In utero exposure to maternal obesity and diabetes: animal models that identify and characterize implications for future health

The developed and developing worlds are experiencing an epidemic of obesity and associated predisposition to diabetes. This epidemic places a major drain on health care resources. It is now clear that maternal obesity and gestational diabetes have major adverse effects on the developing fetus that lead to increased neonatal morbidity and mortality, as discussed elsewhere in this issue. Obesity in pregnancy and gestational diabetes represent a special problem, not only as a result of their immediate adverse effects on maternal health and pregnancy outcome, but also because of growing evidence for their persistent and deleterious effects on the developing child.     

Diabetes and obesity in pregnancy

An epidemic of obesity is affecting growing numbers of women in their childbearing years increasing their risk of obstetric complications including diabetes, hypertension, pre-eclampsia, some malformations, macrosomia and the need for obstetric intervention. There is growing evidence that maternal obesity may increase the risk of obesity and diabetes in the offspring. Obesity and diabetes in pregnancy have independent and additive effects on obstetric complications, and both require management during pregnancy. Management of obesity including weight loss and physical activity prior to pregnancy is likely to be beneficial for mother and baby, although the benefits of bariatric surgery remain unclear at this time. Limiting gestational weight gain to 5-9 kg among pregnant obese women is likely to improve obstetric outcomes, but how to achieve this remains an active area of research. If gestational diabetes develops, there is good evidence that clinical management reduces the risk of adverse pregnancy outcomes.     

Obesity and diabetes: A recipe for obstetric complications

The prevalence of obesity has been increasing worldwide and has reached epidemic proportions in the United States, where well over 20% of the population have a body mass index (BMI) within the obese range. Obesity is associated with a wide spectrum of obstetric and perinatal complications, including increased risks of fetal mortality and morbidity, congenital malformations, maternal hypertensive disorders, gestational diabetes, excessive fetal growth and cesarean delivery. The odds ratios for these risks increase in direct correlation with the severity of obesity, and are significant even among women who are overweight without meeting criteria for obesity. Although obesity is closely associated with diabetes which, in itself, is associated with similar perinatal complications, diabetes and obesity are independent risk factors for adverse pregnancy outcome. Moreover, improving glycemic control in the pregnant woman with diabetes may mitigate the additive adverse effects of diabetes and obesity on pregnancy outcome.     

Obesity and diabetes: A recipe for obstetric complications.

The prevalence of obesity has been increasing worldwide and has reached epidemic proportions in the United States, where well over 20% of the population have a body mass index (BMI) within the obese range. Obesity is associated with a wide spectrum of obstetric and perinatal complications, including increased risks of fetal mortality and morbidity, congenital malformations, maternal hypertensive disorders, gestational diabetes, excessive fetal growth and cesarean delivery. The odds ratios for these risks increase in direct correlation with the severity of obesity, and are significant even among women who are overweight without meeting criteria for obesity. Although obesity is closely associated with diabetes which, in itself, is associated with similar perinatal complications, diabetes and obesity are independent risk factors for adverse pregnancy outcome. Moreover, improving glycemic control in the pregnant woman with diabetes may mitigate the additive adverse effects of diabetes and obesity on pregnancy outcome.     

The implications of obesity on pregnancy

Obesity is a modern day epidemic. The incidence appears to be rapidly increasing in both developed and developing countries and has become much more obvious in the last decade. It is regarded as one of the major risk factors in pregnant women and has particularly gained recognition in obstetric practice due to its potentially adverse effects on pregnancy and the fetus.There is evidence to show that obesity in pregnancy contributes to increased morbidity and mortality in both mother and baby. It is associated with adverse outcomes such as preeclampsia, gestational diabetes, thromboembolism, fetal abnormalities and large for gestational infants. According to the Confidential Enquiries into Maternal Deaths in the United Kingdom, 35% of the women who died had a BMI of 30 or more. All these issues highlight the immense importance in treating women with obesity in maternity practice accordingly.     

