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Maternal obesity: Implications for pregnancy outcome and long-term risks–a link to maternal nutrition
International Journal of Gynecology and Obstetrics 115 Suppl. 1 (2011) S6–S10
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International Journal of Gynecology and Obstetrics j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j g o
ARTICLE
Maternal obesity: Implications for pregnancy outcome and long-term risks—a link to maternal nutrition Amir Aviram, Moshe Hod, Yariv Yogev * Department of Obstetrics and Gynecology, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tiqva, Israel
article info
abstract
Keywords: Maternal nutrition Obesity Pregnancy Pregnancy outcomes Weight gain
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. © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Obesity has long been recognized as a global health concern, be it among adults, adolescents, or children, of both sexes. The World Health Organization’s (WHO) reports convey alarming figures regarding this phenomenon, with up to 1.6 billion overweight adults and 400 million obese adults in 2005 [1]. WHO and the National Institutes of Health (NIH) define overweight as a body mass index (BMI) of 25–29.9 and obesity as a BMI of 30 or greater. Obesity is also subcategorized into 3 subgroups: Class I (BMI 30– 34.9), Class II (BMI 35–39.9), and Class III (BMI 40 or greater) [1]. Current predictions assess that by the year 2015, 2.3 billion adults will be overweight and 700 million obese. Results from the United States National Health and Nutrition Examination Survey (NHANES) indicate that 66.3% of adults in the USA are either overweight or obese, with half of them in the latter category. As obesity becomes an ever-growing concern, the number of women of reproductive age who are overweight or obese increases, and the incidence of obesity among pregnant women is now estimated at between 18.5% and 38.3% [2]. Maternal overweight is now a known risk factor that affects the vast continuum of pregnancy. Fertility and fecundity rates are lower among overweight and obese women, in spontaneous conception as well as in artificial reproductive techniques [2]. During pregnancy, these women are more susceptible to pregnancy hypertensive * Corresponding author. Yariv Yogev. Perinatal Division, Department of Obstetrics and Gynecology, Helen Schneider Hospital for Women, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel. Tel.: +972 3 9377400. E-mail address: [email protected] (Y. Yogev).
disorders, gestational diabetes, respiratory complications, and thromboembolic events [2–4]. As delivery approaches, overweight women have a slower labor progression rate, higher rates of cesarean deliveries, and more surgery-related complications such as difficult spinal, epidural, or general anesthesia, wound infection, and endometritis [2–4]. From the fetal and newborn perspective, complications include congenital malformations, largefor-gestational-age (LGA) infants, stillbirth, shoulder dystocia, and adolescent complications such as obesity and diabetes [2–4]. 2. Hypertensive disorders Hypertensive disorders are associated with obesity in the pregnant as well as the nonpregnant state. The risk of pregnancy-induced hypertension or pre-eclampsia is significantly greater if the mother is overweight as assessed by BMI in early pregnancy, with an up to 2–3-fold increased risk for pre-eclampsia with a BMI greater than 30 [5–7]. Epidemiological studies have shown a relationship between pregnancies complicated by pre-eclampsia and an increased risk of maternal coronary heart disease in later life. The reported increase in the relative risk of death from ischemic heart disease in association with a history of pre-eclampsia or eclampsia is approximately 2-fold [8]. 3. Gestational diabetes mellitus The association between obesity, hypertension, and insulin resistance in type 2 diabetes is well recognized. It has been shown that even minor degrees of carbohydrate intolerance are related to obesity and pregnancy outcome [9,10]. Prepregnancy overweight and obesity were associated with adverse pregnancy outcome
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in glucose-tolerant women [9,10]. Several studies demonstrated a 2–10-fold increase in the rate of gestational diabetes mellitus (GDM) among obese patients [11–13]. A study of 6857 women found a direct association between glucose screening categories, obesity, and rate of GDM [14]. For patients with screening results from 130–189 mg/dL, the rate of obesity was approximately 24–30%. Thereafter, this rate increased 2-fold. In contrast, for nonobese women, the rate of GDM increased for each 10 mg increment in glucose screening. These data demonstrate that the rate of obesity and glucose tolerance are both associated with the development of GDM. Additionally, fetal size and cesarean section rate are associated with the degree of carbohydrate intolerance as represented by screening results. Furthermore, obesity remains a significant contributor impacting fetal size [15]. To date, there is scant data on obesity and being overweight in GDM. The few studies reporting obesity in GDM lack information on the effect of achieving targeted levels of glycemic control and treatment modalities on pregnancy outcome [16–18]. Leiken et al. [16] demonstrated an independent risk for macrosomia among obese women with GDM. They determined that GDM had a frequency of macrosomia no different than that of nondiabetic patients. Nonobese women with GDM and fasting hyperglycemia treated with diet and insulin therapy also had a frequency of macrosomia no different than that of nondiabetic women. However, diet and insulin did not prevent excess macrosomia in women who were obese. These studies had small sample sizes, failed to provide information on glycemic control, and only evaluated single outcome variables. Maternal age, parity, and obesity are all over-represented among women with GDM. These variables need to be controlled