Pregnancy in Women With Obesity

Prepregnancy Body Mass Index

Currently there is no standard definition of obesity in pregnancy. Since 1998, the World Health Organization (WHO) and the National Institutes of Health (NIH) have considered BMI to be the most useful and robust population-level measure of obesity and risk of comorbidity ( Table 60.1 ). ^, However, the BMI cutoffs used are both age and sex independent and not specific to pregnancy. BMI also does not account for variations in adiposity between individuals and populations. BMI does not consider the relative contributions of lean mass (bone and muscle) and fat mass. As a result, BMI overestimates “obesity” in athletic, younger individuals. When percentage body fat is used in lieu of BMI the disparity of obesity significantly decreases between White and Black women. In contrast, among Asian adults, modified BMI categories have been proposed to more accurately capture the risk of coexisting conditions and future morbidity at substantially lower BMI cutoffs compared to other populations.

In studies of obesity and pregnancy, a variety of definitions for obesity have been proposed and used, including WHO and NIH BMI categories, and absolute measures such as gravid weight above 200 lb. Most frequently, studies of obstetric populations use standard WHO and NIH BMI categories with either prepregnancy BMI or BMI measured at delivery, depending on the outcome of interest. Prepregnancy obesity and excessive gestational weight gain (GWG) are distinct, potentially modifiable risk factors with differing associated adverse outcomes. Therefore consideration of BMI prior to and throughout pregnancy may be necessary for individual and population risk assessments.

Extreme maternal obesity is variably defined in pregnancy, including maternal weight greater than 300 lb and BMI ranging from 35 to 50 kg/m ² . Originally proposed in the bariatric surgery and general obesity literature, the emerging categories of maternal super obesity (BMI ≥50 kg/m ² ) and super-super obesity (BMI ≥60 kg/m ² ) have been proposed to investigate outcomes among women at the very extremes of obesity. Super obesity continues to increase and is the fastest growing obesity group in the United States. Currently, nationally representative studies are only available in the United Kingdom and Australia, where rates of pregnant women with super obesity are reported as 8.7/10,000 and 2.1/1000, respectively. ^, In the United States, rates have been reported as high as 2.2% among nearly 20,000 women delivering at a tertiary-care center in South Carolina. Other researchers in the United States noted that rates of BMI >50 kg/m ² in pregnant women in Missouri were similar across all races/ethnicities.

Alternative Measures of Obesity

BMI was originally proposed in the 19th century by Lambert Aldolphe Jacques Quetelet, a mathematician, as a means of accounting for an individual’s height in relation to weight. In 1972, Keys and colleagues proposed the use of this formula and coined the term body mass index as an epidemiologic tool to assess populations for prevalence of obesity. Originally, BMI was proposed as a screening tool for obesity because height and weight require simple and inexpensive tools to assess and are reproducible in a variety of settings. However, BMI does not account for relative contributions of bone, muscle, and adipose tissue. Other methods may have improved sensitivity and specificity for identifying women at increased risk of obesity-related diseases due to excessive adipose tissue accumulation. Increased waist circumference (>88 cm for women) and increased waist-to-hip ratio (WHR; defined as >0.85 among women) correlate relatively better with central adiposity, which is associated with increased risk of comorbidities and future morbidity. ^,

Increased WHR in early pregnancy (defined as >0.85) is associated with increased risk of preeclampsia and gestational diabetes mellitus (GDM) but not mode of delivery. The use of third-trimester WHR is problematic in pregnancy. Others have described multiple methods of assessing maternal body composition in late gestation including skinfold thickness, ^, bioelectric impedance analysis, deuterium dilution technique, and ultrasound measurement of subcutaneous and preperitoneal adipose tissue. Though these other measures of adiposity are used in research contexts in general and obstetric populations, they require special training and expensive equipment.

Gestational Weight Gain

GWG is defined as maternal weight at delivery minus maternal prepregnancy weight. At term, 4–5 kg of weight gain in pregnancy represents the fetus (3.5 kg), placenta (0.5 kg), and amniotic fluid (0.5–1.0 kg), and the remaining weight is adipose tissue (4 kg) and extravascular fluid (1 kg). However, these estimated values are highly dependent on women’s environments and access to a steady source of high-quality nutrition.