Maternal obesity: implications for pregnancy outcome and long-term risks-a link to maternal nutrition

As obesity becomes a worldwide epidemic, its prevalence during reproductive age is also increased. Alarming reports state that two-thirds of adults in the USA are overweight or obese, with half of them in the latter category, and the rate of obese pregnant women is estimated at 18-38%. These women are of major concern to women's health providers because they encounter numerous pregnancy-related complications. Obesity-related reproductive health complications range from infertility to a wide spectrum of diseases such as hypertensive disorders, coagulopathies, gestational diabetes mellitus, respiratory complications, and fetal complications such as large-for-gestational-age infants, congenital malformations, stillbirth, and shoulder dystocia. Recent reports suggest that obesity during pregnancy can be a risk factor for developing obesity, diabetes, and cardiovascular diseases in the newborn later in life. This review will address the implication of obesity on pregnancy and child health, and explore recent literature on obesity during pregnancy.     

Maternal obesity and pregnancy outcome

The increasing prevalence of maternal obesity worldwide provides a major challenge to obstetric practice from preconception to postpartum. Maternal obesity can result in unfavorable outcomes for the woman and fetus. Maternal risks during pregnancy include gestational diabetes and chronic hypertension leading to preeclampsia. The fetus is at risk for stillbirth and congenital anomalies. Intrapartum care, normal and operative deliveries, anesthetic and operative interventions in the obese demand extra care. Obesity in pregnancy can also affect health later in life for both mother and child. For women, these risks include heart disease and hypertension. Children have a risk of future obesity and heart disease. Women and their offspring are at increased risk for diabetes. Obstetrician-gynecologists should be well informed to prevent and treat this epidemic. Interventions directed at weight loss and prevention of excessive weight gain during pregnancy must begin in the preconception period.     

Review: Placental transport and metabolism of energy substrates in maternal obesity and diabetes

Maternal obesity is growing in prevalence and is associated with increased morbidity and mortality for both mother and child. Women who are obese during pregnancy have a greater risk of metabolic complications such as gestational diabetes mellitus (GDM) as well as type 2 diabetes after pregnancy. Children of obese and/or GDM mothers have an increased susceptibility to congenital abnormalities and a range of cardio-metabolic disorders. The placenta is at the interface of the maternal and fetal environments and, its function per se, plays a major role in dictating the impact of maternal health on fetal development. Here, we review the literature on how placental function is affected in pregnancies complicated by obesity, and pre-gestational and gestational diabetes. The focus is on the availability of three key substrates in these conditions: glucose, lipids, and amino acids, and their impact on placental metabolic activity. Maternal obesity and diabetes are not always associated with fetal compromise and the adaptation of the placenta may partially determine the outcome. Understanding the differences in metabolic adaptation may open avenues for therapeutic development.     

Maternal obesity and pregnancy outcomes

PURPOSE OF REVIEW: The rates of obesity are increasing rapidly in the United States and other countries. Because obesity is a major factor in the development of many chronic diseases, it is an important individual and public health issue. This review focuses on the pregnancy complications associated with maternal obesity. RECENT FINDINGS: Maternal obesity adversely impacts pregnancy outcome primarily through increased rates of hypertensive disease (chronic hypertension and pre-eclampsia), diabetes (pregestational and gestational), cesarean section and infections. It is associated with a higher rate of venous thromboembolic disease and respiratory complications, and may be an independent risk factor for neural tube defects, fetal mortality and preterm delivery. Maternal obesity also increases the risk of delivering a large for gestational age or macrosomic neonate, who is in turn at an increased risk of subsequent childhood obesity and its associated morbidity. SUMMARY: Recommendations regarding the counselling of obese pregnant women and specific guidelines for the obstetrician, family physician, or midwife managing the pregnancy are presented. Cultural and political changes with the potential to decrease the epidemic of obesity in our society are discussed.     