in a study to draw accurate conclusions that also control confounding effects. Therefore, it is not clear if obesity, level of glycemia, or treatment modality is independently or cumulatively responsible for fetal growth abnormalities. Langer et al. [19] found that obese and overweight GDM patients achieving established levels of glucose control with insulin therapy showed no increased risk for composite outcome, macrosomia, and LGA compared with normal weight GDM patients. In contrast, even when diet-treated obese patients achieved good glycemic control, there was no improvement in pregnancy outcome compared with normal weight patients. Poorly-controlled overweight and obese patients, regardless of treatment modality, had significantly higher rates of composite outcome, metabolic complications, macrosomia, and LGA. Although obesity in and of itself portends potential adverse outcome in pregnancy, women with GDM treated with insulin and possibly oral antidiabetic drugs who achieve targeted levels of glycemic control will have pregnancy outcomes comparable with those of normal weight women. The improved outcome in the insulin-treated overweight and obese women may be due to an unidentified effect of insulin itself on the fetus or activation of other metabolic fuel pathways. A recent study [20] concluded that a rise in BMI was translated into an increased risk for GDM in consecutive pregnancy (OR 1.71 for gaining 1.0–1.9 BMI units, OR 2.46 for gaining 2.0–2.9 BMI units, and OR 3.40 for gaining 3.0 or more BMI units), and that a decrease in BMI was translated into lower risk for GDM in consecutive pregnancy, but only in overweight or obese women (OR 0.26 for losing at least 2.0 BMI units). 4. The impact of maternal weight change on pregnancy outcome The amount of weight gain recommended in pregnancy is controversial. Historically, obstetricians used to restrict weight gain of up to 15 lb (6.8 kg), regardless of race, ethnicity, or prepregnancy weight. In the 1970s a more lax approach to weight gain was
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followed, allowing weight gain of up to 20–27 lb (9.1–12.3 kg). In 1990, the Institute of Medicine (IOM) published new guidelines based on the effects of weight gain on fetal size. The new recommendations were based on prepregnancy BMI: a weight gain of 28–40 lb (12.7–18.2 kg) for a BMI of 19.8 and lower; 25–35 lb (11.4–15.9 kg) for a BMI of 19.9–26; and 15–25 lb (6.8–11.4 kg) for a BMI of 26.1 and greater. The IOM stated that the effect of weight gain on fetal size diminishes as the mother’s prepregnancy BMI increases [21]. This approach considered only immediate fetal outcomes and disregarded long-term maternal and fetal effects. This concept was challenged in the past 2 decades when studies evaluated the association between maternal weight gain, obesity, pregnancy outcome, and future development of diabetes in the mother and the child. Rooney et al. [22] evaluated a cohort of 540 women who had documented weight over a 5-year postpartum period. They concluded that excess weight gain and failure to lose weight after pregnancy are important and identifiable predictors of long-term obesity. Breastfeeding and exercise may be beneficial in controlling long-term weight. Edwards et al. [23] found that obese patients gained an average of 5 kg less during pregnancy and were more likely to lose the weight or not gain weight at all. Obese women who lost or did not gain any weight had lower mean birth weights of infants and higher rates of small-for-gestational-age (SGA) infants compared with obese women who gained 1 lb (0.45 kg) or more. The incidence of macrosomic fetuses increased significantly only in the group that gained 12 kg or more. No weight gain and weight gain up to 11.5 kg was associated with a macrosomia rate of 12.5– 13.3% with a background rate of 10% in nonobese women. Therefore, they recommend weight gains of 15–25 lb (6.8–11.4 kg) for obese women and 25–35 lb (11.4–15.9 kg) for normal weight women to optimize fetal growth. Neonates of obese women who gained less than 6.8 kg were 3 times more likely to be SGA than neonates of obese women who gained at least 6.8 kg [24]. In addition, it has also been reported that obese pregnant women who gained at least 6.8 kg have been associated with increased frequency of macrosomia [25]. Bianco et al. [13] reported that a weight gain of more than 25 lb (11.4 kg) was strongly associated with the birth of LGA infants. However, poor weight gain did not appear to increase the risk of low birth weight infants. In contrast, Ratner et al. [26] found no difference in fetal outcome in obese women when gaining more or less than 10 lb (4.5 kg). They concluded that limited weight gain in morbidly obese women does not adversely affect fetal outcome. Luke et al. [27] reported that for every kilogram of gestational weight gained, birth weight increased by 44.9 g for underweight women, 22.9 g for normal weight women, and 11.9 g for overweight women. For every kilogram of retained weight, birth weight was increased by 35.6 g for underweight women, 15.9 g for normal weight women, and 5.1 g for overweight women. These findings suggest that beyond a certain level of weight gain, there is an increase in birth weight at the expense of increasing maternal postpartum obesity for the woman who has gained an excessive amount of weight during pregnancy. A systematic review published recently examined outcomes of pregnancies according to the IOM 1990 guidelines in terms of birth weight, fetal growth, and postpartum weight retention [28]. A strong correlation between weight gain below IOM recommendations and lower birth weights was demonstrated; however, only moderate correlation between weight gain in excess of IOM recommendations and higher birth weights was found. As expected, evidence suggested that weight gain in excess of IOM recommendations, both total weight gain and weight gain rate, are correlated with higher incidence of weight retention postpartum in the short and long term.