Adipose tissue accounts for approximately 30% of weight gain in pregnancy. However, the composition of weight gain varies by trimesters and by maternal prepregnancy adiposity. ^, Early pregnancy weight gain is disproportionately made up of adipose tissue. The acquisition of maternal adipose tissue is correlated with prepregnancy BMI. In a prospective study of women followed from preconception through pregnancy, the net weight of adipose tissue varied significantly by maternal prepregnancy BMI, with a mean of 5.3 kg among underweight women, 4.6 kg among normal-weight women, and 8.4 kg among women with obesity. Women who gained above National Academy of Medicine (NAM, previously known as Institute of Medicine) goals gained more fat mass (5.2 kg; interquartile range [IQR], 4.2–8.1 kg) compared to women who gained within or below NAM goals (0.2 kg [IQR, 0.4–2.2 kg] versus −2.7 kg [IQR, −5.2 to −0.7 kg], respectively; P < .001).

In pregnancy, the accumulation of adipose tissue does not occur uniformly but rather in physiologic compartments that allow for the quick utilization of these stores to meet the metabolic demands of pregnancy. ^{, ,} Pregnancy may favor intraabdominal adipose tissue deposition, with an increase in subcutaneous fat layers by the third trimester of pregnancy. ^, Ultrasound has been used to measure preperitoneal subcutaneous adipose tissue to calculate an abdominal fat index as a measure of central versus peripheral fat deposition among women with normal weight compared to those with obesity. As pregnancy progresses in women with normal weight, adipose tissue is preferentially distributed in the visceral compartment; however, among pregnant women with obesity the thickness of preperitoneal fat decreases over time. These studies suggest that the amount of adipose tissue gained in pregnancy is highly dependent on an individual’s prepregnancy BMI.

A growing body of literature suggests that inadequate and excessive maternal GWG may play independent roles in adverse outcomes in pregnancy and postpartum. In 1990 the NAM published the first guidelines for suggested maternal GWG, with the intended purpose of decreasing the risk of fetal growth restriction associated with inadequate GWG.

In 2009, the NAM revised its GWG guidelines and adjusted the recommended GWG, particularly for women with obesity, from at least 15 lb to 11–20 lb. In accordance with the NAM guidelines, the American College of Obstetricians and Gynecologists (ACOG) recommends that prenatal clinicians counsel all pregnant women at the initial prenatal visit regarding recommended GWG by prepregnancy BMI for singleton and twin gestations ( Table 60.2 ). There is insufficient evidence to recommend GWG goals for triplet and other higher order multiple gestations. These revised recommendations attempt to balance decreasing the risk of small-for-gestational-age (SGA) fetuses associated with inadequate GWG and the increasing risks of macrosomia and postpartum weight retention, particularly among overweight women and women with obesity, for excessive GWG. ^,

Although GWG goals differ according to prepregnancy BMI, the energy requirements, or the additional calories women should consume daily, are currently the same for all women regardless of weight prior to pregnancy (e.g., an increase by 340 to 452 kcal/day in the second and third trimesters). Most and colleagues challenged this recommendation for energy requirements with a prospective observational study of 54 women with obesity. They evaluated energy intake with the energy intake-balance method (doubly labeled water and whole-room indirect calorimetry and body composition) at 13 to 16 weeks’ gestation and 35 to 37 weeks’ gestation with the current NAM GWG goals. For women who met GWG goals ( n = 8), mean (SD) daily energy intake was 2,698 (99) kcal/day and energy expenditure was 2824 (105) kcal/day. Therefore these women had a negative energy balance (−125 [52] kcal/day) and still met GWG goals. Women with inadequate GWG ( n = 10) also had a negative energy balance (−262 [32] kcal/day), but the difference was not significantly different compared with that in the recommended gestational weight gain group ( P = .08). In contrast, women with excessive GWG ( n = 36) had a mean (SD) positive energy balance of 186 (29) kcal/day. The body weight gains of the fat-free and fat mass compartments also were compared with linear mixed effect models among the three weight gain groups. There were no differences in the amount of fat-free mass gained among the 3 weight gain groups ( P > .05), but women with excessive GWG had significantly higher increases in fat mass compared with the other two weight gain groups ( P < .001). Energy requirements likely need to be individualized for women with obesity, but further studies with larger sample sizes are needed to support these findings.

