Key Abbreviations
Body mass index BMI
Cell-free DNA cfDNA
Centers for Disease Control and Prevention CDC
Centre for Maternal and Child Enquiries CMACE
First-and Second-Trimester Evaluation of Risk Research Consortium FASTER
Gestational diabetes mellitus GDM
Hemolysis, elevated liver enzymes, low platelets syndrome HELLP
High-density lipoprotein HDL
Institute of Medicine IOM
Insulin sensitivity index ISI
Large for gestational age LGA
Low-molecular-weight heparin LMWH
Magnetic resonance imaging MRI
Maternal-Fetal Medicine Unit MFMU
National Health and Nutrition Examination Survey NHANES
Nonalcoholic fatty liver disease NAFLD
Negative pressure wound therapy NPWT
Randomized controlled trial RCT
Royal College of Obstetricians and Gynaecologists RCOG
Single nucleotide polymorphism SNP
Surgical site infection SSI
Trial of labor after cesarean TOLAC
United States Department of Agriculture USDA
Venous thromboembolism VTE
Very-low-density lipoprotein VLDL
World Health Organization WHO
Overview
Obesity in women is such a common problem that the implications relative to pregnancy often are overlooked, or possibly ignored, because of the lack of specific treatments. For example, medical treatment of hypertension or diabetes mellitus involves medications that have relatively rapid onset, and the effects of treatment can be quantitatively monitored. In contrast, the management of obesity—in addition to medical and surgical treatments—requires long-term approaches that include public health and economic initiatives, nutrition, and behavioral modifications. Therefore an understanding of the management of obesity during pregnancy begins prior to conception and continues through the postpartum period; that is, it must be seen from a life-course perspective. Although the care of the obese women during pregnancy requires the involvement of the obstetrician/gynecologist, depending on the comfort level of the provider, other health care professionals can offer specific expertise relative to management.
Prevalence of Obesity in Women of Reproductive Age
Obesity is commonly classified by the body mass index (BMI), which is weight in kilograms divided by height in meters squared (kg/m 2 ) using the World Health Organization (WHO) criteria. Underweight is less than 18.5, normal weight is 18.5 to 24.9, overweight is 25.0 to 29.9; obese class I, is 30.0 to 34.9, obese class II is 35.0 to 39.9, and obese class III is 40 or more. Based on the 2011 to 2012 National Health and Nutrition Examination Survey (NHANES), the prevalence of obesity in women of reproductive age (20 to 39 years) in the United States was 31.8% (95% confidence interval [CI], 28.5 to 35.5), whereas overweight plus obesity was 58.5% (95% CI, 51.4 to 65.2) of that population. The prevalence of overweight and obesity is higher in non-Hispanic black and Mexican women in the United States ( Table 41-1 ). BMI is often used as a measure that correlates with fat mass. In nonpregnant women of reproductive age, BMI explains about 50% to 70% of the variance in fat mass. However, because of the increase in total body water that occurs with advancing gestation, the correlation becomes progressively less robust. Because of racial differences in body composition, the WHO has discussed different cutoff criteria for the classification of obesity in Asian women.
| ALL RACE/ETHNICITY GROUPS | NON-HISPANIC WHITE | NON-HISPANIC BLACK | HISPANIC | MEXICAN AMERICAN |
|---|---|---|---|---|
| 31.9 (28.6-35.5) | 26.9 (23.0-31.3) | 56.2 (44.3-67.5) | 34.4 (30.9-38.2) | 37.8 (33.2-42.7) |
| 55.8 (49.6-61.9) | 50.7 (43.1-58.2) | 74.2 (65.9-81.1) | 65.4 (59.9-70.5) | 68.8 (62.1-74.8) |
Based on Centers for Disease Control and Prevention (CDC) data, no significant change occurred in the prevalence of obesity in women of reproductive age from 2003 through 2004 to 2011 through 2012. From 1999 through 2010, however, obesity (BMI ≥30) in women aged 20 to 39 years appeared to increase, from 28.4% (95% CI, 24.4 to 32.4) to 34.0% (95% CI, 29.0 to 39.1), again with a higher prevalence in non-Hispanic black and Mexican American women. Of greater concern is the increasing prevalence of grade II obesity (17.2%; 95% CI, 14.2 to 20.7) and grade III obesity (7.5%; 95% CI, 5.8 to 9.7) in women aged 20 to 39 years from 2009 through 2010.