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The IOM issued new guidelines for pregnancy weight gain in 2009, taking into account both maternal and fetal health [29]. For underweight women (BMI < 18.5), a weight gain of 12.5–18 kg at a mean rate of 0.51 kg per week is considered adequate; for normal weight women (BMI 18.5–24.9), 11.5–16 kg at a mean rate of 0.42 kg per week; for overweight women (BMI 25.0–29.9), 7–11.5 kg at a mean rate of 0.28 kg per week; and for obese women (BMI 30 and greater) 5–9 kg with a mean rate of 0.22 kg per week. A recent study examined whether differences exist in infant body composition based on the new IOM guidelines [30]. It was found that infants of obese mothers had a greater percentage of fat compared with infants of normal weight and overweight mothers. Within the excessive weight gain group, infants of normal weight mothers have less fat percentage than infants of obese or overweight mothers. Another study by Vesco et al. [31] found that obese women gaining weight above the new IOM recommendations did not decrease the risk for SGA but increased the risk for delivering LGA or macrosomic infants, and that obese women gaining weight below IOM recommendations had a higher risk for delivering SGA and a lower risk for LGA infants. Bondar et al. [32] demonstrated that the prevalence of excessive gestational weight gain declined, and weight loss increased, as obesity became more severe. Generally, weight loss was associated with an elevated risk of SGA, medically indicated and spontaneous preterm delivery, and high weight gain tended to increase the risk of LGA and medically indicated preterm delivery. Hinkle et al. [33] found that severity of obesity modified associations between gestational weight gain and fetal growth. Compared with weight gains of 5–9 kg, weight loss in Class I obese women significantly increased the odds of SGA, whereas a gestational weight gain of 0.1–4.9 kg was not associated with SGA and did not decrease the odds of macrosomia. In Class II and III women, compared with weight gains of 5–9 kg, a gestational weight gain from −4.9 to 4.9 kg was not associated with SGA but did decrease the odds of macrosomia. In a population-based cohort, Blomberg [34] found that Class III obese women who lost weight during pregnancy had a decreased risk of cesarean delivery (OR 0.77; 95% CI, 0.60–0.99), LGA births (OR 0.64; 95% CI, 0.46–0.90), and no significantly increased risk for pre-eclampsia, excessive bleeding during delivery, instrumental delivery, low Apgar score, or fetal distress compared with Class III obese women gaining weight within the IOM recommendations. There was an increased risk for SGA (OR 2.34; 95% CI, 1.15–4.76) among Class III obese women losing weight, but there was no significantly increased risk of SGA in the same group with low weight gain. Getahun et al. [35] looked at whether BMI changes between 2 consecutive pregnancies were associated with increased risk for LGA in the second pregnancy. They found that overweight or obese women in both pregnancies had an increased risk for LGA infants, and that any decrease in BMI attenuated the risk. They also concluded that 17.1% of LGA infants born to underweight mothers, 13.2% of LGA infants born to normal weight mothers, and 7.6% of LGA infants born to overweight mothers could be prevented if BMI had not increased between pregnancies. Villamor and Cnattingius [36] found that compared with women whose BMI changed between −1.0 and 0.9 units, women who gained 3 or more units had an increased risk of pre-eclampsia, gestational hypertension, GDM, cesarean delivery, stillbirth, and LGA birth [36]. The associations were linearly related to weight change and were also noted in women who had a healthy prepregnancy BMI for both pregnancies. Regarding bariatric surgery, Dell’Agnolo et al. [37] found that women who underwent bariatric surgery had less obesity-related comorbidities such as diabetes mellitus and hypertension, and less pregnancy-related hypertensive disorders, but higher prevalence
of cesarean delivery and postoperative anemia. Their infants were more likely to be appropriate-for-gestational-age (AGA) and be born at term. Sheiner et al. [38] found that bariatric surgery was associated with premature rupture of membranes, labor induction, macrosomia, and obesity. No significant differences were noted regarding pregnancy complications such as placental abruption, labor dystocia, or perinatal complications. A systematic review by Maggard et al. [39] included 75 articles, and concluded that fewer maternal complications occurred following bariatric surgery (such as GDM and pre-eclampsia), and that neonatal outcomes were better than in obese controls. 5. Long-term fetal and neonatal issues Both the Barker [40,41] and fetal insulin hypotheses [42] have proposed that impaired adult cardiovascular health is programmed in utero by poor fetal nutrition, or by genetically determined reduction of insulin-mediated fetal growth, which results in the birth of a small infant. Low birth weight may be a significant variable for the development of the metabolic syndrome in adulthood. Obesity was an independent risk factor in the diabetic populations studied. Therefore, the emphasis today may need to address sedentary lifestyle and issues related to obesity upon fetal programming since undernutrition is now infrequent in highresource societies. Another study [43] reported evidence of a link between maternal obesity and cardiovascular disease in adult offspring, confirming Barker’s hypothesis of higher adult death rates from coronary heart disease in men who were classified as low birth weight. In addition, they observed a positive association between the mother’s BMI upon admission