Maternal obesity and complications during pregnancy

Obesity has become a major health problem all over the world and during pregnancy is associated with an increased risk of complications, including gestational diabetes, preeclampsia, and delivery complications such as macrosomia, shoulder dystocia and higher rates of cesarean sections and infections. Maternal obesity may also be an independent risk factor for neural tube defects and fetal mortality. This review focuses on the consequences of maternal obesity during pregnancy.     

Effects of obesity on pregnancy

OBJECTIVES: To examine physiologic and psychological outcomes associated with maternal obesity in pregnancy and patterns of pregnancy weight gain. To identify effective interventions for maternal obesity. DATA SOURCES AND STUDY SELECTION: Search of obesity and pregnancy research conducted over the past 10 years using CIHAHL, Medline ERIC, and PyscInfo databases. Studies including the following keywords were included in the review: obesity, weight gain, body image, pregnancy weight gain, pregnancy obesity complications, preeclampsia and gestational diabetes. Articles were included based on scientific merit and research outcomes. DATA SYNTHESIS AND CONCLUSIONS: Maternal obesity is a serious condition that significantly impacts not only mothers' health but also the health and future of their children. It is paramount that all levels of health care providers be aware of consequences of obesity and be knowledgeable of effective interventions. No effective long-term interventions have been demonstrated to prevent or control obesity during pregnancy. The paucity of published results of pregnancy and postpartum interventions to address weight gain in pregnancy suggests the need for more community and individualized based intervention studies, especially focusing on long-term effects.     

Pregnancy after bariatric surgery: a narrative literature review and discussion of impact on pregnancy management and outcome

Bariatric surgery (BS) is regarded to be the most effective treatment of obesity with long lasting beneficial effects including weight loss and improvement of metabolic disorders. A considerable number of women undergoing BS are at childbearing age.Although the surgery mediated weight loss has a positive effect on pregnancy outcome, the procedures might be associated with adverse outcomes as well, for example micronutrient deficiencies, iron or B12 deficiency anemia, dumping syndrome, surgical complications such as internal hernias, and small for gestational age (SGA) offspring, possibly due to maternal undernutrition. Also, there is no international consensus concerning the ideal time to conception after BS. Hence, the present narrative review intents to summarize the available literature concerning the most common challenges which arise before and during pregnancy after BS, such as fertility related considerations, vitamin and nutritional deficiencies and their adequate compensation through supplementation, altered glucose metabolism and its implications for gestational diabetes screening, the symptoms and treatment of dumping syndrome, surgical complications and the impact of BS on pregnancy outcome. The impact of different bariatric procedures on pregnancy and fetal outcome will also be discussed, as well as general considerations concerning the monitoring and management of pregnancies after BS.Whereas BS leads to the mitigation of many obesity-related pregnancy complications, such as gestational diabetes mellitus (GDM), pregnancy induced hypertension and fetal macrosomia; those procedures pose new risks which might lead to adverse outcomes for mothers and offspring, for example nutritional deficiencies, anemia, altered maternal glucose metabolism and small for gestational age children.     

Adipositas und Schwangerschaft

Obesity is a major worldwide health problem. The rate of obese women of fertile age is rising continuously. An end to this trend is not in sight. In fact, the direct and indirect associations of obesity and adverse pregnancy outcomes such as gestational diabetes, hypertension in pregnancy, thromboembolism, preterm birth and an increased rate of fetal malformations have been proven in hundreds of studies. Moreover birth itself may be significantly more frequently complicated by severe complications such as shoulder dystocia, prolonged labour, tears and lacerations and is associated with higher rates of caesarean sections. Nevertheless extreme obesity represents an extreme socio-economic burden by an estimated fivefold increase of pregnancy-associated health care costs. Long-term effects such as early onset juvenile diabetes in the offspring of obese mothers seem to be generally underestimated so far. Obstetricians and gynaecologists appear to be one key to address preventive measures (i.e. diet counselling, health programmes) in obese mothers and their families.     