Cardiovascular System

Both pregnancy and obesity have profound cardiovascular effects due to increased tissue demands for oxygen. Pregnancy increases cardiac output by approximately 30%–50%, and blood volume doubles by the third trimester. For every 100 g of fat, cardiac output increases by 30–50 mL/min, and blood volume also increases in order to meet the metabolic demand of adipose tissue. The effect of obesity on the entire cardiovascular system, including cardiac, endothelial, and vascular function, is directly related to the duration of obesity, suggesting that prepregnancy obesity may have a substantial impact on the ability of the cardiovascular system to adapt to normal physiologic changes of pregnancy. In two studies of women with BMI ≥40 kg/m ² or >45 kg above ideal body weight undergoing M-mode echocardiography, left ventricular hypertrophy and/or decreased stroke volume and contractility were more common among women with obesity compared to women without obesity. ^, However, whether maternal cardiac changes are specific to pregnancy, maternal obesity, or their interaction remains unknown.

The effects of obesity on underlying vascular function during pregnancy are considerable. In a study of healthy pregnant women in the third trimester, women with obesity ( n = 23; median first-trimester BMI, 31.0 kg/m ² ) had marked increased hyperinsulinemia and dyslipidemia but also impaired endothelial function, higher blood pressure, and inflammatory upregulation compared to women with normal weight ( n = 24; median first-trimester BMI, 22.1 kg/m ² ). Low-density lipoprotein cholesterol and glycosylated hemoglobin were similar between women with and without obesity; fasting triglyceride concentrations were higher (2.70 mmol/L [IQR, 2.3–3.21 mmol/L] versus 2.20 mmol/L [IQR, 2.0–2.6 mmol/L]; P = .02) and high-density lipoprotein concentrations were lower (1.55 mmol/L [IQR, 1.1–1.7 mmol/L] versus 1.72 mmol/L [IQR, 1.4–2.0 mmol/L]; P = .02) in women with obesity. Levels of leptin (55.6 ng/mL [IQR, 45–64.4 ng/mL] versus 23.8 ng/mL [IQR, 13.2–35.2 ng/mL]; P < .0001) and fasting insulin (14.5 mU/L [IQR, 11.4–27.3 mU/L] versus 6.5 mU/L [IQR, 4.6–9.7 mU/L]; P < .0001) were more than double among women with obesity. In vivo assessment of endothelial-dependent and endothelial-independent microvascular function using laser Doppler imaging showed that both endothelial-dependent and endothelial-independent vasodilatory responses were significantly reduced ( P = .0003 and P = .02, respectively, by analysis of variance) and systolic blood pressure was higher ( P = .01) in women with obesity.

The downstream effects of altered vascular function among women with obesity are likely the underlying cause of the association between maternal obesity, chronic hypertension, and gestational hypertension, which have been coined metabolic syndrome–like complications in late pregnancy. In a large prospective, multicenter study, 4.8% of women without obesity developed gestational hypertension compared to 10.2% of women with class 1 obesity (adjusted odds ratio [aOR] = 2.5; 95% confidence interval [95% CI], 2.1–3.0) and 12.3% of women with class 2 and 3 obesity (aOR = 3.2; 95% CI, 2.6–4.0). [CR] Compared to women without obesity (2.1%), women with class 1, class 2, and class 3 obesity were also more likely to develop preeclampsia (3.0% and 6.3%, respectively; obese class 1 versus nonobese aOR = 1.6; 95% CI, 1.1–2.3; class 2 and 3 versus nonobese aOR = 3.3; 95% CI, 2.4–4.5).