and future death rate from coronary heart disease in male offspring. They concluded that the mother’s obesity may be an independent yet additional contributing factor to infant low birth weight. Fall et al. [44] reported higher adult rates of type 2 diabetes in the offspring of mothers who were above average weight in pregnancy. Therefore, there is an association between maternal (but not paternal) obesity and insulin resistance and the risk for offspring to develop cardiovascular disease in adulthood. In a further study, high maternal weight or BMI accounted for the association between birth weight and adult adiposity [45]. Lawlor et al. [46] found that maternal weight gain (MWG) was associated with offspring BMI. In normal weight women, the positive association between MWG and offspring BMI at age 18 years was driven largely by shared familial risk factors for BMI, whereas in overweight or obese women the correlation seemed to be through shared familial risk factors combined with intrauterine mechanisms. In a review by Bouret [47], it is suggested that maternal obesity and alterations in postnatal nutrition are related, as determined by epidemiological and animal studies, to increased risks of obesity, hypertension, and type 2 diabetes in offspring. Furthermore, several mechanisms may be responsible for the development of such diseases, such as developmental programming of neuroendocrine systems by perinatal environment. As in GDM or pregestational diabetes, maternal obesity can result in fetal growth restriction or macrosomia. Paradoxically, both are related to childhood metabolic syndrome [48]. Cho et al. [49] reported an association between maternal second and third trimester free fatty acid (FFA) concentrations (which increase with maternal obesity) and diastolic blood pressure in the adolescent offspring. The majority of evidence suggests a relationship between low birth weight and adult disease. However, it is reasonable to speculate that overweight infants that are a product of both genetic and environmental factors are programmed in utero for the development of future diabetes, obesity, and metabolic syndrome. Thus, diversity (accelerated and delayed) may
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be a source for adult disease already initiated in intrauterine life. Given that obesity and maternal insulin resistance are not only genetic but also acquired, improvement of periconceptional maternal insulin sensitivity via exercise or diet, and controlling the diabetes throughout pregnancy (improvement in intrauterine environment), may impact not only the mother’s health, but also the future cardiovascular risk for her child. Again, this hypothesis remains speculative and further research is needed to address this issue. 6. Potential management and intervention In obese women, a modification of risk factors prior to or early in pregnancy is recommended. Treatment options during pregnancy using diet, pharmacological, or surgical means are contraindicated. However, increased physical activity in women who are sedentary and healthy food choices rather than fast foods may result in a better pregnancy outcome for both mother and child. A randomized trial of weight-bearing exercise (vs no exercise) from 8 weeks of pregnancy in women who did not normally exercise, resulted in significantly higher birth weights in offspring of women randomized to exercise [50]. In another study, exercise twice a week or less was associated with low birth weight (adjusted odds ratio 2.64; 95% CI, 1.29–5.39) relative to women who exercised 3–4 times per week after adjustment for potential confounders, including social class [51]. Dye et al. [52] demonstrated that women who were obese at the time of conception but exercised regularly had lower rates of GDM. This has since been confirmed by another group. Moderate exercise in pregnancy did not appear to be harmful and there was no association with premature labor or poor Apgar scores [53,54]. 7. Summary Obesity has implications for all aspects of maternal health and outcome during pregnancy. Improved lifestyle changes can mitigate pregnancy complications. Healthcare professionals and social service providers need to actively promote a healthy lifestyle to their patients and clients at every opportunity. Prepregnancy clinics could provide education on healthy diet and exercise regimes similar to those provided for women with diabetes. Improving the health prospects of the mother during pregnancy and the potential risk for developing complications later in life should be the focus of care. A concerted effort by public policy makers and the medical community could also effectively reduce healthcare costs, including those for hospitalization resulting from hypertensive disease, fetal anomalies, fetal assessment, costs associated with the high rate of cesarean delivery, and postpartum complications. Conflict of interest statement The authors report no potential conflicts of interest. References 1. WHO. Obesity: preventing and managing the global epidemic. www.who.int. http://whqlibdoc.who.int/trs/WHO_TRS_894.pdf. Published 2000. 2. Yogev Y, Catalano PM. Pregnancy and obesity. Obstet Gynecol Clin North Am 2009;36(2):285–300. 3. Reece EA. Perspectives on obesity, pregnancy and birth outcomes in the United States: the scope of the problem. Am J Obstet Gynecol 2008;198(1):23–7. 4. Langer O. Management of obesity in GDM: old habits die hard. J Matern Fetal Neonatal Med 2008;21(3):165–71. 5. Sibai BM, Gordon T, Thom E, Caritis SN, Klebanoff M, McNellis D, et al. Risk factors for preeclampsia in healthy nulliparous women: a prospective multicenter study. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Am J Obstet Gynecol 1995;172(2 Pt 1):642–8.