Determinants of Birth-weight in Women with Established and Gestational Diabetes

Summary: Increased birth-weight (macrosomia) can complicate the diabetic pregnancy, but many factors other than hyperglycaemia can influence birth-weight, in particular maternal obesity. In a mixed population (European, Maori and Pacific Islander) with a high prevalence of glucose intolerance and obesity we have examined the relative impact of various maternal factors on birth-weight in women with both established and gestational diabetes. Mean birth-weight was significantly greater in women with established or gestational diabetes than in controls (p < 0.0001), but was similar in women with gestational and established diabetes, despite glycaemic control being significantly poorer (p < 0.0001) in the latter. Birth-weight closely paralleled prepregnancy body mass index rather than glycaemic control, but in Maori women it was lower than expected, probably because of their high prevalence of smoking. Daily cigarette consumption was negatively correlated with birth-weight (p<0.01) despite the smokers having significantly poorer glycaemic control (p<0.001). The most significant variables influencing birth-weight in the diabetic pregnancy were gestational age at delivery, prepregnancy body mass index, maternal height, estimated weight gain during pregnancy, the presence of hypertension and cigarette smoking (the latter 2 having negative effects on birth-weight). Glycaemic control in the last half of pregnancy was not significant in this analysis. We conclude that within the limits of glycaemic control which we obtained, birth-weight was largely determined by maternal factors other than hyperglycaemia. Birth-weight thus has severe limitations as an outcome measure of the diabetic pregnancy.     

Gestational diabetes mellitus in women in the fourth decade--is treatment worthwhile?

AIM: To examine the influence of diet-treated gestational diabetes mellitus on the obstetric performance of mothers aged 40 and above. METHOD: We reviewed the delivery records of 205 mothers aged 40 and above who delivered over a 3-year period. A 75-gram oral glucose tolerance test was performed in all cases and 64 (31.2%) (18 primiparas and 46 multiparas) had gestational diabetes mellitus. This affected group of patients was compared with a group of age- and parity-matched controls to determine the impact of gestational diabetes mellitus on the obstetric outcome. RESULTS: There was no difference in the maternal anthropometric parameters, antenatal complications, or labor performance. While no statistically significant difference was found in the infant anthropometric parameters, the study group had a lower incidence (p = 0.043) of large-for-gestational age infants. CONCLUSION: Our findings suggested the adverse effects of gestational diabetes mellitus on pregnancy outcome were confounded to a large extent by other factors such as age, parity, and obesity. Once compared with matched controls, gestational diabetes mellitus that can be successfully treated with diet therapy probably had minimal adverse effect on the obstetric outcome. Furthermore, diet treatment can probably reverse the effect of advanced maternal age on infant size in these women.     

Diabetic nephropathy: pregnancy performance and fetomaternal outcome

A study of 31 continuing pregnancies complicated by diabetic nephropathy was conducted to determine the effects of diabetes-associated renal disease on maternal health and fetal outcome. Throughout pregnancy there was a significant increase in maternal blood pressure (p less than 0.001) and proteinuria (p less than 0.0001), with nephrotic syndrome (greater than 3.0 gm protein/day) developing in 71% of pregnancies. After birth, however, proteinuria reverted to levels not significantly different from values in early pregnancy. There was no apparent adverse effect of pregnancy on the natural course of the underlying renal disease. Stillbirths occurred in two patients (6%), and the remaining 29 pregnancies resulted in live-births at a mean gestational age of 36 weeks. Seventy percent of these infants were appropriate for gestational age, whereas 16% were small and 13% were large for gestational age. Birth weight was best correlated with gestational age and creatinine clearance (p less than 0.0001). Neonatal complications included respiratory distress syndrome (19%), hyperbilirubinemia (26), and congenital malformations (10%). The uncorrected perinatal survival rate was 94%. These data suggest that with contemporary methods of maternal evaluation and treatment, fetal surveillance, and neonatal care, the risks to patients with diabetic nephropathy during pregnancy are not excessive. The likelihood of a successful fetal and neonatal outcome is comparable to that in other patients with insulin-dependent diabetes.     