Respiratory System

Endocrine System

Obesity is associated with underlying systemic inflammation, which impacts metabolic function. In the nonobstetric literature, obesity—particularly central obesity—has been linked to upregulation of proinflammatory cytokines, including interleukin 6 (IL-6), ^, tumor necrosis factor-α (TNF-α), ^, and leptin, ^, and downregulation of the antiinflammatory cytokine adiponectin compared to lean individuals. Research on adipokines, cytokines produced by adipose, and their role in normal and complicated pregnancy is still in its infancy. Pregnancy is associated with changes in systemic inflammatory markers, particularly of C-reactive protein, IL-6, and TNF-α. Both placental and maternal adipose tissue produces adipokines, which likely play a role in mediating the release of substrate such as stored fatty acids to meet the metabolic demands of pregnancy. In pregnancy, leptin increases as BMI increases and is inversely correlated with adiponectin levels. Leptin, a potent immune activator, activates polymorphonuclear neutrophils, exerting a proliferative effect on T-cells, and upregulates production of cytokines, including TNF-α, IL-6, interleukin-1β, vascular endothelial growth factor, and interferon-γ. Among pregnant women with obesity, gene expression of the adipokines, TNF-α, interleukin-1β, and leptin in adipose tissue is elevated compared to that in lean pregnant women. Increased inflammatory markers are also associated with increased risk of pregnancy complications, including preeclampsia ^{, ,} and GDM. ^, However, the precise mechanisms by which maternal obesity and increased systemic inflammation lead to adverse pregnancy outcomes is still unknown.

Gastrointestinal System

Frequency of gastroesophageal reflux is strongly correlated with increasing BMI. Obesity, increased estrogen, and increased abdominal pressure are all associated with increased risk of gastroesophageal reflux. Although it is unknown whether pregnancy and maternal obesity are additive, it is likely that pregnant women with obesity are at increased risk of regurgitation and aspiration, particularly at the time of cesarean delivery.

Cholelithiasis, biliary sludge, and stones are associated with both pregnancy and obesity. In a large case-control study of gallstone-related hospitalizations among pregnant women, 15% of women in the control group were obese compared to 40.5% of cases. After adjustment for other factors including diabetes and race/ethnicity, maternal obesity was associated with a fourfold increase in hospitalization due to symptomatic gallstone disease (OR = 4.40; 95% CI, 3.89–4.99).

Coagulation

Both obesity and pregnancy are associated with hypercoagulability and increased risk of venous thromboembolism (VTE). The exact mechanism is not clear, but both obesity and pregnancy are associated with higher levels of fibrinogen and plasminogen activator inhibitor type 1 levels. Likewise, studies in adults with obesity have shown impeded venous flow parameters in the lower extremities of those with obesity compared to those of normal weight, specifically demonstrating larger femoral vein diameter, with lower venous peak and minimum velocities. During pregnancy, deep vein thrombosis is more likely to be left-sided and proximal, probably because of compression of the left iliofemoral vein by the right common iliac artery. If compression is severe, it may produce May-Thurner syndrome, a left-sided iliac outflow obstruction with localized adventitial fibrosis and intimal proliferation. Though strongest risks for VTE are thrombophilia (OR = 51.8; 95% CI, 38.7–69.2) and history of thrombosis (OR = 24.8; 95% CI, 17.1–36.0), maternal obesity is one of the most common risk factors for VTE during pregnancy and postpartum.

Placenta

Placental changes associated with obesity are overgrowth and hypoxic stress. In a study of over 400 placentas, the mean placental disk weight was 44 g larger in term placentas from women with obesity compared to those from normal-weight women ( P < .001). After controlling for confounders, additional placental pathology associated with obesity included chronic villitis (aOR = 1.96; 95% CI, 1.18–3.27) and normoblastemia (aOR = 2.42; 95% CI, 1.47–3.97) ( Fig. 60.2 ), measures of chronic inflammation and intrauterine hypoxic stress, respectively. Both chronic villitis and normoblastemia increased with worsening obesity ( P < .001 and P < .034, respectively). Interestingly, placental efficiency, defined by the ratio of fetal to placental weight, was decreased among women with obesity compared to women without obesity (6.71 ± 1.29 versus 6.97 ± 1.25, P = .042). This association remained after controlling for villitis: for every one-unit increase in BMI, placental efficiency decreased by 0.1.