Multiple social, environmental, behavioral, and biologic determinants lead to the development of obesity. Major single-gene defects (homozygosity for recessive alleles) account for about 5% of early-onset severe obesity. About 60 single nucleotide polymorphisms (SNPs) have been associated with obesity based on genome-wide significance levels. Although when taken individually, each of these factors may only account for a small proportion of the variance in obesity, when taken together, their combination and interactions explain a far greater proportion of the variance.
Multiple commonly held beliefs are associated with the development of obesity, and many more are associated with prescriptions to achieve weight loss. In the simplest terms, weight loss or gain is related to the balance between energy intake and energy expenditure, although the relationships are not linear. For example, if a person increases energy expenditure by walking an extra mile per day and maintains caloric intake constant, the weight loss over time will be only approximately 20% of expected. This is because the physiologic compensation for changes in energy expenditure or requirements to maintain the decreased weight are less than would be expected if the relationships were linear.
As obstetrician/gynecologists, we encourage our patients to breastfeed. Although many maternal and neonatal benefits accompany breastfeeding, the concept that infants who are breastfed are less likely to be obese in later life did not hold true in a randomized controlled trial (RCT) of more than 13,000 children followed for more than 6 years. The previous reports may have been affected by confounding and selection bias.
Metabolism in Obese Pregnant Women
Large epidemiologic studies have reported that obese women gain less weight during pregnancy compared with nonobese women. Based on small longitudinal metabolic studies in healthy lean and obese women before and during early and late gestation, significant changes were observed over time and between groups. A significant increase in lean and fat mass was reported in both lean and obese women, but a greater increase in fat mass was seen in lean women ( Fig. 41-1 ). A significant 23% increase in resting energy expenditure over time was not different between groups ( Fig. 41-2, A ). Basal carbohydrate oxidation increased 68% over time and was greater in obese women (see Fig. 41-2, B ). A 40% decrease in insulin sensitivity was reported as estimated by the glucose infusion rate during the hyperinsulinemic-euglycemic clamp divided by the mean insulin concentrations (i.e., the insulin sensitivity index [ISI]) in lean and obese women over time, with a trend ( P = .07) for a greater decrease in obese compared with lean women ( Fig. 41-3 ). As a result of the significant decrease in insulin sensitivity, fat oxidation increased 220% during the clamp in both lean and obese women ( P = .003) because of the decreased ability to suppress lipolysis. Basal free fatty acids decreased 16% over time ( P = .02), and a 62% increase was seen in free fatty acids with insulin infusion during the clamp ( P = .0004), but no significant difference was noted between groups ( Fig. 41-4 ). Although a 61% increase in fasting cholesterol and a 260% increase in triglycerides ( P = .0001) were observed over time, no significant difference was found between lean and obese women ( Fig. 41-5 ). Others have reported that in late pregnancy, obese women have increases in circulating triglycerides, very-low-density lipoprotein (VLDL) cholesterol, and lower high-density lipoprotein (HDL) as compared with that of lean women. In summary, significant increases in many lipid components are seen during pregnancy, some of which are increased to a greater degree in obese, compared with lean, women .
Recommendations for Gestational Weight Gain in Obese Women
Weight gain recommendations for pregnancy were first published by the Institute of Medicine (IOM) in 1990. At that time, prior to the increased prevalence of obesity in the population, the purpose was to establish recommendations for a healthy gestational weight gain for both the mother and her fetus primarily because of concerns for low birthweight and nutritional status. The recommendation for weight gain for women who were obese —defined as a prepregnancy BMI greater than 29—was at least 15 lb. Since that time, a significant increase has been seen in the number of women of childbearing age who are overweight or obese. Women also are becoming pregnant at an older age and with an increasing number of chronic medical conditions such as hypertension and diabetes. Hence, in 2009, the IOM revised the gestational weight guidelines taking into account more recent literature and the increased proportion of overweight and obesity in women of reproductive age ( Table 41-2 ).