Obesity and the placenta: A consideration of nutrient exchange mechanisms in relation to aberrant fetal growth

The obesity epidemic, including childhood obesity, is rapidly gaining strength as one of the most significant challenges to the health of the global community in the 21st Century. The proportion of women who are obese at the beginning of pregnancy is also increasing. These women and their babies are at high risk of pregnancy complications, and of programming for metabolic disease in adult life. In particular, maternal obesity is associated with aberrant fetal growth, encompassing both growth restricted and large for gestational age, or macrosomic fetuses. This article considers the potential effect of obesity and adipose tissue on placental nutrient exchange mechanisms in relation to aberrant fetal growth. The review emphasizes the dearth of work on this topic to date despite its importance to current and future healthcare of the population.     

Gestational diabetes: the forerunner for the development of maternal and childhood obesity and metabolic syndrome?

OBJECTIVE: To examine the risk of obesity and metabolic syndrome in women with a history of gestational diabetes mellitus and in offspring born to mothers with gestational diabetes mellitus. METHODS: A review of studies examining the development of obesity, hypertension, metabolic abnormalities, metabolic syndrome, and type II diabetes in mothers with a history of gestational diabetes mellitus and control mothers, and offspring of mothers with a history of gestational diabetes and control mothers. RESULTS: Longitudinal studies demonstrate that women with a prior history of gestational diabetes mellitus and obesity are at significantly greater risk of developing metabolic syndrome than mothers with no history of gestational diabetes or obesity. The development of metabolic syndrome in children with increasing age is related to maternal gestational diabetes mellitus, maternal glycemia in the 3rd trimester, maternal obesity, neonatal macrosomia, and childhood obesity. CONCLUSIONS: The current prevalence of obesity in both adults and children and associated disorders of blood pressure and lipid metabolism, suggest a perpetuating cycle of increasing obesity, insulin resistance, and abnormal lipid metabolism, which has ominous consequences for future generations.     

Common Sleep Disorders: Management Strategies and Pregnancy Outcomes

Sleep disorders, prevalent in industrialized countries, are associated with adverse health outcomes such as hypertension, diabetes, and obesity. Disturbed sleep during pregnancy is frequently overlooked by health care providers, yet recent studies suggest there is an association between sleep disorders and adverse pregnancy outcomes, including preeclampsia, elevated serum glucose, depression, prolonged labor, and cesarean birth. Growing evidence indicates that the recognition and management of prenatal sleep disorders may minimize adverse pregnancy outcomes and improve maternal and fetal well‐being. This focused review of prenatal sleep disturbance literature suggests there are 3 main sleep disorders of interest: breathing‐related sleep disorders (ie, habitual snoring and obstructive sleep apnea), restless legs syndrome, and insomnia. These sleep disorders are common in pregnancy and have maternal and fetal consequences if left untreated. This article describes sleep disorders of pregnancy, elucidates their relationship with maternal and neonatal outcomes, and presents current evidence regarding diagnostic and management strategies.     

Pregnancy: a stress test for life

PURPOSE OF REVIEW: This review describes how the physiological demands of pregnancy act as a maternal stress test that can predict a woman's health in later life. Pregnancy transiently catapults a woman into a metabolic syndrome that predisposes to vascular endothelial dysfunction. Women who are already predisposed to this phenotype develop gestational hypertension or diabetes mellitus, which re-emerge in later life as the metabolic syndrome returns. Pregnancy can also temporarily unmask sub-clinical disease, which may return in later life when the effects of ageing diminish the limited reserves of a vulnerable organ. RECENT FINDINGS: Recent studies have attempted to assess how gestational syndromes affect the risk for a woman of developing a diverse range of diseases in later life. As well as cardiovascular disease and diabetes mellitus, pregnancy can reveal a vulnerability to thyroid and pituitary disorders, liver and renal disease, depression, thrombosis and even cancer. SUMMARY: Although our knowledge of this phenomenon is incomplete, women who have had gestational syndromes, in particular pregnancy-induced hypertension/preeclampsia or gestational diabetes, should make lifestyle changes that will reduce their risk of cardiovascular disease in later life.