feto-placental unit is a major site of protein and steroid hormone production and secretion, which results in metabolic changes. During in utero development, the fetus relies primarily on glucose as an energy substrate. There is a steady supply of glucose even during maternal fasting by increased hepatic gluconeogenesis in normal pregnancy. During early pregnancy, glucose tolerance is normal as insulin sensitivity and hepatic basal glucose production are normal [5], [6]. In
Clinical impact of placental dysfunction in obesity
Overweight and obese women are at a high risk of immediate and late maternal and fetal complications [28]. Studies show that obese women have a higher prevalence of infertility, recurrent miscarriage and congenital malformations [29], [30]. Pre-pregnancy obesity is a risk factor for gestational diabetes, pre-eclampsia, labour induction and caesarean section *[31], [32], *[33]. Post-delivery maternal complications include low breastfeeding rates [34], caesarean wound infection [33],
Maternal weight gain and fetal growth velocity
Fetal growth velocity depends upon genetic factors and the maternal environment. The maternal environment is reflected by signals transmitted by the placenta including nutrient transfer, blood hormone or oxygen levels. The fetus uses this information to make immediate survival choices and to make longer-term adjustments to maximize its advantage after birth [45]. The amount of weight gained during pregnancy affects the immediate and future health of a woman and her infant. The normal pattern of
Preconception care
Counselling and proper dietary advice are vital for obese mothers as evidence suggests that women's actual weight gain in pregnancy is strongly correlated with health-care provider advice [61]. Women should receive advice and information on interventions to achieve normal weight and be encouraged to undertake a weight-reduction programme [62]. Women should have the opportunity to optimize their weight before pregnancy. Other co-morbidities such as hypertension and diabetes should be treated
Role of metformin in non-GDM pregnant obese women and its effects on placenta
Metformin is an effective oral biguanide insulin sensitizer widely used for treating type 2 diabetes mellitus. It improves tissue sensitivity to insulin while inhibiting hepatic glucose production, enhancing peripheral glucose uptake, and decreasing insulin levels. Increasing obesity is associated with greater insulin resistance. As discussed earlier, inflammation is a central feature of the insulin resistance syndrome in obesity. Metformin has anti-inflammatory actions along with an increase
Conclusion
Maternal obesity poses a challenge in modern obstetrics. It is associated with various short-term and long-term feto-maternal complications. Obesity-induced insulin resistance, hyperglycaemia and inflammatory response causing epigenetic modifications are at the centre of the pathogenesis of fetal endocrine and metabolic changes. Maternal obesity, gestational weight gain and gestational diabetes are independently associated with adverse feto-maternal outcome. Antenatal surveillance; counselling
Conflict of interest
None.
References (114)
- et al.
National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants
The Lancet
(2011) - et al.
Expansion of beta-cell mass in response to pregnancy
Trends Endocrinol Metab
(2010) - et al.
Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta
Placenta
(2008) - et al.
Regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein 1 in follicular fluid accumulate differentially in patients with and without endometriosis undergoing in vitro fertilization
Fertil Steril
(2006) - et al.
A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways
J Biol Chem
(2007) - et al.
Oxidative stress and maternal obesity: feto-placental unit interaction
Placenta
(2014) Markers of endothelial cell dysfunction are increased in human omental adipose tissue from women with pre-existing maternal obesity and gestational diabetes
Metabolism
(2014)- et al.
Maternal obesity is associated with a lipotoxic placental environment
Placenta
(2014) - et al.
Pre-pregnancy body mass index and pregnancy outcomes
Int J Gynaecol Obstet
(2006) Effects of gestational weight gain and body mass index on obstetric outcome in Sweden
Int J Gynaecol Obstet
(2006)
Maternal obesity and risk of stillbirth: a metaanalysis
Am J Obstet Gynecol
Fetal programming of coronary heart disease
TTrends Endocrinol Metab
Maternal obesity and risk of neural tube defects: a metaanalysis
Am J Obstet Gynecol
Associations between gestational weight gain and BMI, abdominal adiposity, and traditional measures of cardiometabolic risk in mothers 8 y postpartum
Am J Clin Nutr
Pregnancy outcome and weight gain recommendations for the morbidly obese woman
Obstet Gynecol
Medically advised, mother's personal target, and actual weight gain during pregnancy
Obstet Gynecol
Error in blood-pressure measurement due to incorrect cuff size in obese patients
Lancet
Obesity in pregnancy
J Obstet Gynaecol Can
Normal birth following PGD for reciprocal translocation after serial vitrification of oocytes from a poor responder: a case report
Reproductive Biomedicine Online
Maternal obesity and venous thromboembolism
Int J Obstet Anesth
Metformin vs insulin in the management of gestational diabetes: a systematic review and meta-analysis
Diabetes Res Clin Pract
Efficacy and safety of metformin during pregnancy in women with gestational diabetes mellitus or polycystic ovary syndrome: a systematic review
Metabolism
Oral hypoglycaemic agents during pregnancy: the evidence for effectiveness and safety
Best Pract Res Clin Obstet Gynaecol
Human placental glucose uptake and transport are not altered by the oral antihyperglycemic agent metformin
Am J Obstet Gynecol
The global epidemic of obesity: an overview
Epidemiol Rev
Body mass index and percent body fat: a meta analysis among different ethnic groups
Int J Obes Relat Metab Disord
Obesity in pregnancy: a retrospective prevalence-based study on health service utilisation and costs on the NHS
BMJ Open
Fetuses of obese mothers develop insulin resistance in utero
Diabetes Care
The short- and long-term implications of maternal obesity on the mother and her offspring
BJOG
Etiology and pathogenesis of gestational diabetes
Diabetes Care
Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study: associations with maternal body mass index
BJOG
The hyperglycemia and adverse pregnancy outcome study: associations of GDM and obesity with pregnancy outcomes
Diabetes Care
Inflammation in obesity is the common link between defects in fatty acid metabolism and insulin resistance
Cell Cycle
Obesity and the role of adipose tissue in inflammation and metabolism
Am J Clin Nutr
IKK-beta links inflammation to obesity-induced insulin resistance
Nat Med
Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity
Am J Physiol Endocrinol Metab
Pregravid obesity associates with increased maternal endotoxemia and metabolic inflammation
Obesity (Silver Spring)
Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects
Diabetes
Fatty acid-induced induction of Toll-like receptor-4/nuclear factor-kappaB pathway in adipocytes links nutritional signalling with innate immunity
Immunology
Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta
Science
The association of body mass index with serum angiogenic markers in normal and abnormal pregnancies
Am J Obstet Gynecol
Maternal obesity and its effect on placental cell turnover
J Matern Fetal Neonatal Med
Fetal muscle development, mesenchymal multipotent cell differentiation, and associated signaling pathways
J Anim Sci
The risk of adverse pregnancy outcomes in women who are overweight or obese
BMC Pregnancy and Childbirth
Maternal and fetal risk factors for stillbirth: population based study
BMJ
Does obesity increase the risk of miscarriage in spontaneous conception: a systematic review
Semin Reprod Med
Effect of prepregnancy maternal overweight and obesity on pregnancy outcome
Obstet Gynecol
Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London
Int J Obes Relat Metab Disord
Weight development over time in parous women – the SPAWN study – 15 years follow-up
Int J Obes Relat Metab Disord
Pre-pregnancy weight and the risk of stillbirth and neonatal death
BJOG
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