| PREPREGNANCY BMI | BMI (kg/m 2 ) | TOTAL WEIGHT GAIN (RANGE) (lb) | RATES OF WEIGHT GAIN * IN TRIMESTERS 2 AND 3 (MEAN AND RANGE) (lb/wk) |
|---|---|---|---|
| Underweight | <18.5 | 28-40 | 1 (1-1.3) |
| Normal weight | 18.5-24.9 | 25-35 | 1 (0.8-1) |
| Overweight | 25.0-29.9 | 15-25 | 0.6 (0.5-0.7) |
| Obese (includes all classes) | ≥30.0 | 11-20 | 0.5 (0.4-0.6) |
* Calculations assume a 0.5-2 kg (1.1-4.4 lb) weight gain in the first trimester.
Although the 2009 IOM recommendations for gestational weight gain are not dramatically different from the 1990 guidelines except in regard to obese women, other substantive differences were apparent. These include using the WHO criteria for defining pregravid BMI and eliminating specific recommendations for certain populations that included women of short stature, pregnant adolescents, and different racial or ethnic groups. Based on these more recent definitions, excessive gestational weight gain occurs in 38% of normal-weight women, 63% of overweight women, and 46% of obese women. Excessive gestational weight gain is a significant factor for postpartum weight retention and hence is a significant contributor to the obesity epidemic .
Some authors have suggested that weight gain for obese women less than that specified in the current IOM recommendations may improve some perinatal outcomes. However, potential fetal risks relate to inadequate gestational weight gain in obese women. Although the issue of gestational weight gain is much debated in the United States, it is noteworthy that recommendations in other countries are not uniform. The Society of Obstetricians and Gynecologists of Canada have adopted the 2009 IOM recommendations, whereas recommendations from Sweden and China are unique to their own populations. Finally, the Centre for Maternal and Child Enquiries (CMACE) and Royal College of Obstetricians and Gynaecologists (RCOG) have no clinical recommendations or clinical guidelines for weight gain during pregnancy.
During pregnancy, medications for weight management are not recommended because of safety concerns and side effects . The classical anorexiants, such as phentermine, alter the release and reuptake of neurotransmitters that impact appetite. Other drugs such as orlistat reduce intestinal fat absorption by inhibiting pancreatic lipase. Metformin, which decreases hepatic glucose production, has been associated with decreased gestational weight gain in some studies when used to treat mild gestational diabetes mellitus (GDM). Metformin has not been used solely to manage gestational weight gain, and it crosses the placenta in significant amounts.
The primary weight-management strategies during pregnancy are dietary control, exercise, and behavior modification. These strategies have been used either alone or in combination to avoid excessive gestational weight gain. None of these strategies is uniform. For example, with diet, some studies have examined the role of food having a low glycemic index, whereas others have used probiotic interventions. Unfortunately, the authors of a recent Cochrane review concluded that there is not enough evidence to recommend any specific intervention for preventing excessive weight gain in pregnancy, because studies have suffered from methodologic limitations, small sample sizes, and insufficient power to detect clinically meaningful effect size. In general, nutritional strategies, rather than exercise, appear to be more useful in avoiding excessive gestational weight gain in pregnancy.
Pregnancy Complications in Obese Women
Early Pregnancy
A number of pregnancy complications are associated with obesity. The risk of spontaneous abortion (odds ratio [OR], 1.2; 95% CI, 1.01 to 1.46) and recurrent miscarriage (OR, 3.5; 95% CI, 1.03 to 12.01) is increased in obese women as compared with age-matched controls. The risk of congenital anomalies is also increased in obese mothers, who are at increased risk for pregnancies affected by neural tube, cardiovascular, orofacial, and limb-reduction anomalies .