Weight Management

Prepregnancy obesity may be the anthropometric measure most strongly associated with adverse pregnancy outcomes. However, there are a few outcomes independently associated with GWG that might be of concern to the maternal-fetal dyad. As such, improving GWG may be important. Excessive GWG is recognized as a significant risk factor for cesarean delivery, preterm birth, GDM, preeclampsia, postpartum weight retention, macrosomia, and low 5-minute Apgar scores. The impact of excessive GWG does not end with pregnancy; both mother and child are more likely to be obese in later life after excessive GWG. Excess GWG results in a 3.1-kg weight retention 3 years postpartum and 4.7 kg after 15 years. Independent of maternal BMI, excessive GWG is associated with increased risk of abnormal cardiovascular and metabolic profiles among offspring in adolescence and adulthood. Though maternal prepregnancy and pregnancy adiposity is associated with adverse cognitive and neurodevelopmental outcomes among children, less is understood about neurodevelopmental outcomes and rate of GWG.

Preventing excessive GWG may be an effective strategy for both reducing adverse perinatal outcomes and curbing the obesity epidemic. However, a minority of women gain the recommended weight during pregnancy. For example, Deputy and colleagues reported on GWG adequacy in a study using the Pregnancy Risk Assessment Monitoring System (PRAMS) for women who had full-term singleton deliveries from 28 states. Prepregnancy BMI was a self-reported value and total GWG was obtained from birth certificate files. After weighting, the final sample size represented approximately 30% of births in the United States from 2010 to 2011. In their analysis, 20.9% and 47.2% of all women had inadequate or excessive GWG, respectively.

Several studies have investigated factors associated with inappropriate GWG. One modifiable factor for GWG is provider advice during prenatal care. Approximately 30%–40% of women do not recall receiving GWG advice. Though 29% of women state that their provider made a recommendation on GWG, only 12% of these women report that they received the correct GWG goal for their BMI. Only one-quarter of women report receiving counseling on risks of excessive GWG. Low rates of appropriate GWG counseling were consistent among type of prenatal clinician, with midwives (16.3%), family medicine physicians (10.3%), obstetricians (9.2%), and other clinicians (5.7%) supplying the appropriate weight goals by the women’s BMI. It is possible that if women are aware of their GWG goals, they may be more likely to meet them. In a study of 6727 nulliparas completing a survey between 6 and 13 weeks’ gestation, 56.5% had a personal GWG goal. For those women who had a GWG goal, 38.5% had a goal that was consistent with the NAM guidelines according to their prepregnancy BMI. Women who had a GWG goal consistent with the guidelines had a reduced risk for excessive (adjusted RRR = 0.77; 95% CI, 0.64–0.92) and inadequate GWG (adjusted RRR = 0.66, 95% CI, 0.53–0.82). There are conflicting data as to whether Hispanic women are more or less likely to have inadequate or excessive GWG than other groups of women. More Spanish speakers compared to English speakers did not know whether their clinician recommended weight gain goals (26% versus 10%; OR = 3.2; 95% CI, 1.5–6.5) or whether there were risks to excessive GWG for mother (27% versus 11%; OR = 3.1; 95% CI, 1.5–6.4) or infant (38% versus 16%; OR = 3.3; 95% CI, 1.7–6.3).

Excessive GWG is associated with postpartum weight retention, subsequent increased prepregnancy BMI in the next pregnancy, and macrosomia. Several studies, including large randomized controlled trials (RCTs), addressed lifestyle intervention, such as diet modification and increasing exercise, among women with obesity. Outcomes included the proportion of women who had excessive GWG and adverse perinatal outcomes, including GDM and large-for-gestational-age (LGA) neonates. Though behavioral intervention appears to decrease GWG among overweight and women with obesity by 1–2 kg, these interventions do not appear to improve perinatal outcomes. Multiple trials including two meta-analyses of available studies have come to similar conclusions: behavioral interventions that begin during pregnancy have a modest effect on preventing excessive GWG but do not improve perinatal outcomes, including GDM and LGA. In a meta-analysis of 13 RCTs, 9 demonstrated a decrease in GWG of 0.9–9.1 kg among participants in the intervention arm compared to controls; 4 studies showed no difference. This review and others suggest that significant heterogeneity among the interventions limited the ability to identify the successful components and develop clinical guidelines. Future research is needed to determine whether GWG should be the same for obesity classes.