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International Journal of Gynecology and Obstetrics j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j g o
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Maternal obesity: Implications for pregnancy outcome and long-term risks—a link to maternal nutrition Amir Aviram, Moshe Hod, Yariv Yogev * Department of Obstetrics and Gynecology, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tiqva, Israel
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abstract
Keywords: Maternal nutrition Obesity Pregnancy Pregnancy outcomes Weight gain
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. © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Obesity has long been recognized as a global health concern, be it among adults, adolescents, or children, of both sexes. The World Health Organization’s (WHO) reports convey alarming figures regarding this phenomenon, with up to 1.6 billion overweight adults and 400 million obese adults in 2005 [1]. WHO and the National Institutes of Health (NIH) define overweight as a body mass index (BMI) of 25–29.9 and obesity as a BMI of 30 or greater. Obesity is also subcategorized into 3 subgroups: Class I (BMI 30– 34.9), Class II (BMI 35–39.9), and Class III (BMI 40 or greater) [1]. Current predictions assess that by the year 2015, 2.3 billion adults will be overweight and 700 million obese. Results from the United States National Health and Nutrition Examination Survey (NHANES) indicate that 66.3% of adults in the USA are either overweight or obese, with half of them in the latter category. As obesity becomes an ever-growing concern, the number of women of reproductive age who are overweight or obese increases, and the incidence of obesity among pregnant women is now estimated at between 18.5% and 38.3% [2]. Maternal overweight is now a known risk factor that affects the vast continuum of pregnancy. Fertility and fecundity rates are lower among overweight and obese women, in spontaneous conception as well as in artificial reproductive techniques [2]. During pregnancy, these women are more susceptible to pregnancy hypertensive * Corresponding author. Yariv Yogev. Perinatal Division, Department of Obstetrics and Gynecology, Helen Schneider Hospital for Women, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel. Tel.: +972 3 9377400. E-mail address: [email protected] (Y. Yogev).
disorders, gestational diabetes, respiratory complications, and thromboembolic events [2–4]. As delivery approaches, overweight women have a slower labor progression rate, higher rates of cesarean deliveries, and more surgery-related complications such as difficult spinal, epidural, or general anesthesia, wound infection, and endometritis [2–4]. From the fetal and newborn perspective, complications include congenital malformations, largefor-gestational-age (LGA) infants, stillbirth, shoulder dystocia, and adolescent complications such as obesity and diabetes [2–4]. 2. Hypertensive disorders Hypertensive disorders are associated with obesity in the pregnant as well as the nonpregnant state. The risk of pregnancy-induced hypertension or pre-eclampsia is significantly greater if the mother is overweight as assessed by BMI in early pregnancy, with an up to 2–3-fold increased risk for pre-eclampsia with a BMI greater than 30 [5–7]. Epidemiological studies have shown a relationship between pregnancies complicated by pre-eclampsia and an increased risk of maternal coronary heart disease in later life. The reported increase in the relative risk of death from ischemic heart disease in association with a history of pre-eclampsia or eclampsia is approximately 2-fold [8]. 3. Gestational diabetes mellitus The association between obesity, hypertension, and insulin resistance in type 2 diabetes is well recognized. It has been shown that even minor degrees of carbohydrate intolerance are related to obesity and pregnancy outcome [9,10]. Prepregnancy overweight and obesity were associated with adverse pregnancy outcome
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in glucose-tolerant women [9,10]. Several studies demonstrated a 2–10-fold increase in the rate of gestational diabetes mellitus (GDM) among obese patients [11–13]. A study of 6857 women found a direct association between glucose screening categories, obesity, and rate of GDM [14]. For patients with screening results from 130–189 mg/dL, the rate of obesity was approximately 24–30%. Thereafter, this rate increased 2-fold. In contrast, for nonobese women, the rate of GDM increased for each 10 mg increment in glucose screening. These data demonstrate that the rate of obesity and glucose tolerance are both associated with the development of GDM. Additionally, fetal size and cesarean section rate are associated with the degree of carbohydrate intolerance as represented by screening results. Furthermore, obesity remains a significant contributor impacting fetal size [15]. To date, there is scant data on obesity and being overweight in GDM. The few studies reporting obesity in GDM lack information on the effect of achieving targeted levels of glycemic control and treatment modalities on pregnancy outcome [16–18]. Leiken et al. [16] demonstrated an independent risk for macrosomia among obese women with GDM. They determined that GDM had a frequency of macrosomia no different than that of nondiabetic patients. Nonobese women with GDM and fasting hyperglycemia treated with diet and insulin therapy also had a frequency of macrosomia no different than that of nondiabetic women. However, diet and insulin did not prevent excess macrosomia in women who were obese. These studies had small sample sizes, failed to provide information on glycemic control, and only evaluated single outcome variables. Maternal age, parity, and obesity are all over-represented among women with GDM. These variables need to be controlled in a study to draw accurate conclusions that also control confounding