Based on the Northern Congenital Abnormality Survey, routine ultrasound detected 46.2% (1146 of 2483) of structural anomalies in fetuses with a normal karyotype. Detection rates decreased significantly with increasing maternal BMI ( P = .0007, test for trend), and the odds of detection of any anomaly were significantly lower in obese women than in those with a normal BMI (adjusted OR [aOR], 0.77; 95% CI, 0.60 to 0.99). Factors associated with the decreased ability to detect congenital anomalies in obese women include the distance from the skin surface to the fetus, resolution/penetration of sonographic equipment, prolonged time to complete the examination, and the experience of the sonographer. Potential means to optimize image quality in obese pregnant women include a vaginal approach in the first trimester, using the maternal umbilicus as an acoustic window, and tissue harmonic imaging. Fetal magnetic resonance imaging (MRI) obviates many of these technical problems, but because its use is limited by cost and availability, the use of MRI for routine screening of anomalies is not recommended.
In the First- And Second-Trimester Evaluation of Risk (FASTER) Research Consortium trial, the detection rate for cardiac anomalies among women with a BMI less than 25 was higher (21.6%) at a significantly lower false-positive rate (FPR, 78.4%; 95% CI, 77.3 to 79.5) compared with obese women (8.3% detection rate with an FPR of 91.7%; 95% CI, 90.1 to 92.2). In a logistic regression model, maternal obesity significantly decreased the likelihood of sonographic detection of common anomalies (aOR, 0.7; 95% CI, 0.6 to 0.9).
Maternal obesity also affects measures of serum analytes because of the increased plasma volume in obese pregnant women. Although weight adjustment for analytes related to neural tube defects (NTDs) and trisomy 18 improves detection rates, this adjustment does not increase detection rates for trisomy 21. In prenatal testing for trisomies 21 and 18 using cell-free DNA (cfDNA), the false-positive rates were significantly lower ( P = .03) than with standard screening (serum biochemical assays with or without nuchal translucency measurement). The positive predictive value for cfDNA was also better for trisomy 21 (45.5% vs. 4.2%) and trisomy 18 (40.0% vs. 8.3%). The median BMI in this study was 27.4 (range, 15.5 to 59). It should be noted, however, that these test characteristics were for “positive” results and did not take into account results from women who were unable to have results obtained from the assay, an occurrence that is more common as BMI increases. Also, maternal obesity is associated with an increase in total, but not fetal, cfDNA. In a small study, total cfDNA increased 1.7% per BMI unit, and when adjusted for blood volume, it increased 3.2% per BMI unit. Therefore in the future, cfDNA values may need to be adjusted for maternal BMI for better interpretation of clinical data.
Mid to Late Pregnancy
The risk of metabolic problems is increased, which includes GDM and preeclampsia, as is the risk of cardiac dysfunction, proteinuria, sleep apnea, and nonalcoholic fatty liver disease (NAFLD) in obese as compared with normal-weight pregnant women . Because of the increased insulin resistance often observed in obese women before pregnancy, preexisting subclinical metabolic dysfunction may become manifest as obstetric conditions such as preeclampsia, gestational diabetes, and obstructive sleep apnea (OSA) and are associated with adverse pregnancy outcomes. These disorders may have a higher prevalence in certain racial or ethnic groups including black Africans and Southern Asians. In early gestation, hypertension, suspected glucose intolerance, or OSA should be screened for at the first antenatal visit with a history, physical examination, and laboratory and clinical studies as needed. Women with suspected OSA—those with symptoms of snoring, excessive daytime sleepiness, witnessed apneas, or unexplained hypoxia—should be referred to a sleep medicine specialist for evaluation and possible treatment. Although universal screening for gestational diabetes is recommended at 24 to 28 weeks gestation, screening for glucose intolerance in early gestation (gestational diabetes or overt diabetes) should be based on risk factors that include maternal obesity, known impaired fasting or 2-hour glucose levels based on a 75-g glucose tolerance test, or previous gestational diabetes (see Chapter 40 ). It has not been determined, however, whether universal testing early in pregnancy to detect overt diabetes is of clinical value or is cost-effective. In addition, NAFLD—the most common liver disease in developed countries—usually presents with elevated liver function tests. NAFLD is related to increased insulin resistance and is often confused with other disorders of liver function during pregnancy such as the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome.
Is there any treatment to prevent metabolic complications such as gestational diabetes in obese women once they are pregnant? Lifestyle interventions in studies of small numbers of obese women to prevent the development of GDM have not been successful. A Cochrane review reported that no conclusive evidence for exercise in pregnancy to prevent GDM was available to guide practice. Supplementation with a probiotic and myo-inositol in two European studies has been reported to reduce the frequency of gestational diabetes. However, these trials were conducted in nonobese populations. Although prevention of preeclampsia with calcium supplementation and vitamin C and E have not been successful, optimizing glucose control in women with GDM may decrease the rate of preeclampsia. The administration of low-dose aspirin (60 to 80 mg/day) in the late first trimester is suggested in women with a medical history of early-onset preeclampsia and preterm delivery at less than 34 0/7 weeks or preeclampsia in more than one prior pregnancy.
Not only is the risk of indicated preterm deliveries increased because of the aforementioned antepartum complications, the risk of idiopathic preterm birth is also increased in overweight and obese pregnant women. The risk of stillbirth also increases (test for trend, P < .01) with progressive degrees of maternal obesity: BMI class I (adjusted hazard ratio [aHR], 1.3; 95% CI, 1.2 to 1.4), BMI class II (aHR, 1.4; 95% CI, 1.3 to 1.6), and extreme obesity (aHR, 1.9; 95% CI, 1.6 to 2.1). A further increased risk of stillbirth was seen in obese black, compared with obese white, mothers. The underlying etiology for intrauterine fetal death in obese women is unknown, and as such, no specific recommendations exist regarding prevention other than optimizing general obstetric care relative to medical or obstetric conditions. Although obese women are at increased risk for adverse perinatal outcomes, data are insufficient to recommend antenatal surveillance in this population without additional clinical indications. As a noninvasive option, fetal movement counts, such as kick counts, are suggested (see Chapter 11 ).
Intrapartum Complications
At delivery, obese women are at increased risk of cesarean delivery, endometritis, wound rupture/dehiscence, and venous thrombosis, and they have an almost twofold increased risk of composite maternal morbidity and a fivefold risk of neonatal injury. The unadjusted ORs of cesarean delivery are 1.46 (95% CI, 1.34 to 1.60), 2.05 (95% CI, 1.86 to 2.27), and 2.89 (95% CI, 2.28 to 3.79) for overweight, obese, and severely obese women, respectively, compared with normal-weight women. Maternal obesity alone is not an indication for induction of labor. However, obese women are at increased risk of a prolonged pregnancy and have an increased rate of induction of labor. Although compared with spontaneous labor, induction of labor is associated with an increased risk of cesarean delivery in obese women, no specific recommendations have been made to decrease the risk of primary cesarean delivery in this population.
The length of labor in nulliparous women is proportional to maternal BMI . In a study that adjusted for maternal height, labor induction, membrane rupture, oxytocin use, epidural anesthesia, net maternal weight gain, and fetal size, the median duration of labor from 0 to 10 cm was significantly longer in overweight and obese women. In overweight women, the prolongation was between 4 and 6 cm, and for obese women, labor was slower before 7 cm. In a mixed nulliparous and multiparous cohort, the second stage of labor was not significantly different among normal, overweight, and obese women . The intrauterine pressure generated during a standardized Valsalva maneuver also was not significantly different among the various weight groups.
The rate of trial of labor after cesarean (TOLAC) has been decreasing since the mid-1990s and is now less than 10% (see Chapter 20 ). TOLAC success rates are inversely related to BMI: for a BMI less than 19.8, the rate is 83.1%; when BMI is between 19.8 and 26, the rate is 79.9%; between 26.1 and 29, the rate is 69.3%; and when BMI exceeds 29, the rate is 68.2% ( P < .001). Similarly, gaining over 40 lb during pregnancy is associated with a decreased TOLAC success rate (66.8% vs. 79.1%, P < .001). Class III women undergoing a TOLAC had greater composite morbidity—which included prolonged hospital stay, endometritis, rupture/dehiscence, and neonatal injury (fractures, brachial plexus injuries, and lacerations)—compared with class III women having an elective cesarean delivery, although absolute morbidities were small. The risk is increased significantly for postpartum atonic hemorrhage (>1000 mL) for class III obese women after a vaginal delivery (5.2%) and instrumental delivery (13.6%), compared with normal-weight women (4.4%), but not after cesarean delivery.