effects. Therefore, it is not clear if obesity, level of glycemia, or treatment modality is independently or cumulatively responsible for fetal growth abnormalities. Langer et al. [19] found that obese and overweight GDM patients achieving established levels of glucose control with insulin therapy showed no increased risk for composite outcome, macrosomia, and LGA compared with normal weight GDM patients. In contrast, even when diet-treated obese patients achieved good glycemic control, there was no improvement in pregnancy outcome compared with normal weight patients. Poorly-controlled overweight and obese patients, regardless of treatment modality, had significantly higher rates of composite outcome, metabolic complications, macrosomia, and LGA. Although obesity in and of itself portends potential adverse outcome in pregnancy, women with GDM treated with insulin and possibly oral antidiabetic drugs who achieve targeted levels of glycemic control will have pregnancy outcomes comparable with those of normal weight women. The improved outcome in the insulin-treated overweight and obese women may be due to an unidentified effect of insulin itself on the fetus or activation of other metabolic fuel pathways. A recent study [20] concluded that a rise in BMI was translated into an increased risk for GDM in consecutive pregnancy (OR 1.71 for gaining 1.0–1.9 BMI units, OR 2.46 for gaining 2.0–2.9 BMI units, and OR 3.40 for gaining 3.0 or more BMI units), and that a decrease in BMI was translated into lower risk for GDM in consecutive pregnancy, but only in overweight or obese women (OR 0.26 for losing at least 2.0 BMI units). 4. The impact of maternal weight change on pregnancy outcome The amount of weight gain recommended in pregnancy is controversial. Historically, obstetricians used to restrict weight gain of up to 15 lb (6.8 kg), regardless of race, ethnicity, or prepregnancy weight. In the 1970s a more lax approach to weight gain was
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followed, allowing weight gain of up to 20–27 lb (9.1–12.3 kg). In 1990, the Institute of Medicine (IOM) published new guidelines based on the effects of weight gain on fetal size. The new recommendations were based on prepregnancy BMI: a weight gain of 28–40 lb (12.7–18.2 kg) for a BMI of 19.8 and lower; 25–35 lb (11.4–15.9 kg) for a BMI of 19.9–26; and 15–25 lb (6.8–11.4 kg) for a BMI of 26.1 and greater. The IOM stated that the effect of weight gain on fetal size diminishes as the mother’s prepregnancy BMI increases [21]. This approach considered only immediate fetal outcomes and disregarded long-term maternal and fetal effects. This concept was challenged in the past 2 decades when studies evaluated the association between maternal weight gain, obesity, pregnancy outcome, and future development of diabetes in the mother and the child. Rooney et al. [22] evaluated a cohort of 540 women who had documented weight over a 5-year postpartum period. They concluded that excess weight gain and failure to lose weight after pregnancy are important and identifiable predictors of long-term obesity. Breastfeeding and exercise may be beneficial in controlling long-term weight. Edwards et al. [23] found that obese patients gained an average of 5 kg less during pregnancy and were more likely to lose the weight or not gain weight at all. Obese women who lost or did not gain any weight had lower mean birth weights of infants and higher rates of small-for-gestational-age (SGA) infants compared with obese women who gained 1 lb (0.45 kg) or more. The incidence of macrosomic fetuses increased significantly only in the group that gained 12 kg or more. No weight gain and weight gain up to 11.5 kg was associated with a macrosomia rate of 12.5– 13.3% with a background rate of 10% in nonobese women. Therefore, they recommend weight gains of 15–25 lb (6.8–11.4 kg) for obese women and 25–35 lb (11.4–15.9 kg) for normal weight women to optimize fetal growth. Neonates of obese women who gained less than 6.8 kg were 3 times more likely to be SGA than neonates of obese women who gained at least 6.8 kg [24]. In addition, it has also been reported that obese pregnant women who gained at least 6.8 kg have been associated with increased frequency of macrosomia [25]. Bianco et al. [13] reported that a weight gain of more than 25 lb (11.4 kg) was strongly associated with the birth of LGA infants. However, poor weight gain did not appear to increase the risk of low birth weight infants. In contrast, Ratner et al. [26] found no difference in fetal outcome in obese women when gaining more or less than 10 lb (4.5 kg). They concluded that limited weight gain in morbidly obese women does not adversely affect fetal outcome. Luke et al. [27] reported that for every kilogram of gestational weight gained, birth weight increased by 44.9 g for underweight women, 22.9 g for normal weight women, and 11.9 g for overweight women. For every kilogram of retained weight, birth weight was increased by 35.6 g for underweight women, 15.9 g for normal weight women, and 5.1 g for overweight women. These findings suggest that beyond a certain level of weight gain, there is an increase in birth weight at the expense of increasing maternal postpartum obesity for the woman who has gained an excessive amount of weight during pregnancy. A systematic review published recently examined outcomes of pregnancies according to the IOM 1990 guidelines in terms of birth weight, fetal growth, and postpartum weight retention [28]. A strong correlation between weight gain below IOM recommendations and lower birth weights was demonstrated; however, only moderate correlation between weight gain in excess of IOM recommendations and higher birth weights was found. As expected, evidence suggested that weight gain in excess of IOM recommendations, both total weight gain and weight gain rate, are correlated with higher incidence of weight retention postpartum in the short and long term.