Maternal obesity significantly increases the risk of anesthetic complications . The CMACE/RCOG recommendations state that women with a pregravid BMI greater than 40 should have an antenatal consultation with an obstetric anesthesiologist to discuss and document anesthetic management plans for labor and delivery (see Chapter 16 ). For all other obese women, early consultation with an obstetric anesthesiologist at the time of admission to labor and delivery should be considered to obtain proper equipment to monitor blood pressure, establish venous access, and screen for relevant comorbid conditions. The risk of epidural failure is greater in obese women, compared with normal weight and overweight women ; therefore early labor epidural placement should be considered. This may mitigate increased time in the obese patient from decision for an emergency cesarean to delivery. Compared with normal-weight women, severely obese women at term have significantly greater hypotension and prolonged fetal heart rate decelerations after controlling for epidural bolus dose and hypertensive disorders. The combination of spinal anesthesia and obesity significantly impairs respiratory function for up to 2 hours after the procedure. General anesthesia also poses a risk for the obese pregnant women because of potential difficulties with endotracheal intubation (see Chapter 16 ). However, general anesthesia is not a contraindication in obese women, but consideration should be given to the need for preoxygenation, proper positioning of the patient, and fiberoptic equipment intubation availability.
Broad-spectrum antimicrobial prophylaxis is recommended for all cesarean deliveries unless the patient is already receiving antibiotics for conditions such as chorioamnionitis. In a study of normal weight, overweight, and obese women, after 2-g dosing 30 to 60 minutes before skin incision, cefazolin concentrations in adipose tissue were inversely proportional to BMI. In obese and extremely obese patients, adipose tissue concentrations of cefazolin at the time of skin incision were less than the minimally inhibitory concentration for gram-negative rods (<4 µg/g of tissue) in 20% and 33% of obese and severely obese patients, respectively. However, differences in clinical outcomes have not been established, and a proper dosing based on BMI has not been recommended.
The optimal type of skin incision for primary cesarean delivery in order to decrease morbidity in obese class II and III patients has not been resolved. Using data from a perinatal database, it was reported that a vertical skin incision was associated with a higher rate of wound complications than a transverse incision. More recent data from a secondary analysis of the Maternal-Fetal Medicine Unit’s (MFMU) cesarean registry, which used a composite of wound complications (infection, seroma, hematoma, wound evisceration, and fascial dehiscence) as the primary outcome, reported that in a univariate analysis, patients with a vertical skin incision had a significantly higher rate of wound complications; however, after adjustment for confounding factors, a vertical incision was associated with a significantly lower risk for wound complications. The discrepancy was most likely explained by selection bias. Others have reported that in obese women with a voluminous panniculus, a supraumbilical incision was associated with favorable outcomes.
Closure with suture of subcutaneous tissue greater than 2 cm in depth can significantly decrease the incidence of wound disruption. The additional use of a subcutaneous drain with bulb suction in obese women with at least 4 cm of subcutaneous fat was not effective in preventing wound complications and may have potentiated postcesarean wound complications. Compared with normal-weight women, the risk of surgical site infections (SSIs) is increased following a cesarean delivery in overweight women (OR, 1.6; 95% CI, 1.2 to 2.2), obese class I women (OR, 2.4; 95% CI, 1.7 to 3.4), and obese class II and III women (OR, 3.7; 95% CI, 2.6 to 5.2; Fig. 41-6 ). Subcutaneous skin thickness greater than 3 cm is a significant risk factor (OR, 2.8; 95% CI, 1.3 to 5.9) for postcesarean wound infection after adjusting for maternal BMI. Types of skin preparation, skin-closure techniques, and supplemental oxygen have not proved useful in decreasing the rate of postcesarean infectious morbidity.