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The IOM issued new guidelines for pregnancy weight gain in 2009, taking into account both maternal and fetal health [29]. For underweight women (BMI < 18.5), a weight gain of 12.5–18 kg at a mean rate of 0.51 kg per week is considered adequate; for normal weight women (BMI 18.5–24.9), 11.5–16 kg at a mean rate of 0.42 kg per week; for overweight women (BMI 25.0–29.9), 7–11.5 kg at a mean rate of 0.28 kg per week; and for obese women (BMI 30 and greater) 5–9 kg with a mean rate of 0.22 kg per week. A recent study examined whether differences exist in infant body composition based on the new IOM guidelines [30]. It was found that infants of obese mothers had a greater percentage of fat compared with infants of normal weight and overweight mothers. Within the excessive weight gain group, infants of normal weight mothers have less fat percentage than infants of obese or overweight mothers. Another study by Vesco et al. [31] found that obese women gaining weight above the new IOM recommendations did not decrease the risk for SGA but increased the risk for delivering LGA or macrosomic infants, and that obese women gaining weight below IOM recommendations had a higher risk for delivering SGA and a lower risk for LGA infants. Bondar et al. [32] demonstrated that the prevalence of excessive gestational weight gain declined, and weight loss increased, as obesity became more severe. Generally, weight loss was associated with an elevated risk of SGA, medically indicated and spontaneous preterm delivery, and high weight gain tended to increase the risk of LGA and medically indicated preterm delivery. Hinkle et al. [33] found that severity of obesity modified associations between gestational weight gain and fetal growth. Compared with weight gains of 5–9 kg, weight loss in Class I obese women significantly increased the odds of SGA, whereas a gestational weight gain of 0.1–4.9 kg was not associated with SGA and did not decrease the odds of macrosomia. In Class II and III women, compared with weight gains of 5–9 kg, a gestational weight gain from −4.9 to 4.9 kg was not associated with SGA but did decrease the odds of macrosomia. In a population-based cohort, Blomberg [34] found that Class III obese women who lost weight during pregnancy had a decreased risk of cesarean delivery (OR 0.77; 95% CI, 0.60–0.99), LGA births (OR 0.64; 95% CI, 0.46–0.90), and no significantly increased risk for pre-eclampsia, excessive bleeding during delivery, instrumental delivery, low Apgar score, or fetal distress compared with Class III obese women gaining weight within the IOM recommendations. There was an increased risk for SGA (OR 2.34; 95% CI, 1.15–4.76) among Class III obese women losing weight, but there was no significantly increased risk of SGA in the same group with low weight gain. Getahun et al. [35] looked at whether BMI changes between 2 consecutive pregnancies were associated with increased risk for LGA in the second pregnancy. They found that overweight or obese women in both pregnancies had an increased risk for LGA infants, and that any decrease in BMI attenuated the risk. They also concluded that 17.1% of LGA infants born to underweight mothers, 13.2% of LGA infants born to normal weight mothers, and 7.6% of LGA infants born to overweight mothers could be prevented if BMI had not increased between pregnancies. Villamor and Cnattingius [36] found that compared with women whose BMI changed between −1.0 and 0.9 units, women who gained 3 or more units had an increased risk of pre-eclampsia, gestational hypertension, GDM, cesarean delivery, stillbirth, and LGA birth [36]. The associations were linearly related to weight change and were also noted in women who had a healthy prepregnancy BMI for both pregnancies. Regarding bariatric surgery, Dell’Agnolo et al. [37] found that women who underwent bariatric surgery had less obesity-related comorbidities such as diabetes mellitus and hypertension, and less pregnancy-related hypertensive disorders, but higher prevalence
of cesarean delivery and postoperative anemia. Their infants were more likely to be appropriate-for-gestational-age (AGA) and be born at term. Sheiner et al. [38] found that bariatric surgery was associated with premature rupture of membranes, labor induction, macrosomia, and obesity. No significant differences were noted regarding pregnancy complications such as placental abruption, labor dystocia, or perinatal complications. A systematic review by Maggard et al. [39] included 75 articles, and concluded that fewer maternal complications occurred following bariatric surgery (such as GDM and pre-eclampsia), and that neonatal outcomes were better than in obese controls. 5. Long-term fetal and neonatal issues Both the Barker [40,41] and fetal insulin hypotheses [42] have proposed that impaired adult cardiovascular health is programmed in utero by poor fetal nutrition, or by genetically determined reduction of insulin-mediated fetal growth, which results in the birth of a small infant. Low birth weight may be a significant variable for the development of the metabolic syndrome in adulthood. Obesity was an independent risk factor in the diabetic populations studied. Therefore, the emphasis today may need to address sedentary lifestyle and issues related to obesity upon fetal programming since undernutrition is now infrequent in highresource societies. Another study [43] reported evidence of a link between maternal obesity and cardiovascular disease in adult offspring, confirming Barker’s hypothesis of higher adult death rates from coronary heart disease in men who were classified as low birth weight. In addition, they observed a positive association between the mother’s BMI upon admission and future death rate from coronary heart disease in male offspring. They concluded that the mother’s obesity may be an independent yet additional contributing factor to infant low birth weight. Fall et al. [44] reported higher adult rates of type 2 diabetes in the offspring of mothers who were above average weight in pregnancy. Therefore, there is an association between maternal (but not paternal) obesity and insulin resistance and the risk for offspring to develop cardiovascular disease in adulthood. In a further study, high maternal weight or BMI accounted for the association between birth weight and adult adiposity [45]. Lawlor et al. [46] found that maternal weight gain (MWG) was associated with offspring BMI. In normal weight women, the positive association between MWG and offspring BMI at age 18 years was driven largely by shared familial risk factors for BMI, whereas in overweight or obese women the correlation seemed to be through shared familial risk factors combined with intrauterine mechanisms. In a review by Bouret [47], it is suggested that maternal obesity and alterations in postnatal nutrition are related, as determined by epidemiological and animal studies, to increased risks of obesity, hypertension, and type 2 diabetes in offspring. Furthermore, several mechanisms may be responsible for the development of such diseases, such as developmental programming of neuroendocrine systems by perinatal environment. As in GDM or pregestational diabetes, maternal obesity can result in fetal growth restriction or macrosomia. Paradoxically, both are related to childhood metabolic syndrome [48]. Cho et al. [49] reported an association between maternal second and third trimester free fatty acid (FFA) concentrations (which increase with maternal obesity) and diastolic blood pressure in the adolescent offspring. The majority of evidence suggests a relationship between low birth weight and adult disease. However, it is reasonable to speculate that overweight infants that are a product of both genetic and environmental factors are programmed in utero for the development of future diabetes, obesity, and metabolic syndrome. Thus, diversity (accelerated and delayed) may
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be a source for adult disease already initiated in intrauterine life. Given that obesity and maternal insulin resistance are not only genetic but also acquired, improvement of periconceptional maternal insulin sensitivity via exercise or diet, and controlling the diabetes throughout pregnancy (improvement in intrauterine environment), may impact not only the mother’s health, but also the future cardiovascular risk for her child. Again, this hypothesis remains speculative and further research is needed to address this issue. 6. Potential management and intervention In obese women, a modification of risk factors prior to or early in pregnancy is recommended. Treatment options during pregnancy using diet, pharmacological, or surgical means are contraindicated. However, increased physical activity in women who are sedentary and healthy food choices rather than fast foods may result in a better pregnancy outcome for both mother and child. A randomized trial of weight-bearing exercise (vs no exercise) from 8 weeks of pregnancy in women who did not normally exercise, resulted in significantly higher birth weights in offspring of women randomized to exercise [50]. In another study, exercise twice a week or less was associated with low birth weight (adjusted odds ratio 2.64; 95% CI, 1.29–5.39) relative to women who exercised 3–4 times per week after adjustment for potential confounders, including social class [51]. Dye et al. [52] demonstrated that women who were obese at the time of conception but exercised regularly had lower rates of GDM. This has since been confirmed by another group. Moderate exercise in pregnancy did not appear to be harmful and there was no association with premature labor or poor Apgar scores [53,54]. 7. Summary Obesity has implications for all aspects of maternal health and outcome during pregnancy. Improved lifestyle changes can mitigate pregnancy complications. Healthcare professionals and social service providers need to actively promote a healthy lifestyle to their patients and clients at every opportunity. Prepregnancy clinics could provide education on healthy diet and exercise regimes similar to those provided for women with diabetes. Improving the health prospects of the mother during pregnancy and the potential risk for developing complications later in life should be the focus of care. A concerted effort by public policy makers and the medical community could also effectively reduce healthcare costs, including those for hospitalization resulting from hypertensive disease, fetal anomalies, fetal assessment, costs associated with the high rate of cesarean delivery, and postpartum complications. Conflict of interest statement The authors report no potential conflicts of interest. References 1. WHO. Obesity: preventing and managing the global epidemic. www.who.int. http://whqlibdoc.who.int/trs/WHO_TRS_894.pdf. Published 2000. 2. Yogev Y, Catalano PM. Pregnancy and obesity. Obstet Gynecol Clin North Am 2009;36(2):285–300. 3. Reece EA. Perspectives on obesity, pregnancy and birth outcomes in the United States: the scope of the problem. Am J Obstet Gynecol 2008;198(1):23–7. 4. Langer O. Management of obesity in GDM: old habits die hard. J Matern Fetal Neonatal Med 2008;21(3):165–71. 5. Sibai BM, Gordon T, Thom E, Caritis SN, Klebanoff M, McNellis D, et al. Risk factors for preeclampsia in healthy nulliparous women: a prospective multicenter study. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Am J Obstet Gynecol 1995;172(2 Pt 1):642–8.
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